BACKGROUND Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM-related parasomnia in which the normal muscle atonia of REM sleep is lost, leading to complex motor behaviors or dream enactments. RBD is increasingly recognized as a prodromal manifestation of neurodegenerative a-synucleinopathy. It is well established in longitudinal studies that isolated RBD is among the strongest predictors of a-synucleinopathies, with more than 80-90% of patients eventually converting to Parkinson disease, dementia with Lewy bodies (DLB), or multiple system atrophy. CASE REPORT We report a 69-year-old woman with a previous history of RBD who was admitted for progressive cognitive and behavioral deterioration after starting antiseizure and antipsychotic medications. On admission, she exhibited bradykinesia and rigidity and dopamine transporter positron emission tomography (PET) imaging demonstrated reduced uptake in the putamina. During hospitalization, dream-enacting behaviors were observed, leading to the decision to conduct polysomnography, which confirmed loss of muscle atonia during REM sleep. Taken together, these findings supported a diagnosis of DLB and RBD. In addition, brain magnetic resonance imaging with susceptibility-weighted sequences revealed multiple cortical microbleeds consistent with cerebral amyloid angiopathy, prompting amyloid PET imaging, which showed diffuse cortical amyloid deposition and indicated concurrent amyloid pathology. CONCLUSIONS This case highlights that RBD and characteristic neuroimaging findings are consistent with DLB as the primary disease, with coexisting amyloid pathology. Additionally, the potential influence of clinical confounders such as cerebral amyloid angiopathy, seizure, and medication effects must be taken into account.
Sepsis is a systemic inflammatory response syndrome triggered by infection, resulting in organ dysfunction. Sepsis-induced acute kidney injury (S-AKI) is one of the most prevalent potential complications. Accumulating studies found that ferroptosis plays an important role in S-AKI. However, the specific regulatory mechanism is not clear. In the present study, we isolated plant-derived exosome-like nanovesicles (PELNs, named PGY-Exo herein) from Dandelion (Taraxacum Genus) and established an in vivo S-AKI model. Human umbilical vein endothelial cells (HUVECs) were stimulated with lipopolysaccharide (LPS) to mimic an in vitro septic injury model for evaluating the therapeutic effects of PGY-Exo. Proteomics was used to reveal the molecular mechanism by which PGY-Exo ameliorate AKI. In this study, PKH26-labeled PGY-Exo were confirmed to be taken up by HUVECs and renal tissues. PGY-Exo treatment alleviated S-AKI by suppressing the accumulation of reactive oxygen species (ROS) and multiple inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Proteomic screening found that solute carrier family 7 member 11 (SLC7A11) was the key downstream target of PGY-Exo. Downregulation of SLC7A11 abrogated the protective effects of PGY-Exo against LPS-induced HUVEC injury and dysfunction. Taken together, this study found that treatment with dandelion-derived exosome-like nanovesicles alleviated sepsis-induced ferroptosis and renal injury by upregulating SLC7A11 expression.
To investigate the prevalence of pain catastrophizing among women with vaginal birth and explore its associated factors. In this cross-sectional study, a total of 282 participants who met the inclusion and exclusion criteria were selected by convenience sampling from Delivery Room Ward of a hospital in Sichuan Province. Pain Catastrophizing Scale, Pain Numerical Rating Scale, Social Support Rating Scale, Hospital Anxiety and Depression Scale, Pain Self-Efficacy Scale and general information questionnaire were used to assess pain catastrophizing (PC), pain intensity, social support, anxiety, depressive symptoms, pain self-efficacy and sociodemographic information of the participants, respectively. Data were collected in two stages: latent period of the first stage of labor (T1) and the second stage of labor (T2). According to the distribution and type of the data, the mean and standard deviation (SD), median and quartiles, frequency and percentages were used for statistical description. The generalized estimating equation (GEE) was used to analyze the associated factors of pain catastrophizing. Crossed-lagged regression was used to explore the relationship between pain intensity and pain catastrophizing. The median and quartiles of PCS scores at T1 and T2 were 30.00 (21.00, 39.00) and 27.00 (17.00, 40.00) among the participants, respectively. The prevalence of pain catastrophizing at T1 and T2 was 29.08% and 29.43%, respectively. Chi-square test showed that the prevalence of pain catastrophizing at T2 was higher than that at T1 (χ2 = 55.387, p<0.001). GEE showed that greater gestational week, greater pain intensity at T1 and T2, and depressive symptoms were potential risk factors of pain catastrophizing (p<0.05), and a higher level of pain self-efficacy was a protective factor of pain catastrophizing among the participants [OR = 0.967, p<0.001]. Compared accompanied by husband, maternities accompanied by others during childbirth were more likely to be pain catastrophic [OR = 0.282, p = 0.010]. The results of cross-lagged analysis showed maternal pain intensity was positively correlated with pain catastrophizing at both T1 (r = 0.357, P < 0.001) and T2(r = 0.603, p < 0.001). There was no correlation between pain catastriphizing at T1 and pain intensity at T2, or pain intensity at T1 and pain catastriphizing at T2. As shown in Fig. 2. There is a high prevalence of pain catastrophizing in women with natural childbirth. Associated factors of pain catastrophizing among women with natural childbirth are multidimensional, including physiological (pain intensity), psychological (gestational age, anxiety, depressive symptoms, pain self-efficacy) and socio-demographic factors (accompanying family members during delivery), suggesting that early evaluation of mental health condition of pregant women should be implemented and targeted interventions should be taken even if during pregnancy by health care workers. During labour, close attention should be paid to the mother's recognition of pain and appropriate measures taken promptly to prevent the occurrence of pain catastrophizing.
