bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated whole‐exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground‐glass nodules
Authors: Zhou Dong , Li Yan‐qi , Liu Quan‐xing , Deng Xu‐feng , Chen Liang , Li Man‐yuan , Zhang Jiao , Lu Xiao , Zheng Hong , Dai Ji‐gang
Published: June 2024

Objective

The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC.

Methods

Thirty‐five patients with ground‐glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole‐exome sequencing (WES) and transcriptome sequencing (RNA‐Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA‐Seq were subsequently analyzed.

Results

The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co‐mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD.

Conclusions

Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.
Biological Properties of Mentha viridis L. Essential Oil and Its Main Monoterpene Constituents
Authors: Omari Nasreddine El , Chamkhi Imane , Bakrim Saad , Aanniz Tarik , Benali Taoufiq , Akhazzane Mohamed , Ullah Riaz , Alotaibi Amal , Bari Ahmed , Elhrech Hamza , Zengin Gokhan , Bouyahya Abdelhakim
Published: June 2024

This research aimed to evaluate the antidiabetic, dermatoprotective, and antibacterial activities of Mentha viridis L. essential oil (MVEO) collected in the province of Ouezzane (Northwest Morocco). Gas chromatography‐mass spectrometry (GC‐MS) analysis revealed that the main constituents of MVEO were carvone (37.26 %), 1,8‐cineole (11.82 %), limonene (5.27 %), α‐terpineol (4.16 %), and β‐caryophyllene (4.04 %). MVEO showed strong inhibitory effects on α‐amylase and α‐glucosidase activities, exceeding those of acarbose, but weak anti‐elastase activity. The main compounds, β‐caryophyllene (IC50=79.91±2.24 and 62.08±2.78 μg/mL) and limonene (IC50=90.73±3.47 and 68.98±1, 60 μg/mL), demonstrated the strongest inhibitory effects on both digestive enzymes (α‐glucosidase and α‐amylase, respectively). In silico investigations, using molecular docking, also showed the inhibitory potential of these bioactive compounds against the enzymes tested. In conclusion, MVEO, due to its main components such as limonene, 1,8‐cineole, β‐caryophyllene, carvone, and α‐terpineol, shows promising prospects for drug discovery and natural therapeutic applications.
A Comprehensive Review of Solar Photocatalysis & Photothermal Catalysis for Hydrogen Production from Biomass: from Material Characteristics to Engineering Application
Authors: Lei Dongqiang , Wang Linhao , Lv Yue , Luo Nengchao , Wang Zhifeng
Published: June 2024

Biomass photoreforming is a promising way of producing sustainable hydrogen thanks to the abundant sources of biomass feedstocks. Solar energy provides the heat and driven force to initial biomass oxidation coupled with H2 evolution. Currently, biomass photoreforming is still far from plant‐scale applications due to the lower solar energy utilization efficiencies, the low H2 yield, and the lack of appropriate photoreactors. The production of H2 from photoreforming of native biomass and platform molecules was summarized and discussed with particular attention to the prospects of scaling up the catalysis technology for mass hydrogen production. The types of photoreforming, including photocatalysis and photothermal catalysis, were discussed, consequently considering the different requirements for photoreactors. We also reviewed the photoreactors that support biomass photoreforming. Numerical simulation methods were implemented for the solid‐liquid two‐phase flow and inter‐particle radiative transfer involved in the reaction process. Developing concentrated photothermal catalytic flowed reactors is beneficial to scale‐up catalytic hydrogen production from biomass.
Household material hardship and distress among parents of children with advanced cancer: A report from the PediQUEST Response trial
Authors: Eche‐Ugwu Ijeoma Julie , Orellana Liliana , Becker Denise , Bona Kira , Avery Madeline , Feudtner Chris , Freedman Jason L. , Kang Tammy I. , Rosenberg Abby R. , Waldman Elisha D. , Ullrich Christina K. , Dussel Veronica , Wolfe Joanne
Published: June 2024

Background

The prevalence and characteristics of household material hardship (HMH) in families of children with advanced cancer and its association with parent distress are unknown and herein described.

Methods

Parents of children aged ≥2 years with advanced cancer at five cancer centers completed baseline surveys as part of the PediQUEST Response trial. HMH (housing, energy, and food) was operationalized as binary (≥1 HMH domains), ordinal (zero, one, or two or more HMH domains), and housing based (none, nonhousing [food and/or energy], only housing, or housing + other). Associations between HMH and parent distress measured by the State‐Trait Anxiety Inventory–State and the 10‐item Center for Epidemiologic Studies Depression Scale were estimated via linear models adjusting for confounders.

