Miracle-dz/UniFAR-FTUs huggingface dataset:
Small-Molecule Conformer Generators: Evaluation of Traditional Methods and AI Models on High-Quality Data Sets

Small-molecule conformer generation (SMCG) is an extremely important task in both ligand- and structure-based computer-aided drug design, especially during the hit discovery phase. Recently, a multitude of artificial intelligence (AI) models tailored for SMCG have emerged. Despite developers typically furnishing performance evaluation data upon releasing their AI models, a comprehensive and equitable performance comparison between AI models and conventional methods is still lacking. In this study, we curated a new benchmarking data set comprising 3354 high-quality ligand bioactive conformations. Subsequently, we conducted a systematic assessment of the performance of four widely adopted traditional methods (i.e., ConfGenX, Conformator, OMEGA, and RDKit ETKDG) and five AI models (i.e., ConfGF, DMCG, GeoDiff, GeoMol, and torsional diffusion) in the tasks of reproducing bioactive and low-energy conformations of small molecules. In the former task, the AI models have no advantage, particularly with a maximum ensemble size of 1. Even the best-performing AI model GeoMol is still worse than any of the tested traditional methods. Conversely, in the latter task, the torsional diffusion model shows obvious advantages, surpassing the best-performing traditional method ConfGenX by 26.09 and 12.97% on the COV-R and COV-P metrics, respectively. Furthermore, the influence of force field-based fine-tuning on the quality of the generated conformers was also discussed. Finally, a user-friendly Web server called fastSMCG was developed to enable researchers to rapidly and flexibly generate small-molecule conformers using both traditional and AI methods. We anticipate that our work will offer valuable practical assistance to the scientific community in this field.
Age‐related differences in hippocampal subfield volumes across the human lifespan: A meta‐analysis

The human hippocampus (Hc) is critical for memory function across the lifespan. It is comprised of cytoarchitectonically distinct subfields: dentate gyrus (DG), cornu ammonis sectors (CA) 1‐4, and subiculum, each of which may be differentially susceptible to neurodevelopmental and neurodegenerative mechanisms. Identifying age‐related differences in Hc subfield volumes can provide insights into neural mechanisms of memory function across the lifespan. Limited evidence suggests that DG and CA3 volumes differ across development while other regions remain relatively stable, and studies of adulthood implicate a downward trend in all subfield volumes with prominent age effects on CA1. Due to differences in methods and limited sampling for any single study, the magnitude of age effects on Hc subfield volumes and their probable lifespan trajectories remain unclear. Here, we conducted a meta‐analysis on cross‐sectional studies (n = 48,278 participants, ages = 4–94 years) to examine the association between age and Hc subfield volumes in development (n = 11 studies), adulthood (n = 30 studies), and a combined lifespan sample (n = 41 studies) while adjusting estimates for sample sizes. In development, age was positively associated with DG and CA3‐4 volumes, whereas in adulthood a negative association was observed with all subfield volumes. Notably, the observed age effects were not different across subfield volumes within each age group. All subfield volumes showed a nonlinear age pattern across the lifespan with DG and CA3‐4 volumes showing a more distinct age trajectory as compared to the other subfields. Lastly, among all the study‐level variables, only female percentage of the study sample moderated the age effect on CA1 volume: a higher female‐to‐male ratio in the study sample was linked to the greater negative association between age and CA1 volume. These results document that Hc subfield volumes differ as a function of age offering broader implications for constructing theoretical models of lifespan memory development.
The kinetics of amino acid disappearance in the small intestine is related to the extent of amino acids absorbed in growing pigs

This study evaluated the importance of a correction for amino acids (AA) released into the hindgut on a measure of AA absorption kinetics and tested whether AA absorption kinetics are related to the extent of AA absorption using the growing pig as a model for humans. Thirty-six nine-week-old pigs (22·3 kg) received a diet containing whey protein as the sole protein source for 8 d. Pigs received their last meal containing the indigestible marker titanium dioxide before being euthanised at 1, 2, 3, 4, 6 and 12 h post-feeding. The entire content of each gastrointestinal tract (GIT) region was collected to determine AA released into the hindgut, and the kinetics and extent of AA absorption (uncorrected and corrected for AA entering the hindgut). Amounts of AA released into the hindgut increased over time (e.g. 33 and 180 mg of Glu for 4 and 6 h post-feeding). The corrected apparent amount of each AA absorbed from the GIT lumen after 4 h post-feeding was generally lower (P ≤ 0·05) than the uncorrected counterpart. Differences in both the kinetics and extent of AA absorption were observed across AA. For example, the time to reach half of the apparent AA absorption (T50) was 1·5 and 3·4 h for Met and Arg, respectively, whereas their extent of apparent absorption was 93 and 73 %. Negative correlations between parameters related to kinetics and the extent of apparent absorption were observed (e.g. for T50 r = −0·81; P < 0·001). The kinetics of AA absorption is related to the extent of AA absorption.
Geoarchaeological Research in Lower Khuzestan: State of the Art

