This review aims to point out the importance of the synergic effects of two relevant and appealing polymeric issues: electrospun fibers and shape-memory properties. The attention is focused specifically on the design and processing of electrospun polymeric fibers with shape-memory capabilities and their potential application fields. It is shown that this field needs to be explored more from both scientific and industrial points of view; however, very promising results have been obtained up to now in the biomedical field and also as sensors and actuators and in electronics. Shape-memory polymers (SMPs) are an emerging class of smart materials that have been widely studied since the 1980s and are capable of recovering their initial shape from a temporary shape through the application of external stimuli: light, temperature, pH, magnetism, electricity, or moisture ,3,4, as However, the shape-memory behavior is not an intrinsic characteristic but can be achieved by designing the molecular structure of the polymer and by setting both the programming and the recovering stages that are generally required in order to fix the temporary shape and to recover the original shape of the polymer, respectively . In partDifferent transitions may be used to establish the temporary shape, including crystallization/melting transitions, vitrification/glass transitions, liquid crystal anisotropic/isotropic transitions, reversible molecule cross-linking, and supramolecular association/disassociation  Figure . trans), which can initiate some of the transformations mentioned above. One of the most-used temperatures is the glass transition temperature (Tg), at which the materials turn from a rigid state to a soft state. This phenomenon occurs due to the increased mobility of the polymeric chains when heating the sample above Tg, and therefore, when an external force is applied, the material can be deformed into a desired temporary shape that corresponds to a change in the molecular conformation and entropy. When cooling below Tg and by gradually removing the external force, the temporary shape can be fixed through freezing the molecular chains and the applied force is stored as entropic energy inside the system. Upon reheating above the Tg, the polymeric chains acquire more mobility, allowing the release of the entropic energy, which is the driving force of the process, and the material is driven back to its entropically favorite state that corresponds to the initial shape [Actually, the most-used SMPs are thermally-induced shape-memory polymers. Their typical mechanism involves heating above a specific temperature, called the transition temperature  , biocompAmong these materials, shape-memory fibers have been studied since the fibers possess particular intrinsic features such as a high axial ratio, and compared with shape-memory polymer bulk, shape-memory fibers exhibit excellent mechanical properties because of their molecular orientation. Many polymers have been used for electrospinning, such as poly(vinyl pyrrolidone) (PVP), poly(vinyl acetate) (PVAc), polystyrene (PS), poly (PVA), poly(ethylene oxide) (PEO), polyacrylonitrile (PAN), polyethersulfone (PES), poly(ε-caprolactone) (PCL), and poly(lactic acid) (PLA) ,22,23,24Electrospinning was developed by Formhals in 1934  and prod2 production, environmental protection, antibacterial properties, etc. [Electrospinning is a technique that produces polymeric fibers of nanometer to micrometer sizes in diameter  and has es, etc. ,40,41,42In the last decades, researchers have tried to combine the features of polymer electrospun nanofibers with SM behavior, developing materials with improved properties. However, this is still considered a new, challenging research topic, since there are not many documents regarding shape-memory fibers : fewer tShape-memory polymers (SMPs) have received great attention for their potential applications in many fields. Indeed, the number of published papers has increased in recent years. Therefore, in recent years, new polymer fibers have been developed and significant advances have been carried out in the production of high-performance fibers, elastic fibers, and nanofibers by using the electrospinning method . The firOne of the most studied shape-memory polymers is the class of polyurethanes (PUs), introduced by Mitsubishi in 1988 . Shape-mrR and fR [Peponi et al. studied a shape-memory poly(ester-urethane) based on triblock copolymers based on poly(L-lactic acid) (PLLA) and PCL ,49. Theyr and Rf . They alr and Rf . rR value of 98% and an fR value of 80% after several cyclic times.In order to combine the properties of SMPs with nanofibers, Zhuo et al.  tried toIn general, SMPU possesses unique properties such as low production cost, low density, flexibility, good processability, and high deformation, but still has some disadvantages such as poor surface wettability, low shape-memory effect, and mechanical strength, thus additives or reinforcements are often incorporated in order to improve these features . Rana etfR and rR above 90% (92.1% for the sample with the highest content in GO); instead, the neat sample revealed an fR value of 89.2%. These results were explained by the presence of GO as reinforcement with a large specific surface area and a very good dispersion into the matrix, and therefore, it improved the modulus, which is advantageous for a better shape fixation [Comparing carbon nanotubes and graphene, the graphene oxide (GO), which possesses several oxygen-containing groups  and weakfixation .Subsequent studies have been based on the production of polymer-based scaffolds. In 2015, Zhang et al.  developeAnother interesting study was carried out by Alhazov et al. , by devefR were above 80% and all rR around 100%.Other studies based on PU were performed by Budun et al. , by fabrMoreover, some researchers have been focusing their attention on the processing of copolymers to achieve porous structures. Especially, Ang et al.  fabricatThe electrospinning technique has been used also to produce porous structures in order to increase the content of water incorporated, and indeed their surface area ,63. The m), the strain-induced crystallization fixes the temporary shape. However, after heating, the SMPU becomes amorphous and maintains this state for more than 60 h, delaying its crystallization. This effect allows for a complete shape-memory cycle to be carried out without using the effect of crystallization, and the authors observed the excellent shape-memory performance of the SMPU in the amorphous state even without the help of the crystallization. Therefore, they suggested that the fixation and recovery shape mechanisms are caused by the inhibition of the chain mobility caused by interlocking the hard segments when decreasing the temperature below the transition temperature, and subsequent heating allows free chain movement and the recovery of the initial shape , εm was subsequently increased from 25 to 50%, and rR values between 89% and 95% and fR values of 82–83% after the second cycle were obtained when small deformations at clinically relevant temperatures were applied. In addition to the class of polyurethanes, PCL has been extensively studied. As one of the biodegradable polyesters and for its great biocompatibility, it can be used in the biomedical field and packaging applications ,71. Nevem semicrystalline polymer into a Tg-based SMP matrix to develop triple-shape polymeric composites (TSPCs), which are a class of smart materials capable of fixing two temporary shapes besides their permanent shape [m of 40 °C) and the Tg of EP (Tg of 80 °C), and dual and triple SM performances were investigated, revealing fR and rR values close to 100% for the former case, whereas fR and rR values for the second shape were lower than the values of the first one. Luo et al.  incorpornt shape . PCL andnt shape . In partg of the EP and the Tm of PCL were used as transition temperatures to fix the two temporary shapes. From the shape-memory performance, it was observed that EP/PCL nanoweb with graphene showed worse SM properties than the unreinforced material, and additionally, EP/PCL with a co-continuous structure revealed the best properties with fR1, fR2, rR1, and rR2 values of 81–82%, 94–95%, 94%, and 85%, respectively.A similar approach was applied by Fejos et al.  by develr around 97% was observed over the 20 cycles, and an fR around 95.5%.Yao et al.  elaboratBirjandi et al.  reportedm of PCL, thus the PCL crystal melts, meanwhile a voltage is applied on the EAP, causing the deformation. Once the material assumed the desired shape, the heat was removed while the voltage was still applied to keep the shape, and when the temperature reached values below the Tm, the temporary shape was fixed and the voltage was removed. The initial shape was recovered by heating the composite  and rR (98%) and the independence of these properties from the content of crosslinking. In 2016, Marlettini et al.  developefR of 95–99% and an rR of 88–100%, respectively. Moreover, on the basis of this work, they evaluated the effect of the solution concentration, photo-initiator concentration, and blend composition (PCL/epoxy ratio) on the spinnability and shape-memory properties [fR and rR values between 95% and 100%.In 2017, Iregui et al.  obtainedoperties . They no® and an inner layer of electrospun PLA mat. Furthermore, many studies were focused on the processing of multiphase shape-memory materials. For instance, Buffington et al.  designedFurther studies based on PCL were performed by Yao et al.  based on® solution and consequently to improve the electrospinnability in order to produce Nafion® nanofibers with shape-memory properties stimulated by heat. In particular, DuPont Nafion® PFSA is composed of a polytetrafluorethylene backbone and perfluorovinyl ether pendant side chains terminated by a sulfonate ionic group and is characterized by high chemical and thermal stability, acidity and electrical conductivity, and mechanical properties [fR and rR values of 95–96% and 87–89%, respectively. Afterward, they investigated such properties by modifying the PEO content: 0.3, 0.5, and 0.7 wt.