bluuebunny/crossref_metadata_2025 huggingface dataset:
Sirolimus‐coated balloon versus everolimus‐eluting stent in de novo coronary artery disease: Rationale and design of the TRANSFORM II randomized clinical trial
Authors: Greco Antonio , Sciahbasi Alessandro , Abizaid Alexandre , Mehran Roxana , Rigattieri Stefano , de la Torre Hernandez Jose M. , Alfonso Fernando , Cortese Bernardo
Published: September 2022

Background

Percutaneous coronary intervention (PCI) with drug‐eluting stent (DES) implantation is a widely adopted strategy for the treatment of de novo coronary artery disease. DES implantation conveys an inherent risk for short‐ and long‐term complications, including in‐stent restenosis and stent thrombosis. Drug‐coated balloons are emerging as an alternative approach to fulfill the “leaving nothing behind” principle and avoid long‐term DES‐related complications.

Design

TRANSFORM II is an investigator‐initiated, multicenter, noninferiority, randomized clinical trial, testing a sirolimus‐coated balloon (SCB) versus the standard of care for native coronary vessels with a 2–3 mm diameter, in terms of 12‐month target lesion failure (TLF; primary endpoint) and net adverse cardiovascular events (coprimary endpoint). Patients undergoing PCI will be randomized to be treated with either SCB or new‐generation everolimus‐eluting stent and will be followed up clinically for up to 60 months. Assuming a TLF rate of 8% at 12 months with DES, a sample size of 1325 patients was chosen to ensure an 80% power to detect a 1.5% lower incidence in the SCB group with a type I error rate of 0.05. The TRANSFORM II trial is registered on clinicaltrials.gov (identification number NCT04893291). Several substudies, including an optical coherence tomography assessment at 9 months (intracoronary imaging substudy), will investigate the study device in different clinical and lesion settings.

Conclusions

The randomized TRANSFORM II trial will determine whether a novel SCB is noninferior to a current everolimus‐eluting stent when adopted for the treatment of de novo lesions in coronary vessels with a diameter between 2 and 3 mm.
Harnessing the parallax for better spatial awareness
Authors: Targoński Radosław , Gąsecka Aleksandra , Luis Marlon S. , Jagielak Dariusz , Jaguszewski Miłosz , Piazza Nicolo
Published: September 2022

Despite easy access to imaging diagnostic procedures and an abundance of spatial data, most cardiac interventions are still performed under two‐dimensional fluoroscopy. Incorporating anatomical data from scans into procedures plans has the potential to improve the swiftness and outcomes of percutaneous cardiac interventions. Therefore, procedure planning based on the specific anatomy is becoming a new standard of excellence in interventional cardiology. Still, we often tend to disregard specific spatial relations and the actual direction of catheter tip movement inside the body, relying on a try and error approach. The precise spatial orientation of instruments and prosthetic devices is crucial, especially during structural heart interventions. Here, we present how deliberate movements of objects under fluoroscopy can reveal the spatial orientation of catheters and other devices. We also propose a novel “two‐point rule” for identifying three‐dimensional relations between points in space. Understanding and applying this rule might substantially increase the spatial awareness of operators performing cardiovascular interventions. Although the concept is pretty simple, using it “live” during interventional cardiology procedures requires thorough understanding and practice. We propose the “two‐point rule” as a crucial rule to develop expertise in spatial orientation under fluoroscopy and ensure high‐quality outcomes.
Oxidation Behavior of Glassy Carbon in Acidic Electrolyte
Authors: Choudhury Sakeb Hasan , Ding Yuxiao , Yi Youngmi , Rohner Christian , Frandsen Wiebke , Lunkenbein Thomas , Greiner Mark , Schlögl Robert , Heumann Saskia
Published: September 2022

Glassy carbon is frequently used in electrochemical research due to its presumed robust electrochemical performance. Although it is widely utilized as a rotating disc electrode material, the modification of glassy carbon during electro‐catalytic process is rarely emphasized or characterized. In this report, we investigated the structural modification of glassy carbon imparted by electrochemical oxidation in acidic media and compared the behavior with graphite. The functional groups generated from electrochemical oxidation in both electrodes possess similar electrochemical properties. However, above an oxidation potential of 1.8 V (vs. reversibly hydrogen electrode), glassy carbon exhibits a lower electrochemical capacitance compared to graphite. We propose that the existence of electrochemically inactive species, originating from the non‐graphitic portion of glassy carbon is attributed to such deterioration. Additionally, high resolution scanning electron microscopy (HR‐SEM) and high‐resolution transmission electron microscopy (HR‐TEM) images corroborate how electrochemical oxidation prevails for glassy carbon electrodes at oxidative potentials. The overall analysis leads us to propose a corrosion mechanism for glassy carbon in acidic solution.
The evaluation of planter downforce on emergence and grain yield in soybean
Authors: Soignier Tyler S. , Plumblee Michael T. , Mueller John D. , Greene Jeremy K. , Kirk Kendall R.
Published: September 2022

