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Objectives This study aims to understand the statistical significance of the associations between diagnoses and symptoms based on simulations that have been used to understand the interpretability of mental illness diagnoses. Methods The symptoms for the diagnosis of major depressive episodes, dysthymic disorder, and manic episodes were extracted from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR, American Psychiatric Association, Philadelphia, Pennsylvania). Without real-world symptom data, we simulated populations using various combinations of symptom prevalence and correlations. Assuming symptoms occurred with similar prevalence and correlations, for each combination of symptom prevalence (0.05, 0.1, 0.3, 0.5, and 0.7) and correlation (0, 0.1, 0.4, 0.7, and 0.9), 100 cohorts with 10,000 individuals were randomly created. Diagnoses were made according to the DSM-IV-TR criteria. The associations between the diagnoses and their input symptoms were quantified with odds ratios and correlation coefficients. P-values from 100 cohorts for each combination of symptom prevalence and correlation were summarized. Results Three mental illness diagnoses were not significantly correlated with their own symptoms in all simulations, particularly when symptoms were not correlated, except for the symptom in the major criteria of major depressive episodes or dysthymic disorder. The symptoms for the diagnosis of major depressive episodes and dysthymic disorder were significantly correlated with these two diagnoses in some simulations, assuming 0.1, 0.4, 0.7, or 0.9 symptom correlations, except for one symptom. The overlap in the input symptoms for the diagnosis of major depressive episodes and dysthymic disorder also leads to significant correlations between these two diagnoses, assuming 0.1, 0.4, 0.7, and 0.9 correlations between input symptoms. Manic episodes are not significantly associated with the input symptoms of major depressive episodes and dysthymic disorder. Conclusion There are challenges to establish the causation between psychiatric symptoms and mental illness diagnoses. There is insufficient prevalence and incidence data to show all psychiatric symptoms exist or can be observed in patients. The diagnostic accuracy of symptoms to detect a disease cause is far from perfect. Assuming the symptoms of three mood disorders may present in patients, three diagnoses are not significantly associated with all psychiatric symptoms used to diagnose them. The diagnostic criteria of the three diagnoses have not been designed to guarantee significant associations between symptoms and diagnoses. Because statistical associations are important for making causal inferences, there may be a lack of causation between diagnoses and symptoms. Previous research has identified factors that lead to insignificant associations between diagnoses and symptoms, including biases due to data processing and a lack of epidemiological evidence to support the design of mental illness diagnostic criteria., Competing Interests: YSC is employed by the Canadian Agency for Drugs and Technologies in Health. YSC conducted this study as an independent researcher out of academic curiosity without any material support. The other authors declared no competing interests. No external funding was received for this study. This study is not associated with any patents, products in development or marketed products., (Copyright © 2024, Chao et al.)

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion ( p = 0.033) and abduction ( p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) ( p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 ( p = 0.042) and S100A9 ( p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

MuRF1 (Muscle-specific RING finger protein 1; gene name TRIM63) is a ubiquitin E3 ligase, associated with the progression of muscle atrophy. As a RING (Really Interesting New Gene) type E3 ligase, its unique activity of ubiquitylation is driven by a specific interaction with a UBE2 (ubiquitin conjugating enzyme). Our understanding of MuRF1 function remains unclear as candidate UBE2s have not been fully elucidated. In the present study, we screened human ubiquitin dependent UBE2s in vitro and found that MuRF1 engages in ubiquitylation with UBE2D, UBE2E, UBE2N/V families and UBE2W. MuRF1 can cause mono-ubiquitylation, K48- and K63-linked polyubiquitin chains in a UBE2 dependent manner. Moreover, we identified a two-step UBE2 dependent mechanism whereby MuRF1 is monoubiquitylated by UBE2W which acts as an anchor for UBE2N/V to generate polyubiquitin chains. With the in vitro ubiquitylation assay, we also found that MuRF2 and MuRF3 not only share the same UBE2 partners as MuRF1 but can also directly ubiquitylate the same substrates: Titin (A168-A170), Desmin, and MYLPF (Myosin Light Chain, Phosphorylatable, Fast Skeletal Muscle; also called Myosin Light Regulatory Chain 2). In summary, our work presents new insights into the mechanisms that underpin MuRF1 activity and reveals overlap in MuRF-induced ubiquitylation which could explain their partial redundancy in vivo., Competing Interests: We declare no conflicts of interest, financial or otherwise., (© 2024 The Authors.)

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

In an ecosystem, environmental changes as a result of natural and human processes can cause some key parameters of the system to change with time. Depending on how fast such a parameter changes, a tipping point can occur. Existing works on rate-induced tipping, or R-tipping, offered a theoretical way to study this phenomenon but from a local dynamical point of view, revealing, e.g., the existence of a critical rate for some specific initial condition above which a tipping point will occur. As ecosystems are subject to constant disturbances and can drift away from their equilibrium point, it is necessary to study R-tipping from a global perspective in terms of the initial conditions in the entire relevant phase space region. In particular, we introduce the notion of the probability of R-tipping defined for initial conditions taken from the whole relevant phase space. Using a number of real-world, complex mutualistic networks as a paradigm, we find a scaling law between this probability and the rate of parameter change and provide a geometric theory to explain the law. The real-world implication is that even a slow parameter change can lead to a system collapse with catastrophic consequences. In fact, to mitigate the environmental changes by merely slowing down the parameter drift may not always be effective: Only when the rate of parameter change is reduced to practically zero would the tipping be avoided. Our global dynamics approach offers a more complete and physically meaningful way to understand the important phenomenon of R-tipping., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly., Methods: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing ( n = 79) and testing ( n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant., Results: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage., Conclusions: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Carbapenem-resistant ST11&#95;KL64 Klebsiella pneumoniae emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 as the sole carbapenemase. In this study, we employed whole-genome sequencing to investigate the molecular underpinnings of ST11&#95;KL64 isolates collected from 2013 to 2021. Phylogenomic analysis revealed a notable genetic divergence between the ST11&#95;KL64 strains in Taiwan and those in China, suggesting an independent evolutionary trajectory. Our findings indicated that the ST11&#95;KL64&#95;Taiwan lineage originated from the ST11&#95;KL64 lineage in Brazil, with recombination events leading to the integration of ICE Kp11 and a 27-kb fragment at the tRNA ASN sites, shaping its unique genomic landscape. To further elucidate this unique sublineage, we examined the plasmid contents. In contrast to ST11&#95;KL64&#95;Brazil strains, which predominantly carried bla KPC-2 , ST11&#95;KL64&#95;Taiwan strains exhibited the acquisition of an epidemic bla OXA-48 -carrying IncL plasmid. Additionally, ST11&#95;KL64&#95;Taiwan strains consistently harbored a multi-drug resistance IncC plasmid, along with a collection of gene clusters that conferred resistance to heavy metals and the phage shock protein system via various Inc-type plasmids. Although few, there were still rare ST11&#95;KL64&#95;Taiwan strains that have evolved into hypervirulent CRKP through the horizontal acquisition of pLVPK variants. Comprehensive characterization of the high-risk ST11&#95;KL64 lineage in Taiwan not only sheds light on its epidemic success but also provides essential data for ongoing surveillance efforts aimed at tracking the spread and evolution of ST11&#95;KL64 across different geographical regions. Understanding the molecular underpinnings of CRKP evolution is crucial for developing effective strategies to combat its emergence and dissemination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wang, Chen, Tang, Chen, Teng, Chiou, Lu and Lai.)

