bluuebunny/crossref_metadata_2025 huggingface dataset:
Host‐associated genetic differentiation and origin of a recent host shift in the generalist parasitic weed Phelipanche ramosa
Authors: Le Corre Valérie , Reibel Carole , Kati Vaya , Gibot‐Leclerc Stéphanie
Published: September 2023

Branched broomrape, Phelipanche ramosa (L.) Pomel, is a globally distributed parasitic weed of economic importance. In Europe, where it is native, it can infest several crops, notably tomato, tobacco, and hemp. In western France, it has recently adapted to a new host crop, oilseed rape, causing substantial damage. The aim of this study was to investigate the evolutionary relationships and genetic differentiation among P. ramosa populations infesting different hosts. We collected 1611 P. ramosa samples from 109 fields cultivated with six different crops (oilseed rape, tobacco, hemp, tomato, lentil, and celery) and distributed among six European countries. All samples were genotyped for ten microsatellite loci and a subset of samples was sequenced for two nuclear genes and two chloroplast genes. Genetic differentiation among populations was high (FST = 0.807) and mainly driven by differentiation among different host crops, with no significant geographic structure. Genetic structure analysis identified up to seven biologically meaningful clusters that matched with host crops of origin. Reconstructed networks of sequence haplotypes and multilocus SSR genotypes showed a large genetic divergence between samples collected on oilseed rape and samples collected on other crops. The phylogeny inferred from DNA sequences placed samples collected from oilseed rape as a basal lineage. Approximate Bayesian Computations were used to compare different evolutionary scenarios of divergence among the three main genetic clusters, associated, respectively, with oilseed rape, tobacco, and hemp as host crops. The best‐supported scenario indicated that P. ramosa infesting oilseed rape derived recently from an ancient, unknown lineage. Our results suggest that a more complete description of the genetic diversity of P. ramosa is still needed to uncover the likely source of the recent adaptation to oilseed rape and to anticipate future new host shifts.
Advances in the natural α‐glucosidase inhibitors
Authors: Şöhretoğlu Didem , Renda Gülin , Arroo Randolph , Xiao Jianbo , Sari Suat
Published: September 2023

α‐Glucosidase (AG) inhibitors, one of the classes of oral antidiabetics used to treat type 2 diabetes mellitus, delay digestion and absorption of glucose, which in turn, has a lowering effect on postprandial blood glucose and insulin levels. Natural products are a great source for the development of new AG inhibitory drug candidates. We aim to summarize advances in natural AG inhibitors according to their secondary metabolite groups in the last decade. Their mechanisms of action and structure–activity relationships will especially be discussed.
Meta‐Ortho Effect on the Excited State Pathways of Chloroanilines
Authors: Nitu Cristina , van der Wal Jacob Jan , Kaul Nidhi , Steen Jorn D. , Hammarström Leif , Fagnoni Maurizio , Crespi Stefano
Published: September 2023

Direct excitation of aromatic compounds grants access to high‐energy intermediates that can be utilised in organic synthesis. Understanding and predicting the substituent effects at the excited state for aromatic molecules remains challenging for the synthetic photochemist. In this work, we present an experimental and computational investigation of the excited state of the isomeric chloroanilines, which promptly react by losing the chloride when the amino group is in para position, but are non‐reactive and non‐emissive in the meta and ortho isomers. XMS‐CASPT2//CASSCF computations explain this apparent contradiction of the meta‐ortho selectivity rule of Zimmerman, which originates from the substituent effects lowering to a different extent the barrier to populate the prefulvenic conical intersection that deactivates non‐radiatively the singlet excited state of the chloroanilines.
Simultaneous detection of trace Pb(II) and Cd(II) cations in ore samples by anodic stripping analysis using pMO/erGO‐modified glassy carbon electrodes
Authors: Diédhiou Ismaila , Sebei Abdelaziz , Fall Modou , Aoun Sami Ben , Zarrougui Ramzi , Raouafi Noureddine
Published: September 2023

Environmental safety is of paramount importance for human well‐being, imposing significant demands for affordable, rapid, portable, and robust analytical tools for real‐time and on‐site water monitoring. In this context, we have developed an analytical method to efficiently detect heavy metal ions, particularly Pb2+ ions, in water samples. This method employs a stepwise‐prepared electrode comprised of a thin film of poly(methyl orange) (pMO) electrochemically deposited onto reduced graphene oxide (erGO), which is in turn coated on a glassy carbon electrode (GCE). The resulting pMO/erGO/GCE electrode was characterized using Raman spectroscopy, scanning electron microscopy (SEM), and electrochemical techniques. Square wave anodic stripping voltammetry (SWASV) was subsequently employed to detect the target ions. Importantly, the pMO/erGO/GCE electrode exhibits excellent analytical performance, featuring a broad linear concentration range spanning from 14 to 595 parts per billion (ppb), a sensitivity of 5.60 μA ppb−1 cm−2, and a theoretical calculated value of the detection limit of 0.82 ppb. The effectiveness of this sensor was validated through successful testing of aqueous samples from dissolved ores containing both lead(II) and cadmium(II) cations, as determined by atomic absorption spectroscopy.
Structural control of bedrock river alignment and morphology in the Fraser Canyon, British Columbia, Canada
Authors: Curran Michael , Steelquist Aaron T. , Larimer Jeff , Seagren Erin , Li Tingan , Heathfield Derek , Menounos Brian , Clague John J. , Church Michael , Venditti Jeremy G.
Published: September 2023

