bluuebunny/crossref_metadata_2025 huggingface dataset:
ENGINEERING T CELLS TARGETING GPC2 FOR TREATING NEUROBLASTOMA
Authors: Quan Alex , Li Nan , Li Dan , Spetz Madeline , Zhang Hongbing , Liu Cheng , Ho Mitchell
Published: July 2023

Background and Significance

Neuroblastoma is a rare pediatric cancer that forms in immature nerve tissue of infants and accounts for 10 to 15 percent of cancer-related deaths in children. The five-year survival for high-risk neuroblastoma is 50% with current treatment practices being a combination of surgery, chemotherapy, and radiation. A more effective therapy is therefore needed to improve overall patient outcomes.

Methods

The CT3 mouse antibody that targets GPC2 was previously identified in the lab and has shown activity in the chimeric antigen receptor (CAR) T cell format against neuroblastoma. Humanization of the CT3 antibody was also done through CDR grafting in human germline sequences to prevent potential adverse immunogenic effects when treating patients. In the present study, the CT3 antibody and humanized CT3 (hCT3) antibody were engineered into T cells based on the engineered gamma/delta TCR scaffold (called AbTCR). The activities of the CT3 and hCT3 AbTCRs were tested in luciferase-based cell killing assays and xenograft mouse models.

Results

Humanized CT3 retains a comparable binding affinity for GPC2. The hCT3 CAR T cell showed its ability to regress tumor expression in mice. Furthermore, the mice treated with the CT3 AbTCR showed tumor regression while the mice treated with the hCT3 AbTCR became tumor free three weeks after treatment.

Conclusions

Overall, the hCT3 AbTCR T cells are very active when combating neuroblastoma tumors in mice. The efficacy at a low treatment dosage indicates that the GPC2 targeted hCT3 AbTCRs are a promising therapeutic for the treatment of neuroblastoma and other GPC2 positive cancers in patients.
ICARUS: flexible protein structural alignment based on Protein Units
Authors: Cretin Gabriel , Périn Charlotte , Zimmermann Nicolas , Galochkina Tatiana , Gelly Jean-Christophe
Published: July 2023

Motivation

Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational variability, or complex evolutionary relationships between proteins such as insertions, circular permutations or repetitions. In such cases, introducing flexibility becomes useful for two reasons: (i) it can help compare two protein chains which adopted two different conformational states, such as due to proteins/ligands interaction or post-translational modifications, and (ii) it aids in the identification of conserved regions in proteins that may have distant evolutionary relationships.

Results

We propose ICARUS, a new approach for flexible structural alignment based on identification of Protein Units, evolutionarily preserved structural descriptors of intermediate size, between secondary structures and domains. ICARUS significantly outperforms reference methods on a dataset of very difficult structural alignments.

Availability and implementation

Code is freely available online at https://github.com/DSIMB/ICARUS.
Molecular property prediction by semantic-invariant contrastive learning
Authors: Zhang Ziqiao , Xie Ailin , Guan Jihong , Zhou Shuigeng
Published: July 2023

Motivation

Contrastive learning has been widely used as pretext tasks for self-supervised pre-trained molecular representation learning models in AI-aided drug design and discovery. However, existing methods that generate molecular views by noise-adding operations for contrastive learning may face the semantic inconsistency problem, which leads to false positive pairs and consequently poor prediction performance.

Results

To address this problem, in this article, we first propose a semantic-invariant view generation method by properly breaking molecular graphs into fragment pairs. Then, we develop a Fragment-based Semantic-Invariant Contrastive Learning (FraSICL) model based on this view generation method for molecular property prediction. The FraSICL model consists of two branches to generate representations of views for contrastive learning, meanwhile a multi-view fusion and an auxiliary similarity loss are introduced to make better use of the information contained in different fragment-pair views. Extensive experiments on various benchmark datasets show that with the least number of pre-training samples, FraSICL can achieve state-of-the-art performance, compared with major existing counterpart models.

Availability and implementation

The code is publicly available at https://github.com/ZiqiaoZhang/FraSICL.
Efficacy of hydrodilatation in frozen shoulder: a systematic review and meta-analysis
Authors: Poku Daryl , Hassan Rifat , Migliorini Filippo , Maffulli Nicola
Published: July 2023

Introduction

It is unclear whether hydrodilatation is beneficial in the management of frozen shoulder compared with other common conservative management modalities. This systematic review evaluates the efficacy of hydrodilatation for the management of frozen shoulder.

Sources of data

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An extensive search of PubMed, Embase, Scopus, Cochrane Central, Web of Science and CINAHL databases using multiple keyword combinations of ‘shoulder’, ‘rotator’, ‘adhesive capsulitis’, ‘hydrodilatat*’, ‘distension’ since inception of the databases to June 2023 was implemented.

Areas of agreement

Hydrodilatation leads to at least transient more marked improvements in shoulder disability and passive external rotation compared with intra-articular corticosteroid injections.