Introduction: This study aimed to investigate the determinants of cancer incidence and mortality in patients with vitamin D deficiency using a real-world population database., Methods: We utilized the International Diagnostic Classification Code (ICD9:268 / ICD10: E55) to define patients with vitamin D deficiency. Additionally, the Cox regression model was used to estimate overall mortality and identify potential factors contributing to mortality in cancer patients., Results: In 5242 patients with vitamin D deficiency, the development of new-onset cancer was 229 (4.37%) patients. Colon cancer was the most prevalent cancer type. After considering confounding factors, patients aged 50-65 and more than 65 indicated a 3.10-fold (95% C.I.: 2.12-4.51) and 4.55-fold (95% C.I.: 3.03-6.82) cancer incidence, respectively compared with those aged <50. Moreover, patients with comorbidities of diabetes mellitus (DM) (HR: 1.56; 95% C.I.: 1.01-2.41) and liver disease (HR: 1.62; 95% C.I.: 1.03-2.54) presented a higher cancer incidence rate than those without DM/ liver disease. In addition, vitamin D deficiency patients with cancer and dementia histories indicated a significantly higher mortality risk (HR: 4.04; 95% C.I.: 1.05- 15.56) than those without dementia., Conclusion: In conclusion, our study revealed that vitamin D deficiency patients with liver disease had an increased incidence of cancer, while those with dementia had an increased mortality rate among cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Chen, Liang, Wu, Wang, Lim and Ho.)

Background: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders., Methods: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan., Results: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction., Conclusions: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs., (© 2023. The Author(s).)

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO 2 NPs) in a Caenorhabditis elegans ( C. elegans ) model. The effects of commercially available (C-TiO 2 ) and synthetically (S-TiO 2 ) prepared TiO 2 NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans . Exposure to TiO 2 NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO 2 NP concentration increased. The longevity of the nematodes was shortened following TiO 2 NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO 2 or 10 mg/L S-TiO 2 . It was therefore concluded that compared with S-TiO 2 , C-TiO 2 possibly causes more toxicity or genotoxicity in the C. elegans model.

Purpose: Transmission-target x-ray tubes generate more x-rays than reflection thick-target x-ray tubes. A transmission x-ray tube combined with radiosensitizers has a better radiation enhancement effect. This study investigated the feasibility of using a transmission x-ray tube with radiosensitizers in clinical radiotherapy and its effect on radiation dose enhancement., Methods: This study used MCNP6.2 to simulate the model of a transmission x-ray tube and Co-60 beam.   The radiation enhancement effect of radiosensitizers was examined with iodine-127 (I-127), radioiodinated iododeoxyuridine (IUdR), and gold nanoparticles (GNPs)., Results: The study results showed that the dose enhancement factor (DEF) of the transmission x-ray tube with GNPs was 10.27, which was higher than that of I-127 (6.46) and IUdR (3.08). The DEF of the Co-60 beam with GNPs, I-127, and IUdR was 1.23, 1.19, and 1.2, respectively. The Auger electron flux of the transmission x-ray tube with GNPs was 1.19E+05 particles/cm 2 ., Conclusions: This study found that a transmission x-ray tube with appropriate radiosensitizers could produce a high rate of Auger electrons to fulfill the radiation enhancement effect, and this procedure has the potential to become a radiotherapy modality., (© 2023 American Association of Physicists in Medicine.)

Ingested galactose can enhance postexercise liver glycogen repletion when combined with glucose but effects on muscle glycogen synthesis are unknown. In this double-blind randomized study participants [7 men and 2 women; V̇o 2max : 51.1 (8.7) mL·kg -1 ·min -1 ] completed three trials of exhaustive cycling exercise followed by a 4-h recovery period, during which carbohydrates were ingested at the rate of 1.2 g·kg -1 ·h -1 comprising glucose (GLU), galactose (GAL) or galactose + glucose (GAL + GLU; 1:2 ratio). The increase in vastus lateralis skeletal-muscle glycogen concentration during recovery was higher with GLU relative to GAL + GLU [contrast: +50 mmol·(kg DM) -1 ; 95%CL 10, 89; P = 0.021] and GAL [+46 mmol·(kg DM) -1 ; 95%CL 8, 84; P = 0.024] with no difference between GAL + GLU and GAL [-3 mmol·(kg DM) -1 ; 95%CL -44, 37; P = 0.843]. Plasma glucose concentration in GLU was not significantly different vs. GAL + GLU (+ 0.41 mmol·L -1 ; 95%CL 0.13, 0.94) but was significantly lower than GAL (-0.75 mmol·L -1 ; 95%CL -1.34, -0.17) and also lower in GAL vs. GAL + GLU (-1.16 mmol· -1 ; 95%CL -1.80, -0.53). Plasma insulin was higher in GLU + GAL and GLU compared with GAL but not different between GLU + GAL and GLU. Plasma galactose concentration was higher in GAL compared with GLU (3.35 mmol·L -1 ; 95%CL 3.07, 3.63) and GAL + GLU (3.22 mmol·L -1 ; 95%CL 3.54, 2.90) with no difference between GLU + GAL (0.13 mmol·L -1 ; 95%CL -0.11, 0.37) and GLU. Compared with galactose or a galactose + glucose blend, glucose feeding was more effective in postexercise muscle glycogen synthesis. Comparable muscle glycogen synthesis was observed with galactose-glucose coingestion and exclusive galactose-only ingestion. NEW & NOTEWORTHY Postexercise galactose-glucose coingestion or exclusive galactose-only ingestion resulted in a lower rate of skeletal-muscle glycogen replenishment compared with exclusive glucose-only ingestion. Comparable muscle glycogen synthesis was observed with galactose-glucose coingestion and exclusive galactose-only ingestion.

Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane. Functionally, the spheroid becomes competent morphogenetic units (CMU) that promote regeneration of tissue patterns. The emergence of new cell types and molecular interactions during CMU formation was analyzed using scRNA-sequencing. Surprisingly, in newborn skin explants, IFNr signaling can induce apical-basal polarity in epidermal cell aggregates. Dermal-Tgfb induces basement membrane formation. Meanwhile, VEGF signaling mediates dermal cell attachment to the epidermal cyst shell, thus forming a CMU. Adult mouse and human fetal scalp cells fail to form a CMU but can be restored by adding IFNr or VEGF to achieve hair regeneration. We find different multi-cellular configurations and molecular pathways are used to achieve morphogenetic competence in developing skin, wound-induced hair neogenesis, and reconstituted explant cultures. Thus, multiple paths can be used to achieve tissue patterning. These insights encourage more studies of "in vitro morphogenesis" which may provide novel strategies to enhance regeneration., (© 2023. The Author(s).)

Global warming and pollution could lead to the destruction of marine habitats and loss of species. The anomalous behavior of underwater creatures can be used as a biometer for assessing the health status of our ocean. Advances in behavior recognition have been driven by the active application of deep learning methods, yet many of them render superior accuracy at the cost of high computational complexity and slow inference. This paper presents a real-time anomalous behavior recognition approach that incorporates a lightweight deep learning model (Lite3D), object detection, and multitarget tracking. Lite3D is characterized in threefold: (1) image frames contain only regions of interest (ROI) generated by an object detector; (2) no fully connected layers are needed, the prediction head itself is a flatten layer of 1 × [Formula: see text] @ 1× 1, [Formula: see text]= number of categories; (3) all the convolution kernels are 3D, except the first layer degenerated to 2D. Through the tracking, a sequence of ROI-only frames is subjected to 3D convolutions for stacked feature extraction. Compared to other 3D models, Lite3D is 50 times smaller in size and 57 times lighter in terms of trainable parameters and can achieve 99% of F1-score. Lite3D is ideal for mounting on ROV or AUV to perform real-time edge computing., (© 2023. The Author(s).)

The identification of catalytic RNAs is typically achieved through primarily experimental means. However, only a small fraction of sequence space can be analyzed even with high-throughput techniques. Methods to extrapolate from a limited data set to predict additional ribozyme sequences, particularly in a human-interpretable fashion, could be useful both for designing new functional RNAs and for generating greater understanding about a ribozyme fitness landscape. Using information theory, we express the effects of epistasis (i.e., deviations from additivity) on a ribozyme. This representation was incorporated into a simple model of the epistatic fitness landscape, which identified potentially exploitable combinations of mutations. We used this model to theoretically predict mutants of high activity for a self-aminoacylating ribozyme, identifying potentially active triple and quadruple mutants beyond the experimental data set of single and double mutants. The predictions were validated experimentally, with nine out of nine sequences being accurately predicted to have high activity. This set of sequences included mutants that form a previously unknown evolutionary "bridge" between two ribozyme families that share a common motif. Individual steps in the method could be examined, understood, and guided by a human, combining interpretability and performance in a simple model to predict ribozyme sequences by extrapolation., (© 2023 Charest et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Introduction: Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan., Methods: Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration., Result: The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter ( n  = 36), 0.13 liter ( n  = 32), 0.04 liter ( n  = 26), and - 0.004 liter ( n  = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George's respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study., Conclusion: Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Wei, Chen, Lai, Hu, Hung, Chu, Chuang and Chang.)

The coronavirus pandemic has become an unprecedented world crisis in which we have struggled against the most potent threat of the twenty-first century. This pandemic has had a profound impact on individuals and families. Therefore, the study aimed to examine family communication as a mediator of the relationship between family resilience and family functioning under the quarantine and coronavirus pandemic in Algeria and Iraq. This study was conducted among individuals in Iraq and Algeria (N = 361). The respondents completed the Family Communication Scale (FCS), Walsh Family Resilience Questionnaire (WFRQ), and Family Functioning Scale (FFS). Structural equation modeling (SEM) with the bootstrapping method was used to conduct the mediated effects of family communication. Using the bootstrapping method in SEM, family resilience and communication significantly affected family functioning (coefficient = 0.808). Moreover, the direct effect and indirect effect (via family functioning) of family resilience on family functioning were both significant, with coefficients of 0.682 and 0.126. In addition, numerous groups from Iraq and Algeria have been analyzed as a sample and have shown no differences in the relationships between family resilience, family communication, and family functioning. In conclusion, the results showed that family communication mediated the relationship between family resilience and family functioning. Moreover, the type of this mediation seemed to be partial because of the significant direct relationship between family resilience and family functioning. According to the findings, healthcare providers should consider improving family resilience and communication to achieve good family functioning.

Objectives: This scoping review assessed systematic reviews on noninvasive temporomandibular disorder therapies to identify evidence gaps and formulate clinical recommendations., Method and Materials: The scoping review was conducted according to the PRISMA scoping review guidelines and Joanna Briggs Institute updated scoping review methodology using a two-step process involving four reviewers. Four key databases (Embase, PubMed, Scopus, and Google Scholar) were thoroughly searched from January 2017 to December 2022. The selected systematic reviews were classified, charted, critically appraised, and synthesized., Results: Of the initial 522 listings, 61 systematic reviews were eligible for inclusion, with the majority bearing very low- to low-quality evidence, and meta-analysis not being conducted in about a third of them. Moderate- to high-quality evidence was available for patient self-management, botulinum toxin, manual, laser, and splint therapy., Conclusions: Further high-quality investigations with consistent patient selection, diagnostic criteria, treatment/assessment protocols, and outcome measures are needed to confirm the effectiveness of the various interventions for temporomandibular disorder pain/dysfunction.

