Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Proteomic-based stratification of intermediate-risk prostate cancer patients.

Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in the Gleason grade group (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or overtreatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign sample runs from 278 patients. Three proteins (F5, TMEM126B, and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomize prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management.

Poly(ethyl ethylene phosphate): Overcoming the "Polyethylene Glycol Dilemma" for Cancer Immunotherapy and mRNA Vaccination.

Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma". PEEPylated liposomes exhibit lower immunogenicity and generate negligible anti-PEEP antibodies (IgM and IgG) after repeated treatments. In vivo studies confirm that PEEPylated liposomes loaded with oxaliplatin (PEEPlipo@OxPt) show better pharmacokinetics compared to PEGlipo@OxPt, and they exhibit potent antitumor performances, which can be further promoted with checkpoint blockade immunotherapy. In addition, PEEPylated lipid nanoparticle is also used to develop an mRNA vaccine with the ability to evoke a potent antigen-specific T cell response and achieve excellent antitumor efficacy. PEEP shows promising potentials in the development of next-generation nanomedicines and vaccines with higher safety and efficacy.

Fabrication of An Immunostimulatory Supramolecular Nanomedicine for Potent Cancer Chemoimmunotherapy.

Chemoimmunotherapy can boost strong antitumor immune responses by triggering immunogenic cell death (ICD), which highlights a promising prospect in clinical applications. However, current chemoimmunotherapy shows limited efficacy due to the low delivery efficiency and insufficient immunogenicity of available chemotherapeutic drugs. A supramolecular polymeric nanomedicine (Pt-Tu@NP) is herein reported using cucurbit[7]uril-based host-guest recognition and noncovalent self-assembly. Pt-Tu@NPs have excellent biodistribution and strongly evoke the endoplasmic reticulum stress-mediated ICD of tumor cells, triggering potent antitumor immune responses by promoting dendritic cell (DC) maturation and cytotoxic T cell infiltration. The coordinated butyrate promotes a positive feedback regulation between DCs and CD8+ T cells. Pt-Tu@NPs stimulate immune cold tumors into hot ones, working in synergy with an immune checkpoint blockade to effectively suppress tumor growth and metastasis, which suggests a promising approach for cancer chemoimmunotherapy.

Flat Warts (Verrucae Planae) Confined to the Pigment of a Tattoo: A Rare Tattoo-associated Complication.

