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Orthopedic implant infections (OIIs) present diagnostic and therapeutic challenges, owing to the lack of methods to distinguish between active infection and sterile inflammation. To address this unmet need, d-amino-acid-based radiotracers with unique metabolic profiles in microorganisms have emerged as a novel class of infection-specific imaging agents. Given the pivotal role of d-glutamine in bacterial biofilm formation and virulence, herein, we explored the potential of positron emission tomography (PET) imaging with d-[5- 11 C]-Glutamine (d-[5- 11 C]-Gln) for early detection and treatment monitoring of OIIs. In vitro studies confirmed an active uptake of d-[5- 11 C]-Gln by Staphylococcus aureus ( S. aureus ) biofilm commonly associated with OIIs. In vivo evaluations included PET imaging comparisons with d-[5- 11 C]-Gln vs l-[5- 11 C]-Gln or 2-deoxy-2-[ 18 F]-fluoroglucose ([ 18 F]-FDG) in a rat OII model with tibial implantation of sterile or S. aureus - colonized stainless-steel screws before and after treatment. These studies demonstrated that the uptake of d-[5- 11 C]-Gln was significantly higher in the infected screws than that in sterile screws (∼3.4-fold, p = 0.008), which displayed significantly higher infection-to-background muscle uptake ratios (∼2-fold, p C]-Gln as compared to l-[5- 11 C]-Gln as compared to l-[5- 11 C]-Gln. Following a 3 week vancomycin treatment, imaging with d-[5- 11 C]-Gln showed a significant reduction in uptake at the infected sites (∼3-fold, p = 0.0008). Further regression analyses revealed a superior correlation of residual infection-associated radiotracer uptake with the postimaging ex vivo bacterial counts for d-[5- 11 C]-Gln ( k = 0.473, R 2 = 0.796) vs [ 18 F]-FDG ( k = 0.212, R 2 = 0.434), suggesting that d-[5- 11 C]-Gln PET had higher sensitivity for detecting residual bacterial burden than [ 18 F]-FDG PET. Our results demonstrate the translational potential of d-[5- 11 C]-Gln PET imaging for noninvasive detection and treatment monitoring of OIIs.

