ANN-GA optimized composite color protectant combined with magnetic field assisted freezing: Effects on the quality of mushroom (Agaricus bisporus).

Due to their high water content, frozen mushrooms (Agaricus bisporus) were greatly affected by ice crystal formation, which can lead to the destruction of tissue structure, serious browning, high juice loss, and difficulty in maintaining good sensory characteristics. In order to improve the quality of frozen Agaricus bisporus, this study employed Artificial neural network and genetic algorithm (ANN-GA) to optimize the amount of composite color protectant, and identified the optimal freezing conditions for freezing Agaricus bisporus by determining the freezing curves under different magnetic field-assisted freezing conditions, the color variance, texture and structure, drip loss, and distribution of moisture. Furthering, using X-ray µCT three dimensional images were taken to characterize the microstructure of the samples. Among them, the 6 mT magnetic field-assisted freezing treatment group was significantly better than the control group, and the results showed that the magnetic field-assisted freezing combined with chemical color protectant as a composite processing technology improved the quality of frozen Agaricus bisporus. This provides a theoretical basis and technical support for enhanced processing of frozen Agaricus bisporus.

Fine mapping of major QTL qshgd1 for spontaneous haploid genome doubling in maize (Zea mays L.).

KEY MESSAGE: A large-effect QTL was fine mapped, which revealed 79 gene models, with 10 promising candidate genes, along with a novel inversion. In commercial maize breeding, doubled haploid (DH) technology is arguably the most efficient resource for rapidly developing novel, completely homozygous lines. However, the DH strategy, using in vivo haploid induction, currently requires the use of mutagenic agents which can be not only hazardous, but laborious. This study focuses on an alternative approach to develop DH lines-spontaneous haploid genome duplication (SHGD) via naturally restored haploid male fertility (HMF). Inbred lines A427 and Wf9, the former with high HMF and the latter with low HMF, were selected to fine-map a large-effect QTL associated with SHGD-qshgd1. SHGD alleles were derived from A427, with novel haploid recombinant groups having varying levels of the A427 chromosomal region recovered. The chromosomal region of interest is composed of 45 megabases (Mb) of genetic information on chromosome 5. Significant differences between haploid recombinant groups for HMF were identified, signaling the possibility of mapping the QTL more closely. Due to suppression of recombination from the proximity of the centromere, and a newly discovered inversion region, the associated QTL was only confined to a 25 Mb region, within which only a single recombinant was observed among ca. 9,000 BC1 individuals. Nevertheless, 79 gene models were identified within this 25 Mb region. Additionally, 10 promising candidate genes, based on RNA-seq data, are described for future evaluation, while the narrowed down genome region is accessible for straightforward introgression into elite germplasm by BC methods.

Pilot Evaluation of Perioperative High Dose Rate Brachytherapy in Head Neck Cancers.

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

A mathematical model of competition between fiber and mucin degraders in the gut provides a possible explanation for mucus thinning.

The human gut microbiota relies on complex carbohydrates (glycans) for energy and growth, primarily dietary fiber and host-derived mucins. We introduce a mathematical model of a glycan generalist and a mucin specialist in a two-compartment chemostat model of the human colon. Our objective is to characterize the influence of dietary fiber and mucin supply on the abundance of mucin-degrading species within the gut ecosystem. Current mathematical gut reactor models that include the enzymatic degradation of glycans do not differentiate between glycan types and their degraders. The model we present distinguishes between a generalist that can degrade both dietary fiber and mucin, and a specialist species that can only degrade mucin. The integrity of the colonic mucus barrier is essential for overall human health and well-being, with the mucin specialist Akkermanisa muciniphila being associated with a healthy mucus layer. Competition, particularly between the specialist and generalists like Bacteroides thetaiotaomicron, may lead to mucus layer erosion, especially during periods of dietary fiber deprivation. Our model treats the colon as a gut reactor system, dividing it into two compartments that represent the lumen and the mucus of the gut, resulting in a complex system of ordinary differential equations with a large and uncertain parameter space. To understand the influence of model parameters on long-term behavior, we employ a random forest classifier, a supervised machine learning method. Additionally, a variance-based sensitivity analysis is utilized to determine the sensitivity of steady-state values to changes in model parameter inputs. By constructing this model, we can investigate the underlying mechanisms that control gut microbiota composition and function, free from confounding factors.

Modulation of starch structure, swallowability and digestibility of 3D-printed diabetic-friendly food for the elderly by dry heating.