The conventional medium chain chlorinated paraffin (MCCP) and zinc dialkyl dithiophosphate (ZDDP) additives have greatly enhanced the extreme pressure (EP) and anti-wear (AW) performance of the metalworking fluids. However, chlorine- and zinc-containing additives are restricted in use due to eco-toxicity issue. Herein, ashless and non-corrosive dimercaptobenzothiadiazole derivatives, namely bis-2,5-benzylsulfanyl-[1,3,4]thiadiazole (BBST) and bis-2,5-octylsulfanyl-[1,3,4]thiadiazole (BOST) consist of three sulfur atoms have been synthesized and evaluated. The performance of BBST shows a weld load ( P D ) of 3089 N and AW value of 5 mm 2 , which represents an improvement of 3.1 and 7.4 folds over naphthenic base oil (NBO). In addition, BBST also outperformed BOST, MCCP, and ZDDP in terms of its weld load and AW properties. Based on XPS analysis and molecular electrostatic potential maps (MEPS), BBST exhibits superior tribology performance due to the interaction between the sulfur (S), nitrogen (N), and π-electrons of the benzene ring with the metal surface. The formation of FeS, Fe 2 O 3 and Fe⋯N coordinate bonds contributes to the creation of an excellent tribofilm., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE)., Methods: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS., Results: We included 91 patients with a median (percentile 25 -percentile 75 ) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001)., Conclusion: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication., Competing Interests: Declaration of Competing Interest M.A.G. was supported by Fundación Alfonso Martín Escudero and the Epilepsy Research Fund. I.S.F. was supported by Fundación Alfonso Martín Escudero, the HHV6 Foundation, and the Epilepsy Research Fund. R.A. receives research support from NIH NINDS R01 NS115929 and Procter Foundation (Procter Scholar Award 2018–2021). C.B.A. was supported by Fundación Alfonso Martín Escudero. J.N.B. has served as a consultant for Novartis. T.A.G. is funded by NIH grants 2U01-NS045911, U10-NS077311, R01-NS053998, R01-NS062756, R01- NS043209, R01-LM011124, and R01-NS065840. He has received consulting fees from Supernus, Sunovion, Eisai, and UCB. He also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medico-legal cases. He receives royalties from a patent license. E.J.N. is a professional advisory board of the Epilepsy Foundation of America and served on Advisory Board for Zogenix. J.J.R. is a member of a data safety monitoring board for GW Pharmaceuticals. His-spouse is an editor for Uptodate. D.T. receives research funding from Children's Miracle Network Hospitals and has previously received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. M.S.W. serves as a scientific consultant and on the clinical advisory board for Sage Pharmaceuticals. A.W. receives research funding from Novartis, Eisai, Pfizer, UCB, Acorda, Lundbeck, GW Pharma, Upsher-Smith, and Zogenix and receives publication royalties from Up to date. T.L. is part of pending patent applications to detect and predict seizures and diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, the Epilepsy Foundation of America Epilepsy Venture Fund (Shark Tank Award), MIKU, and Epitel. He received device donations from Epitel, MIKU, Empatica, and neuroelectrics. In the past, he received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Proximagen, UCB, Mallinckrodt, Pfizer, and Empatica. In the past, he served as a consultant for Engage and Upsher Smith. The remaining authors have no disclosures relevant to this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Background: We describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness., Methods: We retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression., Results: Sixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not., Conclusions: Pediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes., Competing Interests: Declaration of competing interest V.K. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. V.K., A.J.S., T.A.E., J.M.Y., A.A., V.A.H., N.M.S., S.R.R., K.K.M., and K.F. have no financial disclosures or conflicts of interest. T.E.L. has received personal compensation in the range of $5,000 to $9,999 for serving as an Expert Witness for Department of Justice VICP. T.E.L. has received research support from NIH, National MS Society, Sarepta Therapeutics, PTC Therapeutics, and Avexis. T.E.L. has received publishing royalties from a publication relating to health care. J.J.R. has received speaking fees from Wayne State University, Drexel University, and Children's Healthcare of Atlanta. Y.-C.L. has received funding support from the NIH/NINDS and is a member of the Medical and Scientific Advisory Board of the NORSE Institute., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pigeon paramyxovirus-1 (PPMV-1), a genetic variant of avian paramyxovirus-1 (APMV-1), has been identified in Columbiformes and is the primary cause of diseases in captive and free-ranging pigeons. However, it has also been reported that PPMV-1 can infect chickens naturally and experimentally, thus posing a potential threat to the poultry industry. This study investigated a lethal outbreak of paramyxovirus infection that occurred among 16 oriental turtle doves (Streptopelia orientalis) in a walk-in aviary at a zoo from March to April 2021. Necropsies were performed, and histopathological findings revealed mild to moderate lymphoplasmacytic infiltration in several organs, such as the pancreas, liver, kidneys, and lungs. Reverse transcription polymerase chain reaction (RT-PCR) using formalin-fixed paraffin-embedded tissue blocks, virus isolation from fresh tissue, and in situ hybridization against the fusion (F) protein confirmed the diagnosis for PPMV-1 infection. The isolated strain NTU/C239/21 was fully sequenced by next-generation sequencing, and the results of phylogenetic analyses revealed that the F protein of NTU/C239/21 shared 98.8% nucleotide sequence identity with Pigeon/Taiwan/AHRI121/2017, which was isolated from a feral pigeon in Taiwan. The present study is the first to identify PPMV-1 infection in Streptopelia orientalis and suggests that Streptopelia orientalis may also play an important role in spreading the infection, similar to pigeons in APMV-1 spreading., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

People with dementia (PwD) who receive home healthcare (HHC) may have distressing symptoms, complex care needs and high mortality rates. However, there are few studies investigating the determinants of mortality in HHC recipients. To identify end-of-life care needs and tailor individualized care goals, we aim to explore the mortality rate and its determinants among PwD receiving HHC. We conducted a retrospective cohort study using a Taiwanese national population database. People with new dementia diagnosis in 2007-2016 who received HHC were included. We calculated the accumulative mortality rate and applied Poisson regression model to estimate the risk of mortality for each variable (adjusted risk ratios, aRR) with a 95% confidence interval (CI). We included 95,831 PwD and 57,036 (59.5%) of them died during the follow-up period (30.5% died in the first-year). Among comorbidities, cirrhosis was associated with the highest mortality risks (aRR 1.65, 95% CI 1.49-1.83). Among HHC-related factors, higher visit frequency of HHC (> 2 versus ≦1 times/month, aRR 3.52, 95% CI 3.39-3.66) and higher level of resource utilization group (RUG, RUG 4 versus 1, aRR = 1.38, 95% CI 1.25-1.51) were risk factor of mortality risk. Meanwhile, HHC provided by physician and nurse was related to reduced mortality risk (aRR 0.79, 95% CI 0.77-0.81) compared to those provided by nurse only. Anticipatory care planning and timely end-of life care should be integrated in light of the high mortality rate among PwD receiving HHC. Determinants associated with increased mortality risk facilitate the identification of high risk group and tailoring the appropriate care goals. Trial registration number: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