Objective: Atypical parathyroid tumor (aPT) and parathyroid carcinoma (PC) are extremely rare parathyroid neoplasms, accounting together for <2% of all parathyroid tumors. They often present an overlapping clinical phenotype, sharing clinical, biochemical, and some histological features. They are distinguished only by the presence of local invasion, and lymph nodes or distant metastasis, which are all absent in aPTs. To date, only few studies have compared clinical presentation and features between aPTs and PCs. Our purpose was to conduct a retrospective study on a multicenter Italian database of aPT and PC patients., Design and Methods: We comparatively analyzed main features of aPT (n = 57) and PC (n = 74) patients collected at 15 major endocrinology and endocrine surgery centers in Italy., Results and Conclusions: Atypical parathyroid tumors and PCs showed no significant differences in many clinical features and presented similar values of elevated parathyroid hormone and total serum calcium. Renal complications, namely nephrolithiasis and nephrocalcinosis, appeared to be more common in PC, with a significantly higher rate of renal colic, regardless of total serum calcium levels and 24-h calciuria. Parathyroid carcinomas showed significantly higher postoperative disease persistence and recurrence rates, presumably due to an uncomplete resection of the primary tumor in 23.5% of cases and/or presence of unremoved active metastasis, but they had similar disease-free mean time after surgery than aPT. To deepen the study of malignant parathyroid tumors, the institution of a novel Italian retro-prospective multicenter registry of aPTs and PCs is currently ongoing, and a dedicated PC European registry has been recently activated., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Urinary sex hormones are investigated as potential biomarkers for the early detection of breast cancer, aiming to evaluate their relevance and applicability, in combination with supervised machine-learning data analysis, toward the ultimate goal of extensive screening., Methods: Sex hormones were determined on urine samples collected from 250 post-menopausal women (65 healthy - 185 with breast cancer, recruited among the clinical patients of Candiolo Cancer Institute FPO-IRCCS (Torino, Italy). Two analytical procedures based on UHPLC-MS/HRMS were developed and comprehensively validated to quantify 20 free and conjugated sex hormones from urine samples. The quantitative data were processed by seven machine learning algorithms. The efficiency of the resulting models was compared., Results: Among the tested models aimed to relate urinary estrogen and androgen levels and the occurrence of breast cancer, Random Forest (RF) proved to underscore all the other supervised classification approaches, including Partial Least Squares - Discriminant Analysis (PLS-DA), in terms of effectiveness and robustness. The final optimized model built on only five biomarkers (testosterone-sulphate, alpha-estradiol, 4-methoxyestradiol, DHEA-sulphate, and epitestosterone-sulphate) achieved an approximate 98% diagnostic accuracy on replicated validation sets. To balance the less-represented population of healthy women, a Synthetic Minority Oversampling TEchnique (SMOTE) data oversampling approach was applied., Conclusions: By means of tunable hyperparameters optimization, the RF algorithm showed great potential for early breast cancer detection, as it provides clear biomarkers ranking and their relative efficiency, allowing to ground the final diagnostic model on a restricted selection five steroid biomarkers only, as desirable for noninvasive tests with wide screening purposes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Vincenti reports financial support was provided by CRT Foundation. Marco Vincenti reports financial support was provided by Italian Ministry of Education, Universities, and Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Defining the distribution of the chemical species in a multicomponent system is a task of great importance with applications in many fields. To clarify the identity and the abundance of the species that can be formed by the interaction of the components of a solution, it is fundamental to know the formation constants of those species. The determination of equilibrium constants is mainly performed through the analysis of experimental data obtained by different instrumental techniques. Among them, potentiometry is the elective technique for this purpose. As such, a survey was run within the NECTAR COST Action - Network for Equilibria and Chemical Thermodynamics Advanced Research, to identify the most used software for the analysis of potentiometric data and to highlight their strengths and weaknesses. The features and the calculation processes of each software were analyzed and rationalized, and a simulated titration dataset of a hypothetic hexaprotic acid was processed by each software to compare and discuss the optimized protonation constants. Moreover, further data analysis was also carried out on the original dataset including some systematic errors from different sources, as some calibration parameters, the total analytical concentration of reagents and ionic strength variations during titrations, to evaluate their impact on the refined parameters. Results showed that differences on the protonation constants estimated by the tested software are not significant, while some of the considered systematic errors affect results. Overall, it emerged that software commonly used suffer from many limitations, highlighting the urgency of new dedicated and modern tools. In this context, some guidelines for data generation and treatment are also given., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Addressing intraoperative bleeding remains a significant challenge in the field of robotic surgery. This research endeavors to pioneer a groundbreaking solution utilizing convolutional neural networks (CNNs). The objective is to establish a system capable of forecasting instances of intraoperative bleeding during robot-assisted radical prostatectomy (RARP) and promptly notify the surgeon about bleeding risks., Methods: To achieve this, a multi-task learning (MTL) CNN was introduced, leveraging a modified version of the U-Net architecture. The aim was to categorize video input as either "absence of blood accumulation" (0) or "presence of blood accumulation" (1). To facilitate seamless interaction with the neural networks, the Bleeding Artificial Intelligence-based Detector (BLAIR) software was created using the Python Keras API and built upon the PyQT framework. A subsequent clinical assessment of BLAIR's efficacy was performed, comparing its bleeding identification performance against that of a urologist. Various perioperative variables were also gathered. For optimal MTL-CNN training parameterization, a multi-task loss function was adopted to enhance the accuracy of event detection by taking advantage of surgical tools' semantic segmentation. Additionally, the Multiple Correspondence Analysis (MCA) approach was employed to assess software performance., Results: The MTL-CNN demonstrated a remarkable event recognition accuracy of 90.63%. When evaluating BLAIR's predictive ability and its capacity to pre-warn surgeons of potential bleeding incidents, the density plot highlighted a striking similarity between BLAIR and human assessments. In fact, BLAIR exhibited a faster response. Notably, the MCA analysis revealed no discernible distinction between the software and human performance in accurately identifying instances of bleeding., Conclusion: The BLAIR software proved its competence by achieving over 90% accuracy in predicting bleeding events during RARP. This accomplishment underscores the potential of AI to assist surgeons during interventions. This study exemplifies the positive impact AI applications can have on surgical procedures.

