Defective nanographenes containing joined pentagons and heptagons exhibit striking physicochemical properties from both experimental and theoretical perspectives compared with their pure hexagonal counterparts. Thus, the synthesis and characterization of these unique polyarenes with well‐defined defective topologies have attracted increasing attention. Despite extensive research on nonalternant molecules since the last century, most studies focused on the corresponding mutagenic and carcinogenic activities. Recently, researchers have realized that the defective domain induces geometric bending and causes electronic perturbation, thus leading to significant alteration of the photophysical properties. This review discusses the synthesis and characterization of small nonalternant polycyclic hydrocarbons in the early stage and recent developments in embedding pentagon–heptagon (5–7) pairs into large carbon skeletons through in‐solution chemistry. π‐electron systems. This review presents a clear development progress on the synthesis of this kind of defective nanographenes from the last century to up‐to‐date reported examples, which aims to comprehensively understand their structure‐related properties.Defective nanographenes containing edge‐sharing pentagon–heptagon (5–7) pairs exhibit intriguing physicochemical properties when compared to their hexagonal counterparts owning to perturbation on conjugated  The use of graphene has led to new insights into materials science and technology owing to its extraordinary physicochemical properties. However, structural defects appear to be inevitable in graphene networks. Such structural defects occur because of the second law of thermodynamics, which dictates that disorder occurs in the crystal lattice. These defects also occur during the growth or processing, which includes epitaxial growth on metal surfaces.Graphene has a perfect atomic lattice and consists of a planar hexagonal network of all spoperties.2, 3Figure One example of a graphene defect is a class II defect with  and  matching vectors  of 1.04 eV, in sharp contrast to the lack of a bandgap in graphene. Unfortunately, the generation of structural defects in graphene by crystal growth, irradiation, and chemical treatment usually occurs randomly and arbitrarily; thus, precise control of the defect location is challenging. From both fundamental and applied perspectives, a thorough understanding of these topological defects will be of great importance. Accordingly, the investigation of well‐defined defects in atomically precise and monodisperse graphene fragments will play a unique role in engineering defects in graphene to elucidate the structure–property relationships.In general, graphene defects are divided into two categories: 1) intrinsic defects, including point defects (0D), dislocation (1D), and grain boundaries (2D) Figure1; and s Figure ,[9]  nonhexagonal polygons have produced a local Gaussian curvature in the planar carbon network. Generally, pentagons cause a positive (bowl‐shaped) curvature, while heptagons lead to a negative (saddle‐shaped) curvature. Moreover, the electronic properties in defective nanographenes are different from those in pure hexagonal networks. For instance, according to Hückel's rule, pentagons and heptagons can become more stable because they gain additional aromatic stabilization energy when accepting/losing one electron to form a 6π‐aromatic cyclopentadienyl anion/tropylium cation, which has also been experimentally supported.Among these defects in the fragments of graphene (polycyclic hydrocarbons (PHs), also named nanographenes), pentagon‐ and heptagon‐embedded nanographenes have been extensively investigated. For example, since the discovery of fullerenes in the 1980s,14 nonπ‐electron system. However, the abovementioned investigations are severely restricted to characterization within 2D materials and are limited to theoretical studies. Consequently, the physicochemical properties induced by these topological defects in graphene remain elusive. Nevertheless, it is reasonable to speculate that such defective graphene molecules could have distinguishable topologies and properties. For instance, the curvature, aromaticity, chemical activities, and photophysical properties of nanographenes could be affected by the introduction of defects. Thus, the atomically precise construction of 5–7 paired defects in nanographenes is necessary for understanding the structure–property relationships. Nevertheless, integrating edge‐sharing pentagons and heptagons into the polyarene framework is a very challenging task because there is a lack of appropriate synthetic methodologies that form two different nonhexagonal rings in the same molecule.Pentagon–heptagon pairs (5–7 pairs or azulene units), which can be regarded as structural isomer of naphthalene, have often been observed in graphene networks as intrinsic structural defects Figure . Theoretn system.13 Howπ systems exhibit diverse geometries, including bowl‐shaped, saddle‐shaped, and tub‐shaped, and they also exhibit varied electronic configurations. Some reviews on curved nanographenes with five‐ and/or seven‐membered rings have been published recently. Accordingly, this review focuses on defective PHs with edge‐sharing 5–7 pairs, including their synthetic protocols, topological geometries, and physicochemical properties, in terms of recent advances. The main text is categorized into two main parts differentiated by time: pioneering works on the synthesis of nonalternant PHs in the early stage, and their incorporation into a larger carbon skeleton, which has occurred over around the past five years.Pentagon‐ or/and heptagon‐containing nanographenes have been extensively investigated. It is well known that different nonhexagonal polygons integrated into l‐shaped,17 sad2 Additionally, owing to its unique nonhexagonal topology, azulene exhibits a smaller energy gap and abnormal optical behavior (anti‐Kasha's rule) compared to that of naphthalene as a result of the nonmirror related highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Such behavior leads to its intriguing optoelectronic properties, and azulene has attracted significant attention for use in practical applications since it was first discovered by Piesse in 1863.Azulene is an isomer of naphthalene and is the smallest nonalternant and nonbenzenoid aromatic compound; it consists of one electron‐rich pentagon and one electron‐deficient heptagon, which endow it with a large dipole moment of approximately 1.08 D.26 Addπ‐electron networks. This section will focus mainly on small nonalternant molecules containing joined pentagonal and heptagonal rings in the early stage and discuss them chronologically.Furthermore, a separated azulene unit and aligned azulene clusters have been observed experimentally in 2D graphene and are regarded as structural defects. As mentioned above, the 5–7 pair defect (azulene unit) observed in graphene has a low formation energy and is energetically favorable in thermodynamics over other nonhexagonal defects while exhibiting significantly altered electronic configurations. Incorporation of the analogous 5–7 pair defect into polycyclic systems has triggered increasing research interest owing to its unique defective topology and distinctive conjugated  In 1955, Ward et al. further studied whether azulene retains its original properties after fusion with the phenyl group. Accordingly, two structures with different fusion models were selected for preliminary examination: compounds 5 and 5′  absorption spectra and basicity measurements demonstrated that hydrocarbon 5 exhibited common azulenic characteristics. Unfortunately, attempts to synthesize compound 5′ failed in this work.Research interests on the 5–7 pair defect in aromatics date back to the early 20th century. Inspired by the unique chemical properties of azulene, Tazuma suggested a resonance hybrid of covalent and betaine forms.32 In ′ Scheme , it was 1 Scheme .