The use of deep learning methods for the automatic detection and quantification of bone metastases in bone scan images holds significant clinical value. A fast and accurate automated system for segmenting bone metastatic lesions can assist clinical physicians in diagnosis. In this study, a small internal dataset comprising 100 breast cancer patients (90 cases of bone metastasis and 10 cases of non-metastasis) and 100 prostate cancer patients (50 cases of bone metastasis and 50 cases of non-metastasis) was used for model training. Initially, all image labels were binary. We used the Otsu thresholding method or negative mining to generate a non-metastasis mask, thereby transforming the image labels into three classes. We adopted the Double U-Net as the baseline model and made modifications to its output activation function. We changed the activation function to SoftMax to accommodate multi-class segmentation. Several methods were used to enhance model performance, including background pre-processing to remove background information, adding negative samples to improve model precision, and using transfer learning to leverage shared features between two datasets, which enhances the model's performance. The performance was investigated via 10-fold cross-validation and computed on a pixel-level scale. The best model we achieved had a precision of 69.96%, a sensitivity of 63.55%, and an F1-score of 66.60%. Compared to the baseline model, this represents an 8.40% improvement in precision, a 0.56% improvement in sensitivity, and a 4.33% improvement in the F1-score. The developed system has the potential to provide pre-diagnostic reports for physicians in final decisions and the calculation of the bone scan index (BSI) with the combination with bone skeleton segmentation.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients' clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden's index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders ( n = 50) vs. non-responders ( n = 36) with a significant difference in OS. In multivariate LR, cardiac dose-volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

Minimizing the use of water for growing microalgae is crucial for lowering the energy and costs of animal feed, food, and biofuel production from microalgae. Dunaliella spp., a haloterant species that can accumulate high intracellular levels of lipids, carotenoids, or glycerol can be harvested effectively using low-cost and scalable high pH-induced flocculation. However, the growth of Dunaliella spp. in reclaimed media after flocculation and the impact of recycling on the flocculation efficiency have not been explored. In this study, repeated cycles of growth of Dunaliella viridis in repeatedly reclaimed media from high pH-induced flocculation were studied by evaluating cell concentrations, cellular components, dissolved organic matter (DOM), and bacterial community shifts in the reclaimed media. In reclaimed media, D. viridis grew to the same concentrations of cells and intracellular components as fresh media-10 7  cells/mL with cellular composition of 3 % lipids, 40 % proteins, and 15 % carbohydrates-even though DOM accumulated and the dominant bacterial populations changed. There was a decrease in the maximum specific growth rate and flocculation efficiency from 0.72 d -1 to 0.45 d -1 and from 60 % to 48 %, respectively. This study shows the potential of repeated (at least five times) flocculation and reuse of media as a possible way of reducing the costs of water and nutrients with some tradeoffs in growth rate and flocculation efficiency., Competing Interests: Declaration of competing interest The authors report no commercial or proprietary interest in any product or concept discussed in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nonlinear tracking control enabling a dynamical system to track a desired trajectory is fundamental to robotics, serving a wide range of civil and defense applications. In control engineering, designing tracking control requires complete knowledge of the system model and equations. We develop a model-free, machine-learning framework to control a two-arm robotic manipulator using only partially observed states, where the controller is realized by reservoir computing. Stochastic input is exploited for training, which consists of the observed partial state vector as the first and its immediate future as the second component so that the neural machine regards the latter as the future state of the former. In the testing (deployment) phase, the immediate-future component is replaced by the desired observational vector from the reference trajectory. We demonstrate the effectiveness of the control framework using a variety of periodic and chaotic signals, and establish its robustness against measurement noise, disturbances, and uncertainties., (© 2023. Springer Nature Limited.)

The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-β1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl 4 ) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-β1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl 4 -induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.

Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility-increasing events before calming down. The self-organizing processes are controlled by a morphogenetic module composed of molecular sensors, modulators, and executers. Increasing dermal stiffness provides the initial driving force (driver) which activates Yap1 (sensor) in epidermal cysts. Notch signaling (modulator 1) in epidermal cyst tunes the threshold of Yap1 activation. Activated Yap1 induces Wnts and MMPs (epidermal executers) in basal cells to facilitate cellular flows, allowing epidermal cells to protrude out from the CMU. Dermal cell-expressed Rock (dermal executer) generates a stiff force bridge between two CMU and accelerates tissue mixing via activating Laminin and β1-integrin. Thus, this self-organizing coalescence process is controlled by a mechano-chemical circuit. Beyond skin, self-organization in organoids may use similar mechano-chemical circuit structures.

Background: Premature ventricular complex (PVC) without structural heart disease is mostly viewed as a benign arrhythmia. However, the high burden of PVC causes cardiomyopathy due to intraventricular dyssynchrony. The effects of ectopic contraction on left ventricular (LV) hemodynamics in the structurally normal heart are unclear., Objectives: To examine the effect of PVC burden on LV dimension, LV systolic function, and intraventricular blood flow, and to determine whether ectopic ventricular contraction affects LV hemodynamics., Methods: Patients aged ≥ 18 years with PVC ≥ 5% on Holter recording were enrolled and divided into groups G1 (5-10%), G2 (10-20%), and G3 (≥ 20%). We excluded patients with structural heart diseases, pacemakers, and LV systolic dysfunction [LV ejection fraction (LVEF) < 50%]. Clinical characteristics and routine transthoracic echocardiography parameters were compared., Results: The end-systolic LV internal dimension increased according to the PVC burden from G1 to G3 (p = 0.001). LVEF was inversely associated with PVC burden from G1 to G3 (p = 0.002). The same pattern was seen for LV outflow tract (LVOT) maximal velocity (p = 0.005) and maximal pressure gradient (PG) (p = 0.005), LVOT velocity time integral (VTI) (p = 0.03) and LV stroke volume index (LVSI) (p = 0.008)., Conclusions: Systolic function and LV end-systolic dimension were inversely associated with PVC burden. Decreased LVOT flow velocity and PG were related to increased PVC burden. LVOT VTI and LVSI were smaller when the PVC burden exceeded 20%. These negative hemodynamic manifestations of idiopathic PVC were considerable even in structure normal hearts, hence the early elimination of PVC is strongly advised., Competing Interests: All the authors declare no conflict of interest.

The challenging problem of network reconstruction from dynamical data can in general be formulated as an optimization task of solving multiple linear equations. Existing approaches are of the two types: Point-by-point (PBP) and global methods. The local PBP method is computationally efficient, but the accuracies of its solutions are somehow low, while a global method has the opposite traits: High accuracy and high computational cost. Taking advantage of the network symmetry, we develop a novel framework integrating the advantages of both the PBP and global methods while avoiding their shortcomings: i.e., high reconstruction accuracy is guaranteed, but the computational cost is orders of magnitude lower than that of the global methods in the literature. The mathematical principle underlying our framework is block coordinate descent (BCD) for solving optimization problems, where the various blocks are determined by the network symmetry. The reconstruction framework is validated by numerical examples with a variety of network structures (i.e., sparse and dense networks) and dynamical processes. Our success is a demonstration that the general principle of exploiting symmetry can be extended to tackling the challenging inverse problem or reverse engineering of complex networks. Since solving a large number of linear equations is key to a plethora of problems in science and engineering, our BCD-based network reconstruction framework will find broader applications.