Results

Among 150 parents, 41% reported ≥1 HMH (housing, 28% [only housing, 8%; housing + other, 20%]; energy, 19%; food, 27%). HMH was more prevalent among Hispanic, other non‐White race, Spanish‐speaking, and single parents and those with lower education (associate degree or less) or who were uninsured/Medicaid‐only insured. Parents endorsing HMH reported higher anxiety (mean difference [MD], 9.2 [95% CI, 3.7–14.7]) and depression (MD, 4.1 [95% CI, 1.7–6.5]) scores compared to those without HMH. Distress increased with the number of hardships, particularly housing insecurity. Specifically, parents experiencing housing hardship, alone or combined, reported higher distress (housing only: anxiety: MD, 10.2 [95% CI, 1.8–18.5]; depression: MD, 4.9 [95% CI, 1.3–8.6]; housing + other HMH: anxiety: MD, 12.0 [95% CI, 5.2–18.9]; depression: MD, 4.8 [95% CI, 1.8–7.8]).

Conclusions

HMH is highly prevalent in pediatric advanced cancer, especially among historically marginalized families. Future research should investigate whether interventions targeting HMH, particularly housing stabilization efforts, can mitigate parent distress.

Plain Language Summary

In our cohort of parents of children with advanced cancer, household material hardship (HMH) was highly prevalent and significantly associated with higher parent distress. Housing hardship was the primary driver of this association.

Families of children with advanced cancer may benefit from systematic HMH screening as well as targeted HMH interventions, especially stabilizing housing.
Healthy lifestyle and prostate cancer risk in the Million Veteran Program
Authors: Pagadala Meghana S. , Lui Asona , Lynch Julie , Karunamuni Roshan , Lee Kyung Min , Plym Anna , Rose Brent S. , Carter Hannah , Kibel Adam S. , DuVall Scott L. , Vassy Jason , Gaziano J. Michael , Panizzon Matthew S. , Hauger Richard L. , Seibert Tyler M.
Published: June 2024

Background

This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population.

Methods

Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system–based cohort study, were analyzed. Self‐reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes.

Results

After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64–2.02; p < 10−16) and fatal PCa (HR, 2.73; 95% CI, 2.36–3.25; p < 10−16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76–0.98; p = .03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers).

Conclusions

Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa.
Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy
Authors: Robinson Katherine M. , Eum Seenae , Desta Zeruesenay , Tyndale Rachel F. , Gaedigk Andrea , Crist Richard C. , Haidar Cyrine E. , Myers Alan L. , Samer Caroline F. , Somogyi Andrew A. , Zubiaur Pablo , Iwuchukwu Otito F. , Whirl‐Carrillo Michelle , Klein Teri E. , Caudle Kelly E. , Donnelly Roseann S. , Kharasch Evan D.
Published: June 2024

Methadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R‐ and S‐enantiomers. R‐methadone has 30‐to 50‐fold higher analgesic potency than S‐methadone, and S‐methadone has a greater adverse effect (prolongation) on the cardiac QTc interval. Methadone undergoes stereoselective metabolism. CYP2B6 is the primary enzyme responsible for catalyzing the metabolism of both enantiomers to the inactive metabolites, S‐ and R‐2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (S‐ and R‐EDDP). Genetic variation in the CYP2B6 gene has been investigated in the context of implications for methadone pharmacokinetics, dose, and clinical outcomes. Most CYP2B6 variants result in diminished or loss of CYP2B6 enzyme activity, which can lead to higher plasma methadone concentrations (affecting S‐ more than R‐methadone). However, the data do not consistently indicate that CYP2B6‐based metabolic variability has a clinically significant effect on methadone dose, efficacy, or QTc prolongation. Expert analysis of the published literature does not support a change from standard methadone prescribing based on CYP2B6 genotype (updates at www.cpicpgx.org).
Evolution of a late Quaternary succession by interpretation of high‐resolution seismic and bathymetric data, Adriatic Sea
Authors: Da Col Federico , Zecchin Massimo , Civile Dario , Baradello Luca , Deponte Michele , Accaino Flavio
Published: June 2024

This paper presents the results of the interpretation of a set of high‐resolution seismic lines integrated with multibeam echosounder data acquired in a coastal area in the Northern Adriatic Sea. The aim of the study was to reconstruct the stratigraphic evolution of a late Quaternary sedimentary succession offshore the town of Bibione, North‐Eastern Italy, by recognising the key unconformities, identifying the main depositional units, dating them and reconstructing the depositional environments in relation to relative sea‐level variations. Specifically, four sedimentary units, separated by erosional unconformities associated with the development of deep channels, were identified and dated based on literature information. By interpreting the seismic data, sedimentary dynamics were reconstructed and palaeoenvironments identified. The lower unit corresponds to a paludal environment, showing abundant gas seeps and accumulations (bright spots); the two intermediate units correspond to fluvial deposits, filling the deep incisions that characterise the bounding surfaces. Finally, the shallowest unit, bounded by a wave‐ravinement surface incised by tidal currents, corresponds to the Holocenic progradation of the coastal wedge. In addition, several vertical gas chimneys were identified, ranging in width from a few metres to 20–30 m. These were present in all units, often reaching the sea floor. Finally, elongated mounds, about 300 m wide, at the sea floor were recognised. The bathymetric and seismic characteristics of these elongated bodies and their relationship to adjacent sedimentary bodies suggest that they are probably methane‐derived carbonate formations known as ‘Trezze’ or ‘Tegnùe’. These names recall the fact that the trawls of the local fishermen were often hindered (‘tegnù’ in the Venetian language) or even cut off by these formations.
Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double‐blind, placebo‐controlled, crossover study
Authors: Segerdahl M. , Rother M. , Halldin M. M. , Popescu T. , Schaffler K.
Published: June 2024

Background

The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1‐antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1‐antagonist (ACD440 Gel) in healthy subjects.

