bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular‐ and nerve‐sparing bowel resection for deep endometriosis: A retrospective single‐center study
Authors: Ianieri Manuel Maria , De Cicco Nardone Alessandra , Benvenga Greta , Greco Pierfrancesco , Pafundi Pia Clara , Alesi Maria Vittoria , Campolo Federica , Lodoli Claudio , Abatini Carlo , Attalla El Halabieh Miriam , Pacelli Fabio , Scambia Giovanni , Santullo Francesco
Published: August 2023

Objective

Surgical management of bowel endometriosis is still controversial. Recently, many authors have pointed out the potential benefits of preserving the superior rectal artery, thus ensuring better perfusion of the anastomosis. The aim of this study was to evaluate the complication rate and functional outcomes of a bowel resection technique for deep endometriosis (DE) involving a nerve‐ and vascular‐sparing approach.

Methods

A single‐center retrospective study was conducted by enrolling patients who underwent segmental resection of the rectus sigmoid for DE in our department between September 2019 and April 2022. Intraoperative and postoperative complications were recorded for each woman, and functional outcomes relating to the pelvic organs were assessed using validated questionnaires (Knowles‐Eccersley‐Scott‐Symptom [KESS] questionnaire and Gastro‐Intestinal Quality of Life Index [GIQLI] for bowel function, Bristol Female Lower Urinary Tract Symptoms [BFLUTS] for urinary function, and Female Sexual Function Index [FSFI] for sexual function). These were evaluated preoperatively and postoperatively after 6 months from surgery.

Results

Sixty‐one patients were enrolled. No patients had Clavien‐Dindo grade 3 or 4 complications, there were no rectovaginal fistulas or ureteral lesions, and in no cases was it necessary to reoperate. Temporary bladder voiding deficits were reported in 8.2% of patients, which were treated with self‐catheterizations, always resolving within 45 days of surgery. Gastrointestinal function evaluated by KESS and GIQLI improved significantly after surgery, whereas sexual function appeared to worsen, although without reaching the level of statistically significant validity.

Conclusion

Our vascular‐ and nerve‐sparing segmental bowel resection technique for DE had a low intraoperative and postoperative complication rate and produced an improvement in gastrointestinal function after surgery.
Quantification of skin penetration of caffeine and propylene glycol applied topically in a mixture by tailored multivariate curve resolution‐alternating least squares of depth‐resolved Raman spectra
Authors: Choe ChunSik , Pak Gyong Jin , Ascencio Saul Mujica , Darvin Maxim E.
Published: August 2023

The quantitative determination of topically applied substances in the skin is severely limited and represents a challenging task. The porcine skin ex vivo was topically treated with a gel containing caffeine (CF) and propylene glycol (PG), and depth‐resolved Raman spectra were recorded with two confocal Raman microscopes. We applied a novel tailored multivariate curve resolution‐alternating least squares method to the selected spectral regions (512–604 and 778–1148 cm−1) of gel‐treated skin and quantitatively determined the concentrations of CF and PG in the stratum corneum (SC). The highest concentration of CF (181 mg/cm3) was found at the surface, while PG (384 mg/cm3) was found at 10% SC depth, indicating the formation of a reservoir at the superficial SC. The concentrations of CF and PG decreased monotonically and reached the detection limit at ≈60% and ≈80% SC depth, respectively, indicating that neither permeate the SC.
Optimal frequency determination for terahertz technology‐based detection of colitis‐related cancer in mice
Authors: Chen Yong , Li Dan , Liu Yaling , Hu Liwen , Qi Yuanlin , Huang Yi , Zhang Zhenghao , Chen Tingyan , Wang ChengDang , Zhong Shuncong , Ding Jian
Published: August 2023

Colorectal cancer is a prevalent malignancy globally, often linked to chronic colitis. Terahertz technology, with its noninvasive and fingerprint spectroscopic properties, holds promise in disease diagnosis. This study aimed to explore terahertz technology's application in colitis‐associated cancer using a mouse model. Mouse colorectal tissues were transformed into paraffin‐embedded blocks for histopathological analysis using HE staining. Terahertz transmission spectroscopy was performed on the tissue blocks. By comparing terahertz absorption differences, specific frequency bands were identified as optimal for distinguishing cancerous and normal tissues. The study revealed that terahertz spectroscopy effectively differentiates colitis‐related cancers from normal tissues. Remarkably, 1.8 THz emerged as a potential optimal frequency for diagnosing colorectal cancer in mice. This suggests the potential for rapid histopathological diagnosis of colorectal cancer using terahertz technology.
In vivo monitoring of hemodynamic changes in ischemic stroke using photoacoustic tomography
Authors: Li Heren , Zhu Yunhao , Luo Nianwu , Tian Chao
Published: August 2023

