The systematic analysis of museum collections can provide important insights into the dental and skeletal pathology of wild mammals. Here we present a previously unreported type of dental defect and related skull pathology in five juvenile Baltic grey seals that had been collected in the course of a seal culling program along the Danish coast in 1889 and 1890. All five skulls exhibited openings into the pulp cavities at the crown tips of all  or two  canines as well as several incisors and  also some anterior premolars. The affected teeth showed wide pulp cavities and thin dentin. Pulp exposure had caused infection, inflammation, and finally necrosis of the pulp. As was evidenced by the extensive radiolucency around the roots of the affected teeth, the inflammation had extended from the pulp into the periapical space, leading to apical periodontitis with extensive bone resorption. Further spreading of the inflammation into the surrounding bone regions had then caused suppurative osteomyelitis of the jaws. The postcanine teeth of the pathological individuals typically had dentin of normal thickness and, except for one specimen, did not exhibit pulp exposure. The condition may have been caused by a late onset of secondary and tertiary dentin formation that led to pulp exposure in anterior teeth exposed to intense wear. Future investigations could address a possible genetic causation of the condition in the studied grey seals. The systematic analysis of mammalian skeletons from museum collections can provide important information on the spectrum and prevalence of anomalies and diseases of bones and teeth in the studied species –4. The fUrsus maritimus) [Phoca vitulina) [Halichoerus grypus) [Several studies reported dental anomalies and lesions, alveolar bone pathology, and degenerative changes of the temporomandibular joint in pinnipeds from a comparative point of view –14. Otheritimus) , harbor itulina) , 15, 16, grypus) , 18, in The grey seal is a member of the family Phocidae with a cold temperate to subarctic distribution in North Atlantic waters over the continental shelf . As is tviz. the Atlantic grey seal  and the Baltic grey seal (H. g. grypus) [There exist three geographically separated populations of grey seals, present, respectively, in the western North Atlantic, the Eastern North Atlantic and the Baltic Sea , 21. Cur grypus) , 26.The population of Baltic grey seals in the early 1900s was estimated at 88,000 to 100,000 individuals, but intensive hunting in the course of a multi-national culling program led to a decline to about 20,000 animals in the 1940s , 28. AftAs a reaction to an intensifying seal-fishery conflict, a seal culling program was started in Denmark in October 1889 that lasted until 1927 , 30. A bPusa hispida) [Thus far, only few studies have addressed the occurrence of dental anomalies in grey seals , 33, 34.hispida) .The permanent dentition of the grey seal comprises 34–36 teeth, the dental formula being I 3/2, C 1/1, P 4/4, M 1−2/1 [I: incisors (dentes incisivi), C: canines (dentes canini), P: premolars (dentes praemolares), M: molars  tooth eruption and completion of the apical tooth region (in brachydont teeth) is referred to as primary dentin. It includes the initially formed mantle dentin and the outer zone of the subsequently deposited circumpulpal dentin , 40. SecDuring dentinogenesis first an unmineralized organic matrix, the predentin, is secreted that is subsequently mineralized. The mineral initially forms globular structures referred to as calcospherites that gradually enlarge and thereby become confluent , 38, 41.In the course of a research project on the health of marine mammals from the North Sea and the Baltic Sea, the skulls of grey seals held in the skull collection of the Natural History Museum of Denmark were systematically inspected for dental anomalies and lesions. Here we describe a previously unreported type of dental pathology and its sequelae in the skulls of grey seals collected in the southwestern Baltic region in the period 1889−1890.Three complete and two fragmentary skulls of Baltic grey seals from the skull collection of the Natural History Museum of Denmark, University of Copenhagen, exhibited a similar spectrum of pathological dental and osseous changes. None of the other 204 grey seal skulls from the collection that were inspected in the course of our study showed comparable lesions.The five pathological skulls belonged to individuals that had been collected in the Southwestern Baltic in either 1889 (months October to December) or 1890 , Fig 2. 3 and ZMUC 719) had also been collected in 1889 and originated from the same locality  exhibiting pathological changes. The third control skull (ZMUC CN 1157) was that of a modern juvenile male grey seal  and two of the control skulls (ZMUC 713 and ZMUC 719) belonged to animals collected in the months October to December  of specimen ZMUC CN 1157, and the right M1 of specimen ZMUC 719 were extracted, photographed, and embedded in epoxy resin . Canine length of ZMUC 693 falls within the range (32.3 to 38.5 mm) given for 6 to 8 month-old grey seals [The eight skulls were first studied macroscopically. Photos were obtained with a digital camera, and radiographs were taken of all specimens. Subsequently, the right maxillary C (length 33.9 mm) and the right Mey seals . The emb3). Testing was performed in labial enamel and coronal dentin with a Vickers indenter  in a Dura-Scan 20 hardness tester . The probed surfaces were oriented perpendicular to the tip of the diamond pyramid. In each of the two teeth, eight measurements were performed in enamel  and another eight in dentin (four at a distance of 50 μm and four at a distance of 200 μm from the enamel-dentin junction (EDJ). To improve the visibility of the indentations, prior to testing the probed surfaces were sputter-coated with a very thin (15 nm) layer of gold-palladium. Data for enamel and dentin hardness were compared between the two teeth using the Mann-Whitney U-test, with the level of significance set at p < 0.05.To analyze whether the abnormal condition of the teeth in the five pathological skulls was related to a hypomineralization of their enamel and/or coronal dentin, following BSE imaging and prior to etching we performed hardness testing on the polished cut surfaces of the two extracted canines , exposure of the pulp cavity through an opening at the crown tip was observed in all mandibular and maxillary canines from the five pathological skulls. In the affected teeth, both the tip of the enamel cap and the dentin overlying the pulp horn had thus been lost soon after eruption due to wear. No indication of fracturing of the tooth tips was observed. Except for specimen ZMUC 139, no exposure of the pulp cavity was recorded in postcanine teeth.On macroscopic and radiographic inspection, the five pathological grey seal skulls showed a similar spectrum of dental and bone lesions. All specimens exhibited openings into the pulp cavity at the crown tips of incisors and canines, and in one case (ZMUC 139) also of three anterior premolars , Fig 3. In the skulls of the young-of-the-year, radiographic inspection demonstrated that canines with openings at the crown tips had thinner dentin than the unaffected canines of the two controls .Thickness of the canine walls in the control skull . The crowns of the affected teeth had been completely worn away, with only the roots remaining , and the alveoli of these teeth had become partially (C) or completely (P1 and P2) filled with new bone   .4 and ZMUC 303)  Figs  and 8. I03) Figs .The anterior portions of the mandibles of the five pathological specimens were enlarged due to the apposition of porous periosteal new bone . This is3  the enamel covering the crown tip was lost early, while in others  it was still present. As was demonstrated by SEM imaging, the enamel of both teeth showed a normal microstructure, which corresponded to that reported for other pinniped species [The fact that, except for specimen ZMUC 139, only incisors and canines showed pulp exposure might be linked to the feeding mode of the grey seal. During the piercing bite used for prey capturing, the anterior teeth are likely exposed to more intense wear than the posterior ones. It is presently unclear, why in some anterior teeth  dentin layer. This failure to deposit (sufficient) secondary and/or tertiary dentin in response to wear led to exposure, infection, inflammation (pulpitis) and, finally, necrosis of the pulp in these teeth. In contrast, the postcanine teeth of the pathological skulls typically had thick dentinal walls and showed no pulp exposure. Furthermore, contrary to the studied canine from this skull, the analyzed MThe higher dentinal thickness in postcanine teeth of the pathological skulls suggests that the reason for the observed pathological condition may have been a late onset of secondary and tertiary dentin formation rather than the absolute inability to produce these dentin types. According to this view, for posterior teeth this was compatible with maintaining a viable pulp and ongoing dentin apposition, whereas it proved fatal for anterior teeth in which more intense wear led to pulp exposure and necrosis.3, is a typical response of the pulpodentinal complex to caries lesions, particularly slowly progressing and arrested ones [In human dentistry, occlusion of dentinal tubules by mineral deposits, as was observed in the juxtapulpal coronal dentin of the maxillary canine of specimen ZMUC 69ted ones . Tubularted ones . Anotherted ones , 46. RapPhoca groenlandica), layers of interglobular dentin are frequently part of later-formed annual growth layer groups, but not in that representing the first year of growth [3, which was formed in the year of birth, is therefore considered a pathological feature.In teeth of juvenile grey seals (≤ 1 year), formation of interglobular dentin has not been reported . In the f growth . The int3 indicate pronounced external resorption on the tooth root situated in the abscess cavity, the resorptive process penetrating from the cementum into the dentin. The canine also showed signs of internal root resorption in the course of the inflammatory process, which is a common finding in teeth with periapical lesions [In the five pathological grey seals, the inflammation had spread from the pulp into the periapical space, causing severe lytic lesions with extensive destruction of periapical bone, radiographically visible as extended radiolucent spaces around the tooth roots, and the formation of draining tracts for pus discharge. Especially via the large, deeply inserted canines with their still very wide apical foramina  the inflammation could easily spread into the jaws and cause the formation of periapical abscesses. The findings in the maxillary canine from specimen ZMUC 69 lesions .From the periapical space the inflammation extended into the surrounding bone regions, leading to suppurative osteomyelitis of the jaws. The bone lesions formed in the course of the osteomyelitis include perforations and extensive subperiosteal resorption of cortical bone, periosteal new bone formation due to proliferative periostitis, and the formation of sequestra and involucra in the mandibles of two animals. Formation of sequestra, i.e., of pieces of bone that have become necrotic due to ischemia and are separated from the surrounding living bone, is a typical sign of osteomyelitis –52. An iLeptonyches weddellii) following exposure of the pulp cavity by excessive wear [Cervus elaphus) exhibiting dental fluorosis [Periapical abscesses associated with (mostly maxillary) canines and maxillary second incisors have been reported in Weddell seals , a non-collagenous extracellular matrix protein [In humans, teeth with enlarged pulp cavities and only thin dentin layers, referred to as shell teeth, have been reported from individuals with dentinogenesis imperfecta type III (DGI-III), a heritable dentin defect with an autosomal dominant mode of inheritance –64. The  protein –65. The  protein –67.DSPP-/- knockout mice (Mus musculus) exhibit dental defects similar to those seen in humans with DGI-III. The affected mouse teeth have enlarged pulp cavities, pulp exposure and degeneration, periapical bone resorption and abnormally intensified wear [DSPP-/- mice [ied wear . Light a-/- mice . Similar-/- mice .-/- knockout mice, in the pathological grey seals only anterior teeth showed thin dentin and enlarged pulp cavities. This is in our view not consistent with the diagnosis of a pinniped equivalent of DGI-III. However, it could be speculated that the condition in the grey seals was related to a less severe disturbance in the formation, secretion, or processing of DSPP that caused a delay in dentin apposition following the formation of an initial primary dentin layer.Contrary to the presentation of DGI-III in humans and the dental changes seen in the DSPPThe reported dental and skull pathology has thus far been observed only in juvenile grey seals collected in 1889/1890 and within a relatively narrow area of the subspecies, which might be seen as circumstantial evidence for a heritable dentin defect in the animals. Future studies are needed to clarify a possible genetic causation of the reported condition in the Baltic grey seals. The fact that the condition is not known from modern grey seals could mean that it does not exist in today’s populations, although the possibility exists that it is only unreported. Therefore, further studies addressing dental pathology in other grey seal populations are encouraged.Rattus norvegicus) that certain persistent organic pollutants can disturb tooth development and impair dentinogenesis [It has been experimentally demonstrated in rats  in Baltic grey seals from the 19th century. It is hypothesized that a late onset or reduced rate of secondary and tertiary dentin formation led to pulp exposure in anterior teeth that were exposed to more intense wear than posterior ones. The present study underscores the importance of systematic studies of museum collections for a broadening of our knowledge of pathological dental and skeletal conditions in wild mammals.S1 Fig(TIF)Click here for additional data file.


