The Interoceptive Mind: From Homeostasis to Awareness can be seen as a guide to scientific studies of interoception in all of the cases so far. In particular, the essays collected in this book shed light on multisensory integration of interoceptive and exteroceptive feelings (and even self-conscious feelings) across widespread disciplines.To understand the nature of mind, cognitive scientists of all theoretical strands may benefit from considering experimental evidence of cognition  alongside phenomenology of bodily self (or conscious) feelings . Roughly, the former dimension of scientific studies of mind seems to have found its legitimacy; yet, at first glance, the latter could still not be exonerated completely. That is to say, as far as the scientifically evidence-based account of endogenously generated interoceptive feeling is concerned, we will have come a long way toward buttressing its legitimacy. As suggested in its title, the book addresses the difficulties of integrating various dimensions relevant to feelings—from the biological notion of self to the interoceptive origins of self-awareness. The book divides into four sections, and each chapter is worthy of careful attention.Part I introduces the historical background of research in interoception. Based on a case report, the authors elaborate on why the autonomic nervous system is the dominant efferent system and a fine-constructed afferent system. They point out that interoception and then advanced brain functions are dependent upon each other. Thus, a full-fledged theory of self might result from interactions  of bottom-up sensory input and top-down predictions. This point is key to the authors' argument.Part II focuses on the newest research in cognitive neuroscience and experimental psychology and emphasizes interoception's importance to embodied cognitive science by resorting to a popular predictive processing framework. These chapters are the following: Chapter 2 affirms the significance of the body for self-awareness from the perspective of interoceptive predictive processing (IPP) and proposes that interoception serves the stability of self-consciousness. Chapter 3 attempts to assume that the integration of visceral signals probably produces a subject-centered frame of reference, which could be seen as the basis of bodily self. Chapter 4 explores how interoception influences temporal perception. Chapter 5 presents the current debates of “gut feelings” and the brain–gut axis hypothesis. Chapter 6 provides reliable evidence for a more general definition of interoception by scrutinizing the effect of painful/pleasant touch on the surface of the skin relating to bodily-self representation. It is a pity that researches on the influence of interoception on theory of mind, decision-making, and emotion regulation are not mentioned here . Chapter 9 uses examples of anorexia nervosa and bulimia nervosa to illustrate that the dysfunction of interoception is the root cause of maladaptive eating behaviors. Chapter 10 focuses on the dysfunctions of interoceptive mechanisms in various neurological disorders, such as Alzheimer's disease and Parkinson's disease. The authors propose a future direction on understanding manifestations of cerebral damages through the neurology of interoception. Chapter 11 suggests that medically unexplained symptoms could have perceptible symptoms as their root cause. A more effective methodology of tackling symptoms  might be indirect interoceptive differentiation training (p. 223). Chapter 12 confirms that interoception is the core component of subjective happiness valuation and then designs a respiration-based task for characterizing interoception concerning mental health. It would be more interesting if this section involves more discussions about possible ways of training and improving interoception to promote mental health.Lastly, Part IV promotes and integrates multidisciplinary research in philosophy. Chapter 13 points out that it is necessary to distinguish between physiological arousal and experiential arousal. They also address that physiological arousal cannot be reduced to a uniform pattern of sympathetic activation; experiential arousal cannot be reduced to visceral sensations of the autonomic nervous system as well. Chapter 14 reconsiders how interoception contributes to consciousness and self. Chapter 15 argues that homeostasis and allostasis are “complementary strategies for sustaining biological viability” (p. 289) and constructing interoceptive inference. Chapter 16 sums up several essential characteristics of subjectivity and then indicates the consistency between these characteristics and the non-topological dimension of interoception. The last chapter provides a phenomenological investigation of internal bodily experience and presents how the external world influences the bodily experience. This part reflects the editors' acknowledgment of the standpoint that a comprehensive understanding of interoception requires us to integrate the first-person perspective with the third-person perspective within the realm of consciousness science . Part III concludes clinical evidence of interoceptive dysfunctions or illness; however, it pays more attention to neuropathological symptoms and interoception and somewhat neglects possible effective methods of therapeutic interoceptive training. Moreover, in some sense, Part IV deviates from the book's empirically oriented target but falling into philosophical demarcation of generic feelings (even proto-feelings).Notwithstanding, the book presents many illuminating insights about interoception and cognition. Further, the book will be of interest to those critical of Standard Cognitive Science (see e.g., Shapiro, JZ and DD wrote the manuscript, with larger contributions by JZ. DD provided edits and suggestions for revision. All authors contributed to the article and approved the submitted version.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.


The glymphatic system is a newly discovered waste drainage pathway in the brain; it plays an important role in many neurological diseases. Ongoing research utilizing various cerebrospinal fluid tracer infusions, either directly or indirectly into the brain parenchyma, is investigating clearance pathways by using distinct imaging techniques. In the present review, we discuss the role of the glymphatic system in various neurological diseases and efflux pathways of brain waste clearance based on current evidence and controversies. We mainly focus on new magnetic resonance imaging (MRI) modeling techniques, along with traditional computational modeling, for a better understanding of the glymphatic system function. Future sophisticated modeling techniques hold the potential to generate quantitative maps for glymphatic system parameters that could contribute to the diagnosis, monitoring, and prognosis of neurological diseases. The non-invasive nature of MRI may provide a safe and effective way to translate glymphatic system measurements from bench-to-bedside. According to the traditional understanding of cerebrospinal fluid (CSF) dynamics, CSF (which is mainly produced by the choroid plexus at a rate of 0.3–0.4 mL/min) passes from the lateral ventricles to the third ventricle through the interventricular foramen of Monro and then goes to the fourth ventricle through the cerebral aqueduct of Sylvius ,2. From Normal physiology  ,32,33, sThe influx pathways of the glymphatic system through peri-arterial spaces are relatively well-established ,22,23,51The utility of MRI in investigating the glymphatic system has recently gained momentum. Though optical imaging techniques such as two-photon microscopy have classically dominated the field, due to its excellent spatial resolution that is needed to capture small perivascular spaces, its limitations have pushed investigators towards MRI; MRI overcomes the low-penetration depth of two-photon microscopy and allows for whole-brain imaging unlike two-photon microscopy, which is only favorable in imaging small areas of the brain cortex. Beyond the use of contrast agents, image contrast in MRI can be easily altered by the elements of the imaging sequences and parameters, unlike two-photon microscopy. Moreover, different MRI methodologies can capture different elements of the glymphatic system. For example, in vivo, perivascular fluid movement in the glymphatic system and its diffusion properties can be assessed with magnetic resonance diffusion tensor imaging (DTI) ,80. MRI Modeling the glymphatic system using data from MRI can provide insight into the glymphatic flow pathways. Iliff et al.  demonstrTo maintain brain homeostasis, toxic waste products generated in the brain must be evacuated. At first, it was believed that the removal of protein wastes from the brain occurs solely by diffusion, which can be examined utilizing a real-time iontophoresis method , and theLooking at the rapid removal of metabolic wastes out of the brain, it was argued that diffusion alone cannot be responsible for waste drainage. Cserr et al. proposed the bulk flow of ISF through explicit channels as the dominant mechanism of waste drainage compared to diffusion by infusing 2000 KDa blue dextran  and 40 KA computational analysis utilizing the effective diffusion due to the convoluted extracellular spaces demonstrated that dispersion, which is a combination of bulk flow and diffusion, mediates the observed ,115,116 Mathematical modeling utilizing MRI data has been performed by various groups to better understand the dynamics of the glymphatic system flow. In these studies, a mathematical model was developed expressing the dynamics of the nuclear magnetic resonance (NMR) tracer in a contrast-enhanced MRI of rodents. The measured MRI signal was assumed to be proportional to the tracer concentration in the imaging voxels. Therefore, the dynamic changes of the tracer concentration could be measured by consecutive MRI scans. The aim was to develop a mathematical model based on the tracer behavior in the tissues and underlying tissue characteristics to mimic the measured dynamic changes by MRI. Thus, inversely solving these models could provide quantitative maps of the glymphatic dynamic and structure. Lee et al.  introducHowever, our recent study presented the local input functions to visualize the more reliable glymphatic flow pathways of the Gd-DTPA tracer in rats using the two-compartment model . This moRatner et al. ,127 fittElkin et al. analyzed the glymphatic pathways using the OMT algorithm with a Lagrangian framework instead of using the Eulerian framework ,129. TheIn another study by Elkin et al. , they agIn the most recent paper of vascular investigation by Elkin et al., fluid motion was described by applying an OMT regularized model to the human MRI data of ten patients with head and neck squamous cell carcinoma. The advantages of this model are that it provides quantitative information for the fluid flow with and without considering diffusion into account and it provides a clear signal between the neighboring voxels instead of ignoring intervoxel contrast agent movements . This moKim et al.  used a vThis review paper discusses important investigations pertaining to the glymphatic system. The glymphatic system describes CSF flow within the perivascular spaces and extracellular spaces of the brain parenchyma with the help of AQP-4 on astrocytic end-feet for the interstitial waste solute drainage from the CNS. Nonetheless, some controversies and unresolved questions challenge glymphatic system studies and suggest alternative pathways for waste drainage out of the brain. One unresolved question is regarding the dominant solute transport mechanism for the glymphatic system. The roles of bulk flow and diffusion, as well as their driving forces, are still unsettled. Another unresolved question is whether glymphatic system dysfunction is the cause or the effect (or both) of numerous neurological diseases . VariousIn order to further our current understanding of the glymphatic system, future models and research should (1) include both diffusion and bulk flow terms into the modeling algorithm for an improved depiction of waste efflux to provide a more realistic fluid flow analysis; (2) determine the impact of various sedatives, sleep, and wakefulness on the bulk flow and diffusion measurements in the perivascular and extracellular spaces; (3) focus on systematically investigating the glymphatic system efflux pathways, which include the meningeal lymphatic pathway; and (4) develop therapeutic applications for the glymphatic system.


