bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coastal marine megaripple fields are metabolic hotspots with highly dynamic oxygen exchange
Authors: Berg Peter , Huettel Markus 
Published: August 2023

AbstractMegaripples are current‐generated seafloor bedforms of well‐sorted sand or gravel and wavelengths over 1 m. In this aquatic eddy covariance study, we measured large rates of benthic primary production and respiration for a shallow‐water sandy megaripple field exposed to strong tidally driven currents and intense sunlight. Current and light were the main short‐term drivers of a highly dynamic oxygen exchange. Daytime oxygen release as high as 300 mmol m−2 d−1 and nighttime oxygen uptake up to −100 mmol m−2 d−1 were likely sustained by current‐driven transport of oxygen, nutrients, and organic matter (fuel) into and out of the sand and superimposed by rapid internal cycling. Seasonal differences in temperature (45%) and light (69%) between April and September were the main long‐term drivers of substantially greater rates of gross primary production and respiration in September. The megaripples functioned as an intense metabolic hotspot with carbon cycling rates larger than those of most near‐shore sediments.
Development of a scoring system for predicting primary resistance to venetoclax plus hypomethylating agents (HMAs) in acute myeloid leukemia patients
Authors: Zong Lihong , Yin Minyue , Kong Jinyu , Zhang Jian , Song Baoquan , Zhu Jinzhou , Xue Shengli , Wu Xiaojin , Wu Depei , Bao Xiebing , Qiu Huiying 
Published: August 2023

AbstractIn recent years, one of the most promising advances in the treatment of acute myeloid leukemia (AML) is the combination of a hypomethylating agent (HMA) with the BCL2 inhibitor venetoclax (VEN). To better understand the key factors associated with the response of VEN plus HMA, 212 consecutive AML patients were retrospectively recruited to establish and validate a scoring system for predicting the primary resistance to VEN‐based induced therapy. All AML patients were divided randomly into a training set (n = 155) and a validation set (n = 57). Factors were selected using a multivariate logistic regression model, including FAB‐M5, myelodysplastic syndrome‐secondary acute myeloid leukemia (MDS‐sAML), RUNX1‐RUNX1T1 and FLT3‐ITD mutation (FLT3‐ITDm). A nomogram was then constructed including all these four predictors. The nomogram both presented a good performance of discrimination and calibration, with a C‐index of 0.770 and 0.733 in the training and validation set. Decision curve analysis also indicated that the nomogram was feasible to make beneficial decisions. Eventually a total scoring system of 8 points was developed, which was divided into three risk groups: low‐risk (score 0–2), medium‐risk (score 3–4), and high‐risk (score 5–8). There was a significant difference in the nonremission (NR) rate of these three risk groups (22.8% vs. 60.0% vs. 77.8%, p < 0.001). After adjustment of the other variables, patients in medium‐ or high‐risk groups also presented a worse event‐free survival (EFS) than that in the low‐risk group (hazard ratio [HR] = 1.62, p = 0.03). In conclusion, we highlighted the response determinants of AML patients receiving a combination therapy of VEN plus HMAs. The scoring system can be used to predict the resistance of VEN, providing better guidance for clinical treatment.
Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene
Authors: Zhang Yongli , Bi Shaohua , Dai Liying , Zhao Yuwei , Liu Yu , Shi Zifeng 
Published: August 2023

AbstractBackgroundCraniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction.MethodsTrio whole‐exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay.ResultsThe proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon.ConclusionFor this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.
Effect of alumina nano‐particles on collapse behavior and energy absorption of laterally loaded glass/epoxy composite tubes
Authors: Hegazy Dalia A. , Awd Allah Mahmoud M. , Alshahrani Hassan , Sebaey Tamer A. , Abd El‐baky Marwa A. 
Published: August 2023

