bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate prediction of dynamic protein–ligand binding using P‐score ranking
Authors: Ibrahim Peter E. G. F. , Zuccotto Fabio , Zachariae Ulrich , Gilbert Ian , Bodkin Mike 
Published: April 2024

AbstractProtein–ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein–ligand system, solvent‐mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein–ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P‐score. This is illustrated using six different protein–ligand targets as case studies.
Sarcopenia, adiposity and large discordance between cystatin C and creatinine‐based estimated glomerular filtration rate in patients with cancer
Authors: Hanna Paul E. , Ouyang Tianqi , Tahir Ismail , Katz‐Agranov Nurit , Wang Qiyu , Mantz Lea , Strohbehn Ian , Moreno Daiana , Harden Destiny , Dinulos James E. , Cosar Duru , Seethapathy Harish , Gainor Justin F. , Shah Sachin J. , Gupta Shruti , Leaf David E. , Fintelmann Florian J. , Sise Meghan E. 
Published: April 2024

AbstractBackgroundCreatinine‐based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C‐based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer.MethodsThis study is a cross‐sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross‐sectional areas were measured at the level of the third lumbar vertebral body using a validated deep‐learning pipeline. CT‐defined sarcopenia was defined using independent sex‐specific cut‐offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex‐specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE.ResultsOf the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non‐Hispanic white), 320 (58.7%) met the criteria for CT‐defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT‐defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12–3.24; aOR 2.01, 95% CI 1.15–3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21–4.51; aOR 2.23, 95% CI 1.19–4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably.ConclusionsCT‐defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.
Attentional development is altered in toddlers with congenital heart disease
Authors: Bonthrone Alexandra F. , Kyriakopoulou Vanessa , Mason Luke , Chew Andrew , Falconer Shona , Kelly Christopher J. , Simpson John , Pushparajah Kuberan , Johnson Mark H. , Edwards A. David , Nosarti Chiara , Jones Emily J. H. , Counsell Serena J. 
Published: April 2024

AbstractBackgroundCongenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD. Our aim was to characterise visual attention in toddlers with CHD compared to controls and identify associations with parent‐rated effortful control.MethodsThirty toddlers with CHD (19 male, median (IQR) age at assessment 22.2 (22–23.1) months) and 66 controls from the developing human connectome project (36 male, age at assessment 22 (21.5–23.8) months) using eye‐tracking tasks designed to assess multiple components of visual attention. Analyses of co‐variance and regressions were used to identify differences between groups and relationships between gaze behaviours and parent‐rated effortful control.ResultsToddlers with CHD were less accurate when switching behaviours (set‐shifting) [median (IQR) 79%, (28–100)] compared to controls [100% (86–100), pFDR = 0.032], with worse accuracy associated with lower parent‐rated effortful control in CHD but not controls (interaction pFDR = 0.028). Reaction times were slower during selective [CHD 1243 ms (986–1786), controls 1065 ms (0851–1397), pFDR<0.001] and exogenous attention tasks [CHD 312 ms (279–358), control 289 (249–331), (pFDR = 0.032) and endogenous attention was less mature (prolonged looks at facial stimuli CHD 670 ms (518–885), control 500 ms (250–625), (pFDR = 0.006). These results were unrelated to differences in cognition or socioeconomic status. In contrast, the allocation of attentional resources was preserved in CHD.ConclusionsWe identified a profile of altered attention and early executive functioning development in CHD. Eye‐tracking may provide clinically feasible, early objective measures of attention and executive function development in CHD.
Canal disinfection using Nd: YAG Laser, synchronized microbubble‐photodynamic activation, and carbon quantum dots on microhardness, smear layer removal, and extrusion bond strength of zirconia post to canal dentin. An invitro scanning electron microscopic analysis
Authors: Alkhudhairy Fahad 
Published: April 2024