Context: Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently., Objective: The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021., Methods: Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included., Results: Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation., Conclusion: This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host's immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.

Background: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. Systemic involvement in COVID-19 is due to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2) receptor, responsible for the entry in the cells of SARS-CoV-2, Several reports in humans and animal models showed a significant ACE2 mRNA expression in hypothalamus and pituitary cells. Moreover, higher mortality and poorer outcomes have been widely described in COVID-19 patients with obesity, diabetes and vertebral fractures, which are all highly prevalent in subjects with pituitary dysfunctions., Aim: To review the main endocrine manifestations of COVID-19 with their possible implications for pituitary diseases, the possible direct and indirect involvement of the pituitary gland in COVID-19, the impact of COVID-19 on the management of established pituitary diseases which can be already at increased risk for worse outcomes and on neurosurgical activities as well as vaccination., Conclusions: Our review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency.

Since most d-amino acids (DAAs) are utilized by bacterial cells but not by mammalian eukaryotic hosts, recently DAA-based molecular imaging strategies have been extensively explored for noninvasively differentiating bacterial infections from the host's inflammatory responses. Given glutamine's pivotal role in bacterial survival, cell growth, biofilm formation, and even virulence, here we report a new positron emission tomography (PET) imaging approach using d-5-[ 11 C]glutamine (d-[5- 11 C]-Gln) for potential clinical assessment of bacterial infection through a comparative study with its l-isomer counterpart, l-[5- 11 C]-Gln. In both control and infected mice, l-[5- 11 C]-Gln had substantially higher uptake levels than d-[5- 11 C]-Gln in most organs except the kidneys, showing the expected higher use of l-[5- 11 C]-Gln by mammalian tissues and more efficient renal excretion of d-[5- 11 C]-Gln. Importantly, our work demonstrates that PET imaging with d-[5- 11 C]-Gln is capable of detecting infections induced by both Escherichia coli ( E. coli ) and methicillin-resistant Staphylococcus aureus (MRSA) in a dual-infection murine myositis model with significantly higher infection-to-background contrast than with l-[5- 11 C]-Gln (in E. coli , 1.64; in MRSA, 2.62, p = 0.0004). This can be attributed to the fact that d-[5- 11 C]-Gln is utilized by bacteria while being more efficiently cleared from the host tissues. We confirmed the bacterial infection imaging specificity of d-[5- 11 C]-Gln by comparing its uptake in active bacterial infections versus sterile inflammation and with 2-deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG). These results together demonstrate the translational potential of PET imaging with d-[5- 11 C]-Gln for the noninvasive detection of bacterial infectious diseases in humans.

Context: Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma., Objective: To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence., Design: Retrospective, observational study., Setting: Tertiary care center., Patients: We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018., Intervention: rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls., Main Outcome Measure: Risk of tumor recurrence in rhGH-treated and control patients., Results: In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32-0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88-17.22; P < .001) and not having performed radiotherapy (HR 16.97; 95% CI, 7.55-38.16; P < .001), while rhGH treatment was no longer associated with a lower risk of recurrence (HR 0.82; 95% CI, 0.47-1.44; P = .50)., Conclusions: We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors., Précis: Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We combined tenets of learning communities and place-based learning to develop an innovative first-year program for STEM students. Using a quasi-experimental design, we found that participants in the place-based learning community had a stronger sense of belonging, improved academic performance, and increased first-year persistence relative to a matched reference group. We also showed that participation narrowed equity gaps in first-year outcomes for students underrepresented in the sciences. A sense of place arises not just from a location, but from interrelationships between people and the natural world, and these results suggest organizing learning around place can promote inclusive student success., Competing Interests: Conflict of InterestMatt Johnson and Amy Sprowles have received research grants from the US Dept of Education, the Howard Hughes Medical Institute, CSUPERB, the California Institute of Regenerative Medicine, the National Center for Civic Engagement, and the National Science Foundation. Matt Johnson and Steven Margell are members of the California State University Center for Evaluation and Educational Effectiveness., (© The Author(s) 2020.)