[34]11, another isomer of compound 5, was reported by Osborn et al. in 1957. As shown in Scheme de]naphthalene (compound 6), a large‐scale Reformatsky product (compound 7) was prepared. Then, dehydration and base hydrolysis were conducted to afford two isomeric unsaturated acids (compounds 8‐1 and 8‐2). Compound 9 was obtained as a racemic mixture by the reduction of 8‐1 and 8‐2 over Pd/C in acetic acid. Dehydrogenation of the ester of compound 9, followed by hydrolysis and cyclization, afforded compound 10, which bore both a heptagon and pentagon ring. Finally, compound 11, which contained an azulene unit, was synthesized in two successive steps, including reduction of the ketone and aromatization by chloranil. The UV–vis spectrum of compound 11 showed two well‐resolved peaks at 300–350 and 400–440 nm, as well as a broad peak extending from 460 to 650 nm.Compound  in 1957.35 As cd]phenalene  ammonium perchlorate in the presence of methoxide in pyridine afforded a violet phenafulvalene derivative (13), which was converted into the final phenalene‐fused azulene (14) as green leaflets in moderate yield when heated in quinoline at 180 °C. The structure was confirmed by mass spectrometry and elemental analysis. Further experiments of compound 14 demonstrated azulene‐like properties, for example, intense green fluorescence due to the formation of carbonium ions when it was mixed with acetone in an alcoholic mineral acid solution. Compound 14 exhibited several UV–vis absorption bands with central peaks of 741, 702, 666, 633, 614, 451, 426, and 316 nm.Instead of incorporating an azulene unit with naphthalene, in 1966, Dr. Jutz et al. reported the synthesis of azuleno3718  cyclization, and then this intermediate underwent the same steps to afford another ketone (21) with an additional five‐membered ring. Treatment 21 with hydrazine hydrate gave key precursor 22. Subsequently, after a reaction sequence involving a ring‐expansion reaction, hydrolysis, and decarboxylation plus dehydrogenation on Pd/C, azupyrene 23 was obtained as square, bronze platelets with a yield of 2.5%. Its structure was confirmed by NMR and mass analysis. Some investigations, including infrared (IR) spectroscopy and diamagnetic susceptibility were conducted, in which two sharp bands, at 1588 and 1538 cm−1, were similar to those in the azulene unit, and the diamagnetic susceptibility was to some extent indicative of the aromaticity of azupyrene. Azupyrene exhibits distinctive electronic properties compared to those of its alternant isomer pyrene owing to its nonhexagonal rings, such as smaller energy gap, more localized charge distribution, and a different conjugation pathway. Furthermore, a modified synthetic procedure was developed by Anderson and Jutz, affording the product in moderate yield, and detailed studies involving theoretical calculations and photochemical spectroscopies elucidated the influence of the topological structure on the electronic configuration and molecular properties.Azupyrene, a structural isomer of pyrene Scheme 4a, was fScheme 38 It y Scheme . The key28, Scheme  which exhibited electronic properties that were different from those of compound 14. The UV–vis spectrum showed that the longest wavelength of compound 28 was at 1010 nm, whereas the longest wavelength of compound 14 was located at 739 nm, which indicated a significant difference between these two isomers. Similarly, ketone 24 was used as a key building block to expand the ring skeleton, affording compound 26 in several steps, including the Reformatsky reaction, reduction, hydrolysis, cyclization, and dehydrogenation. Isomeric compound 27 was quantitatively converted from 26 after being passed through an alumina column or from 26 after treatment with n‐BuLi followed by quenching with water. Subsequently, a fulvene intermediate was obtained when 27 and dimethyl ammonium perchlorate were treated with sodium methoxide at room temperature. Cyclization of fulvene at 180 °C afforded azulenophenalene (compound 28) as stable dark red plates with a yield of 62%.Another polycyclic skeleton  were obtained in a reaction sequence that included several main steps, such as nucleophilic addition, reduction, and cyclization. The treatment of precursors with reducing agents and then aromatization under high temperature afforded the final fully conjugated, red, plate‐like molecules (39) and black needle‐like molecules (44). Interestingly, compound 39 exhibited a clear blueshift in the absorption spectrum compared to that of compound 5, which had a smaller conjugated network. However, the absorption spectrum of compound 44 was quite similar to that of compound 11. Furthermore, compound 39 showed typical basicity and could be reversibly protonated in degassed trifluoroacetic acid, whereas compound 44 was a nonbasic hydrocarbon.Other isomers of benzo in 1979.48 The48 Thea47, Scheme  The synthesis started from compound 45, which can be prepared according to a modified procedure toward pyrene and compound 28, followed by irradiation or reaction with I2 in dichloromethane (DCM) to afford compound 46 as green needles with yields of 48% and 85%, respectively. Overnight treatment of 46 with chloranil in benzene quantitatively yielded final target 47 as dark violet leaflets. The NMR and electronic spectra of 47, in which absorption traces consisted of two main absorption peaks at 380 and 580 nm, as well as one shoulder peak around 700 nm, suggested that the [22]annulene resonance structure (47a) served as a major contributor rather than the 2,2′‐biazulene, which contained two additional double bonds (47b).In 1981, Itô et al. reported a nonalternant isomer , which was exposed to SOCl2 and CH2N2 to yield diazo sulfoxide (50). Compound 51 can be easily obtained and separated as colorless crystals from the further decomposition of 50 in situ, followed by dehydrogenation in the presence of DDQ to produce α‐chloro sulfoxide 52 as orange needles. The final target, 53, as greenish‐black needles, can be quantitatively converted from 52 through the Ramberg–Bäcklund reaction. The single‐crystal analysis clearly confirmed the nonalternant structure and substantially corroborated the planar molecular skeleton. Furthermore, the bond analysis revealed that [14]annulene with an additional central double bond (53a) was the dominant resonance structure, and this conclusion was also supported by other spectral analyses.Another isomer of pyrene , a mixture of diastereoisomeric sulfoxides (56) was obtained, which was surprisingly converted to the tetracyclic azulene derivative 57 when heated at approximately 55 °C. Owing to the highly reactive site on the free vertex of the pentagon, treatment of 57 with trityl tetrafluoroborate afforded triphenylmethyl‐substituted derivative 58, and then, sequential treatment with trityl‐tetrafluoroborate and diethyl ether yielded the final fully conjugated compound 59b as black needles. The UV–vis spectrum exhibited its longest absorption wavelength at 750 nm. From the analysis of the NMR spectrum, it was proposed that the Kekule structure of compound 59b should sustain a paramagnetic ring current induced by peripheral 16π electrons with an external double bond. Cyclic voltammetry (CV) of 59b showed two oxidation waves at 0.43 and 1.10 V, and one reduction wave at −1.18 V. The first oxidation potential of 59b was comparable to that of its isomer cyclohepta[a]phenalene (Eox = 0.39 V).In 1991, Murata et al. presented a novel nonalternant hydrocarbon55 as In conclusion, because of the lack of effective synthetic protocols for cyclization and incorporation of the 5–7 paired defect into larger carbon skeletons, most of the abovementioned examples applied intramolecular F–C reactions in the presence of strong acids for the cyclization step to form cyclic ketones, and thus, only relatively small PHs were developed during the last century. After F–C acylation, which is normally followed by reduction and dehydration plus aromatization, fully conjugated hydrocarbons can be obtained. Furthermore, analytical techniques during that period are quite limited, which makes it difficult to characterize fully their physicochemical properties and to conduct detailed investigations of the structure‐related differences between alternant and nonalternant topologies. Instead, researchers have focused on the mutagenic and carcinogenic activities of PHs.573 and E. Clar in the first half of the 20th century and further developed over the century. However, owing to the lack of effective synthetic methods and the limited techniques available for characterization, the synthesis of extended PHs (nanographenes or graphene‐type molecules) with well‐defined sizes and edge structures has remained stagnant for decades, and their corresponding structure–property relations have also been elusive. Up to the beginning of the 21st century, great progress was made in modern organic synthesis and analytic techniques, especially in metal‐mediated coupling reactions, thus allowing the construction of various uniform extended PHs under mild conditions and revealing structure‐related properties such as electronic, optical, and magnetic characteristics. Furthermore, research on large PHs has gained new impetus since the first experimental demonstration of graphene in 2004, as graphene could be used in next‐generation nanoelectronics. Although much progress has been achieved during the past decade, incorporating 5–7 pair defects into larger carbon skeletons remains challenging because of the lack of a facile synthetic approach for the construction of odd‐membered rings. Additionally, the influence of molecular topology on properties has been gradually demonstrated by theoretical calculations, and its importance has also been increasingly recognized, resulting in revived attention on nonalternant conjugated systems.Pioneering works on the chemical synthesis of PHs were conducted by R. Scholl59 andπ‐extension of the azulene unit have recently shown potential. This section will focus on the very recent synthetic advancements toward defective nanographenes containing 5–7 pairs on the basis of a key nonhexagon‐forming step.Recently, a growing amount of effort has been made to integrate 5–7 pairs into large polyarenes through solution chemistry followed by detailed characterization of their physicochemical properties. Current strategies for the construction