bluuebunny/crossref_metadata_2025 huggingface dataset:
Household food waste trending upwards in the United States: Insights from a National Tracking Survey
Authors: Li Ran , Shu Yiheng , Bender Kathryn E. , Roe Brian E.
Published: April 2023

Three successive administrations have supported the United States' 2015 goal to reduce food waste. Households waste more food than other supply chain segments, however, few data sources are available to track US households' progress toward this goal. We provide insights from the first four waves of a novel national survey designed to track such waste. We find a 280% year‐over‐year increase in self‐reported waste between early 2021 and early 2022, which militates against national goal achievement. We find households wasted more food during weeks they dined out and that sample households dined out significantly more in 2022 than in 2021.
Pharmacist‐led dosing reduces tacrolimus intrapatient variability in lung transplant recipients
Authors: Yang Anita , McKnight Roxanne , Prom Alyson , Byrne Megan , Evans Rickey A. , Doligalski Christina T.
Published: April 2023

Intrapatient variability (IPV) of tacrolimus has become a marker for predicting transplant outcomes, though minimal data exists regarding strategies to improve tacrolimus IPV. Following the implementation of comprehensive outpatient clinical pharmacy services, the impact of a dedicated lung transplant pharmacist on 1‐year tacrolimus variability and clinical outcomes in lung transplant recipients (LTRs) were investigated. A retrospective study of two LTR cohorts was conducted at a single‐center institution. Cohort 1 included LTRs from January 1, 2015 to December 31, 2017 with tacrolimus dose adjustments made by physicians or nurse practitioners, and were seen by a pharmacist on an ad hoc basis. Cohort 2 included LTRs from January 1, 2018 to December 31, 2019 with tacrolimus adjustments made solely by a pharmacist who saw them at each routine visit with the multidisciplinary team for the first year post‐transplant. The primary outcome assessed tacrolimus variability by the coefficient of variation 12 months post‐transplant. Secondary outcomes assessed post‐transplant hospital readmissions, acute cellular rejection (ACR), donor‐specific antibodies (DSA), and mortality at 12 months post‐transplant. No protocol changes occurred during the study period. Chi‐squared and t‐tests analyses were utilized. Sixty‐three LTRs were included, 39 patients in Cohort 1 and 24 in Cohort 2 with no significant differences between cohorts. At 1‐year post‐transplant, Cohort 2 had lower median tacrolimus variability (35.7% vs. 30.3%, p = 0.02) and more patients had a tacrolimus variability <30% (20.5% vs. 45.8%, p = 0.03). There were no differences in readmission rates, ACR, DSA, or mortality 12 months post‐transplant. Based on this single‐center limited cohort study, the integration of a dedicated ambulatory transplant pharmacist improved tacrolimus variability 1 year following lung transplant. Further studies are needed to assess long‐term morbidity and mortality rates.
Modulating pentenoate‐functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction
Authors: Burkey Kyley , Castillo Kayla , Elrod Philip , Suekuni Murilo T. , Aikman Elizabeth , Gehrke Stevin , Allgeier Alan , Robinson Jennifer L.
Published: April 2023

Knee meniscus tears are one of the most common musculoskeletal injuries. While meniscus replacements using allografts or biomaterial‐based scaffolds are available, these treatments rarely result in integrated, functional tissue. Understanding mechanotransducive signaling cues that promote a meniscal cell regenerative phenotype is critical to developing therapies that promote tissue regeneration rather than fibrosis after injury. The purpose of this study was to develop a hyaluronic acid (HA) hydrogel system with tunable crosslinked network properties by modulating the degree of substitution (DoS) of reactive‐ene groups to investigate mechanotransducive cues received by meniscal fibrochondrocytes (MFCs) from their microenvironment. A thiol‐ene step‐growth polymerization crosslinking mechanism was employed using pentenoate‐functionalized hyaluronic acid (PHA) and dithiothreitol to achieve tunability of the chemical crosslinks and resulting network properties. Increased crosslink density, reduced swelling, and increased compressive modulus (60–1020 kPa) were observed with increasing DoS. Osmotic deswelling effects were apparent in PBS and DMEM+ compared to water; swelling ratios and compressive moduli were decreased in the ionic buffers. Frequency sweep studies showed storage and loss moduli of hydrogels at 1 Hz approach reported meniscus values and showed increasing viscous response with increasing DoS. The degradation rate increased with decreasing DoS. Lastly, modulating PHA hydrogel surface modulus resulted in control of MFC morphology, suggesting relatively soft hydrogels (E = 60 ± 35 kPa) promote more inner meniscus phenotype compared to rigid hydrogels (E = 610 ± 66 kPa). Overall, these results highlight the use of ‐ene DoS modulation in PHA hydrogels to tune crosslink density and physical properties to understand mechanotransduction mechanisms required to promote meniscus regeneration.
Perspectives of Indian dental residents on novel online practical examination during COVID‐19: A cross‐sectional study
Authors: Sajjan Girija S. , Praveen Dalavai , Gadde Praveen , Sajjan Suresh , Swamy Shivakumara , Chaitanya Penmatsa , Ramesh Konathala S. V. , Pulidindi Anil Kumar
Published: April 2023

Purpose

This cross‐sectional study aimed to assess the graduating dental residents’ perspectives on the online clinical examination format.

