Staging Scheme Research Articles

New clinical staging proposal applied to a Fabry cardiomyopathy cohort

Abstract Background Fabry disease (FD) is a rare cause of hypertrophic cardiomyopathy (HCM), and early diagnosis is important considering the response to enzyme replacement or chaperone therapies. Recently, a practical clinical staging for Fabry cardiomyopathy was proposed by Olivotto et al 2023, considering several features, being potentially useful for standardizing the criteria for initiation and response assessment to therapy. Imaging characterization of hypertrophy and fibrosis are critical key items to determine stages. This new proposal suggested 4 main stages (0, I, II, III) according to these parameters. Stages 0 and I are further divided in 2 sub-stages according to minor findings and hypertrophy severity, respectively. Unfortunately, not all patients with Fabry cardiomyopathy are identified early in the disease, limiting the response to treatment. Aim Our study aimed to evaluate retrospectively the staging of Fabry cardiomyopathy at first imaging cardiac evaluation according to the recent proposal (1), in a cohort of 35 patients with FD at a reference centre of Fabry disease. Results At the first cardiac evaluation, the group of patients had a median age of 46 years (28-68 years), 69% were female and 5% were already under enzymatic therapy. The majority of Fabry patients (66%) were in non-hypertrophic stage 0: 4 patients in 0A with no detected cardiac involvement and 19 patients in 0B with subclinical cardiac findings (17% presenting diastolic dysfunction, 14% impaired global longitudinal strain, 6% hypertrabeculation, 6% reduced native T1, 3% short PR duration, 3% cardiac symptoms). In hypertrophic stage I, 14% of patients were classified according to the presence and severity of LVH: 3 in IA (12-15 mm) and 2 in IB (>15mm). All patients (n=3, 9%) in hypertrophic fibrotic stage II presented non-extensive late enhancement (< 3 LV segments) in the first CMR. Patients with overt dysfunction or stage III (n=4; 11%), presented diffuse myocardial fibrosis (> 3 LV segments) or impaired systolic function (LVEF < 50%). Conclusion In our cohort patients, the new staging scheme allows us to identify and classify the different stages of FD cardiomyopathy. The majority of patients were unexpectedly identified in early disease stages, but that could be related to diagnosis in the context of familial screening. This proposal seems useful for clinical staging standardization to facilitate the evaluation of responses to treatments and to predict outcomes, however, needs to be validated in larger and prospective studies.

A Comprehensive Multi-Functional Approach for Measuring Parkinson's Disease Severity.

This research study aims to advance the staging of Parkinson's disease (PD) by incorporating machine learning to assess and include a broader multi-functional spectrum of neurocognitive symptoms in the staging schemes beyond motor-centric assessments. Specifically, we provide a novel framework to modernize and personalize PD staging more objectively by proposing a hybrid feature scoring approach. We recruited thirty-seven individuals diagnosed with PD, each of whom completed a series of tablet-based neurocognitive tests assessing motor, memory, speech, executive functions, and tasks ranging in complexity from single to multi-functional. Then, the collected data was used to develop a hybrid feature scoring system to calculate a weighted vector for each function. We evaluated current PD staging schemes and developed a new approach based on the features selected and extracted using Random Forest and Principal Component Analysis. Our findings indicate a substantial bias in current PD staging systems toward fine-motor skills, i.e., other neurological functions (memory, speech, executive function, etc.) do not map into current PD stages as well as fine-motor skills do. The results demonstrate that a more accurate and personalized assessment of PD severity could be achieved by including a more exhaustive range of neurocognitive functions in the staging systems either by involving multiple functions in a unified staging score or by designing a function-specific staging system. The proposed hybrid feature score approach provides a comprehensive understanding of PD by highlighting the need for a staging system that covers various neurocognitive functions. This approach could potentially lead to more effective, objective, and personalized treatment strategies. Further, this proposed methodology could be adapted to other neurodegenerative conditions such as Alzheimer's disease or ALS.

Pilot implementation of the revised criteria for staging of Alzheimer's disease by the Alzheimer's Association Workgroup in a tertiary memory clinic.

