Temporal recording of mammalian development and precancer.

Key to understanding many biological phenomena is knowing the temporal ordering of cellular events, which often require continuous direct observations [1, 2]. An alternative solution involves the utilization of irreversible genetic changes, such as naturally occurring mutations, to create indelible markers that enables retrospective temporal ordering [3-8]. Using NSC-seq, a newly designed and validated multi-purpose single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo , while incorporating assigned cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during murine embryonic development and identified new intestinal epithelial progenitor states by their unique genetic histories. NSC-seq analysis of murine adenomas and single-cell multi-omic profiling of human precancers as part of the Human Tumor Atlas Network (HTAN), including 116 scRNA-seq datasets and clonal analysis of 418 human polyps, demonstrated the occurrence of polyancestral initiation in 15-30% of colonic precancers, revealing their origins from multiple normal founders. Thus, our multimodal framework augments existing single-cell analyses and lays the foundation for in vivo multimodal recording, enabling the tracking of lineage and temporal events during development and tumorigenesis.

Return to play after anterior cruciate ligament reconstruction in National Football League athletes.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is a common and potentially career-threatening injury in the National Football League (NFL). The return to play (RTP) percentage and the factors affecting RTP after ACL reconstruction in NFL players are not well defined. PURPOSE: To determine the actual rate of return to professional football play in the NFL after ACL reconstruction surgery and to determine what factors can predict ability to RTP. We hypothesize that the RTP percentage in this unique patient population will differ from previously reported populations. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-nine NFL athletes who had undergone primary ACL reconstruction at our institution were followed to determine their RTP percentages and factors predicting RTP. RESULTS: Sixty-three percent (31 of 49) of NFL athletes returned to NFL game play at an average of 10.8 months after surgery. Age at time of surgery, position, and the type and number of procedures were not significantly different between those who did and did not return to play. The average number of games before surgery was 51 for those who did return to play and 28 for those who did not (P = .039). The odds ratio favoring RTP was 5.5 (P = .016) for those players who had more than 4 years of NFL experience before surgery. The average NFL draft round was 3.4 for the group who returned to play and 6.4 for those who did not (P < .001). The odds ratio favoring RTP was 12.2 (P < .001) for those players drafted in the first 4 rounds of the NFL draft compared with those drafted after the fourth round. CONCLUSIONS: The RTP rates after ACL reconstruction in NFL football players are lower than previously perceived. More experienced and established athletes are more likely to return to competition at the same level after this procedure than those with less professional experience. Being selected in the first 4 rounds of the NFL draft was highly predictive of RTP.

Delayed presentation of cervical ligamentous instability without radiologic evidence.

STUDY DESIGN: A case of delayed presentation of unstable cervical ligamentous injury without radiologic evidence is presented. OBJECTIVES: To report a rare case of delayed presentation of cervical ligamentous injury without radiologic evidence, and to discuss diagnosis, initial management, and techniques of operative stabilization. SUMMARY OF BACKGROUND DATA: The literature is reviewed. METHODS: A 48-year-old man who sustained a nondisplaced unilateral C6 pillar fracture with no radiologic evidence of ligamentous injury returned for follow-up with radicular pain and bilateral perched facets at C5-C6. RESULTS: Closed reduction of the cervical subluxation was performed via cervical traction, and subsequent surgical stabilization was undertaken with anterior cervical discectomy and instrumented arthrodesis of C5-C6 with structural interbody autograft. The patient wore a cervical brace for 6 weeks after surgery, and progressed to a stable fusion with pain resolution and no neurologic sequelae. CONCLUSIONS: This is a rare reported case of delayed presentation of an unstable ligamentous injury in a nondisplaced cervical pillar fracture without initial radiologic evidence of instability. If any reason to suspect ligamentous injury exists, workup with upright cervical lateral radiographs, flexion/extension radiographs, or magnetic resonance imaging should be obtained. Awake, closed reduction with cervical traction followed by surgical stabilization with an anterior discectomy and instrumented arthrodesis with structural autograft achieved stable fixation.