Methods

The questionnaire used to assess the perspectives was developed via a focus group discussion and was validated for face and content validity, readability testing, and pilot testing for the online version. This self‐administered, online questionnaire integrated 15 Likert‐scale‐based multiple choice questions and one open‐ended question. It was distributed to the residents across 16 dental schools after the clinical examination was completed. The perspectives regarding examination preparation, the ability to transition to online mode, and the performance in the examination were assessed. Descriptive statistical analysis (counts and percentages) was performed.

Results

A total of 256 subjects participated in the study by returning the online survey. In the preparation phase, 70.7% (n = 181) residents reported anxiety and 56.1% (n = 144) reported stress. During the examinations, only 13.6% (n = 35) of the participants reported difficulty with internet speed. The majority, 64.6% (n = 165) of the participants reported that the absence of an external examiner face‐to‐face reduced anxiety. The compiled answers to the open‐ended question revealed that residents expressed inconvenience in digitizing the academic logbooks and clinical work. The poor quality of sound and images affected the display of skills.

Conclusions

The study revealed a moderate level of acceptance for the novel online practical examination method. The residents reported stress before and during the examination due to the sudden transition to an online examination. The online practical examination with modifications might be a viable alternative to the in‐person clinical examination.
Public perspective on medications to delay Alzheimer's disease symptoms
Authors: Rich Matthew B. , Blout Zawatsky Carrie L. , Botta Joseph J. , Christensen Kurt D.
Published: April 2023

Disease‐modifying treatments for Alzheimer's disease are emerging. Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD‐related genetic testing. Invitations to a web‐based survey were posted on social media sites. Respondents were sequentially assigned to imagine that they had a 5%, 15%, or 35% chance of developing AD. They were then provided a hypothetical scenario describing a medication that delayed AD symptoms. After reporting intentions to ask for the medication, respondents were asked about their interest in genetic testing to predict AD risk. Data from 310 individuals were analyzed. Intentions to ask for a preventative medication were greater for respondents presented AD risks of 35% compared to risks of 15% and 5% (86% vs. 66% vs. 62%, respectively, p < 0.001). The proportion who would ask for genetic susceptibility testing increased from 58% to 79% when respondents were told to imagine that a medication that delayed AD symptoms existed (p < 0.001). Findings suggest that individuals who know they have an increased risk for AD are more likely pursue medications to delay onset of disease symptoms, and the availability of AD‐delaying treatments will increase interest in associated genetic testing. Findings provide insight about who will pursue emerging preventative medications, including individuals for whom the medications may be inappropriate, and the impact on genetic test utilization.
Association between human genetic variants affecting the host NK cell response and the development of herpes simplex virus type 1 encephalitis
Authors: Graninger Marianne , Vietzen Hannes , Puchhammer‐Stöckl Elisabeth
Published: April 2023

Herpes simplex virus encephalitis (HSE) is a rare complication of herpes simplex virus type 1 (HSV‐1) infection or reactivation. It is so far unclear why only few patients develop HSE. As natural killer (NK) cells provide an important defense against HSV‐1, we investigated whether there is an association between distinct human genetic variants associated with the host NK cell response and HSE. Forty‐nine adult patients with confirmed HSE and 247 matched controls were analyzed for the distribution of the following genotypes: CD16A (FcγRIIIA) V/F and IGHG1 G1m3/17, both influencing antibody‐dependent cellular cytotoxicity; HLA‐E*0101/*0103, associated with NK cell activation; and SLFN13 rs9916629C/T associated with NK cell response. Homozygous HLA‐E*0101:0101 and HLA‐E*0103:0103 variants as well as the rs9916629CC genotype were overrepresented in HSE patients compared to controls (p ≤ 0.001). Notably, cooccurrence of the homozygous HLA‐E*0101 and rs9916629CC genotypes was present in 19% of patients but totally absent in controls (p ≤ 0.0001). Distribution of CD16A and IGHG1 variants did not differ between patients and controls. Our data show that the rare combination of HLA‐E*0101:0101 and rs9916629CC is significantly associated with HSE. Possibly, these genetic variations could be useful as clinical markers predicting HSE prognosis and helping to adapt the treatment of HSE in the individual patient.
Thermal behavior of modern and archeological enamel and dentin by in situ temperature‐dependent Raman spectroscopy
Authors: Kiseleva Daria , Pankrushina Elizaveta
Published: April 2023

Teeth and bones are important bioarchives, which can be altered because of diagenesis or burning (cooking, funerary cremations, and fires). Though heating and diagenesis are different processes, an experimental heating of modern bioapatite reproduces in a short time effects similar to diagenetic processes occurring over geological time. The thermal behavior of modern and archeological human enamel and dentin using the in situ thermo‐Raman spectroscopy at 83–873 K was investigated to assess the structural changes in organic and mineral components of a tooth and their interrelationship. The ν1(PO4) vibrational mode in apatite is the most anharmonic and responsible for the reaction of the structure to external influences. The γiP isobaric Grüneisen parameters for archeological (0.41) and modern (0.24) enamel are different from those for fluor‐ (0.17) and chlorapatite (0.17), which indicates a stronger reaction of PO bonds in bioapatite PO4 tetrahedra to temperature changes as compared with geologic samples. The anomalies of the thermal dependences of the ν1(PO4) peak position and
(T) autocorrelation function are caused by the combined effect of different factors such as breaking of hydroxyl and hydrogen bonds, the loss of adsorbed and structural water, collagen denaturation, organic phase combustion, and removal and relocation of B‐ and A‐type carbonate ions. The thermal (273, 313, 341, and 363 K) and cold (~160 K) denaturation of collagen is reflected in the ν1(PO4) and
(T) dependences. The
(T) differences between modern and archeological dentin and enamel are contingent on bioapatite composition (proportions of adsorbed and structural water, hydroxyl and carbonate ions, and trace elements as well as different types of organic matter — low‐molecular noncollagen compounds and high‐molecular collagen). The results obtained contribute to the knowledge about the thermal transformations of the mineral and organic phases of modern and archeological tooth tissues and allow their structural alterations to be evaluated.
Serum infliximab levels and clinical response in hidradenitis suppurativa
Authors: Benassaia Erwin , Bouaziz Jean‐David , Jachiet Marie , Cordoliani Florence , Saussine Anne , Lepelletier Clemence , Goldwirt Lauriane , Cassius Charles , de Masson Adèle , Bagot Martine , Bachelez Hervé , Assan Florence
Published: April 2023