Planter downforce could unify crop emergence by maintaining uniform seeding depth while planting. This research was conducted to determine if planter downforce rate impacted soybean [Glycine max (L.) Merr.] emergence and grain yield in South Carolina. The effects of tillage type, gauge wheel width, and downforce rate (0–300 lbf in 50‐lbf increments) on soybean were evaluated at the Edisto (EREC) and Piedmont (PREC) Research and Education Centers in South Carolina. At EREC, a downforce rate over 200 lbf resulted in decreased plant emergence compared with 0, 50, 100, and 150 lbf. A downforce rate of 0 and 50 lbf had a reduced number of emerged plants at 2, 3, and 4 d after emergence compared with rates over 150 lbf at PREC. As downforce rate increased, the depth at which seed were planted increased up to 35% of the original planting depth at EREC. Planter downforce rate appears to influence overall soybean emergence. However, uniform emergence in soybean does not appear to impact grain yield in these production scenarios in South Carolina.
A Versatile Palladium Synthon: [Pd(NHC)(PhC≡CPh)]**
Authors: Bru Francis , Lesieur Mathieu , Poater Albert , Slawin Alexandra M. Z. , Cavallo Luigi , Cazin Catherine S. J.
Published: September 2022

The synthesis and isolation of [Pd(NHC)(PhC≡CPh)] complexes are reported. These new 14‐electron Pd(0)‐complexes are key synthons leading to known palladium(0) and palladium(II) species, as well as permitting access to unprecedented mixed NHC‐phosphite palladium(0) complexes. This motif permits the facile catalytic hydrosilylation of allenes. DFT calculations have allowed the characterization of the relatively weak interaction between the metal and the diphenylacetylene ligand, with a comparison with a series of ligands with more or less coordinating power, bearing varied structural and electronic properties.
One‐step Oxidative Monofluorination of Electron‐Deficient Sulfoxides to Access Highly Lewis Acidic Sulfur(VI) Cations
Authors: Berreur Jordan , Diez‐Varga Alberto , Manel Augustin , Leroux Frédéric R. , Panossian Armen
Published: September 2022

The strongly oxidizing, powerful electrophilic fluorination reagent [FXe][OTf] is shown to effect direct oxidative monofluorination of sulfoxides. This one‐step, chloride promoter‐free methodology provides access to so far inaccessible, yet highly desirable strongly Lewis acidic fluorosulfoxonium cations from electron‐deficient and/or sterically demanding sulfoxides that are shown to be practically unreactive towards the previously reported XeF2/NEt4Cl system. Experimental and density functional theory studies have been conducted to assess the Lewis acidities of the prepared sulfur(VI) cations. Preliminary results obtained with chiral sulfoxides provide early insights into the mechanism of these fluorination reactions.
Solids flux profiles of Geldart Group A particles in high‐velocity circulating fluidized bed risers
Authors: Issangya Allan S. , Karri S. B. Reddy , Cocco Ray A. , Knowlton Ted , Chew Jia Wei
Published: September 2022

Circulating fluidized bed (CFB) risers using Group A particles have traditionally, mostly, been considered to operate in the fast fluidization regime, which consists of a core‐annulus flow profile with solids refluxing in the annulus layer. High gas and solids flow riser studies, however, suggest the existence of additional types of flow behaviours. Therefore, more studies are still needed to help clear uncertainties of local solids flow patterns in CFB risers of Group A particles, especially at gas and solids flow rates at or near those in commercial units. In this study, riser density and local solids flux profiles were measured in 0.3 m diameter risers of three CFB units at gas velocities of 9–16 m/s and solids fluxes of up to 700 kg/s · m2. A variety of radial solids flux profiles were obtained, including a parabolic profile with a peak flux at about the radial centre, a nearly flat profile across the riser cross‐section and an inverted parabola with peak upwards flux near the wall. At high gas velocity and solids flux, risers have no solids downflow at the wall. Multiple fluidization regimes were found to exist in the riser. The bottom dense part of the riser was in the dense suspension upflow regime, and the dilute upper part was in the dilute pneumatic transport regime. With commercial fluid catalytic cracking (FCC) risers operating at nearly similar conditions as tested here, it is likely that they also have one or both fluidization regimes and not the traditional fast fluidization regime. The data in this study fitted well on the Kim et al. fluidization regime map.
Rh(III)‐Catalyzed Enantioselective Intermolecular Aryl C—H Bond Addition to Aldehydes
Authors: Wu Zhi‐Jie , Wu Zhuo , Zhang Wen‐Wen , Gu Qing , You Shu‐Li
Published: September 2022

Comprehensive Summary

The direct addition of aryl C—H bond to carbon‐heteroatom double bond by transition‐metal‐catalyzed C—H activation has been extensively investigated in the past decade. However, the enantioselective intermolecular C—H addition to aldehyde has not yet been reported and is of significant challenge. Rh(III)‐catalyzed highly enantioselective intermolecular C—H addition of aryl oxime ethers to glyoxylates is reported. Chiral mandelic acid esters were obtained in excellent yields (up to 98%) and enantioselectivity (up to 99% ee) in the presence of a chiral CpRh(III) catalyst under mild conditions. The substituents on the Cp ring and BINOL skeleton were responsible for the high enantioselectivity observed. The method displays a broad substrate scope and good functionality tolerance. These results provide not only a promising C—H addition approach but also a proof of concept for developing broader asymmetric C—H addition reactions.
Synthesis and Biological Evaluation of Cardiac Glycosides for Cancer Therapy by Targeting the DNA Damage Response
Authors: Ainembabazi Diana , Geng Xinran , Gavande Navnath S. , Turchi John J. , Zhang Youwei
Published: September 2022