Abdominal computed tomography (CT) is a frequently used imaging modality for evaluating gastrointestinal diseases. The detection of colorectal cancer is often realized using CT before a more invasive colonoscopy. When a CT exam is performed for indications other than colorectal evaluation, the tortuous structure of the long, tubular colon makes it difficult to analyze the colon carefully and thoroughly. In addition, the sensitivity of CT in detecting colorectal cancer is greatly dependent on the size of the tumor. Missed incidental colon cancers using CT are an emerging problem for clinicians and radiologists; consequently, the automatic localization of lesions in the CT images of unprepared bowels is needed. Therefore, this study used artificial intelligence (AI) to localize colorectal cancer in CT images. We enrolled 190 colorectal cancer patients to obtain 1558 tumor slices annotated by radiologists and colorectal surgeons. The tumor sites were double-confirmed via colonoscopy or other related examinations, including physical examination or image study, and the final tumor sites were obtained from the operation records if available. The localization and training models used were RetinaNet, YOLOv3, and YOLOv8. We achieved an F1 score of 0.97 (±0.002), a mAP of 0.984 when performing slice-wise testing, 0.83 (±0.29) sensitivity, 0.97 (±0.01) specificity, and 0.96 (±0.01) accuracy when performing patient-wise testing using our derived model YOLOv8 with hyperparameter tuning.

Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield. Understanding of seed weight control is limited, especially in soybean plants. Here we show that Glycine max JASMONATE-ZIM DOMAIN 3 (GmJAZ3), a gene identified through gene co-expression network analysis, regulates seed-related traits in soybean. Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation. GmJAZ3 interacted with both G. max RESPONSE REGULATOR 18a (GmRR18a) and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G. max CYTOKININ OXIDASE 3-4 (GmCKX3-4), which usually affects seed traits. Meanwhile, the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression. In GmJAZ3-overexpressing soybean seeds, the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds, indicating that the GmJAZ3 affects seed size/weight and compositions. Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity, higher gene expression and higher seed weight. The Hap3 promoter may be selected and fixed during soybean domestication. JAZ3 orthologs from other plants/crops may also control seed size and weight. Taken together, our study reveals a novel molecular module GmJAZ3-GmRR18a/GmMYC2a-GmCKXs for seed size and weight control, providing promising targets during soybean molecular breeding for better seed traits., (© 2023 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Background and Objectives: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children., Methods: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE., Results: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE., Discussion: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner., Classification of Evidence: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures., (© 2023 American Academy of Neurology.)

Osteosarcoma (OS) is the most common primary malignant bone tumor that produces immature osteoid. Metastatic OS has a poor prognosis with a death rate of >70%. Manoalide is a natural sesterterpenoid isolated from marine sponges. It is a phospholipase A2 inhibitor with anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to investigate the mechanism and effect of manoalide on OS cells. Our experiments showed that manoalide induced cytotoxicity in 143B and MG63 cells (human osteosarcoma). Treatment with manoalide at concentrations of 10, 20, and 40 µM for 24 and 48 h reduced MG63 cell viability to 45.13-4.40% ( p < 0.01). Meanwhile, manoalide caused reactive oxygen species (ROS) overproduction and disrupted antioxidant proteins, activating the apoptotic proteins caspase-9/-3 and PARP (Poly (ADP-ribose) polymerase). Excessive levels of ROS in the mitochondria affected oxidative phosphorylation, ATP generation, and membrane potential (ΔΨ m ). Additionally, manoalide down-regulated mitochondrial fusion protein and up-regulated mitochondrial fission protein, resulting in mitochondrial fragmentation and impaired function. On the contrary, a pre-treatment with n-acetyl-l-cysteine ameliorated manoalide-induced apoptosis, ROS, and antioxidant proteins in OS cells. Overall, our findings show that manoalide induces oxidative stress, mitochondrial dysfunction, and apoptosis, causing the cell death of OS cells, showing potential as an innovative alternative treatment in human OS.

Bone Scan Index (BSI) is an image biomarker for quantifying bone metastasis of cancers. To compute BSI, not only the hotspots (metastasis) but also the bones have to be segmented. Most related research focus on binary classification in bone scintigraphy: having metastasis or none. Rare studies focus on pixel-wise segmentation. This study compares three advanced convolutional neural network (CNN) based models to explore bone segmentation on a dataset in-house. The best model is Mask R-CNN, which reaches the precision, sensitivity, and F1-score: 0.93, 0.87, 0.90 for prostate cancer patients and 0.92, 0.86, and 0.88 for breast cancer patients, respectively. The results are the average of 10-fold cross-validation, which reveals the reliability of clinical use on bone segmentation.

In this study, a water transfer method was developed to fabricate conducive thin-film patterns on 3D curvilinear surfaces. Crystalline silver nanoplates (AgNPLs) with a dimension of 700 nm and a thickness of 35 nm were suspended in ethanol with an anionic surfactant, sodium dodecyl sulfate, to improve the suspension stability. The prepared AgNPL suspension was then spread over the water surface via the Langmuir-Blodgett approach to generate a self-assembled thin film. By dipping an accepting object with a robotic arm, the floating AgNPL thin film with nanometer thickness can be effectively transferred to the object surfaces and exhibited a superior conductivity up to 15% of bulk silver without thermal sintering. Besides good conductivity, the AgNPL conductive thin films can also be transferred efficiently on any curvilinear (concave and convex) surface. Moreover, with the help of masks, conductive patterns can be produced on water surfaces and transferred to curvilinear surfaces for electronic applications. As a proof of concept, several examples were demonstrated to display the capability of this approach for radiofrequency identification and other printed circuit applications.

Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments., (© 2023 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Temporal coherence and spectral regularity are critical cues for human auditory streaming processes and are considered in many sound separation models. Some examples include the Conv-tasnet model, which focuses on temporal coherence using short length kernels to analyze sound, and the dual-path convolution recurrent network (DPCRN) model, which uses two recurring neural networks to analyze general patterns along the temporal and spectral dimensions on a spectrogram. By expanding DPCRN, a harmonic-aware tri-path convolution recurrent network model via the addition of an inter-band RNN is proposed. Evaluation results on public datasets show that this addition can further boost the separation performances of DPCRN., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: To evaluate the effects of 5 manufacturing technologies and 2 finish line designs on the trueness and dimensional stability of 3D-printed definitive dies at finish line regions under different storage conditions and time., Material and Methods: Preparation of light chamfer and round shoulder finish lines were adopted individually on two mandibular first molar typodont teeth and digitalized as standard tessellation language (STL) files. A total of 240 samples (192 AM definitive dies and 48 definitive conventional stone dies) in 20 groups (n = 12) were manufactured based on 2 finishing line designs (chamfer and shoulder), 5 manufacturing technologies (4 additively manufactured technologies and conventional stone die), and 2 storage conditions (light exposure and dark). The 4 additively manufactured (AM) technologies include a DLP 3D-printer, an economic LED 3D-printer, a CLIP 3D-printer, and an SLA 3D-printer. All the study samples were distributed into two storage conditions. Subsequently, samples were digitalized to STL files at 3 different time points (within 36 hours, 1-month, and 3-months). A surface matching software was used to superimpose the sample STL files onto the corresponding original STL files with the best-fit alignment function. The trueness of each printed and stone definitive dies and their dimensional stabilities were measured by the root mean square (RMS, in mm). A linear mixed-effects model was used to test the effects of the finish line design, manufacturing technology, storage condition, and storage time on RMS values (α = 0.05)., Results: While finish line designs had no significant effects [F(1, 220) = 0.85, p < 0.358], the manufacturing technologies [F(3, 220) = 33.02, p < 0.001], storage condition [F(1, 220) = 4.11, p = 0.044], and storage time F(2, 440) = 10.37, p < 0.001] affected the trueness and dimensional stability of 3D-printed dies at finish line regions. No significant interactions were found among the 4 factors. For the manufacturing technologies, Type IV stone groups and LCD 3D-printer groups had significantly higher RMS values than the other 3 printers (p < 0.001) with no significant differences between Type IV stone and LCD 3D-printer groups (p = 0.577). DLP 3D-printer groups had higher RMS values than both SLA 3D-printer groups and CLIP 3D-printer groups (p < 0.001). There were no significant differences between SLA 3D-printer groups and CLIP 3D-printer groups, p = 0.671. For the effects of storage conditions, RMS values were significantly higher in the groups stored with the direct light exposure than the ones stored in the dark, p = 0.044. In terms of the effects of storage time, the RMS values were significantly higher after 1-month storage, p = 0.002; and 3-month storage, p < 0.001, than the ones at the immediate postmanufacturing stage. However, the RMS values after 1-month and 3-month storage were not significantly different from each other (p = 0.169)., Conclusions: Manufacturing technologies, storage conditions, and storage time significantly affected the trueness and dimensional stability of 3D-printed dies at finish line regions, while finish line designs had no significant effects. Among the AM technologies tested, all have produced either comparable or truer 3D-printed dies than the Type IV dental stone dies, and the CLIP and SLA 3D-printers produced the best outcomes. 3D-printed dies showed significant distortion after 1-month and 3-months storage, especially under light exposure storage conditions. These findings may negate the clinical need to preserve 3D-printed dies, and digital data should be preserved instead., (© 2022 The Authors. Journal of Prosthodontics published by Wiley Periodicals LLC on behalf of American College of Prosthodontists.)

Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.

Serious climate changes and energy-related environmental problems are currently critical issues in the world. In order to reduce carbon emissions and save our environment, renewable energy harvesting technologies will serve as a key solution in the near future. Among them, triboelectric nanogenerators (TENGs), which is one of the most promising mechanical energy harvesters by means of contact electrification phenomenon, are explosively developing due to abundant wasting mechanical energy sources and a number of superior advantages in a wide availability and selection of materials, relatively simple device configurations, and low-cost processing. Significant experimental and theoretical efforts have been achieved toward understanding fundamental behaviors and a wide range of demonstrations since its report in 2012. As a result, considerable technological advancement has been exhibited and it advances the timeline of achievement in the proposed roadmap. Now, the technology has reached the stage of prototype development with verification of performance beyond the lab scale environment toward its commercialization. In this review, distinguished authors in the world worked together to summarize the state of the art in theory, materials, devices, systems, circuits, and applications in TENG fields. The great research achievements of researchers in this field around the world over the past decade are expected to play a major role in coming to fruition of unexpectedly accelerated technological advances over the next decade.

New psychoactive substances (NPS) are emerging illegal substances or synthetic drugs that pose public health threats worldwide. This study was aimed at reporting the clinical characteristics of NPS and classical illicit substances used by patients who presented to the emergency room. We conducted a retrospective cohort study on patients with suspected illicit substance use who visited the emergency department (ED) with the suspicion of illicit substance use. We divided the patients into 4 groups based on the NPS testing results: NPS positive, NPS negative, NPS combined with classical illicit drugs (INPS), and subjects with negative testing results. The majority of patients in all groups were male. The NPS users were significantly younger than those with negative results on toxic testing (26.4 vs 37.5, P = .005 < 0.05). The heart rate of NPS users was significantly faster than that of the group with negative results of toxic testing (111.1 vs 93.5 beats per minute, P = .046). The heartbeats of INPS group were also significantly faster than those with a negative result in toxicology screen (119.6 vs 93.5 beats per minute, P = .024). Those who used classical illicit drugs combined with NPS had significantly higher palpitation than those with negative results of toxic testing (27.3% vs 3.1%, P = .017). Patients who were highly suspicious of NPS use were younger, had tachycardia, felt palpitations, and had fair oxygen saturation compared to patients who were negative for urine toxicity screening., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aim: Breast cancer is the most common female malignancy in the world. Nearly ninety percent of screening-detected breast cancers were diagnosed with earlier stages of 0 to II in Taiwan. It's widely acknowledged that mammography screening of breast cancer can achieve the goal of early diagnosis and treatment in terms of preventive task while neglected interval cancers are associated with unfavorable tumor characteristics and worse outcomes. The purpose of this study was to explore the characteristics of screening-detected breast cancers in Taiwan., Materials and Methods: Both screening and diagnostic mammography examinations with accompanied BI-RADS (breast imaging-reporting and data system) classification were extracted from the health information system and linked to cancer registry in Taiwan. Enrolled population included those attending their first mammography between 2012 and 2016, excluding subjects with previous breast cancer, or with missing or incomplete data. We compared treatment outcomes between breast cancers with either initial screening or diagnostic mammography (control group), and investigated the compositions of breast cancers detected by screening mammography through direct chart reviews., Results: A total of 84,246 screening and 61,230 diagnostic mammography sessions were performed from 2010 to 2020. More positive results (BI-RADS 0, 3, 4 and 5) were observed for those attending the first diagnostic than the first screening mammography (43.58% versus 16.12%, p < 0.001). Earlier stages (0 and I) distribution (92% versus 81%, p < 0.0001), better survivorship (overall survival: 96.91% versus 92.17%, p = 0.007) and a lower HER2 (human epidermal growth factor receptor II) positive status and lower tumor grade were noted in breast cancers with initial screening rather than diagnostic mammography. Among 26,103 mammography screening invitees between 2012 and 2016, 325 breast cancers were ascertained from cancer registry. Of these, 234 had one, 72 had two and 19 had three episodes of mammography before cancer diagnosis. Extensive chart reviews revealed that women with and without breast symptoms constituted 29.9 and 70.1% of the 325 screening-detected breast cancers, with the latter further divided into false negative results (interval cancer), diagnosed at the first mammography, diagnostic at the secondary or subsequent mammography and those with a delayed biopsy or confirmatory imaging constituted (5.2, 47, 10.5 and 7.4%)., Conclusion: Screening-detected breast cancers were a mixture of women with and without symptoms, those with a false negative result, true negative results with cancer detected at subsequent mammography and non-adherers. Despite this, efficacy of mammography screening was ascertained in Taiwan from this study. To further enhance earlier detection and decrease false negativity, the impact of repeated mammography, and additional sonography for symptomatic women, compliance following a positive screening mammography should not be overemphasized., (© 2023. The Author(s).)