We aimed to evaluate the feasibility of the 2024 Alzheimer's Association Workgroup's integrated clinical-biological staging scheme in outpatient settings within a tertiary memory clinic. The 2018 syndromal cognitive staging system, coupled with a binary biomarker classification, was implemented for 236 outpatients with cognitive concerns. The 2024 numeric clinical staging framework, incorporating biomarker staging, was specifically applied to 154 individuals within the Alzheimer's disease (AD) continuum. The 2024 staging scheme accurately classified 95.5% AD. Among these, 56.5% exhibited concordant clinical and biological stages (canonical), 34.7% demonstrated more advanced clinical stages than biologically expected (susceptible), and 8.8% displayed the inverse pattern (resilient). The susceptible group was characterized by a higher burden of neurodegeneration and inflammation than anticipated from tau, whereas the resilient group showed the opposite. The 2024 staging scheme is generally feasible. A discrepancy between clinical and biological stages is relatively frequent among symptomatic patients with AD. The 2024 AA staging scheme is generally feasible in a tertiary memory clinic. A discrepancy between clinical and biological stages is relatively frequent in AD. The mismatch may be influenced by a non-specific pathological process involved in AD. Individual profiles like aging and lifestyles may contribute to such a mismatch. Matched and mismatched cases converge toward similar clinical outcomes.

Ocular melanosis in the adult Cairn Terrier population within the United Kingdom.

Prospective investigation to determine the prevalence of ocular melanosis in adult Cairn Terriers within the United Kingdom using a previously established staging scheme. Ophthalmic assessment was performed on adult Cairn Terriers, recruited from various geographic locations within the United Kingdom. Examination included gonioscopy, rebound tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy, performed by one examiner (AM). A total of 93 dogs were examined, including 52 females and 41 males, aged between 15 months and 16 years 4 months. Sixty of 93 dogs (64.5%) were >7 years of age. Nine of 93 dogs (9.6%) demonstrated changes consistent with ocular melanosis. Four of 9 (44.4%) had Stage 1 disease and 5 of 9 (55.6%), Stage 2. Stages 3 or 4 were not identified in any dogs. Mean intraocular pressures in affected and unaffected dogs were 14.7 mmHg (range 12-17 mmHg) and 12.8 mmHg (range 5-21 mmHg), respectively. Incomplete pupil dilation was noted in affected dogs following pharmacologic mydriasis. Ocular melanosis was identified in approximately 10% of examined dogs, over half were dogs of breeding age (<7 years of age). It is possible that Grade 1 disease could go undetected, prior to obvious scleral pigment accumulation (Grade 2 disease). It is therefore recommended that dogs undergoing pre-breeding screens have pre-dilation assessment of the anterior segment using slit lamp biomicroscopy with subsequent gonioscopy to clearly assess for circumferential thickening of the iris base that might otherwise go undetected. Additionally, regular reassessment of breeding dogs is advised as disease progression could be rapid.

SPECTRAL-DOMAIN OCT INSIGHTS INTO IDIOPATHIC EPIRETINAL MEMBRANE SURGERY OUTCOMES.

This study aims to assess the prognostic value of a classification system that includes the presence of ectopic inner foveal layers (EIFL) and other anatomical variables identified in spectral-domain optical coherence tomography (SD-OCT) for idiopathic epiretinal membrane (ERM) surgery. A descriptive-analytic, longitudinal, retrospective study was conducted on patients with idiopathic ERMs treated with pars plana vitrectomy (PPV) from January 2017 to December 2021. Clinical data and SD-OCT images were reviewed pre-surgery and 12 months post-surgery. The primary outcome measured was best corrected visual acuity (BCVA) before and after surgery, analyzing the impact of anatomical factors on BCVA in patients undergoing ERM surgery. The study included 342 eyes from 323 patients. Post-surgical evaluations showed significant reductions in central foveal thickness (CFT) across all ERM stages, with most stage 4 ERMs regressing to stage 3. The mean improvement in BCVA was significant for all stages, with earlier stages showing better results. Presence of macular edema (ME) and ellipsoid zone (EZ) disruption were significant predictors of post-surgical BCVA, while disorganization of the retinal inner layer (DRIL) showed association with visual recovery but was not conclusively predictive. The study highlights the importance of SD-OCT in assessing retinal changes in idiopathic ERMs, demonstrating the prognostic value of EIFL stage scheme and other anatomical variables like EZ disruption and ME presence on BCVA. These findings offer insights for surgical prognostication and the potential for personalized treatment strategies.