Methods

The study comprised two parts.

In part 1, 24 healthy subjects were included in this randomized double‐blind, placebo‐controlled, crossover trial. ACD440 Gel or Placebo was applied once daily and wiped off after 1 h, for 5 consecutive days. Assessments were done in normal skin, skin optimized for penetration (by stripping and occlusive gel application) and UVB‐irradiated skin. Pain induced by thermo‐nociceptive CO2 laser impulses generated laser‐evoked potentials (LEPs), with readouts of peak‐to‐peak (PtP) amplitude in vertex‐EEG and pain assessments by VAS (0–100). Endpoints include effects at 1 hour post‐dose, AUC(Days 1–5) and AUC(0–24, Day 4). In UVB‐irradiated skin, also pain on pinprick and skin redness were assessed.

Part 2 explored the plasma pharmacokinetics of ACD440.

Results

ACD440 Gel reduced LEP PtP amplitude and VAS pain, p < 0.001, in all skin conditions, versus placebo. In UVB‐irradiated skin, pinprick pain was also reduced, p = 0.047. Effects were significant after 1 h, maintaining for at least 9 h. There were no adverse events or drug‐induced erythema. Plasma exposures of ACD440 were too low to establish an elimination half‐life of ACD400.

Conclusions

Topical ACD440 Gel demonstrated a significant analgesic effect on LEP, VAS score and pinprick pain, with low systemic exposures, supporting further clinical development.

Significance

This study demonstrates that the topical administration of a TRPV1‐antagonist, ACD440 Gel, has potential as a new treatment for painful conditions affecting the skin, such as chronic peripheral neuropathic pain, without any local or systemic side effects.
Enhanced optical performance of solar cell using hydrophobic SnO2/TEOS/MTMS antireflection coating
Authors: Chandralekha N. R. , Shanthi J. , Swathi R. , Anoop K. K.
Published: June 2024

Anti‐reflection coatings have potential usage in photovoltaic solar cells, sensors, and display devices to reduce reflectance, glare and enhance light transmission. ARC was developed to increase more efficiency of solar cell cover glasses, by depositing SnO2/TEOS/MTMS coating using the sol–gel spin coating technique. The coating showed a maximum transmittance of 92.70% at 399 nm wavelength with an average refractive index of 1.42. The transmittance of the antireflective film was increased by 2.29% than the bare glass substrate. The surface morphology of the coatings was investigated using FESEM analysis. The mechanical stability of the coating was evaluated using ASTM standard D 3363–05 pencil scratch test, and it demonstrated good performance against 3H hardness pencil. The efficiency of solar cells has been increased by 1.56% after depositing with single layer SnO2/TEOS/MTMS film. Moreover, the coating maintains the solar cell's performance even during dust exposure, because of its self‐cleaning ability with water contact angle of 94°. Thus, the Anti‐reflection coating can be applied to enhance the efficiency of photovoltaic system.
Impact of data processing varieties on DCM estimates of effective connectivity from task‐fMRI
Authors: Zhang Shufei , Jung Kyesam , Langner Robert , Florin Esther , Eickhoff Simon B. , Popovych Oleksandr V.
Published: June 2024

Effective connectivity (EC) refers to directional or causal influences between interacting neuronal populations or brain regions and can be estimated from functional magnetic resonance imaging (fMRI) data via dynamic causal modeling (DCM). In contrast to functional connectivity, the impact of data processing varieties on DCM estimates of task‐evoked EC has hardly ever been addressed. We therefore investigated how task‐evoked EC is affected by choices made for data processing. In particular, we considered the impact of global signal regression (GSR), block/event‐related design of the general linear model (GLM) used for the first‐level task‐evoked fMRI analysis, type of activation contrast, and significance thresholding approach. Using DCM, we estimated individual and group‐averaged task‐evoked EC within a brain network related to spatial conflict processing for all the parameters considered and compared the differences in task‐evoked EC between any two data processing conditions via between‐group parametric empirical Bayes (PEB) analysis and Bayesian data comparison (BDC). We observed strongly varying patterns of the group‐averaged EC depending on the data processing choices. In particular, task‐evoked EC and parameter certainty were strongly impacted by GLM design and type of activation contrast as revealed by PEB and BDC, respectively, whereas they were little affected by GSR and the type of significance thresholding. The event‐related GLM design appears to be more sensitive to task‐evoked modulations of EC, but provides model parameters with lower certainty than the block‐based design, while the latter is more sensitive to the type of activation contrast than is the event‐related design. Our results demonstrate that applying different reasonable data processing choices can substantially alter task‐evoked EC as estimated by DCM. Such choices should be made with care and, whenever possible, varied across parallel analyses to evaluate their impact and identify potential convergence for robust outcomes.
Males with patellofemoral pain have altered movements during step‐down and single‐leg squatting tasks compared to asymptomatic males: A cross‐sectional study
Authors: Hoglund Lisa T. , Hulcher Thomas Alexander , Amabile Amy H.
Published: June 2024