%, and fR and rR values of around 90% were obtained for all samples. An increasing trend in fR and a decreasing trend in rR were observed by increasing the PEO content [PEO has been added several times in solution to adjust some properties. For example, Zhang et al.  used PEOoperties . The fib content . ® have been carried out by researchers to take advantage of its different, interesting properties. In 2016, Hu et al. [rR of approximately 92%. Further studies focused on Nafionu et al.  aimed tou et al. . The comg as transition temperature) and a thermoplastic polyether block amide elastomer (PEBA) as the matrix, by melt impregnation/compaction (fR of 66 ± 14% and an rR of 98 ± 2% at low strain (3–5%).Another polymer investigated by researchers is PVA. Shirole et al.  fabricatmpaction . The sharR higher than 93% and an fR higher than 90% and increased the yield stress, elastic modulus, tensile strength, and breaking strain by 22.6, 213.1, 35, and 39.5%, respectively, compared with randomly oriented nanofibers, due to the higher compactness and density of aligned nanofibers. Furthermore, it was observed that when the alignment angle decreases from 90° to 0°, mechanical properties are enhanced due to an increase in the volume fraction of nanofibers along the strain direction, which better bears the applied loading. In 2020 Guan et al.  studied w/v% of PU in 60/40 (DMF/chloroform) solvent. They observed that the fiber diameter decreased by increasing the needle-to-collector distance and the applied voltage; however, further increases led to an increase in the average diameter, while the diameter was also increased by increasing the feeding rate. The peculiar porous structure of the fibers where cavities act as weak points diminished the mechanical properties compared to those of bulk film, showing lower Young modulus, tensile strength, and elongational break as well as fR values. However, the electrospun scaffolds revealed rR values of 100%.Further research in order to optimize practical parameters was carried out by Banikazemi et al.  by fabrifR, and due to the small content of hard segments, the material showed rR values of 100%.Nahavandizadeh et al.  fabricatOne of the most recent works in the scientific literature, focused on the development of a material with improved thermal and mechanical properties and with shape-memory properties, was reported in 2021 by Liu et al. . They prAnother way to tailor the shape-memory behavior of SMPs directly involves some effects that are observed in many electrospun membranes—for example, the shrinkage that is caused by the stretched conformation of the macromolecular chains . Other tg of PLA through plasticization by blending PLA with oligomers of lactic acid (OLA), obtaining, for the first time, thermally-activated shape-memory electrospun fibers of neat and plasticized PLA for potential biomedical applications. In fact, OLA was revealed to be particularly compatible with PLA due to its chemical composition. Furthermore, OLA and lactic acid are the degradation products of PLA inside the body, which can be metabolized or eliminated through breath or urine [In 2019, Leonés et al.  developeor urine .g than neat PLA (Tg = 60 °C), and the Tg decreased by increasing the OLA content from 50 °C (PLA-OLA: 90:10) to 35 °C (PLA-OLA: 80:20) and 20 °C (PLA-OLA: 70:30). The shape-memory properties were evaluated at 45 °C and 40 °C, temperatures close to that of the human body, with PLA-OLA ratios of 80:20 and 70:30, respectively. From the tests executed at 45 °C, with the formulation PLA-OLA 80:20, fR and rR values of 100% were achieved , while at 40 °C it showed an fR = 98% and a slightly low value of rR due to the smaller temperature difference between the transition temperature and its Tg. PLA-OLA 70:30 (with lower Tg) presented better SM behavior at 40 °C than 45 °C. Indeed, at 45 °C it showed an fR = 90% and rR = 70%, whereas at 40 °C the fR and rR values were 92% and 75%, respectively. Among the studied materials, PLA-OLA with 20% of OLA was identified as the ideal material for biomedical applications, revealing the best mechanical properties at both testing temperatures, as reported in They observed a decrease in the average diameter of fibers by increasing the content of OLA, from 757 ± 193 nm for neat PLA to 768 ± 207 nm, 620 ± 121 nm, and 476 ± 80 nm for PLA-OLA 90:10, 80:20, and 70:30 ratios, respectively. Moreover, the system containing OLA presented a lower TMany researchers have been focusing on the study of structure, properties, and the optimization of parameters in order to obtain SMP fibers with high performance to be used for several applications. In particular, one of the areas in which SMP fibers have been widely used is the biomedical field, as reviewed in the following section.SMPs have been extensively used to develop scaffolds, implants, and biomedical devices due to their high biocompatibility and large shape deformation properties . These pPotential biomedical applications for shape-memory electrospun nanofibers have gained increasing attention, in particular, in tissue engineering, drug delivery, wound dressing, and the development of biomedical devices and medical imaging.In 2013, Tseng et al.  develope3O4) nanoparticles  can be damaged as a consequence of different types of trauma, such as traffic accidents, natural disasters, and others. Generally, when the injuries are small, the nerve can regenerate itself, but when injuries are larger they need to be surgically treated with nerve grafts taken from other parts of the body . TherefoChen et al.  developerac-lactide and then glycolide was incorporated into the network. Finally, poly(rac-lactide-co-glycolide) was obtained and the Tg was tuned by varying glycolide monomer constituents. The SM properties were evaluated: all networks showed an fR value of ~99% after ten thermomechanical cycles, whereas rR decreased from 90% to 50% during the first five cycles and the value stayed constant after the sixth cycle. This fact can be explained by a loss of physical crosslinks during the programming; however, the device will require only one activation. PLLA was modified by substituting L-lactide with rR above 90% and an fR above 92% after seven cycles. Furthermore, the biocompatibility of the material was proven, since the copolymer supported the proliferation of human fetal osteoblastic (hFOB) cells in in vitro culture. The authors subsequently investigated the properties of the same material, also incorporating carbon black to fabricate electrically conductive nanofibers [−1 to 1.8 kΩ mm−1. From the evaluation of SM properties, they noticed the almost complete independence of the SM behavior from the addition of the fillers, given that the fR and rR values showed a slight decrease, however, maintaining the shape recovery ratio above 90% and the shape fixity ratio above 82%, even after five cycles. In addition, the nanofibers showed good biocompatibility. PC12 cells were cultured on the scaffold and the nerve cells showed increased interactions. Many other researchers have studied the fabrication of SM scaffolds for tissue engineering applications. Kai et al.  developenofibers . Indeed,nofibers . They alMejia et al.  used gelm, acted as the physical network. In addition, instead of tuning the shape recovery temperature by varying the composition of copolymers, they used an alternative approach that consists of thermal annealing, where the sample is submitted to a controlled temperature for a limited time [m. After annealing at 15 °C, the material started the recovery at 25 °C and finalized it at 40 °C, while, after annealing at 30 °C, the recovery started at 35 °C and was completed at 55 °C. Both the samples exhibited very high values of fR and rR, that is 98% for the sample annealed at 15 °C and 99% for the one annealed at 30 °C. Moreover, the biocompatibility of the proposed scaffold was demonstrated by using NIH/3T3 fibroblast cells, showing high spread and cell proliferation.In 2017, Marlettini et al.  developeted time , which lSMPs for biomedical applications were also explored by Pandini et al.  by fabriMany other studies were carried out to find scaffolds that mimic the extracellular matrix (ECM), which permits cell motility during tissue repair , but alsco-trimethyl carbonate (P(DLLA-co-TMC)), fabricated by electrospinning, in gelatin-acrylated β-cyclodextrin (β-CD) polyethylene glycol-hydrogel (GCP-hydrogel), where the matrix created a local microenvironment for cell assembly: embryonic stem cells (ESCs) were used in this case and acted as a lubricant. The electrospun fibers showed an average diameter of 800 ± 200 nm, which remained unchanged when incorporated in the matrix. By observing the mechanical properties at 37 °C, it was noticed that nanomesh slightly reinforced the GPC-hydrogel. Furthermore, the shape-memory properties were evaluated by incubating the wrinkled hydrogel at 37 °C, the temperature at which it recovers its initial shape, and it was observed that the material recovers its original morphology in ~15 s with an rR > 95%. The authors discovered that the composite was capable of significantly improving the viability of ESCs and their differentiation towards motor neurons both in vitro and in vivo. Another field where SMPs have been applied concerns the treatment of spinal cord injuries (SCI) that lead to the destruction of nervous tissue . The regThe fabrication of materials to be used in the biomedical field and tissue engineering was studied also by Yao et al.  by incorInverardi et al.  producedSMPs have also been studied to develop scaffolds to be used for treating vascular disorders that are generally caused by endothelial cell malfunctions by causing damage to the arterial wall . The rapm, and SM properties can be changed by varying the PCL/HDI/BD ratio. The nanofibers exhibited great shape-memory performance, in particular PCL/HDI/BD 1:4:3. The nanofibers were placed in water at 60 °C and then stretched to different elongation degrees . Finally, they recovered their original shape when placed again in hot water (at 60 °C), showing high rR (>89%), even when deformed at the greatest elongation (400%). Moreover, human mesenchymal stem cells (hMSCs) were cultured on the meshes, showing alignment along with the fiber orientation, thereby demonstrating the biocompatible nature of the material.Further studies regarding biomedical applications were carried out by Niiyama et al.  by develtrans and dual-SM behavior. Therefore, with the aim of fabricating a material that showed triple-SM behavior constituted by miscible materials, Sabzi et al. [g, through the co-electrospinning method, Additionally, graphene nanoplatelets were included to improve the SM behavior [rR and fR and from cytotoxicity tests, high cell growth and the proliferation of the osteoblasts on the fibrous scaffolds containing graphene were observed. With this purpose, Zare et al. [m close to body temperature) and PEO as the permanent segment, by self-assembly electrospinning and photo-crosslinking, which can be applied