bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of significant functional impairment across cancer diagnosis and care continuum
Authors: Flores Ann Marie , Shah Mitisha , Bedjeti Katy , Franklin Patricia D. , Peipert John Devin , Garcia Sofia F. , Lancki Nicola , Webster Kimberly A. , O’Connor Mary , Cella David
Published: September 2024

Background

The authors examined baseline physical functional (PF) impairment among cancer outpatients in the National Cancer Institute Cancer Moonshot study Northwestern University Improving the Management of Symptoms During and Following Cancer Treatment (NU IMPACT). They hypothesized that PF impairment, measured with the Patient Reported Outcome Measurement Information System–Physical Function (PROMIS‐PF) survey, would (1) be common and more prevalent for patients receiving treatment compared with no treatment and (2) differ across tumor types, independent of cancer continuum phase.

Methods

Adults who were diagnosed with cancer in NU IMPACT (n = 2273) were sampled, and their PROMIS‐PF scores were compared across tumor types and cancer continuum (curative, noncurative, or no treatment), with scores ≤40 indicating moderate–severe impairment. Multivariable logistic regression models were used to evaluate the relation among patient and cancer factors and PF scores using a 95% confidence interval.

Results

Forty percent of the surveyed patients reported moderate–severe PF impairment. Patients with melanoma reported the least impairment, and those with lung cancer were 6.5 times more likely to have moderate–severe impairment (95% confidence interval, 2.393–17.769). The noncurative group was 1.5 times more likely to have moderate–severe impairment (95% confidence interval, 1.045–2.145; mean score, 43; p < .001) than the curative (mean score, 6) and no treatment (mean score, 48) groups. One‐third of those who reported PF impairment also had significant pain and/or fatigue.

Conclusions

A sizeable minority experienced PF impairment across tumor types for which pain and/or fatigue co‐occurred, particularly in the noncurative group. The PROMIS‐PF survey effectively identified variations in physical function. Future studies will explore how screening for PF impairment can be used to refer patients for appropriate cancer rehabilitation services.
Industry Perspective on First‐in‐Human and Clinical Pharmacology Strategies to Support Clinical Development of T‐Cell Engaging Bispecific Antibodies for Cancer Therapy
Authors: Nagaraja Shastri Prathap , Shah Nirav , Lechmann Martin , Mody Hardik , Retter Marc W. , Zhu Min , Li Tommy , Wang Jun , Shaik Naveed , Zheng Xirong , Ovacik Meric , Hua Fei , Jawa Vibha , Boetsch Christophe , Cao Yanguang , Burke John , Datta Kaushik , Gadkar Kapil , Upreti Vijay , Betts Alison
Published: September 2024

T‐cell‐engaging bispecific antibodies (TCEs) that target tumor antigens and T cells have shown great promise in treating cancer, particularly in hematological indications. The clinical development of TCEs often involves a lengthy first‐in‐human (FIH) trial with many dose‐escalation cohorts leading up to an early proof of concept (POC), enabling either a no‐go decision or dose selection for further clinical development. Multiple factors related to the target, product, disease, and patient population influence the efficacy and safety of TCEs. The intricate mechanism of action limits the translatability of preclinical models to the clinic, thereby posing challenges to streamline clinical development. In addition, unlike traditional chemotherapy, the top dose and recommended phase II doses (RP2Ds) for TCEs in the clinic are often not guided by the maximum tolerated dose (MTD), but rather based on the integrated dose–response assessment of the benefit/risk profile. These uncertainties pose complex challenges for translational and clinical pharmacologists (PK/PD scientists), as well as clinicians, to design an efficient clinical study that guides development. To that end, experts in the field, under the umbrella of the American Association of Pharmaceutical Scientists, have reviewed learnings from published literature and currently marketed products to share perspectives on the FIH and clinical pharmacology strategies to support early clinical development of TCEs.
Comparison of the Effects of Different Palatal Morphology on Maxillary Expansion via RME and MSE: A Finite Element Analysis
Authors: Pan Yaohui , Peng Wenjing , Wang Yanyu
Published: September 2024

Objectives

This study aims to compare and analyze the biomechanical effect and the displacement trend of RME and MSE on the maxillofacial complex under different palatal shapes by using finite element analysis.

Methods

The three‐dimensional model of maxillofacial complex was obtained from a computed tomography image of a person with a normal palate. Then, we modified the shape of the palate to obtain the model with a high palate. Additionally, two expander devices were considered. MSE and RME were created and four models were made: Model 1: Normal‐palate craniomaxillofacial complex with RME expander; Model 2: Normal‐palate craniomaxillofacial complex with MSE expander; Model 3: High‐palate craniomaxillofacial complex with RME expander; Model 4: High‐palate craniomaxillofacial complex with MSE expander. Then, lateral forced displacement was applied and the analysis results were obtained.

Results

The lateral displacement of the palatal suture of Model 3 is greater than that of Model 1, and the maxilla has more rotation. The crown/root ratio of Model 1 is significantly greater than that of the other three groups. Compared with Model 1, Model 3 has greater stress concentration in the superstructure of the craniomaxillofacial complex. Both of them have greater stress in the anchorage area than Model 2 and Model 4.