Tattoos are a form of decorative body art in which pigment dyes of different colors are inoculated into the skin. It is estimated that 15-25% of general population has one or more tattoos (1), and the reasons for the popularity of this procedure may include greater social acceptance, aesthetic appeal, or perhaps the option of using laser removal techniques to eliminate unwanted tattoos. Even though modern professional tattoos are usually performed in sterile conditions, complications still occur, and with increasing numbers of people getting tattoos, the incidence of tattoo-associated side-effects presenting to dermatologists, which may be as high as 2%, is likely to increase (2). Herein we present a case of a 43-year-old male patient with multiple HPV-associated flat warts (verrucae planae) confined to the black pigment of a tattoo done 15 years ago. A 43-year-old patient presented to our clinic due to eczema on the trunk. However, during skin examination, we observed asymptomatic verrucous papules confined to the black ink of a tattoo done 15 years ago on the lateral side of his right lower leg (Figure 1a). Clinical examination showed multiple, discrete, skin-colored, verrucous papules disseminated exclusively within the lines of the black-colored tattoo. Full skin examination did not reveal any similar lesions anywhere else on the body. Dermoscopically, papules showed a discretely papillomatous surface and sharp borders (Figure 1b). The patient had another black tattoo on his trunk, in which no similar lesions were found. All his tattoos had been done more than 15 years ago in a professional tattoo salon and with no previous history of cutaneous lesions within tattoos. The patient had no other medical conditions and was not taking any medications. Additionally, no history of warts or other HPV-related lesions of the skin or mucosal membranes could be established. A biopsy of an individual papule was taken and sent for a histopathological analysis, which subsequently showed hyperkeratotic, orthokeratotic, and parakeratotic acanthotic epidermis with hypergranulosis and rare cells with perinuclear halo indicative of koilocytes (Figure 3b). Immunohistochemical analysis showed negative reaction for p16 and p53, while Ki67 was positive only in rare basal and suprabasal cells. These findings were indicative of low-risk HPV, and the diagnosis of HPV-induced verruca plana was ultimately established. The patient was then successfully treated with cautious curettage of the lesions, leaving no scars. Due to the growing popularity of tattoos, especially among younger populations, it is necessary to emphasize the possibility of various tattoo-related side-effects that can still occur due to improper preparation of the tattoo location, contamination of ink products, improperly sterilized instruments, or due to insufficient personal hygiene following tattooing (3). In the past, tattoo-associated infections were significantly more frequent, with the highest prevalence of Staphylococcus and Streptococcus infections causing impetigo, folliculitis, cellulitis, erysipelas, or sepsis (2), but recent improvement and efforts in using sterile techniques in tattooing has led to a significant drop in the number of tattoo-related infections. In this short report, we present a case of a different and a relatively rare type of tattoo-associated infection - flat warts i.e., verrucae planae. Flat warts are usually caused by HPV-3, -6B, -10, -28, and -49. Typical predilection sites are the face, dorsal sides of the hands or feet, arms, and legs, and they usually appear as skin-colored, pink, or brown, flat-topped discrete papules. It is believed that HPV can be inoculated through contaminated ink, instruments, the artist's saliva, or that it may be a pre-existing unnoticed wart in the tattooed area (4-6). The latency period between tattooing and HPV infection can range from several months to 10 years, with a mean period of 5 years (3). This may suggest that the immune system can control the infection for some time, and that some form of immune suppression may result in the development of a clinical disease. In our case, the latency period could not be established due to the patient's unawareness of the lesions, and no potential trigger could be identified. The occurrence of lesions on only one of the patient's tattoos as well as their confinement to the black pigmented ink may indicate a correlation to this specific pigment. Ramey et al. (6) conducted a study in which they assessed the localization of warts in differently colored tattoos. The results showed that black ink tattoos had a seven times higher risk of developing warts when compared with colored ink. At first it was thought that this was due to HPV inoculation via contaminated instruments, ink, or autoinoculation of the patient's own warts, but some evidence indicates that it is unlikely for HPV to survive in ink and that if the warts were inoculated they would occur equally in all ink colors. A different theory by Ruocco et al. (7) explains this phenomenon through an "immunocompromised district" mechanism, in which polycyclic aromatic hydrocarbons found in black ink produce reactive oxygen species (ROS) that can damage cellular structures and consequently increase the risk of a variety of infections, including HPV. Moreover, black ink contains almost pure nanoparticles, which are associated with greater ROS production than the larger particles found in colored ink (7,8). There are several treatment options for verrucae planae, such as liquid nitrogen cryotherapy, topical 5% fluorouracil, topical 5% imiquimod, 0.025-0.050% tretinoin, 10% salicylic acid, or 10-30% glycolic acid. These treatments have differing success rates. Destructive modalities, such as surgical excision, curetting, or laser ablation may significantly damage the tattoo and cause scarring, and are thus not regularly performed. It's necessary to emphasize that despite today's sterile methods of tattooing, complications may still occur and medical professionals, namely dermatologists, should be aware of them. A person who wishes to get a tattoo should be advised to visit a licensed tattoo artist at a licensed tattoo parlour only. Patients with pre-existing dermatoses characterized by an isomorphic phenomenon, such as psoriasis or lichen planus, are particularly prone to developing a tattoo-associated adverse reaction, and those with severe dermatoses should be advised to avoid tattooing. Additionally, people with a previous history of warts should be aware of the possibility of warts occurrence, even years or decades after tattooing. Even though most of tattoo-related side effects are merely inconveniences, there is a potential for serious complications and patients should be advised as such.

Segmental Erythema Multiforme: An Unusual Drug Reaction to Anastrozole.

Erythema multiforme (EM) is an immune-mediated, mucocutaneous hypersensitivity syndrome that can occur as a result of various medications, including a wide range of antineoplastic and hormonal drugs. Anastrozole, a nonselective aromatase inhibitor used in breast cancer management has been associated with different cutaneous side effects, of which EM is rarely seen and usually in a minor or major form with typical target lesions. This is a short report of a patient who developed a rare cutaneous side effect after the use of aromatase inhibitor anastrozole - segmental erythema multiforme in cancer-affected area. Cutaneous adverse effects limited to cancer-affected breast are extremely rare but should be considered in everyday dermatological practice. We find this case instructive not only because of the rarity of the segmental EM, but also because, contrary to classical teaching, drug eruption due to anastrozole occurred months, not days after the initiation of therapy.

