The Pelvic Floor Disorders Network: Evolution Over Two Decades of Female Pelvic Floor Research.

Importance: This review aimed to describe research initiatives, evolution, and processes of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Pelvic Floor Disorders Network (PFDN). This may be of interest and inform researchers wishing to conduct multisite coordinated research initiatives as well as to provide perspective to all urogynecologists regarding how the PFDN has evolved and functions.

Study Design: Principal investigators of several PFDN clinical sites and Data Coordinating Center describe more than 20 years of development and maturation of the PFDN.

Cerebral injury and retinopathy as risk factors for blindness in extremely preterm infants.

Objective: This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP).

Design: Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18-26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants.

Correlation of Digital Rectal Examination and Anorectal Manometry with Patient-Reported Outcomes Among Women with Fecal Incontinence.

Introduction And Hypothesis: Standardized digital rectal examination (DRE) correlates with anorectal manometry (ARM) measures. However, less is known about the relationship between DRE/ARM measures and patient-reported outcomes (PROs), especially among women with fecal incontinence (FI). Our aims were to evaluate associations between DRE and ARM measures and compare PROs with diagnostic evaluation measures for women with FI.

On synergy between ultrahigh throughput screening and machine learning in biocatalyst engineering.

Protein design and directed evolution have separately contributed enormously to protein engineering. Without being mutually exclusive, the former relies on computation from first principles, while the latter is a combinatorial approach based on chance. Advances in ultrahigh throughput (uHT) screening, next generation sequencing and machine learning may create alternative routes to engineered proteins, where functional information linked to specific sequences is interpreted and extrapolated .

The association of the room air challenge with long-term outcomes in extremely preterm infants.

Objective: Evaluate the association between results of the room air (RA) challenge and death, respiratory morbidity, and neurodevelopmental impairment (NDI) at 2 years' corrected age.

Study Design: Cohort study of infants born <27 weeks' gestational age who underwent a RA challenge to determine BPD diagnosis at 36 weeks postmenstrual age.

Results: Of 1022 infants eligible for the RA challenge, 554 underwent testing and 223 passed.

Selection of a promiscuous minimalist cAMP phosphodiesterase from a library of de novo designed proteins.

The ability of unevolved amino acid sequences to become biological catalysts was key to the emergence of life on Earth. However, billions of years of evolution separate complex modern enzymes from their simpler early ancestors. To probe how unevolved sequences can develop new functions, we use ultrahigh-throughput droplet microfluidics to screen for phosphoesterase activity amidst a library of more than one million sequences based on a de novo designed 4-helix bundle.

Dietary Intake and Symptom Severity in Women with Fecal Incontinence.

Introduction And Hypothesis: The goal of this study was to determine whether dietary fat/fiber intake was associated with fecal incontinence (FI) severity.

Methods: Planned supplemental analysis of a randomized clinical trial evaluating the impact of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All subjects completed a food screener questionnaire at baseline.

Transforming Big Data into AI-ready data for nutrition and obesity research.

Objective: Big Data are increasingly used in obesity and nutrition research to gain new insights and derive personalized guidance; however, this data in raw form are often not usable. Substantial preprocessing, which requires machine learning (ML), human judgment, and specialized software, is required to transform Big Data into artificial intelligence (AI)- and ML-ready data. These preprocessing steps are the most complex part of the entire modeling pipeline.

Correlation Between Mobile-Application Electronic Bowel Diary and Validated Questionnaires in Women with Fecal Incontinence.

Introduction And Hypothesis: Despite growing interest in a mobile-app bowel diary to assess fecal incontinence (FI) symptoms, data are limited regarding the correlation between mobile-app diary and questionnaire-based outcomes. The primary aim is to determine whether percentage reduction in FI episodes (FIEs)/week recorded on a mobile-app diary correlates with changes in scores of validated FI-symptom measures from baseline to 12 weeks in women with FI undergoing percutaneous tibial nerve stimulation (PTNS) versus sham.

Methods: This is a planned secondary analysis of a multicenter randomized trial in which women with FI underwent PTNS or sham.

High-Throughput Engineering of Nonribosomal Extension Modules.

Nonribosomal peptides constitute an important class of natural products that display a wide range of bioactivities. They are biosynthesized by large assembly lines called nonribosomal peptide synthetases (NRPSs). Engineering NRPS modules represents an attractive strategy for generating customized synthetases for the production of peptide variants with improved properties.

Age of diagnosis for children with chromosome 15q syndromes.

Objective: The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman syndrome [AS], Prader-Willi syndrome [PWS], and duplication 15q syndrome [Dup15q]).

Methods: Data about the diagnostic process for each condition were contributed by the advocacy organizations. Median and interquartile ranges were calculated for each condition by molecular subtype and year.

Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study.

Objective: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

Study Design: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

Results: We assessed 1452 EP infants and 183 TR infants.

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study.

Objective: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery.

Design: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study.

Setting: Eight clinical sites in the US Pelvic Floor Disorders Network.