of odd‐membered rings, especially for 5–7 pairs in this context, can be classified into several categories including Scholl reactions, F–C cyclization, and metal‐mediated annulation. Moreover, new methods such as photocyclization and 3.1 Thus far, this reaction has been a versatile tool for the synthesis of various fully conjugated π‐electron systems, such as giant nanographenes, graphene nanoribbons, and twisted nanographenes containing odd‐membered rings. Reagents involved in the Scholl reaction normally consist of oxidants and Lewis acid; for example, DDQ/trifluoromethanesulfonic acid (TfOH), FeCl3, Cu(OTf)2/AlCl3, and [bis(trifluoroacetoxy)iodo]benzene (PIFA)/BF3·Et2O have been extensively used in cyclodehydrogenation processes.The Scholl reaction, also called intramolecular oxidative cyclodehydrogenation, has been widely used for the construction of (extended) PHs for over a century since the original report by Scholl et al. in 1910.59 Thu owing to the unexpected migration of alkyl and/or aryl groups and ring skeleton rearrangement. Very recently, several groups have reported this unusual phenomenon during the Scholl‐type process, which has afforded 5–7 pair defects embedded in nanographene scaffolds, thus allowing for detailed investigation of the unique electronic properties of nonalternant topological structures.However, the mechanism of this C—C bond‐forming reaction remains elusive and controversial81 owi3.1.1Scheme 60a in the presence of DDQ/TfOH or FeCl3/CH3NO2 exclusively gave the pentagon‐forming product 61a, in this work, the modified precursor 60b was prepared to conduct the same highly selective Scholl reaction that enabled the generation of azulene‐embedded nanographenes. In contrast, treatment of precursor 60b with FeCl3/CH3NO2, even in a large excess of equivalents, afforded only the pentagon‐containing chlorinated product 61b. In the presence of DDQ/TfOH, two pentagons accompanied by two heptagons were formed, resulting in three unexpectedly substitutional products 62, of which the respective yield was dictated by the concentration of DDQ. In particular, bistriflated product 62a could undergo further postmodification such as a palladium‐mediated cross‐coupling reaction to yield larger aromatics. A high‐quality single crystal of 62c with two dichlorovinylidene (DCV) groups was obtained by slow vapor diffusion of chloroform/methanol, confirming its negatively curved geometry due to the presence of two heptagons in the scaffold. The bond length analysis demonstrated that the embedded 5–7 pairs in 62c exhibited longer bonds and more significant alternation patterns than those of pristine azulene units, which indicated less aromaticity. The optical properties of 62 were investigated using UV–vis absorption and emission spectroscopy. The maximum absorption peaks assigned to the S0–S1 HOMO to LUMO transitions were located in the range of 628–644 nm owing to the gradual extension of the π systems, similar to that of azulene. The emission of 62 was shifted to 648–671 nm, close to the near‐IR (NIR) regime, with a quantum efficiency of up to 27%.As one of the most powerful tools for synthesizing nanographenes, Scholl‐type cyclodehydrogenation can form hexagonal rings in most cases, and odd‐membered rings or azulene units embedded in nanographenes have recently been synthesized through this process. In 2019, the Mastalerz group reported the synthesis of contorted nanographenes with two azulene motifs Scheme 10. On t67) containing two 5–7 pairs through an FeCl3‐mediated Scholl reaction  and 1.354–1.458 Å (conformer 2), while pristine azulene had a more average distribution of 1.387–1.427 Å, which was also consistent with the LOL‐π  calculation showing π‐delocalization over the E/F/B/I/H rings. The UV–vis absorption spectrum of 67 exhibited two bands at 305 to 345 nm and 610 to 666 nm, which were ascribed to the S0–S2 and S0–S1 transitions, respectively. Moreover, this azulene‐containing nanographene 67 showed two emission peaks at 400 and 670 nm corresponding to the S2–S0 and S1–S0 transitions, respectively. On the basis of density‐functional theory (DFT) calculations, the incorporated azulene unit in 67 makes a major contribution to this abnormal anti‐Kasha emission. Furthermore, the electronic properties of 67 were investigated by CV and the construction of organic field‐effect transistors, indicating multiple redox abilities and p‐type semiconducting behavior, with a low average charge mobility of 0.049 cm−2 V−1 s−1 due to the disordered packing.In 2020, Zhang et al. presented another nonalternant nanographene (n Scheme 11.circulene analog 73 from COT congener 72 through cyclodehydrogenation (Scheme 72 with either FeCl3/CH3NO2 or DDQ/Sc(OTf)3 afforded the unexpected product 74, which had a 5–7–5 core. Further experiments demonstrated that skeletal rearrangement could occur at higher temperatures in the presence of DDQ/Sc(OTf)3, generating all hexagonal frameworks 75 from either pristine COT congener 72 or heptagon‐containing 74 , indicating a tendency toward chemical oxidation.In 2017, Tobe et al. reported a stepwise skeletal rearrangement from a cyclooctatetraene (COT) derivative to a 5–7–5 core and finally to all hexagonal rings under Scholl‐type conditions.91 Ini4 Scheme . DFT calScheme  Precursor 77 was prepared from diacetylene 76 through selective ICl‐induced cyclization. Treatment of 77 with DDQ/MsOH exclusively generated unexpected helical nanographene 78 containing an azulene unit with a good yield of 83% instead of the projected heptalene‐embedded compound 79  of 77, followed by skeletal rearrangement  and HI elimination during Scholl‐type oxidative cyclization. To further investigate this interesting result, a larger and flexible precursor 81 was rationally designed and prepared by a reaction sequence that included Diels–Alder cycloaddition and ICl‐mediated benzannulation  exhibited highly helical conformations due to the central heptagon‐containing [6]helicene. Furthermore, the embedded azulene units in these helical nanographenes were found to be highly twisted due to the steric hindrance; for example, compound 82b has a record‐high twisting angle (16.1°). In combination with bond length analysis and DFT calculations, the inner azulene moiety showed weak aromaticity. The optical and electronic properties of 78 and 82 were investigated by UV–vis spectroscopy and CV, and the calculated optical and electronic energy gaps were consistent with each other. Interestingly, superhelicene 82b featured six reversible oxidation waves with Eox1/2 potentials of 0.31, 0.48, 0.87, 1.08, 1.23, and 1.37 V, accompanied by two reversible reduction waves with Ered1/2 at −1.69 and −2.09 V, indicating its amphoteric redox properties.In 2020, a class of unprecedented helical nanographenes containing azulene moiety was reported by Feng and Liu through an unexpected Scholl reaction Scheme 14.helicene 84 and fully fused heptagon‐embedded framework 85  exhibited aromatic properties similar to those of the pristine azulene, which was also supported by the optical spectra including an absorption tail up to 800 nm arising from a forbidden HOMO–LUMO transition and weak photoluminescence in DCM.Another skeletal rearrangement from naphthalene to azulene was reported by Chi et al. in 2020.93 The3.2 TfOH, and MsOH, utilizing carbonyl and carboxylic acids as substrates, in which cyclic ketones are generated. Then, after two consecutive reactions involving nucleophilic addition using Grignard and organolithium reagents and SnCl2‐mediated dehydroxy reduction, the final desired nanographenes can be obtained. While F–C alkylation usually starts from aldehyde‐containing substrates, electrophilic addition affords alcohol species for Lewis acid (such as BF3·OEt2)‐mediated cyclization. The obtained cyclized product can be dehydrogenated using DDQ or p‐chloranil as the oxidant to give fully conjugated nanographenes. In recent years, the F–C reaction has received increasing attention for the construction of odd‐membered rings such as heptagons.The F–C reaction, one of the most typical methods of forming C—C bonds, has been widely used for intramolecular cyclization in nanographene chemistry. Commonly, the F–C reaction can be classified into two categories: F–C acylation and alkylation. F–C acylation normally occurs under strong acid conditions, such as the presence of polyphosphonic acid (PPA),94 TfOScheme  In this work, the easily accessible substrate 87 was obtained through several modular steps including the Suzuki coupling, Sonogashira reaction, and ICl‐mediated cyclization, undergoing a 1,2‐phenyl shift in the presence of DDQ/TfOH to afford 88 with two additional pentagons according to their previous finding. Then, four consecutive steps involving bromination, esterification, hydrolysis, and oxidation proceeded to achieve transformation from methyl groups to aldehyde groups, affording key precursor 89. Following routine procedures, including electrophilic addition and BF3·OEt2‐mediated F–C alkylation and oxidation, the final fully fused compound 91 was obtained as a purple powder, the structure of which was roughly confirmed by high resolution (HR) mass spectrometry. Variable