Graphene (G) can effectively enhance polymers’ and polymer composites’ electric, thermal, and mechanical properties. Nanofibrous mats have been demonstrated to significantly increase the interlaminar fracture toughness of composite laminates, hindering delamination and, consequently, making such materials safer and more sustainable thanks to increased service life. In the present paper, poly(ethylene oxide) (PEO), polycaprolactone (PCL), and Nylon 66 nanofibers, plain or reinforced with G, were integrated into epoxy-matrix Carbon Fiber Reinforced Polymers (CFRPs) to evaluate the effect of polymers and polymers + G on the laminate mechanical properties. The main aim of this work is to compare the reinforcing action of the different nanofibers  and to disclose the effect of G addition. The polymers were chosen considering their thermal properties and, consequently, their mechanism of action against delamination. PEO and PCL, displaying a low melting temperature, melt, and mix during the curing cycle, act via matrix toughening; in this context, they are also used as tools to deploy G specifically in the interlaminar region when melting and mixing with epoxy resin. The high extent of modification stems from an attempt to deploy it in the interlaminar layer, thus diluting further in the resin. In contrast, Nylon 66 does not melt and maintain the nanostructure, allowing laminate toughening via nanofiber bridging. The flexural properties of the nanomodifed CFRPs were determined via a three-point bending (3PB) test, while delamination behavior in Mode I and Mode II was carried out using Double Cantilever Beam (DCB) and End-Notched Flexture (ENF) tests, respectively. The lack of a positive contribution of G in this context is an interesting point to raise in the field of nanoreinforced CFRP. In th . In most , (ii) fl , and  . The fir ,8,9 or a , and the ,12,13, t ,15. In c ,17.Tg) [Nanofibers are versatile nanomaterials used in a wide range of applications, including filtration ,19, healTg) . ThermopTg) .Among nanomaterials, graphene (G) has also attracted great expectations since its discovery in 2004 . Indeed,2 capture [The small dimensions of GRMs allow them to nanomodify even micro- and nanofibers, enhancing thermal  and elec capture , wastewa capture ,58, and  capture .G was already used to modify the nanofibers. However, it is worth pointing out that the literature data on the mechanical properties of graphene-reinforced nanofibers are poor. In some cases, an improvement in the mat’s mechanical properties is reported, while in others, degradation seems to occur, mainly depending on the modification extension ,61,62,63While the integration of polymeric nanofibers for hindering delamination is well established and documented ,64, the Tgs, and low melting temperatures, Tms), allowing their mixing with the surrounding matrix during laminate curing; however, owing to the different chemistry, their relative affinity in the epoxy could be substantially different. In this way, upon dissolution of nanofibrous morphology, G can be released locally, possibly modifying the region where nanofibers are deployed. In this context, nanofibers will be loaded with an extremely high concentration of G in order to significantly reinforce the surrounding epoxy region. In contrast, polyamide has a higher Tm that prevents its melting and mixing with the resin during curing, enabling a different reinforcing mechanism at the laminate interface.The present work aims to evaluate the interlaminar fracture toughness of CFRP laminates modified with graphene-reinforced nanofibers using three different thermoplastic polymers as substrates: PEO, PCL, and Nylon 66. These polymers display essential differences, as well as some similarities. PCL and PEO have comparable thermal properties  (PCL), Mw 70,000–90,000 g/mol, were purchased from Sigma-Aldrich . Nylon 66 (Zytel E53 NC010) was kindly provided by DuPont . Chloroform (CHCl3), acetone, N,N-dimethylformamide (DMF), and formic acid were purchased from Sigma-Aldrich. Polymers and solvents were used without any preliminary treatment.Poly(ethylene oxide) (PEO), M2) in epoxy matrix prepreg (GG204P IMP503Z-HT) for composite lamination was supplied by G. Angeloni s.r.l. .Plain weave carbon fabric .The solutions containing G were prepared with the same polymeric concentration and solvent system as the G-free ones. However, before adding the polymer, the G dispersion underwent sonication. After a coarse G dispersion in a sonication bath , a more vigorous one was carried out using a tip sonicator , as follows: amplitude of 30%, on-off cycles of 5-1 s, 45 min of actual sonication). After that, half of the polymer amount was added to the G dispersion and then stirred at 60 °C until its dissolution. Then, the low-concentrated solution underwent further sonication using the same parameters, except for the amplitude, which was raised to 38%. Finally, the last polymer fraction was added, stirred, and sonicated, as described for the first polymer fraction addition.The nanofibrous mats were produced using an electrospinning machine  equipped with four 5 mL syringes joined via Teflon tubing to translate needles . A rotating drum  covered with polyethylene-coated paper was used as a collector.The electrospinning process was conducted in an air-conditioned room, with 22–23 °C and relative humidity (RH) ranging from 22 to 25%. The selected process parameters and the nanofiber’s diameter evaluation are reported in 2 pressure on five different mat regions.Mats have final dimensions of 20 × 40 cm; the electrospinning process was carried out until reaching a mat thickness of 40 ± 4 μm, measured with an analog indicator , under 360 g/mThe nanofibers’ morphology was evaluated by scanning electron microscopy , recording the images at 10 kV. All analyzed surfaces were previously gold-coated using a Quorum SC7626 sputter coater  to make them conductive. Average diameter values were calculated from at least 100 measurements, manually done on single nanofibers using the Photoshop measurement tool.cχ) was calculated according to the well-known Equation (1):cχ calculation, the following The thermal properties of the nanofibrous mats were evaluated via differential scanning calorimetry . Samples of 6–8 mg were heated/cooled at 20 °C/min under a nitrogen atmosphere. The degree of crystallinity  and End-Notched Flexure (ENF) tests were fabricated stacking 14 prepreg plies, interleaving a nanofibrous mat in the central interface, using a Teflon film as crack trigger. Specimens for the three-point bending (3PB) test were produced by stacking 10 prepreg plies, and the nanofibrous mat was inserted between all interfaces. In addition to the nanomodified specimens, unmodified ones were also produced for the sake of comparison. Details of the DCB, ENF, and 3PB specimens are listed in Mechanical tests were carried out using a universal testing machine  equipped with a 100 N load cell for DCB tests and a 1 kN load cell for DCB and ENF tests.I, in J/m2), both at the initial and propagation stages , was evaluated using Equation (2), according to ASTM D5528-01 [P is the load, δ is the crosshead displacement, a is the crack length, and b is the specimen width. The GRI, was evaluated considering a crack length range of 47–90 mm.DCB and ENF tests were carried out at 3.0 and 2.0 mm/min crosshead separation rates, respectively. The energy release rate for Mode I loading (GD5528-01 :(2)GI=3PII, in J/m2), both at the initial and propagation stages , was evaluated using Equation (3), according to BS EN 6034:2015 [L is the span length between supports. ENF tests were carried out with a 100 mm span (L) between supports, and the specimen was placed in a 3-point bending geometry as follows: 50 mm specimen half-span (L/2) and 30 mm delamination length (a0). The GRII, was evaluated considering a crack length range of 31–43 mm.The energy release rate for Mode II loading (G034:2015 :(3)GII=93PB tests were carried out setting a span of 85 mm (span-to-specimen thickness ratio 32:1) and with a 2.0 mm/min crosshead separation rate, according to ASTM D790.For each sample/test combination, three repetitions were run.After the DCB tests, delamination surfaces for investigating the matrix behavior were evaluated via SEM microscopy .Polymeric nanofibers containing G were prepared by suspending G in solvent systems suitable for polymer solubilization and subsequently adding the polymer stepwise . AnalogoG surely modifies the electrical conductivity of the polymeric solutions, thus affecting their interaction with the applied electrostatic field during electrospinning processing. Generally, if the other process parameters are maintained unchanged, such as flow rate, voltage, and needle-to-collector distance, the net effect is a diameter reduction. However, especially at such a high G percentage, the solution viscosity may also increase, making the polymeric jet less prone to be stretched by the electrostatic field. The resulting overall effect on the fiber diameter derives from these two contrasting phenomena . Here, dTm ≈ 60 °C) and mixing with the resin during the curing cycle, requiring a higher energy input for crack propagation. The polyamide, however, cannot melt and mix during composite curing due to its melting temperature (Tm = 265 °C), which is higher than the typical temperatures (120–140 °C) set for curing high-performance epoxy laminates. In this case, the 3D nanofibrous network is still present in the cured laminate, enabling composite toughening via so-called nanofiber bridging. Additionally, the net effect is increased interlaminar fracture toughness.In the present comparative work, the selected polymers displayed similarities and differences among them. The polyether PEO and the polyester PCL had almost the same thermal properties, as assessed via DSC analysis , but difTg and Tm, c), which was comparable to unreinforced nanofibers. PEO nanofibers represent an exception; the G addition further promoted slight crystallinity development (χc = 87% instead of 83%). Conversely, a decrease in χc was previously observed for similar Nylon 66 nanofibers with the same G amount [It was previously demonstrated that carbon nano-reinforcements could affect the thermal behavior of thermoplastics . Here, tG amount . In the observed .The laminates’ mechanical properties were evaluated using the 3PB test . The oriTm PEO and PCL might also promote G spreading within the surrounding epoxy matrix. In contrast, the high-Tm polyamide cannot transfer G as the other two thermoplastics. In this case, however, the G sheets protruding from the nanofibers may improve the nanofiber–resin interaction thanks to the augmented exposed surface area and a possible anchoring mechanism similar to the action of barbed wire. Delamination resistance was evaluated in Mode I and Mode II via DCB and ENF tests, respectively. As anticipated, the polymers selected for nanofiber fabrication may lead to different interlaminar reinforcing mechanisms: so-called nanofiber bridging and matrix toughening. In addition to mixing with the surrounding epoxy resin, the low-(1)A high average load with frequent drops (DCB_PEO and DCB_PEO + G samples);(2)A medium average load with frequent drops (DCB_NY sample);(3)A medium average load with rare drops (DCB_PCL);(4)A low average load with even rarer drops (DCB_Ref and DCB_PCL + G);(5)A very low average load with very frequent and low drops (DCB_NY + G).Load-displacement curves D represeR-curves , but it did not further enhance the performance of the PEO-only nanofiber-modified CFRP. In fact, graphene lowers GI, especially GCI,. This behavior is general; the other two nanofiber types display a similar trend. While PCL and Nylon 66 unreinforced nanofibers enable a delamination hindering, in line with the literature data [I. The DCB_NY + G sample displayed the worst performance, showing an almost halved GI. This laminate displayed completely different behavior with respect to one of the DCB_NY samples; the load-displacement curve was characterized by frequent and small drops, which may indicate a low adhesion between the nanofibers and the matrix, as already found when polyaramid nanofibers (Nomex) were integrated [The curves of both PEO-modified laminates were positioned at significantly higher loads with respect to the unmodified laminate, hinting that crack advancement required higher loads. The R-curves E derivedDCB_PEO, . Adding ure data ,64,72,73tegrated , and/or I reduction by one-third. As in the case of the DCB_NY + G sample, graphene led to a lowering in the gap between the maximum loads (peaks) and the minimum loads achieved just after crack propagation. Moreover, such behavior is extremely amplified in the case of the DCB_PCL + G laminate. Indeed, the delamination of the DCB_PCL sample occurred with only three crack advancements . The other samples behaved as unmodified laminates, or even slightly worse, such as ENF_PEO + G and ENF_PCL + G. The modification with Nylon 66 nanofibers, with and without graphene, did not lead to any GII variation.The