Many rivers worldwide follow faults because they exploit bedrock damage that occurs in fault zones. However, there has been no quantitative investigation of how closely rivers follow specific faults within a fault zone. Analysis of the Fraser River in southwestern British Columbia reveals the degree of alignment of individual bedrock‐bound canyon reaches with lineaments of the Fraser River Fault. The alignment of the river at the regional scale is controlled by the Fraser River Fault zone, but individual canyons align with subsidiary faults that are visible in elevation data or predicted by the geometry and kinematics of the main fault. We hypothesize canyon reaches that deviate from faults were shifted by large episodic sediment input, creating epigenetic canyons.
Asparagine and nitric oxide jointly enhance antioxidant capacity and nitrogen metabolism to improve drought resistance in cotton: Evidence from long‐term field trials
Authors: Akin Sabri , Kaya Cengiz
Published: September 2023

Asparagine (Asn) and nitric oxide (NO) can enhance plant tolerance to abiotic stress, but their interaction is not well understood. Cotton is a vital resource for the textile industry, but its yield is reduced by drought stress, which could threaten its global supply in a warming and stressful world. Improving cotton's drought tolerance is crucial for supporting the textile industry. Two simultaneous field experiments were conducted to study the effect of Asn and sodium nitroprusside (SNP), a NO donor, on cotton's drought tolerance. Two irrigation treatments were applied: control (C: 100% A pan) and drought stress (50% A pan). The plants were also sprayed with two plant stimulants before imposing drought stress: Mock control, 20 mM Asn, and 0.2 mM SNP, either alone or together. Drought stress impaired plant growth, photosynthesis, yield, nitrogen metabolism, and antioxidant defense, while increasing oxidative stress and free amino acid levels. However, Asn and SNP treatments alleviated these negative effects and improved antioxidant enzyme activity, plant growth, yield, and nitrogen content. The Asn + SNP treatment also increased irrigation water productivity under water‐limited conditions, suggesting its potential for enhancing water use efficiency in cotton production. The combined treatment was more effective than the single treatments, indicating a synergistic effect of Asn and SNP in enhancing drought tolerance in cotton. These results imply that Asn and SNP could be useful tools for sustaining cotton production under drought conditions by boosting nitrogen metabolism and antioxidant defense, thereby contributing to the global supply of cotton and supporting the textile industry.
A multivariate GARCH–jump mixture model
Authors: Li Chenxing , Maheu John M.
Published: September 2023

This paper proposes a new parsimonious multivariate GARCH–jump (MGARCH–jump) mixture model with multivariate jumps that allows both jump sizes and jump arrivals to be correlated among assets. Dependent jumps impact the conditional moments of returns and beta dynamics of a stock. Applied to daily stock returns, the model identifies co‐jumps well and shows that both jump arrivals and jump sizes are highly correlated. The jump model has better out‐of‐sample forecasts compared with a benchmark multivariate GARCH model.
Liquidity premiums, interest rate differentials, and nominal exchange rate prediction
Authors: Wang Yi‐Chiuan , Wu Jyh‐Lin
Published: September 2023

With the use of daily panel data for industrial countries, we study the essentialness of liquidity premiums and interest rate differentials in predicting nominal exchange rates at short horizons. We find that information about higher‐order moments of exchange rates helps predict nominal exchange rates. Before the global financial crisis, interest rate differentials were crucial for forecasting exchange rates. Interest rate differentials and liquidity premia provide additional information for predicting nominal exchange rates in the post‐crisis period even if we have controlled for latent fundamental exchange rates. Moreover, the economic significance analysis results echo those of the statistical significance analysis.
Prosocial development throughout the toddlerhood: A person‐centred approach
Authors: Song Yue , Broekhuizen Martine , Dubas Judith Semon
Published: September 2023

Addressing the debate on whether there are reliable individual differences in toddler's prosociality, this study employed a person‐centred approach to investigate (1) profiles of instrumental helping, sharing and empathic helping at 22, 28 and 34 months, and (2) the predictive role of toddler's temperament (anger/frustration, impulsivity and inhibitory control) to these profiles. Variable‐centred analyses examined cross‐task and over time associations. Participants were 93 Dutch toddlers observed in standardised behavioural assessments at each wave. Parents rated their toddler's temperament at wave 1. Results revealed small but significant across‐task and over time associations of the prosocial behaviours and children were distinguished into three profile groups at 22 months (high prosocial, instrumental helper and low prosocial), three at 28 months (high, moderate and low) and two profiles at 34 months (high prosocial and instrumental and empathic helpers), with low to moderate membership stability across waves. For 34‐month‐olds, those in the high prosocial group were rated as being less impulsive compared to their peers in the helper group. These findings indicate reliable individual differences of prosociality exist at early ages with impulsivity as a potential precursor to these individual differences.
Removal of gemcitabine‐induced senescent cancer cells by targeting glutaminase1 improves the therapeutic effect in pancreatic ductal adenocarcinoma
Authors: Oyama Keisuke , Iwagami Yoshifumi , Kobayashi Shogo , Sasaki Kazuki , Yamada Daisaku , Tomimaru Yoshito , Noda Takehiro , Asaoka Tadafumi , Takahashi Hidenori , Tanemura Masahiro , Doki Yuichiro , Eguchi Hidetoshi
Published: September 2023