simultaneously [Recently, multiple shape-memory polymers have attracted much attention, since they can be easily tailored by changing the transition temperatures without resorting to the synthesis of other polymers, and, besides, can be designed in several ways . Multipli et al.  designedbehavior . The mate et al.  developeaneously ,126, finfR and rR values of 97% and 88–89%, respectively. Cytotoxicity tests with NIH3T3 cells revealed more than 75% cell viability, hence proving the low cytotoxicity of the 3D sponges.Furthermore, gold nanoparticles (GNPs) of 10 nm were incorporated since they have been used in many biomedical applications, for photoablation, diagnostic imaging, as antioxidants, drug delivery vehicles, and for detecting cancer ,152. Theco-glycolic acid) (PLGA) electrospun fibers into inks ideal for 3D printing so as to obtain 3D scaffolds with a controlled shape and porous structure. Three-dimensional printing allows the fabrication of material with a precise form; however, the produced scaffolds presently lack fibrous surface structure, constituting a problem for the development of materials that mimic the ECM structure. Therefore, the combination of electrospinning and 3D printing should lead to the fabrication of a 3D scaffold with an appropriate, controlled shape and high porosity. The 3D scaffold presented showed good elasticity and water-induced shape-memory behavior, and, in addition, when combined with chondrocytes, achieved cartilage regeneration in vivo [Since the electrospinning technique produces 2D woven no-woven scaffolds, in order to produce more suitable scaffolds for tissue engineering, the development of 3D scaffolds was studied to extend the potential applications, as they better mimic the structure of ECM and regulate cellular biological behavior  ,154. Wit in vivo . In 2020, Chen et al.  developeg and increased the Young modulus of the material. In particular, the material showed an fR (>98%) and an rR (>96%) compared to neat PLLA. Moreover, electrospun PLLA-PHBV composite fibers showed enhanced osteogenic-inducing ability in the mouse bone mesenchymal stem cells, which makes this fabricated scaffold suitable for bone tissue repair applications.In order to fabricate materials for biomedical applications, polylactides have been widely used. However, as said before, their brittleness, low toughness, relatively poor retention, and recovery efficiency led the researchers to the production of polylactide-based shape-memory copolymers or blends with other polymers. In 2021, Wang et al.  modifiedFurther studies have been reported in 2021 in order to produce scaffolds and medical devices. For instance, Sarabiyan et al.  fabricat2) with a 3D porous structure and improved electrical signal transduction and self-adhesion, which simulated the myocardium ECM for myocardial infarction (MI) therapy. SMPU has been used for its capability to recover its original shape after a few seconds to minutes under specific conditions, while the presence of conjugated polymers such as PANI provides conductivity since electrical signals are fundamental for the heart’s activity, and, finally, the incorporation of SiO2 into biopolymers improves the bioactivity. The schematic procedure of the fabrication and self-adhesion of the sub-micron fibers cardiac patch is shown in Another interesting work related to tissue engineering was carried out by Feng et al. , by fabr−2 (taking 30 s under 0.6 W cm−2 and 18 s under 1.0 W cm−2).SMPUs were used also by Lv et al.  with the2 domains subsequently formed the reaction between the ends group, constituting the permanent crosslinking point. The chemical interactions between the PCL-TES chain ends and the silanol groups on the nanoparticle surface generated additional crosslinking points that permitted the recovery of the permanent shape, showing an rR and fR above 90%.With the aim of producing materials with shape-memory behavior, sometimes polymers without this property are modified in order to achieve the desired SM properties. For example, Liverani et al.  used PCLEven if nanofibers have been widely used in the biomedical field for tissue engineering, drug delivery is another important field of application. Actually, the large surface areas and high porosity provide high loading capacity and encapsulation efficiency ,165, thufR and rR in the range of 92–98%. Besides that, they explored hydrolytic and enzymatic in vitro degradation.Another polymer that has been investigated is polydioxanone (PDX) since electrospun PDX presents similar mechanical properties to collagen and elastin  and has ® (5863-80A) as a shape-memory component that is enzymatically stable. The temporary shape was fixed sequentially by heating above the Tm of PCL, deforming the material, and, finally, by decreasing the temperature. In this step, PCL was maintained under compression and Pellethane® under tension. Afterwards, the material was placed in a solution of lipase, which is an enzyme produced by both eukaryotes and prokaryotes [® recovered back its original shape. Through shape-memory properties evaluation, it was observed that such behavior was evident only when the highest lipase concentration was used (0.5 mg mL−1) within a 7 days test period. Indeed, lower concentrations of lipase degraded the PCL but no shape recovery was observed.Biocompatible SMPs have been widely produced, generally triggered by heating or by light. However, temperature activation is not always achievable or recommended. For this reason, some researchers have produced intelligent materials that can be triggered by biological activity: enzymatic triggering has been identified as one of the solutions, due to their biological activity and specific localization in the human body . Additiokaryotes , the hydrR > 97% and a recovery time of ~6 s. Lv et al.  designedtrans ≈ 42 °C. A natural antibacterial compound, berberine hydrochloride (BCH), was embedded in the middle layer, and the two outer hydrophobic layers were necessary to extend the drug release period. Such a design permitted the increase of the diffusion path of the drugs from the medium [Another drug delivery system (DDSs) was developed by Yin et al.  by desige medium  to have trans to values close to body temperature. Both electrospun mats (PU-PLGA and PU-PLLA/PEG) showed an fR value above 90%, and rR values of 98% and 99% for PU-PLLA/PEG and PU-PLGA, respectively. In general, the PU-PLGA scaffold presented the best features in terms of mechanical properties while both materials are suitable as drug delivery systems for rapamycin (Rap), revealing a controlled release over 45 days with therapeutic dosage.Bil et al.  fabricat3) solution [rR value above 95% after the first cycle and an fR value above 92% even after three cycles. Because of these SM properties, CNMs can be used for the wound closure process: the force accumulated by the pre-programming of CNMs is used to close the wound slowly, and later, this force is released when recovering the former shape (under body temperature) without applying any external force. Otherwise, immediate recovery could cause pain and nuisance  and water (λmax > 1150 nm). In 2014, Torbati et al. [−1) that gave the highest emission intensities. Moreover, they discovered that the fiber mats showed higher fluorescence intensity and higher uniform dye incorporation with respect to the cast films. Furthermore, fibers contract upon heating or in contact with water due to the SM properties of PVAc. Such behavior can be used for applications such as feeding tubes or catheters.Other studies have been directed to the design of dye-containing polymers. In particular, dyes that absorb and emit light in the near-IR spectrum have also found a place in medical imaging applications in order to replace other, more invasive techniques such as x-ray imaging. Near-infrared fluorescence (NIRF) (700–1000 nm) imaging has been investigated as an alternative since the main tissue absorbing components present minimal absorption in this range: oxy- and deoxyhemoglobin  that also increased the conductivity of the electrospinning solutions, leading to a production of fibers with a low number of structural defects. These materials demonstrated strain-induced deformation on electroactuation at 1.5–2.0 V anodic potential, producing a reversible 20% longitudinal strain, revealing, therefore, the capability to convert an electrical signal to a mechanical response, whereas the application of 2.0 V cathodic potential led to the recovery of the initial shape.One of the fields investigated is robotics, in which SM fibers can find applications as microswitches, microactuators, and micromanipulators (actuators and sensors). However, the polymeric material, in order to be potentially used, should respond to an external stimulus such as a current or electric field with a subsequent strain. Some of them, in reverse, show the capability to transform mechanical movement into an electrical response ,194. In fR value above 95%, significantly improved compared to that of pure CLSMPU nanofibers, which present a lower fR value (~80%) [rR showed values above 90%. The CLSMPU-PySMPU nanofiber revealed outstanding antibacterial activity by showing no growth of S. aureus and K. pneumoniae bacteria beneath the mat, while this growth was observed with the pure CLSMPU mat. Among the various alternative applications, additional studies have been carried out by investigating the antibacterial activity to use them as active antibacterial nanomaterials . In 2011e (~80%) , while ttrans, recovering the initial shape when the retracting force exceeded the stress applied. Upon cooling, the average pore size increased from 154 to 444 nm, thus allowing the separation of substances with different sizes only by changing the temperature. The modulation of the pore dimensions by changing the temperature has been used also for the development of intelligent clothing material.Additionally, since the electrospinning technique permits the fabrication of porous materials, the application of shape-memory electrospun nanofibers as a membrane has been also studied. Ahn et al.  developen). The specimen with higher PCL Mn (4000 g mol−1) with higher hard segment content (33 wt.