Conclusion

Different shapes of the palate interfere with the effects of RME and MSE, and its influence on the stress distribution and displacement of the craniomaxillary complex when using RME is greater than MSE. The lateral displacement of the palatal suture of MSE is significantly larger than that of RME. It is more prone to tipping movement of the anchor teeth using RME under normal palate, and MSE may manage the vertical control better due to the smaller crown/root ratio than RME and intrusive movement of molars.
Industrial processing of chickpeas (Cicer arietinum) for protein production
Authors: Yeasmen Nushrat , Orsat Valérie
Published: September 2024

The increasing global interest in plant‐based proteins stems from concerns about the environmental impact, sustainability, animal welfare, and health implications associated with consuming animal‐based proteins. In the frame of alternative protein sources, chickpea (Cicer arietinum) emerged as a rich source of dietary proteins besides containing good amount of carbohydrate, fat, and fiber. As a protein ingredient, chickpea is available in three forms, namely, flour, concentrate, and isolate. This chickpea protein can be extracted using both wet and dry fractionation methods where the former one includes wet extraction followed by isoelectric precipitation, while the later one indicates dry milling followed by air classification. However, different nonthermal emerging technologies have been seen to assist in extracting protein as well as modifying their functionalities. This review gives an outline of the recently available literature on composition, industrial processing and associated technological challenges, functionality, and application of chickpea protein ingredients. Furthermore, discussion on the modification/improvement of chickpea protein functionality with the assistance of emerging technologies and the potentiality of by‐products produced during chickpea protein processing are also included. Based on the available findings and discussion, it is seen that apart from being a comparable source of alternative animal‐based protein to extract, chickpea derived by‐products can also be a potential source of valued ingredients that might contribute to the circular economy.
Black raspberry extract stimulates glucose uptake via adenosine monophosphate‐activated protein kinase and phosphatidylinositol‐3 kinase pathways in skeletal muscle cells
Authors: Chiu Hui‐Fang , Golovinskaia Oksana , Tandoro Yohanes , Wang Li‐Shu , Wang Chin‐Kun
Published: September 2024

Black raspberry (Rubus occidentalis) shows beneficial health effects, such as antioxidant, anti‐inflammatory, chemopreventive, antiproliferative, and antihyperglycemic activities. The present study investigated the antihyperglycemic activity of black raspberry extract (BRE) and potential mechanisms in skeletal muscle cells. Differentiated C2C12 myotubes were treated with the BRE (1–1000 μg/mL) or metformin (1 mM). The protein levels of various insulin signaling targets were measured by western blot analysis. BRE significantly increased glucose uptake by upregulated insulin receptor and phosphatidylinositol‐3 kinase (PI3K) in C2C12 cells, leading to enhanced translocation of glucose transporter 4 (GLUT4) to the plasma membrane. The expression of phosphorylated (p)‐adenosine monophosphate‐activated protein kinase (AMPK) was also enhanced by treatment with BRE, this resulting in stimulation of GLUT4 translocation to the plasma membrane and hence glucose uptake in skeletal muscles. These results suggest that BRE has an antihyperglycemic effect by stimulating GLUT4 translocation to the plasma membrane via activating the PI3K and AMPK pathways in skeletal muscle cells, thereby upregulating glucose uptake. Black raspberry is a potential functional food and has important implications for preventing and treating type‐2 diabetes. In addition, our study found that the flavonoids fraction is the main contributor fraction to promote glucose uptake in C2C12 cells.
Meta‐analysis of cardiac magnetic resonance in prognosticating left ventricular function in peripartum cardiomyopathy
Authors: Prameswari Hawani Sasmaya , Kamarullah William , Pranata Raymond , Putra Iwan Cahyo Santosa , Undarsa Alberta Claudia , Iqbal Mohammad , Dewi Triwedya Indra , Kusumawardhani Nuraini Yasmin , Akbar Mohammad Rizki , Astuti Astri
Published: September 2024

Aims

Peripartum cardiomyopathy (PPCM) may result in a number of detrimental adverse cardiovascular events, notably persistent left ventricular ejection fraction (LVEF) reduction or even mortality. Imaging parameters on cardiac magnetic resonance (CMR) and their prognostic implications have rarely been perused in PPCM. We aimed to describe CMR's prognostic value in predicting poor left ventricular (LV) function recovery using late gadolinium enhancement (LGE) and T2‐weighted or T2 mapping.

Methods and results

PubMed, Europe PMC, and ScienceDirect were screened for studies on late gadolinium enhancement (LGE) and myocardial oedema using CMR and PPCM. The outcome of interest was poor LV function recovery, with a follow‐up period of at least 6 months. Comparisons between groups with the presence of LGE, myocardial oedema, and recovered against non‐recovered patients were pooled. A random‐effects model was employed to calculate the effect size. All pooled results were expressed as risk ratios (RRs) and 95% confidence intervals (CI). The area under the curve (AUC) was generated to test overall prognostic accuracy. Six cohort studies with 162 patients were included. The mean age of participants in this study was 30.6 years, and the majority of patients were diagnosed with PPCM after delivery. LGE was associated with a higher risk of poor LV function recovery, particularly when conducted at a later stage of disease (≥2.8 months) [RR = 2.83 (95% CI = 1.25–6.40); P = 0.001]. On the contrary, CMR conducted early (<2.8 months) exhibited a greater predictive value for myocardial oedema perceived by T2 mapping [RR = 3.44 (95% CI = 1.04–11.34); P = 0.043]. Diagnostic‐test accuracy meta‐analysis revealed that LGE had a sensitivity of 73% (95% CI, 56–85%), specificity of 79% (95% CI, 45–95%), and AUC of 0.78 (95% CI, 0.75–0.82) in predicting poor LV recovery when performed in the later phase, whereas significant myocardial oedema in those with non‐recovered LV function had a sensitivity of 12% (95% CI, 2–52%), specificity of 68% (95% CI, 39–88%), and AUC of 0.40 (95% CI, 0.36–0.44) while undertaken in the latter phase. Our findings support the notion that inflammation plays a significant role in PPCM and that alterations to tissue composition occur in a time‐dependent manner.