Insufficient cancer treatment can induce senescent cancer cell formation and treatment resistance. The characteristics of induced senescent cancer (iSnCa) cells remain unclear. Pancreatic ductal adenocarcinoma (PDAC) has a low and nondurable response rate to current treatments. Our study aimed to analyze the properties of iSnCa cells and the relationship between cellular senescence and prognosis in PDAC. We evaluated the characteristics of gemcitabine‐induced senescent cancer cells and the effect of senescence‐associated secretory phenotype (SASP) factors released by iSnCa cells on surrounding PDAC cells. The relationship between cellular senescence and the prognosis was investigated in 50 patients with PDAC treated with gemcitabine‐based neoadjuvant chemotherapy. Exposure to 5 ng/mL gemcitabine‐induced senescence, decreased proliferation and increased senescence‐associated β‐galactosidase‐cell staining without cell death in PDAC cells; the expression of glutaminase1 (GLS1) and SASP factors also increased and caused epithelial‐mesenchymal transition in surrounding PDAC cells. iSnCa cells were selectively removed by the GLS1 inhibitor bis‐2‐(5‐phenylacetamido‐1,2,4‐thiadiazol‐2‐yl)ethyl sulfide (BPTES) through apoptosis induction. Cellular senescence was induced in PDAC cells via insufficient gemcitabine in subcutaneous tumor model mice. GLS1 expression was an independent prognostic factor in patients with PDAC who received gemcitabine‐based neoadjuvant chemotherapy. This is the first study to identify the relationship between senescence and GLS1 in PDAC. Low‐dose gemcitabine‐induced senescence and increased GLS1 expression were observed in PDAC cells. Cellular senescence may contribute to treatment resistance of PDAC, hence targeting GLS1 in iSnCa cells may improve the therapeutic effect.
Pregnancy outcomes of women with cardiac disease
Authors: Allen‐Davis Wendy , Hylton Melesia , Gibson Shanea , Rattray Carole , Johnson Nadine , Hunter Tiffany A.
Published: September 2023

Objective

To determine and predict the maternal and neonatal outcomes of pregnancies occurring in patients with cardiac disease.

Method

This retrospective review included 147 pregnancies identified from antenatal, delivery, and nursery records. Information concerning the nature and severity of the pre‐existing cardiac disease, comorbidities, risk scores, obstetric or cardiac complications, and pregnancy outcomes were collected. The data were analyzed using SPSS Windows version 22.

Results

In all, 111 (73.5%) of the cohort had acquired heart disease and 4 (2.7%) of patients belonged to WHO class IV, in which pregnancy is not recommended. Additionally, 12 (8.1%) were categorized as being at significant risk of having a cardiac complication. The proportion of patients that had maternal and perinatal mortality was 6 (4.0%) and 7 (4.8%), respectively. The WHO and CARPREG scoring systems were reliably able to predict cardiac events (P < 0.01). Mothers who received preconception counseling had significantly fewer occurrences of cardiac and obstetric events than those who did not.

Conclusion

Cardiac disease in pregnancy in women managed at our center was most often an acquired disease. The baseline risk assessment scores accurately predicted the likelihood of adverse cardiac outcomes.
Women, girls, and climate change: Human rights, vulnerabilities, and opportunities
Authors: Sidun Nancy M. , Gibbons Judith L.
Published: September 2023

Our world faces potentially catastrophic climate change that can damage human health in multiple ways. The impact of climate change is uneven, disproportionately affecting the lives and livelihoods of women and girls. This conceptual article compiles evidence for a model that argues that climate change has more detrimental consequences for women than men because of women's precarity (unequal power) and corporal (physical) vulnerability. Climate change challenges the human rights of women and girls, triggering displacement, interrupted education, food and water scarcity, economic instability, mental and physical health challenges, reproductive injustice, gender‐based violence, exploitation and human trafficking. Women are effective and essential change agents; their empowerment can directly contravene or mitigate climate change and also break the links between climate change and its negative consequences for women and girls. Gender‐sensitive responses to the effects of climate change are imperative. Women's empowerment will further human rights and achievement of the United Nations Sustainable Development Goals.
Noninvasive detection of diabetes mellitus based on skin fluorescence and diffuse reflectance spectroscopy
Authors: Zhang Yuanzhi , Liu Yong , Zhu Guoqing , Wang Quanfu , Ni Jingshu , Liu Lin , Zhang Jian , Zhang Junqing , Li Zhongsheng , Wang Xia , Huang Yao , Dong Meili , Zhang Yang , Wang Yikun
Published: September 2023