A computational framework for the inference of protein complex remodeling from whole-proteome measurements.

Protein complexes are responsible for the enactment of most cellular functions. For the protein complex to form and function, its subunits often need to be present at defined quantitative ratios. Typically, global changes in protein complex composition are assessed with experimental approaches that tend to be time consuming. Here, we have developed a computational algorithm for the detection of altered protein complexes based on the systematic assessment of subunit ratios from quantitative proteomic measurements. We applied it to measurements from breast cancer cell lines and patient biopsies and were able to identify strong remodeling of HDAC2 epigenetic complexes in more aggressive forms of cancer. The presented algorithm is available as an R package and enables the inference of changes in protein complex states by extracting functionally relevant information from bottom-up proteomic datasets.

Uncovering the dynamics of cellular responses induced by iron-carbohydrate complexes in human macrophages using quantitative proteomics and phosphoproteomics.

Iron-carbohydrate complexes are widely used to treat iron deficiencies. Macrophages play a crucial role in the uptake and fate of these nanomedicines, however, how complexed iron carbohydrates are taken up and metabolized by macrophages is still not fully understood. Using a (phospho-)proteomics approach, we assessed differences in protein expression and phosphorylation in M2 macrophages triggered by iron sucrose (IS). Our results show that IS alters the expression of multiple receptors, indicative of a complex entry mechanism. Besides, IS induced an increase in intracellular ferritin, the loss of M2 polarization, protective mechanisms against ferroptosis, and an autophagic response. These data indicate that macrophages can use IS as a source of iron for its storage and later release, however, the excess of iron can cause oxidative stress, which can be successfully regulated by the cells. When comparing IS with ferric carboxymaltose (FCM) and iron isomaltoside-1000 (IIM), complexes with a higher carbohydrate ligand stability, we observed that FCM and IIM are metabolized at a slower rate, and trigger M2 polarization loss to a lower extent. These results indicate that the surface characteristics of the iron-carbohydrate complexes may influence the cell responses. Our data show that the application of (phospho-)proteomics can lead to a better understanding of metabolic processes, including the uptake, biodegradation and bioavailability of nanomedicines.

Association of Gut Lachnospiraceae and Chronic Spontaneous Urticaria.

(1) Background: Chronic spontaneous urticaria (CSU) has been linked to the dysbiosis of the gut microbiota. Furthermore, various studies have highlighted the anti-inflammatory properties of short-chain fatty acids (SCFAs), whose production is primarily regulated by the gut microbiota. However, only a few studies have investigated the role of major SCFA producers, such as Lachnospiraceae, in skin inflammatory diseases. (2) Goal: This study aimed to compare the abundance of Lachnospiraceae between CSU patients and healthy controls (HCs). (3) Material and methods: In this case-control study, 16S rRNA sequencing was performed to compare the composition of the gut microbiome between 22 CSU patients and 23 HCs. (4) Results: Beta-diversity revealed significant clustering (p < 0.05) between the CSU patients and HCs. Alpha diversity in the CSU group was significantly decreased according to the Evenness index (p < 0.05). The linear discriminant analysis effect size (LEfSe) identified the significant depletion of the Lachnospiraceae family in CSU patients. (5) Conclusion: Our study revealed the dysbiosis of the gut microbiota in CSU patients, including decreased levels of Lachnospiraceae members, responsible for SCFA production, suggesting that SCFAs may contribute to immune dysfunction in the pathogenesis of CSU. We speculate that the modulation of SCFAs could serve as a prospective additional option in CSU treatment.

Psychological Stress and Hand Eczema in Physicians and Dentists: A Comparison Based on Surgical Work.

BACKGROUND: This research looks at the connection between psychological stress and the prevalence of hand eczema (HE) among physicians and dentists (surgeons, non-surgeons). METHODS: This cross-sectional field study involved 185 participants: physicians (surgeons, non-surgeons), dentists (surgeons, non-surgeons) and controls. Hand lesions were examined using the Osnabrueck Hand Eczema Severity Index (OHSI), and participants answered the Nordic Occupational Skin Questionnaire (NOSQ) and Perceived Stress Scale (PSS). Patch tests were performed using commercial contact allergens. RESULTS: The estimated prevalence of HE (self-reported) was 43.9% (physicians 44.6%; dentists 43.2%). HE was significantly more reported by surgeons than controls (p < 0.004; V = 0.288). Degrees of perceived stress (PSS) did not differ significantly between the groups, though physicians non-surgeons most exhibited high stress (50%), and physicians surgeons most exhibited low stress (22.5%). High stress was associated with 2.5 higher odds for self-reported HE (p = 0.008). Low stress was greater among physicians/dentists who did not report eczema (41.0% vs. 24.6%); moderate stress was more common among those who reported eczema (72.3% vs. 51.8%; p = 0.038; V = 0.210). CONCLUSIONS: Since high stress levels may negatively influence physicians'/dentists' work and quality of life, measures to decrease stress could be introduced into the treatment of healthcare workers who are prone to it.