Background

Infliximab (IFX) is a chimeric immunoglobulin G‐1κ monoclonal antibody that neutralises the biologic activity of tumour necrosis factor‐α, and has shown efficacy (off‐label) for the treatment of severe hidradenitis suppurativa (HS). The relationship between clinical response and IFX pharmacokinetics (PK) in HS is currently unknown.

Objectives

To investigate the relationship between the trough serum concentration of IFX (TSI) and the clinical response to IFX in moderate‐to‐severe HS between 12th and 24th week (W12–W24) after IFX treatment onset.

Methods

We conducted a retrospective, monocentric study in a French dermatology tertiary care centre (Saint‐Louis hospital, Paris) between January 2013 and January 2022. Adult patients treated with IFX for moderate‐to‐severe HS were included if (i) they had at least one IFX serum dosage during follow‐up, and (ii) they had a measurable Hidradenitis Suppurativa Clinical Response (HiSCR) score between the 12th and 24th week (W12–W24). Patients received IFX infusions every 4, 6 or 8 weeks at 5, 7.5 or 10 mg/kg of body weight dosages.

Results

Twenty‐two patients (48.9%; median age: 36 [31–43] years; 7 [31.8%] female) who had at least one IFX serum dosage between W12–W24 were enroled. The median TSI between W12 and W24 was significantly higher in the responding group compared to the nonresponding group of patients: 14.8 (12.1–15.7) versus 1.6 (0.8–3.5) µg/mL, respectively (p = 0.01). Using receiver operating characteristics (ROC) analysis curve, a TSI threshold of 7 µg/mL at W12–W24 showed sensitivity and specificity of 0.75 and 0.94, respectively.

Conclusions

This study supports some degree of correlation between clinical response and TSI in HS, and paves the way for prospective studies investigating correlations between PK, immunogenicity and clinical response in severe HS patients receiving IFX.
Mapping Genetic Susceptibility to Stenosis in the Proximal Airway
Authors: Sharif Kayvon , Tierney William S. , Davis Ruth J. , Wohler Elizabeth , Sobreira Nara , Hillel Alexander T. , Collins Samuel , Ramirez‐Solano Marisol , Sheng Quanhu , Gelbard Alexander
Published: April 2023

Objectives

Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Yet despite recent advances, the genetic basis of SGS remains poorly understood. We sought to identify candidate risk genes associated with an SGS phenotype, investigate their biological function, and identify the cell types enriched for their expression.

Methods

The Online Mendelian Inheritance in Man (OMIM) database was queried for single gene variants associated with an SGS phenotype. The functional intersections and molecular roles of the identified genes were explored using pathway enrichment analysis (PEA) computational methods. Cellular localization of the candidate risk genes was measured via transcriptional quantification in an established single cell RNA sequencing (scRNA‐seq) atlas of the proximal airway.

Results

Twenty genes associated with SGS phenotype were identified. PEA resulted in 24 significantly enriched terms including “cellular response to TGF‐β,” “epithelial‐to‐mesenchymal transition,” and “adherens junctions.” Mapping the 20 candidate risk genes to the scRNA‐seq atlas found 3 (15%) genes were enriched in epithelial cells, 3 (15%) in fibroblasts, and 3 (15%) in endothelial cells. 11 (55%) genes were expressed ubiquitously among tissue types. Interestingly, immune cells were not significantly enriched for candidate risk genes.

Conclusion

We identify and provide biologic context for 20 genes associated with fibrotic disease of the proximal airway and form the foundation for future detailed genetic study.

Level of evidence

N/A Laryngoscope, 133:3049–3056, 2023
Oxygen depletion and sediment respiration in ice‐covered arctic lakes
Authors: Schwefel Robert , MacIntyre Sally , Cortés Alicia , Sadro Steven
Published: April 2023

