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Rationale & Objective: Chronic kidney disease (CKD) can progress rapidly, and patients are often unprepared to make kidney failure treatment decisions. We aimed to better understand patients’ preferences for and experiences of shared and informed decision making (SDM) regarding kidney replacement therapy before kidney failure. Study Design: Cross-sectional study. Setting & Participants: Adults receiving nephrology care at CKD clinics in rural Pennsylvania. Predictors: Estimated glomerular filtration rate, 2-year risk for kidney failure, duration and frequency of nephrology care, and preference for SDM. Outcomes: Occurrence and extent of kidney replacement therapy discussions and participants’ satisfaction with those discussions. Analytic Approach: Multivariable logistic regression to quantify associations between participants’ characteristics and whether they had discussions. Results: The 447 study participants had a median age of 72 (IQR, 64-80) years and mean estimated glomerular filtration rate of 33 (SD, 12) mL/min/1.73 m2. Most (96%) were White, high school educated (67%), and retired (65%). Most (72%) participants preferred a shared approach to kidney treatment decision making, and only 35% discussed dialysis or transplantation with their kidney teams. Participants who had discussions (n = 158) were often completely satisfied (63%) but infrequently discussed potential treatment-related impacts on their lives. In multivariable analyses, those with a high risk for kidney failure within 2 years (OR, 3.24 [95% CI, 1.72-6.11]; P < 0.01), longer-term nephrology care (OR, 1.12 [95% CI, 1.05-1.20] per 1 additional year; P < 0.01), and more nephrology visits in the prior 2 years (OR, 1.34 [95% CI, 1.20-1.51] per 1 additional visit; P < 0.01) had higher odds of having discussed dialysis or transplantation. Limitations: Single health system study. Conclusions: Most patients preferred sharing CKD treatment decisions with their providers, but treatment discussions were infrequent and often did not address key treatment impacts. Longitudinal nephrology care and frequent visits may help ensure that patients have optimal SDM experiences.

Rationale & Objective: Digital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed. Study Design: Descriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention. Setting & Participants: 4 CKD clinics within a large integrated health system. Exposure: We developed an integrated suite of digital engagement tools to support patients’ shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients’ preparation for treatments, and an EHR work flow to broadcast patients’ treatment preferences to all health care providers. Outcomes: Uptake and acceptability. Analytic Approach: Mixed methods. Results: From July 1, 2017, through June 30, 2018, the CKD registry identified 1,032 patients in 4 nephrology clinics, of whom 243 (24%) were identified as high risk for progressing to kidney failure within 2 years. Kidney Transitions Specialists enrolled 117 (48%) high-risk patients by the end of year 1. The values tool was completed by 30/33 (91%) patients who attended kidney modality education. Nurse case managers used the tracking application for 100% of patients to document 287 planning steps for kidney replacement therapy. Most (87%) high-risk patients had their preferred kidney replacement modality documented and displayed in the EHR. Nurse case managers reported that the tools facilitated their identification of patients needing support and their navigation activities. Limitations: Single institution, short duration. Conclusions: Digital health system tools facilitated rapid identification of patients needing shared and informed decision making and their preparation for kidney replacement treatments. Funding: This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967). Trial registration: ClinicalTrials.gov NCT02722382.

Rationale & Objective: Chronic kidney disease (CKD) care is often fragmented across multiple health care providers. It is unclear whether patients rely mostly on their nephrologists or non-nephrologist providers for medical care, including CKD treatment and advice. Study Design: Cross-sectional study. Setting & Participants: Adults receiving nephrology care at CKD clinics in Pennsylvania. Predictors: Frequency, duration, and patient-centeredness (range, 1 [least] to 4 [most]) of participants’ nephrology care. Outcome: Participants’ reliance on nephrologists, primary care providers, or other specialists for medical care, including CKD treatment and advice. Analytical Approach: Multivariable logistic regression to quantify associations between participants’ reliance on their nephrologists (vs other providers) and their demographics, comorbid conditions, kidney function, and nephrology care. Results: Among 1,412 patients in clinics targeted for the study, 676 (48%) participated. Among these, 453 (67%) were eligible for this analysis. Mean age was 71 (SD, 12) years, 59% were women, 97% were white, and 65% were retired. Participants were in nephrology care for a median of 3.8 (IQR, 2.0-6.6) years and completed a median of 4 (IQR, 3-5) nephrology appointments in the past 2 years. Half (56%) the participants relied primarily on their nephrologists, while 23% relied on primary care providers, 18% relied on all providers equally, and 3% relied on other specialists. Participants’ adjusted odds of relying on their nephrologists were higher for those in nephrology care for longer (OR, 1.08 [95% CI, 1.02-1.15]; P = 0.02), those who completed more nephrology visits in the previous 2 years (OR, 1.16 [95% CI, 1.05-1.29]; P = 0.005), and those who perceived their last interaction with their nephrologists as more patient-centered (OR, 2.63 [95% CI, 1.70-4.09]; P