Cleft lip and palate (CLP) is the most common congenital anomaly of the head and neck region. The upper airway in CLP patients is affected by retarded maxillary growth. Small size of the nasopharynx can also lead to mouth breathing. This study aimed to compare the size of nasopharynx and adenoids in non-syndromic unilateral CLP (NSUCLP) patients and healthy controls two-dimensionally on lateral cephalograms.This retrospective study was performed on 30 children with NSUCLP (mean age of 11.3 years) and 30 sex- and age-matched healthy controls with class I skeletal relationship. The bony boundaries of the nasopharynx, nasopharyngeal airway and adenoids were outlined on lateral cephalograms and their surface area was calculated and compared between the two groups. The percentage of nasopharynx occupied by the adenoids was calculated for each individual and compared between the two groups using independent t-test.Size of nasopharynx in NSUCLP children was significantly smaller than that in healthy controls (P=0.0001). Size of adenoids was significantly larger in NSUCLP children (P=0.0001). Size of nasopharyngeal airway was smaller in NSUCLP patients than controls (P=0.0001). Percentage of nasopharynx occupied by the adenoids was significantly greater in NSUCLP patients (P=0.0001).The size of nasopharynx is smaller while the size of adenoids is larger in NSUCLP children compared to healthy controls; this can lead to mouth breathing and velopharyngeal incompetence. Oral clefts are the most common craniofacial deformities accounting for 15% of all congenital anomalies . The etiHypertrophy of adenoids may cause complete or partial obstruction of the nasopharyngeal space, which may compromise nasal breathing. Discrepancy between the growth of adenoids and nasopharyngeal airway may be related to the different growth patterns of the bones in the nasopharynx and attached tonsillar tissues. Obstruction of the nasopharynx eventually leads to chronic mouth breathing. This condition is referred to as respiratory obstruction syndrome . PreviouThis retrospective case-control study was conducted on 60 medical records retrieved from the archives of the Orthodontics Departments of Schools of Dentistry of Shahid Behshti and Tehran universities. Sample size was calculated to be 30 in each of the two groups according to a previous study  assumingThirty age- and sex-matched healthy individuals  who had lateral cephalograms were considered as controls. Cephalograms of the control group had been taken before their orthodontic treatment. They had normal craniofacial morphology, class I skeletal relationship , no jaw deformity and no mouth breathing. All medical records of CLP patients and normal individuals had been collected by an orthodontist. Cephalograms had been taken in natural head position. All lateral cephalograms were traced on a negatoscope using a pencil (0.5 mm) and acetate cellulose tracing paper by two researchers, and the bony boundaries of the nasopharynx, soft tissue contour of the nasopharynx, contour of the adenoids and soft tissue contour were outlined. Due to optimal contrast, the boundaries between tissues were clearly visible and traceable. For the purpose of calibration, tracing of 10 randomly selected lateral cephalograms was double checked by an oral and maxillofacial radiologist. During tracing, the magnification scale of each image was also recorded on the tracing paper to prevent magnification error.A shown in Also, the percentage of the asopharyngeal space occupied by the adenoid tissue was calculated and the remaining airway space was calculated for all patients. Data were analyzed using SPSS version 22 . Normal distribution of data was assessed using the Kolmogorov-Smirnov test. The bony boundaries of the nasopharynx, adenoid tissue, nasopharyngeal airway and percentage of nasopharyngeal space occupied by the adenoid tissue were compared between the NSUCLP patients and healthy controls using independent t-test.The Kolmogorov-Smirnov test showed that all variables had a normal distribution in both groups (P>0.05). The adenoids also known as the pharyngeal tonsils affect the shape and size of the nasopharynx and play a role in velopharyngeal competency before puberty. Normally, adenoids are large in children and gradually shrink by an increase in age. Controversy exists regarding the etiologic role of hypertrophic adenoids in childhood and their effect on facial growth and dentoskeletal anomalies . HypertrAdenoids undergo atrophy by an increase in age. In normal individuals, the posterior wall of the pharynx approximates the soft palate, which is a physiological compensatory act for closure of the velopharynx. This physiological compensation does not occur in CLP patients . Mason aWada et al,  in theirOur study showed that the adenoid tissue in children with UCLP occupied a higher percentage of nasopharynx. This decreases the size of airway and complicates nasal breathing. As the result, the children gradually start mouth breathing. Oosterkamp et al.  reportedAfter reparative surgery of the palate, difference between the growth of the flap and the surrounding nasopharyngeal tissue is a possible reason for nasopharyngeal incompetency, because the flap has a retarded growth due to surgical scar, which leads to velopharyngeal incompetency . The effTo sum up, in CLP patients, adenoidectomy and maxillary expansion can enhance nasal breathing; however, some other considerations should also be taken into account prior to surgical treatment planning.Size of the nasopharynx is smaller and size of the adenoid tissue is larger in NSUCLP children compared to normal controls; this can lead to mouth breathing and velopharyngeal incompetency.


Chemotherapy-induced nausea and vomiting (CINV) has remained a much-feared side effect of cancer therapy. Few pharmaceutical choices were available 35 years ago when I started practice, and when the first serotonin antagonist 5-hydroxytryptamine-3 (5-HT₃) was approved in the late 1980s and brought to market in 1991, oncology professionals celebrated. The combination of steroids and serotonin antagonists made a huge difference for patients undergoing emetogenic chemotherapy, yet CINV remained a significant problem. Thorough patient assessment of pertinent factors helped to improve the control of symptoms as practitioners gained knowledge of particular patient populations at a higher risk for CINV.The advent of newer targets such as neurokinin-1 (NK1) receptor antagonists and innovative combinations improved the management of this dreaded side effect dramatically. And in yet another direction, we see expanded interest in cannabinoids as another option to improve our control of CINV.Guidelines and recommendations for the management of CINV are available from several organizations.The Oncology Nursing Society (ONS), the Multinational Association of Supportive Care in Cancer (MASCC), and the National Comprehensive Cancer Network (NCCN) are several of the associations that rigorously assess the current data regarding CINV and make clinical recommendations regarding the optimal management of this side effect. And most recently, the American Society of Clinical Oncology (ASCO) updated its own clinical practice guideline regarding the use of antiemetics for CINV .ASCO used an expert panel to conduct a systematic review of the literature from November 2009 through June 2016. Based on the panel’s assessment of 41 different publications, specific updates for the existing guideline were recommended and included in the guideline for antiemetics in oncology. It is important to note that the guideline included the addition of olanzapine  for patients treated with carboplatin with an area under the concentration-time curve ≥ 4 mg/mL per minute. Patients receiving moderately emetogenic chemotherapy other than the carboplatin dose above should receive a two-drug combination of a 5-HT₃ receptor antagonist and dexamethasone, and patients treated with agents known to cause delayed nausea should be offered dexamethasone on days 2 and 3 following initial therapy.Additional recommendations for the control of low emetic risk agents include the use of a 5-HT₃ receptor antagonist or a single dose of dexamethasone (8 mg) prior to therapy.The use of cannabinoids (approved agents such as dronabinol and nabilone) remains a potential therapy for the prevention of nausea and vomiting; the evidence for the use of medical marijuana remains insufficient based on the review of the panel.The guideline thoroughly discusses the appropriate treatment of patients receiving radiation therapy and other patient scenarios. I urge you to read the entire guideline to familiarize yourself with all the recommendations and updates to the management of CINV.ASCO notes that patients with cancer are increasingly paying larger proportions of their treatment costs. Higher costs can translate into inadequate treatment of CINV, as patients may forgo paying for ordered antiemetics. Although generic formulations exist for some of the agents in our antiemetic armamentarium, many of the drugs are brand names and thus may be priced higher accordingly. If appropriate, ASCO recommends clinicians discuss cost as a critical part of shared decision-making and consider lower-priced combination therapies if they are available .Inadequate treatment of CINV is not only a feared side effect for our patients receiving chemotherapy, but one that may lead to patients giving up potentially life-saving treatments because of CINV. And although the agents themselves can be very costly, it is significantly costly to undergo a hospitalization for the control of CINV. A recently reported abstract at the 2017 Palliative and Supportive Care in Oncology Symposium noted that in a study of 37,730 hospital discharges for nausea and vomiting, the adjusted paid amounts averaged > $15,000 . The stuAs advanced practitioners, we excel in the management of symptoms and often develop and run our own clinics to take care of oncology patients with side effects from chemotherapy. We are at the front line in directing antiemetic regimens for our patients, utilizing patient risk factors, available agents, and the all-important national evidence-based guidelines for optimal care.Poorly managed CINV is expensive, but its most obvious and troubling outcome is the damage done to our patients in terms of quality of life and compliance with future therapy. My experience with this is personal. As my brother experienced unremitting CINV with cisplatin-based therapy for his testicular cancer, he finally gave up and opted to stop therapy. I don’t want another patient to have to suffer like that. As advanced practitioners, we have the tools to do a better job. With the use of national guidelines and an ever-expanding armamentarium of antiemetic agents, let’s try to eliminate CINV once and for all.