Elderly people often experience difficulty in swallowing and have impaired regulation of the nervous system. Furthermore, their blood glucose level can rise easily after eating. Therefore, functional foods that are easy to swallow and can maintain blood glucose at a lower level have been an important research topic in recent years. In this study, 3D printing was combined with dry heating to modify the starch in white quinoa and brown rice to develop whole grain foods with Osmanthus flavor that meet the dietary habits of the elderly. The samples were tested for printability, swallowing performance, and in vitro digestion. The results showed that after dry heating, all samples had shear-thinning properties and could pass through the extrusion nozzle of the printer smoothly. Both white quinoa and brown rice showed improved printability and self-support compared to the control. B45 (white quinoa, dry heating for 45 min) and C45 (brown rice, dry heating for 45 min) had significant elasticity and greater internal interaction strength during swallowing to resist disintegration of food particles during chewing. B45, C30, and C45, conformed to class 4 consistency and were characterized by easy swallowing of the diet. Further, dry heating resulted in greater resistance to enzymatic degradation of white quinoa and brown rice starch, with overall in vitro digestibility lower than the control.

Improved intra-operative decision making in RA-TKR with the help of pre-operative CT scan.

Background: Robotic-assisted total knee replacement (RA-TKR) is a significant advancement in orthopedic surgery, but intra-operative decision-making remains challenging. Pre-operative imaging techniques, particularly CT scans, have gained momentum, providing insights into the patient's anatomy, improving implant positioning and alignment. However, further research is needed to explore their influence on RA-TKR planning and execution. Materials and methods: The hospital based cross-sectional study was conducted in Orthopedics department of Sparsh Speciality Hospital, Bangalore & Sunshine Hospital, Hyderabad. A total of 1020 participants in the age group over 50 years during the study period were included based on convenient sampling. The axial CT images were taken preoperatively and RA-TKA was done for all the patients. Results: The study participant's average age was 64.01 ± 7.13. Out of 1020 patients 259 (24.4%) were males and 761 (74.6%) were females. The median femoral, tibia and Polyethylene predicted and the actual component were same with the side of surgery and BMI. The median femoral predicted actual component was significantly higher among the age category of more than 80 years when compared to other age groups. The median femoral, tibia and Polyethylene predicted was higher in males when compared to females. Conclusion: Pre-operative CT scans enhance RA-TKR procedures by providing precise anatomical insights, enhancing implant placement, and identifying potential issues, improving surgical outcomes and patient satisfaction.

Cone-beam computed tomography (CBCT) dose optimization technique and image quality assessment scoring.

INTRODUCTION: Linear accelerator (LINAC) embedded with kV source-imager system is capable to do image-guided radiotherapy. The only disadvantage of cone-beam computed tomography image acquisition during treatment is the extra radiation dose to the patient. The aim of this study is to optimize the CBCT imaging doses likely to be received by the patient undergoing radiotherapy without affecting image quality. MATERIAL AND METHODS: The imaging dose to the patient was estimated on CTDI phantoms. The effect of additional filters of different materials (copper, brass, aluminum of thickness 0.1 mm each) was evaluated to find the optimized dose imaging technique. For the pelvis, a single imaging protocol available on the machine was used, whereas for the head and neck region, two protocols, high-quality head and standard-dose head were used. The image quality was assessed on CATPHAN-504 phantom using Owl CATPHAN® QA online tool. A new term "Image Assessment score" (IAS) was introduced to evaluate the image quality. RESULT: In the pelvis protocol, CBCT imaging doses with an additional 0.1-mm brass, copper, and aluminum filter were measured to be reduced by 7.1%, 4.7%, and 2.5%, respectively, whereas for high-quality head protocol, the dose reduction was 25.4% (with brass filter), 22% (with copper filter), and 3.1% (with aluminum filter). For the standard-dose head protocol, doses were reduced by 7.5%, 2.8%, and 2.1% with additional 0.1-mm brass copper and aluminum filters, respectively. Acceptable image quality was observed with all the filters. CONCLUSION: Although the reconstructed images were found somewhat noisier, they did not affect the purpose of imaging, that is, treatment position verification. It was observed that these extra filters further reduce the imaging dose without much affecting the image quality.

Challenges in commissioning the "TSET" technique: A new approach towards monitor unit calculation and beam profile measurements.

INTRODUCTION: Total skin electron beam therapy, commonly known as TSET, is a good choice of treatment for patients suffering from mycosis fungoides. The aim of this study was to introduce a new approach to the beam profile measurement using diodes and to calculate the monitor units required for the TSET treatment by the use of a simple setup of output measurement. Dosimetric measurements required for the treatment were taken to establish the Stanford technique in the department, and the measured data was compared with the published data. MATERIALS AND METHODS: High-energy Linear Accelerator Clinac-DHX, Varian medical system, Palo Alto, CA, was commissioned for TSET. The output of the machine was measured by the use of a Parallel-Plate Chamber (PPC40) as per the TRS 398 recommendation. Diode dosimeters (EDD2 and EDD5) were used for beam profile measurements due to easy setup and to reduce the measurement time. RESULTS: Homogeneous dose distribution within a field size of 80 cm x160 cm was observed with the variation of -5.0% on the horizontal axis and -5.4% on the vertical axis. The calculated monitor unit to deliver 200 cGy per fraction per field at the source to surface (SSD) of 416 cm was 489 MU. CONCLUSION: The technique described for the output measurements is simple and accurate. Results of the absorbed dose and MU measured were within good agreement compared to the published literature.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial.

Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Dramatic increase in antimicrobial resistance in ESKAPE clinical isolates over the 2010-2020 decade in India.

RATIONALE AND OBJECTIVES: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) constitute a threat to humans worldwide. India is now the most populous country. The goal was to investigate the evolution of the rates of antimicrobial resistance in ESKAPE pathogens across India over the 2010-20 decade. METHODS: The data (89 studies) were retrieved from the Medline PubMed repository using specific keywords. RESULTS: The study of 20 177 ESKAPE isolates showed that A. baumannii isolates were the most represented (35.9%, n = 7238), followed by P. aeruginosa (25.3%, n = 5113), K. pneumoniae (19.5%, n = 3934), S. aureus (16.3%, n = 3286), E. faecium (2.6%, n = 517) and Enterobacter spp. (0.4%, n = 89). A notable increase in the resistance rates to antimicrobial agents occurred over the 2010-20 decade. The most important levels of resistance were observed in 2016-20 for A. baumannii (90% of resistance to the amoxicillin-clavulanate combination) and K. pneumoniae (81.6% of resistance to gentamycin). The rise in ß-lactamase activities was correlated with an increase in the positivity of Gram-negative isolates for ß-lactamase genes. CONCLUSIONS: This review highlighted that, in contrast to developed countries that kept resistance levels under control, a considerable increase in resistance to various classes of antibiotics occurred in ESKAPE pathogens in India over the 2010-2020 decade.

3D/4D printed super reconstructed foods: Characteristics, research progress, and prospects.

Super reconstructed foods (SRFs) have characteristics beyond those of real system in terms of nutrition, texture, appearance, and other properties. As 3D/4D food printing technology continues to be improved in recent years, this layered manufacturing/additive manufacturing preparation technology based on food reconstruction has made it possible to continuously develop large-scale manufacture of SRFs. Compared with the traditional reconstructed foods, SRFs prepared using 3D/4D printing technologies are discussed comprehensively in this review. To meet the requirements of customers in terms of nutrition or other characteristics, multi-processing technologies are being combined with 3D/4D printing. Aspects of printing inks, product quality parameters, and recent progress in SRFs based on 3D/4D printing are assessed systematically and discussed critically. The potential for 3D/4D printed SRFs and the need for further research and developments in this area are presented and discussed critically. In addition to the natural materials which were initially suitable for 3D/4D printing, other derivative components have already been applied, which include hydrogels, polysaccharide-based materials, protein-based materials, and smart materials with distinctive characteristics. SRFs based on 3D/4D printing can retain the characteristics of deconstruction and reconstruction while also exhibiting quality parameters beyond those of the original material systems, such as variable rheological properties, on-demand texture, essential printability, improved microstructure, improved nutrition, and more appealing appearance. SRFs with 3D/4D printing are already widely used in foods such as simulated foods, staple foods, fermented foods, foods for people with special dietary needs, and foods made from food processingbyproducts.

Inequalities in life expectancy and cardiometabolic disease mortality across and within high-income countries.

Cardiometabolic disease is a leading cause of death and plays a key role in recent life expectancy trends worldwide. We highlight inequalities in cardiometabolic disease mortality across sex, race/ethnicity, geographic region, and urbanicity within the United States, as well as across high-income countries.

Antibiotic resistance: a global crisis, problems and solutions.

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir.

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents which potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into Phase 2a clinical trials. Previous cell culture based viral breakthrough assays identified the HIV-1(Y99H/A128T IN) variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. While both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCDY99H/A128T + PIR complex. Consequently, full-length INY99H/A128T was substantially less susceptible to the PIR induced hyper-multimerization than the WT protein, and HIV-1(Y99H/A128T IN) conferred >150-fold resistance to the inhibitor compared to the WT virus. By rationally modifying PIR we have developed its analog EKC110, which readily induced hyper-multimerization of INY99H/A128T in vitro and was ~14-fold more potent against HIV-1(Y99H/A128T IN) than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.

A High-Efficiency Radio-Frequency-Assisted Hot-Air Drying Method for the Production of Restructured Bitter Melon and Apple Chips.