Conclusions

Contrast‐enhanced CMR can be utilized as an adjunct examination in post‐partum PPCM patients to stratify the risk of poor LV function recovery while conducted at a suitable point in time.
Synthesis, Characterization, and Catalysis of Planar Chiral Ferrocene‐based N‐Heterocyclic Carbene Ligands and Its Metal Complexes
Authors: Shimizu Shungo , Osawa Kazuki , Fukuzawa Shin‐ichi
Published: September 2024

This study presents the development of a novel planar chiral ferrocene‐based NHC ligand and its corresponding metal complexes. The key unit of the imidazolium backbone, planar chiral ortho‐isopropyl ferrocenyl amine, was synthesized starting from (S)‐Ugi's amine. Imidazolium was obtained through the sequential condensation of glyoxal with ferrocenyl amine, followed by the ring‐closure of 1,3‐diferrocenyldiimine with chloromethylethyl ether. Chiral imidazolylidene NHC (IFcPr) metal complexes were prepared by treating imidazolium with silver oxide or base followed by transmetalation with appropriate metal salts. The steric and electronic properties of the IFcPr ligand were assessed using %Vbur and TEP, respectively. These assessments indicated that the ligand was as bulky as the adamantyl NHC ligand and exhibited strong donor ability similar to that of a triazolylidene NHC ligand. The catalytic performance of the copper and palladium complexes was evaluated in the asymmetric borylation of ethyl cinnamate and Suzuki–Miyaura coupling reactions, respectively. The IFcPr−Cu complex catalyzed the borylation of ethyl cinnamate with bis(pinacolato) diboron, followed by oxidation to yield the hydroxy ester with 58 % yield and 30 % ee. In contrast, the IFcPr−Pd‐PEPPSI complex provided the axial chiral binaphthyl compound with 59 % yield and 51 % ee at a low catalyst loading (0.1 mol %, TON=590).
Synthesis of Bicyclo[3.2.0]heptanes by Organophotoredox Catalytic Diastereoselective Anion Radical [2+2] Photocycloadditions of Arylenones under Batch and Flow Conditions
Authors: Benettin Tommaso , Resta Simonetta , Puglisi Alessandra , Rossi Sergio
Published: September 2024

In this study, the anion radical [2+2] photocycloaddition of aryl‐enones was investigated under batch and flow conditions. The reaction was promoted by LiBr as a Lewis acid and catalyzed by Eosin Y under visible light irradiation. Symmetrical enones and asymmetrical unsaturated ketoesters were effectively cyclized to yield substituted bicyclo[3.2.0]heptanes in high yield and diastereoselectivity. Through the exploration of different experimental setups and reaction conditions, a precise control over the diastereoselectivity of the process was achieved, favoring the formation of either cis or trans substituted bicyclo[3.2.0]heptanes. In‐flow experiments allowed to further improve the efficiency of the methodology, leading to higher productivity and space time yields. Furthermore, DFT investigations were conducted in order to elucidate the reaction mechanism.
Sequential Aerial Oxidation and Atom‐Economical C‐3 Chalcogenation of Indolines Facilitated by Potassium tert‐Butoxide
Authors: Majee Suman , Shaw Siuli , Anjali Km. , Bose Sudeep , Patel Dharmik M. , Ghosh Subhash Chandra , Ray Devalina
Published: September 2024

An operationally straightforward and highly efficient potassium tert‐butoxide facilitated protocol for the C‐3 chalcogenation of indolines under catalyst and additive‐free conditions has been established under ambient temperature. The salient features of the process include the development of transition metal‐free, oxidant‐free and iodine‐free, atom‐economic and cost‐effective reaction conditions at room temperature in DMSO as solvent for regioselective generation of 3‐chalcogenyl indoles in high yields. The mechanistic interpretation through controlled experiments and analysis of intermediates suggests the prevalence of the ionic pathway. The reaction is scalable to gram‐scale without a significant decrease in product yield, indicating its potential for large‐scale applications. This protocol offers a practical and environment friendly approach to accessing a diverse range of 3‐arylthioindoles and 3‐arylselenylindoles withstanding electron releasing and withdrawing substituents in good to excellent yields. Interestingly, the biological evaluation of the 3‐arylselenylindole products exhibited significant activity against breast cancer and triple‐negative breast cancer cell lines MCF‐7, and MDA‐MB 231. These results indicate the derivatives to be potent candidates for further SAR study.
Understanding prosocial and antisocial behaviours: The roles of self‐focused and other‐focused motivational orientations
Authors: Joyal‐Desmarais Keven , Euh Hyun , Scharmer Alexandra , Snyder Mark
Published: September 2024