Ischemic stroke occurs when a blood vessel supplying the brain is blocked, leading to decreased blood flow. Early diagnosis and treatment are crucial. However, existing clinical imaging methods have limitations, such as safety issues and low time resolution. To address these challenges, we propose using photoacoustic tomography (PAT) with a contrast agent, known for its high resolution and contrast capabilities. Our study involved imaging brain vasculature in three groups: normal, unilateral common carotid artery ligation (UCAL), and middle cerebral artery occlusion (MCAO). On the ischemic stroke side, we observed reduced blood vessel density and hemodynamic changes were evident after injecting indocyanine green for PAT. The photoacoustic intensity was notably lower in the ligated sides of the UCAL and MCAO groups, with statistically significant differences between the three groups. This work highlights PAT's potential as a powerful tool for early diagnosis and guidance in ischemic stroke cases.
Mechanical characterization and design of biomaterials for nucleus pulposus replacement and regeneration
Authors: Li Zhuoqi Lucas , Lu Qiuji , Honiball John Robert , Wan Sandra Hiu‐Tung , Yeung Kelvin Wai‐Kwok , Cheung Kenneth Man‐Chee
Published: August 2023

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re‐herniation post‐operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices.
Imatinib prevents dexamethasone‐induced pancreatic β‐cell apoptosis via decreased TRAIL and DR5
Authors: Kutpruek Suchanoot , Suksri Kanchana , Maneethorn Petcharee , Semprasert Namoiy , Yenchitsomanus Pa‐thai , Kooptiwut Suwattanee
Published: August 2023

Prolonged administration of dexamethasone, a potent anti‐inflammatory drug, can lead to steroid‐induced diabetes. Imatinib, a medication commonly prescribed for chronic myeloid leukemia (CML), has been shown to improve diabetes in CML patients. Our recent study demonstrated that dexamethasone induces pancreatic β‐cell apoptosis by upregulating the expression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5). We hypothesized that imatinib may protect against dexamethasone‐induced pancreatic β‐cell apoptosis by reducing the expression of TRAIL and DR5, thereby favorably modulating downstream effectors in apoptotic pathways. We test this hypothesis by assessing the effects of imatinib on dexamethasone‐induced apoptosis in rat insulinoma cell line cells. As anticipated, dexamethasone treatment led to increased TRAIL and DR5 expression, as well as an elevation in superoxide production. Conversely, expression of the TRAIL decoy receptor (DcR1) was decreased. Moreover, key effectors in the extrinsic and intrinsic apoptosis pathways, such as B‐cell lymphoma 2 (BCL‐2) associated X (BAX), nuclear factor kappa B (NF‐κb), P73, caspase 8, and caspase 9, were upregulated, while the antiapoptotic protein BCL‐2 was downregulated. Interestingly and importantly, imatinib at a concentration of 10 µM reversed the effect of dexamethasone on TRAIL, DR5, DcR1, superoxide production, BAX, BCL‐2, NF‐κB, P73, caspase 3, caspase 8, and caspase 9. Similar effects of imatinib on dexamethasone‐induced TRAIL and DR5 expression were also observed in isolated mouse islets. Taken together, our findings suggest that imatinib protects against dexamethasone‐induced pancreatic β‐cell apoptosis by reducing TRAIL and DR5 expression and modulating downstream effectors in the extrinsic and intrinsic apoptosis pathways.
Hyperechogenic fetal bowel: Current evidence‐based prenatal diagnosis and management
Authors: Vena Flaminia , Mazza Alessandra , Bartolone Martina , Vasta Adele , D'Alberti Elena , Di Mascio Daniele , D'Ambrosio Valentina , Volpe Gregorio , Signore Fabrizio , Pizzuti Antonio , Giancotti Antonella
Published: August 2023

