bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home‐Cage Behavior
Authors: Krishnan Vaishnav , Wu Jun , Mazumder Arindam Ghosh , Kamen Jessica L. , Schirmer Catharina , Adhyapak Nandani , Bass John Samuel , Lee Samuel C. , Maheshwari Atul , Molinaro Gemma , Gibson Jay R. , Huber Kimberly M. , Minassian Berge A. 
Published: July 2024

ABSTRACTLafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age‐dependent manner in all mouse models of LD. In this study, we applied home‐cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin‐deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6–7 months, and ∼12 months of age, malin‐deficient mice (“KO”) and wild‐type (WT) littermates underwent a standardized home‐cage behavioral assessment designed to non‐obtrusively appraise features of rest/arousal, consumptive behaviors, risk aversion, and voluntary wheel‐running. At all timepoints, and over a range of metrics that we report transparently, WT and KO mice were essentially indistinguishable. In contrast, within WT mice compared across the same timepoints, we identified age‐related nocturnal hypoactivity, diminished sucrose preference, and reduced wheel‐running. Neuropathological examinations in subsets of the same mice revealed expected age‐dependent LB accumulation, gliosis, and microglial activation in cortical and subcortical brain regions. At 12 months of age, despite the burden of neocortical LBs, we did not identify spontaneous seizures during an electroencephalographic (EEG) survey, and KO and WT mice exhibited similar spectral EEG features. However, in an in vitro assay of neocortical function, paroxysmal bursts of network activity (UP states) in KO slices were more prolonged at 3 and 6 months of age, but similar to WT at 12 months. KO mice displayed a distinct response to pentylenetetrazole, with a greater incidence of clonic seizures and a more pronounced postictal suppression of movement, feeding, and drinking behavior. Together, these results highlight the clinicopathologic dissociation in a mouse model of LD, where the accrual of LBs may latently modify cortical circuit function and seizure threshold without clinically meaningful changes in home‐cage behavior. Our findings allude to a delay between LB accumulation and neurobehavioral decline in LD: one that may provide a window for treatment, and whose precise duration may be difficult to ascertain within the typical lifespan of a laboratory mouse.
Identifying Oncogenic Missense Single Nucleotide Polymorphisms in Human SAT1 Gene Using Computational Algorithms and Molecular Dynamics Tools
Authors: Mozibullah Md. , Khatun Marina , Sikder Md. Asaduzzaman , Islam Mohammod Johirul , Sharmin Mehbuba 
Published: July 2024

ABSTRACTBackgroundThe human SAT1 gene encodes spermidine/spermine N1‐acetyltransferase 1 (SSAT1), a regulatory biological catalyst of polyamine catabolism. Numerous essential biological processes, such as cellular proliferation, differentiation, and survival, depend on polyamines like spermidine and spermine. Thus, SSAT1 is involved in key cellular activities such as proliferation and survival of cells and mediates various diseases including cancer. A plethora of studies established the involvement of missense single nucleotide polymorphisms (SNPs) in numerous pathological conditions due to their ability to adversely affect the structure and subsequent function of the protein.AimsTo date, an in silico study to identify the pathogenic missense SNPs of the human SAT1 gene has not been accomplished yet. This study aimed to filter the missense SNPs that were functionally detrimental and pathogenic.Methods and ResultsThe rs757435207 (I21N) was ascertained to be the most deleterious and pathogenic by all algorithmic tools. Stability and evolutionary conservation analysis tools also stated that I21N variant decreased the stability and was located in the highly conserved residue. Molecular dynamics simulation revealed that I21N caused substantial alterations in the conformational stability and dynamics of the SSAT1 protein. Consequently, the I21N variant could disrupt the native functional roles of the SSAT1 enzyme.ConclusionTherefore, the I21N variant was identified and concluded to be an oncogenic missense variant of the human SAT1 gene. Overall, the findings of this study would be a great directory of future experimental research to develop personalized medicine.
A Novel Amino Acid‐Related Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma
Authors: Wang Shuyi , Huang Hong , Hu Xingwang , Xiao Meifang , Yang Kaili , Bu Haiyan , Jiang Yupeng , Huang Zebing 
Published: July 2024

