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DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of six annotation categories showed that evolutionarily conserved regions are the predominant sites for differential DNA methylation and that a core region surrounding the transcriptional start site is an informative surrogate for promoter methylation. We find that 17% of the 873 analyzed genes are differentially methylated in their 5′ UTRs and that about one-third of the differentially methylated 5′ UTRs are inversely correlated with transcription. Despite the fact that our study controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.

Because of their reproductive biology, spiders are extremely promising subjects for testing hypotheses on sexual selection. Further, their genital morphology provides useful characteristics for taxonomy. However, the structure and functional morphology of the genitalia of members of most spider groups are poorly known. This is especially true for members of the Haplogynae. In this article, the female genitalia of three oonopid species are described, using light and scanning electron microscopy. The male palps are also briefly described. The female genitalia of all these three species do not correspond to the description of haplogyne genital systems given in the literature. Receptacula are lacking in the genitalia of Opopaea deserticola and Zyngoonops sp. Sperm are present in the uterus internus of members of these two species, indicating that fertilization occurs there or in the ovary. Females of Zyngoonops sp. have a pouch that possibly holds appendages on the male endites during copulation. Modifications on the endites might allow males to exert copulatory courtship. A secretory sac was found inside the receptaculum of Gamasomorpha lutzi. Previous studies on oonopids with the same type of genitalia showed that the sac contains sperm and that it can be discarded during copulation. Spermatozoa were also found inside the uterus internus of members of G. lutzi. A sclerite in the uterus wall of females of all three species might serve to lock the uterus during copulation in order to prevent sperm from getting into it, as suggested for a variety of other oonopids. The male palps of O. deserticola and Zyngoonops sp. are simple. Furrows on the emboli of G. lutzi suggest that males use the palps as copulatory courtship devices. The present study reveals the complex genital morphology of three species belonging to the little known spider family Oonopidae, and provides new insights into the function of their genitalia in the context of sexual selection.

Background As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting. Objective We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population. Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates. Results 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I–IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%). Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas. Clinical Trial Registration Number: NCT00855348

Background Soft tissue sarcomas (STS) and osteogenic sarcomas (OGS) of the limbs are rare diseases. Nowadays, most patients with STS or OGS undergo tumor resection and subsequent vascular reconstruction for potential limb preservation. Aims Due to very limited data on these complex surgical procedures, the aim of this single‐center, retrospective study was to evaluate the surgical and oncological outcomes of these patients. Methods From 2013 to 2023, demographic, clinical, surgical, and pathological data regarding tumor disease, surgical treatment, and postoperative care of a total of 10 patients with STS and OGS were identified and analyzed. Furthermore, overall survival (OS) and freedom from tumor recurrence (FFT) were retrospectively investigated among all patients. Results The mean age of the patients was 64.4 ± 22.24 years, and six women (60%) and four men (40%) were treated. Overall, 16 major arterial and venous vessels were resected and reconstructed: the lower extremity was affected in nine patients (90%). Autologous veins (n = 12, 75%), polytetrafluoroethylene (PTFE; n = 2, 12.5%), or cryopreserved allografts (n = 2, 12.5%) were mainly used for vascular reconstruction. The follow‐up ranged from 7 to 60 months, with a median OS of 48 months and a median FFT of 54 months. Overall, four patients (40%) developed local tumor recurrence at the primary surgical resection site or metastasis. The primary graft patency for all vascular reconstructions was 90% at the median follow‐up of 24 months. All revascularized limbs among these patients could be salvaged during the follow‐up period. Conclusion Treatment of patients with STS or OGS of the limbs and subsequent vascular reconstruction can be performed safely and effectively. The outcomes described in this cohort suggest that an interdisciplinary team, including vascular surgeons and a carefully planned and rigorous clinical approach, might positively influence the postoperative and oncological outcome and limb salvage.

Fine morphological details of the genitalia have large potential consequences for the understanding of the reproductive biology of a particular species, especially when mating behavioral studies are difficult to conduct. Oonopidae are a highly diverse spider family comprising a variety of species with complex female reproductive systems, which may have evolved under sexual selection by cryptic female choice. The present study describes the female genitalia of five oonopid species belonging to both conventionally recognized subfamilies by means of semi-thin sections and scanning electron microscopy. In addition, the male palps are briefly described. The organization of the female genitalia in Scaphiella hespera and Scaphiella sp. resembles the entelegyne type. A chitinized canal connects the receptaculum, where sperm are stored, with the uterus. Sperm are also present in the uterus and the canal is suggested to function as fertilization duct. The genitalia of the parthenogenetic species Triaeris stenaspis are surprisingly complex. A large sac with glands is proposed to represent the equivalent of a receptaculum in sexually reproducing females. In females of Opopaea recondita, sperm are stored in a bulge derivating from the uterus. Contractions of muscles attached to the bulge may lead to sperm dumping. The uterus can be closed by a sclerite in its anterior wall. The receptacula of females of Stenoonops reductus are joined together and contain masses of spermatozoa. Additional sperm were found in the receptacula connection suggesting that fertilization takes place there. The male palps of all the investigated species, except for S. hespera, seem to lack a distincly sclerotized sperm duct. Spermatozoa and secretions are stored in a large reservoir inside the genital bulb surrounded by glandular epithelium.

