Uncovering key clinical trial features influencing recruitment.

Background: Randomized clinical trials (RCT) are the foundation for medical advances, but participant recruitment remains a persistent barrier to their success. This retrospective data analysis aims to (1) identify clinical trial features associated with successful participant recruitment measured by accrual percentage and (2) compare the characteristics of the RCTs by assessing the most and least successful recruitment, which are indicated by varying thresholds of accrual percentage such as ≥ 90% vs ≤ 10%, ≥ 80% vs ≤ 20%, and ≥ 70% vs ≤ 30%. Methods: Data from the internal research registry at Columbia University Irving Medical Center and Aggregated Analysis of ClinicalTrials.gov were collected for 393 randomized interventional treatment studies closed to further enrollment. We compared two regularized linear regression and six tree-based machine learning models for accrual percentage (i.e., reported accrual to date divided by the target accrual) prediction. The outperforming model and Tree SHapley Additive exPlanations were used for feature importance analysis for participant recruitment. The identified features were compared between the two subgroups. Results: CatBoost regressor outperformed the others. Key features positively associated with recruitment success, as measured by accrual percentage, include government funding and compensation. Meanwhile, cancer research and non-conventional recruitment methods (e.g., websites) are negatively associated with recruitment success. Statistically significant subgroup differences (corrected p-value < .05) were found in 15 of the top 30 most important features. Conclusion: This multi-source retrospective study highlighted key features influencing RCT participant recruitment, offering actionable steps for improvement, including flexible recruitment infrastructure and appropriate participant compensation.

Mammography Screening Outreach Through Non-Primary Care-Based Services.

OBJECTIVE: To estimate the proportion of patients visiting urgent care centers or emergency departments or being hospitalized who were not up to date with recommended mammography screening to assess the potential impact of non-primary care-based cancer screening interventions. METHODS: Adult participants from the 2019 National Health Interview Survey were included. Among participants not up to date with breast cancer screening guidelines based on ACR recommendations, the proportion of patients reporting an urgent care, emergency department visit, or hospitalization within the last year was estimated accounting for complex survey sampling design features. Multiple variable logistic regression analyses were then conducted to evaluate the association between sociodemographic characteristics and mammography screening adherence. RESULTS: The study included 9,139 women between the ages of 40 and 74 years without history of breast cancer. Of these respondents, 44.9% did not report mammography screening within the last year. Among participants who did not report mammography screening, 29.2% reported visiting an urgent care center, 21.8% reported visiting an emergency room, and 9.6% reported being hospitalized within the last year. The majority of patients receiving non-primary care-based services, who were not up to date with mammography screening, were from historically underserved groups including Black and Hispanic patients. CONCLUSION: Nearly 10% to 30% of participants who have not obtained recommended breast cancer screening have visited non-primary care-based services including urgent care centers or emergency rooms or have been hospitalized within the last year.

Predicting strength outcomes for upper limb nerve transfer surgery in tetraplegia.

We report a retrospective study of 112 nerve transfers in 39 participants to investigate predictors of strength outcomes after nerve transfer surgery for upper limb reanimation in tetraplegia. We measured clinical and pre- and intraoperative neurophysiological assessment variables and compared them with strength outcomes 2 years after nerve transfer surgery. We found statistically significant improvement in Medical Research Council strength grades after nerve transfer surgery with lower cervical spine injuries (between one and two grades), lower donor nerve stimulation thresholds (half of a grade), greater motor evoked potential activity in recipient nerves (half of a grade) and greater muscle responses to intraoperative stimulation of donor (half of a grade) and recipient nerves (half of a grade).Level of evidence: III.

Experience with NovoSorb® Biodegradable Temporising Matrix in reconstruction of complex wounds.