Relative clauses (RCs) can be used to recursively embed structures in sentences. Subject-modifying (SM) RCs have been widely used to examine whether there is asymmetry in the ease of processing subject-extracted RCs (SRCs) and object-extracted RCs (ORCs) in Chinese. However, the difference in the beginning sequence of SM-SRCs (verb-noun) and SM-ORCs (noun-verb) may have been a confound in these tests. Unlike SM-RCs, Chinese object-modifying (OM)-RCs are initiated by the same noun-verb sequence. In the current study, participants were asked to read OM clauses (OM-SRCs and OM-ORCs) in Chinese sentences while undergoing fMRI scanning. Activation and Granger causality analyses were both conducted. There were no significant differences in activation elicited by OM-SRCs and OM-ORCs. In contrast, the results of Granger causality analyses showed more ORC-specific connectivity than SRC-specific connectivity, especially from left inferior frontal gyrus to superior temporal gyrus regions, which suggests that ORC processing required more interregional interaction in the brain compared with SRC processing. Taken together, these findings indicate an SRC advantage in processing Chinese OM-RC sentences and that the advantage is more involved in functional connectivity rather than activation. The results support the structural distance hypothesis about RC processing.
Anecdotal accounts of inebriated elephants are widespread across elephant-inhabited regions, yet the molecular and mechanistic basis underlying these observations remains incompletely understood. Alcohol metabolism in mammals is primarily mediated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). We investigated elephant ADH and ALDH at the genomic, transcriptional, and enzymatic levels, comparing them with humans, hamsters, and rats. Elephant liver predominantly expressed three ADH1 genes, as in humans and hamsters that voluntarily consume ethanol, a feature otherwise reported mainly in primates. We measured hepatic ADH and cytosolic ALDH activities in elephants, despite challenges in sample collection. Elephant ADH exhibited high ethanol affinity, allowing enzymatic activity at low substrate concentrations, likely related to large body size. ADH catalytic efficiency was comparable to other species, and cytosolic ALDH showed relatively high efficiency. These results suggest that elephants are less likely to possess exceptionally low hepatic ethanol-metabolizing capacity, although the lack of data on mitochondrial ALDH2 activity should be taken into consideration. Elephants also exhibited unique features, including the absence of ADH4 gene expression, duplication of ALDH1A1, and pseudogenization of ALDH1B1, which appear to have arisen in association with diet and potential functional redundancy among paralogs. In addition to their ecological and evolutionary significance, these findings may contribute to the interpretation of drug metabolism and support evidence-based pharmacological management in elephants, given the role of ADH and ALDH in pharmaceutical metabolism. Together, this study provides a molecular and enzymatic basis for understanding ethanol metabolism in elephants.
Orforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist. The hepatic safety profile in adults with obesity or overweight and/or type 2 diabetes (T2D) across seven orforglipron Phase 3 clinical trials was assessed. Overall, 11 220 participants were included in this analysis (orforglipron N = 6920; pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine] N = 4300) for up to 104 weeks, including safety follow-up. Eligibility criteria for these Phase 3 trials included ALT/AST < 3 × ULN in the weight management programme and ≤ 5 × ULN in the T2D programme. The main analysis sets included placebo-controlled trials by indication for pooled orforglipron doses. Changes from baseline in hepatic analytes were assessed continuously and categorically, and screening for drug-induced liver injury/Hy's Law was conducted. Hepatic AEs were summarised. Subgroup analyses were conducted in participants with elevated baseline aminotransferases. Orforglipron treatment was associated with mean reductions in ALT/AST. Categorical ALT/AST elevations were generally balanced between orforglipron and comparators. Six (0.1%) orforglipron-treated participants and six (0.1%) comparator-treated participants had ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN; however, alternative etiologies accounted for all orforglipron cases and thus did not meet criteria for drug induced liver injury/Hy's Law. The incidence of hepatic AEs was balanced between orforglipron and pooled comparators, suggesting no increased risk with orforglipron. Results were consistent in participants with normal and elevated baseline aminotransferases. In this pooled analysis of orforglipron Phase 3 clinical trials, orforglipron treatment was not associated with drug-induced liver injury, demonstrating a hepatic safety profile similar to placebo or active comparators. There were no cases consistent with drug-induced liver injury/Hy's Law with orforglipron. Aminotransferase trajectories showed a hepatic profile consistent with the metabolic benefits of weight loss. What is the context and purpose of this research study? ○ Orforglipron is an oral GLP‐1 receptor agonist taken as tablet that helps to reduce blood sugar and reduce body weight. We studied how orforglipron may affect the liver in adults with obesity, overweight, and/or type 2 diabetes who participated in the Phase 3 clinical trials. What was done? ○ Across seven trials, orforglipron up to 17.2 mg once daily was compared to placebo, oral semaglutide, dapagliflozin, or insulin glargine. We measured changes in blood liver enzymes like AST, ALT and counted how many participants developed elevated liver enzymes above a set threshold. Analysis included all participants and those with preexisting elevated liver enzymes. We also checked for Hy's law, which signals for serious medicine related liver injury. Hy's Law screening was performed, and hepatic adverse events were summarised. What were the main results? ○ Treatment with orforglipron was not associated with drug‐induced liver injury, and no participant met the Hy's Law criteria. Additionally, ALT and AST levels improved over time with orforglipron, which coincides with the significant weight loss and metabolic improvements previously reported in these trials. Overall, the liver safety profile of orforglipron was comparable to placebo and other comparator medicines, including peptide GLP‐1 receptor agonist semaglutide. What is the originality and relevance of this study? ○ Findings from this analysis suggest that orforglipron was safe in adults with overweight, obesity, or type 2 diabetes—even in those with mildly to moderately elevated liver enzyme levels, which is commonly seen in MASLD. These findings support the need for dedicated studies on people with MASLD or metabolic dysfunction‐associated steatohepatitis (MASH).
In 2023 Israeli Arabs (i.e., Arab Palestinian citizens of Israel) constituted 22% of Israel's working-age population. In that same year, Israeli Arabs constituted 25% of Israel's employed physicians of working age - up significantly from 8% in 2010. The objectives of this study were to: 1) assess whether, and to what extent, there is an Arab-Jewish income differential among Israeli physicians; 2) assess the extent to which any such differential can be attributed to Arab-Jewish differences in the demographic, geographic, and/or work-related characteristics of the medical workforce; and 3) explore the policy implications of the key findings. The analysis utilized the Central Bureau of Statistics' 2022 Population and Housing Census, which included data on 7,089 physicians, of whom 1,333 were Arab and 5,756 were Jewish or other (hereafter "Jewish"). The main income variable examined was "Total annual gross income from work". In 2022, the average annual physician income for Arab physicians was 26% less than for Jewish physicians (NIS 358 thousand vs. NIS 483 thousand). Arab physicians were more likely to be under age 40 (71% v. 28%), male (77% v. 52%), residents of the North region (48% v. 7%), in non-supervisory roles (87% v. 75%), and generalists or family practitioners (33% v. 22%). Controlling for age and sex, via regression analysis, reduced the income differential to 1%. This major reduction was due to Arab physicians being markedly younger than Jewish physicians. Further controlling for regional distribution and work characteristics (managerial status, specialty status/type, and months worked) did not change the ethnicity differential, but did markedly reduce the coefficients of the age variables. The 2022 Arab-Jewish income differential among physicians was due predominantly to differences in age composition. The differential could potentially shrink in the decades ahead, as more Arab physicians reach the ages at which physician incomes are at their highest. However, as part of the effect of age on income is mediated by work characteristics, the extent to which the wage gap will shrink will depend in part on the extent to which Arab physicians will secure prestigious residency training slots and managerial positions. Health system leaders can play an important role in promoting such developments. In particular, steps should be taken to increase the representativeness of Arabs in Israeli medical schools.