effect on GII  was moreSEM images recorded on DCB delamination surfaces confirmed PEO and PCL melting, in addition to maintaining Nylon 66 nanofibers upon the curing cycle. The aspect of fractured surfaces also supported the ability of both low melting thermoplastics (PEO and PCL) to toughen the epoxy resin, highlighting a rougher surface aspect typical of plastic deformation phenomena occurring during crack propagation. No trace of residual nanofibrous morphology can be retrieved from the SEM investigation. Conversely, NY and NY + G laminates both still display reminiscence of the nanofibrous mat persistence clearly appearing within the plastic resin bulk, supporting the fact that the electrospun membrane is well soaked with the epoxy resin during curing. In none of the analyzed G-containing samples , it is pIn the present work, highly G-loaded nanofibers based on different polymers were produced with the aim of using them as reinforcing agents in CFRP laminates. The polymers were chosen considering their thermal properties and, consequently, their mechanism of action against delamination. PEO and PCL, displaying a low melting temperature, melt and mix during the curing cycle; they are used as tools to deploy G specifically in the interlaminar region, with the aim of imparting interlaminar strength via matrix toughening, while Nylon 66 does not melt and maintain the nanostructure, acting via nanofiber bridging. The high extent of modification stems from the attempt to deploy G in the interlaminar layer, which will be diluted further when mixing with the surrounding epoxy resin. In all cases, the flexural properties of the nanomodifed CFRPs, determined via three-point bending (3PB) tests, showed results consistent with the plain CFRP, demonstrating that the nanofibrous approach is not detrimental to overall mechanical performance. While the plain nanofibers made of the same polymers all showed positive results in terms of interlaminar fracture reinforcement, the present unfortunate results demonstrate that the addition of graphene is not relevant, if not even detrimental, in some cases, in terms of interlaminar fracture toughness. It seems that the ability to spread G in specific regions via dissolution of the polymeric nanofibrous carrier during the curing process of the epoxy resin does not contribute further to the potential of hindering delamination. Nor can better results be achieved with the use of G-modified NY nanofibers that, though acting at reinforcing the polymer via bridging action, still do not contribute any further than the plain unmodified fibers to the ability to contrast the delamination phenomenon. It has, however, to be pointed out that thermal and electrical conductivity evaluations are still underway. Indeed, G is known to impart many interesting functionalities, often all at once. Hence, the lack of mechanical performance is not necessarily a fully negative result in light of a more general properties enhancement for overall composite performance.


Dopamine regulates emotional behaviors, including rewarding and aversive behaviors, through the mesolimbic dopaminergic pathway, which projects dopamine neurons from the ventral tegmental area to the nucleus accumbens (NAc). Protein phosphorylation is critical for intracellular signaling pathways and physiological functions, which are regulated by neurotransmitters in the brain. Previous studies have demonstrated that dopamine stimulated the phosphorylation of intracellular substrates, such as receptors, ion channels, and transcription factors, to regulate neuronal excitability and synaptic plasticity through dopamine receptors. We also established a novel database called KANPHOS that provides information on phosphorylation signals downstream of monoamines identified by our kinase substrate screening methods, including dopamine, in addition to those reported in the literature. Recent advances in proteomics techniques have enabled us to clarify the mechanisms through which dopamine controls rewarding and aversive behaviors through signal pathways in the NAc. In this review, we discuss the intracellular phosphorylation signals regulated by dopamine in these two emotional behaviors. Dopamine was discovered as a neurotransmitter in the brain by Dr. Arvid Carlsson in 1957 ,3,4,5. DThere are several dopaminergic pathways in the brain. Two major pathways are the nigrostriatal pathway and mesolimbic pathway, which project dopamine neurons from the substantia nigra to the dorsal striatum, and from the ventral tegmental area (VTA) to the ventral striatum, including the nucleus accumbens (NAc). Nigrostriatal dopamine neurons play an important role in motor functions, and their dysfunction causes Parkinson’s disease . AccumulClassical conditioning is a kind of simple reward-associated learning . ExtraceIn contrast with the phasic firing response of VTA dopamine neurons to rewarding stimuli, their reactions to aversive stimuli are not homologous. The firing of some VTA dopamine neurons is activated, whereas the others are transiently suppressed. The inactivation of VTA dopamine neurons elicited by the optogenetic inhibition of dopamine neurons  or the aDopamine exerts its function through dopamine receptors, which are a class of G-protein-coupled receptors. There are five types of dopamine receptors: D1–5. D1 and D5 are coupled to Gs, the stimulation of which increases the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP) through adenylate cyclase (AC), thereby activating cAMP-dependent protein kinase (PKA). On the other hand, D2, D3, and D4 are coupled to Gi, the activation of which results in the inhibition of the cAMP/PKA signaling pathway . TherefoIn the NAc, approximately 95% of neurons are medium spiny neurons (MSN) receiving dopaminergic regulation from the VTA ,27. TherD1R is coupled to Gs, the stimulation of which activates PKA to trigger D1R-MSN. On the other hand, D2R is coupled to Gi, the activation of which results in the inhibition of the cAMP/PKA signaling pathway and, in turn, the suppression of D2R-MSN. D2R has a markedly higher affinity for dopamine than D1R , and theRewarding and aversive behaviors in rodents are monitored by conditioned place preference (CPP) and passive avoidance tests, respectively. The inhibition of PKA in the NAc blocks amphetamine-induced place preference  and its The PKA-dependent phosphorylation of receptors, ion channels, transcription factors, and other proteins accounts for the structural and functional plasticity regulated by dopamine  Figure . Dr. PauAMPA-type and NMDA-type glutamate receptors are abundantly expressed in the striatum, which is involved in synaptic plasticity ,48. The 2+ is involved in the phosphorylation of CREB. They also showed that cross-talk between PKA and Ca2+ accounted for complex intracellular signaling. Furthermore, CREB activity in D1R-expressing neurons is shown to regulate cocaine-induced place preference [Cyclic AMP response element (CRE) binding protein (CREB) is a transcription factor that is activated by the phosphorylation of Ser133, and it mediates the expression of genes that shape the structure and function of neurons ,56,57. Aeference , indicatBesides CREB, dopamine receptors control gene expression through numerous transcription factors ,62,63 anThe endogenous cannabinoid system has been implicated in reward seeking. Endogenous cannabinoids mediate long-term depression and evoke drug (cocaine and ethanol) and natural reward (saccharin)-seeking behaviors . 2-ArachRibosomal protein S6 (rpS6) is a component of the small 40S ribosomal subunit implicated in mRNA decoding . rpS6 isMajor efforts have been made to identify the target substrates of PKA so as to understand the modes of action of dopamine, and a few of its substrates, including DARPP-32, GluA1, and NR1, have been reported. The PKA-mediated phosphorylation of DARPP-32 indirectly accumulates phosphoproteins through the inhibition of protein phosphatase PP1. However, it remains unclear about the proteins directly phosphorylated by PKA. To identify the PKA substrates that are responsible for the function of dopamine, a Kinase-Oriented Substrate Screening (KiOSS) method, a novel comprehensive phosphoproteomic analysis, has been developed. More than 100 novel PKA substrates downstream of dopamine were identified, including Rasgrp2 and Rap1gap ,85. RasgA previous study demonstrated that Rap1 activated B-raf, resulting in the activation of MAP2K, followed by MAPK1/3 . The actK+ channels of the Kcnq/Kv7 family are proteins that span the cell membrane and, when open, allow the outward flow of K+ ions across the membrane . In the To further identify the MAPK substrates involved in regulating the expression of the genes that account for dopamine functions, Funahashi et al. performed a proteomic analysis using affinity beads coated with CREB-binding protein (CBP), a transcriptional coactivator associated with rewarding behavior . More thhttps://www.phosphosite.org/homeAction.action (accessed on 2 September 2022)), there are approximately 500 protein kinases encoded by the human genome, and the kinases that are directly responsible for these phosphorylation sites currently remain unknown. To overcome this issue, we developed the kinase-interacting substrate screening (KISS) method to isolate substrates by affinity purification with the responsible kinase and to analyze the substrates that interact with the kinase by liquid chromatography tandem mass spectrometry [https://kanphos.neuroinf.jp (accessed on 6 September 2022)). The KANPHOS database allows users to not only search for substrates phosphorylated by a specific kinase, but to also search for kinases phosphorylating a specific protein or to search for kinases and their target substrates involved in a specific signaling pathway.As described above, protein phosphorylation plays important roles in a number of intracellular signaling pathways and physiological functions that are regulated by neurotransmitters in the brain. Although more than 280,000 phosphorylation sites have been identified and are registered in databases such as PhosphoSitePlus , dopamine agonists , and drugs that block dopamine metabolism  are commonly prescribed to treat Parkinson’s disease ,101. TheAlthough the locations of the target receptors of these drugs in the brain have been extensively examined, the underlying mechanisms and the sites at which these drugs act at the cellular and molecular levels remain largely unknown, which has been a major obstacle to the development of new therapeutic drugs. Recent advances in intracellular signaling analyses are expected to overcome these issues. For example, we demonstrated that a D1R agonist activated PKA and induced the phosphorylation of Rasgrp2/Rap1gap in D1R-MSN. A D2R antagonist activated PKA and induced Rasgrp2/Rap1gap phosphorylation in D2R-MSN. Furthermore, the D2R antagonist-induced activation of PKA and Rasgrp2/Rap1gap phosphorylation was suppressed by pretreatment with an A2AR antagonist ,42. The As protein phosphorylation is critical for intracellular signaling pathways and physiological functions that are regulated by neurotransmitters in the brain, researchers have continued the search for kinase substrates in order to elucidate the molecular mechanisms underlying brain functions. Dr. Paul Greengard was the first to examine PKA substrates in various brain regions, and found that DARPP-32 amplified the effects of PKA downstream of dopamine, which gained him the Nobel Prize for Medicine in 2000. We recently focused on the screening of phosphorylation signals downstream of dopamine and shared the information obtained in the newly-established KANPHOS database, which may be freely accessed.According to previous studies and our KANPHOS data, the stimulation of D1R by dopamine increases intracellular cAMP concentrations through AC, and this is followed by the activation of PKA. PKA phosphorylates Rasgrp2 and Rap1gap to induce the activation of Rap1, which promotes the MAPK pathway. MAPK phosphorylates Kcnq2 to increase membrane excitability. MAPK also phosphorylates Npas4 and MKL2 to facilitate the gene expression, accounting for synaptic plasticity regulated by dopamine. The stimulation of A2AR without the inhibition of D2R also increases intracellular cAMP concentrations through AC, and this is followed by the activation of PKA. The activation of Rap1 induces the MAPK pathway to regulate synaptic plasticity. The stimulation of M1R induces the activation of PKC, and this is followed by the phosphorylation of Kcnq2, which accounts for the increased membrane excitability. Therefore, phosphorylation signals downstream of D1R are involved in D1R-MSN-mediated rewarding behavior, and phosphorylation signals downstream of A2AR and M1R without the inhibition of D2R are involved in D2R-MSN-mediated aversive behavior .Although we focused on conditioned place preference and passive avoidance behaviors as emotional behaviors in this review, there are other different rewarding and aversive stimuli  that affect intracellular signaling ,115,116.