Randomized algorithms for large-scale dictionary learning

Dictionary learning is an important sparse representation algorithm which has been widely used in machine learning and artificial intelligence. However, for massive data in the big data era, classical dictionary learning algorithms are computationally expensive and even can be infeasible. To overcome this difficulty, we propose new dictionary learning methods based on randomized algorithms. The contributions of this work are as follows. First, we find that dictionary matrix is often numerically low-rank. Based on this property, we apply randomized singular value decomposition (RSVD) to the dictionary matrix, and propose a randomized algorithm for linear dictionary learning. Compared with the classical K-SVD algorithm, an advantage is that one can update all the elements of the dictionary matrix simultaneously. Second, to the best of our knowledge, there are few theoretical results on why one can solve the involved matrix computation problems inexactly in dictionary learning. To fill-in this gap, we show the rationality of this randomized algorithm with inexact solving, from a matrix perturbation analysis point of view. Third, based on the numerically low-rank property and Nyström approximation of the kernel matrix, we propose a randomized kernel dictionary learning algorithm, and establish the distance between the exact solution and the computed solution, to show the effectiveness of the proposed randomized kernel dictionary learning algorithm. Fourth, we propose an efficient scheme for the testing stage in kernel dictionary learning. By using this strategy, there is no need to form nor store kernel matrices explicitly both in the training and the testing stages. Comprehensive numerical experiments are performed on some real-world data sets. Numerical results demonstrate the rationality of our strategies, and show that the proposed algorithms are much efficient than some state-of-the-art dictionary learning algorithms. The MATLAB codes of the proposed algorithms are publicly available from https://github.com/Jiali-yang/RALDL_RAKDL.

Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup.

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.

Evaluation of combined epiretinal membrane removal with intravitreal triamcinolone injection utilizing ectopic inner foveal layer staging scheme.

To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. After a mean follow-up of 7.69 ± 3.68months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.

Chronology and main stages of vegetation development in the central region of the East European Plain during the Mikulino interglacial

The chronology of the Mikulino Interglacial and its individual phases have been the subject of discussion. The goal of this study was to evaluate the time limits of the main stages of the Mikulino Interglacial on the Russian Plain according to ²³⁰Th/U dating and paleobotanical studies of lake and peat sediments from the known sections located within the Tver region on the Bolshaya Dubenka River, Malaya Kosha River, Granichnaya River, and Sizhina River (“Kileshino-2” section). An improved geochronological approach has been applied to identify layers suitable for the ²³⁰Th/U isochronous approximation. In combination with pollen and carpological studies of the deposits, this made it possible to date units corresponding to relatively narrow time intervals in the development of plant formations at different stages of the Last Interglacial. New paleobotanical studies of buried lake and peat sediments from the sections located on the Bolshaya Dubenka River, Malaya Kosha River, and Granichnaya River allowed us to restore the vegetation development during the Mikulino Interglacial in the interval of pollen zones M1–M7, i.e., more pollen zones have been analyzed and in greater detail than in 1960–1970. A chronological scheme of the main stages of vegetation development in the Mikulino Interglacial is proposed based on the results of ²³⁰Th/U dating and paleobotanical studies of organic-rich deposits from the Tver region sections in combination with previously published data obtained for the “Nizhnyaya Boyarshchina” section from the Smolensk region. The Mikulino Interglacial had begun about 130–126 kyr ago. Its first phase, corresponding to the M2 zone, ended ca. 118 kyr ago. The pre-optimal stages of vegetation development (M3 and M4 zones) fit into the time range of ca. 118–112 kyr ago. The climatic optimum of the interglacial (M5 and M6 zones) began ca. 112 kyr ago and ended ca. 100 kyr ago. The duration of the Mikulino Interglacial was probably at least 25 thousand years.

ВЛИЯНИЕ МЕТИЛЬНОЙ ГРУППЫ НА СКОРОСТЬ РЕАКЦИИ ОКИСЛИТЕЛЬНОГО ДЕГИДРИРОВАНИЯ МЕТИЛЦИКЛОГЕКСАНОЛОВ НА МОДИФИЦИРОВАННОМ ЦЕОЛИТНОМ КАТАЛИЗАТОРЕ

In this article has been carried out the study and comparing the reactivity of cyclohexanol and methylcyclohexanol isomers in the oxidative dehydrogenation reaction over modified zeolite catalysts. For this purpose, have been investigated the kinetic laws for the two unstudied isomers of methylcyclohexanol (2- and 3-methylcyclohexanol), proposed the mechanisms, kinetic stage schemes for the formation of target products, and developed kinetic models of these processes. It has been found that the rates of oxidative dehydrogenation of all methylcyclohexanol isomers are practically the same and exceed the rate of oxidative dehydrogenation of cyclohexanol to cyclohexanone.