Proteobacteria in tumor tissues of the breast has been revealed by gene expression analysis. The link between human papillomavirus infection and cervical cancer has been known for some time, but the relationship between the microbiome and breast cancer (BC) is more novel. There are also recent attempts to investigate the possible link between the brain microbiome and the cognitive dysfunction caused by neurological diseases. Such studies pointing to the role of the brain microbiome in Huntington’s disease (HD) and Alzheimer’s disease (AD) suggest that microbial colonization is a risk factor. In this review, we aim to summarize the studies that associate the tissue microbiome, rather than gut microbiome, with cancer and other diseases using whole-transcriptome analysis, along with 16S rRNA analysis. After providing several case studies for each relationship, we will discuss the potential role of transcriptome analysis on the broader portrayal of the pathophysiology of the breast, brain, and vaginal microbiome.In recent years, a substantial number of tissue microbiome studies have been published, mainly due to the recent improvements in the minimization of microbial contamination during whole transcriptome analysis. Another reason for this trend is due to the capability of next-generation sequencing (NGS) to detect microbiome composition even in low biomass samples. Several recent studies demonstrate a significant role for the tissue microbiome in the development and progression of cancer and other diseases. For example, the increase of the abundance of  The human body hosts a microbiome of microbes, bacteria, and viruses  that resThe link between the human microbiome and some specific diseases/cancer types has been tackled by several comprehensive reviews ; Breast cancer (BC) microbiome  is hypotSome studies have shown that pregnancy and breastfeeding might reduce the risk of BC due to the protective behavior of the lactose fermenting bacterial flora in the mammary ducts . AnotherThe presence of mucosal-associated invariant T (MAIT) cells in the breast ducts intervenes T-helper 17 cell responses that might be regulated during breast carcinogenesis by the indications of breast microbiome and the expression of stress-related ligands by neoplastic breast duct epithelial cells .Proteobacteria, Firmicutes, and Actinobacteria are discovered in breast tumors  and tumor progression  in the etiology of AD has been evident recently, yet studies on the different viruses of the herpes family  are limited . NeverthBorrelia has been identified in structures associated with fungi  to the pathophysiology of the human central nervous system (CNS), including AD, has been potentially important . The preth fungi . Two ind tissues   in the brain microbiome of HD patients. RNA-seq analysis of human neurodegenerative disease tissues (except for AD) reported no significant difference compared to cytotoxic T-lymphocytes (CTL) tissues, indicating that the sub-clinical infections do not result in the inflammation related to the tissue of many neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) (Huntington’s disease is caused by a triplet expansion in the Huntingtin (HTT) gene . Alonso ase (PD) .Bacteroides plebeius and Acinetobacter lwoffii) are significantly more common in HPV positive women, suggesting a specific microbiome as a biomarker to detect changes in the cervical microenvironment indicating HPV infection  expression supports the claim of a distinct relation between tumor formation and HPV-positive cervical cancer , suggestHuman papillomavirus, human immunodeficiency virus (HIV), and HSV have been associated with the growth of genital-related cancers. Proteobacteria/Firmicutes, and the increase of genus Acinetobacter and decrease of genus Lactococcus  that display either positive or negative anomalies common to all cancer tissues discussed above  are enriched in the AD tissues, while they are not abundant in cervical and BC tissues. Additionally, Proteobacteria and Firmicutes are enriched in all types of cancer tissues. Such similarities and/or differences may be attributed to differences in tissue structure. Our mini-review will attract more attention to the reprocessing of the publicly available RNA-seq data to distinguish microbial contamination from tissue microbiome via in silico techniques to clarify the relative composition, abundance, and impact of microbiome in cancer tissues.Variations in the microbiome of cancer patients with different cancer stages have already been known in the literature. For instance, the species of es e.g., . The recin silico techniques are getting developed to discard the studies with bacterial contamination and non-standardized analysis pipelines, the re-analysis of the existing transcriptome data offers a huge potential for the future in silico data-mining microbiome studies from the vast amount of publicly available transcriptomic data.Most of the studies on the possible link between microbiome and diseases associating the presence of many potential microbial biomarkers and their pathways with the advanced stage of the diseases offer new insights into the diagnostic staging e.g., . There iRS wrote the manuscript and TÖS supervised the project. Both authors discussed the results and contributed to the final manuscript.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.


To the Editor—The cluster of novel coronavirus disease 2019 (COVID-19) originating in Wuhan, China, has now exploded into a pandemic via community spread. The COVID-19 epidemic in Japan began sometime between January and mid-February 2020. It is thought to have been brought to Japan by evacuees from Wuhan, China, or by infected passengers aboard a cruise ship. These patients were admitted to hospitals designated by the Japanese government for the treatment and containment of specific infectious diseases. However, these hospitals were unable to cope with the mounting numbers of patients, some of whom were referred to other tertiary-care centers. With the spread of the disease, a number of healthcare workers (HCWs) became infected with COVID-19, and their identity was made public by the Japanese mass media in reports carrying nuances of blame directed at the affected HCWs for having become infected. These media cited inadequate preparedness or insufficient infection control measures at hospitals as grounds for the blame they directed at the affected HCWs and continue to strongly influenced public opinion about the COVID-19 pandemic.1 As infections have continue to spread throughout the community, some hospitals have reported instances of nosocomial transmission between HCWs, especially at facilities that admitted patients with COVID-19 in the early stages of the pandemic. These facts were taken up by the media in the manner described above, undermining the reputation of HCWs in general who daily put their own health at risk to provide care to patients with COVID-19.One of the first outbreaks among HCWs in Japan occurred among a group of resident physicians who held a social gathering.In the wake of such episodes, hospital administrations have been obliged to issue press releases or hold press conferences whenever any of their healthcare staff tested positive or cases of nosocomial transmission of SARS-CoV2 were confirmed within their facility. Such announcements have typically included an apology on behalf of the sick HCWs and for possible in-facility transmission of the virus. As a consequence of the negative press, some hospitals have resorted to removing exposed HCWs from the frontline until they are cleared of COVID-19, hampering efforts to treat patients and control the spread of infections. Furthermore, these hospitals have sometimes reacted to public scrutiny by restricting or intermittently terminating the admission of newly infected patients to contain the nosocomial spread of COVID-19 despite the urgent need to treat more, rather than fewer, patients as the pandemic continues to spread unabated.4Outside the hospital setting, Japan has witnessed instances of discrimination against HCWs who may have had close contact with patients with confirmed or suspected COVID-19; both HCWs and their families have been slandered, and in some cases their children have been barred from entering nurseries or schools. Similar episodes of harassment or stigmatization of HCWs and their families have been reported from Singapore, Philippines, and other Asian nations as well as from Australia and the United States.5 Unfortunately, breaches in infection control can and do occur, given the dimensions, rapidity, and severity of the current pandemic, for which no government or facility was adequately prepared. The use of bulky equipment such as extracorporeal membrane oxygenation has made zoning difficult in the nosocomial setting. Airway management, including endotracheal intubation, requires considerable preparation prior to the procedure. In addition to these difficulties, HCWs also face shortages of personal protective equipment, which exponentially increase the risk of exposure to COVID-19 during patient care.Healthcare workers worldwide are at much higher risk of contracting COVID-19 by virtue of the work they do. Indeed, the number of HCWs who have become critically ill or have died from COVID-19 continues to mount daily.6 Anecdotal reports have described cases of patients receiving treatment for an unrelated illness during hospitalization, only to be found later to have been harboring SARS-CoV-2 unbeknownst to the HCWs. Also, as with the rest of the public, healthcare workers themselves are susceptible to community-acquired COVID-19 and may unwittingly carry the virus into the hospitals where they work if they are asymptomatic or minimally symptomatic.Moreover, the potential for SARS-CoV2 transmission from asymptomatic or minimally symptomatic patients has exacerbated the situation for HCWs.A public mindset of zero tolerance for COVID-19 among HCWs exerts powerful and deleterious pressure on the healthcare system. An attitude of zero tolerance is fueled by the public’s understandable fear of the spread of the disease but ultimately stems from an irrational response that can have only negative consequences for society in general. Criticizing HCWs for having contracted COVID-19 merely dampens their motivation to do their duty, increases their stress levels, and leads to ad hoc policies that set back treatment facilities in their fight against COVID-19.Improving the public’s understanding of COVID-19, in terms of its ease and modes of transmission and the numerous challenges faced by HCWs in battling the disease, is as equally important as effective political leadership in this time of global crisis—not only for the men and women in the frontline of the war against this pathogen but also, by extension, for the well-being of society at large.