Processes regulating the rate of oxygen depletion determine whether hypoxia occurs and the extent to which greenhouse gases accumulate in seasonally ice‐covered lakes. Here, we investigate the oxygen budget of four arctic lakes using high‐frequency data during two winters in three shallow lakes (9–13 m maximal depth) and four winters in 24 m deep main basin of Toolik Lake. Incubation experiments measured sediment metabolism. Volume‐averaged oxygen depletion measured in situ was independent of water temperature and duration of the ice‐covered period. Average rates were between 0.2 and 0.39 g O2 m−2 d−1 in the shallow lakes and between 0.03 and 0.14 g O2 m−2 d−1 in Toolik Lake, with higher rates in smaller lakes with their larger sediment area to volume ratio. Rates decreased to ~ 20%–50% of initial values in late winter in the shallow lakes but less or not at all in Toolik. The lack of a decline in Toolik Lake points to continued oxygen transport to the sediment–water interface where oxygen consumption occurs. In all lakes, lower in situ oxygen depletion than in incubation measurements points toward increasing anoxia in the lower water column depressing loss rates. In Toolik, oxygen loss during early winter was less in years with minimal snow cover. Penetrative convection occurred, which could mix downwards oxygen produced by photosynthesis or excluded during ice formation. Estimates of these terms exceeded photosynthesis measured in sediment incubations. Modeling under ice‐oxygen dynamics requires consideration of optical properties and biological and transport processes that modify oxygen concentrations and distributions.
Tribological properties of hexagonal boron nitride nanoparticles as a lubricating grease additive
Authors: Cheng Yu , Bu Yingbin , Guan Pengxi , Yang Yujie , Qing Jianbo
Published: April 2023

The friction and anti‐wear behaviours of hexagonal boron nitride (h‐BN) nanoparticles as a lithium lubricating grease additive are being investigated under sliding conditions. The grease with 3 wt% 60 nm h‐BN particles and the grease with 1 wt% 500 nm h‐BN particles lead to 22.34% and 20.18% reductions in the wear scar diameter, respectively, although the friction coefficients slightly decrease. The boric acid H3BO3 with layer‐crystal structure produces during the friction process, and the synergistic effect of h‐BN nanoparticles and H3BO3 makes friction reduction and wear‐resistant enhancement. Furthermore, the 60 nm h‐BN particles filled in the asperity valleys of the friction surface make a rolling effect and establish a protective film, while the 500 nm h‐BN particles shield the asperity contact between friction pairs and make a polishing effect as well.
Acquired Stuttering in Parkinson's Disease
Authors: Gooch Eloïse A. , Horne Kyla‐Louise , Melzer Tracy R. , McAuliffe Megan J. , MacAskill Michael , Dalrymple‐Alford John C. , Anderson Tim J. , Theys Catherine
Published: April 2023

Background

Parkinson's disease frequently causes communication impairments, but knowledge about the occurrence of new‐onset stuttering is limited.

Objectives

To determine the presence of acquired neurogenic stuttering and its relationship with cognitive and motor functioning in individuals with Parkinson's disease.

Method

Conversation, picture description, and reading samples were collected from 100 people with Parkinson's disease and 25 controls to identify the presence of stuttered disfluencies (SD) and their association with neuropsychological test performance and motor function.

Results

Participants with Parkinson's disease presented with twice as many stuttered disfluencies during conversation (2.2% ± 1.8%SD) compared to control participants (1.2% ± 1.2%SD; P < 0.01). 21% of people with Parkinson's disease (n = 20/94) met the diagnostic criterion for stuttering, compared with 1/25 controls. Stuttered disfluencies also differed significantly across speech tasks, with more disfluencies during conversation compared to reading (P < 0.01). Stuttered disfluencies in those with Parkinson's disease were associated with longer time since disease onset (P < 0.01), higher levodopa equivalent dosage (P < 0.01), and lower cognitive (P < 0.01) and motor scores (P < 0.01).

Conclusion

One in five participants with Parkinson's disease presented with acquired neurogenic stuttering, suggesting that speech disfluency assessment, monitoring and intervention should be part of standard care. Conversation was the most informative task for identifying stuttered disfluencies. The frequency of stuttered disfluencies was higher in participants with worse motor functioning, and lower cognitive functioning. This challenges previous suggestions that the development of stuttered disfluencies in Parkinson's disease has purely a motoric basis.
Reduced Interoception Abilities in Patients with Restless Legs Syndrome
Authors: Sandri Angela , Mingolla Gloria Pompea , Camonita Giorgia , Lippolis Marianna , Tinazzi Michele , Antelmi Elena
Published: April 2023

Background

Restless legs syndrome (RLS) is a complex sensorimotor disorder occurring with a typical circadian fashion. Association with additional features, like alexithymia and nocturnal compulsive behaviors further complicates the framework.

Objectives

To assess interoception in RLS.

Methods

A total of 25 RLS patients and 28 controls underwent the heartbeat tracking task (interoceptive accuracy [IAC]). RLS symptoms’ frequency, disturbance and duration, nocturnal behaviors, interoceptive awareness (IAW), alexithymia, depressive and anxiety symptoms were also collected.

Results

RLS patients showed significant lower IAC (P = 0.0003) and IAW (P = 0.012), and reported more nocturnal eating behaviors (P < 0.001). IAC positively correlated with IAW (R = 0.32), and negatively correlated with age (R = −0.58). Nocturnal eating behavior negatively correlated with IAC (R = −0.44) and IAW (R = −0.50).