A 66-year-old female presented in the emergency department with Blue-Toe-Syndrome (BTS) and signs of osteitis of her left big toe. Imaging workup of the peripheral vasculature showed no findings. Upon invasive angiography, severe focal stenosis of the dorsalis pedis artery (DPA) could be seen at the talonavicular joint. Complete regression of the stenosis was inducible by dorsal extension in the ankle joint. Further imaging revealed an underlying subluxation of the talonavicular joint as cause of the arterial compression. Entrapment of the DPA is a rare condition and most often described in relation to connective tissue bands or variant muscular tendons (McCabe et al. 70:213–8, 2021; Weichman et al. 24:113, 2010; Smith et al.58:212–4, 2013; Griffin et al. 20:325–8; 2012). In the presented case, bony compression of the PDA due to cranial subluxation of the talus was seen as the cause of BTS and osteitis of the phalanx of the first toe.

The present study reports for the first time on the behavior prior to, during and after the copulation of a member of the haplogyne spider family, Tetrablemmidae and describes the web of this species. Prior to copulation, male and female of Indicoblemma lannaianum from Thailand sometimes avoided each other or the female scared the male away, apparently by vigorous vibrations of her body. When first copulations were initiated, they lasted from 1.21 to 3.8 h with an average of 2.25 ± 0.71 h (n = 17). Some females accepted a second male for mating 3–9 days after first mating. There was no significant difference between the duration of first and second copulations but significantly more trials were needed to induce the second copulations. In the copulatory position, the male was inverted and faced in the same direction as the female. He seized the female's opisthosoma with apophyses on his chelicerae which fit into grooves on a female's ventral plate in this way building a locking mechanism during copulation. The pedipalps were inserted alternately. The web of I. lannaianum consisted of a longish narrow sheet, which was made of many short threads forming a zigzag pattern and additional long oblique threads overdrawing the sheet and functioning as signal threads.

The MMI Symani ® is a recently approved robotic microsurgical system for surgical procedures in adults. The system enables the surgeon to create microanastomoses. Clinical applications so far include lymphatic vessels surgery and the creation of special flap plastics. The use of the system in coronary arteries has not yet been assessed. The aim of this preclinical study was to evaluate the applicability of the Symani ® surgical system in the creation of coronary anastomoses a cadaveric porcine model. A total of 12 anastomoses were performed by three senior cardiovascular surgeons on the left main coronary artery of three porcine hearts. Artificial bypasses (diameter 1 mm) were performed to the left main trunk. The anastomoses were performed with the Symani ® surgical system. Evaluation included procedure times and anastomosis leakage. All anastomoses could be successfully performed. The procedure time decreased due to the learning curve between the first anastomosis 47:28 ± 5:30 min and the last anastomosis 22:37 ± 3:25 min. The final evaluation of the anastomoses showed excellent results with low leakage. The quality of the anastomosis also improved in relation to the increasing learning curve. The Symani ® surgical system could be used to create coronary anastomoses in an acceptable time frame and without technical failures. Hence, the system appears feasible for conventional coronary surgery. Further studies in animal models are mandatory prior to clinical application.

Female Harpactea lepida possess a single genital opening leading into a diverticulum. This diverticulum shows no secretory layer. It continues posteriorly into a receptaculum which is associated with gland cells. In the two already described dysderids, Dysdera crocata and D. erythrina, the bilobed spermatheca lies anteriorly to the diverticulum. Gland cells are associated with the spermatheca and the diverticulum. In H. lepida, the sclerotized genital structures lie dorsally to the diverticulum and consist of a posterior and an anterior part. The posterior part shows a lamella extending laterally to sclerites functioning as muscle attachments. The anterior part has two roundish structures. A hollow stalk-like sclerite functioning as muscle attachment extends towards anterior. The posterior and the anterior part of the sclerotized genital structures fit together. A narrow uterine valve connecting the uterus externus with the diverticulum forms between them. It may be opened by muscles as also suggested for D. erythrina. In H. lepida, spermatozoa embedded in secretion are found in the diverticulum and the receptaculum. There is no evidence that they are stored under different conditions like in D. erythrina. Additional spermatozoa are found in the uterus externus of H. lepida which could be an indication for internal fertilization. Spermatogenesis occurs in cysts in the testes of male H. lepida. In the vasa deferentia, the ductus ejaculatorius and the palpal bulb, the spermatozoa are embedded in homogenous secretion. The palpal bulb has a distal extension bearing a crown-like structure. The embolus is situated at the base of the extension.