Localization and origins of juvenile skeletogenic cells in the sea urchin Lytechinuspictus

The development of the sea urchin larval body plan is well understood from extensive studies of embryonic patterning. However, fewer studies have investigated the late larval stages during which the unique pentaradial adult body plan develops. Previous work on late larval development highlights major tissue changes leading up to metamorphosis, but the location of specific cell types during juvenile development is less understood. Here, we improve on technical limitations by applying highly sensitive hybridization chain reaction fluorescent in situ hybridization (HCR-FISH) to the fast-developing and transparent sea urchin Lytechinus pictus, with a focus on skeletogenic cells. First, we show that HCR-FISH can be used in L. pictus to precisely localize skeletogenic cells in the rudiment. In doing so, we provide a detailed staging scheme for the appearance of skeletogenic cells around the rudiment prior to and during biomineralization and show that many skeletogenic cells unassociated with larval rods localize outside of the rudiment prior to localizing inside. Second, we show that downstream biomineralization genes have similar expression patterns during larval and juvenile skeletogenesis, suggesting some conservation of skeletogenic mechanisms during development between stages. Third, we find co-expression of blastocoelar and skeletogenic cell markers around juvenile skeleton located outside of the rudiment, which is consistent with data showing that cells from the non-skeletogenic mesoderm embryonic lineage contribute to the juvenile skeletogenic cell lineage. This work sets the foundation for subsequent studies of other cell types in the late larva of L. pictus to better understand juvenile body plan development, patterning, and evolution.

467P Novel staging schemes for Siewert type II esophagogastric junction adenocarcinoma: A real-world data cohort study from SEER database

467P Novel staging schemes for Siewert type II esophagogastric junction adenocarcinoma: A real-world data cohort study from SEER database

Symptom-based staging for logopenic variant primary progressive aphasia.

Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. 'Milestone' symptoms were identified that anticipate daily-life functional transitions and care needs. This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

Melanoma of the dog and cat: consensus and guidelines.

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting.

KINETIC MODELS OF CHAOS IN LINEAR CATALYTIC REACTIONS

Chaos (chaotic oscillations, strange attractors) are aperiodic changes in certain parameters of the dynamic system under study, which differ from other types of oscillations (damped, undamped, multi-periodic) by unusually complex, unpredictable dynamic behavior, and can be observed for an arbitrarily long time. From the theory of dynamical systems it follows that chaotic oscillations can be described by nonlinear systems of ordinary differential equations with three or more independent variables. Until now, such differential equations have been used to construct kinetic models within the framework of the ideal law of mass action, describing chaotic oscillations in homogeneous and heterogeneous catalytic reactions. Moreover, these kinetic models describe chaotic oscillations only for reactions occurring according to stage schemes that are nonlinear with respect to intermediate substances. This article explores the possibility of describing chaotic oscillations by linear systems of ordinary differential equations with three independent variables, which, within the framework of the nonideal Marcelin-de Donde kinetic law, correspond to stage schemes linear in intermediate substances. It is shown that in real conditions, when the Marcelin-de Donde law is satisfied, kinetic models of mechanisms linear in intermediate substances make it possible to describe any complex dynamic behavior of catalytic reactions. Four-stage linear schemes in intermediate substances have been established, the kinetic models of which describe chaotic oscillations of the reactions of interaction between nitrogen monoxides and carbon monoxides (2NO + CO → N2O + CO2) and the oxidation of carbon monoxide (2CO + O2 → 2CO2) on platinum catalysts with Marcelin-de Donde kinetics in an isothermal gradientless reactor. For citation: Kol'tsov N.I. Kinetic models of chaos in linear catalytic reactions. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 5. P. 121-127. DOI: 10.6060/ivkkt.20246705.6956.

Geotechnical analysis involving strain localization of overconsolidated soils based on unified hardening model with hardening variable updated by a composite scheme

AbstractStrain localization simulation of overconsolidated soils with high overconsolidation ratio (OCR) has been a long‐standing challenge. Some critical state soil models, including the modified Cam‐clay (MCC) model, have been widely applied, but they may not predict the shear dilatancy of overconsolidated soils well in some cases. Hence, the unified hardening (UH) model, which may be viewed as a generalized version of the MCC model, is implemented. It has been recognized, nonetheless, that without resorting to the regularization mechanism, the standard finite element method (FEM) or the second‐order cone programming optimized finite element method (FEM‐SOCP) often experiences instability or interruption of calculating the hardening‐softening responses of overconsolidated soils. To resolve the aforementioned difficulty, the UH model is developed and implemented in the framework of FEM‐SOCP based on the micropolar continuum (mpcFEM‐SOCP) to predict strain localizations of overconsolidated soils. Furthermore, to obviate non‐convexity of mpcFEM‐SOCP induced by material softening, an effective composite update scheme of hardening variable pc, which refers to the implicit variable (IV) scheme for the hardening stage and then refers to the explicit variable (EV) scheme for the softening stage, is proposed. Based on one biaxial compression problem and one rigid strip footing problem, numerical analyses disclose that by applying mpcFEM‐SOCP in conjunction with the composite update scheme of pc, the UH model of micropolar continuum can effectively predict the strain localization behavior of overconsolidated soil during its failure stage, and the stable hardening‐softening responses of overconsolidated soils can be readily attained.