This paper presents the results of a meta synthesis of 8 qualitative studies that examined resilience among 270 older adult survivors following potentially traumatic adverse events . The primary data involved information about survivors’ critical events during the Holocaust , the Cambodian genocide, and the discriminatory practices of the Jim Crow U.S. South. A narrative approach to gerontology was used to collect and analyze the original data. known as a constant comparison data analysis . This allowed for the understanding of risks such as such as discrimination, imprisonment, genocide, and possible loss of life and the development of themes of resilience at the personal, interpersonal, sociocultural, and societal levels  The meta synthesis of secondary data involved coding the original findings, grouping them into descriptive themes, and generating new overarching analytical themes . The most prevailing theme at the personal-level  was overcoming the grief of losing a loved one. Interpersonal-level themes (relationships between people) were related to staying connected to family. Sociocultural-level themes (the beliefs and mores of the time) centered on making meaning of a critical event within its historical context Societal themes (government and institutions) themes were indicative of being able to contribute or influence one’s current community. Implications for clinical practice and policy formation are provided.


Lip redness is unique to humans and creates an important facial impression, but this redness decreases with age. Here, using histological and immunohistological staining of human upper lip vermilion from donors of different ages, we investigated blood vessels in the upper lip dermis and age-dependent histological changes. We found that both total vessel area in the dermis and vessel number in the upper dermis decreased with aging. Moreover, vessel number in the upper dermis correlated positively with development of rete ridges, which flattened with age, despite no significant change in the thickness of the stratified squamous epithelium. These findings suggest that age-related reductions in lip redness result from a decrease of blood vessels, which in turn leads to a flattening of the epithelium caused by the loss of rete ridges. This is the first study to histologically demonstrate age-related reductions in blood vessels in the lip. Our results provide an opportunity for enhancing blood flow/vascularization to improve the aesthetic appearance of the lips in the elderly. The highly visible reddish vermilion of the labium oris (lip surrounding the mouth) is unique to humans. Although the area of vermilion makes up only a small fraction of the total facial area, the redness of the vermilion profoundly affects the impressions of others. A redder vermilion lightens the perceived complexion , and a rThe red color of the vermilion is thought to be primarily due to the presence of oxygenated blood, though the literature on this topic is limited. The vascular patterns in the skin of the upper lip (intermediate skin zone between the nose and the upper vermilion border) and lower lip (skin zone just beneath the lower vermilion border) have been studied ultrasonographically . In addiUpper lip tissues were dissected and sagittally sectioned, after which the following anatomical structures were analyzed. The vermilion zone was detected as the intermediate zone between the lip skin, which contains the keratinized epidermis, hair follicles, sebaceous glands and the hypodermal fat, and the intraoral labial mucosa, which contains the hypodermal fat and the glandulae labiales on the side beyond the rima oris. This definition is consistent with the vermilion zone confirmed by dye staining from the surface before dissection .To determine whether blood vessels in the vermilion change with age, immunohistochemical staining for CD31  was performed. As expected, the anti-CD31 antibody specifically labeled blood vessels . MoreoveThe histological structure of the stratified squamous epithelium can affect the color of lips seen from the surface. This is because light is reflected by the blood vessels underlying this layer. To investigate the influence of stratified squamous epithelium on lip color, its morphology was histologically examined. The findings are summarized in Dermal papillae, which are located on the opposite side of the dermis from the rete ridges, generally contain blood capillaries. This suggests blood vessels may contribute to the state of the rete ridges. Analysis of the correlation between the blood vessels and rete ridges revealed a significant positive correlation between the number of blood vessels in the upper dermis per surface length and rete ridge elongation  were kindly provided by Obio, LLC  while complying with ethics and all applicable laws, rules and regulations. It was confirmed prior to the study that written informed consent had been obtained from each donor by Obio, LLC. All specimens were identified with a randomly assigned 6-digit alphanumeric code during experiments. The use of human tissue specimens was approved by the institutional review board of POLA Chemical Industries on 22 June 2017.Monoclonal mouse anti-human CD31 antibody (clone JC70A), monoclonal mouse anti-human CD34 antibody (clone QBEnd/10), monoclonal mouse anti-human Ki67 antibody (clone MM1), negative mouse isotype control antibody, and Bond Polymer Refine Detection were purchased from Leica Biosystems . All antibodies were provided in ready-to-use condition.The vermilion of the upper lip was dissected from 1 cm inside from the right corner of the mouth to a width of 3 mm, then fixed in 10% neutral-buffered formalin and embedded in paraffin. Sagittal 4-μm-thick microtome sections (in the direction from the vermilion surface toward the nose) were immunohistochemically stained for CD31, CD34 and Ki67, and also stained with hematoxylin and eosin.After deparaffinization and rehydration, sections were stained with each antibody using the procedure recommended by the manufacturer. Briefly, the sections were incubated first with hydrogen peroxide to quench endogenous peroxidase activity and then with diluted normal rabbit serum to reduce nonspecific reactions. Thereafter, the sections were incubated with each of the primary antibodies listed above and then with Post Primary IgG linker reagent (Leica Biosystems) and Poly-HRP IgG reagent (Leica Biosystems). The labeling was visualized as brown staining using 3,3'-diaminobenzidine tetrahydrochloride (DAB). Hematoxylin counterstaining was also performed to visualize cell nuclei.2 was considered to be a blood vessel. The number of vessels and percentage of the whole dermis and upper dermis  occupied by vessels were calculated as parameters. The whole dermis was defined as the area between the dermo-epithelial junction and the external surface of the orbicularis oris muscle in the vermilion zone. Morphological characteristics of the stratified squamous epithelium were measured as follows: surface length as the external contour of the living cell layer of the stratified squamous epithelium; length of the dermo-epithelial junction as the internal contour of stratified squamous epithelium; mean thickness as the area of the living cell layer of the stratified squamous epithelium divided by the surface length; and rete ridge elongation as the ratio of the length of the dermo-epithelial junction to the surface length. The number of Ki67-positive cells in the stratified squamous epithelium was counted using the cell-counting function (Ki67) in WinROOF software.Stained sections were digitized using a NanoZoomer-XR slide scanner system  and analyzed using WinROOF image-processing software . CD31-immunostained images were used for analyzing blood vessels because similar images were obtained with both CD31 and CD34 immunostaining. A region of CD31-positive staining with an area >25 mmhttp://www.R-project.org). Pearson's correlation coefficient was used for correlation analyses, and values of P < 0.05 were considered significant.The R package was used for all statistical analyses (the R Project,


Lonicera japonica solution in ethanol precipitation process. The results demonstrated the processing trajectory has great advantages and feasibility in the development and optimization of multivariate calibration models as well as the effectiveness of bagging model and variable selection to improve prediction accuracy and robustness.Our work proved that processing trajectory could effectively obtain a more reliable and robust quantitative model compared with the step-by-step optimization method. The use of systematic tracking was investigated as a tool to optimize modeling parameters including calibration method, spectral pretreatment and variable selection latent factors. The variable was selected by interval partial least-squares (iPLS), backward interval partial least-square (BiPLS) and synergy interval partial least-squares (SiPLS). The models were established by Partial least squares (PLS) and Bagging-PLS. The model performance was assessed by using the root mean square errors of validation (RMSEP) and the ratio of standard error of prediction to standard deviation (RPD). The proposed procedure was used to develop the models for near infrared (NIR) datasets of active pharmaceutical ingredients in tablets and chlorogenic acid of  Multivariate calibration is the process of relating the measured response to the analyte amounts, concentrations, or other measured values of physical or chemical properties. Partial least squares (PLS) regression is the most effective and commonly used regression techniques in multivariate calibration because of its calibration model quality and ease of implementation. The statistical results show that approximately 20,000 published papers reports used PLS models from 2005 to 2017. The PLS technique has been effectively applied to different fields, especially in pharmaceutical analysis.l-borneol in Blumea balsamifera (Ai-na-xiang) samples   and PLS to develop the multivariate calibration models for four diesel quality parameters, showing that the prediction accuracy was improved by subagging procedure  and the ratio of standard error of prediction to standard deviation (RPD)  was assayed by high performance liquid chromatography (HPLC). The tablet dataset was supplied in Data Sheet The NIR transmittance spectra of a pharmaceutical tablet were described in Dyrby et al.  and publLonicera japonica has been reported previously  for Lonicera japonica monograph. The dataset of Lonicera japonica was supplied in Data Sheet The NIR spectral dataset of http://www.models.life.ku.dk/iToolbox.The spectral pretreatment of data was performed using chemometric tool in this study . Data analysis was conducted using Unscrambler 9.7 software package  and Matlab version 7.0 . Some of the algorithms were developed by Norgaard et al., readily downloadable from A procedure for the development and optimization of multivariate calibration models using processing trajectory is summarized in Figure Lonicera japonica solution were shown in Figure −1, which originated from several components in the corresponding drug tablet. In addition, there were large fluctuations in the combined region of fundamental vibrations in the raw spectra of Lonicera japonica solution. Therefore, the spectral region of 1,100–1,900 nm was selected.The raw NIR spectra of the tablet and Lonicera japonica solution were shown in Tables The modeling procedure using processing trajectory was showed in Figure Lonicera japonica dataset is shown in Figure The RPD and RMSEP had similar trends in PLS and Bagging-PLS models. In Figure Moreover, this finding indicates that more than one modeling path could ensure a successful model. Data obtained from different modeling paths and model classification were shown in Figure The best nonsystematic parameter combination for the chlorogenic acid Bagging-PLS