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%–1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter‐observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post‐natal follow‐up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.
Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis
Authors: Pham Thach Tuan , Le Anh Hong , Dang Cong Phi , Chong Suet Yen , Do Dang Vinh , Peng Boya , Jayasinghe Migara Kavishka , Ong Hong Boon , Hoang Dong Van , Louise Roma Anne , Loh Yuin‐Han , Hou Han Wei , Wang Jiong‐Wei , Le Minh TN
Published: August 2023

Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes. This uptake is an active process, mediated mainly by endocytosis. Incubation of CD14+ monocytes with RBCEVs induces their differentiation into macrophages with an Mheme‐like phenotype, characterized by upregulation of heme oxygenase‐1 (HO‐1) and the ATP‐binding cassette transporter ABCG1. Moreover, macrophages that take up RBCEVs exhibit a reduction in surface CD86 and decreased secretion of TNF‐α under inflammatory stimulation. The upregulation of HO‐1 is attributed to heme derived from haemoglobin in RBCEVs. Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1. Consequently, RBCEVs exhibit the ability to attenuate foam cell formation from oxidized low‐density lipoproteins (oxLDL)‐treated macrophages in vitro and reduce atherosclerotic lesions in ApoE knockout mice on a high‐fat diet. In summary, our study reveals the uptake mechanism of RBCEVs and their delivery of heme to macrophages, suggesting the potential application of RBCEVs in the treatment of atherosclerosis.
Genetic tools for the study of the mangrove killifish, Kryptolebias marmoratus, an emerging vertebrate model for phenotypic plasticity
Authors: Li Cheng‐Yu , Boldt Helena , Parent Emily , Ficklin Jax , James Althea , Anlage Troy J. , Boyer Lena M. , Pierce Brianna R. , Siegfried Kellee R. , Harris Matthew P. , Haag Eric S.
Published: August 2023

Kryptolebias marmoratus (Kmar), a teleost fish of the order Cyprinodontiformes, has a suite of unique phenotypes and behaviors not observed in other fishes. Many of these phenotypes are discrete and highly plastic—varying over time within an individual, and in some cases reversible. Kmar and its interfertile sister species, K. hermaphroditus, are the only known self‐fertile vertebrates. This unusual sexual mode has the potential to provide unique insights into the regulation of vertebrate sexual development, and also lends itself to genetics. Kmar is easily adapted to the lab and requires little maintenance. However, its internal fertilization and small clutch size limits its experimental use. To support Kmar as a genetic model, we compared alternative husbandry techniques to maximize recovery of early cleavage‐stage embryos. We find that frequent egg collection enhances yield, and that protease treatment promotes the greatest hatching success. We completed a forward mutagenesis screen and recovered several mutant lines that serve as important tools for genetics in this model. Several will serve as useful viable recessive markers for marking crosses. Importantly, the mutant kissylips lays embryos at twice the rate of wild‐type. Combining frequent egg collection with the kissylips mutant background allows for a substantial enhancement of early embryo yield. These improvements were sufficient to allow experimental analysis of early development and the successful mono‐ and bi‐allelic targeted knockout of an endogenous tyrosinase gene with CRISPR/Cas9 nucleases. Collectively, these tools will facilitate modern developmental genetics in this fascinating fish, leading to future insights into the regulation of plasticity.
Mechanistic insights into the inhibition of human placental glutathione S‐transferase P1‐1 by abscisic and gibberellic acids: An integrated experimental and computational study
Authors: Zaid Mohammad Abu , Dalmizrak Ozlem , Teralı Kerem , Ozer Nazmi
Published: August 2023