There is an urgent need for a mass population screening tool for diabetes. Skin tissue contains a large number of endogenous fluorophores and physiological parameter markers related to diabetes. We built an excitation‐emission spectrum measurement system with the excited light sources of 365, 395, 415, 430, and 455 nm to extract skin characteristics. The modeling experiment was carried out to design and verify the accuracy of the recovery of tissue intrinsic discrete three‐dimensional fluorescence spectrum. Blood oxygen modeling experiment results indicated the accuracy of the physiological parameter extraction algorithm based on the diffuse reflectance spectrum. A community population cohort study was carried out. The tissue‐reduced scattering coefficient and scattering power of the diabetes were significantly higher than normal control groups. The Gaussian multi‐peak fitting was performed on each excitation‐emission spectrum of the subject. A total of 63 fluorescence features containing information such as Gaussian spectral curve intensity, central wavelength position, and variance were obtained from each person. Logistic regression was used to construct the diabetes screening model. The results showed that the area under the receiver operating characteristic curve of the model for predicting diabetes was 0.816, indicating a high diagnostic value. As a rapid and non‐invasive detection method, it is expected to have high clinical value.
Recognition of immune reactive proteins as a potential multiepitope vaccine candidate of Taenia solium cysticerci through proteomic approach
Authors: Kaur Rimanpreet , Arora Naina , Rawat Suraj S. , Keshri Anand K. , Singh Gagandeep , Kumar Rajiv , Prasad Amit
Published: September 2023

Metacestode, the larva of Taenia solium, is the causative agent for neurocysticercosis (NCC), which causes epilepsy. The unavailability of a vaccine against human NCC is a major cause for its widespread prevalence across the globe. Therefore, the development of a reliable vaccine against NCC is the need of the hour. Employing a combination of proteomics and immunoinformatics, we endeavored to formulate a vaccine candidate. The immune reactive cyst fluid antigens of T. solium were identified by immune‐blotting two‐dimensional gels with NCC patient's sera, followed by Matrix‐assisted laser desorption‐ionization analysis. We performed a detailed proteomic study of these immune reactive proteins by utilizing immune‐informatics tools, identified the nontoxic, nonallergic, B‐cell epitopes, and collected epitopes with the least sequence homology with human and other Taenia species. These epitopes were joined through linkers to construct a multiepitope vaccine. Different physiochemical parameters such as molecular weight (23.82 kDa), instability (39.91), and aliphatic index (49.61) were calculated to ensure the stability of the linked peptides vaccine. The vaccine demonstrated stable interactions with different immune receptors like Toll‐like receptor 4 and IgG confirming that it will effectively stimulate the host immune response. We anticipate that our designed B‐cell linear epitope‐based vaccine will show promising results in in vitro and in vivo assays. This study provides a platform that would be useful to develop other suitable vaccine candidates to prevent helminthic neglected tropical diseases in near future.
Mutations of family with sequence similarity 20‐member C gene causing lethal and nonlethal Raine syndrome causes hypophosphatemia rickets
Authors: Liu Peihong , Li Jiaxuan , Tang Linghao , Cong Wei , Jin Han , Zhang Hong , Cui Bing , Yang Shan , Xiao Jing , Liu Chao , Saiyin Wuliji
Published: September 2023

Family with sequence similarity 20‐member C (FAM20C) is a kinase specific to most of the secreted phosphoproteome. FAM20C has been identified as the causative gene of Raine syndrome, initially characterized by lethal osteosclerosis bone dysplasia. However, since the identification of the cases of nonlethal Raine syndrome characterized by hypophosphatemia rickets, the previous definition of Raine syndrome has become debatable and raised a question about the role of mutations of FAM20C in controversial skeletal manifestation in the two forms of the disease. In this study, we aimed to investigate the influence of FAM20C mutations on skeletogenesis. We developed transgenic mice expressing Fam20c mutations mimicking those associated with human lethal and nonlethal Raine syndrome. The results revealed that transgenic mice expressing the mutant Fam20c found in the lethal (KO;G374R) and nonlethal (KO;D446N) Raine syndrome exhibited osteomalacia without osteosclerotic features. Additionally, both mutants significantly increased the expression of the Fgf23, indicating that Fam20c deficiency in skeletal compartments causes hypophosphatemia rickets. Furthermore, as FAM20C kinase activity catalyzes the phosphorylation of secreted proteomes other than those in the skeletal system, global FAM20C deficiency may trigger alterations in other systems resulting in osteosclerosis secondary to hypophosphatemia rickets. Together, the findings of this study suggest that FAM20C deficiency primarily causes hypophosphatemia rickets or osteomalacia; however, the heterogeneous skeletal manifestation in Raine syndrome was not determined solely by specific mutations of FAM20C. The findings also implicated that rickets or osteomalacia caused by FAM20C deficiency would deteriorate into osteosclerosis by the defects from other systems or environmental impacts.
High resolution imaging and analysis of extracellular vesicles using mass spectral imaging and machine learning
Authors: Bamford Sarah Elizabeth , Vassileff Natasha , Spiers Jereme G. , Gardner Wil , Winkler David A. , Muir Benjamin W. , Hill Andrew F. , Pigram Paul J.
Published: September 2023