Areas of controversy

Hydrodilatation improves passive external rotation in the longer term. Moreover, hydrodilatation may be a preferable option over manipulation under anaesthesia, given its lower cost and better patient convenience.

Growing points

Intensive mobilization after hydrodilatation is a promising adjuvant treatment option for patients suffering from a frozen shoulder.

Areas timely for developing research

Although current evidence suggests that hydrodilatation provides a transient improvement in disability in patients with frozen shoulder, its clinical relevance remains unclear. Further research is necessary to establish its role in the management of the condition.
Cathepsin-C mutation in an individual with phenotypic features of Haim–Munk syndrome: a case report
Authors: McCarthy Rebecca L , Gnanappiragasam Dushyanth , Scorer Matthew , Taylor Marisa , O’Toole Edel A
Published: July 2023

Haim–Munk syndrome and Papillon–Lefèvre syndrome are rare genodermatoses caused by mutations in CTSC, which encodes cathepsin C. Both syndromes cause palmoplantar keratoderma and are associated with periodontitis. We report a variant in CTSC that has previously been described in Papillon–Lefèvre syndrome but has not previously been reported in Haim–Munk syndrome. We suggest that Papillon–Lefèvre syndrome and Haim–Munk syndrome are a spectrum of diseases, caused by CTSC mutations, with significant overlap in their phenotypic features.
Online attitudes about the first approved systemic treatment for alopecia areata: a sentiment analysis of Reddit posts
Authors: David Eden , O’Hagan Ross , Ungar Benjamin
Published: July 2023

Alopecia areata (AA) is a complex inflammatory skin disease with a tremendous physical and emotional burden. Understanding patient sentiment towards AA treatment, particularly those treatments approved for AA, may help in better addressing patient needs. Here, we analysed 13 771 Reddit posts from the ‘alopecia_areata’ subreddit using sentiment analysis to evaluate online attitudes about the first approved systemic treatment for AA, baricitinib. We show that posts including baricitinib or related terms are more likely to be positive, with a higher likelihood of being positive after Food and Drug Administration approval.
Arsenic speciation in freshwater fish: challenges and research needs
Authors: Hoy Karen S , Davydiuk Tetiana , Chen Xiaojian , Lau Chester , Schofield Jordan R M , Lu Xiufen , Graydon Jennifer A , Mitchell Ruth , Reichert Megan , Le X Chris
Published: July 2023

Food and water are the main sources of human exposure to arsenic. It is important to determine arsenic species in food because the toxicities of arsenic vary greatly with its chemical speciation. Extensive research has focused on high concentrations of arsenic species in marine organisms. The concentrations of arsenic species in freshwater fish are much lower, and their determination presents analytical challenges. In this review, we summarize the current state of knowledge on arsenic speciation in freshwater fish and discuss challenges and research needs. Fish samples are typically homogenized, and arsenic species are extracted using water/methanol with the assistance of sonication and enzyme treatment. Arsenic species in the extracts are commonly separated using high-performance liquid chromatography (HPLC) and detected using inductively coupled plasma mass spectrometry (ICPMS). Electrospray ionization tandem mass spectrometry, used in combination with HPLC and ICPMS, provides complementary information for the identification and characterization of arsenic species. The methods and perspectives discussed in this review, covering sample preparation, chromatography separation, and mass spectrometry detection, are directed to arsenic speciation in freshwater fish and applicable to studies of other food items. Despite progress made in arsenic speciation analysis, a large fraction of the total arsenic in freshwater fish remains unidentified. It is challenging to identify and quantify arsenic species present in complex sample matrices at very low concentrations. Further research is needed to improve the extraction efficiency, chromatographic resolution, detection sensitivity, and characterization capability.
Concerning the eXclusion in human genomics: the choice of sex chromosome representation in the human genome drastically affects the number of identified variants
Authors: Pinto Brendan J , O’Connor Brian , Schatz Michael C , Zarate Samantha , Wilson Melissa A
Published: July 2023

Over the past 30 years, a community of scientists has pieced together every base pair of the human reference genome from telomere to telomere. Interestingly, most human genomics studies omit more than 5% of the genome from their analyses. Under “normal” circumstances, omitting any chromosome(s) from an analysis of the human genome would be a cause for concern, with the exception being sex chromosomes. Sex chromosomes in eutherians share an evolutionary origin as an ancestral pair of autosomes. In humans, they share 3 regions of high-sequence identity (∼98–100%), which, along with the unique transmission patterns of the sex chromosomes, introduce technical artifacts in genomic analyses. However, the human X chromosome bears numerous important genes, including more “immune response” genes than any other chromosome, which makes its exclusion irresponsible when sex differences across human diseases are widespread. To better characterize the possible effect of the inclusion/exclusion of the X chromosome on variants called, we conducted a pilot study on the Terra cloud platform to replicate a subset of standard genomic practices using both the CHM13 reference genome and the sex chromosome complement-aware reference genome. We compared the quality of variant calling, expression quantification, and allele-specific expression using these 2 reference genome versions across 50 human samples from the Genotype-Tissue Expression consortium annotated as females. We found that after correction, the whole X chromosome (100%) can generate reliable variant calls, allowing for the inclusion of the whole genome in human genomics analyses as a departure from the status quo of omitting the sex chromosomes from empirical and clinical genomics studies.
Understanding how whānau-centred initiatives can improve Māori health in Aotearoa New Zealand
Authors: Reweti Angelique
Published: July 2023