Embryonic growth and nutrient utilization during incubation are influenced by both thermal conditions and nutrient availability; however, information on the combined effects of in ovo nutrient supplementation and incubation temperature on embryonic development remains limited. This study investigated the interactive effects of early in ovo feeding and incubation temperature on egg quality traits and embryonic development in broiler breeder eggs. A total of 270 fertile eggs were randomly assigned to a 3 × 3 factorial arrangement comprising three in ovo treatments (phosphate-buffered saline (PBS; control), glucose, and vitamin D3) and three constant incubation temperatures (36.5°C, 37.0°C, and 37.5°C), with three replicates of 10 eggs per treatment combination. On embryonic day (ED) 10, the eggs were injected with 0.2 mL PBS, glucose solution (5 mg/mL), or vitamin D3 solution (25 mg/mL). The egg and embryo measurements were recorded daily from ED15 to ED20. Significant in ovo treatment × incubation temperature interactions (p < 0.05) were observed for several developmental traits. The egg weight was affected only on ED18, while eggshell thickness was influenced on ED15 and ED17-20. In addition, wet embryo weight showed interaction effects on ED15 and ED17-20, whereas femur length was affected on ED15 and ED17, and tibia length on ED16, ED17, and ED19. The results showed that eggshell temperature was influenced on most incubation days except ED16. Wet residual yolk sac weight exhibited an interaction effect only on ED19, while dry residual yolk sac weight was affected from ED17 to ED20 (p < 0.05). Incubation temperature significantly influenced embryonic development, with embryos incubated at 37.0°C generally exhibiting lower dry embryo weight and shorter embryo length than those incubated at 36.5°C and 37.5°C. Glucose supplementation increased dry embryo weight on selected days, whereas vitamin D3 supplementation enhanced embryonic growth, particularly at 36.5°C. Taken together, embryonic responses to nutrient supplementation were temperature-dependent, with vitamin D3-injected eggs incubated at 36.5°C showing the greatest growth and skeletal development, while embryos incubated at 37.0°C exhibited the poorest growth performance.
Vaccination is a key measure to prevent severe influenza in adults aged ≥80 years, who experience the highest burden of respiratory and cardiovascular complications. Because immunosenescence reduces the effectiveness of standard-dose vaccines (SD-IIV), enhanced formulations such as high-dose vaccines (HD-IIV) are recommended in the elderly. Real-world data on their effectiveness in adults aged ≥80 years remain limited. The aim of this study was to quantify the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV in preventing severe influenza disease in adults aged ≥80 years, assessed through respiratory and cardiovascular outcomes. Retrospective, population-based cohort study conducted in Andalusia, Spain, during the 2024-2025 influenza season, including 279,649 vaccinated adults aged ≥80 years. Data on sociodemographic characteristics, influenza vaccines, chronic diseases and clinical outcomes were taken from the Andalusian health population database. We used a directed acyclic graph to illustrate the assumed relationships between variables. The rVE of HD-IIV versus SD-IIV was estimated using augmented inverse probability weighting models. Compared with SD-IIV, HD-IIV was associated with a lower risk of hospitalisation for influenza (rVE=34.0%; 95%CI=15.8% to 52.2%). HD-IIV also showed improved effectiveness against laboratory-confirmed influenza (rVE=42.1%; 95%CI=22.9% to 61.3%), hospitalisation for acute myocardial infarction (rVE=26.4%; 95%CI=5.6% to 47.2%), for stroke (rVE=32.9%; 95%CI=17.4% to 48.4%), for pulmonary embolism (rVE=26.7%; 95%CI=0.7% to 52.6%) and for overall cardiovascular outcomes (rVE=6.6%; 95%CI=0.9% to 12.2%). No association was observed for hospitalisation due to pneumonia, influenza/pneumonia, heart failure, respiratory outcomes, or in-hospital mortality. Among adults aged ≥80 years, HD-IIV seemed more effective than SD-IIV in preventing hospitalisation for influenza and secondary cardiovascular outcomes, supporting its use in this at-risk population.