Conclusions

RLS patients presented reduced interoceptive abilities correlating with higher nocturnal eating behaviors. Future studies are needed to explore the role of interoception in RLS pathophysiology, also in relation to other sensorimotor aspects.
Energy decay of a mixture with local viscoelasticity
Authors: Crenshaw Aaron M. , Liu Zhuangyi , Quintanilla Ramon
Published: April 2023

We consider a binary mixture system with local Kelvin–Voigt damping in one of the components of the mixture. The well‐posedness and the polynomial stability are proved by the semigroup theory and the frequency domain approach.
A narrow‐band overmoded rectangular waveguide filter for high‐power microwaves (HPMs)
Authors: Li Meiling , He Wensi , Zheng Qi , Yang Xuexia , Yi Zixuan
Published: April 2023

An overmoded rectangular waveguide filter with the advantages of narrowband and high power is presented in this paper. The transmission efficiency of each mode in the filter is analyzed based on mode‐matching techniques and optimized by combining it with the calculation method. Due to the overmoded waveguide and direct coupling topology, the designed structure has characteristics of narrowband and high power. The overall size of the proposed filter is only 17.45 × 36.20 × 126.67 mm3 (0.54λ0 × 1.12λ0 × 3.93λ0, λ0 is the wavelength of the center frequency in free space). The test results match well with the simulated ones and they both show that the transmission efficiency of TE10 mode is higher than 99.77%. Meanwhile, the proposed filter achieves 1% fractional bandwidth and 134.5 kW power capacity, which reveals that the filter has both narrow‐band and high‐power characteristics. The designed filter would be an attractive candidate for HPM systems.
A Novel Low‐profile Rectangular Dielectric Resonator Antenna with enhanced gain for 5G New Radio band applications
Authors: Parvathi Vusa Lakshmi , Rajput Anil , Raut Rajesh B. , Mukherjee Biswajeet
Published: April 2023

A wideband low‐profile chamfered rectangular dielectric resonator antenna (RDRA) with high gain is proposed for sub‐6 GHz 5G new radio band applications. RDRA is excited with microstrip cross‐slot aperture coupling which is employed on the substrate. The dielectric resonator antenna with low‐profile produces unwanted back radiation. The reflector placed at the bottom side of the RDRA is accountable for gain improvement on boresight direction by reducing back radiation. Slits, introduced on the copper layer, help to control the phase difference between direct waves and reflected waves. A rectangular stub is added to microstrip feed to enhance the impedance matching between excitation port and the antenna. The proposed antenna offers 2.74–4.35 GHz impedance bandwidth and 9.1 dBi peak gain. The proposed design is fabricated and experimentally verified.
A miniaturized filter design approach using GMDH neural networks
Authors: Sattari Mohammad Amir , Hayati Mohsen , Shama Farzin , Shah‐Ebrahimi Seyed Maziar
Published: April 2023

A miniaturized microstrip low‐pass filter (LPF) has been designed and fabricated using semicircular‐shaped resonators. The designing procedures as well as the LC equivalent circuit of each step have been reported. Due to the small size of the presented filter, flat group delay in the pass‐band, low insertion loss (IL), and high return loss (RL) in operational frequency. By producing adjusted transmission zeros (TZs), the second to fourth unwanted harmonics were attenuated using the proposed LPF. The machine learning approach has been utilized to adjustment of the filter parameters. The 3 dB cut‐off frequency (Fc), TZs, IL, and RL were predicted using the group method of data handling neural network (GMDHNN). Ninety simulations were performed with different inductor and capacitor values. The collected data were used for neural network training. The GMDHNN can diagnose the efficient inputs, so this feature was applied to determine the efficient L and C elements on TZs, Fc, IL, and RL. Finally, the fabricated filter results are well‐matched with the simulation ones. IL and RL of the suggested filter in operational frequency are −0.09 and −17.26 dB, respectively. The total filter size is only 14.65 mm × 3.5 mm.
Bioökonomie in Japan: Bioschmieden und Handwerkskunst
Authors: Schmid Rolf
Published: April 2023

Japan setzt auf Mikroorganismen, Pflanzen und bessere Produktionsverfahren. Zudem soll eine Infrastruktur Unternehmen, Wissenschaft und staatliche Stellen verbinden, um mehr Biotechverfahren zu entwickeln.
Conserved and variable heat stress responses of the Heat Shock Factor transcription factor family in maize and Setaria viridis
Authors: Myers Zachary A. , Wootan Clair M. , Liang Zhikai , Zhou Peng , Engelhorn Julia , Hartwig Thomas , Nathan Springer M.
Published: April 2023

The Heat Shock Factor (HSF) transcription factor family is a central and required component of plant heat stress responses and acquired thermotolerance. The HSF family has dramatically expanded in plant lineages, often including a repertoire of 20 or more genes. Here we assess and compare the composition, heat responsiveness, and chromatin profiles of the HSF families in maize and Setaria viridis (Setaria), two model C4 panicoid grasses. Both species encode a similar number of HSFs, and examples of both conserved and variable expression responses to a heat stress event were observed between the two species. Chromatin accessibility and genome‐wide DNA‐binding profiles were generated to assess the chromatin of HSF family members with distinct responses to heat stress. We observed significant variability for both chromatin accessibility and promoter occupancy within similarly regulated sets of HSFs between Setaria and maize, as well as between syntenic pairs of maize HSFs retained following its most recent genome duplication event. Additionally, we observed the widespread presence of TF binding at HSF promoters in control conditions, even at HSFs that are only expressed in response to heat stress. TF‐binding peaks were typically near putative HSF‐binding sites in HSFs upregulated in response to heat stress, but not in stable or not expressed HSFs. These observations collectively support a complex scenario of expansion and subfunctionalization within this transcription factor family and suggest that within‐family HSF transcriptional regulation is a conserved, defining feature of the family.
A metal‐dependent conformational change provides a structural basis for the inhibition of CTP synthase by gemcitabine‐5′‐triphosphate
Authors: McLeod Matthew J. , Tran Norman , McCluskey Gregory D. , Gillis Tom D. , Bearne Stephen L. , Holyoak Todd
Published: April 2023