The interactions of the classic phytohormones gibberellic acid (gibberellin A3, GA3) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S‐transferase P1‐1 (hpGSTP1‐1), an enzyme that plays a role in endo‐ or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA3 against hpGSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hpGSTP1‐1 and phytohormones was predicted with the aid of molecular docking simulations. The IC50 values of ABA and GA3 were 5.3 and 5.0 mM, respectively. Both phytohormones inhibited hpGSTP1‐1 in competitive manner with respect to the cosubstrates GSH and CDNB. When ABA was the inhibitor at [CDNB]f–[GSH]v and at [GSH]f–[CDNB]v, Vm, Km, and Ki values were statistically estimated to be 205 ± 16 μmol/min‐mg protein, 1.32 ± 0.18 mM, 1.95 ± 0.25 mM and 175 ± 6 μmol/min‐mg protein, 0.85 ± 0.06 mM, 1.85 ± 0.16 mM, respectively. On the other hand, the kinetic parameters Vm, Km, and Ki obtained with GA3 at [CDNB]f–[GSH]v and at [GSH]f–[CDNB]v were found to be 303 ± 14 μmol/min‐mg protein, 1.77 ± 0.13 mM, 3.38 ± 0.26 mM and 249 ± 7 μmol/min‐mg protein, 1.43 ± 0.07 mM, 2.89 ± 0.19 mM, respectively. Both phytohormones had the potential to engage in hydrogen‐bonding and electrostatic interactions with the key residues that line the G‐ and H‐sites of the enzyme's catalytic center. Inhibitory actions of ABA/GA3 on hpGSTP1‐1 may guide medicinal chemists through the structure‐based design of novel antineoplastic agents. It should be noted, however, that the same interactions may also render fetuses vulnerable to the potentially toxic effects of xenobiotics and noxious endobiotics.
Diurnal cycle of precipitation and its possible causes: A case study in Shandong Province, China
Authors: Qiu Can , Dong Xu‐guang , Shen Liu‐cheng , Wen Jia‐hong
Published: August 2023

Accurate information on diurnal precipitation variations is essential for understanding the mechanism of precipitation formation, assessing the regional climate characteristics, and improving the simulation performance of climate models. Taking Shandong Province, East China, as a case study, 123 stations with hourly observational precipitation data were divided into three categories by the harmonic analysis on diurnal variation of precipitation, and the diurnal variations in precipitation amount, frequency and intensity were further analysed to derive the precipitation partition. The results showed that: (1) the peak precipitation frequency at different types of stations occurred steadily around 0400–0600 LST, whereas the peak precipitation intensity existed at different moments such as 0200 and 1700, and precipitation amount mostly showed a double‐peak pattern in the early morning (0400–0600 LST) and late afternoon (1600–1800 LST); (2) early morning precipitation was mainly driven by persistent precipitation, which contributed between 65.2% and 84.3%, while precipitation peaks in the late afternoon with a significant increase in the contribution of short duration precipitation; and (3) the influence of mountain–plain circulation and the increasing effect of topographic uplift on precipitation may be the main reasons for the formation of early morning precipitation peaks. The strength of sea–land winds and local convection was also key factors affecting the diurnal variation of precipitation.
Properties and applications of α‐galactosidase in agricultural waste processing and secondary agricultural process industries
Authors: Menon Anindita , Pandurangan Maragatham Vetriselvi , Samuel Marcus , Arunraj Rex
Published: August 2023

Agriculture products form the foundation building blocks of our daily lives. Although they have been claimed to be renewable resources with a low carbon footprint, the agricultural community is constantly challenged to overcome two post‐harvest bottlenecks: first, farm bio‐waste, a substantial economic and environmental burden to the farming sector, and second, an inefficient agricultural processing sector, plagued by the need for significant energy input to generate the products. Both these sectors require extensive processing technologies that are demanding in their energy requirements and expensive. To address these issues, an enzyme(s)‐based green chemistry is available to break down complex structures into bio‐degradable compounds that source alternate energy with valuable by‐products and co‐products. α‐Galactosidase is a widespread class of glycoside hydroxylases that hydrolyzes α‐galactosyl moieties in simple and complex oligo and polysaccharides, glycolipids, and glycoproteins. As a result of its growing importance, in this review we discuss the source of the enzyme, production and purification systems, and enzyme properties. We also elaborate on the enzyme's potential in agricultural bio‐waste management, secondary agricultural industries like sugar refining, soymilk derivatives, food and confectionery, and animal feed processing. Insight into this vital enzyme will provide new avenues for less expensive green chemistry‐based secondary agricultural processing and agricultural sustainability. © 2023 Society of Chemical Industry.
Sequential Wendler Glottoplasty and Laser Reduction Glottoplasty for Voice Feminization
Authors: Yılmaz Taner
Published: August 2023

Objective

Voice feminizing surgery is frequently needed for transgender female patients. Among several surgical options, Wendler glottoplasty (WG) and laser reduction glottoplasty (LRG) are two endoscopic procedures. However, because a single procedure may not produce sufficient benefit, the two surgeries may sometimes be sequentially performed. This study was carried out to present the voice results of such sequential surgeries.