Local health departments (LHDs) in the United States are charged with preventing disease and promoting health in their respective communities. Understanding and addressing what supports LHD's need to foster a climate and culture supportive of evidence-based decision making (EBDM) processes can enhance delivery of effective practices and services.We employed a stepped-wedge trial design to test staggered delivery of implementation supports in 12 LHDs  to expand capacity for EBDM processes. The intervention was an in-person training in EBDM and continued support by the research team over 24 months (March 2018–February 2020). We used a mixed-methods approach to evaluate: (1) individuals' EBDM skills, (2) organizational supports for EBDM, and (3) administered evidence-based interventions. LHD staff completed a quantitative survey at 4 time points measuring their EBDM skills, organizational supports, and evidence-based interventions. We selected 4 LHDs with high contact and engagement during the intervention period to interview staff (n = 17) about facilitators and barriers to EBDM. We used mixed-effects linear regression to examine quantitative survey outcomes. Interviews were transcribed verbatim and coded through a dual independent process.p < 0.05) and climate cultivation  but improved over time among all participants. Interviewees noted staff turnover, limited time, resources and momentum as challenges to continue EBDM work. Setting expectations, programmatic reviews, and pre-existing practices were seen as facilitators.Overall, 519 LHD staff were eligible and invited to complete quantitative surveys during control periods and 593 during intervention . A total of 434 completed during control and 492 during intervention . In both trial modes, half the participants had at least a master's degree (49.7–51.7%) and most were female (82.1–83.8%). No significant intervention effects were found in EBDM skills or in implementing evidence-based interventions. Two organizational supports scores decreased in intervention vs. control periods: awareness  may disrupt LHDs' abilities to fully embed organizational processes which support EBDM. This study and related literature provides understanding on how best to support LHDs in building capacity to use and sustain evidence-based practices. Local health departments (LHDs) serve as an important frontline for chronic disease prevention in the complex US public health system , 2. BecaProviding training on EBDM to health department staff has been documented as an important and effective strategy to boost staff competency among the workforce and influence organizational practices –11. PrevIn 2018, the Adoption & Implementation of evidence to Mobilize Local Health  trial began and we recruited 12 LHDs in Missouri with the goal of understanding how training and ongoing support and technical assistance could aid LHDs and their unique context in improving capacity to use EBDM, especially with regard to chronic disease prevention. We report qualitative interview findings from LHD staff participants and quantitative survey results which are, to our knowledge, the first to feature a mixed-method, stepped-wedge cluster randomized trial with LHD as the cluster.This study reports results from phase 2 of a two-phase dissemination trial, grounded in Diffusion of Innovation Theory  and InstThis study used an open cohort stepped-wedge design with groups of clusters (LHDs) that crossed over to intervention at various intervals. Each cohort of participants included newly recruited and previously recruited individual participants within clusters , 23. In Previous work demonstrated capacity building within health departments to be highly nuanced to each individual organization because of differing resources , 24. As Eight to 9 weeks after receiving the pre-intervention survey, the intervention group received a 3.5-day, in-person EBPH training led by the research team. The EBPH training was modeled from previously successful workshops to enhance EBDM within local and state health departments , 26. DidIntroduction and overview of EBPH,Assessing and engaging communities,Quantifying the issue,Developing a concise statement of the issue,Searching and summarizing the scientific literature,Developing and prioritizing intervention options,Developing an action plan and building a logic model,Understanding and using economic evaluation,Evaluating the program or policy, andCommunicating and disseminating evidence to local policymakers.evidencebasedpublichealth.org and in previously published evaluation work . Participants were invited via email and reminded by both email and phone to boost response. Surveys were timed with group cross-over in order to collect control measures before each intervention period. We worked with LHDs to identify individuals to replace participants who were no longer at their respective organization (open cohort design) as shown in Tables 3, 4). Importance and availability of each skill was assessed on an 11-point ordered scale. Participants selected from a list of eight evidence-based programs or policies related to chronic disease prevention which were currently implemented at their respective LHD. Twenty-two survey items assessed organizational culture supportive of EBDM processes on a 7-point Likert scale (1 = strongly disagree to 7 = strongly agree). The survey also assessed participant characteristics such as education level, length of employment in public health and at their current agency, gender identity, age, race and ethnicity. The full survey is available in Constructs assessed with the quantitative survey include three main areas of trial outcomes. First was competency for EBDM. Ten skills were assessed and align closely with objectives from the EBPH training that each LHD received . We selected four of the 12 LHDs based on trial randomization group, intervention adoption information, and raw change in outcome measures from baseline to final time point . SelectiThe semi-structured interview guide, based on the team's previous work , 28, askDescriptive statistics for participant and LHD characteristics and main outcomes were compared across trial mode, or intervention and control groups. We calculated gaps in each skill for EBDM by subtracting availability from importance Likert rating (possible range of −10 to +10). An overall skill gap was created by taking the average across all 10 skill items. We summed all 8 possible EBIs to calculate an “EBI score” which had a possible range of 0–8. For organizational culture items, we grouped and averaged Likert items within six main focus areas based on previous work: awareness of culture supportive of EBDM, capacity and expectations for EBDM, resource availability, evaluation capacity, EBDM climate cultivation, and partnerships to support EBDM . A confiEach phone interview was audio-recorded, transcribed verbatim by rev.com, and de-identified. A deductive coding approach was used to analyze interview data. Two coauthors  developed and refined a codebook. Co-authors  independently coded 20% of the transcripts in NVIVO 12 qualitative software and then met to reach consensus (agreement above 95% and Kappa of at least 0.70) on discrepancies and finalize the coding before one co-author (SK) coded the remaining transcripts . The codOverall, 519 LHD staff were eligible and invited to complete quantitative surveys during control periods and 593 during intervention . A total of 434 completed during control and 492 during intervention resulting in 83.6 and 83.0% response, respectively. For each time period, the LHDs averaged 23.2 eligible staff (range 8.5–65.8) and 19.3 staff (range 8.3–46.8) which completed surveys. Of all participants , most weMean skill gaps in EBDM  were similar for both control and intervention trial modes  . Mean skp < 0.05). Two organizational culture support for EBDM factor scores were significantly reduced for intervention: EBDM awareness  and climate cultivation . At the final collection (time 4), significantly larger factor scores were found in awareness , EBDM capacity and expectations , evaluation capacity , and climate cultivation  compared to the first time point.After accounting for clustering by LHD and repeated response in mixed-effects linear models, we found no significant time or intervention effect with regard to EBDM skill gaps . No net A total of 17 interviews were conducted with LHD staff in the trial, representing 4 of the 12 LHDs. Of those interviewed, most were white (71.0%), mostly non-Hispanic (94.0%) and worked an average of 6.7 years at their current agency. Several themes emerged from interviews with LHD staff participants.introduce new staff to what that [EBDM] is and our processes and what we do.” Incorporating EBDM into job descriptions and performance reviews to introduced a level of accountability to “continually working on that [EBDM].” Agency level plans included strategic planning that included EBDM and including EBDM into performance management systems and community health improvement plan development. Also helpful to support EBDM within LHDs was the incorporation of programmatic reviews to align programs with LHD priorities, find evidence-based approaches, compare programs with EBDM process, and enhance or initiate program evaluation. In working with partners, LHDs provided staff time to support partner EBDM use and also facilitated use of EBDM through the CHIP process. Management practices put in place to apply for or maintain PHAB accreditation also helped to support EBDM implementation and served as a “driver” to continue EBDM practices.Management practices, or the way in which various mechanisms within LHDs operate to either challenge or support EBDM including leadership, organization culture, workforce development, agency/system planning, program reviews, partnerships, and accreditation processes/status were facilitators of EBDM processes within LHDs . Leaderswe'll get going for a little while... we'll have some turnover or something will happen where we have to shift our focus and then it can be difficult sometimes sort of going back and saying, okay, how can we get, how can we keep that momentum going?” Staff turnover also makes it hard to keep enough staff trained in EBDM, “our health department had a whole bunch of people that went through the EBDM training, but most of them have left now…But if there was an opportunity to continue offering the EBDM trainings, just because of that staff turnover, that would be one resource that would be amazing.” Time to develop and implement EBDM practices was challenging as one participant described because “in public health agencies, there's never going to be enough time.” The participant stated that LHDs should “start small and just keep moving forward.” Another participant described how implementing EBDM processes after the training “took a backseat because it did take time and effort and staffing in order to develop a plan, continue training, implement it, evaluate, et cetera.” In terms of needing additional support, participants wanted more concrete examples and continued technical assistance that was more formalized. According to one participant, when the research team did “…provide us with really concrete steps or examples, that was really helpful. So for example, some of the website structure that actually had the list of evidence-based programs that we could then kind of replicate here. Or walking us through how to do a logic model. The evaluation series that they offered us, the online trainings that were made available, those were super helpful. So really just kind of that, that concrete examples and technical