This article highlights the significance of prioritizing Indigenous voices and knowledge systems, using whānau-centred initiatives (a concept that encompasses the broader family and community) as a foundation for health promotion within an Indigenous context. Tū Kahikatea, a conceptual framework, is used to demonstrate the relationship between the values underpinning different whānau-centred initiatives and their corresponding outcomes. The framework highlights the capacity of whānau-centred initiatives to support whānau in attaining mana motuhake, which represents collective self-determination and the ability to exercise control over their own future. By doing so, these initiatives contribute to the improvement of whānau health outcomes. With recent changes to Aotearoa New Zealand’s health system, the findings underscore the benefits and potential of whānau-centred initiatives in enhancing whānau health outcomes, and advocate for continued strengths-based practices in Aotearoa New Zealand’s health system. By bridging the gap between academia and grassroots community action, the article demonstrates the potential of whānau-centred initiatives and contributes to a global call for integrating Indigenous viewpoints and practices into Westernized healthcare, in order to improve Indigenous health outcomes.
Variable exposure to multiple climate stressors across the California marine protected area network and policy implications
Authors: Hamilton S L , Kennedy E G , Zulian M , Hill T M , Gaylord B , Sanford E , Ricart A M , Ward M , Spalding A K , Kroeker K
Published: July 2023

The efficacy of marine protected areas (MPAs) may be reduced when climate change disrupts the ecosystems and human communities around which they are designed. The effects of ocean warming on MPA functioning have received attention but less is known about how multiple climatic stressors may influence MPAs efficacy. Using a novel dataset incorporating 8.8 million oceanographic observations, we assess exposure to potentially stressful temperatures, dissolved oxygen concentrations, and pH levels across the California MPA network. This dataset covers more than two-thirds of California’s 124 MPAs and multiple biogeographic domains. However, spatial-temporal and methodological patchiness constrains the extent to which systematic evaluation of exposure is possible across the network. Across a set of nine well-monitored MPAs, the most frequently observed combination of stressful conditions was hypoxic conditions (<140 umol/kg) co-occurring with low pH (<7.75). Conversely, MPAs exposed most frequently to anomalously warm conditions were less likely to experience hypoxia and low pH, although exposure to hypoxia varied throughout the 2014–2016 marine heatwaves. Finally, we found that the spatial patterns of exposure to hypoxia and low pH across the MPA network remained stable across years. This multiple stressor analysis both confirms and challenges prior hypotheses regarding MPA efficacy under global environmental change.
Decadal characteristics of small-scale fishing livelihoods in 13 Pacific Island Countries and Territories
Authors: Roscher M B , Eriksson H , Sharp M , Menaouer O , Andrew N
Published: July 2023

Small-scale fisheries are cornerstones of wealth, food, and tradition for people throughout the Pacific region. Yet, their governance is plagued by a lack of relevant data. Using data collected from household income and expenditure surveys carried out in 13 Pacific Island Countries and Territories over the last decade, we bring enhanced resolution to these fisheries by describing how households engage in small-scale fishing and accounting the income generated from these activities. We find most households do not actively participate in fishing, and most that do, fish only for subsistence. Over time, however, the rates at which households participate in fishing may be declining. Further, the total income generated through aquatic foods caught for subsistence is nearly double that of foods caught for sale, but on a per household basis fishing for commercial purposes is more lucrative. Differences point to important distinctions in how households engage with and generate income from commercial and subsistence fishing, including where activities are often conducted, and the types of aquatic foods targeted. These distinctions have implications for how livelihoods-focused policies and programmes can be developed to ensure aquatic food systems continue to support Pacific Island communities as the deadline for the Sustainable Development Goals approaches.
Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study
Authors: Razaz Neda , Cnattingius Sven , Lisonkova Sarka , Nematollahi Shahrzad , Oskoui Maryam , Joseph K S , Kramer Michael
Published: July 2023

Background

Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown.

Methods

Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs.

Results

A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00–6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants.

Conclusions

Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.
A Synthetic External Control Study Comparing the Clinical Efficacy of Wendan Decoction and 19 Antidepressants
Authors: Yang Yuting , Chen Rui , Li Caixia , Zheng Qingshan , Lv Yinghua , Li Lujin , Tan Hongsheng
Published: July 2023

Background

Wendan decoction (WDD) has been used as a treatment for depression in China since the Tang Dynasty. However, high-quality evidence for this is lacking. This study proposed a novel synthetic external control method to evaluate its clinical efficacy.

