Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

Predictive Modeling of Medical and Orthopaedic-Related 90-Day Readmissions Following Primary Total Hip Arthroplasty.

BACKGROUND: The rate of unplanned hospital readmissions following total hip arthroplasty (THA) varies from 3 to 10%, representing a major economic burden. However, it is unknown if specific factors are associated with different types of complications (i.e., medical or orthopaedic-related) that lead to readmissions. Therefore, this study aimed to: (1) determine the overall, medical-related, and orthopaedic-related 90-day readmission rate; and (2) develop a predictive model for risk factors affecting overall, medical-related, and orthopaedic-related 90-day readmissions following THA. METHODS: A prospective cohort of primary unilateral THAs performed at a large tertiary academic center in the United States from 2016 to 2020 was included (n = 8,893 patients) using a validated institutional data collection system. Orthopaedic-related readmissions were specific complications affecting the prosthesis, joint, and surgical wound. Medical readmissions were due to any other cause requiring medical management. Multivariable logistic regression models were used to investigate associations between pre-specified risk factors and 90-day readmissions, as well as medical/orthopaedic-related readmissions independently. RESULTS: Overall, the rate of 90-day readmissions was 5.6%. Medical readmissions (4.2%) were found to be more prevalent than orthopaedic-related readmissions (1.4%). The area under curve (AUC) for the 90-day readmission model was 0.71 (95% CI [confidence interval]: 0.69 to 0.74). Factors significantly associated with medical-related readmissions were advanced age, black race, education, Charlson comorbidity index (CCI), surgical approach, opioid overdose risk (NARX) score, and nonhome discharge. In contrast, risk factors linked to orthopaedic-related readmissions encompassed body mass index (BMI), PROM phenotype, non-osteoarthritis indication, NARX, and non-home discharge. CONCLUSION: Of the overall 90-day readmissions following primary THA, 75% were due to medical-related complications. Our successful predictive model for complication-specific 90-day readmissions highlights how different risk factors may disproportionately influence medical versus orthopaedic-related readmissions, suggesting that patient-specific, tailored preventive measures could reduce postoperative readmissions in the current value-based healthcare setting.

High Area Deprivation Index is Associated With Not Achieving the Patient-acceptable Symptom State After TKA.

BACKGROUND: The Area Deprivation Index (ADI) approximates a patient's relative socioeconomic deprivation. The ADI has been associated with increased healthcare use after TKA, but it is unknown whether there is an association with patient-reported outcome measures (PROMs). Given that a high proportion of patients are dissatisfied with their results after TKA, and the large number of these procedures performed, knowledge of factors associated with PROMs may indicate opportunities to provide support to patients who might benefit from it. QUESTIONS/PURPOSES: (1) Is the ADI associated with achieving the minimum clinically important difference (MCID) for the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, Joint Replacement (JR), and Physical Function (PS) short forms after TKA? (2) Is the ADI associated with achieving the patient-acceptable symptom state (PASS) thresholds for the KOOS pain, JR, and PS short forms? METHODS: This was a retrospective study of data drawn from a longitudinally maintained database. Between January 2016 and July 2021, a total of 12,239 patients underwent unilateral TKA at a tertiary healthcare center. Of these, 92% (11,213) had available baseline PROM data and were potentially eligible. An additional 21% (2400) of patients were lost before the minimum study follow-up of 1 year or had incomplete data, leaving 79% (8813) for analysis here. The MCID is the smallest change in an outcome score that a patient is likely to perceive as a clinically important improvement, and the PASS refers to the threshold beyond which patients consider their symptoms acceptable and consistent with adequate functioning and well-being. MCIDs were calculated using a distribution-based method. Multivariable logistic regression models were created to investigate the association of ADI with 1-year PROMs while controlling for patient demographic variables. ADI was stratified into quintiles based on their distribution in our sample. Achievement of MCID and PASS thresholds was determined by the improvement between preoperative and 1-year PROMs. RESULTS: After controlling for patient demographic factors, ADI was not associated with an inability to achieve the MCID for the KOOS pain, KOOS PS, or KOOS JR. A higher ADI was independently associated with an increased risk of inability to achieve the PASS for KOOS pain (for example, the odds ratio of those in the ADI category of 83 to 100 compared with those in the 1 to 32 category was 1.34 [95% confidence interval 1.13 to 1.58]) and KOOS JR (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.29 [95% CI 1.10 to 1.53]), but not KOOS PS (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.09 [95% CI 0.92 to 1.29]). CONCLUSION: Our findings suggest that social and economic factors are associated with patients' perceptions of their overall pain and function after TKA, but such factors are not associated with patients' perceptions of their improvement in symptoms. Patients from areas with higher deprivation may be an at-risk population and could benefit from targeted interventions to improve their perception of their healthcare experience, such as through referrals to nonemergent medical transportation and supporting applications to local care coordination services before proceeding with TKA. Future research should investigate the mechanisms underlying why socioeconomic disadvantage is associated with inability to achieve the PASS, but not the MCID, after TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Surgeon Performance as a Predictor for Patient-Reported Outcomes After Arthroscopic Partial Meniscectomy.