temperature (VT) 1H NMR analysis of compound 91 exhibited silencing above −70 °C, while a broad signal appeared when the temperature was reduced below −70 °C, which indicated that triplet species could be easily activated. Accordingly, the magnetic properties of the target were investigated by electron paramagnetic resonance (EPR) and superconducting quantum interference device (SQUID) spectroscopy measurements, and both sets of spectral results indicated singlet biradical character in the ground state, in which the singlet–triplet energy gap (ΔES–T) was estimated as −2.15 kcal mol−1 through the Bleaney–Bowers equation, close to the value determined via DFT calculation . Furthermore, the optical properties of 91 and its precursor 90 were characterized using UV–vis–NIR spectroscopy. In contrast to compound 90, which showed a well‐resolved peak, compound 91 exhibited a broad absorption band in the NIR region with a maximum at 936 nm. Accordingly, it had a small energy gap of 1.13 eV. This optical property of 91 is empirically regarded as a characteristic of open‐shell species and can be used for preliminary judgment of whether nanographene has biradical character. The electronic behavior of open‐shell nanographene 91 was studied by CV. Two low oxidation waves at 0.11 and 0.61 V (vs. Ag/AgCl) were observed, indicating that the compound is easily oxidized in an ambient environment.In 2019, Müllen, Fasel, and Feng presented an open‐shell nonalternant nanographene containing two azulene units Scheme 16.fluorene derivatives  were synthesized by Suzuki coupling in a yield of 81%, 34%, and 70%, respectively. Subsequently, general nucleophilic addition with MesMgBr and followed by intramolecular F–C alkylation of compounds 110, 115, and 119 in the presence of BF3·Et2O afforded dihydro‐precursors 111, 116, and 120, respectively. Final, conjugated compounds 112, 117, and 121 were obtained through oxidative dehydrogenation in the presence of DDQ, which were confirmed by HR–mass spectrometry. Open‐shell characters of these three molecules were supported by UV–vis–NIR, VT‐1H NMR, and EPR analyses. The UV–vis–NIR absorption spectra of 112, 117, and 121 exhibited significantly low‐energy absorption maximum at 1700, 1860, and 1220 nm, respectively, leading to quite narrow optical energy gap of 0.54, 0.52, and 0.69 eV, which are in consistence with DFT calculations. Furthermore, continuous‐wave EPR (cw‐EPR) and VT‐EPR measurements revealed the singlet ground state of nonalternant PHs 112, 117, and 121 with low‐lying triplet states and small ΔES–T , which also supported by VT–1H NMR results. However, DFT calculations demonstrated triplet ground states for PHs 112 and 117, singlet state for PH 121, which mostly can be ascribed to imperfect energy calculation of corresponding functions.Very recently, three benzo‐extended cycloheptadi[7]annulene (BDA) and indenofluorene (IF) subunits in a conjugated framework Scheme 22. annulation of 3,9‐diboraperylene (143) and 1,2‐dibromoacenaphthylene (144) gave a nonalternant molecule (145) containing two azulene moieties in a yield of 15%. The electronic properties of 145 were investigated first by CV and square wave voltammetry. Interestingly, the CV traces of 145 featured two low‐lying reversible oxidation waves at 0.00 and 0.20 V (vs. Fc+/0), indicating electron‐donating ability. Accordingly, stepwise oxidation was conducted by using nitrosonium hexafluoroantimonate (NO•SbF6) to afford radical cation 145•+ and dication 1452+, which could be converted back to the neutral compound 145 by treatment with triethylamine. X‐ray crystallography and DFT calculations of 145, 145•+, and 1452+ revealed reorganization of geometries and distinctive electronic configurations. In the solid‐state, the neutral compound 145 and radical cation 145+ showed a twisted saddle‐shaped structure with cisoid conformations, while 1452+ adopted a more planar transoid conformation due to the electrostatic interactions between the two counterions. Moreover, the electronic configuration changed upon stepwise oxidation of the curved nanographene with two pairs of fused pentagons and heptagons, which exhibited alternating ring currents.Recently, Würthner et al. presented a novel negatively curved polyarene with two pairs of fused pentagons and heptagons Scheme 23.[113.42 and propylene oxide. However, few examples of heptagon‐forming reactions through photocyclization processes have been reported. In 2020, Takasu et al. presented the synthesis of helical pure carbon‐based nanographene 150 containing continuous azulene units  traces. Theoretical calculations determined a high racemization barrier of 150 up to 29.2 kcal mol−1, which was consistent with the experimental result . Furthermore, bond length analysis of 150 revealed obvious alternation between 1.39 and 1.49 Å, similar to that in pristine azulene. The aromaticity of the fused pentagon and heptagon estimated by the NICS (1) value was weaker than that of the unsubstituted azulene. The UV–vis spectra of compound 150 showed two main bands at 477 and 404 nm, in which the absorption peak at 477 nm can be ascribed to HOMO to LUMO+1 and HOMO‐2 to LUMO transitions, as well as two weak bands at 660 and 600 nm arising from HOMO to LUMO and HOMO‐1 to LUMO transitions, respectively. The CV trace of compound 150 exhibited three oxidation waves  and one reduction wave , which was also supported to be stable even after the oxidation and reduction process.Photoinduced cyclization has been widely used to generate phenanthrene substructures from stilbene units in the presence of Is Scheme 24,[11154) containing up to six joined nitrogen‐doped 5–7 pairs in the carbons skeleton  in the presence of potassium tert‐butoxide to afford final wrapped nanographene (154). The structure of compound 154 was unequivocally confirmed by 1H NMR, HR‐mass, and X‐ray crystallographic analysis, of which revealed Monkey‐saddle‐shaped geometry, as well as S6 molecular symmetry. The absorption and emission spectra of 154 exhibited maximum value at 534 and 691 nm, respectively, which was similar to its hexagonal counterpart 155 , leading to a similar energy gap , which can be ascribed to enhanced π‐electron delocalization of peripheral rings. Electronic behaviors of 154 and 155 were estimated by CV, in which compound 154 showed a much lower oxidation potential  owning to the nitrogen‐doped character.Another photo‐induced heptagon‐forming example was reported by Tan et al. in 2022, in which Monkey‐saddle‐shaped nanographene , indicating a large tendency toward chemical oxidation. Accordingly, treatment of 166 and 168 with one and two equivalents of NO·SbF6 afforded the corresponding radical cation and dicationic species 1662+ and 1682+, respectively. From the results of X‐ray crystallographic analysis and DFT calculations, the tropylium rings exhibited aromatic characteristics, whereas the central pentagons were highly antiaromatic and the hexagons were nearly nonaromatic.Additionally, in 2018, Chi et al. presented two azulene‐fused r Scheme 27.[124In this review, we have summarized the synthetic progress toward azulene‐embedded polyarenes from the 20th century to recent years, not only witnessing advancements in synthetic methodologies and characteristic techniques, but also gaining more fundamental insights into defect‐induced structure–property relationships. Although 5–7 defective pairs can be incorporated into a larger conjugated carbon network, the lack of general cyclization reactions of odd‐membered rings such as pentagons and heptagons limits advances in this renewed field. For example, some of the examples shown in this review were separated through ring‐skeleton rearrangement under Scholl‐type conditions and metal‐mediated alkyne annulation. However, conventional intramolecular F–C reactions also remain powerful in the cyclization process as long as reasonable synthetic strategies are provided.π‐electron topology. Accordingly, we look forward to the reaction of more defective nanographenes, such as fragments of pentaheptite and hackelite, and even 1D extended graphene nanoribbons containing different arrangements and orientations of 5–7 pairs may be developed in future works.Despite this progress, difficulties in incorporating joined pentagons and heptagons into different carbon molecular skeletons still restrict the synthesis of defective nanographenes with diverse topologies, thus driving researchers to dedicate more effort to developing efficient and powerful synthetic strategies. Despite the limitations, this field remains dynamic and meaningful to elucidate the appealing physicochemical properties of defective nanographenes, such as optical, electronic, and magnetic behaviors, compared to those of all‐benzenoid analogs, thus providing a fundamental understanding of the defect‐induced changes in molecular geometry and The authors declare no conflict of interest.