AbstractDue to its exceptional mechanical and crashworthiness properties, lightweight nanocomposites have recently been used more and more in aviation, defense, nautical, and automotive applications. Nanocomposite cylinders could be effectively employed in this respect as energy‐absorbing components for decreasing the impact energy during vehicle crashes. The current work examined the crashworthiness response of nano‐alumina (Al2O3) filled glass fiber reinforced epoxy (GFRE) composite tubes using quasi‐static lateral compressive loads. Crushing profiles and crush force–deformation curves of all representative samples were recorded and discussed. The total absorbed energy (AE) and specific absorbed energy (SEA) for tested specimens were assessed. Furthermore, a multi‐attribute decision making (MADM) technique known as complex proportional assessment (COPRAS) was used to compute the optimum nano‐Al2O3 wt%. Based on the experimental results, the addition of 1, 2, and 3 wt% of nano‐Al2O3 enhanced AE by 7.69%, 18.14%, and 51.21% and SEA by 3.43%, 13.98%, and 39.84%, respectively. While deteriorations of 6.59% and 17.41% in AE and SEA, respectively, were recorded with the addition of 4 wt% of nano‐Al2O3. Overall findings showed that (GFRE) composite tubes with 3 wt% of nano‐Al2O3 have a special potential to absorb energy.Highlights
The designed tubes, that is, GFRE tubes filled with 0, 1, 2, 3, and 4 wt% of nano‐alumina (Al2O3) were created using wet‐wrapping by hand lay‐up technique.
The fabricated tubes were subjected to lateral compression loads to investigate their crashworthiness behavior.
The crashing load and absorbed energy versus displacement responses for the laterally loaded tubes were exposed. The histories of deformation were also examined.
Complex proportional assessment (COPRAS) was used to find the optimum nano‐Al2O3 wt%.
Biodegradable and flexible fiber‐reinforced composite sheet from tannery solid wastes: An approach of waste minimization
Authors: Ahmed Hasan , Noyon Md. Ashikur Rahaman , Uddin Md. Elias , Jamal Mamun , Palaniappan Sathish Kumar 
Published: August 2023

AbstractThe rising concern towards environmental issues and non‐recyclable solid wastes preservation needs has led to the development of high‐performance biodegradable composite materials with new functionalities. In this regard, the current study focused on fabricating flexible and biodegradable composite sheets by utilizing waste buffing dust (BD) and sugarcane fiber (SF). Flexible composite sheets were fabricated using simple solution casting method with different mixing ratios of BD and SF. Wide range of characterizations like ultraviolet‐vis spectroscopy, Fourier‐transform infrared spectroscopy, thermogravimetric analysis, tensile tests, x‐ray diffractometry, scanning electron microscopy, oxygen gas transmittance rate, and soil burial tests were conducted to comprehensively evaluate their performance. The obtained results were highly promising which reveals strong bonding between BD and SF along with a uniform surface quality. Particularly, the enhancement in various key characteristics was observed for composite sheets compared to pure BD sheets. The composite sheets with the optimal content of natural rubber latex demonstrated a significant increase in tensile strength, elongation, hardness, and density by 61%, 42%, 37%, and 44%, respectively. Additionally, the composite sheet has witnessed significant improvements with an increase by 36% in gas barrier property and an enhancement of 39% in biodegradability. These findings highlight the potential of these composite sheets as a versatile material suitable for a wide range of applications which includes packaging, interior furnishing industries, and reinforcing elements in the footwear industry. Numerous advantages like simplicity, cost‐effectiveness, and flexibility of these composite sheets offer an environmentally friendly alternative that is capable of reducing waste and promoting sustainable practices.Highlights
Fabricated composite sheets from waste BD and SF.
Strong bonding and uniform surface quality observed.
Improved thermal stability, gas barrier, and biodegradability.
Enhancements in tensile strength, elongation, hardness, and density.
Versatile eco‐friendly material for packaging and furnishings.
Association of amnioinfusion volume at the time of surgery for twin‐twin transfusion syndrome and latency to delivery
Authors: Forde Braxton , Lim Foong‐Yen , McKinney David N. , Habli Mounira , Markham Kara B. , Hoffman Mallory , Tabbah Sammy , Oria Marc , Peiro Jose L. 
Published: August 2023