%), which showed an Rf value of 86% and an rR value of 85%, was chosen to fabricate the ESW, revealing good moisture and air permeability due to the high porosity when kept in its expanded state below the transition temperature. Chung et al.  aimed toy), strain-to-failure (εf), and yield stress (σy) were evaluated according to the fiber orientation angle χ: 0° , 22.5, 45, 67.5, and 90° (transverse), observing Ey average values of 48.8 MPa and 4.0 MPa, εf of 198% and 351%, and σy of 4.6 MPa and 0.9 MPa for longitudinal and transversal loading, respectively. From the SM performance, a decrease in fR was observed by decreasing the orientation angle χ: from 95.6% for 0° to 86.2% for transversal oriented fibers (90°), while rR maintained high values (around 99%) independently from the fiber orientation. In 2013, Rodriguez et al.  fabricat®-based quintuple shape-memory membranes that can find applications in robotics and aerospace engineering, and also as a catalyst. Electrospun Nafion® nanofiber membranes (ENNMs) presented higher specific surface area, higher aspect ratio, and higher pore diameter compared with the bulk films, and these features were employed to improve the catalytic activity [trans: 160, 125, 90, and 55 °C, and the Nafion membrane revealed fR and rR values around 80%, while the rR to recover the initial and permanent shape was above 70%. Zhang et al.  developeactivity , which wr value of approximately 100%. In 2014, the same authors reported another research developing an SM nanocomposite constituted by a Nafion® polymeric matrix with shape-memory behavior and PAN-based carbonization nanofiber, which makes the material sensitive to electrical stimulus . The PANIn 2015, Nejad et al.  carried 2 , which can find applications in the adsorption of proteins. The SiO2@CNF exhibited improved mechanical properties, high water permeability, and enhanced protein absorption capacity for bull serum albumin. The introduction of SiO2 nanoparticles significantly improved the mechanical properties: in fact, by increasing the nanoparticle content, the stiffness of the membranes was decreased, as was revealed by the decrease in the elastic modulus. The shape-memory capabilities were observed by previously bending the sample with 20 wt.% of SiO2 to a radius of <100 μm, without observing any rupture, followed by a subsequent recovery of the initial shape. The enhanced mechanical properties were attributed to the “plasticizer effect” of the embedded nanoparticles.Fan et al.  fabricatIn 2018, Del Sorbo et al.  carried 3 as a catalyst. PPy, in this case, substituted the conductive particles that are generally added in order to provide electrical actuation; however, these fillers can present limitations related to non-uniform dispersion, thus the authors adopted another approach that consisted of the fabrication of core-shell fibers to obtain an almost uniform temperature within the material when electrically activated. The membrane showed a maximum conductivity of 0.5 S cm−1 and the recovery of the permanent shape was achieved in 2 s by applying a voltage of 30 V. Furthermore, it was observed that above 40 V, the heating damaged the membrane, while no SM effect was observed by applying a voltage below 15 V. Zhang et al.  fabricatMoreover, Khalili et al.  aimed tom of PCL) and 10 °C, with the specimen programmed with a strain of 100% and 300%. It was observed that when heating above 60 °C, the material was subjected to contraction, and to elongation when cooling. Furthermore, the reversible strain was measured [In 2019, Zhang et al.  developemeasured  for PCL,The interest in the fabrication of devices suitable for health services has widely increased in the last years, for example in the development of systems to purify different proteins that can be used as therapeutic agents  and that3 mg g−1, a large liquid flux of 1.5 ± 104 L m−2 h−1, and high selectivity to lysozyme from egg white. To overcome these limitations, in 2019, Fu et al.  aimed toAmbient energy harvesting has become the object of interest of many researchers in order to produce mobile devices for capturing, accumulating, and storing energy for later use ,220. In rR values above 94% after the first cycle and fR values higher than 98% in all three cycles. Moreover, Guan et al. , in 2020fR values above 96% and rR values above 97%, which revealed switchable optical transparency and potential applications as skin-like electronic devices.Yoon et al.  fabricatShape-memory polymers are widely used in the field of aeronautics, intelligent robots, and electronics. However, the traditional fabrication methods, e.g., injection molding and liquid molding, produced materials that could crack when they are twisted, limiting their applications. In order to overcome these problems, in 2021, Liu et al.  developetrans is determined by the melting temperature of PEG (60 °C), then the fixation of the temporary shape and the recovery of the permanent shape can be triggered by the phase transition of PEG. The membrane presented excellent shape-memory behavior, which also allows the adjustment of the pore size of the membrane, to transport the moisture in excess and keep the skin dry.More recently, concerns regarding the energy crisis related to global electricity consumption led researchers to develop new materials in order to find new solutions for these issues. In this regard, for instance, Feng et al.  fabricatIzraylit et al.  developeg of SMPU within 10 s. The mechanism of shape recovery and its potential use as a stimuli-responsive sensor is shown in g of SMPU, and the circuit remained disconnected. When heated above Tg, the paper recovered the unrolled shape, connecting the two copper tapes and forming a closed circuit. Furthermore, the SMPU/MXene showed self-extinguishing performance and fire retardancy with respect to SMPU paper, due to the barrier effect of Mxene, with a peak of heat release rate (pHRR) and total heat rate (THR) of 66.0 and 49.8%, respectively.One of the last works was carried out by Zhang et al.  by fabriThe progress in the optimization of the parameters, the architecture, the shape-memory behavior, the triggering methods, and the various applications of electrospun shape-memory nanofibers have been summarized in this review. Tremendous progress has been made since the first research was reported in terms of the study of the electrospinning parameters, which is a suitable, versatile, and cost-effective method that allows a simple way to fabricate continuous polymeric fibers. These electrospun fibers can show shape-memory properties, adjusting their architecture in order to obtain materials with one-way, two-way, and multiple SM behavior. Moreover, the fabrication of electrospun nanocomposites has also been studied and optimized in order to improve their properties and thus extend their field of applications and the triggering stimulus, such as temperature, pH, water, and electric fields as the most important.Different application fields have been reviewed, with particular attention to the use of shape-memory electrospun nanofibers in the biomedical field, taking advantage of their capability to mimic the structure of the extracellular matrix as scaffolds in tissue engineering, tissue repair, wound dressing, and drug delivery. The cell behavior after culturing on the electrospun fibrous scaffold and the shape-memory behavior of the materials have been widely evaluated in vitro, however, it is still a challenge to study these features on cells in vivo. Furthermore, shape-memory electrospun nanofibers, particularly those triggered by the magnetic or electric fields, have recently extended their applications due to novel fabrication techniques in the aerospace field and in robotics, as actuators, sensors, for energy harvesting, etc.Finally, despite the significant and recent progress in the fabrication of shape-memory polymers obtained by electrospinning, further studies are required and several challenges still need to be addressed to optimize the working parameters. Moreover, deeper efforts on the material design are required to exploit the advantages of polymers with multiple shape-memory behaviors with great potential for specific advanced applications in the biomedicine field, robotics, and electronics.


BackgroundandObjectives: This retrospective study evaluated the clinical impact of enhanced personal protective equipment (PPE) on the clinical outcomes in patients with out-of-hospital cardiac arrest. Moreover, by focusing on the use of a powered air-purifying respirator (PAPR), we investigated the medical personnel’s perceptions of wearing PAPR during cardiopulmonary resuscitation. Materialsand Methods: According to the arrival time at the emergency department, the patients were categorized into a conventional PPE group (1 August 2019 to 20 January 2020) and an enhanced PPE group . The primary outcomes of this analysis were the return of spontaneous circulation (ROSC) rate. Additionally, subjective perception of the medical staff regarding the effect of wearing enhanced PPE during cardiopulmonary resuscitation (CPR) was evaluated by conducting a survey. Results: This study included 130 out-of-hospital cardiac arrest (OHCA) patients, with 73 and 57 patients in the conventional and enhanced PPE groups, respectively. The median time intervals to first intubation and to report the first arterial blood gas analysis results were longer in the enhanced PPE group than in the conventional PPE group . However, there were no significant differences in the ROSC rate (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.38–1.67; p = 0.542) and 1 month survival  between the two groups. In total, 67 emergent department (ED) professionals responded to the questionnaire. Although a significant number of respondents experienced inconveniences with PAPR use, they agreed that PAPR was necessary during the CPR procedure for protection and reduction of infection transmission. Conclusion: The use of enhanced PPE, including PAPR, affected the performance of CPR to some extent but did not alter patient outcomes. PAPR use during the resuscitation of OHCA patients might positively impact the psychological stability of the medical staff. Coronavirus disease COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global public health threat with significant morbidity and mortality 9, caused,4. This SARS-CoV-2 is a highly transmissible virus that spreads rapidly and primarily through droplets or even through aerosols in certain circumstances ,9,10,11.It is not often possible to obtain sufficient information about a patient in case of out-of-hospital cardiac arrest (OHCA), making it difficult to determine whether the patient has COVID-19 ,15,16. FSeveral organizations have updated their guidelines for OHCA to cope with the COVID-19 pandemic, recommending the use of an appropriate level of PPE ,15,20. HThis was a single-center study conducted in the ED of Samsung Medical Center, which is a 1960-bed, university-affiliated, tertiary