Frequency of Tommy John Surgery in NCAA Division I College Pitchers Versus Weather Conditions.

Background: Ulnar collateral ligament reconstruction (UCLR) is a common elbow procedure in baseball pitchers. Previous studies of Major League Baseball pitchers identified the weather as a potential risk factor, as warmer climates enable more annual playing time and increase overuse injury risks.

Purpose: To determine whether weather conditions play a role in UCLR rates and timing for National Collegiate Athletic Association (NCAA) Division I (D1) collegiate pitchers in the United States.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma.

Background: Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking.

Return to play and performance after patellar fracture in American professional sports: a case-control cohort analysis.

Objectives: This study describes the effects of patellar fracture on return to play (RTP) and functional outcomes among athletes in American professional sports.

Methods: Professional athletes from the National Football League (NFL), National Basketball Association (NBA), Major League Baseball (MLB), and National Hockey League (NHL) who suffered a patellar fracture between January 1965 and December 2021 were identified through injury reports and public archives. Performance scores, play time, and games played were collected for the season preceding patellar fracture and 2 seasons after RTP, and differences in recorded metrics compared to pre-injury levels and matched controls were analyzed.

EGFR and EGFRvIII coopt host defense pathways, promoting progression in glioblastoma.

Background: Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma.

Methods: We used phospho-proteomics, RNA-sequencing, TCGA data and glioblastoma cell culture and mouse models to study the signal transduction mediated by EGFR and EGFRvIII.

Results: We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockout of TLR2 dramatically improved survival in orthotopic glioblastoma xenografts.

Invited review: Limitations to current mineral requirement systems for cattle and potential improvements.

The mineral requirements or recommendations generated by various NASEM committees are used by many ration formulation programs. The current NASEM dairy requirement system uses the factorial approach (requirements for maintenance, lactation, gestation, and growth) for most minerals, but when data or equations were not available to estimate factorial requirements the committee used available data to estimate adequate intake values. The current beef NASEM uses the factorial method for Ca and P and recommendations for the other minerals.

Relative availability of 5 inorganic magnesium sources in nonpregnant nonlactating Holstein cows.

Inorganic sources of Mg are commonly used in dairy cow diets, but their availability varies significantly. This study assessed the relative availability of 4 commonly used inorganic Mg sources and a novel alkalinizing proprietary mineral blend (PMB; Multesium; GLC Minerals LLC, Green Bay, WI). The study was a duplicated 6 × 6 Latin square, with 12 nonlactating, nonpregnant Holstein dairy cows assigned to a square based on BW and parity.

Reliability of the International Spinal Cord Injury Physical Therapy-Occupational Therapy Basic Data Set.

In interventional clinical trials for persons with spinal cord injury (SCI), the influence of experimental biological, pharmacological, or device-related interventions must be differentiated from that of physical and occupational therapy interventions, as rehabilitation influences motor-related outcomes. The International Spinal Cord Injury (ISCI) Physical TherapyOccupational Therapy Basic Data Set (PT-OT BDS) was developed with the intent to track the content and time of rehabilitation interventions that are delivered concurrently with experimental interventions. We assessed the reliability of the PT-OT BDS based on agreement between users.

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.

SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns.

Preventing Iatrogenic Fibula Fractures Using the Push-Pull Technique: A Biomechanical Comparison of Unicortical Versus Bicortical Post Screws.

Background: Displaced diaphyseal fractures can be reduced using the push-pull technique, wherein a plate is affixed to the distal fragment of the fracture, a post screw is placed proximal to the plate, and a lamina spreader creates distraction. This study evaluated the load to failure and mechanism of failure of bicortical and unicortical post screws during reduction.

Materials And Methods: Four matched pairs of cadaver legs were subjected to a 2-cm oblique osteotomy simulating a displaced, oblique diaphyseal fracture.

Early rhombic lip Protogenin stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.

We identify a population of Protogenin-positive (PRTG) MYC NESTIN stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL). Oncogenic transformation of early Prtg rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG stem cells grow adjacent to a human-specific interposed vascular plexus in the RL, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma.

Aurora Kinase A inhibition enhances DNA damage and tumor cell death with I-MIBG therapy in high-risk neuroblastoma.

Background: Neuroblastoma is the most common extra-cranial pediatric solid tumor. I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma.

MYC phase separation selectively modulates the transcriptome.

Dysregulation and enhanced expression of MYC transcription factors (TFs) including MYC and MYCN contribute to the majority of human cancers. For example, MYCN is amplified up to several hundredfold in high-risk neuroblastoma. The resulting overexpression of N-myc aberrantly activates genes that are not activated at low N-myc levels and drives cell proliferation.

Fluid Dynamic Study of the Penn State Pediatric Total Artificial Heart.

Penn State University is developing a pediatric total artificial heart (TAH) as a bridge-to-transplant device that supports infants and small children with single ventricle anomalies or biventricular heart failure to address high waitlist mortality rates for pediatric patients with severe congenital heart disease (CHD). Two issues with mechanical circulatory support devices are thrombus formation and thromboembolic events. This in vitro study characterizes flow within Penn State's pediatric total artificial heart under physiological operating conditions.

Effect of acid detergent lignin concentration for diets formulated to be similar in neutral detergent fiber content on energy utilization in lactating Jersey cows.

Lignin is a polyphenolic polymer that is an important factor in limiting fiber digestibility by ruminants. The objective of the current study was to evaluate lignin's effects on whole animal energy utilization in diets similar in NDF content. A low-lignin (LoLig) diet was formulated to contain 32.

Development of the PSU Child Pump.

The Pennsylvania State University (PSU) Child Pump, a centrifugal continuous-flow ventricular assist device (cf-VAD), is being developed as a suitable long-term implantable device for pediatric heart failure patients between 10 and 35 kg, body surface area (BSA) of 0.5-1.2 m 2 , 1-11 years of age, and requiring a mean cardiac output of 1.

ALK upregulates POSTN and WNT signaling to drive neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALK) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma.

Aurora Kinase A inhibition enhances DNA damage and tumor cell death with I-MIBG therapy in high-risk neuroblastoma.

Background: Neuroblastoma is the most common extra-cranial pediatric solid tumor. I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma.

Development and validation of a rabbit model of non-ventilated pneumonia for preclinical drug development.

Background: New drugs targeting antimicrobial resistant pathogens, including , have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.

Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.

Effect of screw angulation on the bending performance of polyaxial locking interfaces: a micro-CT evaluation.

Polyaxial locking plates rely on a specific thread-to-thread interface of the screw head and the plate hole. The objective of this study was to evaluate the mechanical performance of single screw interfaces when inserted off-axis and to establish correlations between those parameters and the engagement of the screw head and the plate hole thread. Three polyaxial locking screw systems were inserted into the corresponding plates at various angles (0°, 5°, 10°, and 15° off-axis).