Extracellular vesicles (EVs) are potentially useful biomarkers for disease detection and monitoring. Development of a label‐free technique for imaging and distinguishing small volumes of EVs from different cell types and cell states would be of great value. Here, we have designed a method to explore the chemical changes in EVs associated with neuroinflammation using Time‐of‐Flight Secondary Ion Mass spectrometry (ToF‐SIMS) and machine learning (ML). Mass spectral imaging was able to identify and differentiate EVs released by microglia following lipopolysaccharide (LPS) stimulation compared to a control group. This process requires a much smaller sample size (1 µL) than other molecular analysis methods (up to 50 µL). Conspicuously, we saw a reduction in free cysteine thiols (a marker of cellular oxidative stress associated with neuroinflammation) in EVs from microglial cells treated with LPS, consistent with the reduced cellular free thiol levels measured experimentally. This validates the synergistic combination of ToF‐SIMS and ML as a sensitive and valuable technique for collecting and analysing molecular data from EVs at high resolution.
FLT3‐targeted therapy restores GATA1 pathway function in NPM1/FLT3‐ITD mutated acute myeloid leukaemia
Authors: Sorcini D , Stella A , Scialdone A , Sartori S , Marra A , Rossi R , De Falco F , Adamo FM , Dorillo E , Geraci C , Arcaleni R , Rompietti C , Esposito A , Moretti L , Mameli MG , Martelli MP , Falini B , Sportoletti P
Published: September 2023

One‐third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3‐ITD mutated AML, thus providing a new mechanism of action for this drug.
Surface potential and mobile charge based drain current modeling of double gate junctionless accumulation mode negative capacitance field effect transistor
Authors: Yadav Snehlata , Rewari Sonam , Pandey Rajeshwari
Published: September 2023

An analytical drain current model for double gate junctionless accumulation mode negative capacitance field effect transistor (DG‐JAM‐NC‐FET) has been developed, combining the merits of junctionless accumulation mode and negative capacitance effect such as fabrication feasibility, low power dissipation, and reduced degradation in mobility. The novelty manifested in our work is because of the incorporation of the JAM structure in ferroelectric‐based negative capacitance FET. The benefit of JAM over existing FETs is that it combines the benefits of the junctionless transistor (JLT) and conventional FETs. It avoids excessive parasitic resistance due to stronger doping in the source and drain areas, resulting in higher conductivity and better characteristics than JLT. An analytical surface potential and threshold voltage have been developed using Poisson's equation and Landau Khalatnikov's (L‐K) equation. The drain current is then determined by integrating the mobile charge using the Pao–Sah integral. Various critical parameters such as surface potential, gain, capacitance, mobile charge density, drain current, threshold voltage, subthreshold swing, transconductance, and the switching ratio have been assessed extensively by varying ferroelectric layer and channel layer thicknesses, respectively. The ON current increases with the increase in ferroelectric thickness due to the voltage amplification given by the ferroelectric layer, and the switching curve gets steeper. The analytical modeling is done in MATLAB, and its comparison is made with the TCAD numerical simulation. The obtained analytical results and the numerical simulation results correspond well.
InN TFET with extended gate for high sensitivity label‐free biosensor
Authors: Ren Xinglin , Zhao Hongdong , Guan Song , Geng Lixin , Song Yiheng
Published: September 2023

An extended gate tunneling field effect transistor (EG‐TFET) with narrow bandgap material InN as a label‐free dielectric modulated biosensor is proposed and investigated. An optimum structure of the proposed InN TFET is given by comparing on‐state and ambipolar current. The on‐state current is improved by increasing the length of source overlap, for the rate of forward tunneling increases. Further, the ambipolar current is suppressed by increasing the length of drain offset, for the rate of backward tunneling decreases. A cavity under the gate electrode is formed for sensing biomolecules by dielectric modulation. The performance of EG‐TFET biosensor corresponding to varied dielectric constants of biomolecule is analyzed. In addition, the impacts of charge density and partial filled cavity on the drain current sensitivity are investigated. The electric field, surface potential and energy band profiles are used to explain the working principle of the EG‐TFET biosensor. The simulations reveal that the drain current sensitivity is 3.72 × 107 when neutral biomolecule with κ = 12 is immobilized in the cavity. A linearity fit verification is given, and the results of current sensitivity reveal a good linearity of the EG‐TFET biosensor with fitness coefficient γ2 > 0.99.
Causally interpretable meta‐analysis: Clearly defined causal effects and two case studies
Authors: Rott Kollin W. , Bronfort Gert , Chu Haitao , Huling Jared D. , Leininger Brent , Murad Mohammad Hassan , Wang Zhen , Hodges James S.
Published: September 2023

Meta‐analysis is commonly used to combine results from multiple clinical trials, but traditional meta‐analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently‐introduced causally interpretable meta‐analysis methods and apply their treatment effect estimators to two individual‐participant data sets. These estimators transport estimated treatment effects from studies in the meta‐analysis to a specified target population using the individuals' potentially effect‐modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated‐data meta‐analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta‐analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.
Advantages and limitations of different methods to determine the optimum formulation in surfactant–oil–water systems: A review
Authors: Marquez Ronald , Ontiveros Jesús F. , Barrios Nelson , Tolosa Laura , Palazzo Gerardo , Nardello‐Rataj Véronique , Salager Jean Louis
Published: September 2023