AbstractEvaluation of the impact of the latest root canal disinfectant, that is carbon quantum dots (CQDs), synchronized microbubble‐photodynamic activation (SYMPA), and Nd: YAG laser along with ethylenediaminetetraacetic acid (EDTA) as a final irrigant on the Marten hardness (MH), smear layer (SL) removal, and extrusion bond strength (EBS) of zirconia post to the canal dentin. Eighty intact single‐rooted premolars were obtained and disinfected using 0.5% chloramine‐T solution. Root canal preparation was performed using ProTaper files followed by obturation. The post space was prepared for prefabricated zirconia post and all the teeth were randomly divided into four groups based on the disinfection used (n = 20 each) Group 1: 5.25% NaOCl + 17% EDTA (Control), Group 2: Nd: YAG laser + 17% EDTA, Group 3: SYMPA + 17% EDTA, and Group 4: CQDs + 17% EDTA. MH, SL removal, and EBS of zirconia post‐bonded to root dentin were performed using a microhardness tester, scanning electron microscope (SEM), and universal testing machine, respectively. Both intragroup and intergroup comparisons were performed using one‐way analysis of variance (ANOVA) and posthoc‐Tukey test for significant difference (p < .05). Group 2 samples (Nd: YAG laser + 17% EDTA) (0.24 ± 0.06 GPa) exhibited highest values of MH. Samples in group 3 (SYMPA + 17% EDTA) treated teeth unveiled the lowest MH scores (0.13 ± 0.02 GPa). Moreover, the coronal third of Group 3 specimens (SYMPA and 17% EDTA) (1.54 ± 0.31) eliminated SL from the canal with the greatest efficacy as well as presented the highest EBS (10.13 ± 0.69 MPa). However, the apical third of Group 1 samples (5.25% NaOCl + 17% EDTA) (2.95 ± 0.33) exhibited the least efficient elimination of SL from the radicular dentin as well as the lowest bond strength (5.11 ± 0.19 MPa) of zirconia post to the dentin. The SYMPA technique with 17% EDTA proved highly effective in removing the SL from canal dentin and enhancing the EBS of zirconia posts. The least preferable method for SL removal and MH improvement was found to be 5.25% NaOCl + 17% EDTA. CQDs and Nd: YAG laser demonstrated satisfactory smear layer removal properties from the canal, along with achieving appropriate bond strength of zirconia posts.Research Highlights
Nd: YAG laser and 17% EDTA as canal disinfectant exhibited the highest values of MH.
Specimens irrigated with SYMPA and 17% EDTA eliminated SL from the canal with the greatest efficacy.
The coronal third of Group 3 (SYMPA + 17% EDTA) samples unveiled the highest zirconia post‐bond integrity score to the canal dentin.
Cohesive failure was a dominant failure type among different experimental groups.
Neuropathogenic role of astrocyte‐derived extracellular vesicles in HIV‐associated neurocognitive disorders
Authors: Chemparathy Divya T. , Ray Sudipta , Ochs Chase , Ferguson Natasha , Gawande Dinesh Y. , Dravid Shashank M. , Callen Shannon , Sil Susmita , Buch Shilpa 
Published: April 2024

AbstractOur previous findings demonstrated that astrocytic HIF‐1α plays a major role in HIV‐1 Tat‐mediated amyloidosis which can lead to Alzheimer's‐like pathology‐a comorbidity of HIV‐Associated Neurocognitive Disorders (HAND). These amyloids can be shuttled in extracellular vesicles, and we sought to assess whether HIV‐1 Tat stimulated astrocyte‐derived EVs (ADEVs) containing the toxic amyloids could result in neuronal injury in vitro and in vivo. We thus hypothesized that blocking HIF‐1α could likely mitigate HIV‐1 Tat‐ADEV‐mediated neuronal injury. Rat hippocampal neurons when exposed to HIV‐1 Tat‐ADEVs carrying the toxic amyloids exhibited amyloid accumulation and synaptodendritic injury, leading to functional loss as evidenced by alterations in miniature excitatory post synaptic currents. The silencing of astrocytic HIF‐1α not only reduced the biogenesis of ADEVs, as well as amyloid cargos, but also ameliorated neuronal synaptodegeneration. Next, we determined the effect of HIV‐1 Tat‐ADEVs carrying amyloids in the hippocampus of naive mice brains. Naive mice receiving the HIV‐1 Tat‐ADEVs, exhibited behavioural changes, and Alzheimer's ’s‐like pathology accompanied by synaptodegeneration. This impairment(s) was not observed in mice injected with HIF‐1α silenced ADEVs. This is the first report demonstrating the role of amyloid‐carrying ADEVs in mediating synaptodegeneration leading to behavioural changes associated with HAND and highlights the protective role of HIF‐1α.
Diagnostic Model for Proliferative HCC Using LI‐RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI‐ICI Combination
Authors: Lu Mengtian , Yan Zuyi , Qu Qi , Zhu Guodong , Xu Lei , Liu Maotong , Jiang Jifeng , Gu Chunyan , Chen Ying , Zhang Tao , Zhang Xueqin 
Published: April 2024

BackgroundProliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis.PurposeTo develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI‐RADS) and assess its prognostic value.Study TypeRetrospective.Population241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).Field Strength/Sequence3.0 T, T1‐ and T2‐weighted, diffusion‐weighted, in‐ and out‐phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid‐enhanced imaging.AssessmentLI‐RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high‐ and low‐risk groups. Follow‐up occurred every 3–6 months, and recurrence‐free survival (RFS), progression‐free survival (PFS) and overall survival (OS) in different groups were compared.Statistical TestsFisher's test or chi‐square test, t‐test or Mann–Whitney test, logistic regression, Harrell's concordance index (C‐index), Kaplan–Meier curves, and Cox proportional hazards. Significance level: P < 0.05.ResultsThe diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C‐index of 0.823 (training set) and 0.804 (validation set). Median follow‐up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination‐treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high‐risk and low‐risk groups post‐surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination‐treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years).Data ConclusionThe MR‐based model could pre‐treatment identify proliferative HCC and assist in prognosis evaluation.Level of Evidence4.Technical EfficacyStage 2.
Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection
Authors: Jonas Maureen M. , Romero Rene , Rosenthal Philip , Lin Chuan‐Hao , Verucchi Gabriella , Wen Jessica , Balistreri William F. , Whitworth Suzanne , Bansal Sanjay , Leung Daniel H. , Narkewicz Michael R. , Gonzalez‐Peralta Regino P. , Mangia Alessandra , Karnsakul Wikrom , Rao Girish S. , Shao Jiang , de Jong Jan , Parhy Bandita , Osinusi Anu , Kersey Kathryn , Murray Karen F. , Sokal Etienne M. , Schwarz Kathleen B. 
Published: April 2024

AbstractBackgroundThe safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated.MethodsIn this Phase 2, multicenter, open‐label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group.FindingsAmong 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5‐year‐olds, 93% (68/73) among 6–11‐year‐olds, and 95% (97/102) among 12–17‐year‐olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17‐year‐olds; vomiting, cough, and headache in 6–11‐year‐olds; and vomiting in 3–5‐year‐olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS‐331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight‐based dosing for children in this age range.InterpretationThe pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection.
Does Meal or Water Intake Affect Ultrasound Attenuation Coefficient Estimate?
Authors: Ferraioli Giovanna , De Silvestri Annalisa , Barr Richard G. 
Published: April 2024

ObjectivesTo assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content.MethodsThe study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i‐series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data.ResultsTwenty‐six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B‐mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time‐point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin‐to‐liver capsule into the models.ConclusionsThe measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result.
Surgical complications and subsequent revision surgeries among noma cases treated in Ethiopia
Authors: Gebretsadik Heron Gezahegn 
Published: April 2024