assistance is helpful.”Despite management practices that were described as facilitators, several challenges to EBDM processes were also discussed by LHD staff . Staff tOverall, our mixed methods study highlights the challenge of complex interventions and their implementation with heterogeneous organizations. While the quantitative outcomes were not significantly improved in our analysis, the qualitative data highlight challenges and future directions for continued efforts in building EBDM capacity.We found no intervention effect on skills for EBDM. In a similar randomized control trial with 12 state health departments, Brownson et al.  found siTrial mode was associated with significant reductions in organizational culture factor items including awareness, evaluation capacity, and climate cultivation for EBDM. Brownson et al.  found ththe momentum going” on work to change management policy and/or practices. However, strong and determined leadership may be resilient in the face of turnover and limited resources, as was found in our study and in several other studies exploring supports for evidence-based processes . The pandemic response was another reason we did not conduct interviews with more LHDs. Our purposive sampling approach allowed the research team to obtain rich contextual information from LHDs with mid- to high levels of participation while also minimizing disrupting or burdening all 12 LHDs during a demanding period addressing the COVID−19 pandemic in their communities. It is possible that key participants were uninvolved in the last part of our intervention period. Finally, the stepped-wedge design has several practical limitations that are trade-offs for robustness such as data collection intensity and burden, but allows for all 12 LHDs to be in the intervention group. For example, each participant received four surveys within the 26 month trial period. Staff may have been unable to respond, and therefore, we potentially missed their perspective.LHDs are unique in that they represent the frontline of chronic disease prevention, localized with the ability to engage the communities they serve in evidence-based programs and policies. Our study and related literature serve in understanding how best to build capacity within LHDs to support EBDM processes. LHDs can facilitate integration of EBDM into day-to-day public health practice through leadership support, by fostering a supportive organizational climate and culture, and by embedding EBDM steps into internal written plans, policies, and standardized procedures. Future directions should focus on sustained partnerships that keep LHDs in the driver's seat and give consideration for known challenges .The datasets analyzed during the current study are available from the corresponding author upon reasonable request.The studies involving human participants were reviewed and approved by Washington University in St. Louis Institutional Review Board (#201705026 and #202010031). The Ethics Committee waived the requirement of written informed consent for participation.RP led intervention planning and implementation, quantitative and qualitative data collection, and data management. PA assisted with intervention planning and implementation, quantitative data collection, and qualitative data analysis. RB led the study conceptualization and design and assisted with intervention planning and implementation. YY assisted with study design, data analysis, and statistical support. RJ assisted with data management and led data analysis and manuscript development. SK supported both quantitative and qualitative data collection and coding and analysis. DD assisted with survey tool development, recruitment, and interpretation of results. SM supported quantitative data analyses. All authors contributed to manuscript development and approved the final version.This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health , the National Cancer Institute (Award No. P50CA244431), the Centers for Disease Control and Prevention (Award No. U48DP006395), and the Foundation for Barnes-Jewish Hospital.The findings and conclusions in this article are those of the authors and do not necessarily represent the official positions of the National Institutes of Health or the Centers for Disease Control and Prevention.SK was employed by RAND Corporation. DD was employed by National Association of County and City Health Officials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Momordica charantia  extract were examined for their potential application as an effective wound dressing. Metallic nanoparticles have a wide range of applications in biomedical engineering because of their excellent antibacterial properties; however, metallic NPs have some toxic effects as well. The green synthesis of nanoparticles is undergoing development with the goal of avoiding toxicity. The aim of adding Momordica charantia extract was to reduce the toxic effects of copper oxide nanoparticles as well as to impart antioxidant properties to electrospun nanofibers. Weight ratios of PVA and MC extract were kept constant while the concentration of copper oxide was optimized to obtain good antibacterial properties with reduced toxicity. Samples were characterized for their morphological properties, chemical interactions, crystalline structures, elemental analyses, antibacterial activity, cell adhesion, and toxicity. All samples were found to have uniform morphology without any bead formation, while an increase in diameters was observed as the CuO concentration was increased in nanofibers. All samples exhibited antibacterial properties; however, the sample with CuO concentration of 0.6% exhibited better antibacterial activity. It was also observed that nanofibrous mats exhibited excellent cytocompatibility with fibroblast (NIH3T3) cells. The mechanical properties of nanofibers were slightly improved due to the addition of nanoparticles. By considering the excellent results of nanofibrous mats, they can therefore be recommended for wound dressing applications.Antibacterial and cyto-compatible tricomponent composite electrospun nanofibers comprised of polyvinyl alcohol (PVA), copper II oxide nanoparticles (CuONPs), and  Polyvinyl alcohol (PVA) is a nontoxic, biocompatible synthetic polymer. It is a colorless, odorless, water soluble polymer with good mechanical and thermal properties. The high versatility of its properties makes it suitable for many applications. For example, due to its biocompatibility and nontoxicity, it is a suitable polymer for biomedical applications. It has been already successfully used for the replacement of cartilage, contact lenses, wound dressing, etc. . ExtensiMomordica charantia (MC), commonly known as bitter gourd, is a well-known vegetable and abundantly found in Asia and Africa. It is famous for its medicinal characteristics and used for curing of different diseases such as diabetes, cancer, ulcers, HIV, and viral infections [Wound healing in the case of diabetic patients is always a challenge. To overcome this challenge, many researchers have offered their efforts. fections .MC has potential application in the biomedical field. Its application has been reported in wound care and the synthesis of silver nanoparticles . It alsoElectrospinning is easy, versatile, and is the finest spinning technique to fabricate smooth nanofibers with an excellent morphology. Both natural and synthetic polymers can be used to fabricate the nanofiber mats for several applications ,23,24,25w/w). Therefore, current research is comprised of CuO nanoparticles supported by natural extract (Momordica charantia), which itself is a weak antibacterial agent; however, it is expected that the addition of MC extract will improve the cytocompatibility of CuO nanoparticles and will enhance their significance for biomedical and environmental applications. MC extract is also antibacterial, but it has a lack of mechanical strength, which is expected to be improved by CuO nanoparticles, as metallic nanoparticles tend to impart tensile strength to composites.Copper nanoparticles have excellent antimicrobial activity, antibacterial properties, and good mechanical and thermal stability which make it suitable for the healing of second degree burn wounds and breath masks . Copper Momordica charantia (MC) was purchased from Xi’an Qingzhi Biotechnology Co. . Nano-size powder of copper (II) oxide (<50 nm particle size), to be used as an antibacterial substance, was purchased from Sigma-Aldrich Corporation . Pure water and any additional necessary accessories were sourced from a chemical synthesis laboratory.Polyvinyl alcohol (PVA) in the form of a polymer having a molecular weight in the range of 80,000–120,000, was purchased from Sigma Aldrich Corporation . The water soluble extract of w/w) in distilled water and stirred for 24 h (until a fully homogeneous solution was formed). Next, CuO was added in varying concentrations of 0, 0.2, 0.4, and 0.6 wt.% in spinning solution before electrospinning. The spinning solution was then electrospun to get nanofibers. The electrospinning solution was loaded into a plastic syringe, and the spinning conditions were as follows: the applied voltage was 15 kV, the tip to collector distance was 150 mm, the solution supply speed was 0.5 mL/h, the temperature was 20–25 °C, and the humidity was 55%. The operating parameters of electrospinning were kept the same for all samples. The electrospinning parameters were set according to our previous studies [Electrospun nanofibers of PVA nanofibers were fabricated as detailed in our recent study . PVA and studies ,38,39 anThe morphology analysis of all fabricated PVA/MC and PVA/MC/CuO nanofibers was conducted using a scanning electron microscope . Before studying the nanofibers’ morphology, the nanofibers were sputter-coated with platinum to make them conductive. A diameter of 50 random fibers from SEM by using Image-J software were calculated to analyze the average fiber diameter.The elemental mapping, focusing on Cu, was analyzed using an energy dispersive X-ray analyzer  integrated with a scanning electron microscopy (SEM).The presence of CuO nanoparticles inside the produced nanofibers was confirmed using a transmission electron microscope (TEM), JEOL 2010 Fas TEM, Tokyo, Japan, which was accelerated with 200 kV. The samples were prepared by taking fibers from random places in the nanofibrous sheet. After that, a thin layer of fibers was placed onto the TEM-specific copper grids to take the TEM micrographs.