We examine how individual differences in self‐focused and other‐focused orientations relate to prosocial (e.g., helping, volunteerism) and antisocial (e.g., theft, violence) behaviours/attitudes. Using four datasets (total N = 176,216; across 78 countries), we find that other‐focused orientations (e.g., socially focused values, intimacy motivation, compassionate/communal traits) generally relate positively to prosocial outcomes and negatively to antisocial outcomes. These effects are highly consistent cross‐nationally and across multiple ways of operationalizing constructs. In contrast, self‐focused orientations (e.g., personally focused values, power motivation, assertive/agentic traits) tend to relate positively to both antisocial and prosocial outcomes. However, associations with prosocial outcomes vary substantially across nations and construct operationalizations. Overall, the effects of other‐focused orientations are consistently larger than those of self‐focused orientations. We discuss the implications of these findings for interventions that target self‐focused and other‐focused motivations to influence prosocial and antisocial outcomes.
Simulation and Experimental Research on a New Symmetrical Hydraulic Piezoelectric Energy Harvester
Authors: Zhang Wenjie , Shang Yang , Jiang Hongyu , Meng Fanxin , Zhao Haixia , Shi Weijie
Published: September 2024

This study introduces a new symmetrical hydraulic piezoelectric energy harvester. By integrating theoretical analysis, simulation, and empirical testing, the research delves into the energy‐harvesting potential of monolithic single‐side output, monolithic two‐side parallel‐connected output, stacked one‐side parallel‐connected output, and stacked two‐side parallel‐connected output under varying parameter configurations. Additionally, it elucidates the energy dissipation occurring during the energy‐harvesting process of stacked piezoelectric disks. It has been observed that the primary determinant of voltage is the amplitude of pulsation, not the static pressure. Concurrently, the study also addresses the consistency of power generation between multiple channels. A study is made on whether there is a proportional relationship between single‐channel power generation and multi‐channel power generation. The root mean square (RMS) voltage of each connection sharply rises with resistance from 2 to 100 KΩ. It is found that the performance of parallel connection of monolithic piezoelectric disk is better than that of other connection methods. At 3 MPa and 100 Hz, the optimal resistance is 16 KΩ, yielding a maximum average power of 1155.63 μW and an optimal power density of 1.774 μW (bar mm3)−1. Consequently, the research offers a novel approach to addressing the issue of sustainable energy supply for low‐power electronic devices and sensors.
Identifying and mitigating energy losses in Tesla turbines: A study on CFD optimization
Authors: Galindo Yovany , Núñez José , Beltrán Alberto
Published: September 2024

This study investigates the flow dynamics and energy losses of Tesla turbines using Computational Fluid Dynamics with OpenFOAM. Our goal is to identify the main sources of energy loss. Four main sources of energy loss were identified. The most significant loss occurred during the conversion of pressure energy to kinetic energy, estimated to range from to of the total energy. Energy losses due to leaks between the rotor and the casing were also quantified, ranging from to of the kinetic energy at peak efficiency points. Design modifications, such as incorporating a nozzle at the entrance of the turbine, can improve efficiency. These findings highlight specific areas for efficiency improvement, offering opportunities for improved turbine design and integration into energy‐generation systems.
Pathways from education to mortality, mediated through income
Authors: Bijwaard Govert E. , Barclay Kieron J.
Published: September 2024

Lower levels of education are associated with higher mortality. Lower levels of education are also associated with lower income, which is also associated with higher mortality. We investigate the impact of education on mortality and the extent to which this is mediated through income over the life course. We account for both selective educational attainment and selective income over the life course, through inverse propensity weighting (IPW) of the mortality hazard. We decompose the educational gain, that is, the decrease in mortality from more education, in the hazard into an indirect effect of education, running through changes in income and a direct effect of education, running through other factors. We use Swedish conscription data (men only), linked to parental information and individual annual income for the period 1968 till 2012. Our empirical results indicate large educational gains in mortality. We also find that this educational gradient runs through changes in income, especially for the more educated, and does not run through other factors related to education. We conduct several robustness and sensitivity checks that indicate that the results are robust.
Voluntary private health insurance and cancer screening utilisation in Europe
Authors: Tavares A. Isabel
Published: September 2024

Background

Cancer is a leading cause of death in Europe and prevention measures, like screening, are therefore becoming increasingly important. Although European countries provide universal health coverage, including cancer screenings, many people also have private health insurance.

Aim

The aim of this study is to analyse the relationship between Voluntary private health insurance (VPHI) and cancer screening, specifically breast and colorectal cancer screening.

Method

Using data from SHARE, the Survey of Health, Ageing and Retirement in Europe, different logistic and multilevel regressions were estimated.

Results

The major finding shows a positive correlation between people being screened for cancer and having VPHI.

Conclusions

Three conclusions can be drawn: advantageous selection may exist in private health insurance; spillover effects may exist from the public sector into the private sector, which in turn may result in a lower insurance premium; and there may be a perpetuation of inequalities in health service utilisation. Several policy implications can be drawn from this result, but the most relevant concerns narrowing the inequities that could potentially arise between those who have private health insurance and those who do not.
Fat storage and drought tolerance in a seasonally‐adapted primate: Implications for modeling the effects of animal responses to global climate change
Authors: Veilleux Carrie C. , Tecot Stacey R. , Lewis Rebecca J.
Published: September 2024