referral hospital with an annual census of 70,000 in Seoul, South Korea. This study comprised two sections. In the first section, we conducted a retrospective observational study to investigate the clinical impact of enhanced PPE on the tasks performed during CPR and the prognosis of the OHCA patients. According to the arrival time at the ED, the patients were categorized into a conventional PPE group (from 1 August 2019 to 20 January 2020) and an enhanced PPE group (from 21 January 2020 to 31 August 2020). The primary outcome of this analysis was the recovery of spontaneous circulation (ROSC) rate. In the second section, we conducted a survey regarding the perceptions of the HCPs towards the use of enhanced PPE.OHCA patients aged >18 years were included in this study. Patients who recovered spontaneous circulation at the pre-hospital stage were excluded. The HCPs who performed resuscitation procedures for OHCA patients in both groups were recruited for the survey.Before the COVID-19 pandemic, a surgical mask and rubber gloves with/without disposable, chlorinated polyethylene isolation gowns were used during CPR of OHCA patients. However, after the first COVID-19 patient was identified, HCPs participating in the CPR procedures for OHCA patients were obliged to wear enhanced PPE. This comprised a complete bodysuit or at least a waterproof surgical gown, apron, rubber gloves, boots, N95 respirators (inside the hood), and powered air-purifying respirator (PAPR). The PAPR used in this study consisted of a loose-fitting hood, breathing tube, high-efficiency particulate air filter, and blower. We used two types of PAPRs: 3M Jupiter Powered Air Turbo with a breathing tube (BT-20 L) and a loose-fitting hood (S-433 L-5)  and an AIR WING III PAPR system with a hood kit .We retrospectively reviewed the electronic medical records and our institutional registry for the OHCA patients’ data collected for CPR quality improvement. The following variables were retrieved: age, sex, preexisting conditions , witnessed arrest, bystander CPR, arrest location, pre-hospital CPR duration, hospital CPR duration, initial electrocardiography (ECG) rhythm, intubation trial number, intubation success, time interval to first intubation trial, time interval to first arterial blood gas analysis (ABGA) achieved, targeted temperature management, ROSC, alive ED discharge, and 1 month survival.Three investigators  developed a questionnaire based on previously published literature and the perspectives of ED professionals. Two EM specialists (SYH and TGS) reviewed the questionnaire. The survey response options varied. Most of the questions related to CPR performance used the 5-point Likert scale for the responses. Multiple choices were used for questions related to the reason for the response, and opinions could be described freely in a separate section. The survey was provided to the participants as a paper document; no incentive was offered for participation.p-values < 0.05 were considered statistically significant. Data were analyzed using STATA software, version 15.1 .Data are represented as medians with interquartile ranges (IQR) for continuous variables and numbers and percentages for categorical variables. Wilcoxon rank-sum test or chi-squared test was performed, as appropriate. Multivariable logistic regression analysis was performed to evaluate the association between the use of enhanced PPE and clinical outcomes. The adjusted variables were selected based on clinical plausibility a priori and those exhibiting a significant difference between the conventional PPE group and enhanced PPE group. Preexisting CVA, witnessed or not, bystander CPR, arrest location, and initial ECG rhythm were included in the final model. The results are presented as odds ratios (OR) with 95% confidence intervals (CIs). Responses to the questionnaire using the 5-point Likert scale are presented as means ± standard deviations. A mean value ≥3 points indicated a significant trend. Responses to multiple-choice questionnaires are presented as numbers with percentages, and the results of the questionnaire using a numerical rating scale are represented by the average value. A total of 130 OHCA patients were included in the study, of which whom 73 and 57 were classified into the conventional PPE and enhanced PPE groups, respectively. Baseline characteristics and outcome measurements of all patients are presented in n = 75) were male. There were no significant differences in the sex or age between the two groups. Pre-hospital variables including witnessed arrest, bystander CPR, CPR duration, and arrest location did not differ significantly between the two groups. As compared to the conventional PPE group, the enhanced PPE group showed longer ED CPR duration  vs. 15 min ; p = 0.030), longer time interval to first intubation (3 min (IQR 2–5) vs. 2 min (IQR 1–3); p = 0.020), and longer time interval to report the first ABGA results  vs. 3 min ; p < 0.001). The first-pass success rate , rate of ROSC in the ED , survival until ED discharge , and 1 month survival  were all lower in the enhanced PPE group than in the conventional PPE group, although the difference was not statistically significant.The median age was 68 years , and 56.1% (p = 0.542) or 1 month survival   .n = 36); 10–19 times, 34% (n = 23); and >20 times, 12% (n = 8).In total, 67 HCPs in the ED responded to the survey. The baseline characteristics of the survey respondents are summarized in The survey results on wearing enhanced PPE during resuscitation of OHCA patients are summarized in Overall, 82.1% and 68.7% of the respondents “strongly agreed” or “agreed” that the breathing was comfortable and that the heat buildup was appropriately suppressed while wearing enhanced PPE, respectively. However, 62.7% of the HCPs “strongly disagreed” or “disagreed” that it was easy to secure clear vision. The majority of the respondents reported difficulties in communication among themselves (94.0% responded with “strongly agreed” or “agreed”). They also reported that their movement was limited with enhanced PPE (79.1% responded with “strongly agreed” or “agreed”) and that it impeded each other’s movements (77.7% responded with “strongly agreed” or “agreed”). Only 1.5% and 4.5% of respondents, respectively, “strongly agreed” and “agreed” that donning and doffing enhanced PPE was easy.n = 61) for the following reasons (duplicate answers possible): (1) “I feel protected” (n = 27); (2) “There is a positive effect of reducing the spread of infection” (n = 24); and (3) “I do not know if it is more effective in blocking the transmission of infection than other protective equipment, but in the current situation, an excessive degree of protection is required” (n = 15) (see Most of the respondents answered that enhanced PPE was necessary during resuscitation of OHCA patients ( 15) see . FurtherIn this study, we found that wearing enhanced PPE, including PAPR, affected the resuscitation performance to some extent, including delays in reporting the first blood test results and in ETI; however, there was no statistically significant difference in the clinical prognosis represented by the ROSC rate and 1 month survival.In previous studies, the ROSC rate or survival was lower during the pandemic than that before it ,25,26. DIn our study, the main change at the hospital level during the COVID-19 pandemic in the resuscitation of OHCA patients was wearing enhanced PPE. Cumbersome PPE inevitably hinders the performance of the HCPs. Several studies have shown that it also affects the performance of chest compression, intravenous cannulation, ETI, and defibrillation ,29,30,31In a survey of HCPs with experience in resuscitation of OHCA patients while wearing PAPR, we found that though PAPR had advantages in heat tolerance, the HCPs faced significant challenges in several aspects. This included securing clear vision, risk of contamination, discomfort during donning and doffing, communication problems, limitation of mobility, and interference in movement amongst the staff. Our results support the findings of previous studies that PAPR has advantages in heat tolerance but disadvantages with respect to mobility and communication ,34,35. AThis study has several limitations. First, this was a single-center and retrospective study conducted in the ED of a tertiary referral hospital. Thus, the results of this study may not be generalizable to other settings. Second, the time between the arrival of a patient suffering from cardiac arrest and the delivery of epinephrine in the ED might be a more appropriate indicator for determining whether the wearing of enhanced PPE has a negative effect on clinical tasks. However, precise timing data were lacking. Similarly, the number of shockable patients was inadequate to utilize the time interval between identifying a shockable rhythm and defibrillation as a proxy for the unfavorable effect of enhanced PPE. Therefore, in this study, the impact of enhanced PPE on CPR performance was evaluated in a limited manner. Third, the survey of this study included HCPs of different occupations, and their roles in the resuscitation procedures differed according to the occupational groups. Therefore, in the process of answering the questions regarding the detailed procedure, the respondents may have answered based on indirect experience of procedures that were not part of the respondent’s occupation. Fourth, we employed two different types of PAPR in this study, and we did not assess whether the outcomes would alter depending on the PAPR model. However, there were no significant differences in the shapes of the two devices, suggesting that the shape may have had little effect on the results. Fifth, although the ROSC and 1-month survival rates were lower in the enhanced PPE group than in the conventional PPE group , the difference was not statistically significant. The wide range of 95% CI in multivariable analysis suggests that this study may have limited power to detect statistically significant differences in outcomes between groups. Sixth, we used historical controls in our study. Due to the comparison of different study populations, the findings of our study may not be solely attributable to the level of PPE.The use of enhanced PPE, including PAPR, affected the performance of CPR to some extent but did not alter patient outcomes. Although the HCPs were concerned about the consumption of resources and various inconveniences caused by wearing PAPR, they generally agreed that wearing enhanced PPE was necessary during the resuscitation of OHCA patients in the COVID-19 pandemic.