−1 to 4000 cm−1 in total internal reflection measurement (ATR) mode and in the case of FTIR the range was kept from 400 cm−1 to 4000 cm−1.FTIR spectroscopy was used to investigate the molecular structure and any possible interaction between the PVA/MC and PVA/MC/CuO composites. Fourier transform infrared spectrophotometer  with different wave measurement ranges from 500 cmThe air permeability of the prepared nanofibrous webs was measured using an air permeability tester . Samples with a measurement of 2 × 2 cm were placed into the claws and air was run at a speed of 2 cm/s. The resistance of the webs against air was used to calculate air permeation of the samples. The moisture vapor transport rate (MVTR) for the same samples was measured using the upright cup method (A-2) for breathability measurement. The samples were placed in a chamber at 40 °C and a relative humidity of 50% for a period of 24 h. The weight difference was used to calculate the amount of water transported through the nanofibrous mats.Mechanical strength is an important factor for examining the toughness and practical characteristics of nanofibers. The mechanical performances of the prepared samples of PVA/MC and PVA/MC/CuO were evaluated with a tensile test using a Tensilon universal material tester . Four samples for each individual model were prepared following the ISO 13634 standard, and the experiment was performed at room temperature (25 °C ± 3 °C). The sample was pulled at a rate of 1 mm/min. The available UTM data was used to calculate stress and strain. The stress–strain curves were created and compared.cA is the → control’s absorbance and sA is the sample’s absorbance.The antioxidant activity of the samples was measured by using a free radical of 2, 2-diphenyl minus 1-picryl hydroxyl (DPPH). A 100 mg sample was immersed in a 0.1 mM DPPH and methanol solution and incubated without light for 2 h under temperature control at 37 °C. In addition, a DPPH solution containing no sample was prepared as a control for comparison. The absorbance of the sample incubated at the above time was measured at 517 nm with a UV-Vis spectrophotometer (Jasco V-670). Antioxidant activity is expressed as a formula given below ,41. It wE. Coli  and B. Subtilis  were investigated with the disk diffusion method and the antibacterial properties were evaluated. First, both E. coli and B. Subtilis were shake-cultured for 24 h. Both of the cultured bacteria samples were diluted with phosphate buffer 1.0 × 108. A 100 µL sample of the bacterial solution, prepared as CFU/mL, was placed in a petri dish, 15 mL of agar medium was added, and the mixture was stirred and dried. Then, a sterilized sample disk (diameter: 10 mm) was prepared. The cells were placed into agar medium and cultured at 37 °C for 24 h. After that, by using the following Equation (2), with the diameter of the transparent circle (blocking circle) that blocked the growth of bacteria formed around the disc as C and the diameter of the sample disc as D, each sample became bacterial. The range of inhibition of reproduction (inhibition area I) was analyzed and the antibacterial properties were evaluated.Testing of the antibacterial properties of the prepared NF was carried out according to AATCC 147-1998, and the inhibition areas of 2 atmosphere. The nanofiber mats were sterilized with a 70% ethanol solution and later washed with PBS. The sterilized mats were placed into a 96 well plate. The 96 wells culture plate was reduced to 60 wells by leaving the corner and edge wells blank to avoid the unnecessary evaporation of the media as the incubation time was prolonged (7 days). The well without mats were considered to be the control. The wells were seeded with 1000 cells/well in 200 µL of growth medium. The seeded wells were cultured for 1, 3, 5, and 7 days. At each of the time points , 10 µL of WST-1 was added to the corresponding well and further incubated for 2 h at 37 °C. The metabolically active NIH 3T3 cells were reacted with WST-1 reagent and produced formazan dye which was quantified at 450 nm using a microplate reader . The cell viability was calculated as according to Equation (3). The measurement was performed 3 times.The in vitro cell proliferation was determined by utilizing a WST-1 colorimetric assay. NIH 3T3 mouse fibroblast cells were cultured in Dulbecco’s modified eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS) using a humidified incubator at 37 °C in a 5% COcontrolAbs is a comparative well that does not include a sample.Here, w/w) are shown in SEM images of all fabricated nanofiber samples with increasing ratios of CuO until 0.6%  is the characteristic peak of the –OH hydroxyl group. Overall, these are the characteristic peaks of PVA confirmed in all nanofibers. The peaks around 1500 cm−1 to 1600 cm−1 are peaks characteristic of C=C expansion and the contraction of the benzene ring of the bitter gourd component. This peak was also confirmed in all nanofibers. From these results, it can be confirmed that both MC and PVA components can be synthesized in the produced nanofibers.The peak around 2900 cmIn the literature it is reported that the mechanical properties of the skin vary in strength in the range of 0.1 to 32 MPa and the strain ratio at fracture point varies in the range of 0.42 to 2.26 ,44. Ther2/day, with a decreasing trend as the amount of CuONPs increased. The decrease in air permeability and MVTR may be due to the addition of CuO, as the presence of CuO may block the pores among nanofibers. When the concentration of CuO was kept to a lower level (to prevent toxic effects), the change in AP and MVTR was also negligible.Air permeability is an important parameter, along with moisture vapor transport rate (MVTR), to assess the performance of wound dressing. Escherichia coli and Gram-positive Bacillus subtilis using the disk diffusion method [Bacillus subtilis in this study on the basis that both Escherichia coli and Bacillus subtilis are among the major bacteria that exist in the living environment. Pictures were taken and Image J software was used to calculate the zone of inhibition. The antibacterial properties of the prepared PVA/MC and PVA/MC/CuO nanofibers were observed by testing the antibacterial activity against Gram-negative n method ,39,45,46Bacillus subtilis bacteria as compared to that of Gram-negative Escherichia coli. The main reason for this difference is the different cell wall structure of both types of bacteria. A similar trend of antibacterial activity for both types of bacteria was also observed in previous studies [B. Sub) bacteria, respectively, and 1.37 mm, 2.24 mm, 2.74 mm, and 2.98 mm for Gram-negative (E. coli) respectively. studies ,25,38,47Momordica charantia as an antibacterial agent, it was observed that nanofibers were good in cytocompatibility while weakly antibacterial [Momordica charantia extract. It can be observed by the results of the cytocompatibility test that all these nanofibrous mats were found to be non-toxic.A WST-1 assay was used to assess cell proliferation and the results of the cell viability measurement are shown in acterial . ConsideMomordica charantia, it can be observed that this study provides better cyto-compatible and antibacterial scaffolds, having cell proliferation above 100% when compared to that of the control. Antibacterial activity was also improved against both types of bacteria (E. Coli and B. Subtilis). Taking into account all of the results, it can be concluded that prepared scaffolds may be used as an effective antibacterial wound dressing.PVA/MC nanofibers were successfully electrospun with varying concentrations of CuO in nanofibers. The ensile strength of PVA/MC nanofibers was 5.82 MPa, and the maximum stress of nanofibers carrying 0.4 wt.% CuO was considerably improved to 7.93 MPa. The addition of CuO nanoparticles gave strength to the PVA/MC nanofibers. However, it was a slight increase and when considering the standard deviation, it can be concluded that the addition of nanoparticles caused a very small strength gain. PVA/MC/CuO nanofibers also exhibited uniformity in morphological properties (bead-free nanofibers). The synthesized nanofibers incorporating CuO nanoparticles at a concentration of 0.6 wt.% were superior to other samples in wound dressing. Prepared nanofibers also offered outstanding properties in regard to cell compatibility and antioxidant/antibacterial activity. Comparing the results of previous studies using CuO nanoparticles and


Osteoporotic vertebral compression fracture (OVCF) accompanying huge spinal epidural hematoma (SEH) is fairly rare. The aim of this report is to investigate the management strategies and treatment outcomes of OVCF accompanying SEH.An 89-year-old female patient was admitted to hospital because of severe back pain and numbness of both lower limbs after a slight fall. The magnetic resonance imaging examination of the patient showed a fresh compression fracture at L2 accompanying a large dorsal SEH which extended from the T12 to L3 and deformed the spinal cord.The patient was diagnosed with OVCF accompanying SEH.Given mild neurologic deficits, the hematoma was not treated, and the patient underwent percutaneous vertebroplasty (PVP) only.After the procedure, immediate pain relief was achieved and the numbness of both lower limbs disappeared 3 days later. Three months after the procedure, the follow-up magnetic resonance imaging revealed a complete resolution of the hematoma.OVCF accompanying SEH is fairly rare, and the exact pathophysiological mechanisms are still not clear. In selected patients without or with only slight neurologic symptoms, it is reasonable to perform PVP alone in OVCF accompanying SEH. Moreover, intravertebral stability after PVP might have played a role in spontaneous resolution of SEH. Moreover, most patients suffering acute painful OVCF can be treated with conservative medical therapy. But in an elderly patient cohort with established osteoporosis and severe pain, many patients fail to achieve adequate pain relief and forward progress is stagnant, with serious complications and prolonged recovery.,4In recent years, percutaneous vertebroplasty (PVP) has been widely used to treat painful, osteoporotic vertebral compression fractures (OVCF). For OVCF with spinal canal compromise caused by retropulsion of fractured bone fragments, recent reports have suggested that PVP can be performed safely.,6 However, there are no detailed case reports concerning the management strategies and treatment outcomes of OVCF accompanying SEH, which is a fairly rare cause of spinal canal compromise. In this paper, we assess PVP of symptomatic OVCF with SEH and to systematically review the previously reported cases in the literature.Prior studies have often excluded patients with spinal canal compromise secondary to various etiologies, including spinal epidural hematoma (SEH), from receiving PVP for fear of further spinal canal compromise.2An 89-year-old woman presented at our emergency department after a slight fall several hours earlier. She complained of severe back pain and numbness of both lower limbs. Physical examination revealed the muscle power of 4 limbs were normal and decreased sensation to pin-prick and light touch below L1 dermatomes. Reflexes were normal. No history of anticoagulant therapy was reported. The results of coagulation studies, including prothrombin time, partial thromboplastin time, and bleeding time, were normal. The magnetic resonance imaging examination showed a fresh compression fracture at L2 accompanying a well-defined ovoid lesion in the dorsal epidural region at T12–L3 level that caused compression of the spinal cord. The lesion was isointense signals of the spinal cord with a thin hyperintense signal at the peripheral rim on the T1-weighted images, and mixed signal intensity on the T2-weighted images . However, they did not describe the mechanism, treatment strategies, and prognosis of the SEH. We searched the literature in 4 electronic databases including PubMed (https://pubmed.ncbi.nlm.nih.gov/), EMBASE (https://www.embase.com), Scopus (https://www.scopus.com/home.uri), Web of Science (www.webofknowledge.com/), and ProQuest (https://www.proquest.com/) from January 1990 to December 2020, but only 4 articles on 4 cases were identified–12 . Kang et al reported a case of delay neurological deficit induced by dorasl SEH associated with thoracic OVCF. They concluded that the SEH resulted from the hemorrhage inside the intravertebral cleft. However, in our case, the pathophysiology of SEH seemed different. Our case developed severe low back pain and numbness of both lower limbs soon after a slight fall. The SEH were located posterior to the thecal sac, and the fracture type was fresh. Although little is known, mild trauma is highly associated with SEH in the current