A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short‐term lung function changes in fHP on mortality.Baseline demographics for 145 consecutive patients with a multi‐disciplinary team diagnosis of fHP, as well as baseline and 1‐year follow‐up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all‐cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality.p < 0.001), FVC ≥ 10% , DLCO ≥ 10%  and DLCO ≥ 15%  at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥ 40 mm Hg on echocardiography, in separate models.Baseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5%  ≥ 10% and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 15%, but also marginal declines in FVC ≥ 5% and DLCO ≥ 10%, are predictive of increased mortality.See relatededitorial The majority of patients with hypersensitivity pneumonitis (HP) presenting to specialist centres have a chronic fibrotic form. Within the population of fibrotic HP (fHP) patients, a subgroup of patients display an accelerated rate of progression comparable to idiopathic pulmonary fibrosis (IPF).At the moment, known predictors of fHP mortality are the presence of traction bronchiectasis and honeycombing on thoracic computed tomography (CT),The main aim of our study was to evaluate the impact of short‐term changes in FVC, including a marginal change of ≥5%, and in diffusion capacity of the lung for carbon monoxide (DLCO), including marginal change of ≥10%, on survival in patients with fHP.Consecutive patients with a diagnosis of fHP presenting at the Royal Brompton Hospital (RBH) Interstitial Lung Disease (ILD) Unit from January 2010 to December 2014 were considered for this study. A diagnosis of fHP was made through MDT discussion, following integration of clinical, exposure history, CT, bronchoalveolar lavage (BAL) and histology data, when available, as per current guidelines.All‐cause mortality was collected for all patients until death, transplant, loss to follow‐up or end of the study period (30 March 2021).Patients were included in this study if they had lung function measurements at first presentation to our unit (baseline), and at least one further lung function at 12 months (range: 6–18 months) from baseline. Patients who died within 12 months of baseline, without a follow‐up lung function test, were included in the baseline analysis but excluded from the lung function trends analysis. A categorical change in FVC was computed as a relative change of ≥5% or ≥10% from the absolute values at baseline, while a categorical change in DLCO was defined as a relative change of ≥10% or ≥15% from absolute values at baseline. Further details on clinical findings are available in p‐value of <0.05 was considered significant.Analyses were performed using STATA15.1 software . Determinants of mortality were assessed by Cox proportional hazards analysis. Covariates in multivariable analysis included demographic variables, the composite physiological index (CPI),Baseline characteristics of the 145 patients satisfying inclusion criteria for this study are summarized in Table p < 0.001), forced expiratory volume in 1 s (FEV1) % predicted , DLCO % predicted  and CPI . Age at baseline  and ethnicity (non‐Caucasian)  were also associated with mortality. The presence of honeycombing on CT, observed in 19 (13.1%) patients, was associated with mortality . In patients with an echocardiogram (n = 104), estimated PASP ≥ 40 mm Hg was predictive of mortality . In the 100 patients with BAL, lymphocyte percentage counts were associated with better survival, both when assessed as a continuous variable  and as different lymphocytosis cut‐offs (Table There were 92 deaths (63.4%) during a median follow‐up of 4.8 years (range: 0.5–10.9). Baseline predictors of mortality included FVC % predicted , with a median survival of 2.2 years compared to 6.7 years in those without FVC decline ≥ 10% , with a median survival of 2.5 years compared to 6.7 years in those without DLCO decline of ≥ 15% , with a median survival of 2.9 years compared to 7.0 years , with a median survival of 2.9 years compared to 6.7 years , presence of honeycombing on CT, and CPI Table , and, inTo assess whether the link with worsening lung function was confounded by the presence of BAL lymphocytosis, we analysed the relationship between FVC decline (both ≥5% and ≥10%) and DLCO decline (≥10% and ≥15%), adjusting in separate analyses for different lymphocyte percentage cut‐offs Table . The assWe also performed a sensitivity analysis in which we excluded the 29 patients for whom diagnosis was mainly based on typical/compatible CT findings. In the remaining 116 patients, all four measures of lung function worsening remained significant on both univariable and multivariable analyses (Table p < 0.001), highlighting the severity of outlook for this subgroup of patients. This is similar to the published findings in IPF, where a marginal decline (5%–10%) in FVC is associated with higher mortality.In this study, we find that early lung function decline is predictive of an IPF‐like survival in patients with fHP, confirming the finding by Gimenez et al.A decline in FVC approximating the 5% threshold is very close to the known SD for this measurement, safely stated at 5%, and may therefore represent either real progression of ILD or technical measurement variation.A median survival of only 26.0 months in patients with FVC decline of ≥10% within the first year is worse than the equivalent figure in the Gimenez et al.'s study . This could be related to worse baseline severity in our cohort, although the absence of DLCO measurements in the Gimenez et al.'s study does not allow direct comparisons. Additionally, there were a greater proportion of patients without identifiable exposures in our cohort, a subgroup which is known to have a worse outcome.A third of our cohort had a positive smoking history, although only two out of 48 were current smokers at their baseline visit. Although there is thought to be an inverse relationship between smoking history and development of HP,The majority of patients in this cohort were treated with corticosteroids and/or immunosuppressants. As ours was a retrospective study, it is not possible to accurately assess response to treatment. However, there was clearly a large proportion of patients with stable lung function at 1 year on corticosteroids and/or immunosuppressive treatment, a finding that was associated with a significantly better survival. Immunosuppression has been associated with stabilization of lung function in fHP,One of the strengths of this study is the high proportion of patients with BAL at baseline. BAL lymphocytosis has been reported as a potential marker of a better outcome in patients with fHP. BAL lymphocytosis was associated with stabilization in FVC in response to immunosuppression,This study does have some limitations, mainly due to its retrospective nature. An echocardiogram within 12 months of baseline was not available for all patients. However, short‐term lung function worsening remained predictive of poor survival even after adjustment for PASP echocardiographic measurements available within a year from baseline. Although a detailed exposure history is routinely investigated in all new ILD patients referred to our unit, we do not employ a standardized written questionnaire, nor do we have availability of environmental hygienists to probe potential exposures in the patient's home or work environment. This could have missed potential exposures, as questionnaires and home/work visits may be better at identifying possible HP exposures than clinical history or specific IgG serologies.In summary, in this cohort of consecutive patients with fHP, even a marginal decline in FVC by ≥5% and/or a marginal decline in DLCO by ≥10% is associated with a major increase in risk of death. In light of the very poor survival in a substantial subgroup of patients with fHP, there is a clear need to develop biomarkers of response to treatment (immunosuppressive) without having to wait for worsening. Furthermore, studies exploring the earliest time point from baseline at which change in lung function parameters is associated with survival are needed. There is a clear unmet need to identify this subgroup of patients with fHP much earlier in the course of their illness, by performing large well‐designed prospective studies to evaluate the role of early lung function decline in treatment decisions.None declared.Caudio Macaluso: Data curation ; formal analysis ; investigation ; methodology ; writing – review and editing . Cristina Boccabella: Data curation ; formal analysis ; investigation ; methodology ; writing – review and editing . Maria Kokosi: Data curation ; investigation ; writing – review and editing . Nishanth Sivarasan: Data curation ; investigation ; writing – review and editing . Vasilis Kouranos: Data curation ; investigation ; writing – review and editing . Peter M. George: Data curation ; investigation ; writing – review and editing . George Margaritopoulos: Data curation ; investigation ; writing – review and editing . Philip L. Molyneaux: Data curation ; investigation ; writing – review and editing . Felix Chua: Data curation ; investigation ; writing – review and editing . Toby M. Maher: Data curation ; investigation ; writing – review and editing . Gisli R. Jenkins: Data curation ; investigation ; writing – review and editing . Andrew G. Nicholson: Investigation ; writing – review and editing . Sujal R. Desai: Conceptualization ; data curation ; investigation ; writing – review and editing . Anand Devaraj: Conceptualization ; data curation ; investigation ; writing – review and editing . Athol U. Wells: Conceptualization ; methodology ; writing – review and editing . Elisabetta A. Renzoni: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; writing – original draft ; writing – review and editing . Carmel J.W. Stock: Data curation ; formal analysis ; investigation ; methodology ; writing – original draft ; writing – review and editing .This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Royal Brompton and Harefield Hospitals . Adult participant consent was not required as the research was based on retrospective review of previously collected non‐identifiable information, and patient consent was not required for institutional approval.Supporting informationClick here for additional data file.Visual Abstract Short‐term lung function changes predict mortality in patients with fibrotic hypersensitivity pneumonitis.Click here for additional data file.