Purpose: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR -mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated., Materials and Methods: From January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB-IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis., Results: The univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR <5.0 (p = 0.008)., Conclusion: The benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Chen, Chang, Chen, Lai, Chang and Wei.)

Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we found corresponding changes in subsynaptic regions in the hippocampus. Specifically, we detected significant reductions in the concentrations of Arc in the presynaptic terminal of Schaffer collateral glutamatergic synapses in the stratum radiatum of the CA1 area in TLE, as well as in their adjacent postsynaptic spines. In CA3, there was a significant reduction of Arc only in the presynaptic terminal cytoplasm. Conversely, in CA3, there was a significant increase in the expression of BDNF in the presynaptic terminal, but not in the postsynaptic spine. Significant increase in BDNF concentration in the CA1 postsynaptic density was also obtained. We hypothesize that the observed changes in Arc and BDNF may contribute to both cognitive impairment and increased excitotoxic vulnerability in chronic epilepsy., Competing Interests: Competing interest The authors declare that the study was conducted without any relationship that could be considered as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the classic Kuramoto system of coupled two-dimensional rotators, chimera states characterized by the coexistence of synchronous and asynchronous groups of oscillators are long-lived because the average lifetime of these states increases exponentially with the system size. Recently, it was discovered that, when the rotators in the Kuramoto model are three-dimensional, the chimera states become short-lived in the sense that their lifetime scales with only the logarithm of the dimension-augmenting perturbation. We introduce transverse-stability analysis to understand the short-lived chimera states. In particular, on the unit sphere representing three-dimensional (3D) rotations, the long-lived chimera states in the classic Kuramoto system occur on the equator, to which latitudinal perturbations that make the rotations 3D are transverse. We demonstrate that the largest transverse Lyapunov exponent calculated with respect to these long-lived chimera states is typically positive, making them short-lived. The transverse-stability analysis turns the previous numerical scaling law of the transient lifetime into an exact formula: the "free" proportional constant in the original scaling law can now be precisely determined in terms of the largest transverse Lyapunov exponent. Our analysis reinforces the speculation that in physical systems, chimera states can be short-lived as they are vulnerable to any perturbations that have a component transverse to the invariant subspace in which they live., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Lumbar degenerative disc disease (LDDD) is a leading cause of chronic lower back pain; however, a lack of clear diagnostic criteria and solid LDDD interventional therapies have made predicting the benefits of therapeutic strategies challenging. Our goal is to develop machine learning (ML)-based radiomic models based on pre-treatment imaging for predicting the outcomes of lumbar nucleoplasty (LNP), which is one of the interventional therapies for LDDD., Methods: The input data included general patient characteristics, perioperative medical and surgical details, and pre-operative magnetic resonance imaging (MRI) results from 181 LDDD patients receiving lumbar nucleoplasty. Post-treatment pain improvements were categorized as clinically significant (defined as a ≥80% decrease in the visual analog scale) or non-significant. To develop the ML models, T2-weighted MRI images were subjected to radiomic feature extraction, which was combined with physiological clinical parameters. After data processing, we developed five ML models: support vector machine, light gradient boosting machine, extreme gradient boosting, extreme gradient boosting random forest, and improved random forest. Model performance was measured by evaluating indicators, such as the confusion matrix, accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC), which were acquired using an 8:2 allocation of training to testing sequences., Results: Among the five ML models, the improved random forest algorithm had the best performance, with an accuracy of 0.76, a sensitivity of 0.69, a specificity of 0.83, an F1 score of 0.73, and an AUC of 0.77. The most influential clinical features included in the ML models were pre-operative VAS and age. In contrast, the most influential radiomic features had the correlation coefficient and gray-scale co-occurrence matrix., Conclusions: We developed an ML-based model for predicting pain improvement after LNP for patients with LDDD. We hope this tool will provide both doctors and patients with better information for therapeutic planning and decision-making.

The nucleolar rRNA 2'-O-methyltransferase fibrillarin (FBL) contains a highly conserved methyltransferase domain at the C-terminus and a diverse glycine arginine-rich (GAR) domain at the N-terminus in eukaryotes. We found that a nine-exon configuration of fbl and exon 2-3 encoded GAR domain are conserved and specific in vertebrates. All internal exons except exon 2 and 3 are of the same lengths in different vertebrate lineages. The lengths of exon 2 and 3 vary in different vertebrate species but the ones with longer exon 2 usually have shorter exon 3 complementarily, limiting lengths of the GAR domain within a certain range. In tetrapods except for reptiles, exon 2 appears to be longer than exon 3. We specifically analyzed different lineages of reptiles for their GAR sequences and exon lengths. The lengths of exon 2 in reptiles are around 80-130-nt shorter and the lengths of exon 3 in reptiles are around 50-90 nt longer than those in other tetrapods, all in the GAR-coding regions. An FSPR sequence is present at the beginning of the GAR domain encoded by exon 2 in all vertebrates, and a specific FXSP/G element (X can be K, R, Q, N, and H) exist in the middle of GAR with phenylalanine as the 3rd exon 3-encoded amino acid residue starting from jawfish. Snakes, turtles, and songbirds contain shorter exon 2 compared with lizards, indicating continuous deletions in exon 2 and insertions/duplications in exon 3 in these lineages. Specifically, we confirmed the presence the fbl gene in chicken and validated the RNA expression. Our analyses of the GAR-encoding exons of fbl in vertebrates and reptiles should provide the basis for further evolutionary analyses of more GAR domain encoding proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)