Global warming is changing habitats and affecting biodiversity, and is expected to exacerbate aridification in many regions. Animals and plants in seasonally dry tropical forests often exhibit adaptations to cope with seasonal resource limitation. However, whether these adaptations will facilitate drought tolerance or increase drought vulnerability is unclear. Here, we combine long‐term individual‐based data on phenology, morphometrics, and demographics to investigate how drought impacts the food resources, health, reproduction, and behavior of a population of Verreaux's sifaka (Propithecus verreauxi), a critically endangered lemur inhabiting dry deciduous forests in Madagascar. Between December 2010 and May 2023, the population experienced 3 years of severe drought (2016, 2017, 2022). During green periods in severe drought, the availability of high‐quality sifaka foods (young leaves, fruit) was significantly reduced and fruit tree mortality increased. This reduced availability of fruit persisted in the year after a drought, despite typical rainfall. Yet surprisingly, we found no negative effects on body condition or commonly‐used metrics for reproductive success during drought years or years following a drought. Instead, sifaka exhibited significantly higher levels of subcutaneous body fat during severe droughts. We observed little change in sifaka behavior between drought and non‐drought periods. However, they were more likely to lick dew during severe drought, and spent significantly less time feeding on young and mature leaves. They also significantly increased their time feeding on flowers and fruits, despite the reduced abundance of fruit in the habitat. Together, our results suggest that increased consumption of water‐rich fruit and flowers during severe droughts could facilitate physiological mechanisms that help sifaka cope with water scarcity, including fructose‐mediated fat storage, metabolic water production, and water conservation. These results provide new insights into how critically endangered animals may respond to climate change, suggesting that behavioral and physiological adaptations to seasonal resource limitation may buffer some mammals from the effects of severe drought or other extreme weather events.
Towards zero extinction—A case study focusing on the plant genus Begonia in Thailand
Authors: Radbouchoom Sirilak , delos Angeles Marjorie D. , Phutthai Thamarat , Schneider Harald
Published: September 2024

Plant species with small habitat ranges and specific edaphic requirements are highly vulnerable to extinction and thus require enhanced attention in biodiversity conservation. This study was designed to explore the challenges of protecting such plant species by evaluating the in situ and ex situ conservation capacities available for Thailand's species of the mega‐diverse plant genus Begonia L. A comprehensive assessment of occurrence records across the country was conducted to evaluate the spatial distribution of Begonia diversity in Thailand, identify biodiversity hotspots, assess the extinction threats faced by the 60 Begonia species known in the country, and identify existing conservation capacities and potential gaps. The results show that 78% of Begonia species in Thailand are vulnerable to extinction, with the Northern floristic region identified as both a Begonia species hotspot and a region with major conservation gaps. While in situ conservation efforts have been successful in covering over 88% of the species, they have failed to provide the protection required to achieve zero extinction. Ex situ conservation capacities are poorly developed, with only 13% of species present in botanical gardens, and no seed banking or other related activities have been initiated. This evaluation presents a sharply contrasting message: on one hand, Thailand has assembled substantial capacities to protect these plants through established national parks and other protected areas, but on the other hand, essential capacities are still lacking to render the zero extinction target achievable. We advocate for the implementation of a multi‐component conservation strategy to enable Thailand to move towards zero species extinction, even for plant species with narrow habitat ranges and high edaphic specialisation.
Reference gene considerations for toxicological assessment of the flame retardant triphenyl phosphate in an in vitro fish embryonic model
Authors: Germain Logan , Pereira Delaine , Winn Louise M.
Published: September 2024

The reliability of relative quantification RT‐qPCR depends upon the gene of interest being normalized to one or more reference genes, with the assumption that the chosen reference genes do not experience altered expression with experimental conditions. The correct choice of stable reference genes is critical when investigating alterations to gene transcript levels following exposure to endocrine and metabolic disrupting chemicals, such as the flame retardant triphenyl phosphate (TPhP). This study assessed the stability of eight reference genes following TPhP exposure in embryonic cells derived from rainbow trout (Oncorhynchus mykiss). The genes β‐actin (actb) and 18s rRNA (18s) were stable, while glyceraldehyde‐3‐phosphate dehydrogenase (gapdh) relative expression was found to be increased. gapdh is a popular reference gene and has been previously used in the literature for investigating TPhP exposure in teleost fish models. We discuss the implications of gapdh upregulation in the context of TPhP as a metabolic disrupting chemical. Furthermore, we quantified the expression of the tumor suppressor gene p53 following TPhP exposure in relation to different reference genes to use as an example to report on how discrepancies in findings might arise depending on the stability of the chosen reference gene.
High hydrostatic pressure treatment for advanced tissue grafts in reconstructive head and neck surgery
Authors: Kalle Friederike , Stadler Valentin Paul , Brach Julia Kristin , Grote Vivica Freiin , Pohl Christopher , Schulz Karoline , Seidenstuecker Michael , Jonitz‐Heincke Anika , Bader Rainer , Mlynski Robert , Strüder Daniel
Published: September 2024