Polymerization in living organisms.

Vital biomacromolecules, such as RNA, DNA, polysaccharides and proteins, are synthesized inside cells via the polymerization of small biomolecules to support and multiply life. The study of polymerization reactions in living organisms is an emerging field in which the high diversity and efficiency of chemistry as well as the flexibility and ingeniousness of physiological environment are incisively and vividly embodied. Efforts have been made to design and develop in situ intra/extracellular polymerization reactions. Many important research areas, including cell surface engineering, biocompatible polymerization, cell behavior regulation, living cell imaging, targeted bacteriostasis and precise tumor therapy, have witnessed the elegant demeanour of polymerization reactions in living organisms. In this review, recent advances in polymerization in living organisms are summarized and presented according to different polymerization methods. The inspiration from biomacromolecule synthesis in nature highlights the feasibility and uniqueness of triggering living polymerization for cell-based biological applications. A series of examples of polymerization reactions in living organisms are discussed, along with their designs, mechanisms of action, and corresponding applications. The current challenges and prospects in this lifeful field are also proposed.

Gene expression profiling of human macrophages after graphene oxide and graphene nanoplatelets treatment reveals particle-specific regulation of pathways.

Graphene and its derivatives are attractive materials envisaged to enable a wealth of novel applications in many fields including energy, electronics, composite materials or health. A comprehensive understanding of the potential adverse effects of graphene-related materials (GRM) in humans is a prerequisite to the safe use of these promising materials. Here, we exploited gene expression profiling to identify transcriptional responses and toxicity pathways induced by graphene oxide (GO) and graphene nanoplatelets (GNP) in human macrophages. Primary human monocyte-derived macrophages (MDM) and a human macrophage cell line, i.e. differentiated THP-1 cells, were exposed to 5 or 20 µg/mL GO and GNP for 6 and 24 h to capture early and more persistent acute responses at realistic or slightly overdose concentrations. GO and GNP induced time-, dose- and macrophage type-specific differential expression of a substantial number of genes with some overlap between the two GRM types (up to 384 genes (9.6%) or 447 genes (20.4%) in THP-1 or MDM, respectively) but also a high number of genes exclusively deregulated from each material type. Furthermore, GRM responses on gene expression were highly different from those induced by inflammogenic material crystalline quartz (maximum of 64 (2.3%) or 318 (11.3%) common genes for MDM treated with 20 µg/mL GO and GNP, respectively). Further bioinformatics analysis revealed that GNP predominantly activated genes controlling inflammatory and apoptotic pathways whereas GO showed only limited inflammatory responses. Interestingly, both GRM affected the expression of genes related to antigen processing and presentation and in addition, GO activated pathways of neutrophil activation, degranulation and immunity in MDM. Overall, this study provides an extensive resource of potential toxicity mechanisms for future safety assessment of GRM in more advanced model systems to verify if the observed changes in gene expression in human macrophages could lead to long-term consequences on human health.

Vascular Diameter as Clue for the Diagnosis of Clinically and/or Dermoscopically Equivocal Pigmented and Non-Pigmented Basal Cell Carcinomas and Nodular Melanomas.

Background and objectives: Dermoscopy is a useful tool for the early and non-invasive diagnosis of skin malignancies. Besides many progresses, heavily pigmented and amelanotic skin tumors remain still a challenge. We aimed to investigate by dermoscopy if distinctive morphologic characteristics of vessels may help the diagnosis of equivocal nodular lesions. Materials and Methods: A collage of 16 challenging clinical and dermoscopic images of 8 amelanotic and 8 heavily pigmented nodular melanomas and basal cell carcinomas was sent via e-mail to 8 expert dermoscopists. Results: Dermoscopy improved diagnostic accuracy in 40 cases. Vessels were considered the best clue in 71 cases. Focusing on the diameter of vessels improved diagnosis in 5 cases. Conclusions: vascular diameter in addition to morphology and arrangement may be a useful dermoscopic clue for the differential diagnosis of clinically equivocal nodular malignant tumors.