Background: Surgeon performance has been investigated as a factor affecting patient outcomes after orthopaedic procedures to improve transparency between patients and providers. Purpose/Hypothesis: The purpose of this study was to identify whether surgeon performance influenced patient-reported outcomes (PROMs) 1 year after arthroscopic partial meniscectomy (APM). It was hypothesized that there would be no significant difference in PROMs between patients who underwent APM from various surgeons. Study Design: Case-control study; Level of evidence, 3. Methods: A prospective cohort of 794 patients who underwent APM between 2018 and 2019 were included in the analysis. A total of 34 surgeons from a large multicenter health care center were included. Three multivariable models were built to determine whether the surgeon-among demographic and meniscal pathology factors-was a significant variable for predicting the Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain subscale, the Patient Acceptable Symptom State (PASS), and a 10-point improvement in the KOOS-Pain at 1 year after APM. Likelihood ratio (LR) tests were used to determine the significance of the surgeon variable in the models. Results: The 794 patients were identified from the multicenter hospital system. The baseline KOOS-Pain score was a significant predictor of outcome in the 1-year KOOS-Pain model (odds ratio [OR], 2.1 [95% CI, 1.77-2.48]; P < .001), the KOOS-Pain 10-point improvement model (OR, 0.57 [95% CI, 0.44-0.73), and the 1-year PASS model (OR, 1.42 [95% CI, 1.15-1.76]; P = .002) among articular cartilage pathology (bipolar medial cartilage) and patient-factor variables, including body mass index, Veterans RAND 12-Item Health Survey-Mental Component Score, and Area Deprivation Index. The individual surgeon significantly impacted outcomes in the 1-year KOOS-Pain mixed model in the LR test (P = .004). Conclusion: Patient factors and characteristics are better predictors for patient outcomes 1 year after APM than surgeon characteristics, specifically baseline KOOS-Pain, although an individual surgeon influenced the 1-Year KOOS-Pain mixed model in the LR test. This finding has key clinical implications; surgeons who wish to improve patient outcomes after APM should focus on improving patient selection rather than improving the surgical technique. Future research is needed to determine whether surgeon variability has an impact on longer-term patient outcomes.

Enabling Personalized Medicine in Orthopaedic Surgery Through Artificial Intelligence: A Critical Analysis Review.

¼ The application of artificial intelligence (AI) in the field of orthopaedic surgery holds potential for revolutionizing health care delivery across 3 crucial domains: (I) personalized prediction of clinical outcomes and adverse events, which may optimize patient selection, surgical planning, and enhance patient safety and outcomes; (II) diagnostic automated and semiautomated imaging analyses, which may reduce time burden and facilitate precise and timely diagnoses; and (III) forecasting of resource utilization, which may reduce health care costs and increase value for patients and institutions.¼ Computer vision is one of the most highly studied areas of AI within orthopaedics, with applications pertaining to fracture classification, identification of the manufacturer and model of prosthetic implants, and surveillance of prosthesis loosening and failure.¼ Prognostic applications of AI within orthopaedics include identifying patients who will likely benefit from a specified treatment, predicting prosthetic implant size, postoperative length of stay, discharge disposition, and surgical complications. Not only may these applications be beneficial to patients but also to institutions and payors because they may inform potential cost expenditure, improve overall hospital efficiency, and help anticipate resource utilization.¼ AI infrastructure development requires institutional financial commitment and a team of clinicians and data scientists with expertise in AI that can complement skill sets and knowledge. Once a team is established and a goal is determined, teams (1) obtain, curate, and label data; (2) establish a reference standard; (3) develop an AI model; (4) evaluate the performance of the AI model; (5) externally validate the model, and (6) reinforce, improve, and evaluate the model's performance until clinical implementation is possible.¼ Understanding the implications of AI in orthopaedics may eventually lead to wide-ranging improvements in patient care. However, AI, while holding tremendous promise, is not without methodological and ethical limitations that are essential to address. First, it is important to ensure external validity of programs before their use in a clinical setting. Investigators should maintain high quality data records and registry surveillance, exercise caution when evaluating others' reported AI applications, and increase transparency of the methodological conduct of current models to improve external validity and avoid propagating bias. By addressing these challenges and responsibly embracing the potential of AI, the medical field may eventually be able to harness its power to improve patient care and outcomes.