Methods

We searched public databases for clinical trials of WDD for major depression. The rate of change of the Hamilton Depression Scale score from baseline was used as an efficacy indicator, and a model-based meta-analysis was performed to analyze the clinical efficacy of WDD. To establish a reference standard for efficacy, the antidepressant efficacy distributions of a placebo and 19 antidepressants were virtually synthesized based on the same conditions as the clinical trial characteristics of WDD.

Results

This study included 5 clinical trials with 177 participants. WDD showed a slow onset, with a time to reach the maximum effect of 9.71 weeks. At 8 weeks, the rate of change in the Hamilton Depression Scale score from baseline was 66.4% (95% CI = 62.3%–70.3%) in the WDD group. The pure effect value of WDD, after deducting the placebo effect, was 26.9% (95%CI = 23.0%–30.9%), which was comparable with 5 types of antidepressants and significantly higher than the others.

Conclusion

The proposed external synthetic control method provides a solution to the bottleneck problem of clinical efficacy evaluation in real-world research on traditional Chinese medicine. WDD has high clinical development value for the treatment of depression, and large-scale randomized controlled trials are recommended to confirm its antidepressant effect.
Mammography Information Systems: A Survey of Breast Imaging Radiologist Satisfaction and Perspectives
Authors: Mullen Lisa A , Ambinder Emily B , Talati Nishi , Margolies Laurie R
Published: July 2023

Objective

To assess use of mammography information systems (MISs) and explore features associated with breast imaging radiologist satisfaction.

Methods

A 22-question survey regarding MISs was distributed electronically to the Society of Breast Imaging membership between February 16, 2022 and June 28, 2022. Differences in responses between respondents satisfied and dissatisfied with their MIS were analyzed using Pearson chi-squared test, Fisher exact test, and multivariate logistic regression.

Results

The response rate was 11.4% (228/2007). Most respondents used a commercial MIS (195/228, 85.5%). Most used were Epic (47/228, 21%), MagView (47/228, 21%), and PenRad (37/228, 16%). Only 4.4% (10/228) reported that patient tracking was not integrated with results reporting. The majority (129/226, 57%) reported satisfaction with their MIS. Satisfaction correlated (P < 0.05) with features such as picture archiving and communication system integration, structured reporting, access to physician outcomes metrics, and ability to query data. Less commonly reported features such as non-English language options and recognition of laterality and patient mismatch errors also correlated with satisfaction. Lack of these features correlated with dissatisfaction (P < 0.05). Satisfaction also correlated with adequate training (P < 0.001) and technology support (P < 0.001). On multivariate analysis, longer time using the current MIS was independently associated with satisfaction.

Conclusion

Most respondents used a commercial MIS and were satisfied with their system. Satisfied users reported several helpful MIS features and adequate training and support. The survey results could help MIS companies when designing new products and inform radiologists and administrators when considering a new MIS.
A modified smell agent optimization for global optimization and industrial engineering design problems
Authors: Wang Shuang , Hussien Abdelazim G , Kumar Sumit , AlShourbaji Ibrahim , Hashim Fatma A
Published: July 2023

This paper introduces an Improved Smell Agent Optimization Algorithm (mSAO), a new and enhanced metaheuristic designed to tackle complex engineering optimization issues by overcoming the shortcomings of the recently introduced Smell Agent Optimization Algorithm. The proposed mSAO incorporates the jellyfish swarm active–passive mechanism and novel random operator in the elementary SAO. The objective of modification is to improve the global convergence speed, exploration–exploitation behaviour, and performance of SAO, as well as provide a problem-free method of global optimization. For numerical validation, the mSAO is examined using 29 IEEE benchmarks with varying degrees of dimensionality, and the findings are contrasted with those of its basic version and numerous renowned recently developed metaheuristics. To measure the viability of the mSAO algorithm for real-world applications, the algorithm was employed to solve to resolve eight challenges drawn from real-world scenarios including cantilever beam design, multi-product batch plant, industrial refrigeration system, pressure vessel design, speed reducer design, tension/compression spring, and three-bar truss problem. The computational analysis demonstrates the robustness of mSAO relatively in finding optimal solutions for mechanical, civil, and industrial design problems. Experimental results show that the suggested modifications lead to an improvement in solution quality by 10–20% of basic SAO while solving constraint benchmarks and engineering problems. Additionally, it contributes to avoiding local optimal stuck, and premature convergence limitations of SAO and simultaneously.
Impacts of black soldier fly, (Diptera: Stratiomyidae) larval frass on tomato production
Authors: Chavez Maria Y , Uchanski Mark , Tomberlin Jeffery K
Published: July 2023