Background and Aims

Patellofemoral pain (PFP) is common in males, causing reduced physical activity and chronic pain. One proposed cause of PFP is aberrant biomechanics during tasks loading the patellofemoral joint. Consistent evidence exists for females with PFP, but it is uncertain if males with PFP have altered biomechanics. This study investigated the kinematics of males with PFP compared to pain‐free males during forward step‐down (StDn) and single‐leg squat (SLSq).

Methods

A cross‐sectional study including 40 males aged 20–39 years (28.28 ± 5.46) was conducted (20 PFP, 20 pain‐free). Participants performed StDn and SLSq while motion was captured with a video‐based motion capture system (Motion Analysis Corporation). Triplanar peak angles and angular ranges of motion (ROM) of the trunk, pelvis, and weight‐bearing hip, knee, and ankle were dependent variables. Mixed‐model ANOVA tests were used to determine the presence of significant interactions and main effects of group and task.

Results

Males with PFP had significantly lower peak knee adduction angles compared to pain‐free males (p = 0.01). Significant group x task interactions were found for hip and pelvis ROM (p < 0.05). PFP participants had increased hip and pelvis ROM during StDn in the frontal and transverse planes but reduced or nearly equal ROM for these variables during SLSq. Peak hip adduction, hip internal rotation, contralateral pelvic drop and anterior tilt, trunk flexion, and ankle dorsiflexion were greater during StDn compared to SLSq (p < 0.05). ROM of the hip, pelvis, trunk, and ankle were greater during StDn compared to SLSq (p < 0.05).

Conclusion

Males with PFP had reduced peak knee adduction angles in StDn and SLSq. Males with PFP demonstrated increased hip and pelvis ROM during StDn versus SLSq, particularly in the frontal and transverse planes. Clinicians should consider StDn as a clinical test since aberrant movement may be easier to detect than in SLSq.
Theoretical investigation of thermal and mass stratification effects on unsteady flow across a vertical oscillating plate with periodic temperature variation and variable mass diffusion
Authors: Nath Rupam Shankar , Kumar Himangshu , Deka Rudra Kanta
Published: June 2024

This research paper examines the combined effects of thermal and mass stratification on unsteady flow past a vertical oscillating plate with periodic temperature variation and variable mass diffusion. The Laplace transform technique is introduced to deal with the linear coupled parabolic equations satisfying initial as well as boundary conditions and obtained solutions in closed form for concentration, temperature, and velocity. For example, to find the Laplace transform of an exponentially ordered piece wise continuous function , one can uses the formula , t being the time and s is a parameter. In this study, we explore the effects of different factors such as plate amplitude, plate frequency, thermal Grashof number, and the mass Grashof number on the concentration, velocity, and temperature profiles and shows them graphically. We see a decline in the fluid's velocity for thermal and mass stratification. Most interestingly, in presence of higher temperature gradient, as the frequency of the oscillations increases close to the plate surface, the fluid velocity declines. The reason behind this is that the flow system has a plate with very high fluctuations. We have found that the fluid's temperature goes up while the concentration goes down when there is a decrease in the thermal stratification and a rise in the mass stratification.
A case of central nervous system infection with Scedosporium boydii
Authors: Cai Zhen , Pan Dongchao , Geng Ronghua , Fu Jidi , Qu Fen
Published: June 2024

Scedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients. It also causes serious and fatal central nervous system infections. In this study, a man with brain abscesses infected with S. boydii was diagnosed using multiple methods, including microscopy, culture combined with Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MOLDI‐TOF MS), internal transcribed spacer sequencing and Metagenomic next‐generation sequencing (mNGS). This successful diagnosis highlights the importance of using a variety of techniques to identify and treat infections caused by this dangerous fungus.
In vitro and in vivo investigation of antibacterial silver nanoparticles functionalized bone grafting substitutes
Authors: Abdelmoneim Dina , Coates Dawn , Porter Gemma , Schmidlin Patrick , Li Kai Chun , Botter Sander , Lim Khoon , Duncan Warwick
Published: June 2024