Alternaria is a genus of worldwide fungi found in different habitats such as soil, the atmosphere, plants or indoor environments. Alternaria species are saprobic—largely involved in the decomposition of organic material—but they can also act as animal pathogens, causing disease in humans and animals, developing infections, toxicosis and allergic diseases. A. alternata is considered one of the most important sources of fungal allergens worldwide and it is associated with severe asthma and respiratory status. Among the A. alternata allergens, Alt a 1 is the main sensitizing allergen and its usefulness in diagnosis and immunotherapy has been demonstrated. Alt a 1 seems to define a protein family that can be used to identify related pathogenic fungi in plants and fruits, and to establish taxonomic relationships between the different fungal divisions. Allergic diseases are a group of immune-mediated disorders with a high worldwide prevalence affecting 30% of the general population and increasing dramatically. Asthma, rhinitis; anaphylaxis; drug, food, and insect allergy; eczema; urticaria (hives) and angioedema are included in this group of diseases.Aspergillus and/or Alternaria is related to the severity of an asthmatic arrest [The main allergens causing type I allergies are contained in different sources, of which mites, pollens, epithelia, fungi and some foods are the most important ,2. Fungic arrest .Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum and Penicillium notatum are the ones with the highest prevalence in allergic disease or sensitizations [Alternaria and Cladosporium allergenic sources ranged from 0.2% to 14.4% in the adult general population (aged 20–44) [A. alternata is considered one of the most important fungal allergens worldwide and is associated with severe asthma and respiratory status [There are several epidemiologic studies about fungal allergy prevalence, but the data vary according to the method of diagnosis . It is eizations . Data frd 20–44) . In the d 20–44) . A. altey status . It accoy status .Alternaria is a worldwide genus of Deuteromycetes fungi found in different habitats, such as soil, the atmosphere, plants or indoor environments, that include many saprophytic and pathogenic species. The taxonomy of these fungi has mainly been based on morphological conidial characters and to a lesser extent on host association, biochemistry and metabolites [Alternaria by elevating 26 clades to the subgeneric taxonomic status of section [Alternaria contains most Alternaria species with conidia succession, including important plant, human and postharvest pathogens. In spite of the fact that the majority of Alternaria species are saprobic—largely involved in the decomposition of organic material—many of their species are endophytic, living in various parts of crops including leaves, seeds and fruits [Alternaria [n = 3034) and showed a prevalence of sensitization to A. alternata of 9%, ranging from 2% in Finland to 23.8% in Greece [A. alternata sensitization in the general population (aged 6 to 74 years) was about 13% [abolites . Recent  section . Accordid fruits . To a led fruits ,12. In tternaria ,13,14,15n Greece . In the bout 13% .A. alternata [Alternaria allergic patients being sensitive to this allergen [The diagnosis and treatment of human allergic diseases classically involves the use of extracts obtained from biological material. However, in recent decades the application of molecular diagnostic procedures using individualized allergens has been decisive in the management of atopic individuals and allergic patients . Describlternata ,20,21, wallergen ,22,23. SAspergillus and Penicillium species. The order Capnodiales includes 10 allergens belonging to Cladosporium species, and the Pleosporales order includes 18 allergens belonging to Alternaria, Epicoccum, Ulocladium and Curvularia species [The official WHO/IUIS database currently lists 113 fungal allergens belonging to various protein families, of which 88 belong to Ascomycota species, 23 to Basidiomycota and 2 to Mucorales. The order Eurotiales includes 48 allergens belonging to  species .A. alternata-sensitized individuals, and A. alternata enolase, rAlt a 6, with its potential cross-reactivity to molds and to natural latex allergens. The recombinant allergens rAsp f 1, 2, 3, 4 and 6 from Aspergillus fumigatus for allergy diagnostic purposes, including the specific evaluation of allergic bronchopulmonary aspergillosis (ABPA) and, finally the rCla h 8 allergen, considered the major allergen of Cladosporium herbarum with possible cross-reactivity to other dehydrogenase allergens [To date, only 10 individualized allergens from 5 mold species are available for allergy diagnosis and mold sensitization testing. These include nAlt a 1/rAlt a 1, the major allergen in llergens .Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia in clinical diagnosis [Alternaria and Cladosporium species are considered the most important outdoor allergens and the sensitization to species of these genera is associated with the development of asthma and rhinitis and exacerbation of asthma [Penicillium and Aspergillus species are both involved in allergic diseases as indoor allergens [A. fumigatus is able to colonize the bronchial tract of asthmatic patients, causing acute persistent asthma and ABPA [Malassezia species are common commensals of healthy skin and may be associated with atopic dermatitis [The clinical and diagnostic relevance of individualized allergens and allergen extracts from seven common genera of fungi has been extensively reviewed ,5. Most iagnosis ,27,28,29f asthma ,15,26. TCladosporium, Alternaria, Aspergillus and Penicillium species were found to be present in higher concentrations in homes of asthmatic participants [However, in the association between allergic diseases and fungal species, which have been identified in both indoor and outdoor environments, the fungal concentration and distribution of the species in both environments should be taken into account in any case . Sharpe icipants . The preicipants .Schizophyllum commune and Bjerkandera adusta) to pathogenesis of respiratory diseases, including allergic asthma/rhinitis or allergic bronchopulmonary mycosis [Rapid progress in gene and protein technology over the past decades has contributed significantly to the identification of species-specific and cross-reactive allergen molecules from different allergenic fungal sources . Neverth mycosis .3, such as Agaricus (350 spores/m3); Alternaria (180 spores/m3); Aspergillus/Penicillium (450 spores/m3); Coprinus (500 spores/m3) and Ustilago (750 spores/m3); Cladosporium (4500 spores/m3) [Cladosporium is the genus that gives rise to the highest concentration of airborne spores [Aspergillaceae  and Pleosporaceae , also have significantly higher levels of spores in the air [The distribution and quantification of indoor and outdoor fungal species is strongly associated with the development of fungal allergy ,31. The ores/m3) . Most ste spores ,38,39,40 the air ,38,39,40Alternaria, Aspergillus, Aureobasidium, Bipolaris, Botrytis, Candida, Curvularia, Cladosporium, Drechslera, Epicoccum, Fusarium, Mucor, Penicillium, Phoma, Saccharomyces, Malassezia, Trichphyton, Stemphylium, Ganoderma, Ustilago and Pleurotus [Alternaria, Aspergillus and Cladosporium are the most reported sensitizing genera of fungal nature [The prevalence of fungal sensitization shows a significant geographic variation with several fungal species involved in allergic diseases including the genera leurotus ,23,28,41l nature ,43. Thisl nature .However, it must be considered that the quality of fungal allergenic extracts used as a diagnostic tool is not similar for all species due to several difficulties in the process of obtaining the extract such as fungal identification, culture conditions and standardization, strain variation, biological standardization, use of heterogeneous in-house reference sera and other biological, biochemical and immunochemical parameters ,45,46. TAlternaria, Aspergillus, Penicillium and Cladosporium seem to be the strongest candidates for the development of severe asthma and rhinitis [Pleurotus cornucopiae, Lycopodium clavatum, Dictyostelium discoideum, Rhizopus nigricans and Neurospora [Alternaria, Cladosporium and Aspergillus has a strong link with asthma severity [On the other hand, various fungi are known to cause sensitization in asthmatics, but the most important fungal agents causing severe asthma with fungal sensitization are not well defined . Accordirhinitis ,48,49,50urospora , whereasseverity ,52,53,54severity , while tseverity .The application of genomics and proteomics to the study of allergenic proteins has been the basis for building more accurate diagnostic tools. The identification and production of the individual allergen molecules has been key to addressing hitherto unresolved concepts, such as the causes of cross-reactivity phenomena, through molecular diagnosis.®) [At the beginning of the 21st century, Valenta et al. described the basis for the molecular diagnosis of allergy, a classical technique to measure specific IgE concentrations in serum by coupling individualized native or recombinant allergens to the solid phase (ImmunoCAP®) . A few y®) .Currently, the diagnostic accuracy and effectiveness of replacing allergenic sources by individual allergens is a fact. By applying the CRD, it is possible to minimize several problems with the standardization of allergenic extracts, such as fungal strains and batch-to-batch variability, the choice of fungal structure to be used as raw material, the type of culture and technology used to prepare allergenic extracts and the self-degradation of the extract once obtained .Allergy molecular diagnostic is improving the routine care. Currently, more than 130 allergens from more than 50 sources are commercially available and their use represents an undeniable advance. This is especially noticeable in the case of food and insect allergy and for the selection of allergen immunotherapy ,58.Aspergillus allergens could differentiate Aspergillus sensitization from ABPA [Of the 113 defined individualized fungal allergens, only 8 are available to perform the molecular diagnosis of fungal allergy and define clinical patterns associated with fungal allergens. For example, data reported from the literature show that rom ABPA ,60,61.A. alternata sensitization is the most prevalent in allergic patients to fungi and that Alt a 1 is an accurate marker to test species-specific sensitization or IgE-mediated allergy to A. alternata. Ninety percent of patients or more labeled as allergic to Alternaria react specifically to Alt a 1.Few works have been published addressing the diagnosis of fungal allergy using the CRD with the most common fungal allergens available ,62,63,64Alternaria revealed specific IgE values to Alt a 1, and the other two were positive to Alt a 6, showing highly relevant specific IgE values [A. alternata (Alt a 16) supports the mislabeling of Alternaria allergy and the possible diagnosis of Aspergillus allergy with connotations to ABPA [Curvularia was 4–6 times