Disease diagnosis and arthroplasty type are strongly associated with short-term postoperative patient-reported outcomes in patients undergoing primary total shoulder arthroplasty.

BACKGROUND: Prognostic factors for total shoulder arthroplasty (TSA) clinical outcomes are incompletely understood. This study investigates the associations of preoperative patient, disease-specific, and surgical factors with 1-year postoperative PENN Shoulder Score (PSS) in patients undergoing primary TSA. METHODS: Cleveland Clinic patients undergoing primary anatomic TSA (aTSA) or reverse TSA (rTSA) for glenohumeral osteoarthritis (GHOA) or rotator cuff tear arthropathy (CTA) between February 2015 and August 2019, and having complete preoperative and 1-year postoperative patient-reported outcome measures (PROMs), were included. Twenty preselected preoperative patient, disease-specific, and surgical factors were used to fit multivariable models for 1-year PSS and its subscores. RESULTS: Of 1427 eligible primary TSAs, 1174 had 1-year follow-up by PROMs (82%), with 1042 analyzed after additional exclusions, including 30% rTSAs for CTA (n = 308), 26% rTSAs for GHOA (n = 275), and 44% aTSAs for GHOA (n = 459). All PROMs showed statistically significant improvements postoperatively, with 89% of patients reaching an acceptable symptom state. Lower 1-year PSS was associated with younger age, female sex, current smoking, chronic pain diagnosis, history of prior surgery, worker's compensation claim, lower preoperative mental health, lower baseline PSS, absence of glenoid bone loss, and diagnosis-arthroplasty type (CTA-rTSA < GHOA-rTSA < GHOA-aTSA). The most important prognostic factors associated with 1-year PSS were diagnosis-arthroplasty type, baseline mental health status, and insurance status. CONCLUSIONS: Disease diagnosis, arthroplasty type, and several other baseline factors are strongly and individually associated with PROMs following primary TSA, with patients undergoing aTSA for GHOA demonstrating the highest PROM scores at 1-year follow-up. Patient, disease-specific, and surgical factors can be used to guide postoperative prognosis following primary TSA for improved preoperative patient counseling regarding expected outcomes of these procedures.

What Are the Diagnosis-Specific Thresholds of Minimal Clinically Important Difference and Patient Acceptable Symptom State in Hip Disability and Osteoarthritis Outcome Score After Primary Total Hip Arthroplasty?