This chapter presents an overview of the geoarchaeological research carried out, including new evidence on the Holocene palaeoenvironmental evolution of the plain, in particular the positions of the Persian Gulf coastline and the main rivers. The reconstruction is based on the analysis of the geological and archaeological data collected during the field campaigns in 2004, and new evidence derived from textual sources, maps, satellite images and aerial photographs. It concerns mainly the integration of the results of three recently completed PhD studies and additional remote sensing data. By means of a number of case-studies, the different datasets were integrated with a recently completed geomorphological map. The case-studies provide new insights into the complex human-environmental interactions in the plain, and demonstrate the added value of a multidisciplinary approach in such studies. Keywords:geoarchaeological research; Holocene; human-environmental interaction; Lower Khuzestan; palaeoenvironmental evolution; Persian Gulf coastline
Getting out of the bay faster: Assessing trauma team performance using trauma video review

Better team performance scores on trauma video review = decreased time to the next phase of care for patients in hemorrhagic shock BACKGROUND Minutes matter for trauma patients in hemorrhagic shock. How trauma team function impacts time to the next phase of care has not been rigorously evaluated. We hypothesized better team performance scores to be associated with decreased time to the next phase of trauma care. METHODS This retrospective secondary analysis of a prospective multicenter observational study included hypotensive trauma patients at 19 centers. Using trauma video review, we analyzed team performance with the validated Non-Technical Skills for Trauma scale: leadership, cooperation and resource management, communication, assessment/decision making, and situational awareness. The primary outcome was minutes from patient arrival to next phase of care; deaths in the bay were excluded. Secondary outcomes included time to initiation and completion of first unit of blood and inpatient mortality. Associations between team dynamics and outcomes were assessed with a linear mixed-effects model adjusting for Injury Severity Score, mechanism, initial blood pressure and heart rate, number of team members, and trauma team lead training level and sex. RESULTS A total of 441 patients were included. The median Injury Severity Score was 22 (interquartile range, 10–34), and most (61%) sustained blunt trauma. The median time to next phase of care was 23.5 minutes (interquartile range, 17–35 minutes). Better leadership, communication, assessment/decision making, and situational awareness scores were associated with faster times to next phase of care (all p < 0.05). Each 1-point worsening in the Non-Technical Skills for Trauma scale score (scale, 5–15) was associated with 1.6 minutes more in the bay. The median resuscitation team size was 12 (interquartile range, 10–15), and larger teams were slower (p < 0.05). Better situational awareness was associated with faster completion of first unit of blood by 4 to 5 minutes (p < 0.05). CONCLUSION Better team performance is associated with faster transitions to next phase of care in hypotensive trauma patients, and larger teams are slower. Trauma team training should focus on optimizing team performance to facilitate faster hemorrhage control. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.
Sea Surface Temperature and the Maximum Intensity of Atlantic Tropical Cyclones

Abstract An empirical relationship between climatological sea surface temperature (SST) and the maximum intensity of tropical cyclones in the North Atlantic basin is developed from a 31-year sample (1962–1992). This relationship is compared with the theoretical results described by Emanuel. The theoretical results are in agreement with the observations over a wide range of SST, provided that the tropopause temperature is assumed to be a function of SST. Each storm is examined to determine how close the observed intensity comes to the maximum possible intensity (MPI). Results show that only about 20% of Atlantic tropical cyclones reach 80% or more of their MPI at the time when they are the most intense. On average, storms reach about 55% of their MPI. Storms that are farther west and farther north tend to reach a larger fraction of their MPI. Storms are also more likely to reach a larger fraction of their MPI in August–November than in June–July. There is considerable interannual variability in the yearly .
Body mass index trajectories and mortality risk in Japan using a population-based prospective cohort study: the Japan Public Health Center-based Prospective Study