case. The veins in the epidural venous plexus which are vulnerable to rupture are the most likely source of SEH.SEH is associated with idiopathic, iatrogenic, traumatic, and coagulation diseases, and is relatively rare in clinical practice. The prognosis of SEH appears to be related to the severity of the preoperative neurological deficits and the time to intervention; early surgical treatment is crucial for good outcomes. However, some cases of spontaneous recovery after traumatic SEH have been reported. Although the exact mechanism underlying the spontaneous resolution of SEH is largely unknown, for patients without or with only slight neurologic symptoms, conservative treatment with watchful observation appears to be a safe therapeutic option. However, little is known about the management strategies of OVCF accompanying SEH. Kang et al performed emergent decompressive laminectomy due to the progressive motor weakness and paresthesia of both lower limbs. Kim et al reported a case of chronic SEH related to Kummell disease. They suspected that the continuous instability might have prevented the spontaneous resolution of hematoma. And the stabilization after successful PVP may have contributed to the spontaneous resolution of SEH. This finding was supported by Hirata et al. It is interesting to note that our case regarding the location of SEH and fracture type apparently diverge from those reported in the literature. Given mild neurologic deficits and intractable back pain, the SEH was not treated, and the patient underwent PVP only. However, immediate pain relief was achieved and the neurological symptoms were resolved soon after the PVP procedure. From the experience of the authors and review of the literature, it can be speculated that if the neurological symptoms is mild or normal, PVP alone may be an effective treatment for OVCF accompanying SEH. Moreover, intravertebral stability after PVP might aid in the spontaneous resolution of the hematoma over time. Further investigations are required to confirm our findings.Historically, the mainstay of traumatic SEH management was urgent surgical decompression and evacuation of the hematoma.In conclusion, OVCF accompanying SEH is fairly rare, and the exact pathophysiological mechanisms are still not clear. In selected patients without or with only slight neurologic symptoms, it is reasonable to perform PVP alone in OVCF accompanying SEH. Moreover, intravertebral stability after PVP might have played a role in spontaneous resolution of SEH.The study was supported by a grant from the “Young and Middle-aged Research Project of Fujian Provincial Health Commission of China, 2019-ZQN-86.”Conceptualization: Huafeng Wang, Fengfei Lin.Funding acquisition: Huafeng Wang, Fengfei Lin.Supervision: Fengfei Lin.Validation: Guiqing Liang, Yuhan Lin.Writing – original draft: Huafeng Wang.Writing – review & editing: Huafeng Wang, Fengfei Lin, Guiqing Liang, Yuhan Lin.


Feed molecular structure profile affects nutrient metabolism, utilization, and availability. Feed processing often induces feed internal structure change. These internal structure changes will affect animal nutrition. This study aimed to reveal the molecular structure features among chickpea varieties and detect the molecular structure changes induced by thermal processing methods. Our results show that with vibrational molecular spectroscopy, chickpea structure on a molecular basis was revealed in relation to ruminant nutrition.−1 with a 4 cm−1 resolution. Data were analyzed using the “Mixed” procedure of SAS 9.4. Multiple regression was performed with PROC REG analysis for variable selection. Results showed that amide I area was higher (p = 0.038) in CDC Frontier than CDC Cory (30.85 vs. 24.64 AU). Amide I peak height (p = 0.028) was also higher in CDC Frontier and CDC Alma (0.45 AU in both) than CDC Cory (0.36 AU). Cellulosic compound (CEC) to total CHO (TCHO) area ratio was higher in CDC Frontier (0.05 AU) than the other two varieties (0.14 AU in both). As to thermal treatment impact, the results showed that total amide area was higher (p = 0.013) with autoclave and microwave heating  than dry heating (33.06 AU). The CEC area was also higher (p < 0.001) for autoclave and microwave heating  than dry heating (2.20 AU). Moreover, the ratio of amide I to II height was higher (p = 0.022) with microwave heating than dry heating . Relationship analysis showed that the effective degraded crude protein (EDCP) and bypass dry matter (% BDM) were associated with STCHO peaks and CEC height . Also, feed milk value (FMVDVE) was associated with STC1, STC_A, and CEC_A . In conclusion, vibrational molecular spectroscopy mid-infrared FTIR was able to reveal different molecular spectral characteristics among the cool-season adapted CDC chickpea varieties and detect molecular structure changes induced by thermal processing .To our knowledge, there is no study on the relationship between molecular spectral features and nutrient availability in chickpeas. The purpose of this study was to reveal molecular structure spectral profiles among cool-season adapted CDC chickpea varieties and detect the molecular structure changes induced by thermal processing methods using vibrational Fourier-transform infrared (FTIR) spectroscopy. Three varieties of chickpea samples  were finely ground using a 0.12 mm screen. Spectral analyses were conducted using a JASCO FTIR-4200 spectroscope with Spectra Manager II software in the mid-infrared region from ca. 4000–800 cm Infrared (IR) spectroscopy has been successfully used as an analytical technique in organic chemistry since the 1940s. It has been widely applied in the analysis of chemical composition as a rapid and simple operation to determine multinutrient conformation in a nondestructive and nonpollutive manner .One common method based on IR analysis includes vibrational Fourier-transform infrared (FTIR) spectroscopy. This well-established experimental technique is used to study structural composition, stability, and conformational changes, such as the effects of temperature, pH, and pressure in feed materials . The mat−1. The amide I band is often used for protein structure analysis, as amide II usually overlaps other bands such as lignin at ca. 1515 cm−1 [−1. Cellulose is mainly characterized around ca 1170–1150, 1050, and 1030 cm−1 and hemicellulose could be found at ca. 1732 and 1240 cm−1 [Several chemical functional groups can be detected using FTIR spectroscopy. For instance, protein molecular structure is unique in its peptide bonds, which contain C=O, C–N, and N–H functional groups. Amide-related groups show energy absorbance peaks at around 1700–1500 cm240 cm−1 . Data obIt is well stablished that thermal treatments inactivate antinutritional factors in legume seeds and improve their nutritional value. Additionally, heat processing alters not only the physical but also the intrinsic structures of feeds by (1) disrupting the protein configuration, making it more susceptible to digestive enzymes, (2) disrupting starch crystallites and promoting starch chain interactions within amorphous and crystalline areas, and (3) affecting hydration properties of fiber and modifying its physical properties . As a reThe study of molecular structure characteristics of feedstuffs is hence important to stablish precise feeding techniques for ruminant systems. In our case, there is no systematic analysis on the relationship between molecular structure features of chickpeas and nutrient utilization and availability in ruminants. There is no study on the possible molecular structure changes induced by thermal processing in cool-season adapted chickpea varieties by using advanced vibrational molecular spectroscopy. Hence, the objectives of this study were to (1) study cool-season adapted CDC chickpeas molecular structure features and molecular structure changes induced by thermal processing and (2) reveal the association of molecular profiles with nutrient utilization and availability in ruminant systems. It was hypothesized that (1) the molecular intrinsic structure related to nutrient utilization and availability could significantly differ among CDC chickpea varieties and among thermal heat processing methods, and (2) there was an association between molecular structure features of chickpeas and nutrient utilization and availability in the ruminant system.All cows involved in the present study were cared for in accordance with the guidelines of the Canadian Council on Animal Care . The Ani1x) and energy values  for dairy and beef cattle [Chickpea samples from three different varieties were grown in western Canada. Samples were provided by the Crop Development Center . Three thermal processing methods  were also applied to each chickpea sample. The detailed growth conditions, sampling procedure, and size were reported previously. All samples  were analyzed for (1) chemical composition using AOAC  and Van f cattle ,13; (3) f cattle ; (4) rumf cattle ,16; (5) f cattle ; and (6)f cattle ,19,20 anf cattle ,13,21. Tf cattle . These n−1. Five spectra for each sample were obtained with a resolution of 4 cm−1 using the software JASCO Spectra Manager II [The FTIR analysis was performed using a JASCO-FTIR-4200 spectroscope  at the SRP Feed Research Chair Lab, Department of Animal and Poultry Science at the University of Saskatchewan . Molecular structure features of functional groups were analyzed in the mid-infrared region of ca. 4000–800 cmnager II ,5,23. To3 antisymmetric), ca. 2929 (CH2 antisymmetric), ca. 2877 (CH3 symmetric) or ca. 2848 cm−1 (CH2 asymmetric) [To detect responses and sensitivity of chemical functional groups to thermal processing methods and compare among varieties, various functional groups and ratios can be tested and analyzed. These functional groups include peaks centered at ca. 1740 (carbonyl C=O ester), ca. 1650 (amide I), ca. 1657 (α-helix), ca. 1630 (β-sheet), ca. 1550 (amide II), ca. 1515 (aromatic compounds of lignin), ca. 1428, ca. 1371 and ca. 1245 (cellulosic compounds), ca. 1025 , ca. 1246 , ca. 1160 (CHO), ca. 1150 (CHO), ca. 1080 (CHO), ca. 930 (CHO), ca. 860 (CHO), ca. 2960 (CHmmetric) .Multiple regression was performed to study molecular spectral features that could explain a variation in chemical profiles, protein and carbohydrate fractions, energy values, in situ rumen degradation, intestinal digestion, and truly absorbable nutrient supply. The detailed methods have been reported previously ,5,23.ijk = μ + Ti + S(Ti) + eijk, where Yijk is the observation of the dependent variable ijk; μ represents the population mean of the variable; Ti means the treatment effect as a fixed effect; and S(Ti) represents the subsample nested within treatments. In this case, five scans were made per sample, with eijk representing random errors associated with the observation ijk. The model assumption was tested using the univariate procedure for residual analysis with normal and plot options. All significant analyses were declared at p < 0.05 and trends at 0.05 < p ≤ 0.10. The treatments were compared by using Tukey’s comparison method.Carbohydrate- and protein-related molecular structure spectral data were analyzed using the “Mixed” procedure of SAS 9.4 . The model used for analysis was Y1 × x1 + b2 × x2 + … + bn × xn. Using STEPWISE for selection criteria: “SLENTRY = 0.05, SLSTAY = 0.05.” Collinearity tests were performed using VIF to eliminate the influence of correlated dependent variables. All variables kept in as predictors were significant at the alpha 0.05 level, and models with an R2 greater than 0.65 were selected to report in this study. Univariate procedures were used for residual