AbstractIntroductionNoma, an overlooked infectious disease, inflicts severe facial tissue damage, posing substantial challenges in patient care. This study delves into surgical complications and subsequent revision surgeries among noma cases treated in Ethiopia.Materials and MethodsThe research employed a cross‐sectional retrospective review of medical records treated between 2007 and 2019 retrieved from the Facing Africa database.ResultsThe review encompasses 235 noma cases. Twenty‐four cases (19 females and 5 males) experienced various complications, predominately major complications leading to subsequent revision surgeries. The identified complications included flap necrosis, abscess formation, tenderness, graft site infection, flap bulking, dental misalignment, corner of the mouth dehiscence, infected bone and plate, flap malpositioning, restricted mouth opening with ankylosis, neuropathic pain, recurrent flap infection, and offensive odor. Revision surgeries included wound cleansing, abscess drainage, skin graft removal, exploratory surgery, wound care, debulking, scar removal, debridement, trismus release, commisuroplasty, and flap repositioning.ConclusionThese findings illuminate the intricacies of noma surgery in Ethiopia, emphasizing the importance of understanding the nature and frequency of complications for optimizing treatment outcomes. Insights from this study can guide healthcare providers, especially novice surgeons, and policymakers, in refining surgical interventions and enhancing outcomes for noma patients. Improved knowledge in this realm is crucial for advancing patient care and developing targeted interventions.Level of Evidence5.
Temporal evolution of plankton and particles distribution across a mesoscale front during the spring bloom
Authors: Panaïotis Thelma , Poteau Antoine , Riquier Émilie Diamond , Catalano Camille , Courchet Lucas , Motreuil Solène , Coppola Laurent , Picheral Marc , Irisson Jean‐Olivier 
Published: April 2024

AbstractThe effect of mesoscale features on the distribution of planktonic organisms are well documented. Yet, the interaction between these spatial features and the temporal scale, which can result in sudden increases of the planktonic biomass, is less known and not described at high resolution. A permanent mesoscale front in the Ligurian Sea (north‐western Mediterranean) was repeatedly sampled between January and June 2021 using a SeaExplorer glider equipped with an Underwater Vision Profiler 6 (UVP6), a versatile in situ imager. Both plankton and particle distributions were resolved throughout the spring bloom to assess whether the front was a location of increased zooplankton concentration and whether it constrained particle distribution. Over the 5 months, the glider performed more than 5000 dives and the UVP6 collected 1.1 million images. We focused our analysis on shallow (300 m) transects, which gave a horizontal resolution of 900 m. About 13,000 images of planktonic organisms were retained. Ordination methods applied to particles and plankton concentrations revealed strong temporal variations during the bloom, with a succession of various zooplankton communities. Changes in particle abundance and size could be explained by changes in the plankton community. The front had a strong influence on particle distribution, while the signal was not as clear for plankton, probably because of the relatively small number of imaged organisms. This work confirms the need to sample both plankton and particles at fine scale to understand their interactions, a task for which automated in situ imaging is particularly adapted.
Long‐Term Globus Pallidus Internus Deep Brain Stimulation in Pediatric Non‐Degenerative Dystonia: A Cohort Study and a Meta‐Analysis
Authors: Duga Valentina , Giossi Riccardo , Romito Luigi Michele , Stanziano Mario , Levi Vincenzo , Panteghini Celeste , Zorzi Giovanna , Nardocci Nardo 
Published: April 2024

AbstractBackgroundThe evidence in the effectiveness of deep brain stimulation in children with medication‐refractory non‐degenerative monogenic dystonia is heterogeneous and long‐term results are sparse.ObjectivesThe objective is to describe long‐term outcomes in a single‐center cohort and compare our results with a meta‐analysis cohort form literature.MethodsWe performed a retrospective single‐center cohort study including consecutive pediatric patients with non‐degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual‐patient data meta‐analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke‐Fahn‐Marsden Dystonia Rating Scale‐movement (BFMDRS‐M) score.ResultsThe clinical cohort included 25 patients with a mean study follow‐up of 11.4 years. The meta‐analysis cohort included 224 patients with a mean follow‐up of 3 years. Overall, the BFMDRS‐M mean improvements at 1 year and at last follow‐up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta‐analysis cohort, respectively. TOR1A‐dystonia showed the greatest and most stable BFMDRS‐M improvement in both cohorts at 1 year and at last follow‐up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta‐analysis cohort), followed by SGCE‐dystonia (63% and 63.9% in the meta‐analysis cohort). THAP1‐dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta‐analysis cohort) and KMT2B‐dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta‐analysis cohort) showed a less pronounced or sustained response.ConclusionGlobus pallidus deep brain stimulation long‐term treatment seems effective with a possible gene‐specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.