Adherence to Perioperative Behavioral Therapy With Pelvic Floor Muscle Training in Women Receiving Vaginal Reconstructive Surgery for Pelvic Organ Prolapse.

Objective: The objective of this study was to describe adherence to behavioral and pelvic floor muscle training in women undergoing vaginal reconstructive surgery for organ prolapse and to examine whether adherence was associated with 24-month outcomes.

Methods: Participants were women ≥18 years of age, with vaginal bulge and stress urinary incontinence symptoms, planning to undergo vaginal reconstructive surgery for stages 2 to 4 vaginal or uterine prolapse. They were randomized to either sacrospinous ligament fixation or uterosacral ligament suspension and to perioperative behavioral and pelvic floor muscle training or usual care.

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

Importance: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

Objective: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

Ultrahigh-Throughput Enzyme Engineering and Discovery in Compartments.

Novel and improved biocatalysts are increasingly sourced from libraries via experimental screening. The success of such campaigns is crucially dependent on the number of candidates tested. Water-in-oil emulsion droplets can replace the classical test tube, to provide compartments as an alternative screening format, containing genotype and phenotype and enabling a readout of function.

Ultra-High-Throughput Absorbance-Activated Droplet Sorting for Enzyme Screening at Kilohertz Frequencies.

Droplet microfluidics is a valuable method to "beat the odds" in high throughput screening campaigns such as directed evolution, where valuable hits are infrequent and large library sizes are required. Absorbance-based sorting expands the range of enzyme families that can be subjected to droplet screening by expanding possible assays beyond fluorescence detection. However, absorbance-activated droplet sorting (AADS) is currently ∼10-fold slower than typical fluorescence-activated droplet sorting (FADS), meaning that, in comparison, a larger portion of sequence space is inaccessible due to throughput constraints.

Characteristics associated with subjective and objective measures of treatment success in women undergoing percutaneous tibial nerve stimulation vs sham for accidental bowel leakage.

Introduction And Hypothesis: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial.

Methods: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St.

Association Between Enlarged Genital Hiatus and Composite Surgical Failure After Vaginal Hysterectomy With Uterosacral Ligament Suspension.

Importance: The impact of a persistently enlarged genital hiatus (GH) after vaginal hysterectomy with uterosacral ligament suspension on prolapse outcomes is currently unclear.

Objectives: This secondary analysis of the Study of Uterine Prolapse Procedures Randomized trial was conducted among participants who underwent vaginal hysterectomy with uterosacral ligament suspension. We hypothesized that women with a persistently enlarged GH size would have a higher proportion of prolapse recurrence.

Acoustic sorting of microfluidic droplets at kHz rates using optical absorbance.

Droplet microfluidics allows one to address the ever-increasing demand to screen large libraries of biological samples. Absorbance spectroscopy complements the golden standard of fluorescence detection by label free target identification and providing more quantifiable data. However, this is limited by speed and sensitivity.

Reoperation for prolapse recurrence after sacrospinous mesh hysteropexy: characteristics of women choosing retreatment.

Introduction And Hypothesis: Factors that contribute to reoperation and surgical approaches for the management of recurrent uterovaginal prolapse after vaginal mesh hysteropexy (mesh hysteropexy) are unknown. We aimed to describe surgical management of pelvic organ prolapse recurrence after vaginal mesh hysteropexy, and patient characteristics in those who chose reoperation.

Methods: This is a descriptive analysis of women who experienced treatment failure within 5 years of mesh hysteropexy in a multi-site randomized trial.

Site-Specific Protein Labeling and Generation of Defined Ubiquitin-Protein Conjugates Using an Asparaginyl Endopeptidase.

Asparaginyl endopeptidases (AEPs) have recently been widely utilized for peptide and protein modification. Labeling is however restricted to protein termini, severely limiting flexibility and scope in creating diverse conjugates as needed for therapeutic and diagnostic applications. Here, we use genetic code expansion to site-specifically modify target proteins with an isopeptide-linked glycylglycine moiety that serves as an acceptor nucleophile in AEP-mediated transpeptidation with various probes containing a tripeptidic recognition motif.

Critical review of bariatric surgical outcomes in patients with Prader-Willi syndrome and other hyperphagic disorders.

Objective: The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity.

Methods: Systematic published literature review used the following search terms: "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders.

Percutaneous Tibial Nerve Stimulation vs Sham Stimulation for Fecal Incontinence in Women: NeurOmodulaTion for Accidental Bowel Leakage Randomized Clinical Trial.

Introduction: To determine whether percutaneous tibial nerve stimulation (PTNS) is superior to sham stimulation for the treatment of fecal incontinence (FI) in women refractory to first-line treatments.

Methods: Women aged 18 years or older with ≥3 months of moderate-to-severe FI that persisted after a 4-week run-in phase were randomized 2:1 (PTNS:sham stimulation) to 12 weekly 30-minute sessions in this multicenter, single-masked, controlled superiority trial. The primary outcome was change from baseline FI severity measured by St.