model was raw spectra and iPLS or BiPLS variables selection under 2 latent factors. The model performance was good. However, there were 24 very good models with different systematic parameter combinations in the result of processing trajectory. The best parameter combination of the chlorogenic acid model was that the model was developed by Bagging-PLS with SG(9) spectral pretreatment and SiPLS-selecting variables under 6 factors. It demonstrated that the model obtained through the processing trajectory was better than that step-by-step optimized. It means that the optimal systematic model parameter combination can be obtained via the processing trajectory and bagging ensemble modeling techniques, and variable assignment could improve prediction accuracy and robustness.Lonicera japonica solution was developed using Bagging-PLS with SG(9) spectral pretreatment and SiPLS-selecting variables under 6 latent factors. The RMSEP and RPD were 0.0728 mg/mL and 3.9166, respectively. The RMSEP and RPD of the model step-by-step optimized were 0.0891% and 3.1966, respectively. Figure Lonicera japonica solution in ethanol precipitation process.The model validity was evaluated in terms of RMSEP and RPD values. Taking the tablet dataset as an example, Figure Lonicera japonica solution in ethanol precipitation process. The result illustrated that the processing trajectory has great advantages and feasibility in the development and optimization of multivariate calibration models and the effectiveness of bagging model and variable selection to improve prediction accuracy and robustness.We proposed processing trajectory to optimize the parameters of multivariate calibration such as spectral pretreatment, latent factors, variable selection and calibration methods. The models were developed using PLS and Bagging-PLS with different spectral pretreatments and variable selection methods under different latent factors. The chemometric indicators (RMSEP and RPD) were used to evaluated the model. The different PLS and Bagging-PLS models were used to quantify the API in tablets and chlorogenic acid of In conclusion, the application of processing trajectory for model optimization shows excellent results to develop a reliable and robust model. The proposed should be translated into an algorithm to be integrated into PLS software, helping to obtain better models.YQ and ZW conceived and designed the study. NZ performed the experiment with the help of LM, XH, and XL. NZ and ZW wrote the manuscript. All authors read and approved 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.


In particular, whether macroscopic connectivity supports this given the disproportionate volumetric differences between species in the brain regions that project to the ventral striatum, including the prefrontal and limbic areas, has not been established In this study, the human and macaque striatum was first tractographically parcellated to define the ventral striatum and its two subregions, the nucleus accumbens (Acb)-like and the neurochemically unique domains of the Acb and putamen (NUDAPs)-like divisions. Our results revealed a similar topographical distribution of the connectivity-based ventral striatal components in the two primate brains. Successively, a set of targets was extracted to construct a connectivity fingerprint to characterize these parcellation results, enabling cross-species comparisons. Our results indicated that the connectivity fingerprints of the ventral striatum-like divisions were dissimilar in the two species. We localized this difference to specific targets to analyze possible interspecies functional modifications. Our results also revealed interspecies-convergent connectivity ratio fingerprints of the target group to these two ventral striatum-like subregions. This convergence may suggest synchronous connectional changes of these ventral striatal components during primate evolution.Although the evolutionarily conserved functions of the ventral striatal components have been used as  The primate ventral striatum is comprised of the nucleus accumbens (Acb), the broad continuity between the caudate nucleus and the putamen ventral to the rostral internal capsule, the olfactory tubercle , and theGiven that the ventral striatum  extends slightly into the caudate nucleus and putamen, reaching the medial caudate nucleus border , the dora priori knowledge for further studies  comparative analyses and is one of the few techniques that can truly bridge the gap between species by using identical non-invasive data acquisition schemes and data handling . DiffusiThe goal of this study was to compare the macroscopic connectivity of the ventral striatum and its subregions between humans and macaques. To address this issue, we first recursively parcellated the striatum, based on probabilistic diffusion tractography, to define the connection units of the ventral striatal components for each species. Then, we selected a set of target areas to construct the fingerprint framework for cross-species comparisons. Using these target areas, we characterized the anatomical connectivity patterns of the ventral striatum and its subregions. Finally, we evaluated the similarity of the corresponding connectivity fingerprints between the two species and detected the interspecies single connectivity differences to analyze possible interspecies functional modifications.A human MRI dataset  was extracted from the Human Connectome Project HCP;  because ex vivo; age: 4–23 years; two males; for details, see b-value = 1000 s/mm2 and four non-diffusion weighted images. The data quality controls used on these macaque diffusion images are described in A macaque MRI dataset consisting of eight adult rhesus macaque brain specimens  was used as a reference to decide which subregions should be chosen as the connection units of the ventral striatum and its major components.Unlike previous parcellation procedures , the conThe connection units that had corresponding locations in the two species were treated as seeds for cross-species comparisons. The connectivity fingerprint was chosen as a comparative characteristic  to detecEarlier studies calculated relative connectivity strength (RCS) by normalizing the data to the maximum regional connectivity strength in the brain to build connectivity fingerprints for cross-species comparison . Howeveri) is one of the n ventral striatal subregions; RCS) is the RCS between the given target and seed(i); CR) is the connectivity ratio of seed(i).Where, seed(i)) has values in the interval , and high values indicate that the target tends to connect with the seed(i) when compared with the other ventral striatal subregions. Therefore, the connectivity ratio fingerprint reflects the contrast in the general connectivity trend across the ventral striatal subregions. We used the CR fingerprint to detect possible interspecies differences in the connectivity trends for the ventral striatal components.The CR to reduce false positive connections as was done in earlier studies , temporal pole (TP), caudate nucleus (Ca), putamen (Pu), pallidum (Pa), hippocampus (Hipp), amygdala (Amyg), mediodorsal (MD) part of the thalamus, and midbrain (MidB). The areas located in the lateral orbitofrontal cortex were eliminated from the target group considering the substantial interspecies differences reported in previous studies .The anatomical RCS fingerprints of the human and macaque ventral striatum-like division were calculated and compared . Given tTwo ventral striatum-like subregions, namely the Acb-like and NUDAPs-like divisions, were characterized using the CR fingerprint in both species . When coThe corresponding CR fingerprints of the Acb-like and NUDAPs-like divisions between the two species were extracted and compared to detect their cosine similarity. The permutation tests indicated that the observed cosine similarity between the two ratio fingerprints was not a rare value in the permutation distribution, as can be seen in the histogram. The observed cosine similarity was lesser than the calculated test criterion at the 5% significance level in the right tail . Thus, wBoth the human striatum and macaque striatum were recursively parcellated based on tractography. The ventral striatum-like, Acb-like, and NUDAPs-like connection units were defined in both species and treated as seeds for cross-species comparisons. A set of areas meeting specific criteria was extracted as targets to construct connectivity fingerprints, which were used as the comparative characteristics to characterize and compare the seeds. Our results revealed that the RCS fingerprint of the ventral striatum-like division in humans differed considerably from that of macaques. However, the general connectivity trend of these targets to the ventral striatum-like subregions, the Acb-like and NUDAPs-like divisions, was conserved, based on their convergent CR fingerprints.The gross correspondence between connectivity architecture and microstructural features  has yet to be clarified; in fact, both similar  and discex vivo macaque MRI data enabled the accurate identification of both the ventral striatum-like and the Acb-like connection units in both species. The lateral ventral striatum  was excluded from the Acb-like division given its large localization error with the histological Acb, and was called the NUDAPs-like division only because the histologically-defined patch-like NUDAPs defined in histology is mostly distributed in this region  and the decision-making process via its projection to the ventral striatum . A signiAlthough dissimilar RCS fingerprints of the ventral striatum-like division and some significantly different single connections were revealed between humans and macaques, conservative connectivity trends of these targets to the Acb-like and NUDAPs-like divisions were present. The synchronous changed (strengthen or weaken) connectivity observed in the two subregions in both types of primate brains indicated that the labor division and the cooperation of the two ventral striatum subregions may have not been noticeably altered across species.The same tractography-based recursive parcellations of the striatum were performed in both humans and macaques to delineate their ventral striatum-like, Acb-like, and NUDAPs-like connection units. A set of targets was chosen to enable the construction of fingerprints to characterize and compare such components across species. A dissimilar RCS fingerprint of the ventral striatum-like division was revealed between the species. Furthermore, this connectivity difference was localized to specific targets and such single connectivity differences were used to infer possible interspecies functional modifications. Finally, our results revealed distinct connectivity fingerprints of the Acb-like and NUDAPs-like divisions and interspecies convergent CR fingerprints of this target group to the two ventral striatum-like subregions.Eight adult rhesus macaque brain specimens were used in this study. These monkeys were judged by the veterinarian as appropriate subjects for euthanasia due to the presence of serious physical diseases. All the brain specimens were obtained at necropsy immediately following euthanasia due to reasons not related to the study and acquired following protocols approved by the National Animal Research Authority of China. All experimental procedures were performed in strict accordance with the recommendations in the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All of the animals were handled according to the protocol (#IA-2016-05) approved by the Animal Care and Use Committee of the Institute of Automation, Chinese Academy of Sciences.TJ and HL conceived and designed the experiments. XX, LF, CC, RY, HD, and DZ carried out the research and analyzed the data. XX, LF, HL, and TJ wrote the manuscript. All authors reviewed and approved the manuscript for submission.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.