Aim of the study: Adenoid cystic carcinoma (AdCC) is the second most common salivary gland cancer. This malignant tumor is characterized by its slow growth and in spite of the fact that it has a histological low - grade appearance, a prolonged clinical course usually lasting for years, repeated recurrences, development of distant metastases and high mortality rate are typical signs. New facts of its biological behavior as well as new fusion oncogenes probably responsible for its carcinogenesis were described in the last few years. In light of these facts, the authors evaluate their own case series of patients suffering from AdCC in this manuscript. Methods: The retrospective case series included 27 patients with AdCC, who were treated at the University Hospital in Pilsen in the last 30 years (01/1986-01/2016). Clinical and demographic para-meters were identified and evaluated. Detection of the 1p36 deletion and the tumor-specific MYB-NFIB fusion oncogene by fluorescence in situ hybridization were performed. Results: The incidence of AdCC in minor salivary glands, submandibular gland, parotid gland and sublingual gland was 41%, 26%, 22 % and 11% respectively. The following staging was observed: the 1st stage in 26%, the 2nd stage in 18%, the 3rd stage in 26% and the 4th stage in 30% of cases. Metastases to regional lymph nodes were diagnosed in 26% and distant metastases in 30% of patients (55% to lung, 27% to liver, 9% to bones and 9% of peritoneal metastases). The average follow-up was 76.4 ± 67.0 months (range 7-287 months). An outcome of the treatment during follow-up was as follows: 59% of patients were with no evidence of the disease, 22% of patients died because of the disease and 19% of patients were alive with a recurrence or metastases of AdCC. The MYB-NFIB fusion transcript was detected in 79% of cases (19/24) and the 1p36 deletion in 13% of cases (3/23). Conclusion: The AdCC of salivary glands shows a greater tendency to development of regional lymph node metastases than previously thought. The MYB-NFIB gene fusion is the major tumor-specific oncogenic event in AdCC with high detection rate. The MYB-NFIB fusion oncogene could currently only be used as a potential diagnostic tool in difficult histopathological cases of AdCC, especially in late distant metastases.

Introduction: Intraosseous mucoepidermoid carcinoma is a relatively rare variant of the histologically identical malignant tumor affecting salivary glands. It is a recently described separate nosological entity with a clearly defined histopathological feature. To date, only hundreds of cases of this disease have been reported in the literature worldwide. According to its typical occurrence this tumor is classified as a primary intraosseous carcinoma of the jaw. Methods: In the present paper, the authors describe two patients with this diagnosis, in both cases with tumors afflicting upper jaw diagnosed and treated at the Department of maxillofacial surgery in Pilsen since the years 2008. The treatment outcomes are evaluated after five-year follow-up. Results: The first patient was treated by the radical surgical procedure and adjuvant cancer therapy. Long-term complete remission was achieved and today the patient is with no evidence of malignant disease. The second patient is of advanced age and with much co-morbidity. For this reason, only radiotherapy was indicated, but without any therapeutic response in terms of tumor regression. The subsequently indicated palliative chemotherapy led to the significant tumor shrinkage. Currently, the patient is in the partial remission of malignant disease, with no evidence of tumor progression or metastases. Conclusion: The pathogenesis of intraosseous mucoepidermoid carcinoma is still not well understood. The diagnosis is based on histological examination performed by experienced pathologist. Immunohistochemical examination seems to be of no benefit for the diagnosis. A squamous cell carcinoma and glandular odontogenic cyst is necessary to be considered in histopathological differential diagnosis. A clinician has to rule out metastasis of salivary mucoepidermoid carcinoma in the jaws. Most intraosseous mucoepidermoid carcinomas are classified as low-grade tumors with the little metastatic potential. The radical resection procedure should be the first choice for the treatment of this cancer. Radiotherapy and chemotherapy are only indicated as an adjuvant therapy, especially in high-grade tumors. Despite its clear malignant nature the intraosseous mucoepidermoid carcinoma is not an aggressive tumor with high mortality.