Cardiac glycosides (CGs) are bioactive compounds originally used to treat heart diseases, but recent studies have demonstrated their anticancer activity. We previously demonstrated that Antiaris toxicaria 2 (AT2) possesses anticancer activity in KRAS mutated lung cancers via impinging on the DNA damage response (DDR) pathway. Toward developing this class of molecules for cancer therapy, herein we report a multistep synthetic route utilizing k‐strophanthidin as the initial building block for determination of structure–activity relationships (SARs). A systematic structural design approach was applied that included modifications of the sugar moiety, the glycoside linker, stereochemistry, and lactone ring substitutions to generate a library of O‐glycosides and MeON‐neoglycosides derivatives. These molecules were screened for their anticancer activities and their impact on DDR signaling in KRAS mutant lung cancer cells. These results demonstrate the ability to chemically synthesize CG derivatives and define the SARs to optimize AT2 as a cancer therapeutic.
Enzyme‐Responsive Hydrogel for Delivery of the Anti‐Inflammatory Agent Zingerone
Authors: Sunnapu Omprakash , Khader Rajamohammed , Dhanka Mukesh , Kumar Vemula Praveen , Karuppannan Sekar
Published: September 2022

Inflammation highly fluctuates, and the level of inflammation varies in patients. Therefore, as opposed to conventional sustained release systems, delivering drugs in response to the inflammation and inflammation‐associated enzymes may have a beneficial effect in managing inflammatory diseases such as arthritis. Hence, we have developed an inflammation‐associated enzymes‐responsive hydrogel system. Zingerone is an active component in ginger and is known to exhibit a beneficial effect. We have studied the zingerone anti‐inflammatory properties using macrophages, and zingerone‐encapsulated self‐assembled hydrogels have been prepared and characterized in detail. Additionally, we have demonstrated that inflammation‐associated enzymes such as lipase could trigger the release of zingerone in a responsive manner, in vitro. In vivo efficacy of zingerone‐encapsulated hydrogel will be evaluated in preclinical models in the future.
Prenatal presentation of an adrenocortical tumor
Authors: Schwartz Jeffrey H. , Smith Erlyn
Published: September 2022

Background

Prenatally identified suprarenal masses are most often found to be adrenal hemorrhage. The most common tumor in this situation is neuroblastoma.

Case Presentation

We report the case of a rare adrenocortical tumor found prenatally on ultrasound. While most patients with adrenocortical tumors present with virilizing symptoms, our patient did not have evidence of virilization and was presumed to have neuroblastoma.

Conclusion

Following a period of observation, our patient underwent surgical resection due to tumor growth revealing the unexpected diagnosis.
Mesomeric Tuning at Planar Bi centres: Unexpected Dimerization and Benzyl C−H Activation in [CN2]Bi Complexes
Authors: Hynes Toren , Masuda Jason D. , Chitnis Saurabh S.
Published: September 2022

Planar bismuth(III) compounds featuring a N3‐pincer ligand environment are an unusual class of main group compounds that exhibit Lewis acidity via a 6p orbital. The ability to tune their acidity via Hammett and Coulomb effects has been demonstrated previously. Here we test the ability to tune them via mesomeric effects by replacing the central nitrogen of the [N3] pincer ligand with a less π‐donating carbon atom to achieve a [CN2] ligand environment. This strategy boosts the Lewis acidity at the metal to such an extent that only strongly‐bound dimers can be accessed in the condensed phase, or, if dimerization is sterically prohibited, an unusual reductive elimination occurs to give Bi(I) compounds. These results highlight the fine line separating donor/acceptor and redox chemistry at planar bismuth centres.
Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype
Authors: Gammal Roseann S. , Pirmohamed Munir , Somogyi Andrew A. , Morris Sarah A. , Formea Christine M. , Elchynski Amanda L. , Oshikoya Kazeem A. , McLeod Howard L. , Haidar Cyrine E. , Whirl‐Carrillo Michelle , Klein Teri E. , Caudle Kelly E. , Relling Mary V.
Published: September 2022

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources. We classify these medications as high, medium, or low to no risk based on a systematic review of the published evidence of the gene–drug associations and regulatory warnings. In patients with G6PD deficiency, high‐risk medications should be avoided, medium‐risk medications should be used with caution, and low‐to‐no risk medications can be used with standard precautions, without regard to G6PD phenotype. This new document replaces the prior Clinical Pharmacogenetics Implementation Consortium guideline for rasburicase therapy in the context of G6PD genotype (updates at: www.cpicpgx.org).
The Effect of Tobacco Use on the Expression of Placental Transporters in Alaska Native Women
Authors: McColl Eliza R. , Kwok Jacinda , Benowitz Neal L. , Patten Christi A. , Hughes Christine A. , Koller Kathryn R. , Flanagan Christie A. , Thomas Timothy K. , Hiratsuka Vanessa Y. , Tyndale Rachel F. , Piquette‐Miller Micheline
Published: September 2022