Infection is a major concern in surgery involving grafting and should be considered thoroughly when designing biomaterials. There is considerable renewed interest in silver nanoparticles (AgNPs) owing to their ability to potentiate antibacterial properties against multiple bacterial strains. This study aimed to develop two antibacterial bone regenerative scaffolds by integrating AgNPs in bovine bone particles (BBX) (Product 1), and a light cross‐linked hydrogel GelMA (Product 2). The constructs were characterized using scanning electron microscopy. Metabolic activity of osteoblasts and osteoclasts on the constructs was investigated using PrestoBlue™. Disk diffusion assay was conducted to test the antibacterial properties. The regenerative capacity of the optimized AgNP functionalized BBX and GelMA were tested in a rabbit cranial 6 mm defect model. The presence of AgNPs appears to enhance proliferation of osteoblasts compared to AgNP free controls in vitro. We established that AgNPs can be used at a 100 μg dose that inhibits bacteria, with minimal adverse effects on the bone cells. Our rabbit model revealed that both the BBX and GelMA hydrogels loaded AgNPs were biocompatible with no signs of necrosis or inflammatory response. Grafts functionalized with AgNPs can provide antibacterial protection and simultaneously act as a scaffold for attachment of bone cells.
Antenatal diagnosis and management of fetal inguinoscrotal hernia: A case report with literature review
Authors: Seong Ji‐Su , Kim Yoo‐Min , Nam Gina , Kim Gwang‐Jun
Published: June 2024

Primary inguinal hernia is a common pediatric surgical condition with an incidence of 1%–4%, which is higher in male or premature newborns. It is characterized by the protrusion of abdominal contents through inguinal canal in newborns. However, prenatal fetal inguinal hernia is a rare condition because the pressure of amniotic fluid is similar to intra‐abdominal pressure. Only 19 English publications were found with 21 reported cases until now. We report belatedly discovered inguinoscrotal hernia at 38+0 weeks' gestation. Usually, the fetal testicular descent begins from 24 to 25 weeks' gestation, and it is found after 32 weeks of gestational age in 97% of the fetuses. Therefore, it is necessary to get into the habit of checking fetal testicles during routine US after at least 32 weeks of gestational age.
Why dental schools should engage with dental support organizations
Authors: Vitzthum Kelly C. , Rashti Rebecca , Lee Steve Y. , Piskorowski Wilhelm A.
Published: June 2024

It is incumbent on dental educators to prepare students for careers in various practice settings and modalities. As the dental practice market continues to evolve away from a predominantly solo private practice model, schools are tasked with training future providers to deliver quality care to diverse patient populations in diverse settings. While no single health delivery model will solve access to care, exposing dental students to various practice environments prepares them to better understand and navigate nontraditional postgraduate practice opportunities. The University of California, Los Angeles (UCLA) School of Dentistry established a community‐based clinical education (CBCE) program that has grown to include dental support organizations. By partnering with a more diverse portfolio of practice types, including large corporate entities, the UCLA CBCE program has strengthened its financial accountability while also delivering on the goal of enhancing dental education and improving access to care for vulnerable populations.
Measurement properties of the Swedish version of the anterior cruciate ligament return to sport after injury scale (ACL‐RSI): A Rasch analysis
Authors: Piussi Ramana , Alenius Sara , Webster Kate E. , Thomeé Roland , Westergren Albert , Hagell Peter , Hamrin Senorski Eric
Published: June 2024

Purpose

This study aimed to investigate the measurement properties, according to the Rasch Measurement Theory, of the anterior cruciate ligament return to sport after injury scale (ACL‐RSI) in patients treated with ACL reconstruction in Sweden.

Methods

ACL‐RSI responses from 1065 patients treated with ACL reconstruction were extracted from a rehabilitation‐specific registry. Rasch analyses were performed on ACL‐RSI item response data using the RUMM2030plus software. The analyses focused on targeting (person‐item threshold distribution), item hierarchy, response category thresholds, overall and individual item and person fit, differential item functioning (DIF), unidimensionality and reliability.

Results

The ACL‐RSI had compromised fit to the Rasch model, including DIF and malfunctioning response categories. Several items correlate with each other and the presumptions to aggregate item responses into one single score were not met. When accounting for local dependency, the measurement properties of the ACL‐RSI improved in terms of model fit and DIF and unidimensionality were supported.

Conclusion

The ACL‐RSI was found to have signs of multidimensionality and local dependency, that is, the answers to one item are influenced by the answers to other items. As such, researchers should be careful when using the ACL‐RSI as one single score to evaluate patients treated with ACL reconstruction, unless local dependency is accounted for in the scoring process.