Aim of the study: To characterize the current population of patients with squamous cell carcinoma of the lip with focus on the biological behavior and prognosis of these tumors. To evaluate the lip cancer treatment at the department of maxillofacial surgery in Pilsen. Methods: The retrospective study included 72 patients with 73 lip squamous cell carcinomas diagnosed and treated within seven years (January 2002 - December 2008). Clinical and demographic parameters were identified and evaluated. Results: Patients mean age was 73.2 ± 9.5 years. Male to female ratio was 2,4:1. The lower lip was affected in 68 cases (93%), upper lip in 5 cases (7%). The persistence of a lip tumor before a medical examination (identified in 55 patients) was on average 7.2 months. T1 tumors were diagnosed in 60 cases (83%), T2 in 12 cases (16%) and T4 in one case (1%). Regional lymph node metastases were not detected at the time of diagnosis in any patient (N0). Histological grading (identified in 54 tumors) was: G1 - 39 tumors (72%), G2 - 13 tumors (24%), G3 - 2 tumors (4%). Histologically verified actinic cheilitis was observed in 15 patients (21%), in one patient the lip cancer had origin in oral lichen planus. Immunodeficiency was detected in four patients (6%). 43 patients had medical record of smoking cigarettes, nine (21%) of them were smokers, 34 (79%) were non-smokers. Synchronous or metachronous non-melanoma skin cancer of the head and neck occurred in 11 patients (15%). Primarily all patients were treated surgically. Follow-up period was on average 48.3 months (median 44.5). Seven patients (10%) developed regional lymph node metastases during the follow-up on average 26.3 months from the time of diagnosis. Distant metastasis was detected in one patient (1,39%) with the terminal stage of disease. Local recurrences were observed in five patients (7%) on average 15 months after the surgery. Oncological therapy was indicated in nine patients (13%). 5 patients died as a consequence of cancer, an average of 15.6 months from the time of diagnosis (mortality 7%). Complete remission of malignant disease was achieved in 92% of patients (in 86% of patients only by the surgery alone). Conclusion: In the Czech Republic a squamous cell carcinoma of the lip is diagnosed most often in the 1st clinical stage. It is a slow growing, well differentiated tumor affecting the lower lip with a low metastatic potential to regional lymph nodes in most cases. Although these tumors are supposed to have a good prognosis, they may have a lethal course even in the cases of small size and well differentiated tumors because of recurrences or metastatic disease. A lymph node involvement may not be detectable at the time of diagnosis. That's why follow-up is necessary for all patients. Screening of premalignant lesions and lip squamous cell carcinomas should be a role for all physicians performing head and neck examination because of a well examinable localization.

Objectives: Osteonecrosis of the jaws is a rare side effect of bisphosphonate therapy, occurring especially in oncological patients but also in patients with metabolic bone diseases. Because it is a relatively recently described disease (year 2003), the etiopathogenesis of these lesions has not yet been fully clarified, there is also no consensus for their treatment. Conservative as well as surgical therapy leads to complete healing in a small percentage of cases only, the emphasis is therefore placed on preventive measures. The diagnosis is based primarily on patient's history and clinical examination, without the need of using imaging methods. Pathological changes in this jawbone necrosis imagined by any of known methods are nonspecific only, distinction of these lesions from other pathological condition is difficult. Imaging of jawbones is important for disease staging and determining the real extent of bone lesion, which does not correlate with the extent of exposed necrotic bone into the oral cavity. These information are useful mainly during the planning of surgical therapy, ie. resections of the jaws. Detection of associated complications such as pathological fractures, deep neck space infections or maxillary sinusitis is another kind of use. Some of the imaging methods seem to be good in early detection of subclinical lesions or even for differentiation of osteonecrosis from neoplastic jawbone disease. The ability to fulfill these criteria is different for each type of imaging examination, so far the most useful imaging methods are hybrid methods which combine functional and morphological imaging. This hybrid imaging gives information not only about structural pathological changes in the jaws and surrounding soft tissues, but also about osteoblast activity and bone metabolism. There is not enough reported cases of such an imaging in the indication of bisphosphonate-related osteonecrosis of the jaw. High price of some of these examinations is also a limiting factor. Aim of study: In this review article the authors summarize the current knowledge of the use of all available imaging methods in the diagnosis of bisphosphonate-related osteonecrosis of the jaw (radiography, computed tomography, cone beam computed tomography, magnetic resonance imaging, bone scintigraphy and single photon emission computed tomography, positron emission tomography and hybrid imaging methods)

Orbital floor fractures of the blow-out type are not the most frequent in traumatology of orofacial region, but the consequences (particularly persisting diplopia) may seriously handicap the patient in personal and professional life. Opinions of the correct mode of therapy of this injury have been changing throughout the history. New recommendations concerning indications for surgical or conservative treatment arrive all the time as well as questions of the correct time for intervention. In their retrospective study the authors deal with a statistical evaluation of the therapy of 63 patients with blow-out fractures, which was applied in the period of January 2001 through March 2010 at the Stomatology Clinic of Medical Faculty, Charles University and Teaching Hospital at Pilsen. In the present group were followed the age, sex, etiology of the injury, and in surgically treated patients also the used accesta the orbit and the implant types. The results of treatment (conservative/surgical) were then evaluated in view of the lasting diplopia.