One of the main goals of community ecology is to measure the relative importance of environmental filters to understand patterns of species distribution at different temporal and spatial scales. Likewise, the identification of factors that shape symbiont metacommunity structures is important in disease ecology because resulting structures drive disease transmission. We tested the hypothesis that distributions of virus species and viral families from rodents and bats are defined by shared responses to host phylogeny and host functional characteristics, shaping the viral metacommunity structures at four spatial scales . The contribution of host phylogeny and host traits to the metacommunity of viruses at each spatial scale was calculated using a redundant analysis of canonical ordering (RDA). For rodents, at American Continental scale the coherence of viral species metacommunity increased while the spatial scale decreased and Quasi-Clementsian structures were observed. This pattern suggests a restricted distribution of viruses through their hosts, while in the Big Mass , the coherence decreased as spatial scale decreased. Viral species metacommunities associated with bats was dominated by random structures along all spatial scales. We suggest that this random pattern is a result of the presence of viruses with high occupancy range such as rabies (73%) and coronavirus (27%), that disrupt such structures. At viral family scale, viral metacommunities associated with bats showed coherent structures, with the emergence of Quasi- Clementsian and Checkerboard structures. RDA analysis indicates that the assemblage of viral diversity associated with rodents and bats responds to phylogenetic and functional characteristics, which alternate between spatial scales. Several of these variations could be subject to the spatial scale, in spite of this, we could identify patterns at macro ecological scale. The application of metacommunity theory at symbiont scales is particularly useful for large-scale ecological analysis. Understanding the rules of host-virus association can be useful to take better decisions in epidemiological surveillance, control and even predictions of viral distribution and dissemination.Supplementary material is available for this article at 10.1556/168.2018.19.2.9 and is accessible for authorized users. Supplementary material, approximately 21 KB.


Wound is defined as primarily damaged or disruption of skin contributed to the loss of its microstructure stability and which undergoes complex wound healing process. However, there are tons of factors that could affect the wound healing process such as infection and slow angiogenesis. Involvement of nanotechnologies therapies in wound care research aims to facilitates this healing process. Quantum dots (QDs) are an advanced nanomaterial technology found to be useful in clinical and biomedical applications. This review has been carried out to provide a summary of the application of QDs in acute or chronic wound healing. A thorough searching was done via Web of Science and SCOPUS database to obtain relevant articles including the in vivo, in vitro and in ovo studies. The results demonstrated a similar effect of different types of QDs, or an improvement of QDs in wound healing, antibacterial and angiogenesis properties. This review demonstrated the effectiveness of QDs for the wound healing process mainly by their antibacterial activity. Uniquely, the antibacterial effect unraveled an increasing trend over time influenced by the various concentration of QDs. In conclusion, the application of QDs support the wound healing phases and proven to be effective in vivo, in vitro and in ovo. However, the future QDs work should focus on the molecular level for the details of cellular interactions and pathways. Skin is the largest organ of the body which acts as a front-liner of defense mechanism . It is vThere are four stages of skin wound: superficial which involve the epidermal layer only (Stage 1), partial-thickness skin loss which affects the epidermis and dermis (Stage 2), full-thickness skin loss extends into the dermis and affects the adipose tissues (Stage 3) and full-thickness skin loss which also extend through the dermis and adipose tissues that expose the muscle or bone Stage 4) . F. F5]. FiRapid wound closure and regeneration of the damaged skin is essential to maintain and re-develop the skin integrity . Re-estaThere are also other factors that may influence the healing process such as oxygenation, stress and other related-diseases . Lack ofHowever, the topmost common factors affecting wound healing is a secondary bacterial infection. One of the most efficient way to fight against the growth of bacteria is exposure towards antibacterial metals such as zinc, silver, titanium etc. Nevertheless, the uses of these large quantity of these metals could have negative impacts on human health and the environment. Therefore, the development of nanoparticles become the best solution to decode the problems arise in the uses of heavy metals as well as increases the efficiency of the metal towards the antibacterial activity. Recent technological advancement has improved the biomedical fields especially with the development of nanotechnologies.The development of nanotechnologies provided an improvement in health industries with current innovation of functional and smarter nanomaterials to tackle the drawbacks for unintended wound as well as provide better outcomes among patients. Recently, the nano-based technologies have shown significant roles in wound healing and regenerative medicine applications. Nanotechnologies also improved the interaction between tissue and materials through biomimetic approach, helps in tissue regeneration whilst provide better micro-morphology and properties resembling the native tissues . There aOrganic nanomaterials are fabricated through organic compound e.g., chitosan, curcumin, etc. The main objective for organic nanomaterials in wound healing application is to carry out the treatment or active ingredients to targeted cells . NanocapMeanwhile, the inorganic nanomaterials are fabricated substances through inorganic compound such as polymer and metallic component. Metallic nanoparticles including silver, zinc, and gold exhibits unique physicochemical properties that excellent in accelerating wound healing process. In addition, silver nanoparticles have been used in wound dressings as they display oligodynamic effects towards bacteria . FabricaQDs were first discovered by Ekimov and Onushenko in 1981, and are nanoscale semiconductor crystals and first nanotechnologies to be applied in biological science made of heavy metals ,33. QDs The synthesis of QDs results in organic capping ligands that make them biocompatible, and a biological targeting development which achieved by surface modification and linking with antibodies, peptides or small molecules ,36. QDs There have been increasing research on QDs in wound healing as these nanoparticles equip the same properties as their bulk counterparts and more stable due to their large surface area . The uniIn this review, a literature search was done through electronic databases was carried out to identify the in vivo, in vitro and in ovo study performed on the application of QDs in chronic and acute wound healing. Literature search was done on the reports regarding the effect of quantum dots (QDs) on biomedical and clinical applications, especially in the wound healing process. The outcomes from the review highlighted the advantageous of quantum dots (QDs) in wound healing. There are various reports on the application of QDs in wound healing and it has been tested in vivo, in vitro and in ovo model. The overall result of QDs seems to be beneficial towards wound healing as the treatment group obtains better results compared to the control group. However, the combination of QDs with polymer e.g., carbon quantum dots with hybrid tannic acid and keratin (CQDs-TA/KA) hydrogel yields a more appealing result compared to QDs itself . in vivo studies were used to study the biological effect of QDs in a dynamic and complex biosystem e.g., the wound closure. Apart from having QDs derived from various types of heavy metals, the papers were primary aim to assess their biological effect in selected wound model in each study. Most of the studies inflict a cutaneous incisional wound and there only one study that inflicts burn wound on the animal. The wound healing assessments were performed by gross morphology of the wound, the size of wounds and the histological evaluation using hematoxylin and eosin (H & E) staining to determine the condition of the regenerated tissue [The d tissue . The in Based on the results obtained, the QDs supports the wound healing process in vivo. The histological assessment shows the regeneration of tissue and formation of blood vessel when treated with QDs. Xiang et al., 2019 show even disposition of collagen and dense collagen fibers when treated with QDs . HaghsheEscherichia coli  and Staphylococcus aureus . Generally, the antibacterial properties of QDs were analyzed using a plate counting method to calculate the colony-forming unit (CFU) of remaining bacteria after exposure to the particular treatment modalities and morphological studies on bacteria were conducted to compare the bacterial structure pre- and post-treatment. When the bacteria were exposed to QDs, the microbial membrane disrupt due to the high production of reactive oxygen species (ROS) which triggers significant lipid peroxidation on membrane [S. aureus even inhibits the growth of different drug-resistant bacteria e.g., Methicillin-resistant Staphylococcus aureus (MRSA) [The elevated prevalence of microbial infection increases the complication in wound healing especially in skin injuries. Thus, a higher rate of morbidity in conventional therapeutics creates a demand for alternative antibacterial agents to treat microbial infections such as QDs, silver and others. Briefly, the common antibacterial mechanism of QDs takes place via three molecular mechanisms: (1) disruption of cell walls or cells membrane, (2) production of reactive oxygen species (ROS) and (3) binding with nuclei materials such as DNA or RNA to inhibit the cell proliferation. The most common bacteria used in the antibacterial studies were membrane . The coms (MRSA) .E. coli than with S. aureus [This review has stated that the antibacterial properties of QDs have a strong reaction towards both gram-negative and gram-positive bacteria . However. aureus . The mai. aureus ,63. QDs . aureus . The pho. aureus . Table 3Angiogenesis is one of the important factors in wound repair which function to deliver the gaseous  and nutrients at wound sites to further support the cell growth and tissue regeneration . AngiogeThere are three articles on the angiogenesis properties of QDs ,69,70. ZAngiogenesis occurs with the migration and mitogenic activation of the endothelial cells in the extracellular matrix of the wound bed. This results in a temporary increase of blood vessels at the wound site and included in the granulation tissue formation . The excSharma et al., 2019 have been investigating the interaction of carbon dot (CD)-urea towards endothelial cells . The resFrom this literature search, most of the studies on QDs found were related to its self-illuminate properties. Accordingly, the result of the QDs were limited to its application in bio-sensing and bio-imaging. However, in terms of wound healing application, there are limitation in the literature distribution. Consequently, the underlying cellular mechanisms of QDs are yet to be known. Hence, more studies should be properly performed such as the effect of QDs in cell mechanism and longer observation period to learn the side effect of QDs. The data collected in the review also described that different types of QDs have distinguished findings which can be improved by focusing on one type of QDs to have a better understanding of its biological properties. Various type of wound could also influence the efficacy of the QDs e.g., full-thickness skin loss have slower healing rate than an acute wound which cause the time period of wound healing to differ even treated with the similar type of QDs . AnotherStudies included in this overview have shown the efficiency of the application of quantum dots  in biomedical applications due to their wound healing, antimicrobial, and angiogenesis properties. There are many articles that proved the effect of QDs in wound healing and had been tested in vivo, in vitro and in ovo models. In terms of wound management, the high antibacterial properties of QDs towards drug-resistant bacteria making them one of alternative antimicrobial therapy. QDs also can enhance angiogenesis in the injury site as it helps in the expression of angiogenic proteins. From our perspective, the in vivo studies of QDs provide more impactful data on the efficiency of these nanoparticles in wound healing research as these data shown the effects of QDs in reconstruction of tissue and closure of wound. The data shown in our review supports the inkling of QDs in wound healing process. Therefore, further studies are required to be done for further understand the applications of QDs in wound healing especially in the molecular levels as well as the details involvement of nanoparticles at different wound healing stages.