Alkynylphosphines or their borane complexes are available either through C–P bond forming reactions or through modification of the phosphorus or the alkynyl function of various alkynyl phosphorus derivatives. The latter strategy, and in particular the one involving phosphoryl reduction by alanes or silanes, is the method of choice for preparing primary and secondary alkynylphosphines, while the former strategy is usually employed for the synthesis of tertiary alkynylphosphines or their borane complexes. The classical C–P bond forming methods rely on the reaction between halophosphines or their borane complexes with terminal acetylenes in the presence of a stoichiometric amount of organometallic bases, which precludes the access to alkynylphosphines bearing sensitive functional groups. In less than a decade, efficient catalytic procedures, mostly involving copper complexes and either an electrophilic or a nucleophilic phosphorus reagent, have emerged. By proceeding under mild conditions, these new methods have allowed a significant broadening of the substituent scope and structure complexity. Alkynylphosphines are relevant versatile compounds due to the presence of two important functions, a phosphorus atom—a key-atom in metal coordination —and an aIn the past, these phosphines were mainly used in coordination chemistry for the assembly of various mono- or bi-metallic complexes and clusters , by takiIt is only recently that the high potential of alkynylphosphines as ligands for homogeneous catalysis has emerged through a few relevant catalytic applications . NotablyThe classical method for preparing alkynylphosphines is based on the nucleophilic substitution reaction at the phosphorus atom of a halophosphine by a metal  acetylide at low temperature , path A.Catalytic variants of this reaction have been recently described as useful alternative approaches when sensitive functional groups are present , path B.The scope of this review encompasses the synthesis of alkynylphosphines and their borane complexes . The stoTertiary alkynylphosphines are classically prepared through the reaction of chlorophosphines and metal acetylides. For secondary alkynylphosphines, only those bearing sterically encumbered substituents are available through this procedure. 1 with various alkyne Grignard reagents in diethyl ether at low temperature , which could be isolated for the first time and fully characterized via experimental and computational methods [Preliminary mechanistic studies are consistent with the involvement of a copper(I) phosphido-borane complex as the reactive species. Indeed neutral copper phosphido-boranes [R methods , were shThe putative mechanism of the reaction involves oxidative addition of the copper(I) phosphido-borane complex to the 1-bromoalkyne, followed by reductive elimination, leading to the cross-coupling product and allowing the release of the copper(I) catalyst .Regarding the synthesis of tertiary alkynylphosphines, modification of the alkynyl or the phosphorus function of alkynyl phosphorus derivatives is a less commonly used method in comparison to C–P bond formation. On the other hand, in the case of secondary and primary alkynylphosphines, the reduction of the phosphoryl moiety of phosphine oxides and phosphonates respectively, is the method of choice for their preparation.Classical alkyne chemistry has been applied in the functionalization of alkynylphosphines through their metalation and subsequent reaction with an electrophile. With the aim of preparing dendrimers, Caminade and Majoral  generate2. The next step was the silyl deprotection by treatment with TBAF. It was followed by deprotonation with sec-BuLi and methylation of the resulting lithium derivative with methyl iodide. Finally borane removal by treatment with DABCO  afforded the bis-alkynylphosphine. The Imamoto group  describe4 from alkynyldichlorophosphine 3 (The nucleophilic substitution at the phosphorus atom of alkynylchlorophosphines by Grignard reagents has been used for the building of complex structures. As an example, the Yoshifuji group  describesphine 3 .in situ generated diethyl alkynyl-1-phosphonite 5 and Grignard reagents (Besides chlorophosphines, phosphonites can serve as precursors of alkynylphosphines. The Aguiar group  reportedreagents .As described in the 2 as reducing agent. The best yields were obtained when the reaction was performed at low temperature in diethyl ether or THF (A more straightforward and general access to unstabilized primary and secondary alkynylphosphines relies on the reduction of phosphoryl derivatives by alanes or silanes . Guillemin situ generated PhSiHCl2. The presence of chlorine atoms on silicon, by increasing the oxophilic properties of the silane reagent, would explain its higher reactivity.A mild and practical synthesis of secondary alkynylphosphines was reported by Gaumont and Denis . It is bThe synthetic pathways towards alkynylphosphines used to be restricted to stoichiometric procedures involving the use of organometallic bases, which limited the scope of the substitution pattern to robust functional groups. Since less than a decade, benefiting from the renaissance of copper catalysis for C–C and C–Heteroatom bond forming reactions, catalytic procedures have emerged, which involve either an electrophilic or a nucleophilic phosphorus derivative. By proceeding under mild conditions, these new catalytic methods have broadened the substituent scope and have been successfully applied to the synthesis of functionalized complex phosphine structures.Future developments comprise catalytic procedures avoiding the use of halogen-containing derivatives, such as oxidative cross-couplings, which have proven their efficiency for the synthesis of alkynylphosphonates , but who


Understanding the amount of degradation using nondestructive evaluation (NDE) methods provides an effective way of determining the fitness to service and the residual life of structural components. Due to uncertainties introduced by the single NDE method, a combined damage index using multi-sensor data increases the reliability of damage assessment. In this paper, the outputs of three NDE methods including acoustic emission (AE), linear ultrasonics (LUT), and nonlinear ultrasonics (NLUT) are merged to identify the amount of plastic deformation in aluminum 1100. The sensitivities of individual and combined methods to microstructural changes are evaluated. The coupon samples are loaded up to different strain levels and then unloaded. AE data is recorded in real time and ultrasonic data is recorded from the unloaded samples. The major features combined in the damage index are cumulative AE absolute energy and nonlinear coefficient. The microstructural state is verified with microscopic analysis and hardness testing. The developed damage index can nondestructively assess the amount of plastic deformation with higher reliability. Aluminum is the second-most used metal due in part to its superior mechanical performance and versatility . The appThe integration of multiple sensing techniques increases the reliability of NDE. Aggelis et al. used both AE and UT to identify damage in composite materials . Shah anIn this paper, the outputs of AE, LUT, and NLUT are merged to identify the amount of plastic deformation in aluminum 1100. The sensitivities of individual and combined methods to microstructural changes are evaluated. The coupon samples are loaded up to different strain levels and then unloaded. AE data is recorded in real time and ultrasonic data is recorded from the unloaded samples. The major features studied to define the damage index are cumulative AE absolute energy, linear attenuation coefficient, and nonlinear coefficient. The microstructural state is verified with microscopic analysis and hardness testing. The developed damage index can nondestructively assess the amount of plastic deformation. The outline of this paper is as follows. The material preparation and experimental procedure are described in Al 1100 used in this study has the composition of 99% Al and 1% Si + Fe . All of In order to generate the different strain levels, each specimen was loaded up to certain strain level and then unloaded using Instron electromechanical load frame machine as shown in The nondestructive testing consisted of online and offline methods: (i) the online monitoring setup includes recording AE and elongation continuously during the tensile test, see in The UT measurement was performed using pocket UT device manufactured by Mistras Group Inc. The setup is shown in The sample profiles after tensile tests are shown in Hardness is a measure of how resistant a material is to permanent shape change when a compressive force is applied , which dAs discussed above, the evaluation of damage progress consisted of real-time and post-test assessment methods. Plastic deformation is the main AE source for the tensile loading of aluminum . FirstlyThe distribution of AE hits with the loading information is shown in In order to further characterize AE signals from different strain levels, the spectrograms of AE signals are obtained using complex wavelet transform, shown in It is important to define a damage index (DI) correlated to the exposed plastic deformation. DI is defined based on the average cumulative absolute energy at the end of each loading normalized to the average cumulative absolute energy obtained from the fractured sample (reference sample), and calculated as Equation (1):The correlations between LUT attenuation and NLUT acoustic coefficient with different plastic strains are sought. The major LUT outputs related to the damage state are attenuation properties and wave velocity. The nonlinear harmonic generation technique is used to measure the acoustic nonlinearity parameters (ANP). When a sinusoidal ultrasonic wave propagates through a nonlinear medium, higher harmonics are produced due to heterogeneity. The acoustic nonlinearity parameter (ANP) for the third harmonic generation is defined to characterize the nonlinearity as :(2)γ=6AThe 5 MHz ultrasonic transducer was used as transmitter, and the frequency of the receiver was 10 MHz. In order to generate the third harmonic with the current transducer configuration, an excitation signal of 4 MHz was used, and the received signals show good resolution at the third harmonic frequency using the transducer with 10 MHz frequency . As showneration . The thineration .AE and DINLUT are shown in AE and UT parameters can represent the damage level individually or concurrently. The correlations of DINLUT has the highest sensitivity because the NLUT is more sensitive to the microstructure change in the initial stage. DIAE and DIcombined are more sensitive when the material approaches failure.The combined damage index of AE and NLUT measurement is shown in In this paper, the passive and active NDE methods were utilized concurrently to assess the plastic deformation in aluminum 1100 such that each method could be combined for more reliable damage assessment. The damage index equations for individual and combined NDE methods were defined. For the AE testing as a real-time and in-situ NDE method, three major regions with different AE activities were determined: elastic-plastic region, strain hardening-necking region, and failure region. Most activities were detected in the elastic-plastic region. Due to ductile behavior of Al 1100, no significant AE were detected at the strain hardening-necking region. The AE-based damage index was defined as the cumulative value of AE absolute energy at the end of loading. The sensitivities of linear and nonlinear ultrasonics to plastic deformation were studied. While both methods indicated an increase in damage index, linear ultrasonics has higher variation in repeated measurements. The damage index of nonlinear UT was defined using the fundamental and third harmonic frequencies. In general, both AE and nonlinear UT methods have good relations with the increase of plastic deformation. However, the combined damage index reduces the influence of error sources introduced by individual NDE method. The concept shows the potential of combined AE and UT methods in the damage assessment of large-scale structures. The AE method as a real-time method provides qualitative information and can pinpoint the location of major damage, which can be validated further and quantified with the in-situ nonlinear UT method.