Introduction and aim: This study aims to evaluate and predict importance of characteristics that lead to medication-related osteonecrosis of the jaw (MRONJ) and is done by using streamlined multimodal machine learning models with strategy that seeks to facilitate early diagnosis and accurate identification of important risk variables. Methodology: In machine learning, regression analysis is a statistical technique that forecasts a dependent variable's value from the values of one or more independent variables. In this work, we concentrate on four widely used regression models: (1) Linear: the most basic and popular technique, (2) Random Forest: collective learning method that combines several decision trees to provide more reliable predictions, (3) Decision Tree: divide the data into various regions according to the feature values, and (4) Gradient Boosting: builds new models that forecast the errors or older model residuals, then aggregates them using a weighted majority vote. Results: Our cohort comprised 35 female and 23 male patients who visited the University Hospital in Pilsen. Medical evaluations revealed patients with cancer and osteoporosis, with relative number of them taking bisphosphonate (32) and denosumab (38), while 12 patients took both. Extracted teeth totaled 168, either with or without preventative measures, 32 patients in very high risk, 22 in high risk and 4 in low risk level. However, MRONJ developed the most in "very high risk" level (48.39%). While preventive measures have not made a significant difference in subsequent MRONJ incidence compared to non-preventive conditions (52.63% vs. 47.37%). Conclusion: The effectiveness of our unique triad categorization risk system, which greatly improved predicted accuracy across all models tested, is crucial to our conclusions. Since a larger proportion of patients fall into the "very high risk" category and this group is more strongly linked to the eventual development of MRONJ, more innovative and strict preventive measures, like the ones we proposed, are necessary. [ABSTRACT FROM AUTHOR]

The author reports the overview of possible etiology of the osteonecrosis of the jaws including the most interesting historical cases of these lesions.

Úvod a cíl: Čelistní kosti postihuje široké spektrum benigních a maligních onemocnění odontogenního i neodontogenního původu. U zhoubných solidních nádorů a některých benigních lokálně agresivních tumorů je primárním cílem chirurgické terapie jejich radikální odstranění nehledě na zachování přidružených zubů. Management příčinných zubů benigních lézí se řídí doporučeními odborných společností, avšak nejasnosti zůstávají v přístupu k zubům, které do příslušné léze svým kořenem pouze zasahují. Tyto zuby bývají indikovány k endodontickému ošetření nebo k extrakci. Důvodem mohou být jednak historické zvyklosti daných pracovišť nebo i to, že se vychází z předpokladu, že chirurgický výkon v periapikální oblasti vede k ztrátě vitality zubu. Cílem studie bylo stanovit diagnosticko-terapeutický algoritmus těchto zubů. Metodika: Prospektivní studie probíhala na Stomatologické klinice LF UK a FN Plzeň v období 5/2022-12/2023. Inkluzní kritéria byla: pacient s cystickou benigní neagresivní lézí indikovanou k chirurgickému odstranění s vitálními zuby zasahujícími svým apexem do jejího nitra. Vedle klinického vyšetření byly tyto zuby předoperačně a pooperačně posuzovány laser dopplerem (MoorLab), chladovým testem a rentgenovým vyšetřením podle schématu studie. Výsledky: Celkově bylo měřeno 75 zubů, 37 prominujících do defektu, z nichž sedm již bylo v době diagnostiky endodonticky ošetřeno. Během studie vykazovalo pět zubů negativní chladový test již před výkonem a devět zubů v pooperačním období. Deset zubů vykazovalo během sledování pokles průtoku krve. Po 12 měsících však byly pouze tři zuby hodnoceny negativně -- jeden zub byl extrahován, jeden endodonticky ošetřen a jeden má nejistou prognózu. Podařilo se prokázat, že dobrý výsledek lze očekávat s více než 95% jistotou u více než 70 % pozorovaných subjektů. Všechny negativní události se staly do tří měsíců od výkonu. Závěr: Podle výsledků studie lze říci, že zuby, u jejichž apexu se provádí chirurgický zákrok, nemusejí být endodonticky ošetřeny před výkonem. A v případě tzv. ztráty vitality lze reinervaci očekávat do jednoho roku po výkonu. [ABSTRACT FROM AUTHOR]

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The use of antiangiogenic and antiresorptive medications, particularly in patients with cancer or osteoporosis, can lead to osteonecrosis of the jaw following tooth extraction, trauma or arising spontaneously- A condition known as medication-related osteonecrosis of the jaw (MRONJ). In this article, we present a unique case of MRONJ in a patient with no history of antiresorptive or antiangiogenic drug use, who was instead taking the anti-interleukin 17-A (Secukinumab) medication for severe psoriasis. This association has not been previously reported in the literature., Competing Interests: The authors report no conflicts of interest in this work, and there is no financial interest to declare., (© 2024 Hauer et al.)