CTP synthases (CTPS) catalyze the de novo production of CTP using UTP, ATP, and l‐glutamine with the anticancer drug metabolite gemcitabine‐5′‐triphosphate (dF‐dCTP) being one of its most potent nucleotide inhibitors. To delineate the structural origins of this inhibition, we solved the structures of Escherichia coli CTPS (ecCTPS) in complex with CTP (2.0 Å), 2′‐ribo‐F‐dCTP (2.0 Å), 2′‐arabino‐F‐CTP (2.4 Å), dF‐dCTP (2.3 Å), dF‐dCTP and ADP (2.1 Å), and dF‐dCTP and ATP (2.1 Å). These structures revealed that the increased binding affinities observed for inhibitors bearing the 2′‐F‐arabino group (dF‐dCTP and F‐araCTP), relative to CTP and F‐dCTP, arise from interactions between the inhibitor's fluorine atom exploiting a conserved hydrophobic pocket formed by F227 and an interdigitating loop from an adjacent subunit (Q114‐V115‐I116). Intriguingly, crystal structures of ecCTPS•dF‐dCTP complexes in the presence of select monovalent and divalent cations demonstrated that the in crystallo tetrameric assembly of wild‐type ecCTPS was induced into a conformation similar to inhibitory ecCTPS filaments solely through the binding of Na+‐, Mg2+‐, or Mn2+•dF‐dCTP. However, in the presence of potassium, the dF‐dCTP‐bound structure is demetalated and in the low‐affinity, non‐filamentous conformation, like the conformation seen when bound to CTP and the other nucleotide analogues. Additionally, CTP can also induce the filament‐competent conformation linked to high‐affinity dF‐dCTP binding in the presence of high concentrations of Mg2+. This metal‐dependent, compacted CTP pocket conformation therefore furnishes the binding environment responsible for the tight binding of dF‐dCTP and provides insights for further inhibitor design.
Model‐based approach to identify predictors of paclitaxel‐induced myelosuppression in “real‐world” administration
Authors: Salem Ahmed M. , Dvergsten Erik , Karovic Sanja , Maitland Michael L. , Gopalakrishnan Mathangi
Published: April 2023

Taxanes are currently the most frequently used chemotherapeutic agents in cancer care, where real‐world use has focused on minimizing adverse events and standardizing the delivery. Myelosuppression is a well‐characterized, adverse pharmacodynamic effect of taxanes. Electronic health records (EHRs) comprise data collected during routine clinical care that include patients with heterogeneous demographic, clinical, and treatment characteristics. Application of pharmacokinetic/pharmacodynamic (PK/PD) modeling to EHR data promises new insights on the real‐world use of taxanes and strategies to improve therapeutic outcomes especially for populations who are typically excluded from clinical trials, including the elderly. This investigation: (i) leveraged previously published PK/PD models developed with clinical trial data and addressed challenges to fit EHR data, and (ii) evaluated predictors of paclitaxel‐induced myelosuppression. Relevant EHR data were collected from patients treated with paclitaxel‐containing chemotherapy at Inova Schar Cancer Institute between 2015 and 2019 (n = 405). Published PK models were used to simulate mean individual exposures of paclitaxel and carboplatin, which were linearly linked to absolute neutrophil count (ANC) using a published semiphysiologic myelosuppression model. Elderly patients (≥70 years) constituted 21.2% of the dataset and 2274 ANC measurements were included in the analysis. The PD parameters were estimated and matched previously reported values. The baseline ANC and chemotherapy regimen were significant predictors of paclitaxel‐induced myelosuppression. The nadir ANC and use of supportive treatments, such as growth factors and antimicrobials, were consistent across age quantiles suggesting age had no effect on paclitaxel‐induced myelosuppression. In conclusion, EHR data could complement clinical trial data in answering key therapeutic questions.
Modeling Alzheimer's disease progression utilizing clinical trial and ADNI data to predict longitudinal trajectory of CDR‐SB
Authors: Jamalian Samira , Dolton Michael , Chanu Pascal , Ramakrishnan Vidya , Franco Yesenia , Wildsmith Kristin , Manser Paul , Teng Edmond , Jin Jin Y. , Quartino Angelica , Hsu Joy C. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2023

There is strong interest in developing predictive models to better understand individual heterogeneity and disease progression in Alzheimer's disease (AD). We have built upon previous longitudinal AD progression models, using a nonlinear, mixed‐effect modeling approach to predict Clinical Dementia Rating Scale – Sum of Boxes (CDR‐SB) progression. Data from the Alzheimer's Disease Neuroimaging Initiative (observational study) and placebo arms from four interventional trials (N = 1093) were used for model building. The placebo arms from two additional interventional trials (N = 805) were used for external model validation. In this modeling framework, CDR‐SB progression over the disease trajectory timescale was obtained for each participant by estimating disease onset time (DOT). Disease progression following DOT was described by both global progression rate (RATE) and individual progression rate (α). Baseline Mini‐Mental State Examination and CDR‐SB scores described the interindividual variabilities in DOT and α well. This model successfully predicted outcomes in the external validation datasets, supporting its suitability for prospective prediction and use in design of future trials. By predicting individual participants' disease progression trajectories using baseline characteristics and comparing these against the observed responses to new agents, the model can help assess treatment effects and support decision making for future trials.
Silibinin attenuated pseudo‐allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway
Authors: Wang Yuejin , Hu Shiting , Dang Baowen , Zhang Yonghui , Zheng Guodong , Zhao Chenrui , Huang Yihan , Zhang Tao
Published: April 2023

Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cells. Many endogenous or exogenous factors could cause this reaction. Silibinin is the main chemical component of silymarin and has been reported to have pharmacological activities. However, the anti‐allergic reaction effect of silibinin has not yet been investigated. This study aimed to evaluate the effect of silibinin to attenuate pseudo‐allergic reactions in vivo and to investigate the underlying mechanism in vitro. In this study, calcium imaging was used to assess Ca2+ mobilization. The levels of cytokines and chemokines, released by stimulated mast cells, were measured using enzyme immunoassay kits. The activity of silibinin was evaluated in a mouse model of passive cutaneous anaphylaxis (PCA). Western blotting was used to explore the related molecular signaling pathways. In results, silibinin markedly inhibited mast cell degranulation, calcium mobilization, and preventing the release of cytokines and chemokines in a dose‐dependent manner via the PLCγ and PI3K/Akt signaling pathway. Silibinin also attenuated PCA in a dose‐dependent manner. In summary, silibinin has an anti‐pseudo‐allergic pharmacological activity, which makes it a potential candidate for the development of a novel agent to arrest pseudo‐allergic reactions.
Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF‐κB signaling pathway
Authors: Yang Xiaojiang , Qian Hong , Meng Jia , Jiang Hui , Yuan Tao , Yang Shaoqiang , Luo Yibin , Bao Ninrong , Zhao Jianning , Wang Dongsheng
Published: April 2023

The present study aimed to evaluate anti‐rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti‐inflammatory and immunomodulatory properties. Nevertheless, the exact role of LON in RA remains elusive. In this test, the anti‐RA effect of LON was evaluated in collagen‐induced arthritis (CIA) mouse model. Relevant parameters were measured during the experiment; ankle tissue and serum were collected at the end of the experiment for radiology, histopathology, and inflammation analysis. ELISA, qRT‐PCR, immunofluorescence, and western blot were used to explore the effect of LON on the polarization of macrophages and related signal pathways. It was discovered that LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. LON treatment significantly decreased M1 marker levels in CIA mice and LPS/IFN‐γ‐induced RAW264.7 cells, while slightly increasing M2 marker levels in CIA mice and IL‐4‐induced RAW264.7 cells. Mechanistically, LON attenuated the activation of the NF‐κB signaling pathway, which contributes to M1 macrophage polarization and inflammasome activation. In addition, LON inhibited NLRP3 inflammasome activation in M1 macrophages, thereby reducing inflammation by inhibiting IL‐1β and IL‐18 release. These results indicated that LON might exert anti‐RA effects by regulating the polarization of M1/M2 macrophage, especially by inhibiting macrophage polarization toward M1.
A Quantum Algorithm for Solving Eigenproblem of the Laplacian Matrix of a Fully Connected Weighted Graph
Authors: Liu Hai‐Ling , Wan Lin‐Chun , Yu Chao‐Hua , Pan Shi‐Jie , Qin Su‐Juan , Gao Fei , Wen Qiao‐Yan
Published: April 2023

Solving eigenproblem of the Laplacian matrix of a fully connected weighted graph has wide applications in data science, machine learning, and image processing, etc. However, this is very challenging because it involves expensive matrix operations. Here, an efficient quantum algorithm is proposed to solve it. Specifically, the optimal Hamiltonian simulation technique based on the block‐encoding framework is adopted to implement the quantum simulation of the Laplacian matrix. Then, the eigenvalues and eigenvectors of the Laplacian matrix are extracted by the quantum phase estimation algorithm. The core of this entire algorithm is to construct a block‐encoding of the Laplacian matrix. To achieve this, how to construct block‐encoding of operators containing the information of the weight matrix and the degree matrix, respectively are shown in detail, and the block‐encoding of the Laplacian matrix is further obtained. Compared with its classical counterpart, this algorithm has a polynomial speedup on the number of vertices and an exponential speedup on the dimension of each vertex. It is also shown that this algorithm can be extended to solve the eigenproblem of symmetric (non‐symmetric) normalized Laplacian matrix.
Automated high‐throughput characterization of microbial metabolites and species using array ballpoint electrospray ionization technique
Authors: Fu Xian , Wang Yu , Zhou Yan , Xia Bing
Published: April 2023

Rationale

Microbial metabolites are widely used in agriculture, food, environment, and medicine. However, there is a lack of high‐throughput, nonclogging, and simple methods for the identification of microbial metabolites and their subspecies using ambient mass spectrometry (MS). Here, we proposed a method for analyzing the microbial metabolites and identifying their species using the array ballpoint electrospray ionization (aBPESI) technique.

Methods

The previously developed BPESI was combined with the array analysis technique to form a high‐throughput analysis technique called aBPESI. The bacteria cultured on the plate medium were directly analyzed using MS with aBPESI. Principal component analysis–linear discriminant analysis (PCA‐LDA) algorithm was used to analyze the different subspecies groups.

Results

The results showed that aBPESI was capable of completing a sample analysis within 30 s, and the level of metabolite detection was comparable to existing techniques. The accuracy of bacterial subspecies identification was 90% (Pseudomonas aeruginosa) and 100% (Serratia marcescens).