The increasing importance of regenerative medicine has resulted in a growing need for advanced tissue replacement materials in head and neck surgery. Allo‐ and xenogenic graft processing is often time‐consuming and can deteriorate the extracellular matrix (ECM). High hydrostatic pressure (HHP)‐treatment could allow specific devitalization while retaining the essential properties of the ECM. Porcine connective tissue and cartilage were HHP‐treated at 100–400 MPa for 10 min. Structural modifications following HHP‐exposure were examined using electron microscopy, while devitalization was assessed through metabolism and cell death analyses. Furthermore, ECM alterations and decellularization were evaluated by histology, biomechanical testing, and DNA content analysis. Additionally, the inflammatory potential of HHP‐treated tissue was evaluated in vivo using a dorsal skinfold chamber in a mouse model. The devitalization effects of HHP were dose‐dependent, with a threshold identified at 200 MPa for fibroblasts and chondrocytes. At this pressure level, HHP induced structural alterations in cells, with a shift toward late‐stage apoptosis. HHP‐treatment preserved ECM structure and biomechanical properties, but did not remove cell debris from the tissue. This study observed a pressure‐dependent increase of markers suggesting the occurrence of immunogenic cell death. In vivo investigations revealed an absence of inflammatory responses to HHP‐treated tissue, indicating a favorable biological response to HHP. In conclusion, application of HHP devitalizes fibroblasts and chondrocytes at 200 MPa while retaining the essential properties of the ECM. Prospectively, HHP may simplify the preparation of allo‐ and xenogenic tissue replacement materials and increase the availability of grafts in head and neck surgery.
Adsorption behavior of graphite‐like walnut shell biochar modified with ammonia for ciprofloxacin in aqueous solution
Authors: Wang Qingkun , Zhang Yanping , Li Fen , Liu Wenxiao , Ma Liran
Published: September 2024

BACKGROUND

Graphite‐like biochar of NWSC600K was prepared at 900 °C using walnut shell as the raw material and aqueous ammonia (NH3·H2O) as an activator, and characterized using transmission and scanning eletron microscopy (TEM, SEM), X‐ray diffraction (XRD), Brunauer–Emmett–Teller (BET), Raman spectroscopy and Fourier transform infrared (FTIR). The study investigated the adsorption performance and mechanism of NWSC600K for ciprofloxacin (CIP).

RESULTS

The results showed that extremely tiny pores were found on the surface of NWSC600K, which increased its specific surface area to 823.91 m2 g−1, whereas the average pore size of NWSC600K decreased to 3.23 nm. The results of TEM, XRD and Raman spectroscopy detected well‐arranged lattice stripes as well as characteristic peaks corresponding to the graphite lattice appearing on the surface of NWSC600K. Moreover, the ID/IG value for NWSC600K was 1.429. The FTIR results showed that functional groups including the amino group were formed on NWSC600K.

CONCLUSION

The adsorption capacity of NWSC600K for CIP was 158.14 mg g−1 and the corresponding removal rate was 97.5% at pH 7. The pH value impact on the removal efficiency of CIP greatly, and the removal rate of CIP decreased linearly with increasing pH. The coexisting ions also would inhibit the adsorption of CIP on NWSC600K. Results obtained from kinetic and isotherm models, thermodynamics and characterization analyses suggested that pore‐filling, π–π stacking, hydrogen bonding, hydrophobicity and electrostatic interaction existed during the adsorption process. The adsorption was a nonspontaneous exothermic reaction. © 2024 Society of Chemical Industry (SCI).
Human lung cancer classification and comprehensive analysis using different machine learning techniques
Authors: Priyadarshini K. , Ali S. Ahamed , Sivanandam K. , Alagarsamy Manjunathan
Published: September 2024

Lung cancer is the most common causes of death among all cancer‐related diseases. A lung scan examination of the patient is the primary diagnostic technique. This scan analysis pertains to an MRI, CT, or X‐ray. The automated classification of lung cancer is difficult due to the involvement of multiple steps in imaging patients' lungs. In this manuscript, human lung cancer classification and comprehensive analysis using different machine learning techniques is proposed. Initially, the input images are gathered using lung cancer dataset. The proposed method processes these images using image‐processing techniques, and further machine learning techniques are utilized for categorization. Seven different classifiers including the k‐nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), multinomial naive Bayes (MNB), stochastic gradient descent (SGD), random forest (RF), and multi‐layer perceptron (MLP) classifier are used, which classifies the lung cancer as malignant and benign. The performance of the proposed approach is examined using performances metrics, like positive predictive value, accuracy, sensitivity, and f‐score are evaluated. Among them, the performance of the MLP classifier provides 25.34%, 45.39%, 15.39%, 41.28%, 22.17%, and 12.12% higher accuracy than other KNN, SVM, DT, MNB, SGD, and RF respectively.

Research Highlights

Lung cancer is a leading cause of cancer‐related death. Imaging (MRI, CT, and X‐ray) aids diagnosis.

Automated classification of lung cancer faces challenges due to complex imaging steps.

This study proposes human lung cancer classification using diverse machine learning techniques.

Input images from lung cancer dataset undergo image processing and machine learning.

Classifiers like k‐nearest neighbors, support vector machine, decision tree, multinomial naive Bayes, stochastic gradient descent, random forest, and multi‐layer perceptron (MLP) classify cancer types; MLP excels in accuracy.
The resurgence of influenza A/H3N2 virus in Australia after the relaxation of COVID‐19 restrictions during the 2022 season
Authors: Wang Xinye , Walker Gregory , Kim Ki W. , Stelzer‐Braid Sacha , Scotch Matthew , Rawlinson William D.
Published: September 2024