As a discipline of dentistry, oral implantology deals with the diagnosis, design, insertion, restoration, and/or management of alloplastic or autogenous oral structures for the purpose of regaining contour, function, aesthetics, and speech in a partially or completely edentulous patient. The present review aims to provide the currently available knowledge about the impact of certain systemic disorders and the usage of some medications on the survival rate of dental implant therapy and to highlight the importance of patient management under these conditions. Diabetes, osteoporosis, cardiovascular diseases, and the intake of some medications can increase the risk of the failure of a dental implant. Even though there are relatively few medical contraindications to dental implant treatment, certain conditions may increase the risk of failure or complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Samara et al.)

Chronic hyperplastic candidiasis (CHC) presents a distinctive and relatively rare form of oral candidal infection characterized by the presence of white or white-red patches on the oral mucosa. Often mistaken for leukoplakia or erythroleukoplakia due to their appearance, these lesions display nonhomogeneous textures featuring combinations of white and red hyperplastic or nodular surfaces. Predominant locations for such lesions include the tongue, retro-angular mucosa, and buccal mucosa. This paper aims to investigate the potential influence of specific anatomical locations, retro-angular mucosa, on the development and occurrence of CHC. By examining the relationship between risk factors, we present an approach based on machine learning (ML) to predict the location of CHC occurrence. In this way, we employ Gradient Boosting Regression (GBR) to classify CHC lesion locations based on important risk factors. This estimator can serve both research and diagnostic purposes effectively. The findings underscore that the proposed ML technique can be used to predict the occurrence of CHC in retro-angular mucosa compared to other locations. The results also show a high rate of accuracy in predicting lesion locations. Performance assessment relies on Mean Squared Error (MSE), Root Mean Squared Error (RMSE), R-squared (R 2 ), and Mean Absolute Error (MAE), consistently revealing favorable results that underscore the robustness and dependability of our classification method. Our research contributes valuable insights to the field, enhancing diagnostic accuracy and informing treatment strategies.

In our study, the effect of the use of autofluorescence (Visually Enhanced Lesion Scope-VELscope) on increasing the success rate of surgical treatment in oral squamous carcinoma (OSCC) was investigated. Our hypothesis was tested on a group of 122 patients suffering from OSCC, randomized into a study and a control group enrolled in our study after meeting the inclusion criteria. The preoperative checkup via VELscope, accompanied by the marking of the range of a loss of fluorescence in the study group, was performed before the surgery. We developed a unique mucosal tattoo marking technique for this purpose. The histopathological results after surgical treatment, i.e., the margin status, were then compared. In the study group, we achieved pathological free margin (pFM) in 55 patients, pathological close margin (pCM) in 6 cases, and we encountered no cases of pathological positive margin (pPM) in the mucosal layer. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases, and pFM in 40 of all cases in the mucosal layer. This study demonstrated that preoperative autofluorescence assessment of the mucosal surroundings of OSCC increased the ability to achieve pFM resection 4.8 times in terms of lateral margins.

The objective of this study was to compare the distribution of stress in the maxillary bone, dental implants, and prosthetic components supporting implant-supported maxillary overdentures with partial palatal coverage, in both splinted and unsplinted designs. Two models of maxillary overdentures were designed using the Exocad Dental CAD program, which included cancellous and cortical bone. The complete denture design and abutments (locator abutments in the unsplinted and Hader bar with Vertix attachments placed distally in the splinted variant) were also designed. The denture material was PEEK (Polyetheretherketone), and the method used to analyze patient-specific 3D X-ray scans was 3D QCT/FEA (three-dimensional quantitative computed tomography-based finite element analysis). Loading was divided into three load cases, in the frontal region (both incisors of the denture) and distal region (both molars and first premolar of the denture). The forces applied were 150 N with an oblique component with a buccal inclination of 35° in the frontal region, and 600 N with a buccal inclination of 5° (molars) or solely vertical (premolar) in the distal region. The model with locator abutments showed higher stresses in all load cases in both analyzed implant variants and in the maxilla. The differences in stress distribution between the splinted and unsplinted variants were more significant in the distal region. According to the results of the present study, the amount of stress in bone tissue and dental implant parts was smaller in the splinted, bar-retained variant. The findings of this study can be useful in selecting the appropriate prosthetic design for implant-supported maxillary overdentures with partial palatal coverage.