Methods

This is an individual retrospective cohort study, performed at a tertiary referral center, that is a university hospital. 18 transgender patients were treated with WG initially and then underwent LRG; 17 had LRG first then WG. All 35 cases were performed during a 15‐year period and followed for at least 1 year postoperatively. Voice Handicap Index (VHI‐30), transsexual voice questionnaire (TVQ), and acoustic analysis with /a/ and running speech were obtained pre‐ and postoperatively.

Results

VHI and TVQ improved significantly postoperatively (p < 0.05). Their preoperative, first, and second postoperative mean sF0 were 146, 175, and 215 Hz, respectively; these differences were statistically significant (p < 0.001). Their postoperative mean jitter percent, shimmer percent, noise to harmonic ratio (NHR), cepstral peak prominence (CPP), and cepstral spectral index of dysphonia (CSID) worsened significantly compared to preop values (p < 0.05); however, mean postoperative acoustic results were still within normal limits. Patients' self‐ratings of their postsurgery voices revealed all feminine, leading to a patient gratification score of 100%.

Conclusion

If transgender female patients are unsatisfied with their voice after WG or LRG, the addition of the alternative procedure may significantly feminize their voice. Sequential WG and LRG is a successful surgical option for voice feminization.

Level of Evidence

4 Laryngoscope, 134:1133–1138, 2024
Coastal marine megaripple fields are metabolic hotspots with highly dynamic oxygen exchange
Authors: Berg Peter , Huettel Markus
Published: August 2023

Megaripples 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

In 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

Background

Craniofacial 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.

Methods

Trio 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.

Results

The 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.

Conclusion

For 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

Due 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

The 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

Objective

To 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).

Methods

Retrospective 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.

Results

Patients 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).

Conclusion

Amnioinfusion ≥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

Purpose

The objective was to compare the risk of malignancies in real‐world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS).

Methods

A 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.

Results

From 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]).

Conclusions

Compared 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

Protein 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

Background

Radical 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.

Methods

Following 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.

Results

A 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.

Conclusions

Our 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

The 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

BACKGROUND

Periplocoside 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.

RESULTS

The 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.

CONCLUSION

Our 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

The 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”.
The PH‐ILD Detection tool: External validation and use in patients with ILD
Authors: Parikh Raj , O'Sullivan David M. , Farber Harrison W.
Published: August 2023

Pulmonary hypertension (PH) results in increased morbidity and mortality in patients with interstitial lung disease (ILD). Early recognition of PH in this population is essential for planning diagnostic testing, initiating therapy, and evaluating for lung transplantation. The previously developed PH‐ILD Detection tool has significant potential in the evaluation and treatment of ILD patients; the aim of this study was to validate the tool in an independent, multicenter cohort of patients. We conducted a retrospective review of prospectively collected data from 161 ILD patients. Patients were stratified into low‐ (n = 78, 48.4%), intermediate‐ (n = 54, 33.5%), and high‐risk (n = 29, 18.0%) groups based on the score obtained with the tool. Intermediate‐ and high‐risk patients underwent follow‐up echocardiogram (TTE); 49.4% (n = 41) had an abnormal TTE suggestive of underlying PH. These patients underwent right heart catheterization; PH‐ILD was diagnosed in 73.2% (n = 30) of these cases. The PH‐ILD Detection tool has a sensitivity of 93.3%, specificity of 90.9%, and area‐under‐the‐curve of 0.921 for diagnosing PH in ILD patients, validating the findings from the original study and establishing the tool as a fundamental resource for early recognition of PH in ILD patients.
SurfinPES: Performing automated analysis of activation strain, energy decomposition, and reaction force
Authors: Quintal Alan , Dzib Eugenia , Murillo Fernando , Ortíz‐Chi Filiberto , Fernández Israel , Merino Gabriel
Published: August 2023

Analyzing activation strain, energy decomposition, and reaction force models is crucial for studying chemical reactivity and gaining quantitative insights into the factors that control energy barriers. However, manually preparing and processing the necessary data can be challenging and prone to errors. To address this issue, we introduce SurfinPES, a Python‐based module in Eyringpy that automates data extraction and processing for these analyses. SurfinPES also allows monitoring of the evolution of primitive properties (geometrical and electronic) along the reaction coordinate. The module is user‐friendly with a simple input format, making it accessible to any user in the field of computational chemistry.