The binding interactions between HSA and PpIX have been studied by means of molecular docking simulation using the CLC Drug Discovery Workbench (CLC DDWB) computer program. PpIX creates a strong ‘sandwich-type’ complex between its highly conjugated porphine system and aromatic side chains of tryptophan and tyrosine. In summary, fluorescent studies on binding interactions between HSA and PpIX have been confirmed by the results of computer simulation.Human serum albumin (HSA) is the main plasma protein responsible for a distribution of drugs in the human circulatory system. The binding to HSA is one of the factors that determines both the pharmacological actions and the side effects of drugs. The derivative of heme, protoporphyrin IX (PpIX), is a hydrophobic photosensitizer widely used in photodynamic diagnosis and therapy of various malignant disorders. Using absorption and fluorescence spectroscopy, it has been demonstrated that PpIX forms complexes with HSA. Its binding sites in the tertiary structure of HSA were found in the subdomains IB and IIA. PpIX binds to HSA in one class of binding sites with the association constant of 1.68 × 10 The laser light affecting tissues can be used in the treatment of cancers and pre-cancerous lesions. An illumination initiates a photochemical reaction leading to the formation of cytotoxic compounds, which induce cell death ,2. DamagPDD and PDT of cancer and pre-cancerous lesions require photosensitizers, which are activated by light ,4. Any pThe porphyrin is a macrocycle composed of four pyrrole rings bridged by four sp2 hybridized carbon atoms . ProtopoSince human serum albumin (HSA) is a component of the circulatory system , the undOne of the most important properties of HSA is its ability to bind and transport many endo- and exo-genic compounds, which have no designed transport proteins. Nevertheless, compounds having specific transport proteins can also be transported by HSA. The formation of albumin-ligand complexes in the blood serum preserves ligands against oxidation, reduces their toxicity and improves their solubility, and therefore, the formation of the complexes improves the transportation of ligands.Preclinical studies are crucial in order to support and develop PDD and PDT. In our study, absorption and fluorescence UV spectroscopy was used to find PpIX binding sites in transporting protein tertiary structure. Molecular docking was applied to check and confirm our experimental study. The CLC Drug Discovery Workbench (CLC DDWB) molecular docking computer program is an integrated virtual environment for exploring various biochemical processes, such as binding of small molecules  to bioactive macromolecules . In the study, molecular docking simulation was used for the simulation of binding interactions between the macromolecule of HSA and the molecule of PpIX.The absorption spectra of HSA (I), PpIX (II), as well as the PpIX-HSA system (III) are shown in To obtain evidence of the complex formation between HSA and PpIX, fluorescence analysis was conducted.ex = 280 nm and 295 nm was quenched by PpIX  and tyrosine (Tyr) fluorophores in the HSA and chromophores in the PpIX. That may occur when the donor-acceptor distance does not exceed 10 nm :[HSA]) = F/F0), of HSA in the presence of PpIX have been plotted . The quenching of HSA fluorescence caused by PpIX was used to determine [PpIXb] from:t the total concentration of HSA; By using fluorescence data, the quenching curves, i.e., (The concentration of unbound (free) PpIX was obtained from:The association constants of PpIX to HSA were estimated by the method described by Hiratsuka .S-V is the collisional quenching constant; [Q] is the quencher (PpIX) in the complex HSA-PpIX.The Stern–Volmer constants were calculated according to the equation :RFo/RF The docking experiment was performed using the CLC Drug Discovery Workbench (CLC DDWB) computer program . DockingThe crystal structure of HSA (Chains A and B) required for computer simulation was downloaded from the Protein Data Bank (PDB) database  with 4-lThe two-dimensional (2D) structure of PpIX was built using the ChemDraw Ultra  program Molecular docking simulation consists of four steps: finding binding sites, docking ligand to the binding sites, virtual screening and, finally, visualization of the docking results.3 were discarded) and analyzed by selecting neighboring amino acids within a 10–15 Å radius from the center of each binding site. In the second step, the PpIX molecule was fitted separately into each detected ligand-binding site of HSA by the CLC DDWB search algorithm with standard docking simulation settings . In this step, the rotation around flexible bonds was changing the conformation of the ligand. During the experiment, the binding energy for each obtained complex was automatically scored by the PLANTSPLP scoring function used in the CLC DDWB program and presented in arbitrary units (a.u.) [Initially, potential ligand-binding sites in the HSA structure were automatically detected by the Find Binding Pockets algorithm implemented in CLC DDWB. Then, the detected binding sites were classified according to their molar volumes  . FinallyThe binding of medicines to plasma proteins determines their pharmacological actions and side effects. A significant role in the drug carriage is played by HSA. In this work, spectroscopic and molecular docking studies were applied in order to identify the likely PpIX binding sites of HSA and to explain the mechanism of binding the PpIX to this carrier protein.The formation of the complex between PpIX and HSA was confirmed by the analysis of the difference of the UV-VIS spectra and spectrofluorescence quenching analysis.Based on the absorption analysis, it was concluded that PpIX may form complexes with HSA in human plasma. Additionally, the fluorescence analysis results show that PpIX is able to interact with both Trp and Tyr residues. These results suggest that PpIX most likely binds to HSA near Subdomains IIA (where Trp 214 and Tyr 263 are located). Furthermore, the binding site of PpIX on HSA may be located near Subdomains IB , IIB  and/or IIIA .The spectroscopic studies were confirmed by the results of computer simulation. The docking results clearly indicate Subdomains IB (hemin binding site) and IIA (Sudlow’s Site 1) as the major binding sites for PpIX on the HSA molecule. Most likely, PpIX forms a strong “sandwich-type” complex between its highly conjugated porphine system and aromatic side chains of Trp and Tyr.Finally, nine amino acid residues  involved in the binding with PpIX in Site 1 of HSA are the same as those for heme, which was described by Wardell et al. . This re


Redo surgery in patient who underwent aortic valve replacement with an aortic homograft can result technically challenging because of the massive calcification of the conduit.We present a case of a patient who underwent open surgery on cardiopulmonary bypass assistance to implant a standard transcatheter aortic bioprosthesis through aortotomy in an off-label procedure and we discuss its safety and feasibility.The combination of open cardiac surgery and open trans-aortic implant of a transcatheter prosthesis may reduce the surgical risk shrinking the technical difficulties that the implantation of a standard surgical prosthesis would have given. Surgical aortic valve replacement (SAVR) with a stentless root such as homografts may offer some clinical advantages, like improved hemodynamics performances and enhanced positive remodeling of the left ventricle , no needHereby we present a case of a male patient who underwent what we named TAVI-in-Homograft (TiH) procedure.A 75-years-old Caucasian male was admitted to our clinic with a mixed aortic valve pathology. He had a positive cardiovascular anamnesis, since he underwent aortic valve replacement with a 27 mm size aortic homograft twenty-two years earlier.Since then he, performed yearly echocardiographic follow-ups. The first signs of homograft degeneration presented 12 years after the implant with moderate aortic regurgitation and fibro-sclerosis of the aortic wall.Ten years later there was evidence of worsening of aortic regurgitation in association with moderate stenosis .C. hominis, which lead to the diagnosis of endocarditis and specific antibiotic therapy was started with Meropenem and Ceftriaxone. After three weeks of therapy, the inflammatory markers were negative, the clinical aspects of the patient were ameliorated and the echocardiogram showed improvement of the EF (52%) and positive remodeling of the left ventricle (EDV 161 ml) while vegetations and severe aortic regurgitation were confirmed, and echocardiographic aortic stenosis parameters worsened . Echocardiographic and CT scan images did not show any image suggestive of abscess.After 8 months from the last instrumental evaluation the patient went to the emergency department because of new onset dyspnea and fever. A new trans-thoracic echocardiogram showed worsening of the left ventricular ejection fraction (EF 42%), new evidence of left ventricle dilation with an end-diastolic volume (EDV) of 245 ml and vegetation on the aortic leaflets. Blood cultures were positive for Because of the frailty of the patient, the complexity of a redo-surgery in the setting of an extremely calcified and dilated homograft the heart team proposed an implantation of a transcatheter aortic valve on cardiopulmonary bypass (CPB) through median sternotomy.A small aortotomy was performed 2 cm above the calcified and dilated homograft and then the leaflets were explored. The leaflets appeared retracted and heavily calcified Fig. , and perEdwards Lifesciences, Irvine, USA) balloon-expandable prosthesis was performed under direct view . The patient was discharged in the 7th post-operative day.After 14 months from the procedure the patient is alive and well, asymptomatic, and the residual mild aortic regurgitation is stable.Valvular and vascular tissues from a cadaveric donor are often utilized in congenital malformation and in the adult in the setting of acute endocarditis due to their more likely resistance to the infections.We previously report other cases of severe calcified degenerated homograft that needed other than surgical replacement due to the impossibility to perform secure decalcification . The traTrans-aortic TAVR was chosen after exclusions of the sutureless valves. First of all, we could not use the Intuity prosthesis because of the impossibility to place any stitches on the homograft. The other possible choice was the Perceval prosthesis, but we avoided it because of the higher profile of the prosthesis  and because of the higher and larger aortotomy that it would have needed. Moreover, any peripheral approach was excluded to avoid the need of a wire, that could have easily teared up the spotted calcifications expanding from the homograft to the ascending aorta. Instead, a trans-apical approach has been excluded because of the low EF.In such cases a TAVI-in-Homograft (TiH) procedure may be the only reasonable possibility to overcome the anatomical finding discovered at the operating theatre, as also other groups , 10 haveIn this case we have presented the heart team evaluated the frailty of the patient and the anatomy of the homograft. The graft was so calcified that a standard surgery requiring stitches would have been technically impossible, but it would have also made very dangerous a standard transcatheter procedure because of the aortic calcification , 12 and The combination of open cardiac surgery with CPB and open trans-aortic implant of a transcatheter prosthesis decreased the surgical risk and permitted to perform the procedure safely, shrinking the technical difficulties that the implantation of a standard surgical prosthesis would have given.Larger series and studies on this particular subpopulation of patients are warranted to drive final conclusion.