analysis with normal and plot options.The associations between molecular structure spectral parameters and chemical composition, rumen degradation, intestinal digestion, and truly absorbable nutrient supply were analyzed using SAS 9.4. Multiple regression study was carried out using the PROC REG procedure. The following model was used: Y = a + bp < 0.05) were observed in the protein-related spectral profiles among three CDC chickpea varieties: CDC Alma, CDC Cory, and CDC Frontier (p < 0.05). No differences (p < 0.05) among the three varieties were observed for cellulosic compounds (CEC) or total carbohydrates (TCHO) related spectral profiles.In this study, significant differences (Frontier . CDC Frop < 0.001) in CDC Alma and CDC Frontier  than CDC Cory (0.29 AU). The CEC: TCHO area ratio was higher (p < 0.001) in CDC Frontier (0.05 AU) than CDC Alma and CDC Cory (0.04 AU for both). In a study from Sun et al. (2018) [Peak ratios of STCHO: TCHO area were higher (. (2018) , it was p = 0.013) when using autoclave and microwave heating  than dry heating (33.06 AU). Amide I peak height was higher (p = 0.028) in CDC Alma and CDC Frontier (0.45 AU for both) than CDC Cory (0.36 AU). This indicates that thermal processing induced changes in protein-related spectral profiles, but the sensitivity and response to each processing method differed among treatments. Moreover, the absorbance for STCHO area was higher (p = 0.014) with dry heat and microwave treatments. Conversely, CEC area was lower (p < 0.01) with dry heat (2.20 AU) than autoclave and microwave heating . These results also indicate that thermal processing induced changes in CHO-related molecular spectral profiles, but the sensitivity and response to each processing method differed among treatments.Molecular structure spectral characteristics of CDC chickpeas among thermal processing methods are presented in p = 0.022) with microwave than dry heat treatment (1.44 vs. 1.16 AU). No significant difference was observed in the other spectral peak ratios analyzed (p < 0.05).Results related to peak ratios showed that the height peak ratio of amide I to II was higher (p < 0.05) with molecular spectral variables related to STCHO peaks and CEC height (R2 = 0.68).The spectral studies showed that several important nutritional parameters could be predicted using protein- and carbohydrate-related molecular spectral features. In rumen degradation kinetics study, the results  showed tNDF, hemicellulose, and starch were highly associated (p < 0.05) with CEC_STC ratio (R2 > 0.63), followed by TC-related peak heights and STC1.In the chemical profile study , ADFNDF,p < 0.05) with spectral features of STC1, STC_A, and CEC_A (R2 between 0.65 and 0.85).In the chemical and nutrient profile and predicted protein supply studies , the nutThe results are in partial agreement with Sun et al. (2018) , where tThere is very limited published research on spectral features of chickpeas with which to compare our current findings. There is no systematic study on the relationship between molecular structure features of chickpeas and nutrient utilization and availability in ruminant system. There is no study on molecular structure changes induced by thermal processing in cool-season adapted CDC chickpea varieties revealed by advanced vibrational molecular spectroscopy either. Hence, this study provided an insight on specific molecular spectral features that might be associated with nutritional and digestive characteristics of CDC chickpeas.In this study, heating treatments did impact both nutritional and molecular structure profiles of CDC chickpeas. The response and sensitivity to each thermal processing differed among dry heating, autoclaving, and microwave treatments. This agrees with the effects observed when moisture, pressure, or dry heating is applied to improve the nutritive value of feeds by physical and molecular modifications. Rodriguez-Espinosa et al.  indicateDVE) was associated with three spectral variables of STC1, STC_A, and CEC_A , and absorbed rumen undegraded protein (ARUP) was associated with spectral variables of STC1, STC_A, and CEC_A . Total true protein supply (DVE) to dairy cows and total metabolizable protein (MP) were associated with three spectral variables of STC1, STC_A and CEC_A . The studies conducted by Xin et al. [Brassica carinata during microbial digestion, chemical profiles were used to correlate with structural change, which cannot reflect the utilization and digestion condition of the feed.In this study, rumen degradation kinetics, intestinal digestibility and true nutrient supply to dairy cows were highly associated with molecular structure features in chickpeas. For example, feed milk value  an et al.  showed tn et al. ,31 to co−1.Molecular spectral analysis is a useful method to associate with nutrient values. The spectral variable analysis showed that with molecular spectroscopic technique-FTIR, the true nutrient supply to dairy cows was associated with a few specific molecular spectral parameters in the vibrational mid-infrared region—ca. 4000–800 cmThese results show us the potential of the molecular spectroscopic technique of FTIR in using spectral parameters in the vibrational mid-infrared region to predict the nutrient supply in ruminant systems. The implication of this study is that feed nutritional value is not only related to total chemical composition but also inherent molecular structure. Future NRC models or any other feed evaluation systems could consider feed molecular structure features as an important part of developing modern and improved nutrition models.In conclusion, CDC Frontier and CDC Alma showed higher peak heights in protein-related profiles. However, CDC Alma, CDC Cory, and CDC Frontier tended to differ in peak area of cellulosic compound profiles. Area of protein-related molecular spectral profiles differed among dry heat, autoclave, and microwave treatments in amide I and amide II. STCHO peak heights were higher in the 1st and 3rd peaks for dry heat treatment. Greater values were observed in the CEC spectral area in autoclave and microwave treatments (average 3.65 AU) and lower absorbance in dry heat treatment with 2.20 AU. The peak height ratio in the amide I to II area was higher than in the microwave treatment.Vibrational molecular mid-infrared FTIR spectroscopy was able to reveal different molecular spectral characteristics among the cool-season adapted CDC chickpea varieties and detect molecular structure changes induced by thermal processing . There is an association between molecular structure spectral features of chickpeas and nutrient availability in ruminant systems.


Graph theoretical molecular descriptors alias topological indices are a convenient means for expressing in numerical form the chemical structure encoded in a molecular graph. The structure descriptors derived from molecular graphs are widely used in quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) studies. The reason for introducing new indices is to obtain predictions of target properties of considered molecules that are better than the predictions obtained using already known indices. In this paper, we apply the reduced reverse degree based indices introduced in 2021 by Vignesh et al. In the QSPR analysis, we first compute the reduced reverse degree based indices for a family of benzenoid hydrocarbon molecules and then we obtain the correlation with the Physico-chemical properties of the considered molecules. We show that all the properties taken into consideration for the benzenoid hydrocarbons can be very effectively predicted by the reduced reverse degree based indices. Also, we have compared the predictive capability of reduced reverse degree based topological descriptors against 16 existing degree based indices. Further, we compute the defined reduced reverse degree based topological indices for Hyaluronic Acid-Paclitaxel Conjugates  The most important part of the drug discovery process is finding and improving promising lead compounds as quickly and cheaply as possible. Drug design methodologies can be classified into two primary groups: ligand based and ligand-receptor interaction based approaches. Ligand based apporaches depend only on the structure of ligands. Ligand-receptor interaction based approaches are often referred to as structure-based methods .1 is a new approach used to design and select new molecules, particularly new pharmaceuticals. It uses topological factors rather than physical or geometric dimensions. Molecular topology not only provides an alternate method but also a different paradigm compared to conventional drug design methodologies. Molecular topology has proven to be useful in molecular design despite its inability to account for the physical or chemical properties of ligands and receptors or the ligand-receptor interaction. In drug development and design, molecular topology has been used to find new hits and leads. The discovery of novel lead compounds using molecular topology has enabled the interpretation of results in terms of their structural and physicochemical properties. The toxicity profile of a drug can be affected by its physicochemical properties, which are thought to play a role in its absorption, distribution, metabolism, and elimination. Physicochemical descriptors form the basis of most current approaches to molecular and drug design3. In this manner, a direct connection can be established between the experimental properties and chemical structures.The past decade has seen tremendous progress in computational approaches to drug design, and this has played a crucial part in the creation of several currently available medications. Molecular topology4. However, this critique may be answered by the fact that topology determines physical and geometrical magnitudes, a claim backed by both experimental and theoretical physicists. This results in molecular topology becoming a self-consistent and independent paradigm describing the molecular behavior. The results of molecular topology can be understood both in terms of structure and in terms of physicochemical characteristics This leads to both the mechanisms of action and the underlying physical chemistry to be deduced from the mathematical topological pattern. This is the most rational explanation, as it is the physical variable that is dependent on mathematics, not the other way around.A common critique of molecular topology, however, is that it functions like a “black box,” bypassing the mechanism of action that offers neither a physical explanation nor a chemical explanation of the processes8. Additionally, molecular topology has become more relevant recently in terms of novel or unexpected uses. For instance, Speck-Planche et al. developed the multi-scale de novo drug design paradigm, which provides instructions to create novel compounds with desirable drug-like properties9.Molecular topology is independent of physicochemical molecular descriptors. This fact explains why it is feasible to find new lead compounds using only the knowledge gleaned from mathematical-topological patterns and to interpret the findings in terms of their structural and physicochemical properties. Molecular Topology has transformed from a potential intriguing option to a cornerstone of the drug discovery process. One of them is Quantitative Structure Analysis Relationship (QSAR), which is still effective and common and is also coupled with machine learning1. Based on the parameterization type, the descriptors are sorted into distinct categories: geometric, quantum-chemical, electrostatic, constitutional, and topological10. Descriptors based on the molecular graph