ABSTRACTBackground and AimsHepatocellular carcinoma (HCC) is an extremely harmful malignant tumor in the world. Since the energy metabolism and biosynthesis of HCC cells are closely related to amino acids, it is necessary to further explore the relationship between amino acid‐related genes and the prognosis of HCC to achieve individualized treatment. We herein aimed to develop a prognostic model for HCC based on amino acid genes.MethodsIn this study, RNA‐sequencing data of HCC patients were downloaded from the TCGA‐LIHC cohort as the training cohort and the GSE14520 cohort as the validation cohort. Amino acid‐related genes were derived from the Molecular Signatures Database. Univariate Cox and Lasso regression analysis were used to construct an amino acid‐related signature (AARS). The predictive value of this risk score was evaluated by Kaplan–Meier (K–M) curve, receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression analysis. Gene set variation analysis (GSVA) and immune characteristics evaluation were used to explore the underlying mechanisms. Finally, a nomogram was established to help the personalized prognosis assessment of patients with HCC.ResultsThe AARS comprises 14 amino acid‐related genes to predict overall survival (OS) in HCC patients. HCC patients were divided into AARS‐high group and AARS‐low group according to the AARS scores. The K–M curve, ROC curve, and univariate and multivariate Cox regression analysis verified the good prediction efficiency of the risk score. Using GSVA, we found that AARS variants were concentrated in four pathways, including cholesterol metabolism, delayed estrogen response, fatty acid metabolism, and myogenesis metabolism.ConclusionOur results suggest that the AARS as a prognostic model based on amino acid‐related genes is of great value in the prediction of survival of HCC, and can help improve the individualized treatment of patients with HCC.
Alveolar Ridge Preservation With Fibro‐Gide or Connective Tissue Graft: A Randomized Controlled Trial of Soft and Hard Tissue Changes
Authors: Ibrahim Ammar , Saymeh Rowaida 
Published: July 2024

ABSTRACTObjectiveThe aim of this study was to evaluate the effectiveness of a novel biomaterial (FG) for alveolar ridge preservation compared to CTG in terms of soft tissue thickness and bone dimensional changes.Materials and MethodsA randomized clinical trial was conducted on 30 patients who required extraction of 30 hopeless mandibular posterior teeth. All patients went through atraumatic tooth extraction, and then, they were randomly allocated to either a CTG, an FG, or a spontaneous healing (SH) group (1:1:1). All patients received a dental implant placed 6 months postoperatively. The soft tissue thickness and bone dimensional changes were measured before and 6 months after the procedure.ResultsThe study's analysis revealed statistically significant differences in buccal gingival thickness and dimensional bone changes across the three examined groups after 6 months (p < 0.05). The SH group had lower gingival thickness (1.31 ± 0.65 mm) and higher vertical resorption (−1.46 ± 1.67 mm at the buccal aspect) compared with the CTG and FG groups. The CTG and FG groups had similar gingival thickness (2.42 ± 0.70 and 3.00 ± 0.71 mm, respectively) and bone width reduction (+0.86 ± 2.31 and +0.93 ± 2.38 mm, respectively), whereas the CTG group had lower vertical bone loss (−0.30 ± 1.09 mm at the buccal aspect) than the FG group (−0.47 ± 2.30 mm at the buccal aspect).ConclusionFG and CTG demonstrate equivalent soft tissue thickness and comparable horizontal bone dimension outcomes in ARP.
Instrumental Occlusal Analysis in Migraine Patients: A Quantitative Cross Sectional Study
Authors: Nikolaos Zokaris , Marcus Greven , Dimitrios Naoumis , Michail Tzakis , Dimitrios Mitsikostas Dimos , Vasileios Psarras 
Published: July 2024