The anterior digastric muscle belly (ADMB) may present significant variations of substantial surgical importance. We present an unusual complex bilateral asymmetry of an accessory ADMB found when dissecting the submental area in a 72-year-old Greek male cadaver. A rare variant was recognized in the submental area constituted by a combination of bilateral asymmetry of the ADMB with unilateral absence of the intermediate tendon. The complex variant caused an obvious morphological asymmetry in the submental area. Such muscular variations may alter the surgical approach to the submental region. Clinicians involved in the treatment of this area should be aware of any possible variant, particularly when dealing with neck mass patients.  The digastric muscle (DM), located in the suprahyoid region, consists of an anterior and a posterior digastric belly (ADMB and PDMB), each of them arising from different embryological precursors and thus supplied by different nerves. The ADMB is innervated by the mylohyoid nerve , while the PDMB is supplied by the facial nerve. Different innervation is explained by the separate derivation of the two bellies from the first and second brachial arch mesenchyme. The ADMB and PDMB are converged to the intermediate tendon (IMT) connecting with the hyoid bone (HB) through a fascial sling closely associated with the stylohyoid muscle (SHM) insertion. The ADMB originates from the digastric fossa. An aponeurotic layer gives off the tendon to the HB body and great horn. The DM may lack the IMT, thus be attached directly to the HB. The muscle is vascularized by the submental artery  .The ADMB presents a great variability in size, shape, and form. The ADMB variations may present double or extra slips spreading to the jaw or the mylohyoid muscle (MHM) or crossing over the midline to the opposite MHM or the opposite digastric fossa. These unilateral or bilateral muscle bundles or slips may occur as a result of a phylogenetic DM reduction or an unusual development of the ontogenetic material . The ADMThe current case report highlights the occurrence of a bilaterally asymmetrical accessory ADMBs and the unilateral absence of the IMT. The complex muscular variant caused an obvious asymmetry over the submental area. Knowledge of this kind of variability is of paramount importance in neck mass imaging interpretation and differential diagnosis. During the submental region dissection in a 72-year-old Greek male cadaver, a bilateral accessory ADMB was observed Figure . On the Contralateral, the left SHM typically attached to the HB, via a single bundle, coursing along the inner aspect of the IMT and ending up into an extended strong fibrous band (representing an IMT extension in terms of function) without any attachment to the HB. Towards the superior and inferior aspect of the SHM, thin muscle bundles attached in a pennate fashion, the superior one ultimately crossed the midline over the MHM, while the inferior counterpart spread out freely over the HB. The main left-sided ADMB possessed two origins, one larger extended over the inferior mandibular rim, and a separate smaller one originating from the digastric fossa. Both parts merged further, forming a common belly and typically attached partially to the anterior end of the IMT and partially to the commencement of the fibrous band Figure .Embryological background of DM aberrationsZlabek, studying the ADMB variants, found that the muscle expansion towards the midline was characterized by its rectangular oblongation . In aberThe ADMB variability among various studiesSeveral anatomical studies described the ADMB and DM fibrous sling variations ,10. The Clinical significanceAsymmetrical or symmetrical ADMBs variations are of clinical importance since they indicate asymmetry cases over the anterior region of the neck or even in the movement of the floor of the mouth or the temporomandibular joint and perhaps imbalance in laryngeal movement . The asyThe DM variability is of paramount importance during platysma myocutaneous flap mobilization in reconstructive procedures ,20. ThorBy using computed tomography (CT) and magnetic resonance imaging (MRI), typical and variable anatomic structures and pathologic entities of the floor of the mouth can be evaluated .The described aberration represents a variant in the MHM-DM group in the floor of the mouth. This kind of ADMBs aberrations has to be taken into consideration when evaluating the floor of the mouth, as they can be confused with pathological conditions in imaging. Therefore, normal anatomical variants have to be considered on CT and MRI when an asymmetry over the floor of the mouth is encountered .Submental and submandibular areas are very well vascularized, and knowledge of their muscular abnormalities is essential when a myocutaneous flap is mobilized in reconstructive plastic surgery. Vascular variations may coexist, and in order to maintain and increase flap’s viability, vessels’ branching pattern must be well preserved, intraoperatively. CT and MRI are valuable imaging tools in the differential diagnosis of the muscular abnormalities from pathological lesions, as due to the muscular tissue density, accessory, and hypertrophied DM can be easily misinterpreted as a tumor or a lymph node. Cases of asymmetrical aberrancies in submental region should be very carefully identified in order to avoid misinterpretation.