Prenatal tobacco use among Alaska Native (AN) women has decreased substantially over the past two decades. Previous research suggests that providing AN women with feedback regarding fetal exposure to tobacco may further promote cessation. Transporters in the placenta regulate fetal exposure to nutrients and xenobiotics, including compounds associated with tobacco use. We examined whether prenatal tobacco use impacts transporter expression in the placenta, and whether this is influenced by fetal sex, degree of tobacco exposure, or transporter genotype. At delivery, we obtained placental samples from AN research participants who smoked cigarettes, used commercial chew or iqmik (oral tobacco), or did not use tobacco during pregnancy. Transporter expression was evaluated using qRT‐PCR and Western blotting and tested for correlations between transcript levels and urinary biomarkers of tobacco use. The impact of BCRP/ABCG2 and OATP2B1/SLCO2B1 genotypes on protein expression was also examined. Oral tobacco use was associated with decreased P‐gp and increased MRP1, MRP3, LAT1, and PMAT mRNA expression. Transcript levels of multiple transporters significantly correlated with tobacco biomarkers in maternal and fetal urine. In women carrying male fetuses, both smoking and oral tobacco were associated with decreased P‐gp. Oral tobacco was also associated with decreased LAT1 in women carrying female fetuses. BCRP and OATP2B1 genotypes did not appear to impact protein expression. In conclusion, prenatal tobacco use is associated with altered expression of multiple placental transporters which differs by fetal sex. As transcript levels of multiple transporters were significantly correlated with tobacco use biomarkers, eliminating prenatal tobacco use should alleviate these changes.
Excited‐State Intramolecular Charge‐Transfer Dynamics in 4‐Dimethylamino‐4′‐cyanodiphenylacetylene: An Ultrafast Raman Loss Spectroscopic Perspective
Authors: Barak Arvind , Dhiman Nishant , Sturm Floriane , Rauch Florian , Lakshmanna Yapamanu Adithya , Findlay Karen S. , Beeby Andrew , Marder Todd B. , Umapathy Siva
Published: September 2022

Photo‐initiated intramolecular charge transfer (ICT) processes play a pivotal role in the excited state reaction dynamics in donor‐bridge‐acceptor systems. The efficacy of such a process can be improved by modifying the extent of π‐conjugation, relative orientation/twists of the donor/acceptor entities and polarity of the environment. Herein, 4‐dimethylamino‐4′‐cyanodiphenylacetylene (DACN‐DPA), a typical donor‐π‐bridge‐acceptor system, was chosen to unravel the role of various internal coordinates that govern the extent of photo‐initiated ICT dynamics. Transient absorption (TA) spectra of DACN‐DPA in n‐hexane exhibit a lifetime of >2 ns indicating the formation of a triplet state while, in acetonitrile, a short time‐constant of ∼2 ps indicates the formation of charge transferred species. Ultrafast Raman loss spectroscopy (URLS) measurements show distinct temporal and spectral dynamics of Raman bands associated with C≡C and C=C stretching vibrations. The appearance of a new band at ∼1492 cm−1 in acetonitrile clearly indicates structural modification during the ultrafast ICT process. Furthermore, these observations are supported by TD‐DFT computations.
Ionic liquid‐based materials for electrochemical biosensing
Authors: Khorsandi Danial , Zarepour Atefeh , Rezazadeh Ilia , Ghomi Matineh , Ghanbari Roham , Zarrabi Ali , Esfahani Faranak Tarkesh , Mojahed Nooshin , Baghayeri Mehdi , Zare Ehsan Nazarzadeh , Makvandi Pooyan
Published: September 2022

Due to their interesting features including negligible volatility, ease of designing in the construction, good chemical, and thermal stability, and excellent ionic conductivity, ionic liquids (ILs) have attracted a lot of attention to themselves in recent years. They are constructed from asymmetric anions and cations and are found in a liquid state lower than 100°C. Their unique features introduce them as candidates for the application in the structure of different types of electrochemical biosensors, in which they could act as electrolytes, or could be used as detecting agents. According to these features, this review aims to present an overview of the application of ILs in the structure of electrochemical sensors and biosensors. Based on this, after a brief description of the ILs and biosensors, the application of ILs in the structure of some of the recent electrochemical biosensors has been discussed and then, remarks and perspectives on these types of biosensors are explained.
Solasonine alleviates high glucose‐induced podocyte injury through increasing Nrf2‐medicated inhibition of NLRP3 activation
Authors: Zhang Qianjin , Hu Yichuan , Hu Jin‐E , Zhang Min
Published: September 2022