Attachment Loss Attributable to Third Molar Malposition/Extraction: The Case for Classification

Background: The 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions established a periodontitis staging and grading scheme that—for the first time—integrates an assessment of disease severity with an appraisal of therapeutic complexity and risk for disease progression. Individuals exhibiting attachment loss attributable to third molar malposition or extraction represent a large cohort of non-periodontitis patients highly likely to respond favorably to treatment. The purpose of this clinical report is to illustrate the value in formally categorizing this common periodontal condition. Case Description: Two male patients were referred to the Department of Periodontics, Army Postgraduate Dental School, for evaluation of bone and attachment loss limited to distal surfaces of mandibular second molars. Each patient was treated using a combination of guided tissue regeneration and bone replacement grafts. Favorable clinical and radiographic outcomes were observed over follow-up periods ranging from 4 months to 4 years. Practical Implications: Many patients experiencing bone and attachment loss attributable to third molar malposition or extraction lack periodontitis risk factors/indicators, have low susceptibility to the disease, and are highly likely to respond favorably to treatment. Future classification systems of periodontal diseases and conditions should formally categorize this commonly encountered periodontal condition.

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC.

There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR. Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy. Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers.

A developmental atlas of male terminalia across twelve species of Drosophila.

How complex morphologies evolve is one of the central questions in evolutionary biology. Observing the morphogenetic events that occur during development provides a unique perspective on the origins and diversification of morphological novelty. One can trace the tissue of origin, emergence, and even regression of structures to resolve murky homology relationships between species. Here, we trace the developmental events that shape some of the most diverse organs in the animal kingdom-the male terminalia (genitalia and analia) of Drosophilids. Male genitalia are known for their rapid evolution with closely related species of the Drosophila genus demonstrating vast variation in their reproductive morphology. We used confocal microscopy to monitor terminalia development during metamorphosis in twelve related species of Drosophila. From this comprehensive dataset, we propose a new staging scheme for pupal terminalia development based on shared developmental landmarks, which allows one to align developmental time points between species. We were able to trace the origin of different substructures, find new morphologies and suggest possible homology of certain substructures. Additionally, we demonstrate that posterior lobe is likely originated prior to the split between the Drosophila melanogaster and the Drosophila yakuba clade. Our dataset opens up many new directions of research and provides an entry point for future studies of the Drosophila male terminalia evolution and development.

ОБЛІКОВО-АНАЛІТИЧНЕ ЗАБЕЗПЕЧЕННЯ ІМПОРТУ МЕДИЧНОГО ОБЛАДНАННЯ

The aim of the research was to assess the state of the medical equipment market and its import, construct an algorithm (stages) of this process, and identify components related to accounting organization to enhance the efficiency of such assets in unstable conditions. To achieve this, the positions of modern scholars dedicated to the import of medical equipment and its accounting and analytical support were critically evaluated. The dynamics of the global market for medical technologies and their import into Ukraine were identified. Based on the obtained results, a reasoned scheme of import stages was constructed. The components, sequence of implementation, significance, and content of each stage were justified. The proposed step-by-step logical scheme of medical equipment import includes organizational, methodical-accounting, and analytical components. The main characteristics of each stage were identified, and improvements were proposed for elements belonging to the accounting system, such as the use of accounting records, the ability to simultaneously use various equipment acquisition sources, and the conduct of valuation procedures to justify the optimal selection. The proposed import stages will allow healthcare entities to organize the process of medical equipment procurement efficiently and with maximum benefit. They contribute to improving vital classical management functions, namely accounting and analysis, by enhancing their informativeness and completeness. Adherence to the import stages will not only contribute to the efficiency of representatives responsible for medical equipment supply and quality within our country but also enable consumers to actively participate in improving its utilization through improved accounting and analysis methods.