The optimum formulation in a surfactant–oil–water (SOW) system is defined as the physicochemical situation at which the surfactant adsorbed at the interface exhibits exactly equal interactions for both oil and water. Identifying the optimum formulation of SOW systems is crucial in various industrial applications, ranging from pharmaceuticals to cosmetics and to petroleum issues like dehydration and enhanced oil recovery. Multiple techniques are available to identify the optimum formulation, often with its own advantages and limitations. In this comprehensive review, we provide an in‐depth analysis of the systematic use of formulation scans to identify the optimum formulation in SOW systems. We critically assess different methods, including conventional ones, such as phase behavior observation, determination of the minimum interfacial tension from equilibrated systems, and the localization of the minimum emulsion stability using formulation scans. We also mention a new promising technique that can be applied in practice, such as oscillating spinning drop interfacial rheology (OSDIR) as well as others that allow an understanding of some structural features of the domains present in the surfactant‐rich phase in SOW systems. Among these methods, dynamic light scattering (DLS), small angle scattering (SAXS and SANS), nuclear magnetic resonance (NMR), X‐ray microcomputed tomography (Micro‐CT), and differential scanning calorimeter (DSC), can be found in the literature. Finally, we discuss potentially unusual behaviors that can appear in complex systems, thus providing guidance on the selection of the most suitable method tailored to the specific application.
Covalent and non‐covalent interaction of myofibrillar protein and cyanidin‐3‐O‐glucoside: focus on structure, binding sites and in vitro digestion properties
Authors: Liao Guangming , Kang Jiajia , Zhang Haiping , Cui Ying , Xiong Shanbai , Liu Youming
Published: September 2023

BACKGROUND

The aim of this study was to investigate the effects of covalent and non‐covalent interactions between myofibrillar protein (MP) and cyanidin‐3‐O‐glucoside (C3G) on protein structure, binding sites, and digestion properties. Four methods of inducing covalent cross‐linking were used in the preparation of MP‐C3G conjugates, including tyrosinase‐catalyzed oxidation, alkaline pH shift treatment, free radical grafting, and ultrasonic treatment. A comparison was made between MP‐C3G conjugates and complexes, and the analysis included sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), C3G binding ratio, liquid chromatography–tandem mass spectrometry (LC–MS/MS), protein side‐chain amino acids, circular dichroism spectroscopy, three‐dimensional fluorescence, particle size, and in vitro simulated digestion.

RESULTS

Covalent bonding between C3G and amino acid side chains in MP was confirmed by LC–MS/MS. In covalent bonding, tryptophan residues, free amino groups and sulfhydryl groups were all implicated. Among the 22 peptides covalently modified by C3G, 30 modification sites were identified, located in lysine, histidine, tryptophan, arginine and cysteine. In vitro simulated digestion experiments showed that the addition of C3G significantly reduced the digestibility of MP, with the covalent conjugate showing lower digestibility than the non‐covalent conjugate. Moreover, the digestibility of protein decreased more during intestinal digestion, possibly because covalent cross‐linking of C3G and MP further inhibited trypsin targeting sites (lysine and arginine).

CONCLUSION

Covalent cross‐linking of C3G with myofibrillar proteins significantly affected protein structure and reduced protein digestibility by occupying more trypsin binding sites. © 2023 Society of Chemical Industry.
Measurement and modeling of peroxides half‐life: A thermo‐kinetic approach
Authors: Dan Florin , Bagaria Pranav , Habersberger Brian , Koziol Amy
Published: September 2023

Half‐life values of organic peroxides at elevated temperature conditions are important in characterizing the reactivity and are often available in literature or through vendors. However, there is often lack of details/accuracy on methods used to obtain these values, as well as differences in methods across vendors and publications, thus resulting in discrepant reactivity profile. To address this, a method involving calorimetric experiment and thermo‐kinetic modeling was developed. The current approach was applied on five peroxides samples to obtain kinetic parameters and estimate their half‐life in the temperature range of interest. The measurements were performed by DSC under non‐isothermal conditions on the dilute peroxide solutions (∼0.12 M in mineral oil) and the data were kinetically treated according to three model‐based and one model‐free kinetic equations. A very good agreement was found between the half‐life calculated by all kinetic methods, but significant differences were noticed with the kinetic parameters reported in literature. Additionally, the obtained half‐life results, based on non‐isothermal measurements developed kinetic models, were validated through isothermal calorimetric testing. Given the accuracy and robustness of our results, the current method can be applied to estimate half‐life of organic peroxides at elevated temperature conditions.
Circ_0084188 promotes colorectal cancer progression by sponging miR‐654‐3p and regulating kruppel‐like factor 12
Authors: Wu Cui‐Cui , Hou Bai‐Chun , Yang Yu‐Han , Li Xue‐Feng , Ma Hong‐Chao , Li Bin‐Xian
Published: September 2023

To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real‐time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA‐654‐3p (miR‐654‐3p) and circ_0084188 or Kruppel‐like factor 12 (KLF12) was confirmed by a dual‐luciferase reporter, RNA immunoprecipitation and RNA pull‐down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR‐654‐3p, and circ_0084188 regulated CRC cell behaviors via sponging miR‐654‐3p. Moreover, KLF12 was a target of miR‐654‐3p, and miR‐654‐3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR‐654‐3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR‐654‐3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.
Longitudinal Performance of Cochlear Implants in Neurofibromatosis Type 2
Authors: Seo Stefanie , Shen Sarek , Ding Andy S. , Creighton Francis X.
Published: September 2023

Objective

Cochlear implants (CIs) are a well‐established treatment modality for hearing loss due to neurofibromatosis type 2 (NF2). Our aim is to investigate variables that affect longitudinal performance of CIs among patients with NF2.