Abstract Background Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. Methods The data were extracted from Japan Public Health Center-based Prospective Study—a population-based prospective cohort study in Japan with participants aged 40–69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. Results Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05–1.16; Group 5, aHR: 1.16, 95% CI: 1.08–1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21–1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13–1.33) than Group 2 (low-to-high normal BMI trajectory). Conclusions Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population.
Associations among metabolic health, weight status, and various physical fitness components in Japanese adolescents: a cross-sectional study (NICE EVIDENCE study- Agano 3)

ABSTRACT Aim was to examine associations among metabolic health, weight status, and various physical fitness (PF) components in 1744 Japanese adolescents aged 13–14. Anthropometric measurements and PF tests (20 m shuttle run test [20mSRT], handgrip strength/body mass [HG], standing long jump [SLJ], and sit ups [SU]) were administered. The bottom sex-specific quintile of PF indicated “low fit”. Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to the International Obesity Task Force. Clustered metabolic risk was defined as the sum of Z scores for mean arterial pressure, non-high-density lipoprotein cholesterol, and HbA1c, divided by three, and ≥ 1 SD. Combination of weight status and scores for HG or SU were additively associated with clustered metabolic risk. Compared with the non-OW-moderate-high fit group, the OW-low HG group was 3.05 (95%CI: 1.88–4.97) times more likely to have clustered metabolic risk although risk was not significantly elevated in the OW-moderate-high HG group (1.52 [95%CI: 0.88–2.62]). A similar association was observed between OW and low SU scores but not between OW and low 20mSRT or SLJ scores. Adolescents with OW and moderate-high HG or SU scores had a lower prevalence of an unfavourable metabolic state than those with OW and low HG or SU results.
Evolving metallogenesis at the Troodos spreading axis

Summary An area of the eastern Troodos Massif has been mapped in detail to identify stages of volcanism, faulting and metallogenesis which could be related to the evolution of the late Cretaceous Troodos spreading axis. The field relations and comparisons with modern spreading ridges suggest the following succession of events. Pillowed and massive flows making up most of the lava volume were erupted on a relatively flat sea floor at the axis of a well-defined median valley. Volcaniclastic sediments accumulated during a hiatus in volcanism. The Mathiati massive sulphide formed in the vicinity of ridge-parallel fractures towards the margins of the rift valley, whilst ferromanganiferous oxide-sediments were deposited in the surrounding area. Normal faulting, at first parallel to the rift axis, then at 30–40° to it, accompanied formation of the rift-valley walls, together with renewed eruption of lavas, equivalent to the Upper Pillow Lavas. Small grabens and half-grabens, which formed during this stage, were fringed with lava talus, then gradually filled, first with ferromanganiferous umbers precipitated from local hydrothermal vents, then, as the spreading axis migrated away, by more hydrogenous metal-oxide sediments and later deep-sea deposits. In Cyprus, metallogenesis persisted from the median valley to the flanks of particular regions of crust. Also the inferred site of formation of the Mathiati sulphide towards the margin of the rift valley differs from that of the known ‘smokers’ which are active closer to the spreading axis.
Stylolites; their nature and origin

ABSTRACT Stylolites are defined in terms of rock grain fabrics; aggregate stylolites and intergranular stylolites are differentiated. A classification of stylolites is given on the basis of the pure geometry of the stylolites themselves and on their relationship to the bedding plane. Megascopic and microscopic observations on stylolite features from the Joppa Limestone Member of the Ste. Genevieve Limestone Formation (Upper Mississippian), the Downeys Bluff Limestone Formation (Upper Mississippian), from Cave-In-Rock fluorspar mines in southern Illinois, and from the Jefferson City Formation (Lower Ordovician) near Rolla, Missouri, are described and their interpretation discussed. Under the microscope, bituminous material, clay minerals, silica, dolomite, sulfides, and fluorite are observed near or within the stylolite seams. Dissolution, recrystallization (neomorphism), grain growth, grain orientation, pressure-twinning, pressure-shadows, micro-faulting and shearing, cavity filling, and geopetal features have been observed along stylolite seams. Difficulties entailed in the mechanism of stylolitization by the pressure-solution theory and contraction-pressure theory are brought out. This study indicates that stylolites form during the various stages of diagenesis. Most frequently, stylolitization in tectonically and metamorphically non-affected carbonates is initiated during the early burial stage, that is, the stage of radiaxial and "dog-tooth" type cementation, and probably ends concordantly with the complete elimination of pore space by drusy mosaic carbonate. It appears that stylolites in tectonites are more the result of pressure-solution and recrystallization phenomena due to the physical factors involved rather than to the chemical factors. It is proposed that in solving the stylolite problem, various diagenetic fabric and chemical changes should be considered.
Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses

Abstract Background Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX‐2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Hypothesis Furosemide‐induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Animals Eight healthy mares. Methods Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30‐minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Results Four‐hour urine volume was (mean ± SD) ~25% less (P < .001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P < .001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Conclusions and Clinical Importance Though COX‐2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide‐induced diuresis, and possibly, risk of nephrotoxicosis.
Private healthcare sector spine surgery: patient and surgeon profiles from a large open medical scheme in South Africa.

Background It is generally understood that the profile of spine surgery varies by setting, based on factors such as the age profile of the population, the economic context and access to healthcare. Relatively little is known about the profile of spine surgery in South Africa, although one previous report from the public healthcare sector suggested a high burden of trauma and infection-related surgery. To our knowledge, there has been no formal investigation in the private sector. A holistic understanding of spine surgery within our setting may be beneficial for applications such as resource allocation and informing the training needs of future specialists. Objectives To provide insight into spinal surgery in the South African private healthcare sector by describing spine surgery characteristics within a large open medical scheme, including both patient and surgeon profiles. Methods This retrospective review included adult inpatient spine surgeries funded by the largest open medical scheme in South Africa between 2008 and 2017. An anonymized dataset extracted from the scheme records included patient demographics, ICD-10 codes, procedure codes and surgeon specialization. Descriptive patient and surgery data were presented. Furthermore, the association between patient and surgery factors and surgeon specialization was investigated using univariate and multivariate analyses. Results A total of 49,576 index spine surgeries were included. The largest proportion of surgeries involved members 40-59 years old (n=23,543, 48%), approximately half involved female members (n=25,293, 51%) and most were performed by neurosurgeons (n=35,439, 72%). At least 37,755 (76%) surgeries were for degenerative pathology, 2,100 (4%) for trauma and 242 (0.5%) for infection. Adjusted risk ratios (aRR) significantly associated with orthopaedic surgeon specialization included cervical spine region aRR = 0.49 (95% C.I. 0.39-0.61), trauma aRR = 1.50 (95% C.I. 1.20-1.88), deformity aRR = 1.77 (95% C.I. 1.33-2.35) and blood transfusion aRR = 1.46 (95% C.I. 1.12-1.91). Conclusion Spine surgery in South Africa's largest open medical scheme was dominated by surgery for degenerative pathology in older adults and was performed largely by neurosurgeons. This constituted a stark contrast to a previous report from the public sector and highlighted a mismatch between exposure during public sector registrar training and private practice post-specialization. The findings support the need for private-public collaboration as well as the importance of spine fellowships for all specialists intending to practice spine surgery.
Macrostructural Cerebellar Neuroplasticity Correlates With Motor Recovery After Stroke

Background Motor recovery varies across post-stroke individuals, some of whom require a better rehabilitation strategy. We hypothesized that macrostructural neuroplasticity of the motor control network including the cerebellum might underlie individual differences in motor recovery. Objectives. To gain insight into the macrostructural neuroplasticity after stroke, we examined 52 post-stroke individuals using both the Fugl-Meyer assessment and structural magnetic resonance imaging. Methods We performed voxel-based lesion symptom mapping and cross-sectional voxel-based morphometry to correlate the motor scores with the lesion location and the gray matter volume (GMV), respectively. Longitudinal data were available at ~8 and/or 15 weeks after admission from 43 individuals with supratentorial lesions. We performed a longitudinal VBM analysis followed by a multiple regression analysis to correlate between the changes of the motor assessment scores and those of GMV overtime. Results We found a cross-sectional correlation of residual motor functioning with GMV in the ipsilesional cerebellum and contralesional parietal cortex. Longitudinally, we found increases in GMV in the ipsilesional supplementary motor area, and the ipsilesional superior and inferior cerebellar zones, along with a GMV decrease in the ipsilesional thalamus. The motor recovery was correlated with the GMV changes in the superior and inferior cerebellar zones. The regaining of upper-limb motor functioning was correlated with the GMV changes of both superior and inferior cerebellum while that of lower-limb motor functioning with the GMV increase of the inferior cerebellum only. Conclusions The present findings support the hypothesis that macrostructural cerebellar neuroplasticity is correlated with individual differences in motor recovery after stroke.