Nowadays, consumers are increasingly demanding processed food products with high levels of beneficial components. Bitter melon and apple are both nutritious foods rich in bioactive compounds. In this study, restructured bitter melon and apple chips were processed using four drying techniques: hot-air drying with/without exhaust air recirculation (EAR), and radio-frequency-assisted hot-air drying (RFHAD) with/without EAR. The drying characteristics, effective moisture diffusivity (Deff), specific energy consumption (SEC), total energy consumption (TEC), and some selected quality characteristics of the dehydrated chips were evaluated. The experimental results show that the application of radio frequency (RF) energy significantly facilitates water evaporation in the drying material, resulting in a significant (p < 0.05) reduction of drying duration by 31~39% over the experimental test parameters. The higher Deff values obtained from RFHAD and RFHAD + EAR were 6.062 × 10-9 to 6.889 × 10-9 m2/s, while lower SEC values ranged from 301.57 to 328.79 kW·h/kg. Furthermore, the dried products possessed better or fairly good quality (such as a lower color difference of 5.41~6.52, a lower shrinkage ratio of 18.24~19.13%, better antioxidant capacity, higher chlorophyll, total flavonoid, and total phenolic content, a lower polyphenol oxidase activity of 49.82~52.04 U·min-1g-1, smaller diameter and thickness changes, and a lower hardness of 27.75~30.48 N) compared to those of hot-air-dried chips. The combination of RF-assisted air drying and partial recirculating of dryer exhaust air achieved the highest saving in TEC of about 12.4%, along with a lower moisture absorption capacity and no deterioration of product quality attributes. This drying concept is therefore recommended for the industrial drying of several food materials.

Single-atom catalysts supported on a hybrid structure of boron nitride/graphene for efficient nitrogen fixation via synergistic interfacial interactions.

Hexagonal boron nitride (BN) shows significant chemical stability and promising thermal nitrogen reduction reaction (NRR) activity but suffers from low conductivity in electrolysis with a wide band gap. To overcome this problem, two-dimensional (2D) BN and graphene (G) are designed as a heterostructure, namely BN/G. According to density functional theory (DFT), the higher conductivity of G narrows the band gap of BN by inducing some electronic states near the Fermi energy level (Ef). Once transition metals (TMs) are anchored in the BN/G structure as single atom catalysts (SACs), the NRR activity improves as the inert BN basal layer activates with moderate *NH2 binding energy and further the band gap is reduced to zero. V (vanadium) and W (tungsten) SACs exhibit the best performance with limiting potentials of -0.22 and -0.41 V, respectively. This study helps in understanding the improvement of the NRR activity of BN, providing physical insights into the adsorbate-TM interaction.

Construction of photocatalytic coating for alleviating the shriveling of postharvest fruit cucumber after simulated transportation.

The shriveling of fruit cucumber was commonly occurred during supply chain, photocatalyst exposed to UV light can endow the coatings with ethylene removal capacity to reduce the respiration of fruit and water loss. The study developed a novel photodynamic technology responsive photocatalytic coating with exceptional ultraviolet (UV) photocatalytic degradation of ethylene ability to decay the shriveling of postharvest fruit cucumber during supply chain. This coating involved the integration of Carbon dots (CDs)-loaded nano ZnO and the skillful selection of pullulan (Pul) and apple pectin (AP) matrix. The CDs/ZnO coatings boasted an impressive array of photocatalytic degradation of ethylene and adhesion properties, including high ethylene removal rates of 32.04 % in 60 min UV light stimulation. The decrease of cell-wall strength, degradation of the cell wall polysaccharides and water loss resulted in cucumber shriveling. Compared with CK sample, after UV-CDs/ZnO coating treatment, the higher firmness and cell wall polysaccharides were found in cucumbers with lower cell wall degrading enzymes activities, weight loss and water movement, which was associated with the decrease of respiration and ethylene accumulation. The UV-CDs/ZnO coatings possessed promising potential for alleviating the shriveling of postharvest fruit cucumber and applications in fruits preservation in the future.

Macroscopic resting-state brain dynamics are best described by linear models.

It is typically assumed that large networks of neurons exhibit a large repertoire of nonlinear behaviours. Here we challenge this assumption by leveraging mathematical models derived from measurements of local field potentials via intracranial electroencephalography and of whole-brain blood-oxygen-level-dependent brain activity via functional magnetic resonance imaging. We used state-of-the-art linear and nonlinear families of models to describe spontaneous resting-state activity of 700 participants in the Human Connectome Project and 122 participants in the Restoring Active Memory project. We found that linear autoregressive models provide the best fit across both data types and three performance metrics: predictive power, computational complexity and the extent of the residual dynamics unexplained by the model. To explain this observation, we show that microscopic nonlinear dynamics can be counteracted or masked by four factors associated with macroscopic dynamics: averaging over space and over time, which are inherent to aggregated macroscopic brain activity, and observation noise and limited data samples, which stem from technological limitations. We therefore argue that easier-to-interpret linear models can faithfully describe macroscopic brain dynamics during resting-state conditions.

Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.