Advanced mathematical and deep learning (DL) algorithms have recently played a crucial role in diagnosing medical parameters and diseases. One of these areas that need to be more focused on is dentistry. This is why creating digital twins of dental issues in the metaverse is a practical and effective technique to benefit from the immersive characteristics of this technology and adapt the real world of dentistry to the virtual world. These technologies can create virtual facilities and environments for patients, physicians, and researchers to access a variety of medical services. Experiencing an immersive interaction between doctors and patients can be another considerable advantage of these technologies, which can dramatically improve the efficiency of the healthcare system. In addition, offering these amenities through a blockchain system enhances reliability, safety, openness, and the ability to trace data exchange. It also brings about cost savings through improved efficiencies. In this paper, a digital twin of cervical vertebral maturation (CVM), which is a critical factor in a wide range of dental surgery, within a blockchain-based metaverse platform is designed and implemented. A DL method has been used to create an automated diagnosis process for the upcoming CVM images in the proposed platform. This method includes MobileNetV2, a mobile architecture that improves the performance of mobile models in multiple tasks and benchmarks. The proposed technique of digital twinning is simple, fast, and suitable for physicians and medical specialists, as well as for adapting to the Internet of Medical Things (IoMT) due to its low latency and computing costs. One of the important contributions of the current study is to use of DL-based computer vision as a real-time measurement method so that the proposed digital twin does not require additional sensors. Furthermore, a comprehensive conceptual framework for creating digital twins of CVM based on MobileNetV2 within a blockchain ecosystem has been designed and implemented, showing the applicability and suitability of the introduced approach. The high performance of the proposed model on a collected small dataset demonstrates that low-cost deep learning can be used for diagnosis, anomaly detection, better design, and many more applications of the upcoming digital representations. In addition, this study shows how digital twins can be performed and developed for dental issues with the lowest hardware infrastructures, reducing the costs of diagnosis and treatment for patients.

Medical digital twins, which represent medical assets, play a crucial role in connecting the physical world to the metaverse, enabling patients to access virtual medical services and experience immersive interactions with the real world. One serious disease that can be diagnosed and treated using this technology is cancer. However, the digitalization of such diseases for use in the metaverse is a highly complex process. To address this, this study aims to use machine learning (ML) techniques to create real-time and reliable digital twins of cancer for diagnostic and therapeutic purposes. The study focuses on four classical ML techniques that are simple and fast for medical specialists without extensive Artificial Intelligence (AI) knowledge, and meet the requirements of the Internet of Medical Things (IoMT) in terms of latency and cost. The case study focuses on breast cancer (BC), the second most prevalent form of cancer worldwide. The study also presents a comprehensive conceptual framework to illustrate the process of creating digital twins of cancer, and demonstrates the feasibility and reliability of these digital twins in monitoring, diagnosing, and predicting medical parameters.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation oral fumaric acid ester (FAE) that was developed as a formulation with better GI tolerability. The improved tolerability is assumed to be related to a lower synthesis of gut-irritating methanol. Other explanations for DRF's lower extent of GI irritation include a more modest off-target activity due to its chemical structure. The superior GI tolerability of DRF compared to DMF could be proven in clinical trials and lead to approval of DRF for the treatment of relapsing forms of MS/relapsing-remitting MS (United States Food and Drug Administration and European Medicines Agency, respectively). Here, we summarize the mode of action of oral FAE and compare the chemical and physiological characteristics of DMF and DRF. Moreover, we discuss the adverse effects of FAE and introduce the emerging preclinical and trial data leading to the approval of DRF in MS. This article additionally reviews our current understanding of coronavirus disease 2019 (COVID-19) and the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in people treated with FAE., Competing Interests: LH has nothing to disclose. JS received honoraria for presentations and the assembly of educational material from Alexion, Angelini, BMS, Biogen, Boehringer, Immunic, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi. He is a member of scientific advisory boards of Alexion, BMS, Biogen, Boehringer, Novartis, Sandoz and Sanofi., (© 2022 Hauer and Sellner.)