The “insects as food and feed” movement is gaining considerable momentum as a novel means to provide protein to people (i.e., food) and other animals (i.e., feed). Insects require significantly fewer resources, such as water and land, to produce, process, and distribute as a food or feed source. While the production of insect biomass has received considerable attention for use as food or feed, little is known about the value of the residual materials remaining after digestion. One insect, the black soldier fly, Hermetia illucens (L.) (Diptera: Stratiomyidae), can generate large quantities of residual (i.e., frass) that is high in nitrogen, phosphorus, and potassium. These materials could serve as a partial replacement for fertilizer or peat, thus creating added value to the insects as food and feed sector. Greenhouse studies were designed to investigate the use of frass in vegetable production. In pot studies with tomatoes, different ratios of peat:vermicompost and peat:insect frass were compared to a 100% peat control. Across all other parameters, tomato fruits and vegetative biomass did not produce significant differences across treatments, indicating results were comparable to the control (i.e., 100% peat). Thus, replacing peat with black soldier fly frass is a viable option and could allow for the peat industry to become more sustainable and regenerative. However, it should be noted that average individual tomato fruit weight was significantly (P < 0.05) higher (by 19%) in the vermicompost 10% treatment compared to the control, which did not differ from treatments including black soldier fly frass.
Salvage percutaneous coronary intervention for failed graft itself three days after minimally invasive direct coronary artery bypass
Authors: Narita Masahiko , Kunioka Shingo , Kitani Yuya , Shirasaka Tomonori , Takeuchi Toshiharu , Kamiya Hiroyuki
Published: July 2023

Minimally invasive direct coronary artery bypass is preferred due to its less invasive nature; however, it carries the risk of graft failure owing to inherent technical challenges. We present a case where minimally invasive direct coronary artery bypass grafting was performed and graft failure was detected via coronary angiography 3 days post-operation. Successful percutaneous coronary intervention was subsequently performed on the failed graft itself to salvage myocardial cellular damage. Consequently, the combination of minimally invasive direct coronary artery bypass and percutaneous coronary intervention, both less-invasive revascularization approaches, effectively achieved the primary treatment objective.
Invasive pulmonary aspergillosis real-world outcomes: Clinical features and risk factors associated with increased mortality
Authors: Henao-Martínez Andrés F , Corbisiero Michaele Francesco , Salter Ixchel , Chastain Daniel B , Thompson George R
Published: July 2023

Invasive pulmonary aspergillosis (IPA) is a severe fungal infection that primarily affects immunocompromised patients and is associated with high mortality. Contemporary clinical characteristics of IPA and "real-world" estimates and predictors of associated mortality are inadequate. TriNetX, a global research network, was queried to identify adult patients with IPA diagnoses based on the ICD-10 code B44.0. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 1 year. We identified 4371 patients with IPA. We found neoplasms, solid organ transplant recipients, hematologic malignancies, and aplastic anemia as the most predominant risk factors. The overall 1-year mortality was 32% for IPA. 1-year mortality was highest for patients with COVID-19 in the ICU, followed by those with acute myeloid leukemia and aplastic anemia (54%, 50%, and 39%, respectively). After propensity score matching, severe sepsis, pleural effusion, and candidiasis were mortality contributors within a year after diagnosis. Liver injury, systemic glucocorticoid exposure over the previous 6 months, lower lymphocyte and CD4 counts, elevated ferritin, LDH, thrombocytopenia, anemia, or elevated glycosylated hemoglobin (HbA1c) were independent predictors of mortality at 1 year. Voriconazole was the most common treatment (67%). The annual incidence of IPA was 0.001%, increasing to 0.02% among critically ill patients in the ICU. IPA continues to have a very high mortality. We encourage prospective studies to validate and refine the identified clinical markers linked to increased mortality.
A candidate of binary black hole system in AGN with broad Balmer emission lines having quite different line widths
Authors: Zhang XueGuang
Published: July 2023

In this paper, a candidate of sub-pc binary black hole (BBH) system is reported in SDSS J1257+2023 through different properties of broad Balmer emission lines. After subtractions of host galaxy contributions, Gaussian functions are applied to measure emission lines in SDSS J1257+2023, leading line width (second moment) 760 km s−1 of broad H β to be 0.69 times of line width 1100 km s−1 of broad H α, quite different from normal line width ratio 1.1 of broad H β to broad H α in quasars. The quite broader component in broad H α in SDSS J1257+2023 can be confirmed with confidence level higher than 5σ through F-test technique, through different model functions applied to measure emission lines. The broad Balmer emission lines having different line widths can be naturally explained by a BBH system with different obscurations on central two independent broad emission line regions. Meanwhile, through Zwicky Transient Facility (ZTF) light curves and corresponding phase folded light curves well described by sinusoidal function, BBH system expected optical quasi-periodic oscillations (QPOs) can be detected with periodicity about 1000 d, confirmed with confidence level higher than 3σ by generalized Lomb–Scargle periodogram. And through Continuous AutoRegressive process simulated light curves, confidence level higher than 2σ can be determined to support the optical QPOs in SDSS J1257+2023 not from intrinsic AGN activities, although the ZTF light curves have short time durations. Moreover, through oversimplified BBH system simulated results, studying different broad Balmer lines as signs of BBH systems in normal quasars with flux ratios around 4 of broad H α to broad H β could be done in near future.
Unraveling Prevalence and Effects of Deleterious Mutations in Maize Elite Lines across Decades of Modern Breeding
Authors: Sun Shichao , Wang Baobao , Li Changyu , Xu Gen , Yang Jinliang , Hufford Matthew B , Ross-Ibarra Jeffrey , Wang Haiyang , Wang Li
Published: July 2023