The rubber hand illusion paradigm allows investigating human body ownership by inducing an illusion of owning a life-sized fake hand. Despite the wide consensus on the fact that integration of multisensory signals is the main interpretative framework of the rubber hand illusion, increasing amount of data show that additional factors might contribute to the emergence of the illusion and, in turn, explain the strong inter-individual differences of the illusory patterns. Here, we explored whether and how personality features contribute to the emergence of the illusion by administering to healthy participants the rubber hand illusion paradigm along with two well-known personality tests, i.e., the Personality Assessment Inventory (PAI) and the Rorschach test. Results showed that two Rorschach domains (i.e., "Perception and Thinking Problems" and "Self and Other Representation") were positively correlated with the illusory mislocalization of the own left hand toward the fake hand. Further analyses suggested that while the tendency to perceive unconventionally is related to mislocalizing the own hand toward the fake hand, the association of the RHI index and other personality features measured by the Rorschach remain uncertain. However, our findings in general suggest that personality features might have a role in the emergence of the rubber hand illusion. This, in turn, could explain the high inter-individual variability of the illusory effects., (Copyright © 2019 Burin, Pignolo, Ales, Giromini, Pyasik, Ghirardello, Zennaro, Angilletta, Castellino and Pia.)

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Serratia fonticola is an unusual human pathogen, previously described primarily as causing skin and soft tissue infections following trauma. There is little information in the literature about its treatment or susceptibilities. We describe the case of a 67-year-old male with paraplegia who developed urosepsis due to S. fonticola. Blood and urine cultures obtained prior to the initiation of antimicrobials both grew S. fonticola. The patient completed a 15-day course of antimicrobials and had an uneventful recovery. We reviewed 17 other patients with clinical cultures positive for S. fonticola. Of these, 11 isolates were from the genitourinary system, most often as part of a polymicrobial culture. The majority of the other organisms recovered were recognized pathogens from the Enterobacteriaceae family. The cases suggest that when recovered in conjunction with other organisms, S. fonticola does not lead to enhanced virulence or worse clinical outcomes and may be a bystander. When detected alone, which is a rare occurrence, S. fonticola may function as a human pathogen.

The purpose of this study is to develop a new cancer risk score for preoperative assessment of thyroid nodules (TN) trying to reduce unnecessary thyroidectomies. On the basis of a recent meta-analysis of published literature, we assigned a matching value to the clinical (C) and ultrasonographic (U) features of TN with increased malignancy risk (MR). The created "CUT" score derived from "C+U" score, (CU[1-10] ), along with the five-tiered "T" (T[1-5] ), represents the cytologic result of the fine-needle aspiration. The C+U score was prospectively applied to 683 consecutive patients with 705 TN and validated through a ROC curve analysis. The CUT score was correlated with the histopathological diagnoses of 110 surgically resected TN. Fifty-five histologically benign TN had a mean C+U score of 2.4 versus 5.7 of 55 malignant TN (p < 0.001). Three categories were identified: low risk for C+U score ≤2.5 (MR: 9 %), intermediate risk for C+U score ≥2.75 and ≤5 (MR: 38 %), and high risk for C+U score ≥5.25 (MR: 95 %). Sensitivity and specificity were, respectively, 95 and 60 % for a cut-off value >2.5, and 69 and 96 % for >5. The "CUT" score can be easily applied, aiding clinicians in the evaluation of TN, especially in cases with indeterminate or repeated non-diagnostic FNA.

Hyperandrogenism is a common finding in premenopausal age and is generally caused by polycystic ovarian syndrome or other benign disease. Androgen-secreting tumors represent only 0.2 % of the causes of hyperandrogenism and usually present with severe clinical features, abrupt onset, and very high androgens levels. We describe here three cases of occult ovarian Leydig cell tumors suspected on the basis of severe clinical features of hyperandrogenism rapidly worsening, with elevated serum total testosterone levels, in which bilateral ovariectomy was performed and tumor was confirmed by post-operative histology. In all three cases, imaging was negative for ovarian tumor. Moreover, in one case the confounding concomitant finding of bilateral adrenal masses posed an additional challenge. Our experience highlights that testosterone levels represent the most helpful marker in the diagnosis of androgen-secreting ovarian tumor. In the absence of imaging findings, bilateral ovariectomy should be indicated, if supported by unequivocal clinical and laboratory data.