BACKGROUND: The NovoSorb® Biodegradable Temporising Matrix (BTM) is a synthetic polyurethane dermal matrix used to reconstruct complex wounds including deep dermal and full-thickness burns, necrotising fasciitis and free flap donor site. We hope to further explore its potential applications in this series. METHODS: Patients who received BTM application across four centres over an 18-month period were included. Patients were followed up to assess BTM and graft take, the aesthetic, the return of sensation and complications. RESULTS: A total of 27 patients with 35 wounds were identified with a range of aetiologies. Thirty-three wounds had 100% integration of BTM at the time of sealing membrane removal. Seven wounds had partial graft loss that later healed by secondary intention. In two cases, re-epithelialisation occurred with BTM alone without split-skin graft. CONCLUSION: BTM offers a safe and reliable reconstructive option in challenging wounds that would otherwise require more complex operations.

Evolutionary history of burrowing asps (Lamprophiidae: Atractaspidinae) with emphasis on fang evolution and prey selection.

Atractaspidines are poorly studied, fossorial snakes that are found throughout Africa and western Asia, including the Middle East. We employed concatenated gene-tree analyses and divergence dating approaches to investigate evolutionary relationships and biogeographic patterns of atractaspidines with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1). We sampled 91 individuals from both atractaspidine genera (Atractaspis and Homoroselaps). Additionally, we used ancestral-state reconstructions to investigate fang and diet evolution within Atractaspidinae and its sister lineage (Aparallactinae). Our results indicated that current classification of atractaspidines underestimates diversity within the group. Diversification occurred predominantly between the Miocene and Pliocene. Ancestral-state reconstructions suggest that snake dentition in these taxa might be highly plastic within relatively short periods of time to facilitate adaptations to dynamic foraging and life-history strategies.

Dorsal Block Splinting of Volar Plate Injuries at Neutral Position.

PURPOSE: Volar plate injuries of the proximal interphalangeal joint (PIPJ) of a finger are common, often occurring in sporting or workplace incidents. Treatment of a stable dorsal dislocation entails a conservative approach, directed at preventing hyperextension and allowing the ligament to heal in position that does not negatively impact on healing. Current treatment regimens include dorsal block splinting (DBS) in 30° of flexion, which maintains the PIPJ in flexion in order to prevent any strain on the healing tissue while attempting to restore anatomical position. Recognized complications of DBS are flexion deformities of the joint and hyperextensibility. We propose that DBS in neutral position, rather than 30° flexion, reduces hyperextensibility as well as preventing flexion deformities of the PIPJ, allowing sooner return of function and participation in daily activities. METHODS: A retrospective review of patients sustaining volar plate injuries was undertaken. Inclusion criteria involved patients splinted at either 30° or neutral position, both those having undergone surgical or conservative regimens and the joint assessed as stable. Data were collected focusing on the number of hand therapy sessions, the time from injury to discharge, active angles of flexion and extension of the PIPJ, and pain. RESULTS: Over 2 years, 125 patients were treated for volar plate injuries: 20 with DBS at neutral position and 105 DBS at 30°. There were no significant differences in patient demographics. There were fewer hand therapy appointments required for those splinted in neutral position and weeks of hand therapy predischarge. There were no flexion deformities for patients undergoing DBS at neutral position, but no difference in PIPJ extension. There were no differences in hyperextensibility or pain. CONCLUSIONS: Dorsal block splinting at neutral position results in fewer flexion deformities following volar plate injuries of the PIPJ, without resultant hyperextensibility. There are fewer demands on hand therapy. Dorsal block splinting at neutral position may result in better function for patients suffering this injury, with decreased complications and quicker return to daily activities.

CXCL12-CXCR4 signalling plays an essential role in proper patterning of aortic arch and pulmonary arteries.

AIMS: Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals. METHODS AND RESULTS: Novel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning. CONCLUSION: CXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system.

The Simple Chordate Ciona intestinalis Has a Reduced Complement of Genes Associated with Fanconi Anemia.