BACKGROUND: This study aimed to determine the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) thresholds for Hip Disability and Osteoarthritis Outcome Score (HOOS) pain, physical short form (PS), and joint replacement (JR) 1 year after primary total hip arthroplasty stratified by preoperative diagnosis of osteoarthritis (OA) versus non-OA. METHODS: A prospective institutional cohort of 5,887 patients who underwent primary total hip arthroplasty (January 2016 to December 2018) was included. There were 4,184 patients (77.0%) who completed a one-year follow-up. Demographics, comorbidities, and baseline and one-year HOOS pain, PS, and JR scores were recorded. Patients were stratified by preoperative diagnosis: OA or non-OA. Minimal detectable change (MDC) and MCIDs were estimated using a distribution-based approach. The PASS values were estimated using an anchor-based approach, which corresponded to a response to a satisfaction question at one year post surgery. RESULTS: The MCID thresholds were slightly higher in the non-OA cohort versus OA patients. (HOOS-Pain: OA: 8.35 versus non-OA: 8.85 points; HOOS-PS: OA: 9.47 versus non-OA: 9.90 points; and HOOS-JR: OA: 7.76 versus non-OA: 8.46 points). Similarly, all MDC thresholds were consistently higher in the non-OA cohort compared to OA patients. The OA cohort exhibited similar or higher PASS thresholds compared to the non-OA cohort for HOOS-Pain (OA: ≥80.6 versus non-OA: ≥77.5 points), HOOS-PS (OA: ≥83.6 versus non-OA: ≥83.6 points), and HOOS-JR (OA: ≥76.8 versus non-OA: ≥73.5 points). A similar percentage of patients achieved MCID and PASS thresholds regardless of preoperative diagnosis. CONCLUSIONS: While MCID and MDC thresholds for all HOOS subdomains were slightly higher among non-OA than OA patients, PASS thresholds for HOOS pain and JR were slightly higher in the OA group. The absolute magnitude of the difference in these thresholds may not be sufficient to cause major clinical differences. However, these subtle differences may have a significant impact when used as indicators of operative success in a population setting.

Diagnosis-Specific Thresholds of the Minimal Clinically Important Difference and Patient Acceptable Symptom State for KOOS After Total Knee Arthroplasty.

UPDATE: This article was updated on May 1, 2024 because of a previous error, which was discovered after the preliminary version of the article was posted online. The byline that had read "Ahmed K. Emara, MD 1 *, Ignacio Pasqualini, MD 1 *, Alison K. Klika, MS 1 , Melissa N. Orr, BS 1 , Pedro J. Rullán, MD 1 , Nicolas S. Piuzzi, MD 1 , and the Cleveland Clinic Arthroplasty Group†" now reads "Ahmed K. Emara, MD 1 *, Ignacio Pasqualini, MD 1 *, Yuxuan Jin, MS 1 , Alison K. Klika, MS 1 , Melissa N. Orr, BS 1 , Pedro J. Rullán, MD 1 , Nicolas S. Piuzzi, MD 1 , and the Cleveland Clinic Arthroplasty Group†". BACKGROUND: Literature-reported minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) thresholds for patient-reported outcome measures demonstrate marked variability. The purpose of this study was to determine the minimal detectable change (MDC), MCID, and PASS thresholds for the Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subdomain, Physical Function Short Form (PS), and Joint Replacement (JR) among patients with osteoarthritis (OA) who underwent primary total knee arthroplasty (TKA). METHODS: A prospective cohort of 6,778 patients who underwent primary TKA was analyzed. Overall, 1-year follow-up was completed by 5,316 patients for the KOOS Pain, 5,018 patients for the KOOS PS, and 4,033 patients for the KOOS JR. A total of 5,186 patients had an OA diagnosis; this group had an average age of 67.0 years and was 59.9% female and 80.4% White. Diagnosis-specific MDCs and MCIDs were estimated with use of a distribution-based approach. PASS values were estimated with use of an anchor-based approach, which corresponded to a response to a satisfaction question at 1 year postoperatively. RESULTS: The MCID thresholds for the OA group were 7.9 for the KOOS Pain, 8.0 for the KOOS PS, and 6.7 for the KOOS JR. A high percentage of patients achieved the MCID threshold for each outcome measure (KOOS Pain, 95%; KOOS PS, 88%; and KOOS JR, 94%). The MDC 80% to 95% confidence intervals ranged from 9.1 to 14.0 for the KOOS Pain, 9.2 to 14.1 for the KOOS PS, and 7.7 to 11.8 for the KOOS JR. The PASS thresholds for the OA group were 77.7 for the KOOS Pain (achieved by 73% of patients), 70.3 for the KOOS PS (achieved by 68% of patients), and 70.7 for the KOOS JR (achieved by 70% of patients). CONCLUSIONS: The present study provided useful MCID, MDC, and PASS thresholds for the KOOS Pain, PS, and JR for patients with OA. The diagnosis-specific metrics established herein can serve as benchmarks for clinically meaningful postoperative improvement. Future research and quality assessments should utilize these OA-specific thresholds when evaluating outcomes following TKA. Doing so will enable more accurate determinations of operative success and improvements in patient-centered care. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

New approach to testing treatments for osteoarthritis: FastOA.