AbstractObjectiveTo evaluate the impact of amnioinfusion and other peri‐operative factors on pregnancy outcomes in the setting of Twin‐twin transfusion syndrome (TTTS) treated via fetoscopic laser photocoagulation (FLP).MethodsRetrospective study of TTTS treated via FLP from 2010 to 2019. Pregnancies were grouped by amnioinfusion volume during FLP (<1 L vs. ≥1 L). The primary outcome was latency from surgery to delivery. An amnioinfusion statistic (AIstat) was created for each surgery based on the volume of fluid infused and removed and the preoperative deepest vertical pocket. Regression analysis was planned to assess the association of AIstat with latency.ResultsPatients with amnioinfusion of ≥1 L at the time of FLP had decreased latency from surgery to delivery (61 ± 29.4 vs. 73 ± 28.8 days with amnioinfusion <1 L, p < 0.001) and increased preterm prelabor rupture of membranes (PPROM) <34 weeks (44.7% vs. 33.5%, p = 0.042). Amnioinfusion ≥1 L was associated with an increased risk of delivery <32 weeks (aRR 2.6, 95% CI 1.5–4.5), 30 weeks (aRR 2.4, 95% CI 1.5–3.8), and 28 weeks (aRR 1.9, 95% CI 1.1–2.3). Cox‐proportional regression revealed that AIstat was inversely associated with latency (HR 1.1, 95% CI 1.1–1.2).ConclusionAmnioinfusion ≥1 L during FLP was associated with decreased latency after surgery and increased PPROM <34 weeks.
Risk of cancer with immunosuppressants compared to immunomodulators in multiple sclerosis: A nested case–control study within the French nationwide claims database
Authors: Bosco‐Lévy Pauline , Boutmy Emmanuelle , Guiard Estelle , Foch Caroline , Lassalle Régis , Favary Clélia , Sabidó Meritxell , Blin Patrick 
Published: August 2023

AbstractPurposeThe objective was to compare the risk of malignancies in real‐world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS).MethodsA nested case–control study was designed within a new‐user cohort of all patients with MS who initiated a first IM or IS between 2008 and 2014, and without cancer history, using the information of the SNDS nationwide French claims database. Incident cancer cases were matched with up to six controls on year of birth, sex, initiation date, and disease risk score of cancer. A conditional logistic regression (odds ratio [95% confidence interval]) was used to compare exclusive IS versus IM use during follow‐up and according to three use durations.ResultsFrom 28 720 newly treated patients with MS, 407 incident cancers were observed during the follow‐up with 2324 matched controls. A significant increase in cancer risk was observed for IS compared with IM (1.36 [1.05, 1.77]), with similar increases for the first 2 years of use but not for ≥2 years (1.06 [0.65, 1.75]). Similar increase was also observed for IS with indications other than MS (1.37 [1.04, 1.81]) but not for IS indicated only in MS (1.03 [0.45, 2.34]).ConclusionsCompared with IM, a 37% increase in cancer risk was observed for IS with indications other than MS and used for a short duration (≤2 years) but not for IS indicated only in MS. The absence of risk for prolonged exposure of IS with indications other than MS is not in favor of a causal relation with these drugs.
SalmonellaYqiC exerts its function through an oligomeric state
Authors: Huang Wei‐Chun , Chen Wai‐Ting , Chen Yueh‐Chen , Fang Shiuh‐Bin , Huang Tzu‐Wen , Chang Pei‐Ru , Chang Yu‐Chu 
Published: August 2023