Time-domain reflectometry (TDR) has been a powerful tool for measuring soil dielectric properties. Initiating from apparent dielectric constant ( Time-domain reflectometry (TDR) has been a robust tool for measuring soil dielectric properties, ranging from apparent dielectric constant  spectrum from input functions and scattering functions ,11,12,13A vector network analyzer (VNA) is widely used to characterize the CDP spectrum of the MUT in a laboratory environment ,15. MeasLin et al. , therefoIn general, a TDR instrument sends a step pulse input into the transmission line, up until the end of the probe sensing section. The propagating electromagnetic (EM) wave interacts with the particles of the MUT at the sensing section that induces polarization, in which this effect would be reflected on the reflection signal recorded by the oscilloscope of the TDR system. The first two major reflections of interest come from the beginning and end of the probe sensing section, particularly for an open-ended probe with an impedance-matched probe head (to the leading cable). These major reflections are due to discontinuity in characteristic impedance , After truncating ransform , as showThe CDP spectrum of the MUT is measured by optimizing n et al. . The latD is the inner diameter of the outer conductor while d is the outer diameter of the inner conductor. For sensing probes with irregular cross sections, As for system parameter calibration in the DRA approach, there are only two system parameters to be calibrated once, the length (ws below :(9)Zp=12Simulated TDR signals were generated synthetically to compare the DRA results against the experimental signals, in order to investigate the potential difference between simulated and experimental signals. A transmission line model, consisting of three sections, was formulated to emulate experimental results, including a 42 m coaxial cable with a characteristic impedance of and Tang  and usinand Tang  as the dA laboratory measurement system is used to evaluate the performance of DRA in eight MUT with different dispersion degrees and dielectric characteristics, as shown in Simulated and experimental signals of the four non-dispersive MUT are shown in The measured CDP spectrum of the four MUT are shown in The effective CDP spectrum bandwidth of the experimental signals is slightly narrower than of the simulated signals. The effective bandwidth is influenced by several factors. The long leading cable physically filters out the spectral content of higher frequencies. The existence of random noise aggravates this condition, thus reducing the higher effective frequency region of the experimental signals. As for the lower bound frequency, cable resistance effect increases the risetime of reflected waves and causes tail leakage of a) and (b) respectively. Some experimental signals differed from the simulated signals due to the input scaling consistency of the TDR pulser and no amplitude scaling was applied to the experimental signals. Nevertheless, this is not an issue for DRA as this input scaling effect would be eliminated through the spectral comparison of Apart from non-dispersive MUT, DRA was further evaluated using alcohols with high dispersion, where methanol, ethanol, isopropanol, and butanol were used. Their time-domain signals are presented in DRA generated CDP spectrums for the four dispersive MUT are shown from Since the signal truncation effect has a significant impact on the CDP spectrum of dispersive MUT, the extraction time window of Using the experimental signal of isopropanol as an example b, the fiapproach , which fIn this study, Dual reflection analysis (DRA) of TDR signals were proposed and evaluated to perform dielectric spectroscopy from 10 MHz to 1 GHz. The proposed DRA method is a simple, robust, model-free, and source-function free algorithm to measure the complex dielectric permittivity (CDP) spectrum with decoupled real and imaginary parts. DRA extracts the first two major reflections from the sensing section and fast Fourier Transforms the time-domain signal into spectral DRA ratios for CDP spectrum fitting. This approach is validated using eight materials with different dielectric characteristics and its performance is investigated through the comparison of simulated and experimental data. DRA is capable of measuring the CDP spectrum of non-dispersive materials very well, with satisfactory effective frequency bandwidth. As for dispersive alcohol type materials, DRA with long-time-window (LTW) extraction is recommended to suppress the significant signal truncation effect and extend the effective frequency range. The DRA approach is suitable for field applications that can only record a limited amount of data points and in-situ dielectric spectroscopy. This approach is potentially advantageous in geotechnical and geo-environment industries for soil moisture monitoring, groundwater and soil contamination monitoring, liquid quality detection, and so forth. This method can be extended to multiple reflection analysis (MRA), which fully considers all multiple reflections in its formulations but requires longer recording time to allow the TDR signal to fully reach the steady state.


Rice is a staple food in Asia and it contributes significantly to the Gross Domestic Product (GDP) of Malaysia and other developing countries. Brown Planthopper (BPH) causes high levels of economic loss in Malaysia. Identification of BPH presence and monitoring of its abundance has been conducted manually by experts and is time-consuming, fatiguing and tedious. Automated detection of BPH has been proposed by many studies to overcome human fallibility. However, all studies regarding automated recognition of BPH are investigated based on intact specimen although most of the specimens are imperfect, with missing parts have distorted shapes. The automated recognition of an imperfect insect image is more difficult than recognition of the intact specimen. This study proposes an automated, deep-learning-based detection pipeline, PENYEK, to identify BPH pest in images taken from a readily available sticky pad, constructed by clipping plastic sheets onto steel plates and spraying with glue. This study explores the effectiveness of a convolutional neural network (CNN) architecture, VGG16, in classifying insects as BPH or benign based on grayscale images constructed from Euclidean Distance Maps (EDM). The pipeline identified imperfect images of BPH with an accuracy of 95% using deep-learning’s hyperparameters: softmax, a mini-batch of 30 and an initial learning rate of 0.0001. Nilaparvata lugens , the whiteback planthopper, Sogatella furcifera (Harvath), and the leafhopper, Nephotettix virescens. The most destructive hopper among them is the BPH, which is considered as the most serious pest of rice in both temperate and tropical region of east and south Asia. Tr. Tr3]. TAdvances in machine learning have revolutionized computer vision and object recognition in general and in pest identification in particular . MachineSeveral pest identifications and classification systems have been proposed that based on machine learning. Image analysis with scene interpretation was proposed by Kumar et al.  by develAnother method used a network of cameras for the continuous survey of a greenhouse in estimating the population of pests. In this system, one camera was observing the sticky trap while the second was observing the plant and none flying insect pests . The strThe bag-of-words approach and gradient-based features were proposed for developing a framework that can classify insect pests from the paddy field . The datAlgorithmically, insect classification needs features to be recognized by classifiers that include wing structures –9], col, col9], In trap-based pest monitoring especially with sticky pads, there are many challenges such as low image quality, inconsistencies derived from illumination, movement of the trap, movement of the pests, camera out of focus, the appearance of other objects, decay or damage to the insect, the presence of benign insects and many more. Among these challenges, the effects of decay or damage on insect images are still not yet overcome. Decayed or damaged insects have different outlines and morphology compared to intact insects. Sticky pads usually trap while they are flying towards the pad surface. The impact of the collision between the pad and the insects distort the body and morphology of insects. It is difficult to design an automated system that can identify distorted insect pests. Thus, a method for such a system is in urgent need. Various datasets have been utilized to push this area forward , 31]; y; y31]; yo27’55.94”N, 101o11’33.33”E), Tanjung Karang, Selangor, Malaysia . The paddy was about 70 days after planting and infested with BPH. Sticky glue was sprayed on plastic sheet which stick on the steel board plate. The plate was put on the base of paddy stem, where the BPH are usually located. Then, the stems were tapped for few times to ensure BPH were adhered on the glued. These methods were repeated few times at different paddy plant to get enough samples.This section describes the collection, curation and pre-processing of sticky pad images. Samples of insects were collected from the granary area Sawah Sempadan .The plates, the sticky pad, consisting of trapped BPH were brought to a laboratory. The BPH, either short or long winged, were then manually identified and labelled with bounding circles by an entomologist. The digital images of the sticky pads were then captured by a Huawei P9 Plus smartphone camera under the laboratory room illumination and stored in JPEG format. The smartphone camera is dual 12 megapixels monochrome and colour camera, with focal length of 27mm and F2.2 aperture. All images do not have a temporal correlation with each other, which makes all the labelled BPH unique. Every single BPH and benign insect image was cropped from the sticky pad image to become an independent image patch. The positions and locations of these insects were random and unstructured. The dataset of both BPH and benign insects was split randomly into 3 sets: the training, validation and test sets. The statistics of each set is the same as the entire dataset as shown in The sticky pad images were collected in real production environments which resulted in different imaging conditions at different times. As shown in A schematic diagram of PENYEK is shown in Next, the binary images were transformed by one of the six selected binary operations as shown in The CNN architecture typically consists of three different layers: convolutional layer, pooling layer and a fully connecter layer.x is pixel, h is filter, and N is the number of elements in x. The output vector is y. The subscripts denote the nth element of the vector and k is the current kernel.This layer consists of kernels (filters) which slide across the insect image. A kernel is the matrix to be convolved with the input image and stride length controls how much the filter convolves across the input image. This layer performs the convolution on the input image with the kernel using Eq .yk=∑n=0This down-sampling layer reduces the dimension of output neurons from the