Phase 2C clinical trial of novel short-course regimens for the treatment of pulmonary tuberculosis: TBTC study 38/CRUSH-TB design.

Introduction: Preclinical and clinical study data show that combining bedaquiline (B or BDQ), moxifloxacin (M), and pyrazinamide (Z), known as BMZ, has potent antimicrobial activity that might shorten treatment duration for drug-susceptible pulmonary tuberculosis.

Methods/design: We describe the design of Tuberculosis Trials Consortium (TBTC) Study 38/CRUSH-TB (NCT05766267), an open-label multicenter international randomized controlled phase 2C trial that compares two four-month regimens, BMZ plus rifabutin (Rb) (2BMZRb/2BMRb) or BMZ plus delamanid (D or DLM) (2BMZD/2BMD), with standard 6-months isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE). All drugs are administered seven days per week, under direct observation, at least five days per week.

Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.

Targeted protein degradation (TPD) through the ubiquitin-proteasome system is driven by compound-mediated polyubiquitination of a protein-of-interest by an E3 ubiquitin (Ub) ligase. To date, relatively few E3s have been successfully utilized for TPD and the governing principles of functional ternary complex formation between the E3, degrader, and protein target remain elusive. FBXO22 has recently been harnessed by several groups to target different proteins for degradation.

Closing the flexion gap: Differences in femoral sizes, level of constraint, and joint anatomy between robotic assisted and conventional high volume orthopedic surgeons.

Background: One of the most common reasons for revision TKA is flexion instability. Using conventional methods, it is potentially difficult to fully assess flexion instability which can lead to pain and disability following TKA. The purpose of this study was to assess femoral size differences between surgeons with different techniques to determine the difference in femoral sizing or polyethylene constraint.

Mechanical and kinematic alignment in total knee arthroplasty: A comparative study on sizing discrepancies.

Background: Kinematic alignment (KA) in total knee arthroplasty (TKA) aims to restore natural knee kinematics by aligning components to the patient's pre-arthritic anatomy, unlike mechanical alignment (MA), which prioritizes the mechanical axis. Proper prosthesis sizing is essential for optimizing knee kinematics, yet most systems are designed around a MA philosophy, potentially affecting sizing when utilizing a KA philosophy. This study investigated whether intrinsic differences between kinematic and mechanical alignment techniques lead to discrepancies in femoral and tibial prosthesis sizing in primary TKA.

Novel Roles of Sonic Hedgehog Signaling in Retinal Patterning and Neurogenesis During Mammalian Eye Development.

The Sonic Hedgehog (Shh) signaling pathway is essential for the patterning, growth, and morphogenesis of many tissues. During early eye development, Shh is critical for the formation of the two optic vesicles, which give rise to the retina, retinal pigment epithelium (RPE), and optic stalk. It also regulates the balance between cell proliferation and differentiation during retinal histogenesis, a key process in shaping the cellular architecture of the mature retina.