To estimate the efficacy of app-based interventions designed to support medication adherence and investigate which behaviour change techniques (BCTs) used by the apps are associated with efficacy.Systematic review of randomised controlled trials (RCTs), with meta-analysis.Medline/PubMed, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Embase and Web of Science were searched from 1990 to November 2018 for RCTs conducted in any healthcare setting.Studies of participants of any age taking prescribed medication for any health condition and for any duration.An app-based intervention delivered through a smartphone, tablet computer or personal digital assistant to help, support or advise about medication adherence.One of (1) usual care, (2) a control app which did not use any BCTs to improve medication adherence or (3) a non-app-based comparator.The primary outcome was the pooled effect size of changes in medication adherence. The secondary outcome was the association between BCTs used by the apps and the effect size.The initial search identified 13 259 citations. After title and abstract screening, full-text articles of 83 studies were screened for eligibility. Nine RCTs with 1159 recruited participants were included. The mean age of participants was >50 years in all but one study. Health conditions of target populations included cardiovascular disease, depression, Parkinson’s disease, psoriasis and multimorbidity. The meta-analysis indicated that patients who use mobile apps to support them in taking medications are more likely to self-report adherence to medications  than those in the comparator groups. Meta-regression of the BCTs did not reveal any significant associations with effect size.App-based medication adherence interventions may have a positive effect on patient adherence. Larger scale studies are required to further evaluate this effect, including long-term sustainability, and intervention and participant characteristics that are associated with efficacy and app usage.PROSPERO Protocol Registration Number: CRD42017080150. This systematic review and meta-analysis of randomised controlled trials offers new information on the efficacy of mobile device apps in supporting medication adherence across a range of medical conditions.This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.A sensitive search strategy was designed, and screening of articles and data extraction were performed independently by one clinical researcher and one non-clinical researcher.The review protocol was prospectively registered, and the scope of the review, inclusion and exclusion criteria remained unchanged throughout.Two reviewers independently considered the abstracts and full-text articles for inclusion, extracted the data, and assessed the included studies for risk of bias in the same way.Adherence to medication is defined as the extent to which patients take medications as prescribed and agreed with their healthcare providers.Interventions for improving adherence should be reliable, contemporary, acceptable and readily available to the person. Mobile devices can meet these needs, and in 2018 Ofcom reported that 78% of adults and 95% of individuals aged 16–24 years old in the UK own a smartphone, demonstrating that smartphones are a growing part of modern life.Hundreds of apps are now available to patients to support them in taking regular medication.The objectives of this review are (1) to establish whether apps designed to support medication adherence demonstrate efficacy and (2) to identify the intervention characteristics and BCTs associated with efficacy. The conclusions drawn have potential to inform future large-scale public health interventions for the improvement of medication adherence.This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.This research was done without patient involvement. Patients were not invited to comment on the study design and were not consulted to develop patient-relevant outcomes or interpret the results. Patients were not invited to contribute to the writing or editing of this document for readability or accuracy.Medline/PubMed, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Embase and Web of Science electronic databases were searched from 1990 to November 2018. A sensitive search strategy was designed based on preliminary searches, relevant papers and keywords. Key search terms included adherence, non-adherence, smartphone app and randomised controlled trials (RCTs). An example detailed search strategy for the Medline/PubMed database can be found in 10.1136/bmjopen-2019-032045.supp1Supplementary dataTwo reviewers (LCA and AK) independently screened all citations by title and abstract and excluded those which were irrelevant or clearly did not meet the eligibility criteria. Full-text articles were obtained for all remaining citations and screened against the eligibility criteria by the same reviewers. Any discrepancies at any stage in the screening process were settled through discussion between LCA, AK and a third reviewer (SS).RCTs relevant to this review were those that investigated the use of an app on a mobile device to support medication adherence. The inclusion criteria were as follows:Participants of any age who were taking one or more prescribed medications for any health condition and for any duration.An intervention group which received an app-based intervention delivered through a smartphone, tablet computer or personal digital assistant to help, support or advise about medication adherence.A comparator group which received usual care, a control condition which did not use an appMedication adherence data were reported for both the intervention and comparator groups.The exclusion criteria were as follows:Complex interventions of which an app was just one component.Interventions delivered by text messaging or telemedicine.Outcome assessed was adherence to treatment components other than prescribed medication. For example, one study reported outcome data as a composite score, combining adherence to other aspects of the medical regimen (such as clinic attendance and laboratory work) with adherence to medication.A study population of healthy recruits who were required to adhere to a placebo medication.Comparator group received an adherence intervention in another format, such as a different medication adherence app.Published articles were required to be in the English language.Data were extracted independently by two reviewers (LCA and AK) using a custom data extraction form. Participants’ baseline characteristics were extracted, including age and sex. Raw data on medication adherence were extracted either from the published articles or by contacting the authors of the primary studies by email. When two measures of adherence were reported, that which was considered most comparable with the outcome measures of the other included studies was used for meta-analysis. For example, one study reported adherence according to both the number of times an electronically chipped dispenser was actioned by the patient and the weight of the dispensing canister at study follow-up, and the reviewers agreed that the action of dispensing was more comparable with that of the other included studies.The included trials were assessed for risk of bias using the Cochrane Risk of Bias Tool.2 statistics were used to estimate heterogeneity between the included studies.Outcome data on medication adherence were extracted from each of the included studies at the final observation point. Authors were contacted for raw final observation point adherence data if these were not reported in published manuscripts. Trials were considered homogeneous based on the content of the intervention and comparator groups and the outcome measurement of medication adherence. The Comprehensive Meta-Analysis SoftwareThe initial electronic database search identified 13 259 potentially eligible studies, and 2 were identified from the reference lists of identified articles. After removal of duplicates, 9971 citations were screened by title and abstract. We considered 83 of these to be eligible and retrieved the full-text articles. Of these, nine studies reported outcome data eligible for meta-analysis.The characteristics of the nine studies are shown in The mean age of participants in the intervention group was reported by eight studies and ranged from 20.3 (SD 4.0)Health problems of the target population varied between studies. Five studies sampled a patient population with cardiovascular disease,A number of measures of medication adherence were used in the included studies. Of the nine studies, four measured adherence using the eight-item Morisky Medication Adherence Scale,2 value was 9.8, indicating low statistical heterogeneity between the studies included in the meta-analysis. The forest plot of the meta-analysis is shown in Meta-analysis was performed, pooling results from the nine eligible studies which reported data on 988 participants, to estimate the effect of mobile apps in improving medication adherence.A focused meta-analysis was performed, pooling results from the five studies which reported medication adherence according to the Morisky Medication Adherence Scale.The most common BCT used by apps was ‘Tailored’, which was used by all studies. The next most common was ‘Prompts and Cues’, used by seven studies,A summary of the risk of bias analysis is shown in The most common source of risk of bias among the studies was the absence of blinding of participants and personnel to the outcome measure. The second most common risk of bias arose from a lack of objective measurements of medication adherence. This was due to the use of self-report measures of adherence: six of the studies included in the meta-analysis reported adherence based on a self-assessment scale,Self-assessment scales are a form of self-report and therefore a source of potential bias, including those of social desirability, and those arising from selective recall and the duration of the recall period.A funnel plot of effect size estimates of each of the studies included in the meta-analysis is provided in We conducted a rigorous systematic review of the literature to investigate whether mobile device apps demonstrate efficacy in supporting medication adherence. A random-effects meta-analysis of the pooled results from all nine studies indicated that people who use medication reminder apps are significantly more likely to adhere to their medications than those who do not, but the results should be interpreted with caution owing to the data for six of the nine studies included in the meta-analysis being based on self-reported measures of adherence.2 measure of statistical heterogeneity was low, and meta-regression of the BCTs used by the studies was not able to account for variance in effect observed between studies, there are other potential sources of methodological and clinical heterogeneity which may account for this. One potential explanation might be the variation in adherence measurement. This may be illustrated by three studies which incorporated five of the same BCTs,et al’sIntervention effects reported between the studies varied, as shown in the forest plot . All ninet al,et al.A further possible explanation for variance in effect size might be the techniques, beyond those reported in the BCT taxonomy, used by the apps. For example, in the study by Labovitz Further participant-related factors which may have contributed to variance in the effect size seen between studies, include disease burden, non-adherence behaviours, perceived benefit from the medication and any side effects. Interpretation of the overall result of the meta-analysis and generalisability to the wider population should therefore be cautious.Based on the assessment of the risk of bias undertaken as part of this review, the evidence included in this meta-analysis is of moderate quality. The most common weaknesses in this evidence are small sample size, lack of objectivity of the outcome measurement, lack of blinding of participants and personnel, and limited follow-up time.Our comprehensive literature search and search of the PROSPERO database indicate this is the first systematic review and meta-analysis to investigate the efficacy of mobile apps in supporting medication adherence. This offers new knowledge to the field; however, as such there are no comparable studies with which the results of this review can be compared.The pooling of data from a group of studies which used a variety of methods for measurement of medication adherence and targeted at patients with different healthcare problems is a limitation of this review. As further studies in this field are published, it will become more feasible to conduct subgroup analysis or meta-regression analyses against variables such as age, health condition, targeted medication, intervention content and app characteristics. A standardised protocol for measuring adherence and reporting the content and characteristics of app interventions may facilitate further analysis of the latter two variables.This review cannot report on the likely sustainability of the effect on medication adherence given the short study duration of the studies included in this review; across the nine studies, the maximum follow-up period was 16 weeks. Furthermore, the optimal frequency and duration of app use that are required to achieve improvements in medication adherence are not known. Long-term and large-scale research is required in this field to address the question regarding the sustainability of the observed effect found in this meta-analysis.This systematic review and meta-analysis included studies with a range of ages of participants. The lowest mean age of participants in the included studies was 20.9 years and the highest was 70.9 years. The ubiquity and use of mobile devices vary across age groups,Finally, the reviewers set out to perform a meta-regression of the BCTs used by app interventions in the included studies.This meta-analysis indicates that medication adherence interventions delivered by smartphone apps are associated with higher levels of self-reported adherence to prescribed medications. However, when considering whether to recommend an app to patients, these results should be interpreted with caution owing to variance in effect size seen between the studies, the small sample sizes taken from different patient populations, the heterogeneity among included studies and the prominence of self-reported scales to measure medication adherence. Further research should aim to first establish a standard protocol for measuring and reporting of adherence in the context of evaluating digital interventions. Subsequently, further research investigating intervention characteristics associated with an app’s effect and the sustainability of any effect gained would add to this field.