Level of Evidence

Level III.
A sensitive bioanalytical ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantitation of lactone and carboxylate forms of topotecan in plasma and vitreous
Authors: Mudrova Barbora , Hrabakova Katerina , Kozlik Petr , Hobzova Radka , Sirc Jakub , Bosakova Zuzana
Published: June 2024

Topotecan (TPT) is used in the treatment of retinoblastoma, the most common malignant intraocular tumor in children. TPT undergoes pH‐dependent hydrolysis of the lactone ring to the ring‐opened carboxylate form, with the lactone form showing antitumor activity. A selective, and highly sensitive ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed for the determination of both forms of TPT in one mobile phase composition in plasma and vitreous humor matrices. The method showed an excellent linear range of 0.375–120 ng/mL for the lactone. For the carboxylate, the linear range was from 0.75 to 120 ng/mL. The matrix effect and the recovery for the lactone ranged from 98.5% to 106.0% in both matrices, for the carboxylate form, it ranged from 94.9% to 101.2%. The dynamics of the transition between TPT lactone and TPT carboxylate were evaluated at different pH environments. The stability of TPT forms was assessed in plasma and vitreous humor at 8 and 37°C and a very fast conversion of lactone to carboxylate form occurred at 37°C in both matrices. The method developed facilitates the investigation of TPT pharmacodynamics and the release kinetics in the development of the innovative local drug delivery systems.
AI Detection of Glottic Neoplasm Using Voice Signals, Demographics, and Structured Medical Records
Authors: Wang Chi‐Te , Chen Tsai‐Min , Lee Nien‐Ting , Fang Shih‐Hau
Published: June 2024

Objective

This study investigated whether artificial intelligence (AI) models combining voice signals, demographics, and structured medical records can detect glottic neoplasm from benign voice disorders.

Methods

We used a primary dataset containing 2–3 s of vowel “ah”, demographics, and 26 items of structured medical records (e.g., symptoms, comorbidity, smoking and alcohol consumption, vocal demand) from 60 patients with pathology‐proved glottic neoplasm (i.e., squamous cell carcinoma, carcinoma in situ, and dysplasia) and 1940 patients with benign voice disorders. The validation dataset comprised data from 23 patients with glottic neoplasm and 1331 patients with benign disorders. The AI model combined convolutional neural networks, gated recurrent units, and attention layers. We used 10‐fold cross‐validation (training–validation–testing: 8–1–1) and preserved the percentage between neoplasm and benign disorders in each fold.

Results

Results from the AI model using voice signals reached an area under the ROC curve (AUC) value of 0.631, and additional demographics increased this to 0.807. The highest AUC of 0.878 was achieved when combining voice, demographics, and medical records (sensitivity: 0.783, specificity: 0.816, accuracy: 0.815). External validation yielded an AUC value of 0.785 (voice plus demographics; sensitivity: 0.739, specificity: 0.745, accuracy: 0.745). Subanalysis showed that AI had higher sensitivity but lower specificity than human assessment (p < 0.01). The accuracy of AI detection with additional medical records was comparable with human assessment (82% vs. 83%, p = 0.78).

Conclusions

Voice signal alone was insufficient for AI differentiation between glottic neoplasm and benign voice disorders, but additional demographics and medical records notably improved AI performance and approximated the prediction accuracy of humans.

Level of Evidence

NA Laryngoscope, 134:4585–4592, 2024
Underway measurement of cyanobacterial microcystins using a surface plasmon resonance sensor on an autonomous underwater vehicle
Authors: Ussler William , Doucette Gregory J. , Preston Christina M. , Weinstock Chloe , Allaf Nadia , Roman Brent , Jensen Scott , Yamahara Kevan , Lingerfelt Louise A. , Mikulski Christina M. , Hobson Brett W. , Kieft Brian , Raanan Ben‐Yair , Zhang Yanwu , Errera Reagan M. , Ruberg Steven A. , Den Uyl Paul A. , Goodwin Kelly D. , Soelberg Scott D. , Furlong Clement E. , Birch James M. , Scholin Christopher A.
Published: June 2024

Freshwater cyanobacterial harmful algal blooms (CHABs) are a well‐known global public health threat. Monitoring and early detection of CHAB toxins are currently accomplished using labor‐intensive sampling techniques and subsequent shore‐based analyses, with results typically reported 24–48 h after sample collection. We have developed and implemented an uncrewed, autonomous mobile sampler‐analytical system capable of conducting targeted in situ toxin measurements in < 2 h. A surface plasmon resonance (SPR) instrument was combined with the environmental sample processor (ESP) to fully automate detection and quantification of particle‐associated cyanobacterial microcystins (pMC). This sensor‐sampler system was integrated with a long‐range autonomous underwater vehicle (LRAUV) and deployed in western Lake Erie for field trials in the summer of 2021. The LRAUV was remotely piloted to acquire samples at selected locations within and adjacent to a CHAB. Sixteen pMC measurements ranging from 0.09 to 0.55 μg/L lake water were obtained over a 14‐day period without recovery of the LRAUV. The SPR/ESP/LRAUV system complements existing satellite, aerial, and manual sampling CHAB survey techniques, and could be used to enhance predictive models that underpin bloom and toxicity forecasts. This system is also extensible to detection of other algal toxins in freshwater and marine environments, with its near real‐time assessment of bloom toxin levels potentially offering additional socioeconomic benefits and public health protection in a variety of settings.
Promoting Periodical Poling in Lithium Niobate Crystal Through Surface Acoustic Wave‐Induced Local Lattice Activation
Authors: Liu Qilu , Song Yukun , Bai Linyu , Zhang Longxi , Chen Xu , Zhao Xuezhi , Wang Fulei , Liu Hong , Wang Dongzhou , Li Yanlu , Sang Yuanhua
Published: June 2024