The worldwide high prevalence of diabetic nephropathy is one of the common causes of renal failure in diabetic patients. Hyperglycemia‐caused podocyte injury is considered as a major contributor to diabetic kidney disease, accompanied by a chronic inflammatory condition. Pyroptosis, a characterized inflammatory form of programmed cell death, is believed to be involved in the pathogenesis of diabetic nephropathy. Solasonine (SS) is a natural alkaloid and received attention as a potential anticancer agent. However, its protective effect against hyperglycemia‐caused podocyte injury remains to be determined. Our study found that SS alleviates cell apoptosis, and reduces pyroptosis and oxidative damage in high glucose (HG)‐treated MPC5 podocytes. Pro‐inflammatory cytokines, including interleukin (IL)‐1β and IL‐18, and caspase‐1 activity were markedly suppressed by SS in HG‐treated MPC5 podocytes. SS also reduced HG‐induced oxidative damage in MPC5 podocytes. Nrf2 expression was activated by SS in vitro under a HG condition. In addition, Nrf2 silencing attenuated the protective effect of SS against apoptosis, pro‐inflammatory cytokines release, caspase‐1 activity, and oxidative damage in MPC5 podocytes under a HG condition. Taken together, our findings revealed for the first time that SS alleviated high glucose‐induced podocyte apoptosis, pyroptosis, and oxidative damage via regulating the Nrf2/NLRP3 signaling pathway. Our results indicate that SS has the potential as a therapeutic agent for podocyte injury in diabetic nephropathy.
Autogenous self‐healing of concrete: Experimental design and test methodsA review
Authors: Lahmann Daniel , Edvardsen Carola , Kessler Sylvia
Published: September 2022

Cracks in concrete structures can serve as pathways for aggressive chemical substances that can lead to a progressive deterioration of the cement stone as well as of the reinforcement, affecting the load capacity, service life and useability of concrete structures. However, concrete and reinforced concrete exhibit an intrinsic ability to heal cracks, defined as autogenous self‐healing. This effect includes the precipitation of calcium carbonate in the presence of water and CO2 and is accompanied by continued hydration, swelling, and mechanical blocking of the crack pathway. Experiments led to the inclusion of crack sealing by autogenous self‐healing in Eurocode 1992–3 for water retaining concrete structures. However, despite code restrictions, autogenous self‐healing of concrete shows limited effectiveness in practice. This indicates the need for further research to provide engineers with reliable design rules. Therefore, this study aims for giving a broad literature review on the state‐of‐the‐art knowledge on autogenous self‐healing, the boundary conditions, consensus, and controversy of processes and factors influencing the efficiency of autogenous self‐healing. Regarding the transferability of laboratory results to real concrete constructions, materials, crack initiation techniques, experimental concepts, and methods for assessing the effectiveness of autogenous self‐healing are discussed and recommendations for future experiments are set.
Layer‐specific microstructural patterns of anterior hippocampus in Alzheimer's disease with ex vivo diffusion MRI at 14.1 T
Authors: Zhao Zhiyong , Zhang Lei , Luo Wanrong , Cao Zuozhen , Zhu Qinfeng , Kong Xueqian , Zhu Keqing , Zhang Jing , Wu Dan
Published: September 2022

High‐resolution ex vivo diffusion MRI (dMRI) can provide exquisite mesoscopic details and microstructural information of the human brain. Microstructural pattern of the anterior part of human hippocampus, however, has not been well elucidated with ex vivo dMRI, either in normal or disease conditions. The present study collected high‐resolution (0.1 mm isotropic) dMRI of post‐mortem anterior hippocampal tissues from four Alzheimer's diseases (AD), three primary age‐related tauopathy (PART), and three healthy control (HC) brains on a 14.1 T spectrometer. We evaluated how AD affected dMRI‐based microstructural features in different layers and subfields of anterior hippocampus. In the HC samples, we found higher anisotropy, lower diffusivity, and more streamlines in the layers within cornu ammonis (CA) than those within dentate gyrus (DG). Comparisons between disease groups showed that (1) anisotropy measurements in the CA layers of AD, especially stratum lacunosum (SL) and stratum radiatum (SR), had higher regional variability than the other two groups; (2) streamline density in the DG layers showed a gradually increased variance from HC to PART to AD; (3) AD also showed the higher variability in terms of inter‐layer connectivity than HC or PART. Moreover, voxelwise correlation analysis between the coregistered dMRI and histopathology images revealed significant correlations between dMRI measurements and the contents of amyloid beta (Aβ)/tau protein in specific layers of AD samples. These findings may reflect layer‐specific microstructural characteristics in different hippocampal subfields at the mesoscopic resolution, which were associated with protein deposition in the anterior hippocampus of AD patients.
Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta‐analysis
Authors: van den Bosch Sven , Czerwinski Michal , Govers Tim , Takes Robert P. , de Bree Remco , Al‐Mamgani Abrahim , Hannink Gerjon , Kaanders Johannes H. A. M.
Published: September 2022

The aim of this meta‐analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow‐up as reference. A bivariate generalized linear mixed model approach was used for the meta‐analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86–0.96) and 0.97 (95% CI: 0.94–0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quality of life when omitting elective neck treatment based on SLNB.
Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion
Authors: van Zwol Willemien , Rimbert Antoine , Wolters Justina C. , Smit Marieke , Bloks Vincent W. , Kloosterhuis Niels J. , Huijkman Nicolette C. A. , Koster Mirjam H. , Tharehalli Umesh , de Neck Simon M. , Bournez Colin , Fuh Marceline M. , Kuipers Jeroen , Rajan Sujith , de Bruin Alain , Ginsberg Henry N. , van Westen Gerard J. P. , Hussain M. Mahmood , Scheja Ludger , Heeren Joerg , Zimmerman Philip , van de Sluis Bart , Kuivenhoven Jan Albert
Published: September 2022

Background and Aims:

The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co−expressed with the MTTP gene that encodes for microsomal triglyceride transfer protein, key to the lipidation of apolipoprotein B, the core protein of VLDL. Using human and murine transcriptomic data sets, we identified small leucine−rich protein 1 (SMLR1), encoding for small leucine−rich protein 1, a protein of unknown function that is exclusively expressed in liver and small intestine.