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure of drug and treatment development in osteoarthritis is due, in part, to the advanced stage of disease of patients in trials and suggests that mirroring the animal model approach might be more successful. It suggests a path forward by enriching trial enrollees with those likely to develop post traumatic OA quickly.

Image-guided superficial radiation therapy has superior 2-year recurrence probability to Mohs micrographic surgery.

Introduction: Non-melanoma skin cancers (NMSCs) are the most common cancers in the USA, and their incidence is rising. Mohs micrographic surgery (MMS) is commonly performed to excise NMSCs. MMS replaced superficial radiotherapy (SRT) as a first line treatment, given its superior efficacy. Image-guided superficial radiation therapy (IGSRT) was invented to improve the precision of SRT. This study investigates how the 2-year recurrence probability of IGSRT-treated NMSCs compares to that of MMS-treated lesions. Methods: This retrospective cohort study compared the 2-year recurrence probability of early stage NMSCs (squamous and basal cell carcinomas (SCCs and BCCs)) treated by IGSRT (2,286 lesions) to data on NMSCs treated by MMS (5,391 lesions) via one sample proportion tests. Medical Subject Headings were used to search PubMed for reports of 2-year recurrence probability rates of NMSCs treated by MMS. Seventeen studies were screened; 14 studies were excluded for lack of 2-year time to event analysis, or irrelevant patient population (non-BCC/SCC study, advanced disease), leaving 3 studies for comparison. Results: IGSRT-treated NMSCs have a statistically significantly improved 2-year recurrence probability than those treated by MMS, P < 0.001 for pooled data. Conclusion: The 2-year recurrence probability IGSRT-treated NMSCs is superior to MMS-treated and supports IGSRT as an effective treatment option for individuals with early stage NMSCs.

Predictors of Return to Activity at 2 Years After Anterior Cruciate Ligament Reconstruction Among Patients With High Preinjury Marx Activity Scores: A MOON Prospective Cohort Study.

BACKGROUND: Predictors of return to activity after anterior cruciate ligament reconstruction (ACLR) among patients with relatively high preinjury activity levels remain poorly understood. PURPOSE/HYPOTHESIS: The purpose of this study was to identify predictors of return to preinjury levels of activity after ACLR, defined as achieving a Marx activity score within 2 points of the preinjury value, among patients with Marx activity scores of 12 to 16 who had been prospectively enrolled in the Multicenter Orthopaedic Outcomes Network (MOON) cohort. We hypothesized that age, sex, preinjury activity level, meniscal injuries and/or procedures, and concurrent articular cartilage injuries would predict return to preinjury activity levels at 2 years after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: All unilateral ACLR procedures from 2002 to 2008 performed in patients enrolled in the MOON, with preinjury Marx activity scores ranging from 12 to 16, were evaluated with a specific focus on return to preinjury activity levels at 2 years postoperatively. Return to activity was defined as a Marx activity score within 2 points of the preinjury value. The proportion of patients able to return to preinjury activity levels was calculated, and multivariable modeling was performed to identify risk factors for patients' inability to return to preinjury activity levels. RESULTS: A total of 1188 patients were included in the final analysis. The median preinjury Marx activity score was 16 (interquartile range, 12-16). Overall, 466 patients (39.2%) were able to return to preinjury levels of activity, and 722 patients (60.8%) were not able to return to preinjury levels of activity. Female sex, smoking at the time of ACLR, fewer years of education, lower 36-Item Short Form Health Survey Mental Component Summary scores, and higher preinjury Marx activity scores were predictive of patients' inability to return to preinjury activity levels. Graft type, revision ACLR, the presence of medial and/or lateral meniscal injuries, a history of meniscal surgery, the presence of articular cartilage injuries, a history of articular cartilage treatment, and the presence of high-grade knee laxity were not predictive of a patient's ability to return to preinjury activity level. CONCLUSION: At 2 years after ACLR, most patients with high preinjury Marx activity scores did not return to their preinjury level of activity. The higher the preinjury Marx activity score that a patient reported at the time of enrollment, the less likely he/she was able to return to preinjury activity level. Smoking and lower mental health at the time of ACLR were the only modifiable risk factors in this cohort that predicted an inability to return to preinjury activity levels. Continued effort and investigation are required to maximize functional recovery after ACLR in patients with high preinjury levels of activity.