Achieving precise construction of ferroelectric domain structure in lithium niobate (LN) crystals holds significance for expanding the applications of periodically poled lithium niobate (PPLN), especially in nonlinear frequency conversion. However, challenges exist during the application of electric field for poling, especially for small‐period PPLN crystals, where ferroelectric domains in LN crystals tend to unevenly expand laterally, making it hard to precisely control the domain structures. LN, as a piezoelectric crystal, has the capability to generate energy‐carrying surface acoustic waves (SAW). Herein, an method is presented to optimize the periodic poling process by integrating SAW and poling on a LN chip, which remarkably reduces the poling electric field by 10%, attributed to the enhanced local lattice vibrations during SAW propagation. The integrated SAW and poling chip achieves a 9 µm‐period PPLN crystal. Through second harmonic generation, a nonlinear light conversion from 1158 to 579 nm is realized, exhibiting a nonlinear optical efficiency up to 17.4%. This efficiency aligns with the theoretical prediction, validating the high‐quality domain structure. This integrated chip provides a unique opportunity for manipulating ferroelectric domain with high‐precision, benefiting a wide range of applications in nonlinear‐optics, ferroelectrics, and integrated optics.
3D Puzzle at the Nanoscale–How do RNA Viruses Self‐Assemble their Capsids into Perfectly Ordered Structures
Authors: Kordys Martyna , Urbanowicz Anna
Published: June 2024

The phenomenon of RNA virus self‐organization, first observed in the mid‐20th century in tobacco mosaic virus, is the subject of extensive research. Efforts to comprehend this process intensify due to its potential for producing vaccines or antiviral compounds as well as nanocarriers and nanotemplates. However, direct observation of the self‐assembly is hindered by its prevalence within infected host cells. One of the approaches involves in vitro and in silico research using model viruses featuring a ssRNA(+) genome enclosed within a capsid made up of a single type protein. While various pathways are proposed based on these studies, their relevance in vivo remains uncertain. On the other hand, the development of advanced microscopic methods provide insights into the events within living cells, where following viral infection, specialized compartments form to facilitate the creation of nascent virions. Intriguingly, a growing body of evidence indicates that the primary function of packaging signals in viral RNA is to effectively initiate the virion self‐assembly. This is in contrast to earlier opinions suggesting a role in marking RNA for encapsidation. Another noteworthy observation is that many viruses undergo self‐assembly within membraneless liquid organelles, which are specifically induced by viral proteins.
4D Printing of Magneto‐Thermo‐Responsive PLA/PMMA/Fe3O4 Nanocomposites with Superior Shape Memory and Remote Actuation
Authors: Doostmohammadi Hossein , Baniassadi Majid , Bodaghi Mahdi , Baghani Mostafa
Published: June 2024

This study presents the development and 4D printing of magnetic shape memory polymers (MSMPs) utilizing a composite of polylactic acid (PLA), polymethyl methacrylate (PMMA), and Fe3O4 nanoparticles. The dynamic mechanical analysis reveals that the integration of Fe3O4 maintains the broad thermal transition without significantly affecting α‐relaxation time, indicating high compatibility and homogeneous distribution of the nanoparticles within the polymer matrix. Field emission scanning electron microscopy further confirms the high compatibility of PLA and PMMA phases as well as uniform dispersion of Fe3O4 nanoparticles, essential for the effective transfer of heat during the shape memory process. Significantly, the incorporation of magnetic nanoparticles enables remote actuation capabilities, presenting a substantial advancement for biomedical applications. 4D‐printed MSMP nanocomposites exhibit exceptional mechanical properties and rapid, efficient shape memory responses under both inductive and direct heating stimuli, achieving 100% shape fixity and 100% recovery within ≈85 s. They are proposed as promising candidates for biomedical implants, specifically for minimally invasive implantation of bone scaffolds, due to their rapid remote actuation, biocompatibility, and mechanical robustness. This research not only demonstrates the 4D printability of high‐performance MSMPs but also introduces new possibilities for the application of MSMPs in regenerative medicine.
Impacts of supply chain leadership on dynamic pricing under consumer patience information asymmetry
Authors: Wang Jun , Ma Wenkang , Xia Liangjie , Hou Pengwen
Published: June 2024