Future breeding is likely to involve the detection and removal of deleterious alleles, which are mutations that negatively affect crop fitness. However, little is known about the prevalence of such mutations and their effects on phenotypic traits in the context of modern crop breeding. To address this, we examined the number and frequency of deleterious mutations in 350 elite maize inbred lines developed over the past few decades in China and the United States. Our findings reveal an accumulation of weakly deleterious mutations and a decrease in strongly deleterious mutations, indicating the dominant effects of genetic drift and purifying selection for the two types of mutations, respectively. We also discovered that slightly deleterious mutations, when at lower frequencies, were more likely to be heterozygous in the developed hybrids. This is consistent with complementation as a potential explanation for heterosis. Subsequently, we found that deleterious mutations accounted for more of the variation in phenotypic traits than nondeleterious mutations with matched minor allele frequencies, especially for traits related to leaf angle and flowering time. Moreover, we detected fewer deleterious mutations in the promoter and gene body regions of differentially expressed genes across breeding eras than in nondifferentially expressed genes. Overall, our results provide a comprehensive assessment of the prevalence and impact of deleterious mutations in modern maize breeding and establish a useful baseline for future maize improvement efforts.
BLM helicase protein negatively regulates stress granule formation through unwinding RNA G-quadruplex structures
Authors: Danino Yehuda M , Molitor Lena , Rosenbaum-Cohen Tamar , Kaiser Sebastian , Cohen Yahel , Porat Ziv , Marmor-Kollet Hagai , Katina Corine , Savidor Alon , Rotkopf Ron , Ben-Isaac Eyal , Golani Ofra , Levin Yishai , Monchaud David , Hickson Ian D , Hornstein Eran
Published: July 2023

Bloom's syndrome (BLM) protein is a known nuclear helicase that is able to unwind DNA secondary structures such as G-quadruplexes (G4s). However, its role in the regulation of cytoplasmic processes that involve RNA G-quadruplexes (rG4s) has not been previously studied. Here, we demonstrate that BLM is recruited to stress granules (SGs), which are cytoplasmic biomolecular condensates composed of RNAs and RNA-binding proteins. BLM is enriched in SGs upon different stress conditions and in an rG4-dependent manner. Also, we show that BLM unwinds rG4s and acts as a negative regulator of SG formation. Altogether, our data expand the cellular activity of BLM and shed light on the function that helicases play in the dynamics of biomolecular condensates.
CRISPR interference screens reveal growth–robustness tradeoffs inSynechocystissp. PCC 6803 across growth conditions
Authors: Miao Rui , Jahn Michael , Shabestary Kiyan , Peltier Gilles , Hudson Elton P
Published: July 2023

Barcoded mutant libraries are a powerful tool for elucidating gene function in microbes, particularly when screened in multiple growth conditions. Here, we screened a pooled CRISPR interference library of the model cyanobacterium Synechocystis sp. PCC 6803 in 11 bioreactor-controlled conditions, spanning multiple light regimes and carbon sources. This gene repression library contained 21,705 individual mutants with high redundancy over all open reading frames and noncoding RNAs. Comparison of the derived gene fitness scores revealed multiple instances of gene repression being beneficial in 1 condition while generally detrimental in others, particularly for genes within light harvesting and conversion, such as antennae components at high light and PSII subunits during photoheterotrophy. Suboptimal regulation of such genes likely represents a tradeoff of reduced growth speed for enhanced robustness to perturbation. The extensive data set assigns condition-specific importance to many previously unannotated genes and suggests additional functions for central metabolic enzymes. Phosphoribulokinase, glyceraldehyde-3-phosphate dehydrogenase, and the small protein CP12 were critical for mixotrophy and photoheterotrophy, which implicates the ternary complex as important for redirecting metabolic flux in these conditions in addition to inactivation of the Calvin cycle in the dark. To predict the potency of sgRNA sequences, we applied machine learning on sgRNA sequences and gene repression data, which showed the importance of C enrichment and T depletion proximal to the PAM site. Fitness data for all genes in all conditions are compiled in an interactive web application.
Use of extended reality in sleep health, medicine, and research: a scoping review
Authors: Goldsworthy Adrian , Chawla Jasneek , Birt James , Baumann Oliver , Gough Suzanne
Published: July 2023

Study Objectives

This scoping review explores the use of extended reality (virtual, augmented, and mixed reality) within sleep health, sleep medicine, and sleep research. It aims to provide insight into current uses and implementation considerations whilst highlighting directions for future research.

Methods

A systematic scoping review was undertaken informed by the preferred reporting items for systematic reviews and meta-analyses for scoping reviews and Johanna Briggs Institute.