EP1 activation inhibits doxorubicin-cardiomyocyte ferroptosis via Nrf2.

Chemotherapeutic agents, such as doxorubicin (DOX), may cause cardiomyopathy, even life-threatening arrhythmias in cancer patients. Ferroptosis-an iron-dependent oxidative form of programmed necrosis, plays a pivotal role in DOX-induced cardiomyopathy (DIC). Prostaglandins (PGs) are bioactive signaling molecules that profoundly modulate cardiac performance in both physiologic and pathologic conditions. Here, we found that PGE2 production and its E-prostanoid 1 receptor (EP1) expression were upregulated in erastin (a ferroptosis inducer) or DOX-treated cardiomyocytes. EP1 inhibition markedly aggravated erastin or DOX-induced cardiomyocyte ferroptosis, whereas EP1 activation exerted opposite effect. Genetic depletion of EP1 in cardiomyocytes worsens DOX-induced cardiac injury in mice, which was efficiently rescued by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Mechanistically, EP1 activation protected cardiomyocytes from DOX-induced ferroptosis by promoting nuclear factor erythroid 2-related factor 2 (Nrf2)-driven anti-oxidative gene expression, such as glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). EP1 was coupled with Gαq to elicit intracellular Ca2+ flux and activate the PKC/Nrf2 cascade in ferroptotic cardiomyocytes. EP1 activation also prevents DOX-induced ferroptosis in human cardiomyocytes. Thus, PGE2/EP1 axis protects cardiomyocytes from DOX-induced ferroptosis by activating PKC/Nrf2 signaling and activation of EP1 may represent an attractive strategy for DIC prevention and treatment.

One-year patient-reported outcomes following primary arthroscopic rotator cuff repair vary little by surgeon.

Background: This study's purpose was to investigate the extent to which differences among operating surgeons may influence 1-year patient-reported outcome measures (PROMs) in patients undergoing rotator cuff repair (RCR) surgery, after controlling for general and disease-specific patient factors. We hypothesized that surgeon would be additionally associated with 1-year PROMs, specifically the baseline to 1-year improvement in Penn Shoulder Score (PSS). Methods: We used mixed multivariable statistical modeling to assess the influence of surgeon (and alternatively surgical case volume) on 1-year PSS improvement in patients undergoing RCR at a single health system in 2018, controlling for eight patient- and six disease-specific preoperative factors as possible confounders. Contributions of predictors to explaining variation in 1-year PSS improvement were measured and compared using Akaike's Information Criterion. Results: 518 cases performed by 28 surgeons met inclusion criteria, with median (quartiles) baseline PSS of 41.9 (31.9, 53.9) and 1-year PSS improvement of 42 (29.1, 55.3) points. Contrary to expectation, surgeon and surgical case volume were neither statistically significantly nor clinically meaningfully associated with 1-year PSS improvement. Baseline PSS and mental health status (VR-12 MCS) were the dominant and only statistically significant predictors of 1-year PSS improvement, with lower baseline PSS and higher VR-12 MCS predicting larger 1-year PSS improvement. Conclusion: Patients generally reported excellent 1-year outcomes following primary RCR. This study did not find evidence that the individual surgeon or surgeon case volume influences 1-year PROMs, independently of case-mix factors, following primary RCR in a large employed hospital system.

Aromatic Terpenes and Their Biosynthesis in Dendrobium, and Conjecture on the Botanical Perfumer Mechanism.

This review presents a systematic analysis of the studies on volatiles in Dendrobium. Among the various components, aromatic terpenes are a crucial component in the development of the aromatic characteristics of Dendrobium and other plants. Recent advancements in detection and sequencing technology have resulted in a considerable rise in research on the biosynthetic processes of aromatic terpenes in Dendrobium and other flowering plants. Nevertheless, the inquiry into the precise means by which plants regulate the proportion of diverse aromatic terpenes in their floral scent, thereby preserving their olfactory traits, requires further investigation. A conjecture on the botanical perfumer mechanism, which condensed the findings of earlier studies, was put forward to address this area of interest. Specific transcription factors likely govern the coordinated expression of multiple key terpene synthase (TPS) genes during the flowering stage of plants, thereby regulating the proportional biosynthesis of diverse aromatic terpenes and sustaining the distinctive aromatic properties of individual plants. This review serves as a significant theoretical reference for further investigations into aromatic volatile compounds in Dendrobium.