From Morphea to Dermatofibrosarcoma Protuberans.

Dear Editor, Morphea profunda (MP) is a chronic autoimmune disease, a subtype of localized scleroderma that presents clinically as local discomfort due to the impairment of skin motility (1). Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue neoplasm that not only infiltrates the dermis and subcutaneous tissue, but can also affect the muscles and bones with finger-like extensions, usually present on the trunk and the proximal extremities (2). DFSP is known for its indolent clinical course, locally aggressive behavior, and high local recurrence rates, but relatively low risk of metastatic spread (2). DFSP frequently arises in middle-aged adults, affecting both sexes equally with an incidence of 4 per 1,000,000 people (3). We report the case of a 39-year-old female patient who first presented to our clinic at the age of 20 years due to a brownish atrophic coin-sized lesion appearing on the left side of the abdomen. Medical reports indicated that biopsies had been performed previously on 3 occasions, and histopathologic findings confirmed the diagnosis of MP. The aforementioned lesion on the abdomen had been growing slowly over the years, and the patient finally visited our clinic 15 years later after noticing two palpable nodules developing within the affected skin (Figure 1, A, B). Clinical examination revealed an indurated ill-defined plaque measuring 10 cm with partially atrophic surface and 2 centrally located palpable nodules measuring between 3 and 5 mm. A deep biopsy of the lesion was performed, and histopathology and immunohistochemical analysis of CD34 expression confirmed the diagnosis of dermatofibrosarcoma protuberans (Figure 1, C, D). Computed tomography scans of the thorax, abdomen, and pelvic region were subsequently performed, revealing no further disease progression. Complete excision of the tumor was performed and followed by wide scar re-excision due to narrow surgical margins of only 1 mm. No further disease progression or recurrences have been noted during the follow-up, and the patient has been disease-free for one year postoperatively. Although the etiology of DFSP is unknown, trauma has been hypothesized as a predisposing factor. It usually presents on the trunk and the proximal extremities (4). Patients usually report disease progression over a long period of time, ranging from several months to years. The tumor is associated with variable color changes, even proximal skin discoloration, and often presents with a slowly growing indurated dermal plaque or firm nodule attached to the skin (4). Clinically, it can be difficult to distinguish DFSP from a wide number of diagnoses, including morphea, idiopathic atrophoderma, atrophic scar, anetoderma, lipoatrophy, cellular dermatofibroma, fibrosarcoma, malignant fibrous histiocytoma, atypical fibroxanthoma, desmoplastic melanoma, Kaposi sarcoma, and solitary fibrous tumors (5). Immunohistochemistry staining for CD34 cells can be helpful in differentiation, since spindle cells stain positively in DFSP (6). Due to alteration of dermal collagen, histopathological differential diagnoses of DFSP includes lichen sclerosus, atrophic scars and keloids, as well as morphea (7), atrophic dermatofibroma, and undifferentiated pleomorphic sarcoma (6). The mainstay of DFSP treatment is tumor excision performed either by wide local excision or Mohs surgery and having surgical margins between 1 and 5 cm. Several studies have confirmed that patients treated with the Mohs technique have significantly lower recurrence rates (8). Due to the high number of unsatisfactory primary excisions, wide free surgical margins are important for disease control (3). Radiotherapy might be considered as a therapeutic option for inoperable tumors or relapses, as well as an adjuvant therapy after primary excision or re-excision with positive margins (8). Furthermore, recent findings indicate positive therapeutic efficacy after administration of imatinib mesilat - a tyrosine kinase inhibitor due to over expression of PDGFß (9). Clinical follow-up of patients with DFSP after tumor excision should be performed every six months for the first five years, followed by yearly intervals thereafter for up to 10 years (3). Previous case reports have claimed that the diagnosis of DSFP is commonly delayed as a result of slow tumor growth and nonspecific initial clinical findings (10). To the best of our knowledge, our case is the first description in the literature of DFSP developed within a MP plaque. We speculate that trauma from repeated punch biopsies taken from the sclerotic morpheaform plaque may represent the trigger for the development of the DFSP. Another notable clinical challenge was the surgical excision itself, since the majority of cases presented in literature mentioned unsatisfactory resection margins and a high risk of local disease recurrence. Although complete excision of the neoplasm was performed, re-excision was performed in order to provide wider resection margins. Surgical resection remains the main treatment for dermatofibrosarcoma protuberans, with the main challenge being the achievement of clean excision margins. Proper management of the disease and continuous follow-up are important in order to prevent local recurrence of dermatofibrosarcoma protuberans or its potential metastases.