Study Design

Retrospective review at a single academic institution consisting of patients who have received cochlear implants following hearing loss due to NF2.

Methods

The primary outcome examined was CI disuse or explantation. Associated clinical and surgical variables were analyzed using descriptive statistics. These included postoperative pure tone average (PTA) at 500, 1000, and 2000 Hz, tumor size, previous surgery, and comorbid depression.

Results

A total of 12 patients and 14 cochlear implants received at our institution from 2001 to 2022 were included. Notably, 35.7% of CIs (5 out of 14 cases) resulted in disuse or explantation. The average interval until explant was 9.4 years (range 3–14 years). In explanted CI cases, 20% had previous surgery and 80% had a diagnosis of comorbid depression as compared to 22.2% and 22.2%, respectively, in intact CI cases. Maximum tumor diameter was the only variable found to impact CI usage outcome (p = 0.028). Long‐term data showed that on average, patients benefit from 13.85 years of CI utility and a maximum PTA improvement of 45.0 ± 29.0 dB.

Conclusion

Despite the recurrent nature of NF2, patients continue to receive audiological benefit from cochlear implants. We found that larger tumor size may be associated with longitudinal CI failure.

Level of Evidence

4 Laryngoscope, 134:1847–1853, 2024
Treatment Outcome in Head and Neck Cancer With Distant Metastasis at Initial Diagnosis
Authors: Omata Jo , Ueki Yushi , Takahashi Yuto , Tanaka Ryoko , Yokoyama Yusuke , Takahashi Takeshi , Shodo Ryusuke , Yamazaki Keisuke , Togashi Takafumi , Matsuyama Hiroshi , Takahashi Nao , Okabe Ryuichi , Horii Arata
Published: September 2023

Objective

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease.

Methods

In this multi‐institutional retrospective study, 98 patients with HNSCC were initially diagnosed with M1 disease between 2007 and 2021. The patients were divided into the non‐palliative (received any systemic chemotherapy, n = 60) and palliative (did not receive systemic chemotherapy, n = 38) groups. Overall survival (OS) was compared between the groups. In the non‐palliative group, predictors of OS were explored based on patient characteristics and treatment details.

Results

The median OS in the non‐palliative group was 15 months (95% confidence interval [CI], 10–20), which was significantly longer than that in the palliative group (3 months, 95% CI, 2–5) (p < 0.001). Multivariate analysis revealed that administration of locoregional radiation therapy (RT) (hazard ratio [HR] 0.407 [95% CI 0.197–0.844]; p = 0.016), ICIs (HR 0.216 [95% CI 0.088–0.532]; p < 0.001) and RT/surgery for distant metastasis (HR 0.373 [95% CI 0.150–0.932]; p = 0.034) were the independent prognostic factors of OS.

Conclusion

An intensive treatment strategy combining systemic therapy using ICIs with RT/surgery for locoregional or distant metastasis may yield a survival benefit for patients with HNSCC with M1 disease.

Level of Evidence

4 Laryngoscope, 134:1679–1686, 2024
A jurisdictional risk assessment for the whole community: A new, systematic approach to participatory decision‐making in public health emergency preparedness using the analytic hierarchy process
Authors: Ray Madhury , Tornello Alana R. , Pickart Françoise , Stripling Mitch , Ali Mustafa , Vargas Luis G.
Published: September 2023

In 2018, the New York City (NYC) Department of Health and Mental Hygiene piloted a novel jurisdictional risk assessment (JRA) for public health disasters using the analytic hierarchy process (2018 JRA‐AHP). This new approach offers a replicable and equitable model for consensus decision‐making that incorporates the complexities of disaster preparedness. Its main contribution to the field is to offer a practical manifestation of emergency management's Whole Community Approach. The 2018 JRA‐AHP applied this principle by expanding traditional definitions of ‘expertise’ to include lived experience of disaster and facilitating direct participation in the risk decision by a variety of individuals with diverse backgrounds, expertise and knowledge of public health disasters. This paper describes the theory, methods and results behind the JRA‐AHP. The paper also presents a critical analysis of public health disaster risk assessments; contextualizes the Whole Community Approach using models of the relationship between democratic governments and communities; and addresses the practical applications of the 2018 JRA‐AHP in NYC while exploring the potential challenges that other jurisdictions may face in attempted adaptation.
An algebraic approach to the structural properties of positive state control systems
Authors: Ricarte Beatriz , Romero‐Vivó Sergio
Published: September 2023