A multitude of visualization techniques are available to inspect the coronary arteries in Steady-State Free-Precession (SSFP) MRI cardiac data, both 2D  and 3D (volume rendering and maximum intensity projection). The workflow required to generate the visualizations includes user interactions such as segmentation, path tracking, and geometry manipulation . When these interactions are performed manually, the workflow becomes time consuming, and the inter-user reproducibility is low.We describe a method that optimizes the workflow of local visual inspection of the coronary arteries by reducing the user interaction to a single mouse click. No a priori segmentation or path tracking is required, and the optimal position, orientation, and zoom factor of the views are found automatically, thereby increasing the efficiency and reducing and inter-user variability.The method presented here should be considered as an advanced magnifying glass applied to the coronaries. When the user needs to inspect a particular location at one of the coronaries, a single mouse click locally computes a vessel centerline at the cursor position (yellow arrow in Figure The accuracy of the local path tracking has been evaluated on 11 data sets used in the work presented in . The meaOur path tracking technique is very fast, it takes only tenths of a second including the generation of the visualizations. The user thus receives live feedback about the local coronary anatomy. The fact that all visualizations are automatically properly aligned decreases the inter-user variability associated with manual interactions. When different users click at about the same location, the same renderings will be generated.The method presented in this article greatly improves the workflow required to inspect the coronaries locally, while at the same time reducing the inter-user variability. A single mouse click generates optimal visualizations of the local geometry of the coronary vessels.


Avena chinensis) fields under different planting patterns were collected at different growth stages by standardized sweep netting sampling, and the differences in arthropod communities and temporal dynamics were analyzed. Taking this information as an example, the effects of crop diversity at the landscape scale caused by different planting patterns on arthropod communities were studied. It was found that herbivores were the most abundant functional group in the arthropod community in naked oat fields, accounting for 70.13% of the total abundance, followed by natural enemies, accounting for 23.45%, and, finally, other insects. The abundance and species richness of natural enemies in naked oat fields under diversified planting pattern were significantly higher than those under intensive planting pattern, while the abundance and species richness of herbivorous pests showed no significant difference between the two planting patterns. Planting patterns significantly affected the composition and structure of arthropod communities in naked oat fields. Significantly higher ratio of natural enemy to pest and more diverse natural enemies under the diversified planting pattern have shown better biological control potential and the significance of biodiversity protection.The expansion of agriculture and intensive mechanized production have resulted in the loss of habitats and biodiversity, which has led to the loss of ecological services such as the biological control of pests and diseases, and insect-borne pollination. Current studies mainly focus on the impact of small-scale crop diversity (such as intercropping) on ecological service but lack research on the effects of crop diversity at the landscape scale. In this study, vegetation-dwelling arthropods in naked oat ( Agricultural land is the most important land use mode on the earth, accounting for 40% of the surface of nonfrozen land and providing an important source of food for human survival . With thIn agricultural landscapes, habitats are mainly divided into crop habitats and non-crop habitats . Non-croIncreasing attention has been paid to the management of farmland landscape habitats, which is considered to be an effective way to increase the abundance of natural enemies and, thus, support important ecosystem services such as biological pest control . Pest biAt present, most studies on landscape heterogeneity focus on the effects of overall landscape heterogeneity  or on the effects of the proportion of natural and semi-natural habitats ,23,24, wAvena chinensis) fields  caused by different planting patterns were studied as research examples in order to explore the impact of crop diversity on the vegetation-dwelling arthropod communities at the landscape scale. In addition, the dynamic changes of vegetation-dwelling arthropod communities in naked oat fields during different growth stages were studied to explore the changes of arthropod communities in different growth stages of naked oat. Ultimately, management suggestions and theoretical support are expected to be provided for biodiversity conservation and sustainable agricultural development.Therefore, the effects of crop diversity at the landscape scale on the composition and structure of vegetation-dwelling arthropod communities in naked oat  of Zhangjiakou City, Hebei Province, China in 2018 . The cliSesamum indicum), silage corn (Zea mays), potato (Solanum tuberosum), cabbage (Brassica oleracea), etc. The planting pattern of agriculture mainly includes the diversified planting pattern and intensive planting pattern. The former is a small-scale peasant economy planting model with a long history, with each family planting a small area of farmland separately. The latter is a modern intensive mechanized large-scale single crop planting pattern. Some farmers in this region have transferred farmland to enterprises, and enterprises have centralized and unified the management of large areas of land for agricultural production, forming an intensive planting pattern. Some farmers have retained their own farmland and planted different crops according to their needs, forming a diversified planting pattern. The farmland with different crops forms different landscape units. The main crop of this region, naked oat, is present in both planting patterns  according to their feeding habits. Arthropods were also classified into winged and wingless according to their flying ability.H’) was calculated as H’ = −iP is the proportion of the ith species in the community and ln is the natural log [Community structure indices were calculated based on species individual data. The Shannon–Wiener diversity index  and linear mixed-effects models (LMMs). The abundance and species richness of vegetation-dwelling arthropods in naked oat fields under different planting patterns were analyzed with Poisson GLMMs because this distribution is usually applied to count data . The comDifferences in the vegetation-dwelling arthropod community in naked oat fields under different planting patterns were determined by conducting a one-way permutational multivariate analysis of variance (PERMANOVA) using Bray–Curtis dissimilarity matrices. A non-metric multidimensional scaling (NMDS) graph was drawn to visually investigate the differences between arthropod communities in naked oat fields under different planting patterns more intuitively. Differences in the abundance and the percentage of different functional groups between two planting patterns and among three growth stages were tested, respectively, by applying one-way ANOVAs, followed by Tukey’s honestly significant difference post hoc test.All data presented in this paper were analyzed using R version 3.6.0 , with the “lme4” package for the GLMMs and LMMs, the “vegan” package for the NMDS, the “multcomp” package for the ANOVAs, the “car” package for testing the validity of all the models, and the “ggplot2” package for plotting all the statistical charts.In the three growth stages of naked oat in Guyuan County, 5330 vegetation-dwelling arthropods were collected spanning 2 classes, 12 orders, and 62 families in naked oat fields. The abundance of Insecta accounted for more than 95% of the population. The Diptera in the Insecta occupied the largest number of both species and individuals, including 25 families and accounting for 31.74% of the total arthropods. Aphididae, Thripidae, Agromyzidae, Chrysomelidae, and Syrphidae were the five families with the largest abundance in the arthropod community, accounting for 59.27% of the total arthropods. In terms of functional groups, there were 23 families of herbivores, accounting for 70.13% of the total arthropods, which was the main component of the arthropod community in naked oat fields. In additional, there were 25 families of natural enemies, accounting for 23.45% of the total arthropods. The main natural enemies were Syrphidae, Araneae, Asilidae, Chrysopidae, Braconidae, and Ichneumonidae. Other insects comprised 14 families, accounting for 6.42% of the total arthropods.p < 0.001) and more species (p < 0.001) than did that under the intensive planting pattern. When looking at each of functional groups, the abundance of natural enemies and other insects under the diversified planting pattern were significantly higher than those under the intensive planting pattern (p < 0.05). However, there was no significant difference in the abundance of herbivores (p = 0.298). Similar to the results for the abundance of different functional groups, the species richness of natural enemies and other insects of the vegetation-dwelling arthropod communities in naked oat fields under the diversified planting pattern was significantly higher than that under the intensive planting pattern (p < 0.05). Similarly, there was no significant difference in the species richness of herbivores (p = 0.071).The analysis results of the GLMMs showed that the crop diversity caused by the different planting patterns had an effect on the abundance and the species richness  in the vp < 0.05).The plot of the NMDS analysis showed intuitively that the compositions of the vegetation-dwelling arthropod communities in naked oat fields under different planting patterns were different . At the p < 0.05). In contrast, the proportion of herbivores was significantly higher in the flowering stage than in the tillering stage (p < 0.05). Comparisons between different planting patterns revealed that there were no significant differences between natural enemies and herbivores under the different planting patterns in the tillering stage. In the jointing and flowering stages, natural enemies under the diversified planting pattern were significantly higher than those under the intensive planting pattern, while the trend of herbivores was the opposite (p < 0.05). In total, the comparisons between different planting patterns were the same as that of the jointing and flowering stages. In addition, the vegetation-dwelling arthropod communities under the diversified planting pattern had a significantly higher ratio of natural enemy to pest than those under the intensive planting pattern .The Shannon–Wiener diversity index can reflect the community structure of an arthropods community . The anap < 0.05). However, under the intensive planting pattern, the abundance did not differ significantly among the three growth stages. In addition, the abundance of total arthropods under the diversified planting pattern was significantly higher than that under the intensive planting pattern in the jointing stage (p < 0.05). In terms of the abundance of arthropods in different functional groups, the abundance of herbivores was the lowest in the tillering stage, followed by the jointing stage, and the highest in the flowering stage under both planting patterns. The