As the online market rapidly develops, firms will face strategic consumers who differ in buying times. Given that the leadership structure in supply chains affects the chain members' decision‐making and performance, we study this impact in a two‐period dynamic pricing setting with an upstream manufacturer and a downstream retailer, where the patience degree of consumers is the retailer's private information. We examine two leadership scenarios: retailer dominance and manufacturer dominance. The two members play a signaling game under retailer dominance, whereas the manufacturer can only set its wholesale price based on its prior belief under manufacturer dominance. Our analysis indicates that when consumers are more patient, the retailer tends to share its private information with the manufacturer under retailer dominance to avoid the reduction of its retail margin and enhance its profitability. However, the retailer may keep the consumers' patience information private when the manufacturer dominates the supply chain because the manufacturer will set a compromised wholesale price and passively cede profits to the retailer. Finally, we examine consumer surplus and social welfare. We demonstrate that retailer dominance is the Pareto optimal strategy.
Prediction of blood‐brain barrier permeability using machine learning approaches based on various molecular representation
Authors: Liang Li , Liu Zhiwen , Yang Xinyi , Zhang Yanmin , Liu Haichun , Chen Yadong
Published: June 2024

The assessment of compound blood‐brain barrier (BBB) permeability poses a significant challenge in the discovery of drugs targeting the central nervous system. Conventional experimental approaches to measure BBB permeability are labor‐intensive, cost‐ineffective, and time‐consuming. In this study, we constructed six machine learning classification models by combining various machine learning algorithms and molecular representations. The model based on ExtraTree algorithm and random partitioning strategy obtains the best prediction result, with AUC value of 0.932±0.004 and balanced accuracy (BA) of 0.837±0.010 for the test set. We employed the SHAP method to identify important features associated with BBB permeability. In addition, matched molecular pair (MMP) analysis and representative substructure derivation method were utilized to uncover the transformation rules and distinctive structural features of BBB permeable compounds. The machine learning models proposed in this work can serve as an effective tool for assessing BBB permeability in the drug discovery for central nervous system disease.
State‐space realization of periodic input/output quaternionic linear systems
Authors: Aleixo José C. , Serôdio Rogério
Published: June 2024

The investigation of linear periodic systems is a prominent subject of research within the domain of linear systems theory. In this context, the state‐space realization of such systems is of particular significance. In fact, after successfully treating the realization problem for time‐invariant systems, various researchers have directed their attention toward investigating the case of linear periodic systems. Meanwhile, in the late 1980s, Jan C. Willems proposed an approach that broadened the range of systems studied, now referred to as the behavioral approach. This approach views the behavior of a system as its fundamental element, including all signals that adhere to the system laws (also called system trajectories). More recently, the behavioral framework has also been extended separately to periodic and quaternionic behavioral systems. Our work consists of considering linear periodic input/output quaternionic behavioral systems and using recent developments in order to obtain quasi‐minimal and uniform state‐space realizations.
Enhanced spectral collocation Gegenbauer approach for the time‐fractional Fisher equation
Authors: Atta Ahmed Gamal , Youssri Youssri Hassan
Published: June 2024

In this study, we utilize a specific combination of orthogonal Gegenbauer polynomials as basis functions that satisfy homogeneous boundary conditions in the spatial variable and homogeneous initial conditions in the temporal variable. We derive an expression for the fractional derivative of the temporal basis and another expression for the second‐order derivative of the spatial basis. Subsequently, we discretize the nonlinear Fisher problem using the spectral collocation method to transform the problem into the solution of a nonlinear system of algebraic equations. We then solve this resulting system using Newton's method with an initial guess approaching zero. Furthermore, we conduct an error analysis of the proposed method and assess its applicability through three test problems, providing comparisons for validation.
Synthesis of hierarchical ZSM‐5 using polymer macro template for selective C‐alkylation of m‐cresol with tert‐butanol
Authors: Hsu Hsiu‐Ling , Roselin L. Selva , Savidha R. , Ramaraj Sankar Ganesh , Selvin Rosilda
Published: June 2024

The present study reports nanocrystalline hierarchical zeoite ZSM‐5 as a potential alternative to homogeneous catalysts for the liquid phase tert‐butylation of m‐cresol. Polydiallyldimethylammonium chloride macro‐template was used to develop vacuum‐concentration dual template nano‐precursors by hydrothermal process. The catalytic performance was analyzed for the given reaction and the high percent conversion of reactants with excellent selectivity towards the ortho isomer, 2‐tert‐butyl‐5‐methylphenol was recorded. In contrast, the low activity and selectivity towards the tert‐butylation of m‐cresol, and the selectivity towards the desired product are noticed with the nanocrystalline zeolite ZSM‐5 synthesized without macro‐template. In addition, the catalyst is recoverable due to its robust nature, which indirectly reduces industrial wastage. Various parameters that affect the rate of the reaction were optimized. Kinetic analysis studies showed that the reaction followed first‐order kinetics with respect to tert‐ and the reaction obeyed the Langmuir‐Hinselwood mechanism. The activation energy was determined as 43.0 ± 0.2 kJ/mole. The study reveals that nanocrystalline hierarchical zeolite ZSM‐5 is an efficient, selective, simple, economical and environment‐friendly catalyst for the tert‐butylation of m‐cresol.