We study the equilibrium properties and the wetting behavior of a simple liquid on a polymer brush, with and without the presence of lubricant by multibody Dissipative Particle Dynamics simulations. The lubricant is modeled as a polymeric liquid consisting of short chains that are chemically identical with the brush polymers. We investigate the behavior of the brush in terms of the grafting density and the amount of lubricant present. Regarding the wetting behavior, we study a sessile droplet on top of the brush. The droplet consists of nonbonded particles that form a dense phase. Our model and choice of parameters result in the formation of a wetting ridge and in the cloaking of the droplet by the lubricant; i.e., the lubricant chains creep up onto the droplet and eventually cover its surface completely. Cloaking is a phenomenon that is observed experimentally and is of integral importance to the dynamics of sliding droplets. We quantify the cloaking in terms of its thickness, which increases with the amount of lubricant present. The analysis reveals a well-defined transition point where the cloaking sets in. We propose a thermodynamic theory to explain this behavior. In addition, we investigate the dependence of the contact angles on the size of the droplet and the possible effect of line tension. We quantify the variation of the contact angle with the curvature of the contact line on a lubricant free brush and find a negative value for the line tension. Finally we investigate the effect of cloaking/lubrication on the contact angles and the wetting ridge. We find that lubrication and cloaking reduce the contact angles by a couple of degrees. The effect on the wetting ridge is a reduction in the extension of the brush chains near the three phase contact line, an effect that was also observed in experiments of droplets on cross-linked gels.

The presence of supercooled water in polar regions causes anchor ice to grow on submerged objects, generating costly problems for engineered materials and life-endangering risks for benthic communities. The factors driving underwater ice accretion are poorly understood, and passive prevention mechanisms remain unknown. Here we report that the Antarctic scallop Adamussium colbecki appears to remain ice-free in shallow Antarctic marine environments where underwater ice growth is prevalent. In contrast, scallops colonized by bush sponges in the same microhabitat grow ice and are removed from the population. Characterization of the Antarctic scallop shells revealed a hierarchical micro-ridge structure with sub-micron nano-ridges which promotes directed icing. This concentrates the formation of ice on the growth rings while leaving the regions in between free of ice, and appears to reduce ice-to-shell adhesion when compared to temperate species that do not possess highly ordered surface structures. The ability to control the formation of ice may enable passive underwater anti-icing protection, with the removal of ice possibly facilitated by ocean currents or scallop movements. We term this behavior cryofouling avoidance. We posit that the evolution of natural anti-icing structures is a key trait for the survival of Antarctic scallops in anchor ice zones., (© 2022. The Author(s).)

Wet and dry foams are prevalent in many industries, ranging from the food processing and commercial cosmetic sectors to industries such as chemical and oil-refining. Uncontrolled foaming results in product losses, equipment downtime or damage and cleanup costs. To speed up defoaming or enable anti-foaming, liquid oil or hydrophobic particles are usually added. However, such additives may need to be later separated and removed for environmental reasons and product quality. Here, we show that passive defoaming or active anti-foaming is possible simply by the interaction of foam with chemically or morphologically modified surfaces, of which the superamphiphobic variant exhibits superior performance. They significantly improve retraction of highly stable wet foams and prevention of growing dry foams, as quantified for beer and aqueous soap solution as model systems. Microscopic imaging reveals that amphiphobic nano-protrusions directly destabilize contacting foam bubbles, which can favorably vent through air gaps warranted by a Cassie wetting state. This mode of interfacial destabilization offers untapped potential for developing efficient, low-power and sustainable foam and froth management., (© 2021. The Author(s).)

Aims: The aim of the present study was to evaluate the general and oral health status of a group of preterm one-year-old very low (VLBW) and extremely low birthweight (ELBW) infants and make a comparison with full-term one-year-old normal birthweight infants (NBW)., Methods: A cross-sectional study was conducted in 102 one-year-old preterm VLBW and ELBW infants, and the data obtained were compared to 87 one-year-old full-term NBW infants. The infants' medical histories were obtained from hospital records and interviews with the mothers. The oral cavities of all infants were examined under the same conditions. The chi-square test, Pearson's chi-square test of independence and Mann-Whitney test were used for the statistical evaluation, with P < 0.05 considered statistically significant. Relative risk (RR) and 95% confidence interval (CI) estimates for variables significantly associated with oral findings were calculated., Results: Both perinatal variables (gestational age, mode of delivery, birthweight, Apgar score, resuscitation, orotracheal intubation and presence of intraoral pathology) and neonatal variables (antibiotic treatment and infections) had a significant association with prematurity, VLBW and ELBW. The one-year-old preterm VLBW and ELBW infants frequently suffered from general diseases, frequently received regular medication and had fewer erupted primary teeth; they also had a higher prevalence of developmental defects of the enamel and deformations of the hard palate., Conclusion: This study confirmed anamnestic, medical and oral differences between one-year-old preterm VLBW and ELBW and full-term NBW infants.