In this paper, we deal with discrete‐time linear control systems in which the state is constrained to lie in the positive orthant
independently of the inputs involved, that is, the inputs can take negative values. Such (positive state) systems appear, for example, in ecology models where the removal of individuals from a population is described. Controllability and reachability are fundamental properties of a system that show its ability to move in space, which are analyzed from an algebraic point of view throughout the text, paying special attention to the single‐input case. Copyright © 2017 John Wiley & Sons, Ltd.
The impact of (simulated) resolution on breast cancer diagnosis based on high‐resolution 3D micro‐CT microcalcification images
Authors: Brahimetaj Redona , Cornelis Jan , Van Ongeval Chantal , De Mey Johan , Jansen Bart
Published: September 2023

Background

Breast microcalcifications (MCs) are considered to be a robust marker of breast cancer. A machine learning model can provide breast cancer diagnosis based on properties of individual MCs ‐ if their characteristics are captured at high resolution and in 3D.

Purpose

The main purpose of the study was to explore the impact of image resolution (8 µm, 16 µm, 32 µm, 64 µm) when diagnosing breast cancer using radiomics features extracted from individual high resolution 3D micro‐CT MC images.

Methods

Breast MCs extracted from 86 female patients were analyzed at four different spatial resolutions: 8 µm (original resolution) and 16 µm, 32 µm, 64 µm (simulated image resolutions). Radiomic features were extracted at each image resolution in an attempt, to find a compact feature signature allowing to distinguish benign and malignant MCs. Machine learning algorithms were used for classifying individual MCs and samples (i.e., patients). For sample diagnosis, a custom‐based thresholding approach was used to combine individual MC results into sample results. We conducted classification experiments when using (a) the same MCs visible in 8 µm, 16 µm, 32 µm, and 64 µm resolution; (b) the same MCs visible in 8 µm, 16 µm, and 32 µm resolution; (c) the same MCs visible in 8 µm and 16 µm resolution; (d) all MCs visible in 8 µm, 16 µm, 32 µm, and 64 µm resolution. Accuracy, sensitivity, specificity, AUC, and F1 score were computed for each experiment.

Results

The individual MC results yielded an accuracy of 77.27%, AUC of 83.83%, F1 score of 77.25%, sensitivity of 80.86%, and specificity of 72.2% at 8 µm resolution. For the individual MC classifications we report for the F1 scores: a 2.29% drop when using 16 µm instead of 8 µm, a 4.01% drop when using 32 µm instead of 8 µm, a 10.69% drop when using 64 µm instead of 8 µm. The sample results yielded an accuracy and F1 score of 81.4%, sensitivity of 80.43%, and specificity value of 82.5% at 8 µm. For the sample classifications we report for F1 score values: a 6.3% drop when using 16 µm instead of 8 µm, a 4.91% drop when using 32 µm instead of 8 µm, and a 6.3% drop when using 64 µm instead of 8 µm.

Conclusions

The highest classification results are obtained at the highest resolution (8 µm). If breast MCs characteristics could be visualized/captured in 3D at a higher resolution compared to what is used nowadays in digital mammograms (approximately 70 µm), breast cancer diagnosis will be improved.
Heme oxygenase‐1 therapy attenuates muscle atrophy following global brachial plexus avulsion in juvenile rats
Authors: Qin Hongjiu , Rui Jing , Lao Jie
Published: September 2023

Introduction/Aims

Brachial plexus injury can seriously affect distal target muscle function, and long‐term denervation leads to irreversible structural damage. In the present study, we examined the effect of hemin, a heme oxygenase‐1 (HO‐1) inducer, on intrinsic forepaw muscle atrophy induced by pan‐plexus injury in juvenile rats, as well as its underlying mechanism.

Methods

A global brachial plexus avulsion (GBPA) model of rat was established, and thirty 6‐wk‐old male rats were randomly divided into five groups: control, GBPA plus scramble small intering RNA (siRNA), GBPA plus scramble siRNA plus hemin, GBPA plus HO‐1 siRNA, and GBPA plus HO‐1 siRNA plus hemin. Hemin (50 mg/kg) was administered intraperitoneally once daily and the siRNA (5 μg) was injected intramuscularly twice a week. Intrinsic forepaw muscles were used for analysis. Myofiber cross‐sectional area (CSA), capillary‐to‐fiber ratio (C/F), and fiber‐type composition were assessed. The levels of inflammatory factors, ubiquitin‐protein ligases, and autophagy‐related proteins were also measured.

Results

We found that hemin treatment could effectively ameliorate denervated intrinsic forepaw muscle atrophy and suppress type I to II myofiber‐type conversion. Hemin treatment failed to prevent muscle capillary loss after denervation. The levels of inflammatory factors (tumor necrosis factor alpha [TNFα] and interleukin 6 [IL‐6]), ubiquitin‐protein ligases (MuRF‐1 and MAFbx), and autophagy‐related proteins (BNIP3 and LC3B‐II/I ratio) were increased by denervation and HO‐1 therapy attenuated the increment.

Discussion

Upregulation of HO‐1 might potentially be an effective strategy to alleviate denervation‐related muscle atrophy and might be a promising adjunctive treatment to improve hand function in children with pan‐plexus injury.