Fanconi anemia (FA) is a human genetic disease characterized by congenital defects, bone marrow failure, and increased cancer risk. FA is associated with mutation in one of 24 genes. The protein products of these genes function cooperatively in the FA pathway to orchestrate the repair of DNA interstrand cross-links. Few model organisms exist for the study of FA. Seeking a model organism with a simpler version of the FA pathway, we searched the genome of the simple chordate Ciona intestinalis for homologs of the human FA-associated proteins. BLAST searches, sequence alignments, hydropathy comparisons, maximum likelihood phylogenetic analysis, and structural modeling were used to infer the likelihood of homology between C. intestinalis and human FA proteins. Our analysis indicates that C. intestinalis indeed has a simpler and potentially functional FA pathway. The C. intestinalis genome was searched for candidates for homology to 24 human FA and FA-associated proteins. Support was found for the existence of homologs for 13 of these 24 human genes in C. intestinalis. Members of each of the three commonly recognized FA gene functional groups were found. In group I, we identified homologs of FANCE, FANCL, FANCM, and UBE2T/FANCT. Both members of group II, FANCD2 and FANCI, have homologs in C. intestinalis. In group III, we found evidence for homologs of FANCJ, FANCO, FANCQ/ERCC4, FANCR/RAD51, and FANCS/BRCA1, as well as the FA-associated proteins ERCC1 and FAN1. Evidence was very weak for the existence of homologs in C. intestinalis for any other recognized FA genes. This work supports the notion that C. intestinalis, as a close relative of vertebrates, but having a much reduced complement of FA genes, offers a means of studying the function of certain FA proteins in a simpler pathway than that of vertebrate cells.

Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of ß-Cell Replacement.

The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.

Genetics, Morphology, Advertisement Calls, and Historical Records Distinguish Six New Polyploid Species of African Clawed Frog (Xenopus, Pipidae) from West and Central Africa.

African clawed frogs, genus Xenopus, are extraordinary among vertebrates in the diversity of their polyploid species and the high number of independent polyploidization events that occurred during their diversification. Here we update current understanding of the evolutionary history of this group and describe six new species from west and central sub-Saharan Africa, including four tetraploids and two dodecaploids. We provide information on molecular variation, morphology, karyotypes, vocalizations, and estimated geographic ranges, which support the distinctiveness of these new species. We resurrect Xenopus calcaratus from synonymy of Xenopus tropicalis and refer populations from Bioko Island and coastal Cameroon (near Mt. Cameroon) to this species. To facilitate comparisons to the new species, we also provide comments on the type specimens, morphology, and distributions of X. epitropicalis, X. tropicalis, and X. fraseri. This includes significantly restricted application of the names X. fraseri and X. epitropicalis, the first of which we argue is known definitively only from type specimens and possibly one other specimen. Inferring the evolutionary histories of these new species allows refinement of species groups within Xenopus and leads to our recognition of two subgenera (Xenopus and Silurana) and three species groups within the subgenus Xenopus (amieti, laevis, and muelleri species groups).

Between a rock and a hard polytomy: rapid radiation in the rupicolous girdled lizards (Squamata: Cordylidae).

Girdled lizards (Cordylidae) are sub-Saharan Africa's only endemic squamate family and contain 80 nominal taxa, traditionally divided into four genera: Cordylus, Pseudocordylus, Chamaesaura and Platysaurus. Previous phylogenetic analysis revealed Chamaesaura and Pseudocordylus to be nested within Cordylus, and the former genera were sunk into the later. This taxonomic revision has received limited support due to the study's poor taxon sampling, weakly supported results and possible temporary nomenclatural instability. Our study analyzes three nuclear and three mitochondrial genes from 111 specimens, representing 51 in-group taxa. Parsimony, likelihood and Bayesian analyses of concatenated and partitioned datasets consistently recovered a comb-like tree with 10, well-supported, monophyletic lineages. Our taxonomic reassessment divides the family into 10 genera, corresponding to these well-supported lineages. Short internodes and low support between the non-platysaur lineages are consistent with a rapid radiation event at the base of the viviparous cordylids.