abundance in the flowering stage was significantly higher than that in the tillering stage (p < 0.05). There was no significant difference in the abundance of herbivores under the different planting patterns over the three growth stages. Unlike herbivores, the abundance of natural enemies showed a downward trend among the three growth stages. The abundance in the tillering stage was significantly higher than that in the flowering stage under the intensive planting pattern (p < 0.05). Furthermore, the abundance of natural enemies under the diversified planting pattern was significantly higher than that under the intensive planting pattern in both the jointing stage and the flowering stage (p < 0.05).The temporal dynamics of the abundance of the whole vegetation-dwelling arthropod community and the different functional groups in naked oat fields in three growth stages under the two planting patterns were analyzed . The resFrom the analysis of the composition of the vegetation-dwelling arthropod communities in naked oat fields, we show that the arthropod communities were mainly dominated by a few dominant species. In addition, the herbivores were the main components of the arthropod community, and abundance was more than twice the abundance of natural enemies and other insects. This is similar to the results of the arthropod community survey in the grassland biodiversity experiment at the Cedar Creek Ecosystem Science Reserve , where hp < 0.05), while there was no significant difference in the abundance and species richness of herbivores of low trophic level between the two planting patterns (p > 0.05). The agricultural landscape structure and habitat type have different effects on different trophic levels of arthropod food webs in crops. In the same community, the higher is the trophic level of the species, the larger is the niche it occupies. Conversely, the lower is the trophic level, the smaller is the niche. Species that occupy a larger niche are more affected by habitats ,35. In op < 0.001, p = 0.557, The abundance of natural enemies determines the effectiveness of biological control, and the species diversity of natural enemies is linked to the stability of this ecological service . The higThe results of the NMDS in our study were similar to those of Liu et al.’s  field-scThe ecological balance of pests and natural enemies is the key factor in determining the biological pest control effect. A diverse and abundant natural enemy community supports higher pest control ,37,38. CIn this study, more and more diverse natural enemies under the diversified planting pattern with more heterogeneous landscapes and more diverse habitat types is more conducive to pest control ,40. HoweIn the agro-pastoral transitional zone of Northern China, the diversified planting pattern of the traditional small-scale peasant economy coexists with the modern mechanized intensive planting pattern, which provides a convenient condition for us to study the effects of crop diversity on arthropod communities at the landscape scale. This study complements the gaps in the large-scale study of the response of arthropod communities to crop diversity. Our study found that there were significant differences in arthropod community compositions between the two planting patterns, and the landscape-scale crop diversity caused by a diversified planting pattern could significantly increase the overall abundance and species richness of the arthropod community in farmland. Among these attributes, the abundance and species richness of natural enemies in naked oat fields under diversified planting pattern were significantly higher than those of naked oat under intensive planting pattern, while herbivorous pests did not differ significantly between the two planting patterns. Moreover, the differences in community composition between the two planting patterns were mainly caused by winged arthropods with a larger active radius and stronger migration ability. At different growth stages, the abundance of natural enemies in naked oat fields under diversified planting structure was higher than that of naked oat under intensive planting pattern, and the growth trend of herbivorous pests was also smaller than that under intensive planting pattern. Moreover, significantly higher ratio of natural enemy to pest and more diverse natural enemies under the diversified planting pattern have shown better biological control potential and the significance of biodiversity protection. Compared with the ecological service value exhibited by the crop diversity at the farmland scale, the improved biological pest control effect produced by crop diversity at the landscape scale is of greater significance to farmers. Because the realization of crop diversity at the landscape scale does not require complex habitat management, agricultural activities are simpler, and there are no complicated changes to the methods of sowing, fertilization, and harvesting. It is only necessary to reduce each farmland to a certain extent and increase the types of crops planted at the landscape scale. If the plan is thorough, the workload of farmers will not increase, but a good biological pest control effect will be achieved.


The pathophysiological mechanisms responsible for male subfertility/infertility caused by or complicated by genital heat stress remains unclear in many respects. Because seminal plasma creates the environment for the proper functioning of spermatozoa, in this study, we verified the associations among standard spermiograms, seminal biochemical parameters  and oxidative stress markers  in distinct entities associated with male infertility with and without long-time exposure to local hyperthermia. We demonstrated that men exposed to prolonged environmental or clinically recognized local heat stress in adulthood may suffer from dysregulation of seminal antioxidant components, which can be directly associated with epididymal and prostate function. The comparative analysis of the studied parameters showed numerous correlations among all biochemical parameters  with low standard semen quality in almost all the investigated infertile groups. In light of the data obtained in this originally designed study, we conclude that more attention should be paid to the epididymis and accessory gland function in subfertile and infertile men exposed to genital heat stress, especially in the context of novel treatment algorithms (targeted therapies). It is well known that, for effective sperm production, the male gonads require stable thermal environments at a minimum 2 °C below the temperature of the body core. Prolonged exposure of the scrotum to elevated temperature leads to disturbances in thermoregulatory mechanisms and, as a consequence, can result in the phenomenon of testicular overheating. In this context, the exposure of the testes to increased temperature is considered a risk factor for male infertility . A majorClinical abnormalities such as varicocele and cryptorchidism are the most controversial factors; however, simultaneously, they may be the most common pathologies that may be fundamental for causing male infertility. A varicocele is an enlargement of veins of the pampiniform plexus, which under normal conditions is responsible for venous blood return from the scrotum. Patients with varicoceles often but not always demonstrate reduced fertility potential. Combinations of factors such as hyperthermia, hormonal imbalance, hypoxia, hypoperfusion, oxidative stress, increased apoptosis, and exogenous toxicants are thought to be involved in abnormal sperm spermiogram in men with this pathology ,5. In tuIt is well known that an imbalance between pro- and antioxidant systems in semen can contribute to male infertility. The results of recent experimental prospective studies suggest that oxidative stress can also be involved in suppression of spermatogenesis caused by scrotal hyperthermia. Men exposed to transient experimental hyperthermia showed increased seminal lipid peroxidation as measured by malondialdehyde (MDA) levels . There aThe biochemical components of seminal plasma produced by the epididymis and accessory glands create an environment conducive to the proper functioning of spermatozoa. The role of seminal biochemical compounds such as neutral alpha-glucosidase (NAG), γ-glutamyltranspeptidase, fructose, zinc, citric acid and others in the pathogenesis of male subfertility/infertility has long being discussed, especially in the context of their recommendation for the use as discriminatory markers in the diagnosis of hypofunction of different topographical regions involved in reproductive tract disorders. Interestingly, previous published data have suggested that a reduction of fertilizing capacity in men with varicocele can result from damage not only testis but also epididymis demonstrating the lower levels of NAG activity concomitant with higher sperm DNA fragmentation levels and reduced sperm binding to hyaluronic acid in the patients with this pathology . NeverthThe present clinical retrospective study, for the first time, offers an integrative analysis of seminal biochemical parameters of the testis, epididymis and accessory glands as well as oxidative stress markers in distinct entities of male infertility with or without exposure to genital heat stress. Additionally, correlations between the analysed biochemical parameters and spermiogram findings were determined. Due to the multifactorial nature of varicocele and cryptorchidism, to better understand the role of thermogenic factors in these pathologies, a group of professional drivers was also included in the study. It was noted that, to the best of our knowledge, to date, there have been no clinical studies that offer similar seminal plasma quality measures in infertile adult men with history of cryptorchidism in childhood.p < 0.001). The neutral alpha-glucosidase levels in cryptorchid men were also significantly lower than those obtained for men with varicocele and for drivers . Regarding fructose and citric acid levels, no significant differences among the studied groups were demonstrated.The comparison of biochemical parameters among the studied groups is summarized in p < 0.05). In the same groups exposed to genital heat stress, the significant reduction of TAC was accompanied by statistically significant increase in catalase activity compared to values obtained for the control fertile group (p < 0.05). There were no significant differences in seminal plasma SOD activity and MDA concentration among the groups under study.The comparison of oxidative stress markers among the studied groups is summarized in In No associations were found between oxidative stress parameters and standard semen characteristics in the studied groups.Additionally, in the group of professional drivers, positive correlations between all the biochemical parameters were observed. A positive correlation between fructose and citric acid was also observed in men with varicocele and cryptorchidism in childhood.The significance of seminal plasma biochemical quality for male fertility has not been properly recognized in many aspects. In the majority of previous published reports, biochemical components of seminal plasma between normozoospermic and pathological seminal conditions were compared, and varying results were obtained ,19,20,21The results obtained in the groups exposed to long-term scrotal hyperthermia, namely, professional drivers and infertile patients with varicoceles, did not show significant variations in the three biochemical markers compared to the control group as well as to the group of infertile men not exposed to prolonged thermogenic factors . Such fiThe importance of the assessment of NAG activity in seminal