This study retrospectively analyzed the genetic characteristics of influenza A H3N2 (A/H3N2) viruses circulating in New South Wales (NSW), the Australian state with the highest number of influenza cases in 2022, and explored the phylodynamics of A/H3N2 transmission within Australia during this period. Sequencing was performed on 217 archived specimens, and A/H3N2 evolution and spread within Australia were analyzed using phylogenetic and phylodynamic methods. Hemagglutinin genes of all analyzed NSW viruses belonged to subclade 3C.2a1b.2a.2 and clustered together with the 2022 vaccine strain. Complete genome analysis of NSW viruses revealed highly frequent interclade reassortments between subclades 3C.2a1b.2a.2 and 3C.2a1b.1a. The estimated earliest introduction time of the dominant subgroup 3C.2a1b.2a.2a.1 in Australia was February 22, 2022 (95% highest posterior density: December 19, 2021–March 13, 2022), following the easing of Australian travel restrictions, suggesting a possible international source. Phylogeographic analysis revealed that Victoria drove the transmission of A/H3N2 viruses across the country during this season, while NSW did not have a dominant role in viral dissemination to other regions. This study highlights the importance of continuous surveillance and genomic characterization of influenza viruses in the postpandemic era, which can inform public health decision‐making and enable early detection of novel strains with pandemic potential.
Clinical and molecular epidemiology of enterovirus infections in cerebrospinal fluid samples, 2019–2023
Authors: Pan Daniel , Mohamed Basant , Gupta Abhishek , Arshad Zaki , Strachan Charlie , Celma Cristina , Kapoor Sonal , Toovey Oliver T. R. , Beard Stuart , Tang Julian W.
Published: September 2024

We performed a comparative, retrospective analysis (March 2019–April 2023) of children diagnosed with non‐polio enterovirus (NPEV) central nervous system (CNS) infections (n = 47 vs. 129 contemporaneous controls without NPEV, all <18 years old), requiring cerebrospinal fluid (CSF) testing upon presentation to hospital. We found that showed that admissions decreased during pandemic restrictions (13% vs. controls 33%, p = 0.003). The median age of children with NPEV was 41 days (IQR: 18–72), most were male (n = 76, 59%) and were less likely to present with symptoms of irritability (11% vs. controls 26%, p = 0.04), but more likely to be febrile (93% vs. controls 73%, p = 0.007), have higher respiratory rates (mean 44 bpm, SD 11, vs. controls 36 bpm, SD 14, p = 0.001), higher heart rates (mean 171 bpm, SD 27 vs. controls 141 bpm, SD 36, p < 0.001), higher CSF protein (median 0.66 g/L, interquartile range [IQR] 0.46–1.01, vs. controls 0.53 mg/mL, IQR 0.28–0.89, p = 0.04), higher CSF white cell count (WCC) (median WCC 9.5×106/L, IQR 1–16 vs. controls 3.15×106/L, IQR 2.7–3.6, p < 0.001), but lower CSF glucose (median 2.8 mmol/L, IQR 2.4–3.1 vs. controls 3.1 mmol/L, IQR 2.7–3.6, p < 0.001). Phylogenetic analysis showed that these NPEVs originated from Europe (EV A71, CV B4, E21, E6, CV B3, CV B5, E7, E11, E18), North America (CV B4, E18), South America (E6), Middle East (CV B5), Africa (CV B5, E18), South Asia (E15), East/Southeast Asia (E25, CV A9, E7, E11, E18), and Australia (CV B5).
Harnessing PROTACs to combat H5N1 influenza: A new frontier in viral destruction
Authors: Mukerjee Nobendu , Maitra Swastika , Mukherjee Dattatreya , Ghosh Arabinda , Alexiou Athanasios T. , Thorat Nanasaheb D.
Published: September 2024

H5N1, a highly pathogenic avian influenza virus, poses an ongoing and significant threat to global public health, primarily due to its potential to cause severe respiratory illness and high mortality rates in humans. Despite extensive efforts in vaccination and antiviral therapy, H5N1 continues to exhibit high mutation rates, resulting in recurrent outbreaks and the emergence of drug‐resistant strains. Traditional antiviral therapies, such as neuraminidase inhibitors and M2 ion channel blockers, have demonstrated limited efficacy, necessitating the exploration of innovative therapeutic strategies. Proteolysis‐targeting chimeras (PROTACs) emerge as a novel and promising approach, leveraging the ubiquitin‐proteasome system to selectively degrade pathogenic proteins. Unlike conventional inhibitors that only block protein function, PROTACs eliminate the target protein, providing a sustained therapeutic effect and potentially reducing the development of resistance. This paper offers a comprehensive examination of the current landscape of H5N1 infections, detailing the pathogenesis and challenges associated with existing treatments. It further explores the mechanism of action, design, and therapeutic potential of PROTACs in inhibiting H5N1. By targeting essential viral proteins, such as hemagglutinin and the RNA‐dependent RNA polymerase complex, PROTACs hold the potential to revolutionize the treatment of H5N1 infections, offering a new frontier in antiviral therapy.
Headspace aroma and secondary metabolites profiling in 3 Pelargonium taxa using a multiplex approach of SPME‐GC/MS and high resolution‐UPLC/MS/MS coupled to chemometrics
Authors: Mansour Khaled Ahmed , El‐Mahis Amira Ali , Farag Mohamed A.
Published: September 2024

BACKGROUND

The present study focuses on the aroma and secondary metabolites profiling of three Pelargonium graveolens cultivars, baladi (GRB), sondos (GRS) and shish (GRSH), grown in Egypt. Utilizing a multiplex approach combining high resolution‐ultraperformance liquid chromatography (HR‐UPLC)/tandem mass spectrometry (MS/MS) and gas chromatography (GC)‐MS coupled with chemometrics, the study aims to identify and profile various secondary metabolites and aroma compounds in these cultivars.