higher [Curvularia major allergen is a homolog of the Alt a 15, it could be considered the mislabeling of the Alternaria allergy and the possible diagnosis of an allergy to Curvularia [Alternaria [Postigo et al. reported that 28 out of 30 patients diagnosed with an allergy to E values . The dem to ABPA . Postigos higher . Considervularia . These rternaria . In thesternaria . A recenternaria ,69.Although Alt a 1 has been a defined allergenic protein since 1991 , in 2012Alternaria by elevating 26 clades to the subgeneric taxonomic status of section [Alternaria section consists of only 11 phylogenetic species and 1 species complex [Current phylogenetic studies have made significant changes to the systematic taxonomy of  section . Alterna complex ,72,73.Alternaria spp. and related taxa into several species-groups: infectoria, alternata, porri, brassicicola, sonchi, radicina and embellisia group. The monophyly of the Nimbya group was moderately supported and the monophyly of the Ulocladium group was weakly supported [Alt a 1 gene sequences contain more parsimony-informative sites than other phylogenetic markers. Analyses of Alt a 1 gene strongly support the clustering of upported . Despiteupported ,12,74.A. alternata from the environment, this being of particular interest for associating Alternaria with sensitization or respiratory allergy [A. alternata, A. tenuissima, A. infectoria, U. botrytis and S. botryosum using different Alt a 1 expression gene sequences. The specific sequence of Alt a 1 was able to detect an amplicon of approximately 390 bp from Alt a 1, encoding genes from species closely related taxonomically to A. alternata, such as A. tenuissima. By contrast, the PCR system using a conserved sequence of Alt a 1 homologs was able to detect an amplicon of approximately 180 bp from Alt a 1 and Alt a 1-like encoding genes from A. alternata, A. tenuissima, A. infectoria, U. botrytis and S. botryosum [A. alternata [Alternaria-Nimbya-Embellisia-Ulocladium and other clade with Stemphylium belonging to clade a very close to the mentioned above. A. alternata and A. tenuissima are taxonomically closely related species and are placed in a different group from those including A. infectoria, U. botrytis, and S. botryosum. Other analyzed Pleosporaceae, as Curvularia lunata or Drechslera tritici-repentis did not revealed homologous genes to Alt a 1 [Pleosporaceae species studied, the recognition of Alt a 1 homologs by antibodies is always relevant and Alt a 1 can be considered an excellent tool to be used in the serological diagnosis of allergic diseases caused by Alternaria.According to this concept, several authors have used Alt a 1 DNA sequence or Alt a 1 protein to identify and quantify  allergy ,75,76. Gotryosum . Similarlternata  and othelternata ,80. All  Alt a 1 . DespitePleosporaceae species, defines a protein family [Pleosporaceae family because Alt a 1 defines a group of phylogenetically related species.If we accept that the gene encoding Alt a 1-homologous-proteins is a taxonomic marker  and thatn family , it woulUnfortunately, so far, no data on the biological role of Alt a 1 has been conclusively elucidated.A. alternata extract, whether used in skin tests or for the detection and quantification of specific IgE/IgG [Alternaria respiratory allergy [From an allergological point of view, it could be suggested that the Alt a 1 protein, both in its native and recombinant form, is an excellent diagnostic marker to replace the  IgE/IgG . The Alt allergy .Alternaria species is a common saprophyte found on many plants and other substrates worldwide. It is an opportunistic pathogen that infects many agricultural crops in the field and during postharvest storage of vegetables and fruits. Alternaria species have been isolated from a wide range of fruits and vegetables. Certainly, this group includes the main pathogenic fungi in agriculture and food industry, resulting in severe agricultural and economic losses [c losses . Accuratc losses ,83.Alternaria species. Molecular approaches based on barcoding the gene region or gene fragments, such as the internal transcribed spacer (ITS) [A. alternata major allergen (Alt a 1) [Alternaria-Nimbya-Embellisia-Ulocladium in the Ascomycete family Pleosporaceae relationships [Alternaria sections, with accurate molecular differentiation and identification of isolates showing that the Alternaria section consists of 11 phylogenetic species and 1 species complex [The development of DNA technology has provided effective methods for the study of different fungi, and several genetic markers have been provided for their identification. These markers are widely used in PCR or chip detection . In receer (ITS) ,86,87,88Alt a 1) ,90, glycAlt a 1) , anonymoAlt a 1) ,88,89, tionships . Current complex ,72,73.Recently, some fungal allergens (Alt a 1 and Asp n 3) have been presented as valuable molecular markers of taxonomy and pathology/contamination in vegetables and fruits and also as molecular markers of allergenic contamination in indoor environments ,84,91.A. alternata, were able to detect the infection of citrus fruits by A. alternata at the onset of infection [Alternaria section, but the fragment encoding of the Alt a 1 gen (390 bp) only detected A. alternata and A. tenuissima. They also suggest that this protein could play a role in the pathogenicity and virulence of Alternaria species [Alternaria species of the plant [Gabriel et al., using primers defining the Alt a 1 encoding gen (390 bp) and the conserved region of Alt a 1 encoding gen (180 bp) from nfection . The con species ,91. Garrhe plant .Alternaria, a phylogenetic related species belonging to Pleosporaceae family. Although the Alternaria taxonomy has benefited from recent phylogenetic revisions, the basis of differentiation among the major phylogenetic clades of the group is not yet understood [Alt a 1 defines the respiratory allergy caused by derstood ,12,71,74It could be accepted that Alt a 1 is a protein associated with pathological phenomena in both animals and plants. Alt a 1 is useful for detecting and identifying indoor and outdoor amounts of the most important fungal allergen causing respiratory allergy and sensitization. It is tacitly accepted that Alt a 1 is an important marker for assessing the risk factor and severity of allergic respiratory disease . While m


Background: Heart failure (HF) and atrial fibrillation (AF) commonly coexist and patients with both diseases have a worse prognosis than those with HF or AF alone. The objective of our study was to identify the factors associated with one-year mortality in patients with HF and AF, depending on the left ventricular ejection fraction (LVEF). Methods: We included 727 patients with HF and AF consecutively admitted in a clinical emergency hospital between January 2018 and December 2019. The inclusion criteria were age of more than 18 years, diagnosis of chronic HF and AF , and signed informed consent. The exclusion criteria were the absence of echocardiographic data, a suboptimal ultrasound view, and other cardiac rhythms than AF. The patients were divided into 3 groups: group 1 (337 patients with AF and HF with reduced ejection fraction (HFrEF)), group 2 (112 patients with AF and HF with mid-range ejection fraction (HFmrEF)), and group 3 (278 patients with AF and HF with preserved ejection fraction (HFpEF)). Results: The one-year mortality rates were 36.49% in group 1, 27.67% in group 2, and 27.69% in group 3. The factors that increased one-year mortality were chronic kidney disease , coronary artery disease , and diabetes  in patients with HFrEF; and hypertension in patients with HFpEF . Conclusions: One-year mortality in patients with HF and AF is influenced by different factors, depending on the LVEF. Heart failure (HF) and atrial fibrillation (AF) are common cardiac diseases, which are frequently related and share common risk factors, such as old age, hypertension (HT), coronary artery disease (CAD), valvular heart disease, diabetes mellitus (DM), and chronic kidney disease (CKD) ,2,3,4,5.The management of patients with HF differs according to their LVEF . PatientAF is the most common sustained cardiac arrhythmia, with important impacts on morbidity, mortality, and quality of life ,7,8,9,10The objective of the study was to identify the risk of one-year mortality patients with chronic HF and AF and to determine the comorbidities that increase one-year mortality, according to LVEF. The risk of one-year mortality after discharge was chosen because this timeframe is critical for the response to recommended treatment and for assessing the impacts of comorbidities on patient prognosis.This was a prospective, observational case–control study. We recruited 2878 consecutively admitted patients with the diagnosis of HF, hospitalized in the Clinical Emergency Hospital of Bucharest, Romania, between January 2018 and December 2019. Of these patients, we selected 942 patients with AF .The inclusion criteria were age of more than 18 years, diagnosis of HF and AF, and signed informed consent to participate in this study.The exclusion criteria were the absence of echocardiographic data, a suboptimal ultrasound view leading to the imposibility to obtain minimum echocardiographic data (at least the LVEF), and other cardiac rhythms than AF.After applying the inclusion and exclusion criteria, 727 patients with AF and HF remained in the study. The diagnosis of HF was established based on the European Society of Cardiology Guidelines .The diagnosis of AF was made using a standard 12-lead electrocardiogram or automated continuous monitoring of cardiac rhythm for 24–72 h.The patients were divided into three subgroups according to the LVEF: subgroup 1 included 337 patients with HFrEF (46.29%), subgroup 2 included 112 patients with HFmrEF (15.38%), and subgroup 3 included 278 patients with HFpEF (38.18%). The study protocol is shown in 2, with a prior diagnosis of DM, or with newly diagnosed DM.Baseline demographics were obtained at inclusion in the study. We collected the following data about the patients: general and demographic data, medical history, current disease status, reason for hospitalization, current therapy, and comorbidities. The diagnosis of the comorbidities was established at inclusion in the study. Valvular pathologies were assessed by echocardiography and only patients with moderate or severe valvular disease were included in the study. The diagnosis of CAD was established by non-invasive tests for myocardial ischemia, such as stress echocardiography, stress myocardial scintigraphy, cardiac magnetic resonance imaging, or by invasive assessment by angiography. Patients with all degrees of myocardial ischemia were included. These included enrolled patients with a prior diagnosis of CKD and with a glomerular filtration rate < 60 mL/min/1.73 mThe study respected the ethical standards of the Helsinki Declaration of 1975, as revised in 2008(5), as well as the national law. We ensured that patients’ rights were protected and the confidentiality of their data was maintained. The study was approved by the Ethics Committee of the Clinical Emergency