plasma as a critical and non-invasive marker for evaluating the pathological changes of epididymis, especially in the context of the diagnosis of an obstruction in patients with azoospermia, has been demonstrated by a number of researchers ,19. In tThe relationship between the biochemical constituents of seminal plasma and standard semen characteristics is still discussed. The results of our study are partly in accordance with those of other reports demonstrating positive correlations between NAG, fructose and/or citric acid with semen volume in men with impaired fertility ,26. In tThe decline in male reproductive potential that has been observed for many years was ascribed mainly to the harmful effects of the surrounding environment. One of the factors considered when explaining the pathophysiology of male infertility could be genital heat stress. Our results obtained in the group of professional drivers support the premise that local long-term exposure to thermogenic factor suggests changes in the epididymis and accessory glands with direct consequences for semen quality. This was evidenced by numerous significant moderate correlations among all the studied biochemical parameters as well as by significant correlations of the biochemical markers with sperm count . MoreoveSince spermatozoa are characterized by high susceptibility to peroxidative damage, semen contains abundant antioxidant system which include enzymatic and nonenzymatic factors for effective protection of spermatozoa against the ROS attack. Some authors consider the total antioxidant capacity (TAC) in seminal plasma to be a principal measurement of redox status that may disturb fertility . In the Oxidative stress is known to be implicated in a variety of pathophysiological events that cause male infertility. Although majority of research (including present study) on heat-induced oxidative stress and ROS-scavenging mechanisms involving antioxidants are conducted in semen, it should be mentioned that biological effects of heat-induced oxidative stress in reproductive organs are quite complex and they can differ from those observed in the ejaculates . There aThe level of lipid peroxidation in semen based on the MDA concentration in seminal plasma was also evaluated in this study. Surprisingly, regarding this parameter, there were no significant differences among the studied groups . These fOne of the specific objectives of the research aims undertaken in this study was an attempt to determine the principal correlations between level of seminal oxidative stress intensity and level of biochemical seminal compounds in the studied groups. Our data revealed such a direct relationship and showed specific correlations in males exposed to genital heat stress both in childhood and adulthood. In the groups of drivers, infertile men with varicocele and those with history of cryptorchidism, similar negative correlations of TAC with citric acid content were observed. Additionally, in the varicocele group, seminal TAC correlated with NAG . These rSuperoxide dismutase is a principal component of the antioxidative defense system in the male reproductive tract. Some studies indicated the role of seminal SOD as a predictive factor for male infertility and detected a positive correlation of seminal SOD activity with sperm concentration, motility, viability and/or morphology ,54. In cSome limitations of our study should be briefly mentioned. First, the study was conducted on 226 participants, which is a relatively small study group. It is possible that if we had increased the number of samples, the obtained results would have achieved higher statistical significance. Second, the study participants did not have scrotal temperature measurement because this is not a common andrological practice and the precise devices for taking scrotal temperature are not widely available. Nevertheless, the design of this study, the inclusion of distinct groups of men exposed to both external or internal thermogenic factors and the strict exclusion criteria of the study allowed us to reduce selection bias. Third, the study was a part of a multi-centre research project and variations in laboratory measurements of standard semen parameters, especially sperm motility, could limit the validity of some data. Nevertheless, all researchers responsible for standard semen analysis were experts in sperm biology and male infertility. Fourth, the study did not provide the full picture of the impact of the post-testicular glands on antioxidant activity of seminal plasma, limiting it only to the enzymatic component and TAC.In conclusion, in this originally designed study, we demonstrated that the biochemical status of seminal plasma may be responsible for low sperm quality in men exposed to both environmental and internal genital heat stress. Dysregulation of seminal antioxidant components can be principally associated with the epididymal and prostate functions. Moreover, each group of these parameters forms a unique micro-pattern in semen characteristics for the particular entities of male infertility. The obtained data may hopefully provide valuable insight into the molecular mechanisms that help us understand the pathophysiology of male infertility caused or complicated by genital heat stress, which would establish new diagnostic biomarker(s) and treatment (targeted therapy) algorithms for male subfertility/infertility associated with scrotal hyperthermia.The study was a part of a multi-center research project which was approved by the Local Bioethical Committee at the Poznan University of Medical Sciences, Poland . Written informed consent was obtained from all subjects. The information about the participants was anonymously coded to protect personal data. All experiments were performed in accordance with relevant guidelines and regulations.The male participants included 226 patients and volunteers of reproductive age (22–40 years) who were recruited from the Andrology Outpatient Clinics in Poznan, Szczecin and Lviv as well as via traditional and social media advertising. All participants were subjected to a routine infertility work-up that included their medical history as well as andrological and ultrasound examinations. Men who had failed to achieve conception for at least 12 months without any apparent reason on the partner’s side were classified as infertile. Men who had at least one offspring at two years maximum were classified as fertile. The varicoceles were diagnosed when dilation of the vessels of the pampiniform plexus were ≥3 mm in diameter. Additionally, the men were asked to complete a questionnaire containing a series of questions on general health, genitourinary diseases, working conditions and lifestyle. On the basis of the collected clinical and survey data, the men were qualified to one of the following five research subgroups: (A) group of fertile men not exposed to prolonged thermogenic factor; serving as the control group (n = 21); (B) group of professional drivers; minimum 2 years in profession (n = 52); (C) group of infertile men treated for cryptorchidism in childhood (n = 50); (D) group of infertile men with varicocele (n = 71); (E) group of infertile men not exposed to prolonged thermogenic factor (n = 32). The main exclusion criteria included the factors that may additionally affect redox status, i.e., age over 40 years, body mass index ≥ 30, smoking, drug usage, co-existing systemic or local active inflammatory process, and double thermogenic factors. All semen samples were collected for the study before any medical treatment .All semen samples were obtained by masturbation after 3–5 days of sexual abstinence. Within 60 min of ejaculation and liquefaction, standard semen analysis was performed manually according to the World Health Organization 2010 criteria . In brieNeutral α-glucosidase, fructose and citric acid were determined using commercially available test kits from FertiPro N.V. . For all parameters, duplicates of each standard and unknown sample were read on 96-well microplates compatible with a spectrophotometric plate reader , and the mean of the two optical density (OD) values was taken.An improved NAG assay with the usage of glucose as an enzyme inhibitor for background correction was performed . The priThe principle of the test was based on the reaction of fructose with indole in the presence of HCl at 37 °C. The absorbance of a coloured complex was measured spectrophotometrically at a wavelength of 450 nm. The fructose content in seminal plasma was calculated by comparing the absorbance against a standard curve. The results were expressed as mg/ejaculate .3+ ions. The intensity of a yellow colour was measured spectrophotometrically at a wavelength of 405 nm. The results were calculated based on the absorbance of standard and were expressed as mg/ejaculate [The principle of the assay was based on the formation of complex of citrate and Fejaculate .Total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and catalase activity were determined with commercially available test kits from Cayman Chemical . The OXISelect TBARS Assay Kit  was used for malondialdehyde (MDA) quantification. Each standard and unknown sample were determined in two repetitions. The absorbance was measured in a spectrophotometric plate reader .®) to ABTS®+ radical cation, which was compared with that of Trolox, a water-soluble tocopherol analogue. Suppression of the absorbance of blue-green ABTS®+ was measured spectrophotometrically at a wavelength of 405 nm. The results were reported as µM of Trolox equivalent [Before determination of TAC, seminal plasma was diluted (1:9) by with TAC Assay kit assay buffer. The principle of the assay was based on ability of antioxidants to inhibit oxidation of the 2,2′-azinodisulfinate 3-ethylbenztiazoline  which then reacted with tetrazolium salts to form red formazan dye. The degree of inhibition of this reaction was measured spectrophotometrically at a wavelength of 450 nm. The SOD activity in seminal plasma was calculated on the basis of the linear regression curve for standard samples. The results were finally expressed as U/mL [Before determination of SOD activity, seminal plasma was diluted (1:2) with SOD Assay kit sample buffer. The principle of the assay was based on the reaction of xanthine and xanthine oxidase to generate superoxide anion . The intensity of purple colour was measured spectrophotometrically at a wavelength of 540 nm. Formaldehyde content was calculated on the basis of the linear regression curve for standard samples. The results were finally expressed as nM/min/mL [The principle of the assay was based on the reaction of catalase with HM/min/mL .v/v). The absorbance of the butanol fraction was measured spectrophotometrically at a wavelength of 532 nm. The MDA content in seminal plasma was read directly from the MDA standard curve. The results were expressed as µM/mL. Water served as the blank control sample [The principle of the assay was based on the formation of a colour complex of lipid peroxidation products with thiobarbituric acid (TBA) at high temperature and acidic environment. The chromogen was then extracted using n-butanol , Matplotlib (https://matplotlib.org/), SciPy (https://www.scipy.org/) and scikit-posthoc (https://pypi.org/project/scikit-posthocs/) libraries. The distribution of the results was evaluated using the Shapiro-Wilk test. Statistical differences among the studied subgroups were determined by non-parametric Kruskal–Wallis test. In the post-hoc analysis, the Dunn test with Holm’s correction was applied. Correlations were assessed using the Spearman rank test. p-values < 0.05 were considered to be significant.The data were analysed using the Python 3 with Pandas (