PCfun: a hybrid computational framework for systematic characterization of protein complex function.

In molecular biology, it is a general assumption that the ensemble of expressed molecules, their activities and interactions determine biological function, cellular states and phenotypes. Stable protein complexes-or macromolecular machines-are, in turn, the key functional entities mediating and modulating most biological processes. Although identifying protein complexes and their subunit composition can now be done inexpensively and at scale, determining their function remains challenging and labor intensive. This study describes Protein Complex Function predictor (PCfun), the first computational framework for the systematic annotation of protein complex functions using Gene Ontology (GO) terms. PCfun is built upon a word embedding using natural language processing techniques based on 1 million open access PubMed Central articles. Specifically, PCfun leverages two approaches for accurately identifying protein complex function, including: (i) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector and (ii) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing a hypergeometric statistical test to enrich the top NN GO terms within the child terms of the GO terms predicted by the RF models. The documentation and implementation of the PCfun package are available at https://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.

Tailoring Design of Nanomaterials and Systems to Individualize Patient Treatments.

Nanomedicine encompasses usage of materials smaller than 100 nm for diagnosis, monitoring and treatment of disease. A frequent application of these materials is in reformulation of active drugs, which were previously approved for clinical use. As illustrated with chemotherapeutics, delivery of a drug within a nanocarrier can represent a clear clinical benefit as it can increase its targeted uptake and reduce the off-target toxicity. Matching nanomedicine treatments with patient-specific biomarkers provides an exciting prospect for moving the filed towards precision medicine. In parallel, a strong potential for personalized treatments comes from employing nanomaterials for the delivery of patient-tailored biologically active molecules. Recent research and clinical data have highlighted mRNA and siRNA molecules, as well as short peptides, as powerful new drug classes that can be designed according to patient profiles and effectively delivered within nanoparticles. Particles used for therapeutic delivery are based on biodegradable and safe materials, frequently lipids and polymers, which can be further functionalized into more complex forms. Currently, there is a strong interest in developing specific nanocarrier formulations which can achieve optimal delivery of active molecules to targeted cells while reducing unwanted side-effects. Here, we discuss recent developments and future perspectives in the nanomedicine field and specifically highlight innovative approaches for the personalized patient treatments.

Painful and Itchy Dermatoses Carry the Highest Psychological Burden for Dermatovenereological Patients.

BACKGROUND: Most dermatovenereological diseases are not life-threatening but nevertheless are highly prevalent disorders. Psychosocial aspects of skin diseases and physical symptoms strongly influence patient's quality of life (QoL) which results in the development of different coping mechanisms in patient's behaviour. Development of psychiatric comorbidity in patients with skin diseases is well known. On the other hand, little is known about psychological comorbidity associated with dermatovenereological diseases. Aims of this study were to investigate QoL and psychological burden among dermatovenereological patients. SUBJECTS AND METHODS: Two hundred and ninety patients suffering from different dermatological and venereological diseases participated in the study, divided into three study groups: itchy/painful dermatoses, non-itchy/non-painful dermatoses and venereological diseases. Participants completed standardized psychological questionnaires: Dermatology Specific Quality of Life (DSQL), Beck Depression Inventory (BDI) and State and Trait Anxiety Inventory (STAI). Intensity of the disease and localisation of the lesions were also assessed. RESULTS: Physical aspect of QoL was mostly influenced by itchy/painful dermatoses but psychological aspect and everyday activities and choices were mostly affected by patients with non-itchy/non-painful dermatoses and venereological diseases. 4.1% of participants had serious depressive symptoms, 11.5% had high and very high anxiety symptoms as state and 15.6% as trait. However, participants with severe skin conditions were more depressed, while participants with always and sometimes exposed lesions were more anxious. CONCLUSION: It is essential to recognise subgroups of dermatovenereological patients whose treatment approach should be interdisciplinary. Further studies are needed to detect psychosocial needs of patients with venereological diseases.