Conclusions

A new high‐throughput and robust MS technique aBPESI was proposed. It does not require sample pretreatment and greatly reduces the sample analysis time. aBPESI shows a strong ability in microbial analysis and is expected to be further applied in other research fields.
Singular value decomposition based learning identification for linear time‐varying systems: From recursion to iteration
Authors: Song Fazhi , Li Li , Liu Yang , Dong Yue
Published: April 2023

System identification is a critical task in various engineering applications such as motion control, signal processing and robotics. In this article, the identification of linear time‐varying (LTV) systems that perform tasks repetitively over a finite‐time interval is investigated. Traditional LTV system identification typically adopts recursive algorithms in the time domain, which are incapable of tracking drastic‐varying parameters and are subject to estimation lag and numerical instability. To address these issues, this article proposes the utilization of an iteration axis in addition to the time axis for estimating repetitive time‐varying parameters. Specifically, the proposed approach involves an estimation algorithm for the time‐varying parameters based on a recursive least squares (RLS) method along the iteration axis, as well as an update algorithm for the covariance matrix based on singular value decomposition (SVD) to enhance numerical stability. Additionally, a bias compensation method based on noise variance estimation is introduced for the sake of eliminating estimation error induced by measurement noise. Numerical comparisons with existing methods are conducted to demonstrate the effectiveness and superiority of the proposed method.
Numerical analysis of the thermomechanical behavior of rubber concrete at high temperatures
Authors: Karim Serroukh Hamza , El Marzak Mounir , Benaicha Mouhcine , Li Wenlong , Zhu Jianguo , Hafidi Alaoui Adil
Published: April 2023

Insufficient research has been done on the mechanical and thermal properties of rubber concrete in the presence of fire. In this paper, we do detailed numerical modeling of the rubber concrete's thermomechanical behavior under dynamic conditions at high temperatures (800°C) using different percentages of rubber aggregate (0%, 10%, 20%, and 30%). The novelty of this work lies in its analysis of the temperature profiles over time in rubber concrete. This analysis is carried out using finite difference models developed with the MATLAB tool to predict thermomechanical parameters such as elastic modulus, thermal strain, tensile strength, and compressive strength. In addition, the dynamic behavior of the rubber concrete under impact loading was predicted, including stress and velocity change as a function of time at elevated temperatures. By the equations of motion and transient conduction, the mathematical model developed is based on density, thermal conductivity, heat capacity, and thermal expansion. The comparison between numerical and experimental results, and the analysis of the influence of the percentage of rubber aggregates on thermomechanical parameters, as well as the influence of temperature on the evolution of stress and velocity as a function of time, have shown the effectiveness of the mathematical and numerical model developed.
Recyclable thermally conductive poly(butylene adipate‐co‐terephthalate) composites prepared via forced infiltration
Authors: Li Chenglin , Han Yi , Du Qingyuan , Wu Daming , Sun Jingyao , Wang Zhao , Zhang Liqun
Published: April 2023

With the rapid development of electronic equipment and communication technology, the demand for polymer composites with high thermal conductivity and mechanical properties has increased significantly. However, its nondegradable polymer matrix will inevitably bring more and more serious environmental pollution. Therefore, it is urgent to develop biodegradable thermally conductive polymer composites. In this work, biodegradable poly(butylene adipate‐co‐terephthalate) (PBAT) is used as the matrix material, and vacuum‐assisted filtration technology is employed to prepare carbon nanotube (CNT) and cellulose nanocrystal (CNC) networks with high thermal conductivity. Then CNT–CNC/PBAT composites with high thermal conductivity and excellent mechanical properties are prepared by the ultrasonic‐assisted forced infiltration method. Both experiment and simulation methods are used to systematically investigate the thermally conductive and dissipation performances of the CNT–CNC/PBAT composites. Above all, a simple alcoholysis reaction is applied to realize the separation of the PBAT matrix and functional fillers without destroying the conductive network skeleton, which makes it possible for the recycling of thermally conductive polymer composites.
Introduction to the Silala River and its hydrology
Authors: Muñoz José F. , Suárez Francisco , Alcayaga Hernán , McRostie Virginia , Fernández Bonifacio
Published: April 2023

The Silala River basin is located in a remote area in the Andes Mountain range, where hydro‐meteorological and hydrogeological data are scarce. Consequently, the hydrological functioning of this river system was not well understood. Due to a dispute between Chile and Bolivia over the status and use of the waters of the Silala River, Chile requested the International Court of Justice to adjudge the Silala River system to be an international watercourse. To support the case, scientific studies were carried out in both countries to fill hydrological and hydrogeological knowledge gaps. This article reviews the Silala River basin topographic characterization, historical water use, and the dominant hydrological processes, and briefly summarizes an enhanced monitoring programme, reported in more detail elsewhere in this Special Issue. The longitudinal topographic profile and river slope show that Silala fluvial system is an exorheic watershed; waters from the Cajones and Orientals wetlands in Bolivia, the two headwater sources of the Silala fluvial system, naturally flow from Bolivia to Chile, demonstrating that the Silala River system is indeed an international watercourse. New hydro‐meteorological, hydrological and hydrogeological measurement stations were installed in both countries and provided improved process insights and spatiotemporal coverage within the basin. These new observations helped to populate hydraulic, hydrological, and hydrogeological models, aimed to improve understanding of the functioning of the system, including the effects of historical disturbance due to channelization of the Bolivian wetlands.

This article is categorized under:

Science of Water > Hydrological Processes

Human Water > Rights to Water