ABSTRACTObjectivesThis study aimed to investigate possible differences of functional occlusal variables between a group of migraine patients (MG) and a control group (CG).Materials and MethodsEach group included 50 individuals. Instrumental functional analysis and digital occlusal analysis were performed. Variables examined were condylar displacement from a reference position to maximum intercuspation; angular difference between the steepness of the articular eminence and the contra‐lateral canine guidance; and angular difference between the steepness of the articular eminence and the ipsilateral central incisor guidance and occlusal plane inclination. Self‐reported grinding and occlusal index were also investigated.ResultsThere were statistically significant differences in the extent of retral condylar displacement assessed both clinically [MG: 0.49 mm (SD 0.67 mm), CG: 0.29 mm (SD 0.27 mm), p = 0.012] and digital‐mechanically [MG: 1.53 mm (SD 0.95 mm), CG: 0.9 mm (SD 0.66 mm), p = 0.001], the angular difference between the steepness of the articular eminence and the contra‐lateral canine guidance [MG: 13.11° (SD 8.33°), CG: 9.47° (SD 7.08°), p = 0.021 and MG: 12.94° (SD 8.71°), CG: 9.44° (SD 8.70°), p = 0.017], and the occlusal plane inclination [MG: 11.16° (SD 4.66°), CG: 9.09° (SD 4.37°), p = 0.024]. Self‐reported grinding (MG: 39/50, CG: 12/50, p < 0.001) and occlusal index [MG: 1.92 (SD 0.46), CG: 0.21 (SD 0.66), p < 0.001] were also significantly higher in migraineurs.ConclusionsArticular and occlusal structures could play a role in migraine and thus should be considered in an interdisciplinary approach.
Detection of thyroid hormones in urine by liquid chromatography coupled to tandem mass spectrometry
Authors: Martinez Brito Dayamin , Leogrande Patrizia , de la Torre Xavier , Botrè Francesco 
Published: July 2024

AbstractRecently, the trend of thyroid hormones (TH) consumption in the sports community has been published. It is known the capacity of the exogenously administered TH to enhance metabolism, being an attractive feature for athletes, who search for weight control and increased caloric expenditure. This paper aimed the validation of a method to measure TH and related compounds in urine by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The method was applied to urine samples collected before and after the administration of a diiodothyronine (3,5‐T2) supplement. A method to detect nine TH included an enzymatic hydrolysis, liquid–liquid extraction, and solid‐phase extraction. The extracts were analyzed by LC‐MS/MS. Validated parameters showed good results for accuracy (85%–104%), precision (3%–16%), LOD (10–40 pg/mL, except for thyronacetic acids that was 200 pg/mL), and the combined uncertainty (2.2%–22%). Maximum concentration of 3,5‐T2 in pre‐administration samples was 0.71 ng/mL, and after 30 h of the last administration, concentrations returned to pre‐administration values. Maximum values of ratios between the analyte and thyronine, T3, and T4 were 0.09, 0.19, and 0.12, respectively, and after 30 h of the last administration, the ratios reached back the basal values. Acidic or basic metabolites were not found in urine at least at the method LOD. A proposed method to assess TH in urine was validated, and as a proof of concept, its efficacy was demonstrated with an excretion study of 3,5‐diiodothyronine. The consumption of 3,5‐T2 was detected in urine measuring the analyte concentration and ratios between the analyte and thyronine, T3, and T4.
Evaluation of underground hard rock mine pillar stability using gene expression programming and decision tree‐support vector machine models
Authors: Kadkhodaei Mohammad H. , Ghasemi Ebrahim , Zhou Jian , Zahraei Melika 
Published: July 2024