convolutional layer to lessen the computational intensity and prevent the overfitting. The max-pooling operation is used in this study. Max-pooling operation selects only the maximum value in each feature map and consequently reducing the number of output neurons.This layer has full connection to all the activations in the previous layer.The chosen binary operator is combined with CNN VGG16 architecture to form a complete PENYEK pipeline. In this last step, the binary operator + CNN VGG16 trained on a large volume of annotated data is used. In other words, this study uses VGG16 architecture instead of training a custom CNN from scratch for the task of BPH classification. VGG16 architecture is one of the transfer learning approaches in deep learning that has several advantages such as the architecture’s weights and biases have been trained over millions of images to classify thousands of object and classes. This makes the weights and biases connecting its neurons have been optimally calculated. As the used dataset is small in nature, training VGG16 on a small dataset greatly affects the VGG16’s ability to generalize, often result in overfitting.To overcome aforementioned problems in training CNN, this research uses fine-tuning technique using the following strategies:Use a smaller learning rate,Truncate the last layer from 1000 classes to 2 classes, andFreeze the weights of the first few layers.The VGG16 architecture that performs these strategies is shown in The CNN structures and VGG16 architecture are evaluated based on the intact/imperfect insect pest image patches. These image patches contain 2 distinct categories: positive and negative.Positive patches are derived from manually labelled bounding circle, where each one represents a BPH. In machine learning, the larger the dataset, the better the generalization performance. In this study, the amount of training data, which is represented by the number of training patches, is much smaller than standard small-scale image classification datasets frequently used by the deep learning field. Therefore, data augmentation was performed to increase the number of images for training, and incorporated invariance to basic geometric transformations into the classifier.This section quantitively describes the results of the PENYEK performance and then discusses qualitative visual results.The first experiment is a pilot study to evaluate binary filtering operations: Outline, Fill holes, Skeletonize, Watershed, Voronoi and Euclidean distance map. Seven different CNN structures were devised to create a novel pipeline for identification and classification of heterogenous BPH to test the filters. PENYEK pipeline is shown in Eventually, the performance of PENYEK pipeline is compared with state-of-the-art approaches for image analysis in digital pest identification and classification. These include handcrafted texture and colour descriptors such as the GLCM features, Gabor filter-bank features, LBP histograms, gray histograms, HSV histograms and RGB histograms followed by random forest machine learning. The average classification accuracy and AUC using the state-of-the-art methods is shown in Accurate insect pest detection is very important in agriculture for the estimation of pest population density and dynamics in fields which allows for precision pesticide application. Due to the complex environment background of living pests, it is a big challenge to automatically identify them by image processing. The major challenge in the state-of-the-art automated system is to identify imperfect images. To replace human expertise and to overcome the aforementioned major challenges in the automated system, this study proposed an automated detection pipeline for Brown Planthopper in paddy fields called PENYEK. The PENYEK pipeline leveraged the architecture of VGG16 and Euclidean Distance Map (EDM) by applying the pre-trained weights and biases for classifying imperfect images. VGG16 network pre-trained on the large ImageNet dataset is fine-tuned to learn features of the BPH image dataset. The VGG16 architecture learned to identify BPH based only on positive and negative training samples. The insect pest images are in grayscale and achieves lower accuracy in RGB.The first component of the proposed pipeline is image processing by applying binary filtering operations and other pre-processing techniques on image patches. From the performance of several CNN structures, EDM shows the best performance of all in term of accuracy. The second component is the VGG16 pre-trained architecture that has been fine-tuned to be trained in a small dataset. The performance of VGG16 architecture increases when fed with EDM images in term of accuracy, sensitivity, specificity and AUC. Moreover, the VGG16 architecture outperforms the state-of-the-art methods in image analysis in term of accuracy and AUC. All in all, qualitative and quantitative empirical results demonstrate the effectiveness of PENYEK pipeline on an insect pest image dataset.


This preface introduces the content of the BioMed Central Bioinformatics journal Supplement related to the 15th annual meeting of the Bioinformatics Italian Society, BITS2018. The Conference was held in Torino, Italy, from June 27th to 29th, 2018. BITS, the Italian Society of Bioinformatics , is the The environment created during the BITS2018 meeting provided a unique opportunity for all participants to meet, debate with, and get to know the latest activities of the Italian Bioinformatics community.Since 2004, the BITS society has organized the annual meeting to gather not only the BITS members but all the researchers interested in the bioinformatics field. These events soon became the most important annual meeting for the Italian bioinformatics community, and every year the local organizing committee complements the BITS meeting with workshops and activities centered on the main current hot research topics.Algorithms for Bioinformatics to Gene regulation, Transcriptomics and epigenomics, Protein structure and function, Systems Biology, Bioimaging and more. In addition, a special session was devoted to the Bioinformatic challenge in microbiome research.The BITS2018 meeting was held in Torino, from June 27th to 29th in the Aula Magna of the Cavellerizza Reale of the University of Turin. BITS2018 highlights keynotes talks by excellent scientists in bioinformatics and its applications, oral presentations of the state-of-the-art research in computational biology, and poster session on the latest research progress. The meeting was organized by Francesca Cordero , Raffaele A. Calogero  and Michele Caselle , with the support of the BITS steering committee. About 180 participants attended the meeting and most of them submitted contributions as oral presentation or poster. After the abstracts evaluation, the BITS2018 Program Committee  were accepted and included in this supplement. A brief summary of each contribution is reported in the following.In this paper, the authors introduced TACITuS, a web-based system supporting rapid query access to high-throughput microarray and NGS repositories. The system is equipped with modules capable of managing large files, storing them in a cloud environment and extracting subsets of data in a efficient way. The system also supports the import of data into Galaxy for further analysis.The authors proposed a comprehensive study which updated the number of human-specific genes following a critical bibliographic survey. Human-specific genes were functionally assessed providing unique information. The results presented are consistent with environmental changes, such as immune challenges and alterations in diet, as well as neural sophistication, as significant contributors to recent human evolution.The authors present STRAIN (ST Reduced Assembly IdentificatioN), an R package implementing a hybrid strategy between assembly and mapping of the reads to assign the ST to an isolate starting from its read-sets. STRAIN is designed for single allele typing as well as MLST. Its implementation in R makes allele and ST assignment simple, direct and prompt to be integrated in a wider pipeline of downstream bioinformatics analyses.The authors present MetaCon a novel tool for unsupervised metagenomic contig binning based on probabilistic k-mers statistics and coverage. MetaCon uses a signature based on k-mers statistics that accounts for the different probability of appearance of a k-mer in different species, also contigs of different length are clustered in two separate phases.The authors present YALFF (Yet Another Lossy Fastq Filter), a tool for quality scores compression by smoothing leading to improve compressibility of FASTQ files. Authors used FM-Index to reduce the storage requirements of a dictionary of k-mers and an effective smoothing algorithm to maintain high precision for SNP calling pipelines, while reducing quality scores entropy.The authors present metaSPARSim, a sparse count matrix simulator intended for usage in development of 16S rDNA-seq metagenomic data processing pipelines. metaSPARSim implements a new generative process that models the sequencing process with a Multivariate Hypergeometric distribution to effectively simulate 16S rDNA-seq count table, resembling real experimental data compositionality and sparsity.The authors explored the use of deep learning in evolutionary biology and implemented a program, called ImaGene, applying convolutional neural networks on population genomic data for the detection and quantification of natural selection. To detect and quantify signatures of positive selection, ImaGene implements a convolutional neural network which is trained using simulations.The authors address cancer related signaling pathways to investigate miRNA therapeutics. Their approach is based on drug discovery and miRNA therapeutics and uses a digital circuit simulation for cancer pathways. The most effective combination of drugs and miRNAs are then validated by the literature. Two different case studies on non-small cell lung cancer and melanoma are described.The authors investigate the performance of the Logic Learning Machine (LLM) - an innovative method of supervised analysis capable of constructing models based on simple and intelligible rules - in classifying patients with cancer. Performance was evaluated using a set of eight publicly available gene expression databases for cancer diagnosis. The set of simple rules generated by LLM could contribute to a better understanding of cancer biology, potentially addressing therapeutic approaches.Caenorhabditis elegans early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development.The authors focus their research on Transposable Elements (TE) which are mobile sequences elements that make up large portions of eukaryote genomes. They analyzed TE expression among different cell types of the In this work, the authors addressed another aspect of TEs: their presence in cis on the expression of flanking genes by producing associations between polymorphic TEs and flanking gene expression levels in human lymphoblastoid cell lines. They exploit an expression quantitative trait loci approach integrated with additional bioinformatics data mining analyses.