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Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heterogeneous tissues, where assumptions about data distribution (e.g. sparsity, label-specific distribution, and lateral-axial similarity) and system priors (e.g. independent and identically distributed noise and linear shift-invariant point-spread functions are often invalid. Here, we introduce SSAI-3D, a weakly physics-informed, domain-shift-resistant framework for robust isotropic three-dimensional imaging. SSAI-3D enables robust axial deblurring by generating a diverse, noise-resilient, sample-informed training dataset and sparsely fine-tuning a large pre-trained blind deblurring network. SSAI-3D is applied to label-free nonlinear imaging of living organoids, freshly excised human endometrium tissue, and mouse whisker pads, and further validated in publicly available ground-truth-paired experimental datasets of three-dimensional heterogeneous biological tissues with unknown blurring and noise across different microscopy systems. Three-dimensional imaging is crucial for biomedical research, yet microscopy faces axial resolution limitations. Here, authors introduce SSAI-3D that adapts training datasets and sparsely finetunes a network to achieve robust results across various biological samples and microscopy systems.

A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM “sheddase” function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor–driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.

Purpose To compare laparoscopic supracervical hysterectomy (LSH) with total laparoscopic hysterectomy (TLH) with regard to relevant surgical parameters and risk factors of conversion to laparotomy and complications. Methods This prospective, open, single-center, interventional study included women with benign gynecologic disease who underwent standardized LSH or TLH. The techniques were compared for conversion rate and mean operating time, hemoglobin drop, hospital stay, and complication rates using descriptive statistics and standard non-parametric statistical tests. Risk factors of conversion and complications were identified by logistic regression analysis. Results During January 2003 to December 2010, 1,952 women [mean age (SD): 47.5 (7.2) years] underwent LSH [1,658 (84.9 %)] or TLH [294 (15.1 %)], mostly (>70 %) for uterine fibroids. Significant differences in surgical parameters were observed for conversion rate (LSH/TLH: 2.6/6.5 %), mean operating time [87 (34)/103 (36) min], hemoglobin drop [1.3 (0.8)/1.6 (1.0) g/dL], and hospital stay [4.3 (1.5)/4.9 (2.8) days]. Overall intraoperative (0.2/0.7 %) and long-term (>6 weeks) post-operative (0.8/1.7 %) complication rates did not differ significantly, but the short-term LSH complication rate was significantly lower (0.6 vs. 4.8 %). Spotting (LSH, 0.2 %) and vaginal cuff dehiscence (TLH, 0.7 %) were long-term method-specific complications. Logistic regression showed that uterine weight and extensive adhesiolysis were significant factors for conversion while previous surgery, age, and BMI were not. Major risk factors of short-term complications were age, procedure (LSH/TLH), and extensive adhesions. Conclusions Both procedures proved effective and were well tolerated. LSH performed better than TLH regarding most outcome measures. LSH is associated with very low rates of re-operation and spotting.

PurposeThis study aimed at evaluating the diagnostic yield for core needle biopsies of uterine fibroids before laparoscopic radiofrequency volumetric thermal ablation (RFVTA) with the aim of sonographic imaging. This study was in the context of a randomized, prospective, single-center, longitudinal comparative study in which RFVTA and laparoscopic myomectomy for symptomatic uterine fibroids were compared.MethodsAll patients of the RFVTA-arm received a core needle biopsy under the guidance of an intraoperative laparoscopic ultrasound system. The Tissue samples were observed histologically.Results24 patients were included and received in the median 3.17 biopsies (range 2–7). 45.8% of the fibroids were intramural. In 92% uterine leiomyoma was detected, in 4% a cell rich leiomyoma and in 4% a smooth muscle tumor with uncertain malignant potential (STUMP). There were no complications caused by core needle biopsy.ConclusionsUltrasound guided core needle biopsy can be used to receive a histological result before treating uterine fibroids with thermo surgical methods like RFVTA.