Pain-stimulus input is transmitted by mechanisms that respond to real or perceived tissue injury and propagate the information to the spinal cord for reflex withdrawal and to the brain for intentional withdrawal. To be useful, perception of the pain signal needs to be a reliable indicator of the magnitude and duration of the sensory input, i.e., threat, so that appropriate action can be taken, such as fight or flight. Two components of signal transmission are the "ascending pathways," mediating sensory input → perception, and the "descending pathways," mediating perception → response. Ascending pathways are often modulated by descending pathways. We previously introduced Lotka-Volterra-style coupling to model ascending and descending pain pathways as a coupled control and feedback loop. Here, we apply the model to examine the value of modulatory feedback to the fight-or-flight response and identify separate response functions that allow for both a quantitative assessment of the immediate threat, i.e., the magnitude of the acute pain signal, and damping of the signal in order to preclude sensory overload leading to counterproductive inaction. As a result of increasing inhibitory modulation that accompanies increasing pain-stimulus magnitude, pain perception rises rapidly as a function of stimulus intensity and then begins to decay as modulation ramps up, but not to zero. Instead, it saturates or plateaus at a value intermediate between zero and peak/maximum perception, at a level that is related to the stimulus intensity. Although the contribution of this work is conceptual and application-focused rather than presenting new mechanistic insights, the observed response functions, i.e., pain perception and modulation, allow for both a quantitative assessment of the immediate threat and damping of the pain signal in order to preclude sensory overload that might lead to counterproductive inaction. Moreover, the fact that plateau pain perception is less than peak/maximum pain perception for respective sensory inputs prevents obscuration of subsequent new, i.e., cumulative, injury.
Protein-protein interactions (PPIs) are dynamic and critical to adaptive homeostasis. While there have been massive efforts to catalogue proteome-wide PPIs, global quantification of changes remains a challenge. Here, we integrate dynamic protein correlation profiling - mass spectrometry (PCP-MS) and quantitative cross linking-mass spectrometry (qXL-MS) using multiplexed stable isotope labelling to characterise global PPI remodelling following the development of chronic skeletal muscle insulin resistance (IR) with or without acute insulin stimulation. We quantify >7,000 unique PPIs amongst 5,346 proteins and show changes in the interactome network dominate the proteome response. Our data show the dysregulation of protein processing in the endoplasmic/sarcoplasmic reticulum involving changes in PPIs with protein chaperones and disulfide isomerases is a major hallmark of skeletal muscle IR. Mechanistically, we show the dysregulation of PPIs with Protein-Disulfide Isomerase 6 (PDIA6) regulates cysteine oxidation and insulin sensitivity. Taken together, we show in vivo quantitative interactome mapping is a powerful approach to understand disease mechanisms and provide new insights into protein network re-organisations with IR.
Hypospadias represents one of the most frequent congenital anomalies in male neonates, and corrective surgery is generally advised within the first 6 to 18 months of life. Nevertheless, the most appropriate time to perform the repair remains debated, especially concerning its impact on patients' long-term psychological well-being. The present systematic review evaluated how the age at which surgery is performed affects subsequent psychological and psychosexual outcomes. A structured search of PubMed, ScienceDirect, Embase, and Cochrane Library was undertaken in May 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 reporting framework. Eligible studies were comparative investigations and cohorts that reported psychiatric, psychological, or psychosexual outcomes after primary hypospadias correction in pediatric populations. Two independent reviewers appraised risk of bias with the Newcastle-Ottawa Scale, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was applied to assess the certainty of evidence. As substantial heterogeneity precluded statistical pooling, a narrative synthesis was conducted. A total of 15 studies (more than 10,000 patients), published between 1997 and 2025 and originating from Europe, Asia, the Middle East, Australia, and North America, were ultimately included. The majority of patients who underwent hypospadias repair reached adequate psychosocial functioning in the long term, although a recurring subgroup demonstrated symptoms of anxiety, depression, obsessive-compulsive features, or dissatisfaction with body image. Large registry-based cohorts indicated heightened susceptibility to neurodevelopmental and psychiatric conditions, whereas smaller institutional series tended to highlight concerns related to genital self-perception. Whether surgical timing meaningfully alters these outcomes was not consistently supported across studies. Overall certainty of the evidence ranged from low to moderate. Taken together, psychological outcomes following hypospadias correction tend to be favorable, but the role of operative age in shaping long-term psychosocial well-being remains unclear. Well-designed prospective investigations with extended follow-up are warranted to address this question.