AbstractAssessing the stability of pillars in underground mines (especially in deep underground mines) is a critical concern during both the design and the operational phases of a project. This study mainly focuses on developing two practical models to predict pillar stability status. For this purpose, two robust models were developed using a database including 236 case histories from seven underground hard rock mines, based on gene expression programming (GEP) and decision tree‐support vector machine (DT‐SVM) hybrid algorithms. The performance of the developed models was evaluated based on four common statistical criteria (sensitivity, specificity, Matthews correlation coefficient, and accuracy), receiver operating characteristic (ROC) curve, and testing data sets. The results showed that the GEP and DT‐SVM models performed exceptionally well in assessing pillar stability, showing a high level of accuracy. The DT‐SVM model, in particular, outperformed the GEP model (accuracy of 0.914, sensitivity of 0.842, specificity of 0.929, Matthews correlation coefficient of 0.767, and area under the ROC of 0.897 for the test data set). Furthermore, upon comparing the developed models with the previous ones, it was revealed that both models can effectively determine the condition of pillar stability with low uncertainty and acceptable accuracy. This suggests that these models could serve as dependable tools for project managers, aiding in the evaluation of pillar stability during the design and operational phases of mining projects, despite the inherent challenges in this domain.
Correlated responses to selection across diverse environments during experimental evolution of Tetrahymena thermophila
Authors: Tarkington Jason , Zufall Rebecca A. 
Published: July 2024

AbstractCorrelated responses to selection have long been observed and studied; however, it remains unclear when they will arise, and in what direction. To contribute to a growing understanding of correlated responses to selection, we used experimental evolution of the ciliate Tetrahymena thermophila to study direct and correlated responses in a variety of different environmental conditions. One experiment focused on adaptation to two different temperatures and the correlated responses across temperatures. Another experiment used inhibitory concentrations of a variety of compounds to test direct and correlated responses to selection. We found that all populations adapted to the environments in which they evolved. We also found many cases of correlated evolution across environments; few conditions resulted in trade‐offs and many resulted in a positive correlated response. Surprisingly, in many instances, the correlated response was of a larger magnitude than the direct response. We find that ancestral fitness predicts the extent of adaptation, consistent with diminishing returns epistasis. Unexpectedly, we also find that this pattern of diminishing returns holds across environments regardless of the environment in which evolution occurs. We also found that the correlated response is asymmetric across environments, that is, the fitness of a population evolved in one environment and assayed in a second was inversely related to the fitness of a population evolved in the second environment and assayed in the first. These results support the notion that positive correlated responses to selection across environments are frequent, and worth further study.
Estimating Octanol–Water Partition Coefficients of Novel Brominated Flame Retardants by Reversed-Phase High-Performance Liquid Chromatography and Computational Models
Authors: Sigman-Lowery Anthony J. , Di Toro Dominic M. , Chin Yu-Ping 
Published: July 2024

Abstract
Legacy brominated flame retardants, including polybrominated diphenyl ethers (PBDEs), have been classified as persistent organic pollutants and replaced with novel brominated flame retardants (NBFRs). The octanol–water partition coefficients (log KOW) of NBFRs have been computationally estimated, but the log KOW values provided by these methods can differ by 1 to 3 orders of magnitude. Given the importance of this parameter in fate and toxicity models, we indirectly measured the log KOW values of eight NBFRs by their capacity factor (k′) on a reversed-phase high-performance liquid chromatography (HPLC) C18 column by isocratic elution and compared these measured values with those estimated by nine computational models. Log KOW values were obtained for the NBFRs 1,2-bis(2,4,6-tribromophenoxy) ethane, pentabromobenzene, pentabromoethylbenzene, pentabromotoluene, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate, allyl 2,4,6-tribromophenylether, 2,3-dibromopropyl-2,4,6-tribromophenyl ether, and bis(2-ethylhexyl) tetrabromophthalate. A training set of phthalates, polychlorinated biphenyls, PBDEs, and halogenated benzenes were chosen to obtain the log k′–log KOW calibration for the NBFRs. The computational models KowWIN, XLogP3, EAS-E Suite, COSMOtherm, DirectML, and Abraham polyparameter linear free energy relationships all predicted the log KOW values of the calibration compounds to within 1 order of magnitude without significant bias. The median of these models predicted log KOW values for the calibration compounds that were close to those known in the literature with root mean square error (RMSE) = 0.224 and for the NBFRs that were close to those measured by HPLC (RMSE = 0.334). Environ Toxicol Chem 2024;43:2105–2114. © 2024 SETAC
Clinical outcomes and considerations in outpatient with COVID‐19 receiving remdesivir therapy
Authors: Siami Zeinab , Rasooli Aziz , Zebardast Jayran , Jalali Illahay , Jamalimoghadamsiahkali Saeidreza 
Published: July 2024