Approach and Results:

To assess the role of SMLR1 in the liver, we used somatic CRISPR/CRISPR−associated protein 9 gene editing to silence murine Smlr1 in hepatocytes (Smlr1−LKO). When fed a chow diet, male and female mice show hepatic steatosis, reduced plasma apolipoprotein B and triglycerides, and reduced VLDL secretion without affecting microsomal triglyceride transfer protein activity. Immunofluorescence studies show that SMLR1 is in the endoplasmic reticulum and Cis−Golgi complex. The loss of hepatic SMLR1 in female mice protects against diet−induced hyperlipidemia and atherosclerosis but causes NASH. On a high−fat, high−cholesterol diet, insulin and glucose tolerance tests did not reveal differences in male Smlr1−LKO mice versus controls.

Conclusions:

We propose a role for SMLR1 in the trafficking of VLDL from the endoplasmic reticulum to the Cis−Golgi complex. While this study uncovers SMLR1 as a player in the VLDL assembly, trafficking, and secretion pathway, it also shows that NASH can occur with undisturbed glucose homeostasis and atheroprotection.
Clinical significance of MYD88 non‐L265P mutations in diffuse large B‐cell lymphoma
Authors: Xie Jialing , Shen Xia , Shi Qin , Yi Hongmei , Ouyang Binshen , Zhang Zhihan , Gu Yijin , Dong Lei
Published: September 2022

Diffuse large B‐cell lymphoma (DLBCL) is a group of heterogeneous tumors with different molecular traits and clinical features. MYD88 is an oncogene that activates the nuclear factor κB pathway in DLBCL. MYD88 L265P mutation frequently occurs in DLBCL with poor prognosis, while the clinical significance of non‐L265P mutations needs to be clarified. Next‐generation sequencing was performed on a cohort of 356 patients with DLBCL to investigate the impact of MYD88 mutation. Ten MYD88 mutated variants were detected in 32% (114/356) of the cases. V217F, S219C, S222R, M232T, S243N, and T294P were identified as pathogenic variants. MYD88 non‐L265P mutations occurred less than L265P mutation in DLBCL of the central nervous system and breast tissue. The coexistence of MYD88 non‐L265P mutations with PIM1 mutation was also less than that of L265P mutation. The progression‐free survival in patients with DLBCL with MYD88 non‐L265P mutation was statistically better than in patients with MYD88 L265P mutation. The interpretation of variants of MYD88 mutation offers a precise guide for the management of DLBCL.
The emergence of e‐cigarette retail shops in a regulated tobacco control environment
Authors: Scott Lucy , McCausland Kahlia , Maycock Bruce , Jancey Jonine
Published: September 2022

Issue addressed

E‐cigarettes are of growing concern. We aimed to determine the location and characteristics of retail shops selling e‐cigarette products in Perth, Western Australia.

Methods

Two phase study: (i) identifying all e‐cigarette retailers in the Greater Capital City Statistical Area of Perth; (ii) audit at the point‐of‐sale to assess products, promotions and shop characteristics (n = 41).

Results

Ninety‐eight retailers selling e‐cigarette products were identified: 43 tobacconists (44%), 21 vape shops (21% – up from one shop in 2017), 14 supermarkets (14%), 12 service stations (12%) and 8 smoke shops (8%). The most common e‐cigarette product was non‐nicotine e‐liquid, available at 38 (93%) stores audited. Most stores sold parts of e‐cigarette devices (n = 25, 61%). Front counter displays were the most frequent form of promotion (n = 40, 98%). Vape shops differed from other retailers, having bar‐style layouts (n = 15, 71%), lounge areas (n = 7, 33%) and free e‐liquid samples (n = 17, 89%).

Conclusion

The availability of e‐cigarette products from retail shops and particularly vape shops is increasing. E‐cigarette retailers are using traditional promotional techniques including point‐of‐sale displays to market their products, while vape shops are extending their appeal through bar style, lounge layouts and free trials.

Implications for public health

Understanding the e‐cigarette retail store environment is essential for identifying emergent trends, potential regulations and future research.

So what?