representation are widely used because they incorporate precious chemical information like size, degree of branching, neighbourhood of atoms, flexibility and overall shape. Molecular topological indices can be broken down into structure-explicit descriptors like quantum chemical ones and structure-implicit ones like hydrophobicity or electronic constants ones11. Incorporating ideas from molecular topology makes computing these indices straightforward. In fact, many physicochemical and biological properties can be quickly and accurately estimated using molecular topology12.In general, descriptors are classified into two types, namely, Experimental  and Theoretical  descriptors13 (QSAR) models is particularly important for the design of fine chemicals and pharmaceuticals that are made for a specific purpose. For Structure Activity Relationship (SAR) connections to be developed for medicinal compounds using computational or theoretical methods, accurate representations of molecular structure are essential. The molecular descriptor is the final outcome of applying a logical and mathematical procedure that enables the transformation of chemical information encoded in the symbolic representation of a molecule into a meaningful number.Based on the known features of existing pharmaceuticals, topological indices can be used to design new lead compounds. These medications have superior pharmacokinetic, pharmacodynamic and toxicological qualities compared to those already available. This can be accomplished at a very low computational cost and economic cost within a short period of time. Due to the need to reduce the costs associated with both the synthesis and clinical testing of pharmaceuticals, the pharmaceutical industry has contributed to the increased interest in molecular descriptors. The development of the predictive quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship14 model because they quantitatively represent the chemical information that is encoded. They allow researchers to delve into the mechanical aspects of a biochemical process and aid in uncovering the mathematical correlation that exists between chemical structure information and the response of interest. For instance, natural bio-polymer monomers (nucleotides and amino acids) can act as nodes in a graph, with the edges representing covalent bonds, hydrogen bridges, electrostatic interactions, and van der Waals bonds. As a result, the structure of complex biopolymers can be reduced to the topology of a graph, revealing useful information about these molecular systems. Topological indices can be used to characterize graphs that represent molecular systems. Topological indices store information about the connections between molecular atoms and the properties of those atoms. Natural biopolymers such as DNA, RNA, and protein sequences can also be characterized in this manner.Lead discovery and lead optimization are only two examples of how topological indices are put to use in the drug design and discovery process. Topological indices play an important part in the process of developing any QSPR or QSAR4. Traditionally it has been believed that topology is dependent on energy. This false assumption gave rise to the criticism that topological descriptors serve as a “black box” since they lack a physical interpretation. Now, if topology  is what determines energy  rather than the other way around, as advanced physicists and chemists claim, then mathematical descriptors can be used to predict the energy of any system along with other physical or experimental properties dependent on it. This is precisely what happens when novel active molecules are created or found utilising topological indices.Considering that a theoretical physics starting hypothesis was proved for the first time in experimental physics, the following result is pertinent15 studies rely heavily on molecular descriptors, many of which are based on topological indices.Quantitative structure-property relationship (QSPR) and Quantitative structure-activity relationship (QSAR)d(u)16.In a chemical graph, nodes represent atoms or molecules and the links denote the chemical bonding between the atoms or molecules. Graph theoretical molecular descriptors are topological indices. These are graph invariants that play an important role in pharmaceutical science, chemistry, materials science and engineering, etc. The value of a molecular descriptor is not dependent on the particular molecular representation, such as atom numbering or labeling. Molecules of hydrocarbons are modeled using the corresponding molecular graph. Here the vertices represent the carbon atoms and the edges represent the bonds between them. The degree of a vertex represents the number of edges that are incident on that vertex and it is denoted by i.e.), vertices of degree 2 or 318. In benzenoids, there are only 3 types of edges, (i.e.), ,  and  where the numbers in each tuple denote the degree of the end vertices of the corresponding edge. Twelve physico-chemical properties of benzenoid hydrocarbons have been selected based on the availability of data: Boiling Point (BP), Critical Temperature (CT), Critical Volume (CV), Critical Pressure (CP), Exact Mass, Heavy Atom Count, HL, GE, LogP, MR, PI and Molecular Weight (MW). The data for the benzenoid hydrocarbon molecules is presented in Table 19. The experimental values of boiling points were taken from Basak et al.20.Benzenoid hydrocarbons are represented through benzenoid graphs comprising of hexagons. Here there are only two types of vertices, , Critical Pressure (CP), Critical Temperature (CT), Critical Volume (CV), Exact Mass, Heavy Atom Count, HL, GE, LogP, MR, PI and Molecular Weight (MW). The experimental values of physico-chemical properties of benzenoid hydrocarbon molecules are given in Table In this section, we analyze the aforesaid reduced reverse degree based topological indices with respect to the following physico-chemical properties of the benzenoid hydrocarbon molecules: Boiling Point , Critical Pressure (CP) and LogP with corresponding CV), Exact Mass (EM), Heavy Atom Count (HAC), Molar Refraction (MR) and Molecular Weight (MW) with corresponding GE) with CT) with PI) with HL) with Hence the linear regression models for predicting Boiling Point (BP), Critical Pressure (CP), Critical Temperature (CT), Critical Volume (CV), Exact Mass, Heavy Atom Count, HL, GE, LogP, MR, PI and Molecular Weight (MW) are:Using Eq. , we obtamentclasspt{minimaentclass1pt{minimaBP is We obtain the predicted values for all properties using the proposed linear models and we summarize the results in Table Proposed regression model is a good fit.Proposed regression model is not a good fit.The hypotheses which we considered for checking the goodness of fit of the regression models are: The table value for goodness of fit  and LogP with corresponding CP), Critical Volume (CV), Exact Mass (EM), Heavy Atom Count (HAC), Molar Refraction (MR) and Molecular Weight (MW) with corresponding GE) with CT) with PI) with HL) with Among the quadratic models, we listed the best predictive models from Eqs. (BP), Critical Pressure (CP), Critical Temperature (CT), Critical Volume (CV), Exact Mass, Heavy Atom Count, HL, GE, LogP, MR, PI and Molecular Weight (MW) are:Using Eq. , we obtarom Eqs.  to 35)  \documenThe table value for the goodness of fit (From Table The quadratic models (second order) obtained by us are a good fit for predicting all the properties. Hence we stop with the quadratic regression models.Figures In this section, we present the comparison of our proposed indices against 16 well known degree based indices.23 and Hyper Zagreb  is predicted well by the index We formulated the linear regression models for the physico-chemical properties vis-a-vis these 16 degree based indices. Among these indices, we selected the best models based on the In Table Cancer is one of the leading factors of mortality in the world, and its fatality rate is on the rise, with breast, stomach, lung, and colon cancers responsible for the bulk of deaths. Although there have been significant advancements in cancer biology and treatments. There are still challenges in the treatment of primary and metastatic disease. Furthermore, present anticancer medications cause limited selectivity and significant toxicity, greatly restricting their usefulness. In recent years, there have been some advancements in molecularly targeted anticancer therapy.33. Because of its unique biodegradable, biocompatible, harmless, hydrophilic, and non-immutable properties, HA is a prospective cancer treatment compound; also, HA receptors are over-expressed on numerous tumour cells. HA intends to improve antitumor therapeutics by targeting CD44-overexpressing cells, which is a rapidly developing platform nowadays36. HA is an excellent medication transporter and target.37. Paclitaxel (PTX) is an effective medication that is prescribed for a variety of malignancies, notably ovarian, breast, lung, bladder, prostate, and esophageal tumors. Although PTX treatment has its own set of drawbacks, such as poor solubility and associated adverse effects, as well as the excipients commonly utilised in its formulation. The key benefits of HA-PTX conjugates include increased water solubility and activity retention, as well as the possibility of using it as a drug carrier to boost anti-tumor potency40. Figure 41 and Hyaluronic Acid-Paclitaxel conjugates44 have been proposed by researchers.Hyaluronic acid (HA) is a compound that occurs naturally. It is a glycosaminoglycan polymer composed of a linear structure of units of D-glucuronic acid and N-acetyl-D-glucosamine. These are linked via alternating There are still no reduced reverse degree based topological results on the molecular structures of HA-Paclitaxel conjugates. As a result of the immense pharmaceutical significance of HA-Paclitaxel conjugates, present study intends to investigate the reduced reverse degree based topological indices of the chemical structure of HA-Paclitaxel conjugates. Furthermore, these findings may serve as a theoretical base for pharmacological engineering.n and n.Figure Here we compute the reduced reverse degree based topological indices of If If If Applying the reduced reverse degree based edge partitions as given in Table In this article, novel topological descriptors QSPR study using curvilinear models reveals that both linear and quadratic regression models provide good estimates for the physico-chemical properties of the 26 Benzenoid Hydrocarbons. From quadratic regression models, we observe that our proposed indices have high correlation with all the physico-chemical properties considered in the above sections.BP, LogP.CP, CV, EM, HAC, MR and MW.GE.RRGA is best suited for predicting CT.RRABC is best suited for predicting PI.RRF is best suited for predicting HL.On comparing the proposed reduced reverse degree-based indices with the existing degree-based topological indices, we found that our proposed indices are well correlated with all the physico-chemical properties of 26 benzenoid hydrocarbons. The errors are significantly reduced for our proposed indices. This demonstrates the significance of the reduced reverse degree-based descriptors in predicting the physico-chemical properties of benzenoid hydrocarbons over the existing degree-based descriptors.The best models that predict the physico-chemical properties are as follows: The defined reduced reverse degree based topological indices have been determined for Hyaluronic Acid-Paclitaxel Conjugates In future, these indices can be applied to various transformations of graphs and to analyze different chemical networks.