Mutational inactivation of the chromatin regulator gene ATRX (a-thalassemia mental retardation X-linked) represents a defining molecular abnormality in multiple cancer types. Recent findings suggest that the multifaceted consequences of ATRX deficiency on global chromatin landscapes fundamentally alter cellular differentiation and other complex phenotypes relevant to cancer, particularly in neuroepithelial and mesenchymal lineages. To comprehensively define ATRX-deficient epigenomic abnormalities and their transcriptional and phenotypic sequelae in a disease-relevant context, we conducted an array of high-throughput epigenome mapping studies in isogenic Atrx- and Atrx+ murine neuroepithelial progenitors (mNPCs). These investigations revealed that Atrx loss widely impacts 3D chromatin architecture and looping, with specific changes in topologically associating domains (TADs) and CCCTC-binding factor binding sites overlying neurodevelopmental gene sets. TAD shifts closely approximated disrupted large histone H3K9me3-marked laminin-associated domains, along with reprogrammed enhancer/superenhancer regions at neurodevelopmental effectors, including a novel regulator of cell migration, Slitrk6, and the cancer-implicated HoxA cluster. Pharmacologic inhibition of HOXA-PBX binding selectively impaired the in vivo growth of patient-derived ATRX-deficient glioma stem cells. Taken together, our findings reveal that rewiring of chromatin topology and heterochromatin structure promotes cancer-associated phenotypes in ATRX-deficient glioma through induction of therapeutically targetable neurodevelopmental gene expression.
Voluntary horizontal sharing of confidential food safety data among companies for joint analysis can improve food safety, efficiency, and decision-making, especially for rare events. Despite its potential benefits, horizontal data sharing in the food industry has lagged, with limited research exploring the reasons for hesitation. To address this gap, we conducted in-depth semi-structured interviews with 27 food industry leaders. Four themes emerged: (1) benefits of data sharing, (2) technical barriers, (3) trust as a determinant of data sharing decisions, and (4) data governance as a solution. Across these themes, we found that companies face trade-offs when deciding to share food safety data, weighing risks against benefits. Data sharing decisions were strongly influenced by trust in stakeholders (e.g., industry peers, regulatory bodies, customers) and in data protection measures. Data governance emerged as a solution to concerns stemming from trust, such as loss of control once data is shared. Taken together, the findings reveal underlying tensions between individual firm incentives and collective benefits, including uneven cost-benefit distributions, opportunism concerns, and participation cost asymmetries. These findings offer timely insights to guide data sharing initiatives and prioritize areas for future research.
When a macromolecular crystal lattice targeted for study is closely related to a previously studied crystal lattice, phasing the target crystal by difference (fast-)Fourier transform (DFFT) methods is preferable to performing molecular replacement. The application Scotty, within the Phasertng codebase, is software for the identification of coincident lattices and downstream processing. All crystallographic PDB entries are organized into a scikit-learn `BallTree' index under the Niggli cell distance metric `NCDist'. Nearest neighbours under the metric are progressed to test structure-factor intensity correlation. The structure from the lattice with the highest correlation with the target is used to phase the target lattice, and the coordinates are taken forward to coordinate refinement using a wide convergence radius protocol. The method can identify lattice coincidences accounting for very significant non-isomorphism. The nearest-neighbour search is space-group agnostic, so that coincident lattices are identified even when the nominal space groups are different, the symmetry of one lattice being described as a subgroup of the other or a higher metric symmetry.