AbstractIntroductionThis retrospective cross‐sectional study aimed to assess the outcomes of Covid‐19 patients who received remdesivir therapy at the outpatient department of Ziaian Hospital.MethodA total of 514 eligible patients were included between May and September 2021. Covid‐19 diagnosis was confirmed through positive SARS‐COV‐2 PCR tests or chest CT scans. Due to limited hospital beds, patients received remdesivir on an outpatient basis.ResultsPatients received six daily doses of remdesivir for 5 days. Those referred to a physician within 7 days of symptom onset had similar hospitalization rates compared to later referrals. Lower blood saturation levels were associated with a higher likelihood of hospital admission, indicating that earlier administration of remdesivir may be more effective. Patients with over 50% lung involvement had higher rates of disease progression despite treatment. Corticosteroids did not significantly improve outcomes in patients with saturation above 90%. Discontinuation of remdesivir due to side effects was rare, with only 1% experiencing increased liver enzymes, 1.2% facial redness and tremors, and 1.5% allergies. After 1 week of treatment, patients commonly reported symptoms such as hair loss, fatigue, body pain, lethargy, and anorexia, particularly among hospitalized patients.DiscussionPatients generally preferred outpatient treatment over hospitalization. Body mass index (BMI) did not significantly impact hospitalization rates, although average weight tended to be higher among inpatients. The study confirmed the effectiveness of remdesivir therapy with a low occurrence of side effects.ConclusionThis retrospective study evaluated the outcomes of Covid‐19 patients receiving remdesivir at an outpatient department. Early administration of remdesivir showed better outcomes, while corticosteroids had limited benefits. Outpatient treatment was favored, and BMI did not significantly influence hospitalization rates. Remdesivir demonstrated efficacy with a low incidence of side effects.
The prevalence of depression and anxiety in premenopausal and menopausal women: A cross‐sectional study
Authors: Vaziri‐harami Roya , Kazemi Seyyedeh Neda , Vaziri‐harami Saharnaz , Hazari Vajiheh , Farokh Parisa , Valadbeigi Tanaz 
Published: July 2024

AbstractBackground and AimsTargeted research on physiological and psychological changes during menopause is crucial. Most studies have prioritized the investigation of psychological disorders during menopause, with a limited comparison of mental health among women in the various stages surrounding menopause. This study aims to explore the difference in depression and anxiety prevalence between women in premenopausal and menopause.MethodsThis cross‐sectional study was conducted on 242 female participants referred to Imam Hossein (AS) Educational and Therapeutic Hospital affiliated with Shahid Beheshti University of Medical Sciences. These 242 individuals were selected through accessible sampling. 122 individuals were placed in the menopausal group and 120 individuals in the premenopausal group. First, the medical history of all participants was taken, and then the Beck questionnaire was administered to examine the levels of depression and anxiety. The association between the occurrence and severity of depression and anxiety in menopausal and premenopausal groups was statistically analyzed.ResultsIn this study, the age range of the participants was 45−70, the overall prevalence of depression was estimated to be 33.5% and the overall prevalence of anxiety was estimated to be 54.2%. The prevalence of depression was 30.2% and 36.6% in the menopausal and premenopausal groups, respectively. The prevalence of anxiety was estimated to be 52.5% and 55.7% in the menopausal and premenopausal groups, respectively. No significant difference was observed between the two groups in terms of the occurrence and severity of depression and anxiety.Conclusionour study found a higher incidence of depression during premenopause compared to menopause, possibly due to greater hormonal fluctuations. Despite this, there wasn't a significant confirmation of this hypothesis compared to other groups. Nonetheless, there's a higher prevalence of depression and anxiety among premenopausal women, emphasizing the need for screening and intervention, such as hormone therapy, to prevent severe outcomes.