A number of theories about the origins of musicality have incorporated biological and social perspectives. Darwin argued that musicality evolved by sexual selection, functioning as a courtship display in reproductive partner choice. Darwin did not regard musicality as a sexually dimorphic trait, paralleling evidence that both sexes produce and enjoy music. A novel research strand examines the effect of musicality on sexual attraction by acknowledging the importance of facial attractiveness. We previously demonstrated that music varying in emotional content increases the perceived attractiveness and dating desirability of opposite-sex faces only in females, compared to a silent control condition. Here, we built upon this approach by presenting the person depicted (target) as the performer of the music (prime), thus establishing a direct link. We hypothesized that musical priming would increase sexual attraction, with high-arousing music inducing the largest effect. Musical primes  varied in arousal and pleasantness, and targets were photos of other-sex faces of average attractiveness and with neutral expressions (2 s). Participants were 35 females and 23 males  matched for musical background, mood, and liking for the music used in the experiment. After musical priming, females’ ratings of attractiveness and dating desirability increased significantly. In males, only dating desirability was significantly increased by musical priming. No specific effects of music-induced pleasantness and arousal were observed. Our results, together with other recent empirical evidence, corroborate the sexual selection hypothesis for the evolution of human musicality. For example, studying humans’ ability to sing may offer insights into the basis of human musicality, whereas studying the diverse forms and social functions of songs across cultures may be an endeavor followed by ethnomusicologists. Both approaches can mutually support each other. Musicality as a stable human trait can be discussed within a bio-musicological framework  = 0.930 for attractiveness ratings and r(62) = 0.944 for dating desirability ratings. In the group of males, the average within-subject correlation across the five conditions was r(30) = 0.955 for attractiveness ratings and r(30) = 0.964 for dating desirability ratings.Based on the results reported in see also . Therefof, directly computed from partial eta-squared reported in r = 0.93 were used to obtain a minimum sample size for attractiveness ratings of contrast 1. The results yielded a sample size of six with an actual power of 0.82. If the within-subject correlation was lowered to r = 0.80, to be more conservative, the sample size increased to 13 with an actual power of 0.82. For dating desirability ratings and contrast 1, we predicted a large effect (Cohen’s f = 0.593), and a within-subject correlation of r = 0.944, which yielded a sample size of three and an actual power of 0.85. With a lower correlation of r = 0.80, the sample size increased to five with an actual power of 0.87. Sample sizes for contrast 2 were similarly determined by basing the computation on the exact results reported in p2 < 0.001) were expected. For dating desirability ratings and contrasts 3 and 4, the effect sizes were also negligible. For the group of males, we did not predict any significant effects on attractiveness ratings. For dating desirability ratings a marginally significant effect was observed in For the current group of females, a medium effect size of 0.274  were tested, out of which 22 were excluded prior to the exploratory data analysis. Eleven students were excluded due to technical problems (during the experiment it was discovered that one version of the computer program used to conduct the experiment had the wrong rating order in one of the two blocks). Two participants were excluded because they were using hormonal contraception, and seven were excluded because they had their menstruation on the day of the experiment. Two female participants reported more than 3 years of musical training and were thus also excluded.Thirty heterosexual male participants were tested, and one person had to be excluded because he previously participated in a similar experiment. Three male participants reported more than 3 years of musical training, and one participant was not wearing the headphones in an appropriate way during the experiment. One male participant reported mild hearing loss in one ear, but was not excluded because the experiment was not measuring fine-grained music perception skills.After an exploratory data analysis of the background variables, two other male participants were excluded: in order to balance the number of participants of the experimental conditions, one male participant was excluded because he reported extreme tiredness. Another male participant reported very low liking ratings of Romantic piano music , and was thus excluded. It is important to note that all exclusions were made prior to the main analysis of the experimental data.2(1) = 0.77, p = 0.38.Our final two groups of 35 females and 23 males were matched across several background variables , 2. All very unattractive to (7) very attractive, and the instructions were: “Please report the perceived sexual attractiveness of the face.” Dating desirability was also assessed on a 7-point scale, ranging from (1) no, by no means to (7) yes, by all means, with the following instruction: “Please report whether you would like to date this person.”The same materials as reported in th-century piano solo music). Furthermore, participants were asked to report on their willingness to have a one-night stand or to enter a long-term relationship with the most attractive people shown in the experiment. Females were asked to provide information regarding their menstrual cycle and hormonal contraceptive use. To be specific, we asked the following questions: Did you like the music heard in the experiment? (1) not at all … (7) very much; What role does music play in your life? (1) no role … (7) a very large role; How often do you listen to classical music? (1) never … (7) very often; Have you ever received musical training ? Report of years of musical training and when it was finished; How often and how do you listen to music? Passive, while doing other things: (1) never … (7) very often; Active, while not doing other things: (1) never … (7) very often; Active in a concert: (1) never … (7) very often; Please think of the faces that you regarded as particularly attractive. Report on your wish to have a one-night stand or a long-term relationship with these persons. For each part: (1) very much … (7) not at all. They also reported on how difficult it was for them to judge facial attractiveness on a scale ranging from (1) very easy to (7) very difficult. Using open questions, participants were asked to report on their thoughts about the research question/hypothesis underlying the experiment. In addition, three standardized questionnaires on emotional intelligence, empathy and personality were administered but not evaluated for this study.We used the short form A of the three-dimensional mood questionnaire [MDBF A] by The study was approved by the local ethics committee of the University of Innsbruck, Austria . Participants were recruited from a pool of (mostly undergraduate) psychology students. The study was advertised to investigate the perception of facial attractiveness. There was no reference to music to avoid selection bias. Students either received course credits or a monetary compensation of 12 Euro.Participants were tested in a quiet room with constant lighting conditions and no window. The experiment was run in Matlab R2017a  and the music was played through Sennheiser HD 380 Pro headphones at a fixed loudness level (70 dB as measured with a dB meter). Instructions and faces were presented on a 24 inch screen  placed approximately 70 cm away from the sitting participant. After having signed the informed consent form, participants were asked to report on their mood prior to the experiment, then the actual experiment started.The experiment consisted of two blocks (priming and control), which were counterbalanced across participants. Moreover, there were two rating scales , whose order was also counterbalanced across participants of the two block orders. For each participant the rating order was the same in both blocks. After a practice trial, participants began the experiment. To avoid fatigue, participants were encouraged to take a self-paced break after half of the trials were completed in the priming block.