Results

The use of virtual reality (VR) as a research tool in the investigation of areas such as dreaming and memory reactivation is growing. Thirty-one articles were identified in total with 20 utilizing VR to improve sleep as a clinical intervention.

Conclusions

Research exploring the utility of VR as a clinical intervention in various patient populations and clinical settings is therefore warranted. Researchers and clinicians should ensure that extended reality interventions are developed based on clinical reasoning and informed by evidence of both sleep medicine and the effects of virtual and augmented reality. Where possible future research should utilize up-to-date technology and reporting frameworks to assist in the translation of research into clinical practice.
Tbx2 knockdown alleviated sevoflurane-induced cognitive disorder and neuron damages in aged rats via suppressing oxidative stress and ferroptosis
Authors: Xu Ying , Wang Xueting , Xu Ziyang , Sun Fengwei , Tian Yue
Published: July 2023

Anesthesia with sevoflurane contributes to perioperative neurocognitive disorder (PND), which is characterized by the deficiency in study and memory. T-Box transcription factor 2 (Tbx2), which is involved in the development of hippocampus neurons, was upregulated in the hippocampus of rats exposed to sevoflurane. Our study aimed to explore the role of Tbx2 in sevoflurane-induced cognitive disorder and hippocampus neuron damages. The expression of Tbx2 in hippocampus was upregulated after sevoflurane exposure, which was accompanied by the accumulation of reactive oxygen species and lipid peroxidation, as well as the loss of neurons in hippocampus. In vitro, silencing Tbx2 suppressed oxidative stress and ferroptosis induced by sevoflurane, whereas exogenous overexpression of Tbx2 exacerbated these processes. Importantly, Tbx2 knockdown improved sevoflurane-induced cognitive disorder in aged rats, as evidenced by the increases in behavioral indexes. Mechanistically, the expression of brain-derived neurotrophic factor (BDNF), as well as the downstream nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, was repressed by Tbx2. Mimicking the activation of BDNF with 7,8-dihydroxyflavone rescued the effects of Tbx2 overexpression on oxidative stress and ferroptosis in vitro, indicating that the BDNF/Nrf2/HO-1 signaling may mediate the role of Tbx2 in sevoflurane-induced cognitive disorder and neuron damages. In summary, Tbx2 may contribute to neuronal damages via enhancing the oxidative stress and ferroptosis caused by sevoflurane. BDNF/Nrf2/HO-1 signaling mediates the role of Tbx2 in sevoflurane-induced cognitive disorder. Knockdown of Tbx2 improves sevoflurane-induced cognitive impairment. Our finding provides a novel insight for PND treatment.
A mnemonic for managing acute exacerbations of chronic obstructive pulmonary disease
Authors: El Hussein Mohamed Toufic , Favell Daniel
Published: July 2023

Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory disorders in the world. Pharmacologic management of an acute exacerbation of COPD can be guided by the mnemonic ABC, for Antibiotics and anticholinergics, Beta2 adrenergic agonists, and Combination therapies and corticosteroids.
Post-Fasciotomy Classification System for Acute Compartment Syndrome of the Leg
Authors: Bouklouch Yasser , Bernstein Mitchell , Bosse Michael , Cota Adam , Duckworth Andrew D , Dunbar Robert P , Gamulin Axel , Guy Pierre , Hak David J , Haller Justin M , Hayda Roman , Jarragh Ali , Johnstone Alan J , Karunakar Madhav , Lawendy Abdel-Rahman , Leighton Ross , Mavrogenis Andreas F , Mauffrey Cyril , Miclau Theodore , Obremskey William T , Renninger Chris , Sanders David W , Schmidt Andrew H , Schneider Prism , Sen Milan K , Taitsman Lisa , Van Lancker Hans , Harvey Edward J
Published: July 2023

Objective:

Acute compartment syndrome (ACS) is a true emergency. Even with urgent fasciotomy there is often muscle damage and need for further surgery. Although ACS is not uncommon, no validated classification system exists to aid in efficient and clear communication. The aim of this study was to establish and validate a classification system for the consequences of ACS treated with fasciotomy.

Methods:

Using a modified Delphi method, an international panel of ACS experts was assembled to both establish a grading scheme for the disease and then validate the classification system. The goal was to articulate discrete grades of ACS related to fasciotomy findings and associated costs. A pilot analysis was used to determine questions that were clear to the respondents. Discussion of this analysis resulted in another round of cases used for 24 other raters. The twenty-four individuals implemented the classification system two separate times to compare outcomes for 32 clinical cases. The accuracy and reproducibility of the classification system were subsequently calculated based on the providers' responses.

Results:

The Fleiss’ Kappa of all raters was at 0.711 showing a strong agreement between the 24 raters. Secondary validation was performed for paired 276 raters and correlation was tested using the Kendall coefficient. The median correlation coefficient was 0.855. All 276 pairs had statistically significant correlation. Correlation coefficient between the first and second rating sessions was strong with the median pair scoring at 0.867. All surgeons had statistically significant internal consistency.