A groundwork and milestone for an innovative, trendsetting, and international school of thought in gynecology. A superb work of art as well as an outstanding clinical reference, this book continues the rich tradition of earlier editions by providing unparalleled coverage of the entire field of gynecologic surgery. This new fourth edition offers completely updated content, user-friendly features, and the cornerstone of the book: an art program of astounding quality. It is indispensable for gynecologic surgeons or residents who need to review, refresh, or fine-tune their skills in preparation for surgery, while being alerted to pitfalls and possible complications at every juncture. Special features of the new 4th edition of this world-famous atlas: * Nearly 1, 200 stunning watercolor drawings that provide a visual depiction of operative steps unequalled in the literature * Detailed, point-by-point descriptions of routine as well as more complex procedures * Full coverage of abdominal, vaginal, and endoscopic approaches in sections on the adnexa, uterus, vulva/vagina, and pelvic floor * Introduction of the new \"Procedure Navigator\" section, which facilitates a convenient search from disease to indication to medical or surgical treatment of choice * A truly international perspective, with leading specialists from Europe and the United States sharing heir clinical experience and wisdom Complete with expert foundational chapters on pre- and postoperative treatment, informed consent, instrumentation, indications and contraindications, risks and complications, and more, this book is both beautiful and informative. Its step-by-step didactic concept is ideal for residents-in-training, while its detailed description of both common and rare procedures makes it useful for experienced surgeons. For all specialists, Atlas of Gynecologic Surgery is a standard, must-have reference on current methodology and clinical protocols in this rapidly evolving field.

PurposeThis review covers the most recent evidence to discuss the incidence of occult uterine sarcoma, whether morcellation increases tumor dissemination or mortality, and whether there is a difference between different types of morcellation. We will also discuss techniques to reduce the spread of an undiagnosed uterine sarcoma.MethodA comprehensive literature search was made in Pubmed, Medline, the Cochrane Library, and Google Scholar for articles related to the incidence of occult uterine sarcoma after morcellation.ResultsFibroids are benign uterine tumors and are a common indication for gynecologic surgery. Increasingly, gynecologists are approaching these surgeries with minimally invasive techniques. Uterine sarcomas are rare malignant mesenchymal tumors that are difficult to distinguish preoperatively from uterine fibroids.ConclusionDuring a minimally invasive surgery, there is a risk of disseminating an occult sarcoma during tissue extraction. Minimally invasive gynecologists are tasked with balancing taking a minimally invasive approach, which is shown to result in better patient outcomes, with minimizing the risk of spreading an occult sarcoma.

Introduction Office hysteroscopy (OH) remains a valuable but underutilized tool in evaluation and treatment of abnormal uterine bleeding,1 Fostering a clinic environment in which patients have access to a \"one-stop shopping\" experience has benefits for them, the gynecologist,2-5 and the medical system.6,7 In our minimally invasive gynecologic surgery (MIGS) clinic with only two providers, we perform approximately 15 OHs each week while we see our normal patient schedule. [...]the minimal pressure to obtain uterine distention is the pressure that should be used. Some studies have shown benefits of cervical preparation with vaginal misoprostol before OH.33-35 However, a meta-analysis of randomized controlled trials evaluating use of cervical preparations to reduce pain during outpatient hysteroscopy showed no reduction in pain in premenopausal or postmenopausal women who required cervical dilation of 5 mm or less.36 We do not routinely use any cervical preparation, since in our experience, most patients do not require cervical dilation with our vaginoscopic approach and pre-procedure misoprostol can be associated with bothersome side effects such as pre-procedural cramping and greater leaking of fluid.37 Be prepared OH is a safe procedure with a complication rate of less than 1%.38 However, unusual events such as severe vagal reactions, drug allergies and overdose, uterine perforation, bleeding and various cardiac events do occur. Even without using oral or local anesthesia, over 90% of patients can successfully undergo a diagnostic hysteroscopy, RESOURCES Office hysteroscopy * The American Congress of Obstetricians and Gynecologists: The use and development of checklists in obstetrics and gynecology acog.org/Resources-And-Publications/Committee-Opinions/Committee-onPatient-Safety-and-Quality-Improvement/The-Use-and-Development-ofChecklists-in-Obstetrics-and-Gynecology * Centers for Medicare and Medicaid Services: The physician fee schedule search cms.gov/apps/physician-fee-schedule/search/search-criteria.aspx DRS. WONG AND MILLER report no potential conflicts of interest with regard to this article.

The human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone cycles is linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during IL-1β-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases. Competing Interest Statement L.G.G. and V.H.G. have a patent application pending related to the hydrogel system. The rest of the authors have no competing interests. Footnotes * Manuscript text was revised to emphasize the key findings and provide a more detailed discussion and interpretation of the data presented; the conclusions remains the same. Section 3 was revised and additional figures were added to clarify points that were left unclear in the first version; additional references were included.