The e‐cigarette retail market in the Perth is growing, shops using traditional and new promotional techniques to market e‐cigarette products. Our findings identify a need for public health surveillance, regulations and legislation.
Bone marrow‐derived mesenchymal stem cells alleviate paclitaxel‐induced mechanical allodynia in rats
Authors: Sezer Gulay , Yay Arzu H. , Sarica Zeynep S. , Gonen Zeynep B. , Onder Gozde O. , Alan Aydın , Yilmaz Secil , Saraymen Berkay , Bahar Dilek
Published: September 2022

Anticancer drug paclitaxel (PTX) frequently causes painful peripheral neuropathy; however, no medication has been shown to be effective in the treatment of this debilitating side effect. We aimed to investigate the efficacy of two different doses of allogeneic bone marrow‐derived mesenchymal stem cells (BM‐MSCs) on PTX‐induced mechanical allodynia and spinal cytokine levels and their localization to target tissues such as the spinal cord and sciatic nerve. After the development of mechanical allodynia with repeated PTX administration, two different doses of rat BM‐MSCs, low or high (1 × 106–5 × 106), were transplanted into rats and the evaluation continued for 30 days. Interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, and IL‐10 levels in spinal cord samples of animals were analyzed by enzyme‐linked immunosorbent assay. PTX‐induced mechanical allodynia was relieved significantly 15 days after the transplantation of high‐dose of BM‐MSCs. Both MSCs doses were effective in alleviating allodynia, but the onset of effect was earlier with the high dose. High‐dose of BM‐MSCs significantly decreased spinal IL‐1β and TNF‐α levels compared to the PTX group. Fluorescent dye‐labeled BM‐MSCs were observed much more frequently in the sciatic nerve and spinal cord samples of the high‐dose BM‐MSCs transplanted group than in the low‐dose group animals. In conclusion, we found that the antiallodynic effects of BM‐MSCs appeared earlier when high‐dose of cells were administered. We think that other mechanisms may play a role in the effects of MSCs, besides localization to damaged tissues and reducing spinal inflammatory cytokine levels. We show that BM‐MSCs can be a novel approach in PTX‐induced mechanical allodynia.
Developing a multiplex PCR‐based assay kit for bloodstream infection by analyzing genomic big data
Authors: Zhang Dijun , Luo Yong , Zeng Xianping , Yu Yunsong , Wu Yong
Published: September 2022

Background

In recent years, the incidence of bloodstream infections (BSI) has increased, the composition of pathogenic bacteria has changed, and drug resistance among bacteria has gradually increased due to the widespread use of interventional techniques, broad‐spectrum antibacterial drugs, hormones, and immunosuppressive agents. Here, we have developed a multiplex PCR assay kit for the detection of pathogens (14 Gram‐negative bacteria, 15 Gram‐positive bacteria, and 4 fungi) in whole blood from patients with BSI using five‐color fluorescent multiplex PCR followed by capillary electrophoresis. Our assay exhibits a diagnosis of higher quality and an improved detection rate for common pathogens.

Methods

A local genome DNA database of 33 pathogenic bacteria was constructed. Next, “Exhaustive” primer search of the full coding sequence of the reference genomes of these bacteria was performed. Panels with minimal interactions between primers and amplicons were selected by random sampling and testing by a recursive algorithm. Primers and Mg2+ concentrations and PCR reaction procedures were optimized to maximize the detection efficacy.

Results

The LOD of the kit was determined as 100 copies/μl. Using clinical samples, results generated by this kit and regular blood culture method were found to be 95.08% consistent. Additionally, six pathogens which were unidentifiable by blood culture were successfully detected by this kit.

Conclusion

Our study provided a bioinformatics approach to the challenge of primer design in multiplex PCR, and combined with optimized wet lab practice, a multiplex PCR‐based assay kit for BSI with higher sensitivity and accuracy than blood culture was produced.
A complex haptic exercise to predict pre‐clinic operative dentistry performance: A prospective study
Authors: Urbankova Alice , Palomo Leena , Engebretson Steven P.
Published: September 2022

Purpose/objectives

The purpose of this study was to determine whether performance on a complex manual dexterity haptic test was associated with preclinical operative dentistry practical examination scores in handpiece naïve students.

Methods

Thirty‐nine first‐year pre‐clinical operative dentistry students completed a 15‐min complex manual dexterity exercise “D‐circle” repeated eight times in succession before the beginning of the preclinical operative dentistry course. A composite haptic score was compared with students’ subsequent preclinical operative examination performance and perceptual ability test scores.

Results

Mean accuracy scores on the haptic test increased, and failures decreased across the eight repetitions. Thirty students were successful at least twice in eight attempts, while nine failed all or all but one attempt. The group that failed all or all but one had lower mean scores on the first practical examination (Exam 1) (78.4 vs. 82.2, p = 0.23 Student's t‐test), and 7.0 odds of failing the examination (confidence interval 0.95–51.4, p = 0.06). As a diagnostic predictor of pre‐clinical operative dentistry performance, failing all, or all but one attempt at the haptic test had 60% sensitivity and 82% specificity as a predictor of failure on Exam 1. This resulted in correct classification of 79%.

Conclusions

These data provide evidence for the first time that a complex manual dexterity test on a haptic simulator given to dental students was predictive of early pre‐clinical success. These prospective results confirm previous retrospective studies and if replicated in larger cohorts may lead to improvements in the dental school admissions process.
Monitoring adherence to antiretroviral therapy among adolescents in Southern Uganda: comparing Wisepill to Self‐report in predicting viral suppression in a cluster‐randomized trial
Authors: Kizito Samuel , Namuwonge Flavia , Brathwaite Rachel , Neilands Torsten B. , Nabunya Proscovia , Bahar Ozge Sensoy , Damulira Christopher , Mwebembezi Abel , Mellins Claude , McKay Mary M. , Ssewamala Fred M.
Published: September 2022

Introduction

Optimal antiretroviral therapy (ART) adherence is crucial for improved patient outcomes; however, ART adherence among adolescents living with HIV (ALHIV) is low. Also, the performance of various adherence measures among ALHIV is under contention. We monitored ART adherence and compared Self‐report (SR) and Wisepill electronic monitoring (EM) performance in measuring ART adherence and predicting HIV viral suppression among ALHIV.