“The next trial will follow soon”), then the photograph followed for 2 s on a black background. After the photograph had disappeared, one of the two rating scales was shown on the screen and participants answered by mouse click. Then the other scale was shown. All faces were randomly presented.In the (silent) control condition, participants were asked to rate 37 faces (20 targets and 17 same-sex distractor faces to prevent demand characteristics) of potential partners on facial attractiveness and dating desirability. Each trial was announced with a statement shown on the screen for 5 s . These 80 trials were intermingled with 17 distractor trials. All trials were randomly presented and announced for 5 s with a statement saying The only difference between the procedure described in When the experiment was completed, participants were asked to fill in a short self-developed questionnaire. In total, the experimental session lasted around 90 min. Participants were either paid or assigned course credits, thanked and debriefed.superb package in R.All analyses were conducted using IBM Statistics SPSS 26. In the case of violations of sphericity , Greenhouse–Geisser corrections were performed. Effect sizes for eta or partial eta squared were interpreted by following Distractor trials  were not analyzed and removed from the data set. Males and females were analyzed separately because the target faces differed between groups . A set oF  = 2.90, p = 0.058, ηp2 = 0.08 (medium effect). The planned contrast analyses revealed that attractiveness ratings were significantly higher in the music conditions  than in the control condition , F = 4.44, p = 0.043, ηp2 = 0.12 (medium effect). Ratings did not significantly differ between low-arousing  and high-arousing music , F = 0.53, p = 0.470, ηp2 = 0.02 . Music-induced pleasantness did not affect attractiveness ratings, F = 0.01, p = 0.916, ηp2 < 0.001 (no effect). There was no significant interaction between music-induced arousal and pleasantness on attractiveness ratings, F = 0.001, p = 0.981, ηp2 < 0.001 (no effect).We first tested whether attractiveness ratings were affected by musical priming in females . A repeaF = 4.81, p = 0.014, ηp2 = 0.12 (medium effect). Contrast 1 comparing the control condition to the four music conditions was significant, F = 6.45, p = 0.016, ηp2 = 0.16 (large effect), with lower dating desirability ratings for the control condition  than for the music conditions . There was no significant difference between the conditions of low-and high-arousing music, F = 0.04, p = 0.848, ηp2 = 0.001 (no effect). Similarly, there was no significant effect of musical pleasantness, F = 1.73, p = 0.196, ηp2 = 0.05 . The interaction between music-induced arousal and pleasantness was not significant, F = 0.12, p = 0.733, ηp2 = 0.003 (no effect).Next, we analyzed dating desirability ratings and how they were affected by musical priming in females . A repeaF = 0.67, p = 0.521, ηp2 = 0.03 . Contrast 1 showed no significant difference between the silent control and the four music conditions, F = 0.57, p = 0.458, ηp2 = 0.03 . Contrast 2 revealed that there was no difference between the low-and high-arousing conditions, F = 0.09, p = 0.771, ηp2 = 0.004 (no effect). Contrast 3 showed no significant difference between the unpleasant and pleasant primes, F = 2.52, p = 0.127, ηp2 = 0.10 (medium effect). Contrast 4 tested the interaction between music-induced arousal and pleasantness, which was not significant either, F = 0.16, p = 0.695, ηp2 = 0.007 (no effect).In males, facial attractiveness ratings were not affected by musical priming . A repeaF = 2.84, p = 0.067, ηp2 = 0.11 (medium effect). Contrast 1 was significant, F = 6.88, p = 0.016, ηp2 = 0.24 (large effect), with higher ratings of dating desirability for the music conditions  than for the control condition . Contrast 2 testing for the effects of music-induced arousal was not significant, F = 0.08, p = 0.784, ηp2 = 0.003 (no effect). Contrast 3 testing for the effects of pleasantness was not significant, F = 1.49, p = 0.235, ηp2 = 0.06 (medium effect). Last, the interaction between music-induced arousal and pleasantness was not significant, F = 0.16, p = 0.697, ηp2 = 0.007 (no effect).Finally, we examined the effects of musical priming on dating desirability in males . A repeaSince the group of male participants was smaller than the group of female participants, we repeated the analysis with 25 participants including the two outliers that were removed after the exploratory data analysis. The pattern of results was very similar for both attractiveness and dating desirability ratings see .M = 3.97, SD = 2.12) reported to a larger degree than males  that they would be willing to have a one-night stand with the most attractive persons shown in the experiment, U = 288.00, p = 0.065, η2 = 0.06 (medium effect). There was no significant difference between females  and males  reporting on their desire to have a long-term relationship with the most attractive persons shown in the experiment, U = 396.50, p = 0.922, η2 < 0.001 (no effect).U = 398.00, p = 0.921, 2η < 0.001 (no effect), which was generally rated as of intermediate difficulty, M = 4.78, 95% CI  on a 7-point scale.Participants were invited to report on their thoughts about the purpose of the experiment. All except two participants reported that the study is about the effect of music  on attractiveness. One male and one female participant referred to the effect of musical talent  on attractiveness. Speculations about the role of music in the experiment mostly comprised mood induction (positive vs. negative) and references to effects of musical parameters such as tempo and loudness. Males and females did not differ regarding their reported difficulty in judging the facial attractiveness of faces, People use multiple cues in partner choice , and thuOur findings are consistent with Contrary to our expectations, and not in line with Darwin’s theory, high-arousing, more complex music did not yield the largest effects on sexual attraction but see . This diThe descent of man Darwin stresses the charming character of sounds during mate choice in animals and humans, which spurs the discussion about the mutual role of affective and cognitive cues in musical signals. Musical complexity as a signal of advanced motor skills, intelligence, and creativity may not be the only way through which music affects romantic attraction (Interestingly, traction . There mtraction . Thus, fAt present the role of individual differences in musical priming effects on sexual attraction was not examined. Previous research has shown that subjective experience of music-induced complexity and arousal depends on person-related factors such as personality traits and musical background in females . AlthougThere are several limitations of the present research that need to be addressed. At the moment, our findings are not generalizable beyond the Western population studied in the experiment , thus crOur empirical findings have important implications for a better understanding of mating behavior observed in real-life settings in which music and dancing plays a role. For example, nightclubs have been identified as human mating grounds  in whichIn conclusion, crossmodal priming paradigms may be useful to study the evolution of music from a psychological and behavioral perspective. We show that being exposed to music may increase sexual attraction in both sexes when rating faces of average attractiveness. In light of growing evidence for Darwin’s sexual selection theory, we will need to discuss whether his theory should stand on its own, or whether it should be integrated into broader, adaptationist theories which include other aspects of social bonding, such as singing to infants and social grooming .https://osf.io/dp3es/?view_only=6a3d15fad004479bae839dc8c9efcf79.The dataset and musical stimuli presented in the study can be found at: OSF: The studies involving human participants were reviewed and approved by the Board for Ethical Questions in Science of the University of Innsbruck. The patients/participants provided their written informed consent to participate in this study.MM developed the study concept and the study design. Testing and data collection were performed by IR and MM. IR performed the data analysis and interpretation under the supervision of MM, and provided critical revisions. MM drafted the manuscript. All authors contributed to the article and approved the submitted version.Our work was funded by the Tiroler Wissenschaftsförderung grant number UNI-0404/2418. Open access funding provided by University of Vienna.The 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.