AbstractProtein oligomerization occurs frequently both in vitro and in vivo, with specific functionalities associated with different oligomeric states. The YqiC protein from Salmonella Typhimurium forms a homotrimer through its C‐terminal coiled‐coil domain, and the protein is closely linked to the colonization and invasion of the bacteria to the host cells. To elucidate the importance of the oligomeric state of YqiC in vivo and its relation with bacterial infection, we mutated crucial residues in YqiC's coiled‐coil region and confirmed the loss of trimer formation using chemical crosslinking and size exclusion chromatography coupled with multiple angle light scattering (SEC‐MALS) techniques. The yqiC‐knockout strain complemented with mutant YqiC showed significantly reduced colonization and invasion of Salmonella to host cells, demonstrating the critical role of YqiC oligomerization in bacterial pathogenesis. Furthermore, we conducted a protein–protein interaction study of YqiC using a pulled‐down assay coupled with mass spectrometry analysis to investigate the protein's role in bacterial virulence. The results reveal that YqiC interacts with subunits of Complex II of the electron transport chain (SdhA and SdhB) and the β‐subunit of F0F1‐ATP synthase. These interactions suggest that YqiC may modulate the energy production of Salmonella and subsequently affect the assembly of crucial virulence factors, such as flagella. Overall, our findings provide new insights into the molecular mechanisms of YqiC's role in S. Typhimurium pathogenesis and suggest potential therapeutic targets for bacterial infections.
Surgical and functional outcomes of Retzius‐sparing robotic‐assisted radical prostatectomy versus conventional robotic‐assisted radical prostatectomy in patients with biopsy‐confirmed prostate cancer. Are outcomes worth it? Systematic review and meta‐analysis
Authors: O'Connor‐Cordova Mario A. , Macías Alan Gabriel Ortega , Sancen‐Herrera Juan Pablo , Altamirano‐Lamarque Francisco , Vargas del Toro Alexis , Peddinani Bharat Kumar , Canal‐Zarate Pia , O'Connor‐Juarez Mario A. 
Published: August 2023

AbstractBackgroundRadical prostatectomy is the standard of care for prostate cancer. Retzius‐sparing robotic‐assisted radical prostatectomy (RS‐RARP) is being widely adopted due to positive functional outcomes compared to conventional robotic‐assisted radical prostatectomy (c‐RARP). Concerns regarding potency, oncological outcomes, and learning curve are still a matter of debate.MethodsFollowing Preferred Instrument for Systematic Reviews and Meta‐Analysis guidelines and PROSPERO registration CRD42023398724, a systematic review was performed in February 2023 on RS‐RARP compared to conventional c‐RARP. Outcomes of interest were continence recovery, potency, positive surgical margins (PSM), biochemical recurrence (BCR), estimated blood loss (EBL), length of stay (LOS), operation time and complications. Data were analyzed using R version 4.2.2.ResultsA total of 17 studies were included, totaling 2751 patients, out of which 1221 underwent RS‐RARP and 1530 underwent c‐RARP. Continence was analyzed using two definitions: zero pad and one safety pad. Cumulative analysis showed with both definitions statistical difference in terms of continence recovery at 1 month (0 pad odds ratio [OR] = 4.57; 95% confidence interval [CI] = [1.32–15.77]; Safety pad OR = 13.19; 95% CI = [8.92–19.49]), as well as at 3 months (0 pad OR, 2.93; 95% CI = [1.57–5.46]; Safety pad OR = 5.31; 95% CI = [1.33–21.13]). Continence recovery at 12 months was higher in the one safety pad group after RS‐RARP (OR = 4.37; 95% CI = [1.97–9.73]). The meta‐analysis revealed that overall PSM rates without pathologic stage classification were not different following RS‐RARP (OR = 1.13; 95% CI = [0.96–1.33]. Analysis according to the tumor stage revealed PSM rates in pT2 and pT3 tumors are not different following RS‐RARP compared to c‐RARP (OR = 1.46; 95% CI = [0.84–2.55]) and (OR = 1.41; 95% CI = [0.93–2.13]), respectively. No difference in potency at 12 months (OR = 0.98; 95% CI = [0.69–1.41], BCR at 12 months (OR = 0.99; 95% CI = [0.46–2.16]), EBL (standardized mean difference [SMD] = −0.01; 95% CI = [−0.31 to 0.29]), LOS (SMD = −0.01; 95% CI = [−0.48 to 0.45]), operation time (SMD = ‐0.14; 95% CI = [−0.41 to 0.12]) or complications (OR = 0.9; 95% CI = [0.62–1.29]) were observed.ConclusionsOur analysis suggests that RS‐RARP is safe and feasible. Faster continence recovery rate is seen after RS‐RARP. Potency outcomes appear to be similar. PSM rates are not different following RS‐RARP regardless of pathologic stage. Further quality studies are needed to confirm these findings.
Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain‐containing protein
Authors: Lim Dahwan , Jeong Da Eun , Shin Ho‐Chul , Choi Joon Sig , Seo Jinho , Kim Seung Jun , Ku Bonsu 
Published: August 2023