Hospital of Bucharest, Romania .In order to completely assess the comorbidities of patients with HF and AF, such as CAD, CKD, DM, dyslipidemia, and liver diseases, blood tests were performed on all patients enrolled in the study using an ABX pentra XL 80 hematology autoanalyzer for complete cell blood counts  and a BioMajesty biochemistry autoanalyzer for creatinine (0.7–1.4 mg/dL), blood urea nitrogen (19–43 mg/dL), serum sodium (137–145 mmol/L), serum potassium (3.5–5 mmol/L), aminotransferases , glycemia (75–110 mg/dL), troponin I (<5 ng/mL), creatine kinase (55–170 U/L), creatine kinase-MB (10–16 U/L), total cholesterol (140–200 mg/dL), and triglycerides (30–150 mg/dL).In this study, 2D transthoracic echocardiography was performed on all patients enrolled in the study, either at inclusion in the study or the data were extracted from the medical records of the patients if the data were consistent with our examination protocol.We used commercially available ultrasound systems, such as the Phillips CX 50 or Vivid 9 machine. Conventional measures, such as the dimensions of the LV walls, LV end-diastolic and end-systolic diameters and volumes, left atrial diameter and volume, right atrial diameter and area, and right ventricular diameter were obtained. LVEF was calculated in the apical 4- and 2-views using the modified Simpson’s biplane method, or if this was not possible, LVEF was visually estimated. Valvular pathologies were evaluated using color, pulse, and continuous Doppler measurements. The aorta and pericardium were also assessed.2 test) was used to estimate whether there were statistically significant differences between the frequencies of several characteristics and comorbidities of the patients in the three groups. A value of p < 0.05 was considered to be statistically significant.Statistical analysis was performed using R software version 4.0.2 (c) R Core Team 2020 . Descriptive statistics are presented as absolute frequencies, mean values ± standard deviation, and medians with interquartile range. In order to identify the factors that may influence the mortality in the group of study, a binomial univariate logistic regression was used. At first, a simple logistic regression was used with a single predictor rather than multiple logistic regression, with a backward selection algorithm for multiple predictors of mortality. The dependent variable (“output”) was the rate of mortality and the independent variables (“input”) were the individual clinical  and demographic  characteristics and the comorbidities of the patients. Normally distributed data are expressed as means ±standard deviation. Data deviating from the normal range are expressed as median values. The analysis of variance (ANOVA) was applied to compare the differences among the mean ages of the three groups of patients. The chi-squared test  than those with HFrEF (mean age 70.77 ± 11.15 years). The proportion of females was greater compared to males (60.08% versus 39.92%) in the group of patients with HFpEF. In the group of patients with HFrEF, there were more men than women (68.84% versus 31.16%).The rate of one-year mortality for patients with HF and AF depending on their LVEF was 27.69% in patients with HFpEF, 27.67% in those with HFmrEF, and 36.49% in HFrEF.Firstly, a simple binomial regression model was performed to identify the one-year mortality predictors for every subgroup of patients. HT was associated with increased one-year mortality in patients with HFpEF  . MoreoveIn patients with HFrEF, we determined the following factors associated with increased mortality: CAD–OR 1.67, 95% CI 1.06 to 2.62; aortic regurgitation (AR)–OR 1.95, 95% CI 1.09 to 3.50; aortic stenosis (AS)–OR 2.00, 95% CI 1.04 to 3.83; CKD–OR 2.35, 95% CI 1.45 to 3.83; DM–OR 1.66, 95% CI 1.05 to 2.67 . In thesNYHA class IV was associated with higher risk of mortality in all three groups of patients compared to NYHA class II, as follows: in patients with HFpEF, NYHA class IV had a 2.45-fold higher OR than NYHA class II; in patients with HFmrEF, NYHA class IV had a 4-fold higher OR than NYHA class II; in patients with HFrEF, NYHA class IV had a 3.86-fold higher OR than NYHA class II. In patients with HFrEF, NYHA class III was also associated with a greater risk of mortality compared to NYHA class II (2.25-fold increase of OR).Uncommon comorbidities in the study group, such as mitral stenosis, chronic obstructive pulmonary disease, and sleep apnoea syndrome, were mentioned in the general description of the patients  but wereA multiple univariate binomial logistic regression model was performed in patients with HFpEF, revealing that the independent predictors for one-year mortality were age (one-year increase in age was associated with a 9% higher OR), NYHA class IV (3-fold higher OR than NYHA class I/II), and HT  ; thus, iA multiple univariate binomial logistic regression model was also performed in patients with HFrEF, using all statistically significant predictors that influenced mortality in the simple model in order to identify the independent predictors. Not all predictors of mortality from the simple regression model appeared as independent predictors in the multiple regression model, such as reduced LVEF, CAD, and DM ; therefoThe objective of this study was to identify the characteristics and comorbidities that influence the one-year mortality in patients with HF and AF according to their LVEF and the differences between the three subgroups of patients.Advanced age represents a risk factor for mortality in patients with HFrEF and HFpEF. Patients with severe symptoms, namely NYHA class III or IV, had a higher risk of mortality than those with mild symptoms, regardless of their LVEF. Patients with HFpEF were older than those with HFrEF. Sex differences were noticed between the subgroups; therefore, patients with HFpEF were more frequently women, while those with HFrEF were more frequently men. The predominance of women among patients with HFpEF represents one of the most important differences between patients with HFpEF and those with HFrEF. Women have higher myocardial stiffness, leading to increased LV filling pressures and diastolic dysfunction but greater LVEF compared to males ,28. WomeIn the current study, patients with HFrEF had a higher risk of one-year mortality compared to those with HFmrEF or HFpEF. The risk of mortality was similar in patients with HFpEF and HFmrEF. The risks of mortality in patients with AF and HF have been discussed in several clinical trials, including patients with all types of HF ,32,33. TOur study focused on determining if there are different factors and comorbidities influencing mortality in the three subgroups of patients. In patients with HFpEF and AF, HT was a risk factor that increased one-year mortality. HT is a well-known cardiovascular risk factor and is the most common comorbidity in patients with HFpEF . SystemiIn the current study, CAD, CKD, and DM increased the risk of death in the subgroup of patients with HFrEF and AF. Myocardial ischemia, especially if prolonged or recurrent, leads to LV remodelling, dilation, and systolic dysfunction. After myocardial infarction, a proinflammatory reaction appears as a response to cardiomyocyte injury in order to mediate tissue repair; however, an excessive inflammatory response may induce myocardial injury; thus, the degree of the inflammatory reaction seems to be an important point in HF development after myocardial infarction . IncreasThe therapeutic options for patients with CAD include medical, interventional, or surgical treatment. Several studies have evaluated the efficiency of these therapeutic methods regarding the prognosis of patients with HFrEF and CAD ,39,40. M2, is that these patients are less likely to receive the specific therapies that reduce mortality in HFrEF, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ARNI, SGLT-2 inhibitors, and mineralocorticoid antagonists, because of kidney dysfunction and hyperkalemia. Patients with HFrEF and glomerular filtration rates < 30 mL/min/1.73 m2 have usually been excluded from clinical trials that have evaluated the effects of the drugs mentioned above because of their possible toxicity in these patients; therefore, patients with HFrEF and advanced CKD represent a special category of patients with fewer therapeutic options and a worse prognosis.The results of the current study showed that patients with HFrEF, AF, and CKD had a higher risk of mortality than those with HFrEF, AF, and normal renal function. HF and CKD are chronic disorders that frequently coexist . Their iDM is another factor that increased the risk of mortality in patients with HFrEF and AF enrolled in this study. DM is a frequent comorbidity in patients with HF, which leads to a higher risk of death in patients with both HFrEF and HFpEF compared to patients without DM ,56,57,58Our results showed that advanced age, advanced functional class of HF, and reduced LVEF increased the one-year mortality in patients with HF and AF. We demonstrated that there are different comorbidities that influence one-year mortality in patients with HF and AF, depending on the LVEF, such as HT in patients with HFpEF and CAD, CKD, and DM in patients with HFrEF. All these diseases aggravate each other and their association leads to a significantly worse prognosis and reduced survival.The main limitation of our study is the relatively low number of patients with HFmrEF included, which is fewer than those with HFpEF and HFrEF; this could explain why we have not found any particular factors associated with one-year mortality in this group of patients, except for age and functional class of HF. There were also possible differences in appreciating the ultrasound parameters because of the different examiners who performed transthoracic echocardiography.Future research may be focused on evaluating whether an early diagnosis and treatment of the comorbidities in patients with HF and AF may influence the prognosis of these patients with multiple pathologies by reducing the mortality. Another area of research may be focused on evaluating the benefits of the therapeutic strategy of CAD, namely interventional (angioplasty) versus surgical (coronary artery bypass grafting) options, in patients with HF and AF. Another point of interest for research may be to determine whether the duration of AF influences the one-year mortality in patients with HF. Research may be also focused on determining how the severity levels of CAD (stable CAD or acute coronary syndrome), CKD , and DM  may influence mortality in each of the subgroups of patients with HF and AF.HF and AF are some of the most common cardiovascular disorders, which frequently coexist. The association of these two pathologies leads to an important rate of mortality, especially in patients with HFrEF. This study demonstrated whether advanced age and functional class of HF are predictors of mortality in all patients with HF, regardless of the LVEF. Furthermore, we determined that one-year mortality is influenced by different factors, such as HT in patients with HFpEF and CAD, CKD, and DM in patients with HFrEF.