The management of postoperative pain is a critical ethical concern and a challenge in laboratory animal research, particularly for mice. Surgical procedures are routinely conducted in mice, but the use of analgesic drugs is underreported and the assessment of their efficacy is limited. This systematic review assesses the efficacy of analgesic drugs for postoperative pain in mice, addressing the influence of various factors, including sex, surgical invasiveness, pain modalities and analgesic classes. A systematic literature search resulted in 48 eligible studies included in the qualitative analysis and 43 in the quantitative analysis. The overall pooled standardized mean difference (SMD) for analgesic drugs was 0.46 (95% confidence interval 0.31 to 0.60), indicating a positive pain-reducing effect. Subgroup analysis revealed that analgesic treatment was significantly more effective in male (SMD 0.84; 0.60 to 1.08) than in female mice, in mild (SMD 0.57; 0.38 to 0.75) than in severe surgical procedures and in reducing evoked pain (SMD 1.12; 0.83 to 1.41) than in reducing spontaneous pain. In addition, almost all analgesic drug classes tested, including opioids, nonsteroidal anti-inflammatory drugs, acetaminophen and local anesthetics were effective in reducing evoked pain but not spontaneous pain (SMD 0.12; -0.03 to 0.27). However, most studies present limitations that could produce a high risk of bias. Taken together, our results indicate that, although analgesic drugs can reduce postoperative pain in mice, their efficacy is reduced in females, severely invasive surgeries and spontaneous pain. Thus, high-quality studies are still needed to answer ethical concerns and to guarantee full analgesia in laboratory mice submitted to surgical procedures.
This study compared three practice approaches for expressive performance-modeling, structural understanding, and narrative imagery-among 54 undergraduate and graduate piano majors. Participants were randomly assigned to one of the three practice conditions and completed a pretest-practice-posttest protocol using the opening excerpt from Chopin's Nocturne in E-flat major, Op. 9, No. 2. During a 60-min practice session, participants practiced according to their assigned condition while annotating their scores and recording and reviewing their performances. Pretest and posttest performances were evaluated by three expert pianists across multiple dimensions, including phrasing, tone color, dynamics, tempo rubato, balance, articulation, overall expressiveness, and accuracy. Participants also completed a postsession questionnaire assessing goal clarity, perceived improvement, cue awareness, personal interpretation, engagement, and transfer intention. Mixed-design ANOVAs revealed significant Time × Group interactions for tone color, dynamics, tempo rubato, and articulation. The modeling group showed greater improvement than the narrative imagery group in tone color, tempo rubato, and articulation, and both the modeling and structural understanding groups showed greater improvement than the narrative imagery group in dynamics. Learner-reported outcomes, however, favored structural understanding and narrative imagery. Specifically, narrative imagery yielded higher perceived improvement than modeling, and both structural understanding and narrative imagery yielded higher cue awareness, personal interpretation, and transfer intention than modeling. Goal clarity and engagement did not differ significantly across groups. Open-ended responses indicated that modeling heightened awareness of specific expressive cues but was sometimes experienced as restrictive, whereas narrative imagery was reported to enhance engagement and interpretive agency. Taken together, these findings suggest that expressive performance is multidimensional and that different practice approaches may support different aspects of expressive development, with implications for how expressive performance is taught and evaluated comprehensively.
Objective Based on existing CT performance testing methods, the test-retest reliability of subjective and objective results for both spatial resolution and low-contrast detectability were evaluated and analyzed under different scanning conditions. Methods A prospective research method was adopted, using clinical routine scanning protocols and parameters for the head, chest and abdomen. Eight CT scanners from different regions underwent two rounds of testing, with each round tested three times. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were used to evaluate inter-CT test-retest reliability. Bland-Altman analysis was used to evaluate intra-CT test-retest reliability. Results For head scanning, the CV range for spatial resolution was 8.85%-21.66%, with ICCs from 0.26 to 0.72; the CV range for density resolution was 5.53%-47.84%, with ICCs from 0.16 to 0.75. For chest scanning, the CV range for spatial resolution was 9.13%-19.65%, with ICCs from 0.41 to 0.75; the CV range for density resolution was 12.25%-38.89%, with ICCs from 0.18 to 0.68. For abdomen scanning, the CV range for density resolution was 5.91%-37.33%, with ICCs from 0.23 to 0.77. For the same CT, the successive results of subjective spatial resolution from head protocols demonstrated statistical significance under the first enhancement strength. Moreover, the successive results of objective spatial resolution from chest protocols demonstrated statistical significance under the first, second and third enhancement level. No statistical significance was observed under other scanning conditions. Conclusion The objective contrast evaluation method demonstrated better variability and consistency compared to the subjective evaluation method under most test conditions. Even for the same CT with iterative reconstruction algorithm at the same levels, there may exist statistical significance of the spatial resolution values from successive head and chest scanning. Cautions should be taken when test results of objective spatial resolution are analyzed. 基于现有的CT性能检测方法，在不同扫描条件下分别对空间分辨率和密度分辨率的主观检测结果和客观检测结果的重测信度进行评价和分析。. 采用前瞻性研究方法，基于临床上头部、胸部和腹部的常规扫描协议，对8台处于不同区域的CT设备进行前后两轮检测，每轮检测重复3次。首先采用变异系数（coefficient of variation，CV）和组内相关系数（intraclass correlation coefficient，ICC）评价不同设备之间的重测信度，然后利用Bland-Altman分析评价单台设备前后两轮的重测信度。. 不同设备之间，头部扫描空间分辨率的CV为8.85%~21.66%，ICC为0.26~0.72；密度分辨率的CV为5.53%~47.84%，ICC为0.16~0.75。胸部扫描空间分辨率的CV为9.13%~19.65%，ICC为0.41~0.75；密度分辨率的CV为12.25%~38.89%，ICC为0.18~0.68。腹部扫描密度分辨率的CV为5.91%~37.33%，ICC为0.23~0.77。对于同一台设备，增强等级为1级时，头部主观空间分辨率两轮检测结果之间的差异具有统计学意义（ P＜0.05）。增强等级为1、2和3级时，胸部客观空间分辨率两轮检测结果之间的差异具有统计学意义（ P＜0.05）。在其余扫描条件下，两轮检测结果之间的差异无统计学意义。. 在大部分扫描条件下，采用客观评价方法分析不同CT检测结果之间的差异性和一致性优于主观评价方法。对于同一台设备，即使采用相同强度的迭代重建算法，前后两轮头部和胸部空间分辨率的检测结果也可能存在显著差异，在进行客观空间分辨率检测时需要关注结果的一致性。.
Numerous studies have shown that metagenomics has opened a dimension in reading the contents of archaeological remains as time capsules. Corn mummies are ritual objects from ancient Egypt, created by forming human-shaped figures from cereal grains grown in a mixture of water and earth. The aim of our study was to determine whether ancient DNA could be preserved in the mummy, and if so, which organisms it might have originated from. To find answers, we performed metagenomic analyses on samples taken from a corn mummy dating to the second half of the third century BC. Alongside a number of clearly modern contaminants, we identified organisms that cannot be excluded as being of historical origin. Besides considerable amounts of bacterial sequences belonging to the genus Bacillus, Mesobacillus, Metabacillus, Neobacillus, Niallia, Peribacillus and Paenibacillus, we also found traces of plants, animals, and humans. Sequences assigned to the genus Triticum showed the highest similarity to ancient T. turgidum ssp. dicoccum specimens from Egypt and the southern Levant. The fragments identified as of Lepidopteran origin showed the greatest similarity to Sphingidae genomes. Analysis of the human-derived sequences revealed L3 (mtDNA), E, and J (Y chromosome) haplotypes, which are common lineages in Africa today.
Thyroid hormones regulate cardiovascular functions and energy homeostasis including thermogenesis through binding to nuclear thyroid hormone receptors. The thyroid hormone analogue 3,3',5-triiodothyroacetic acid (TRIAC) has recently emerged as a therapeutic candidate for thyroid hormone transporter deficiencies (Allan-Herndon-Dudley Syndrome) or thyroid hormone resistance β. Although TRIAC shows promise for these conditions, a comprehensive characterization focussing on heart and body temperature regulation has not been systematically performed in mice. As this knowledge is critical for determining its safety profile and therapeutic advantages over conventional thyroid hormone therapy, we administered TRIAC to wild-type mice for 14 days and assessed molecular (Realtime PCR, Western Blot, Immunoassays) and physiological responses (Infrared Thermography, Blood Pressure). TRIAC treatment reduced circulating thyroxine levels and induced robust upregulation of hepatic thyroid hormone-responsive genes including Dio1 and Me1, demonstrating classical thyromimetic activity. However, cardiovascular analysis revealed normal blood pressure and heart rate, and no signs of cardiac hypertrophy despite specific molecular changes in cardiac gene expression. On the metabolic level, we surprisingly did not observe any effect on brown fat thermogenesis or body temperature, while in muscle Ucp3 and Gpd2 were reduced. Taken together, our comparative in vivo analysis demonstrates variable TRIAC responsiveness across tissues. Under defined conditions, the drug produces defined metabolic responses while avoiding classical hyperthyroid manifestations such as tachycardia or hyperthermia, thus supporting its potential therapeutic use in thyroid hormone resistance conditions.