Standardization of abdominal wall closure is suggested to improve quality and reduce the risk for late abdominal wall complications. The purpose of this study was to explore the impact of a structured introduction of guidelines for abdominal wall closure on the rates of incisional hernia and wound dehiscence.All procedures performed via a midline incision in 2010–2011 and 2016–2017 at Capio St Göran’s Hospital were identified and assessed for complications and risk factors.p < 0.05). In multivariate logistic regression analysis, male gender and chronic obstructive pulmonary disease were risk factors for wound dehiscence (both p < 0.05).Six hundred two procedures were registered in 2010–2011, and 518 in 2016–2017. Four years after the implementation of new guidelines, 93% of procedures were performed using the standardized technique. There was no significant difference in the incidence of incisional hernia or wound dehiscence between the groups. In multivariate Cox proportional hazard analysis, BMI > 25, wound dehiscence, and postoperative wound infection were found to be independent risk factors for incisional hernia (all The present study failed to show a significant improvement in rates of incisional hernia and wound dehiscence after the introduction of Small Stitch Small Bites. When introducing a new standardized technique for closing the abdomen, education and structural implementation of guidelines may have an impact in the long run. The risk factors identified should be taken into consideration when closing a midline incision to identify patients with high risk.The online version contains supplementary material available at 10.1007/s00423-022-02530-8. The midline abdominal incision is widely used in abdominal surgery since it enables access to the whole abdominal cavity, spares nerves, and vessels , 2, and In this study, we intended to investigate how the introduction of SSSB in 2012 as standard surgical technique influenced the rate of midline incision complications in a real-life material. We chose to include acute surgery in the study as our hospital has a profile of acute surgery. All cases performed in 2016–2017 were included in the study, to compare complications, and risk factors with cases performed prior to introduction in 2010–2011 were chosen as controls. The primary aim was to investigate the difference in incisional hernia and wound dehiscence rates between the cohorts. A secondary aim was to investigate any significant risk factors for incisional hernia and wound dehiscence.Based on the evidence presented by Milbourn et al. , Capio SIn this follow-up, all abdominal procedures performed in 2010–2011 and 2016–2017 were identified through a search for ICD10 codes in the Cambio COSMIC medical records database . AssuminStatistical analyses were performed using SPSS 26.0. Analyses were performed to estimate incisional hernia and wound dehiscence rates and to assess the impact of potential risk factors. In the intention to treat analysis, patients undergoing surgery in 2016–2017 were compared to controls undergoing surgery in 2010–2011. We also performed per protocol analysis where all patients sutured with appropriate SSSB technique, with the ratio noted in the operation records, were compared to controls sutured at the surgeon’s choice. Risk factors for wound dehiscence were analyzed in uni- and multivariate logistic regression analysis; variables assumed to be risk factors at the beginning of the study were included in the multivariate analysis. Risk factors for incisional hernia were analyzed in uni- and multivariate Cox proportional hazard analysis ; adjustmAltogether, 1120 midline laparotomies were included in the study, 518 in the 2016–2017 study cohort and 602 in the 2010–2011 control cohort. Mean follow-up time was 32 and 73 months in the study and control groups, respectively. The rate of emergency surgery was approximately 60% in both groups. In the study cohort, 481 (93%) appropriate SSSB suturing was applied and a sufficient suture length to wound length ratio (≥ 4:1) was noted in the procedure notes compared to 7 (1%) in the control cohort. Altogether, 31 procedures in the study cohort and 593 procedures in the control cohort were closed at the surgeon’s choice. No significant differences in wound dehiscence rates and incisional hernia rates were seen between the two cohorts. In a per protocol analysis, cases sutured with SSSB were compared to procedures closed according to surgeon’s choice. There was no significant differences in incisional hernia or wound dehiscence between the groups in the per protocol analysis.p = 0.15). Of these, 44 required emergency reoperation, 15 in the SSSB group and 29 in the surgeon’s choice group. Nine patients (18%) with a documented wound dehiscence later developed an incisional hernia.A total of 51 patients developed wound dehiscence, 17 (3.5%) in the SSSB group and 33 (5.3%) of surgeon’s choice closure group (p = 0.52). There was no significant difference in survival analysis between the groups. Figure p = 0.40 log rank). Surgical site infection (SSI) that required antibiotic treatment was seen in 15 patients (3.1%) in the SSSB group and 23 (3.7%) in the surgeon’s choice group. This difference was not statistically significant.In the SSSB group, 21 (4.3%) and, in the surgeon’s choice group, 32 (5.1%) developed incisional hernias (p = 0.03) and SSI (p = 0.03) were significant risk factors for wound dehiscence. BMI > 25 (p = 0.002), SSI (p < 0.001), and wound dehiscence (p = 0.009) proved to be risk factors for incisional hernia. Acute surgery, high age, chronic obstructive pulmonary disease (COPD), and previous midline incision did not show significant association in this group.Table Tables p = 0.003) and COPD (p = 0.022) were significant risk factors for wound dehiscence. History of a previous midline incision (p = 0.051) and SSI (p = 0.053) showed tendencies to increased risk of wound dehiscence, although not significant at the p < 0.05 limit.Male gender (p = 0.004), SSI (p = 0.01), and wound dehiscence (p < 0.001) as independent risk factors for incisional hernia. Figures Cox proportional hazard regression analysis identified BMI > 25 p = 0.00, SSI Below is the link to the electronic supplementary material.