Plasmonic Bound States in the Continuum to Tailor Exciton Emission of MoTe2.

Plasmon resonances can greatly enhance light-matter interactions of two-dimensional van der Waals materials. However, the quality factor of plasmonic resonances is limited. Here, we demonstrate a plasmonic quasi-bound state in the continuum (quasi-BIC), which is composed of gold nanorod pairs. Through controlling the rotation angle of the nanorods, the quality factor of the plasmonic BIC mode can be tuned. Simulation results show that the plasmonic BIC combines the advantages of high-quality factor from the BIC effect and small mode volume from plasmonic resonance. Experiment results show that the designed plasmonic BIC mode exhibits a quality factor higher than 15 at the wavelength of around 1250 nm. Through integrating the plasmonic bound state structure with monolayer molybdenum ditelluride (MoTe2), the exciton emission of MoTe2 in the PL spectrum split into two exciton-polariton modes, which is attributed to the high Q factor and strong interaction between the BIC mode and excitons of MoTe2.

Influence of ADT on B7-H3 expression during CRPC progression from hormone-naïve prostate cancer.

Androgen deprivation therapy (ADT) is the standard care for advanced prostate cancer (PCa) patients. Unfortunately, although tumors respond well initially, they enter dormancy and eventually progress to fatal/incurable castration-resistant prostate cancer (CRPC). B7-H3 is a promising new target for PCa immunotherapy. CD276 (B7-H3) gene has a presumptive androgen receptor (AR) binding site, suggesting potential AR regulation. However, the relationship between B7-H3 and AR is controversial. Meanwhile, the expression pattern of B7-H3 following ADT and during CRPC progression is largely unknown, but critically important for identifying patients and determining the optimal timing of B7-H3 targeting immunotherapy. In this study, we performed a longitudinal study using our unique PCa patient-derived xenograft (PDX) models and assessed B7-H3 expression during post-ADT disease progression. We further validated our findings at the clinical level in PCa patient samples. We found that B7-H3 expression was negatively regulated by AR during the early phase of ADT treatment, but positively associated with PCa proliferation during the remainder of disease progression. Our findings suggest its use as a biomarker for diagnosis, prognosis, and ADT treatment response, and the potential of combining ADT and B7-H3 targeting immunotherapy for hormone-naïve PCa treatment to prevent fatal CRPC relapse.

Methodologic Issues Specific to Prediction Model Development and Evaluation.

Developing and evaluating statistical prediction models is challenging, and many pitfalls can arise. This article identifies what the authors believe are some common methodologic concerns that may be encountered. We describe each problem and make suggestions regarding how to address them. The hope is that this article will result in higher-quality publications of statistical prediction models.

Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice. Methods: Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. In vitro, steatotic L-02 cells were used to explore the underlying mechanism. Results: In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells. Conclusion: Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes.

Practical guide to the typical analysis of prognostic factors and biomarkers without the use of P-values.

OBJECTIVES: We have seen an increasing number of studies evaluating biomarkers and prognostic factors. Biomedical researchers like to draw conclusions based on P-values. However, P-values are often not needed for this type of study. In this article, we show how most biomedical research problems in this area could be organized into three main analyses, each avoiding the use of P-values. METHODS: The three main analyses follow the framework of prediction modeling when the outcome of interest is binary or time-to-event. The analyses make use of figures such as boxplots, nonparametric smoothing line, and nomogram, and also incorporate prediction performance measures such as the Area under the receiver operating characteristic curve, and index of predictive accuracy. RESULTS: Our proposed framework is easy to follow. It is also in line with most of the research in the field of biomarkers and prognostic factors evaluation, such as reclassification table, net reclassification index, Akaike information criterion/Bayesian information criterion, receiver operating characteristic curve, and decision curve analysis. CONCLUSION: Overall, we provide a step-by-step guideline that biomedical researchers could easily follow to conduct statistical analysis without using P-values, especially with the goal of evaluating biomarkers and prognostic factors.