Methods

Between January 2014 and December 2015, we recruited 702 ALHIV aged 10–16 years into our cluster‐randomized controlled trial (2012–2018) in 39 clinics in Uganda. The intervention included a long‐term savings child development account, four micro‐enterprise workshops and 12 mentorship sessions. Using the entire sample, we performed multilevel logistic regression to predict monthly ART adherence trends for the first year of follow‐up. Since it is possible that the intervention had different effects on SR and EM adherence, we used participants in the control arm only to compare adherence using SR and EM and to calculate their sensitivity and specificity in predicting viral suppression.

Results

There was a significant decline in adherence for each month throughout the entire follow‐up period regardless of the group assigned. Good ART adherence was measured at 79.2% (75.2–82.6%) and 97.0% (95.4–98.1%) using EM and SR, respectively. Overall, 64.3% (60.6–67.9%) had suppressed viral loads. The specificities for EM and SR in predicting viral non‐suppression were 80.4% (73.6–85.7%) and 96.7% (93.3–98.4%), while the sensitivities were 22.9% (15.0–33.3%) and 1.8% (0.4–6.9%), respectively. The area under the curve was low for both EM and SR, at 53.6% (45.7–61.5%) and 56.2% (53.2–59.3%), respectively. There was high agreement (78%) between SR and EM in monitoring adherence.

Conclusions

Our findings highlighted the need for strategies for sustained optimal adherence. SR and EM measure adherence with a considerable agreement; however, neither is an accurate predictor of virological outcome. There is still a need for an acceptable, feasible and affordable method that predicts viral suppression among ALHIV.
A strong anion exchanger of poly(glycidyl methacrylate‐divinylbenzene) substrate functionalized with cationic quaternary ammonium monomer
Authors: Li Zongying , Chen Xin , Zhang Feifang , Yang Bingcheng
Published: September 2022

A strong anion exchanger applied for ion chromatography is described by grafting methacrylamido propyl trimethyl ammonium chloride onto hydrolyzed poly(glycidyl methacrylate‐divinylbenzene) substrate. The anion exchanger has been in detail characterized and the final capacity of the anion exchanger can be readily manipulated by different monomer amounts. It exhibited obvious temperature‐sensitive properties and large tolerance to the samples with high ionic strength. The obtained anion exchanger demonstrated effective separation ability towards the common seven inorganic anions within 12 min and high separation efficiency, for example, 58 000/m of theoretical plate count for chloride.
A simple and green liquid chromatography method for the determination of ibuprofen in milk‐containing simulated gastrointestinal media for monitoring the dissolution studies of three‐dimensional‐printed formulations
Authors: Doumtsi Antigoni , Manousi Natalia , Karavasili Christina , Fatouros Dimitrios G. , Tzanavaras Paraskevas D. , Zacharis Constantinos K.
Published: September 2022

A fast and green ultra‐high‐performance liquid chromatographic method was developed for the determination of ibuprofen in milk‐containing simulated gastrointestinal media to monitor the dissolution of three‐dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The β‐expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01 μg/ml and the lower limit of quantitation was established as 2 μg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.
Long non‐coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2‐mediated epigenetic modification
Authors: Yu Yi , Zou Yu‐Feng , Hong Run‐Qi , Chen Wen‐Jie , Chen Liang , Chen Wen‐Qi , Wang Hui‐Peng , Yu Yuan
Published: September 2022

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine‐resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine‐resistant PC cells (PANC‐1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild‐type PC cells and in gemcitabine‐resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p‐Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation‐quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p‐Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2‐mediated epigenetic modification.
A single bounded input‐feedback control to the generalized Korteweg–de Vries–Burgers–Kuramoto–Sivashinsky equation
Authors: Al Jamal Rasha , Smaoui Nejib
Published: September 2022

The generalized Korteweg–de Vries–Burgers–Kuramoto–Sivashinsky equation (GKdVBKS) is a nonlinear partial differential equation that models propagation of waves in a thick elastic tube filled with a viscous fluid. First, the dynamics of the GKdVBKS equation that depend on the physical parameters
and
, where
is a positive parameter and
is a real number, are presented. We show that the set of constant equilibrium solutions is unstable when
, Lyapunov stable when
, and globally exponentially stable when
. Second, we show that the controlled GKdVBKS equation has a unique strong solution. Then, we synthesize a single bounded input‐feedback controller for the GKdVBKS equation through its linearized system avoiding any spillover. The approach used is valid due to the Fréchet differentiability of the nonlinear
‐semigroup generated by the nonlinear GKdVBKS equation with its derivative being the linear
‐semigroup generated by the linearized system. Finally, numerical results for different values of the parameters of the equation are presented to illustrate the developed theory.