AbstractThe activation or inactivation of B‐cell lymphoma‐2 (Bcl‐2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization‐dependent apoptosis. Its pro‐apoptotic activity is controlled by intermolecular interactions with the Bcl‐2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl‐2‐interacting protein 5 (Bnip5) is a noncanonical BH3 domain‐containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro‐apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak‐activating pro‐apoptotic factor peroxisomal testis‐enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak‐mediated apoptosis.
Periplocoside P affects synaptic transmission at the neuromuscular junction and reduces synaptic excitability in Drosophila melanogaster by inhibiting V‐ATPase
Authors: Luo Jiaojiao , Sun Anqi , Yu Yang , Pei Yakun , Zuo Yayun , Hu Zhaonong 
Published: August 2023

AbstractBACKGROUNDPeriplocoside P (PSP) is a major component of Periploca sepium Bunge known for its potent insecticidal activity. V‐Type adenosine triphosphatase (V‐ATPase), which is widely distributed in the cytoplasmic membranes and organelles of eukaryotic cells, plays a crucial role in synaptic excitability conduction. Previous research has shown that PSP targets the apical membrane of goblet cells in the insect midgut. However, the effects of PSP on synaptic transmission at the neuromuscular junction are often overlooked.RESULTSThe bioassay revealed that Drosophila adults with different genetic backgrounds showed varying levels of susceptibility to PSP in the order: parats1 > parats1;DSC1−/− ≈ w1118 > DSC1−/−. Intracellular electrode recording demonstrated that PSP, similar to bafilomycin A1, had an impact on the amplitude of the excitatory junction potential (EJP) and accelerated excitability decay. Furthermore, the alteration in EJP amplitude is concentration‐dependent. Another surprising discovery was that the knockout DSC1 channel showed insensitivity to PSP.CONCLUSIONOur findings confirm that PSP can influence synaptic transmission at the neuromuscular junction of Drosophila larvae by targeting V‐ATPase. These results provide a basis for investigating the mechanism of action of PSP and its potential application in designing novel insecticides. © 2023 Society of Chemical Industry.
“Super‐covariates”: Using predicted control group outcome as a covariate in randomized clinical trials
Authors: Holzhauer Björn , Adewuyi Emmanuel Taiwo 
Published: August 2023

AbstractThe power of randomized controlled clinical trials to demonstrate the efficacy of a drug compared with a control group depends not just on how efficacious the drug is, but also on the variation in patients' outcomes. Adjusting for prognostic covariates during trial analysis can reduce this variation. For this reason, the primary statistical analysis of a clinical trial is often based on regression models that besides terms for treatment and some further terms (e.g., stratification factors used in the randomization scheme of the trial) also includes a baseline (pre‐treatment) assessment of the primary outcome. We suggest to include a “super‐covariate”—that is, a patient‐specific prediction of the control group outcome—as a further covariate (but not as an offset). We train a prognostic model or ensembles of such models on the individual patient (or aggregate) data of other studies in similar patients, but not the new trial under analysis. This has the potential to use historical data to increase the power of clinical trials and avoids the concern of type I error inflation with Bayesian approaches, but in contrast to them has a greater benefit for larger sample sizes. It is important for prognostic models behind “super‐covariates” to generalize well across different patient populations in order to similarly reduce unexplained variability whether the trial(s) to develop the model are identical to the new trial or not. In an example in neovascular age‐related macular degeneration we saw efficiency gains from the use of a “super‐covariate”.