Conclusion:

This new ACS classification system may be applied to better understand the impact of ACS on patient outcomes and economic costs for leg ACS.

Level of Evidence:

Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Regulation of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Abdominal Aortic Aneurysm
Authors: Wang Shuo , Liu Dan , Zhang Xiaolin , Tian Xiaoxiang
Published: July 2023

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by destruction and progressive expansion of the abdominal aortic wall. An AAA is typically defined as an enlargement of the abdominal aorta with diameter ≥3 cm or ≥50% greater than the suprarenal diameter. The pathological changes associated with AAA include inflammatory cell infiltration, extracellular matrix (ECM) destruction and remodeling, and vascular smooth muscle cell loss. The matrix metalloproteinase (MMP) family of proteins plays an important role in initiation and progression of AAA. Since understanding the regulation of MMP-2 and MMP-9 in AAA is essential for treatment of AAA, this review summarized the regulatory mechanisms of MMPs to provide a reference for exploring novel therapeutic approaches.
Risk for Developmental Delay Among Infants Born During the COVID-19 Pandemic
Authors: Giesbrecht Gerald F. , Lebel Catherine , Dennis Cindy-Lee , Silang Katherine , Xie E. Bailin , Tough Suzanne , McDonald Sheila , Tomfohr-Madsen Lianne
Published: July 2023

Objective:

Attempts by governments around the world to mitigate the spread of COVID-19 have substantially altered the early rearing environment, raising concerns about potential negative consequences for babies born during this time. The objective of this study was to determine whether infants born during the COVID-19 pandemic were at greater risk of screening positive for developmental delay compared with infants born before the pandemic.

Methods:

Participants were from 2 longitudinal cohorts. The prepandemic cohort, Impact of Maternal and Paternal Postpartum Depression, recruited postpartum individuals in the period between 2015 and 2018. Infant development milestone data (Ages and Stages Questionnaire [ASQ-3]) were collected at 1-year postpartum (n = 2903), between 2016 and 2019. The pandemic cohort, Pregnancy during the Pandemic, recruited pregnant individuals between April 2020 and April 2021. Infant development milestone data (ASQ-3) were collected at 1-year postpartum (n = 3742), between May 2021 and December 2022. Sociodemographic information, pregnancy outcomes, and depression symptom data were also collected.

Results:

In covariate-adjusted analyses, pandemic-born infants had lower mean scores and higher odds of screening positive for delay on the Communication, Gross Motor, and Personal-Social domains of the ASQ-3 compared with prepandemic infants. Sex differences showed that males and females screened “at risk” in different domains.

Conclusion:

Most pandemic-born infants display typical development, and differences between prepandemic and pandemic-born infants were small. Nevertheless, an increased risk for delayed development among pandemic-born infants suggests the need for ongoing monitoring to determine what, if any, resources and interventions are needed to support healthy child development.
Two Types of Variational Artery’s Course from the Superior Mesenteric Artery to Supply the Splenic Flexure: Gross Anatomical Study
Authors: Okazaki Tomokazu , Omotehara Takuya , Kawata Shinichi , Amano Takahiro , Enomoto Masanobu , Nagakawa Yuichi , Itoh Masahiro
Published: July 2023

BACKGROUND:

Complete mesocolic excision with central vascular ligation is a standard method for colon cancer. However, there is no consensus on its procedure, especially for cancer in the splenic flexure of the transverse colon. This is because various types of variational arteries are distributed to the region, and their running course below and near the pancreas leads to difficulty in ligating the artery.

OBJECTIVE:

This study aimed to clarify the arterial distribution to the SF of the transverse colon using cadavers.

DESIGN:

The arteries in the transverse mesocolon distributed to the colon were dissected in cadavers, and their route was quantitatively visualized using drawing software.

SETTINGS:

This study was conducted at the Department of Anatomy, Tokyo Medical University.

PATIENTS:

Sixty cadavers donated to Tokyo Medical University in 2017–2021 were used.

MAIN OUTCOME MEASURES:

The arterial courses to the splenic flexure of the transverse colon in the mesocolon and their patterns were evaluated.

RESULTS:

We found 34 variational arteries distributed to the splenic flexure of the transverse colon. Most originated from the superior mesenteric artery and middle colic artery, with their typical course below the pancreas. We identified another arterial course, crossing the mesocolon away from the pancreas toward the splenic flexure of the transverse colon. Furthermore, the origin of these arteries was not behind the pancreas and can be found in the caudal region of the pancreas.

LIMITATIONS:

We cannot discuss how the arteries within the transverse mesocolon are observed by computed tomography examination.

CONCLUSIONS:

This study showed two types of arterial courses (below the pancreas and within the mesocolon) toward the splenic flexure of the transverse colon for the first time. In the latter case, the complete mesocolic excision with central vascular ligation is likely performed more easily than in the former.