Intracranial artery calcification can be detected on nonenhanced brain computer tomography (NECT) and is a predictor of early vascular events. Here, we assessed the impact of vertebrobasilar artery calcification (VBC) on the long-term risk for recurrent stroke and vascular events. We performed a case-control trial of all consecutive stroke patients admitted to the University Hospital of Maribor, Slovenia over a period of 14 months. VBC was defined as presence of a hyperdense area within vertebrobasilar arteries that exceeds > 90 Hounsfield units as seen on NECT. Clinical follow-up information was obtained from the hospital documentation system and mortality registry of the district and included recurrent stroke, subsequent vascular events (myocardial infarction, heart failure, peripheral arterial occlusive disease), and death. We followed a total of 448 patients for a median of 1505 days (interquartile range, IQR 188-2479). Evidence for VBC was present in 243 (54.2%) patients. Median age was 76 years, recurrent stroke occurred in 33 (7.4%), any vascular events in 71 (15.8%), and death in 276 (61.6%). VBC was associated with a higher risk of recurrent stroke (hazard ratio, HR 3.13, 95% confidence interval (CI 1.35-7.20)) and vascular events (HR 2.05, 95% CI 1.21-3.47). Advanced age, male gender, and ischemic stroke involving the entire anterior circulation raised the likelihood for death. We conclude that the presence of VBC in patients with ischemic stroke is a short- and long-term prognostic factor for stroke recurrence and subsequent manifestation of acute vascular disease. Further understanding of the pathophysiology of VBC is warranted., Competing Interests: The authors declare no conflict of interest.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

Background: Medication - related osteonecrosis of the jaw (MRONJ) is a rare but serious complication of antiresorptive and/or antiangiogenic therapy. It mainly affects oncological patients, however, it can occur in patients with metabolic bone diseases, although this is less frequent. These lesions not only significantly impair the quality of life but can also have impact on the treatment of any underlying disease. In some rare cases MRONJ can be life-threatening. There is still no ideal consensus for treatment, though surgical therapy has been mostly preferred in recent years., Materials and Methods: A monocentric retrospective evaluation of surgical therapy of MRONJ in osteoporotic patients, treated in the time period 3/2014-3/2018 using the uniform department-specific protocol., Results: 26 osteoporotic patients with 32 MRONJ lesions of stage 1 (9%), stage 2 (75%) and stage 3 (16%) were treated surgically. The maxilla: mandibula ratio was 1:2.2, in 19% of patients there was multiple jaw involvement. 69.2% of patients had received bisphosphonates, 15.4% denosumab and 15.4% had a history of both types of antiresorptive treatment. Complete healing was observed in all patients, in 9% of cases by secondary intention in the mean period of 6 weeks. The mean follow-up was 20.5 months., Conclusion: The presented protocol for surgical therapy was effective in the management of all MRONJ stages in the osteoporotic patients described here. The surgery is indicated as an early treatment to prevent complications and the progression of the lesions. It leads to improvement in quality of life and option to resume antiresorptive therapy if interrupted.

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.

Hypertrophic pachymeningitis is a rare inflammatory condition characterized by the thickening of the dura mater. We describe a patient who presented with intractable headache and complex cranial nerve palsy. Hypertrophy of the frontal dura was accompanied by pleocytosis and detection of Epstein-Barr virus (EBV) by PCR in cerebrospinal fluid. Clinical symptoms gradually improved after acyclovir and corticosteroid treatment, whereas dural pathology remained unchanged on neuroimaging. This case points at an expansion of the spectrum of neurological manifestations for EBV.

Repetitive transcranial magnetic stimulation (rTMS) may be effective for enhancing cognitive functioning. In this review, we aimed to systematically evaluate the effects of rTMS on attention in psychiatric diseases. In particular, we searched PubMed and Embase to examine the effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC) on this specific cognitive domain. The search identified 24 articles, 21 of which met inclusion and exclusion criteria. Among them, nine were conducted in patients with depression, four in patients with schizophrenia, three in patients with autism spectrum disorder (ASD), two in patients with attention deficit hyperactivity disorder, one each in patients with Alzheimer's disease and in patients with alcohol or methamphetamine addiction. No evidence for cognitive adverse effects was found in all the included rTMS studies. Several studies showed a significant improvement of attentional function in patients with depression and schizophrenia. The beneficial effects on attention and other executive functions suggest that rTMS has the potential to target core features of ASD. rTMS may influence the attentional networks in alcohol-dependent and other addicted patients. We also reviewed and discussed the studies assessing the effects of rTMS on attention in the healthy population. This review suggests that prefrontal rTMS could exert procognitive effects on attention in patients with many psychiatric disorders.

Background: Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV)., Aim of the Study: To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection., Methods: Systematic literature review from January 2000 to July 2018., Results: We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations., Conclusion: We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.