RESULTS

HR‐UPLC/MS/MS analysis led to the annotation of 111 secondary metabolites, including phenolics, flavonoids, terpenes and fatty acids, with several compounds being reported for the first time in geranium. Multivariate data analysis identified vinylanisole, dimethoxy‐flavonol, and eicosadienoic acid as discriminatory metabolites among the cultivars, particularly distinguishing the GRS cultivar in its phenolics profile. In total, 34 aroma compounds were detected using headspace solid‐phase microextraction coupled with GC‐MS, including alcohols, esters, ketones, ethers and monoterpene hydrocarbons. The major metabolites contributing to aroma discrimination among the cultivars were β‐citronellol in GRB, α‐farnesene in GRS and isomenthone in GRSH.

CONCLUSION

The study provides a comprehensive profiling of the secondary metabolites and aroma compounds in the three Pelargonium graveolens cultivars. The GRS cultivar was identified as particularly distinct in both its phenolics and aroma profiles, suggesting its potential as a premium variety for cultivation and use. Future studies should focus on isolating and investigating the newly detected metabolites and exploring the biological effects of these compounds in food applications and other uses. © 2024 Society of Chemical Industry.
Tonsillectomy Versus Tonsillotomy in Pediatric Sleep‐Disordered Breathing: A Systematic Review and Multi‐subgroup Meta‐analysis
Authors: Lao Jiahong , Jian Feitong , Ge Rongrong , Wu Shuo
Published: September 2024

Objectives

To evaluate the potential of tonsillotomy (TT) as an alternative to tonsillectomy (TE) for treating children with obstructive sleep‐disordered breathing (oSDB).

Data Sources

Two independent reviewers searched PubMed, the Cochrane Library, Embase, and additional sources to identify controlled studies comparing TT versus TE in pediatric patients with oSDB.

Review Methods

We evaluated post‐surgery symptom relief, and short‐ and long‐term postoperative benefits for children. Fixed‐effect meta‐analysis, sensitivity analysis, and subgroup analysis were conducted.

Results

In our analysis of 32 studies with 9,430 children, the analysis revealed TT group had a similar therapeutic effect on improvement of OSA‐18 as TE group (MD = 5.20, 95% CI: −32.67 to 43.07, p = 0.96). In terms of short‐term outcome, the days to return to normal diet for TT group were shorter than that for TE group (MD = −2.49, 95%CI: −3.57 to −1.28; p < 0.001), less analgesics use (MD = −3.19, 95% CI = −3.44 to −2.93, p < 0.001), and lower postoperative secondary bleeding (RR = 0.33; 95%CI: 0.23 to 0.47; p < 0.001). But the risk of reoperation (OR = 8.28; 95%CI: 2.66 to 12.64; p < 0.001), oSDB recurrence (OR = 2.16; 95%CI: 1.20–3.86; p = 0.01), and postoperative infection (OR = 1.82; 95%CI: 1.34 to 2.47; p < 0.001) in TT group was significantly higher than that in TE group.

Conclusions

Tonsillotomy reduces postoperative pain and bleeding, speeding up recovery for children with oSDB, and improving their quality of life. Yet, the risk of recurrent infections from residual tonsil tissue, which may require reoperation, calls for a careful evaluation of the procedure's short‐term gains against its long‐term risks.

Level of Evidence

NA Laryngoscope, 135:529–539, 2025
Corneal epithelial ingrowth after small incision lenticule extraction surgery: Insights from a case series and mechanistic studies
Authors: Zhang Miao , Chong Ieng , Chen Xiaoniao , Yang Juan , Cheng Linling , Yan Zonghui
Published: September 2024

Corneal epithelial ingrowth (EI) is a rare but significant complication following Small Incision Lenticule Extraction (SMILE) surgery. During the procedure, the opaque bubble layer (OBL) formation may create microchannels that disrupt Bowman's layer, providing a pathway for epithelial cells to migrate into the corneal stroma. In this study, we investigated the mechanisms behind EI development and proposed preventive strategies. We analyzed four cases of EI post‐SMILE surgery, utilizing anterior segment optical coherence tomography (AS‐OCT) and corneal tomography for diagnosis. Preventive measures, including careful anesthetic application and precise suction cone positioning, were employed to minimize OBL formation. Here, we show that subflap debris removal surgery led to significant clinical improvement, with no EI recurrence observed. Our findings suggest that the microchannels created by OBL during surgery may play a crucial role in EI development, challenging previous assumptions that EI is primarily due to trauma at the flap edges. This underscores the importance of precise surgical technique and effective postoperative management. Further research, including clinical studies and advanced imaging, is needed to confirm this proposed mechanism and improve outcomes in refractive surgery. The study highlights the necessity for ongoing advancements in surgical protocols and technology to prevent and manage EI effectively.
Nonexistence for a system of time‐fractional diffusion equations in an exterior domain
Authors: Jleli Mohamed , Samet Bessem
Published: September 2024

A system of time‐fractional diffusion equations posed in an exterior domain of
(
) under homogeneous Dirichlet boundary conditions is investigated in this paper. The time‐fractional derivatives are considered in the Caputo sense. Using nonlinear capacity estimates specifically adapted to the nonlocal properties of the Caputo fractional derivative, the geometry of the domain, and the boundary conditions, we obtain sufficient conditions for the nonexistence of a weak solution to the considered system.