Modality Specificity Research Articles

Light induces a rapid increase in cAMP and activates PKA in rod outer segments of the frog retina.

The phototransduction cascade enables the photoreceptor to detect light over a wide range of intensities without saturation. The main second messenger of the cascade is cGMP and the primary regulatory mechanism is calcium feedback. However, some experimental data suggest that cAMP may also play a role in regulating the phototransduction cascade, but this would require changes in cAMP on a time scale of seconds. Currently, there is a lack of data on the dynamics of changes in intracellular cAMP levels on this timescale. This is largely due to the specificity of the sensory modality of photoreceptors, which makes it practically impossible to use conventional experimental approaches based on fluorescence methods. In this study, we employed the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. The study employed highly sensitive metabolomics approaches to measure levels of cAMP. Additionally, PKA activity was measured in the samples using a western blot. The results indicate that when exposed to near-saturating but still moderate light, cAMP levels increase transiently within the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, resulting in the phosphorylation of PKA-specific substrates in frog retinal outer segments.

RETROSPECTIVE ANALYSIS OF DISCORDANT RESULTS BETWEEN UROVYSION FISH AND URINE CYTOLOGY IN THE DETECTION OF HIGH-GRADE UROTHELIAL CARCINOMA (HGUC): A STUDY OF 118 PATIENTS

Abstract Introduction/Objective Accurate detection of high-grade urothelial carcinoma (HGUC) relies on multiple diagnostic modalities, including UroVysion FISH and urine cytology; however, discordant results between these diagnostic tools can present a challenge. We present this study, scrutinizing the discordant results between UroVysion FISH and urine cytology to explore the potential factors that could contribute to discrepancies. Methods/Case Report A cohort of 118 patients, who underwent both UroVysion FISH and urine cytology testing for evaluation of HGUC, was selected from our cytopathology archives. Results of both the modalities were compared, and a retrospective review of original slides was done by experienced cytopathologists. Results (if a Case Study enter NA) Among the 118 cases, Urovysion FISH yielded positive results in 14 cases and negative in 104. In contrast, urine cytology reported 1 case as positive, 102 as negative, 10 as atypical (8 atypical and 2 rare atypical), and 5 as suspicious. Discordant findings were observed in 20 cases, accounting for 17% of the cases. After retrospective review of original slides, few cases were reclassified. 2 cases as atypical (initially labeled as negative), 2 cases as negative (initially labeled as atypical), 3 cases as positive (initially labeled as atypical/suspicious), 3 cases as suspicious (initially labeled as negative/atypical). Conclusion This reclassification highlights complexity of cytological interpretation, including the challenges of distinguishing between benign cellular alterations, reactive changes, ambiguous findings, suspicious features and malignant cytological changes. Integrating molecular and morphological assessment is essential for evaluation of urothelial carcinoma. Discrepancy between the two is an area which is open to study and can be related to differences in sensitivity and specificity of the testing modalities, sampling methods, variation in interpretation, limitations of testing modality and varying tumor characteristics. Review of clinical history, imaging studies, cystoscopy, and repeat testing may be considered in such cases for diagnostic accuracy.

ThP1.1 - Unilateral Nipple Discharge: Contemporary Approaches to Investigation and Management across a Multi-site Trust

Abstract Nipple discharge, in the absence of a palpable breast lump, constitutes 3-9% of referrals to breast services[i],[ii]. While the ABS released updated guidelines on nipple discharge in 2019, a standardised management protocol is yet to be established. This study aims to scrutinize the efficacy of imaging (mammogram, USS, MRI) and nipple discharge cytology in predicting malignancy outcomes in patients with unilateral nipple discharge. Aims Determine the incidence of malignancy in women presenting with unilateral nipple discharge. Assess sensitivity, specificity, and positive predictive value of imaging modalities (mammogram, USS, MRI) and cytology. Methodology 110 patients presenting with unilateral nipple discharge between 11/2022-12/2023 were retrospectively analysed. Data encompassing patient demographics, diagnostic procedures, and outcomes were systematically collected. Results 31.6% underwent surgical intervention, revealing a malignancy rate of 5.6%. Positive predictive values for detecting malignancy were 75% for mammogram, 50% for ultrasound, and 66% for nipple discharge cytology. No patients underwent MRI or ductoscopy as part of investigations. Conclusion This study highlights variable diagnostic accuracy of imaging and cytology and the necessity for large-scale collaborative data to draw substantive conclusions. The National Unilateral Discharge Study is anticipated to provide comprehensive insights and contribute to the establishment of a national investigative framework for patients presenting with unilateral nipple discharge. [i] Vargas HI, Romero L, Chlebowski RT. Management of bloody nipple discharge. Curr Treat Options Oncol 2002; 3: 157–161. [ii] Seltzer MH. Breast complaints, biopsies, and cancer correlated with age in 10,000 consecutive new surgical referrals. Breast J 2004; 10: 111–117.

ADVANCES IN DIAGNOSIS AND TREATMENT OF CONGENITAL HEART DISEASE: A COMPREHENSIVE REVIEW

The purpose of this article is to provide a comprehensive review of recent advances in the diagnosis and treatment of congenital heart disease (CHD). CHD, which affects about 1% of live births worldwide, is still a major problem in pediatric cardiology. The most prevalent congenital cardiac defects—Ventricular Septal Defect (VSD), Tetralogy of Fallot (TOF), Coronary Artery Fistula, Coarctation of the Aorta (CoA), Aortic and Pulmonary Stenosis, Valve Insufficiency, Double Outlet Right Ventricle (DORV), Ebstein Anomaly, Transposition of the Great Arteries (TGA), Anomalous Venous Return, and Hypoplastic Left Heart Syndrome (HLHS) are all thoroughly examined in this review. The review examines current diagnostic and treatment strategies, highlighting the benefits, drawbacks, sensitivity, and specificity of several imaging modalities, including as CT, MRI, and echocardiography. It also discusses the historical evolution of treatment outcomes, emphasizing the tremendous advances in patient care and surgical procedures that have significantly mproved survival rates and quality of life for CHD patients.

Autism-associated neuroligin 3 deficiency in medial septum causes social deficits and sleep loss in mice.

Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in the neuroligin 3 (NLG3) gene are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we found that the conditional knockout of Nlg3 (Nlg3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. Nlg3 CKO in the MS caused hyperactivity of MSGABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induced social memory deficits and sleep loss in C57BL/6J mice. In contrast, inactivation of these neurons ameliorated social memory deficits and sleep loss in Nlg3-CKO mice. Sleep deprivation led to social memory deficits, while social isolation caused sleep loss, both resulting in a reduction in NLG3 expression and an increase in activity of GABAergic neurons in the MS from C57BL/6J mice. Furthermore, MSGABA-innervated CA2 neurons specifically regulated social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively controlled sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MSGABA neurons impair social memory and disrupt sleep resulting from Nlg3 CKO in the MS, and achieve the modality specificity through their divergent downstream targets.

Comparative study between ultrasound and MR enterography in evaluation of Crohn’s disease

BackgroundCrohn’s disease is a chronic inflammatory bowel disease that can affect any part of the gut. Endoscopy is the gold standard for diagnosis, but it only assesses mucosal lesions. Magnetic resonance enterography (MRE) can assess disease presence and activity, but it has limitations such as motion sensitivity, long scan time, and high cost. Bowel sonography has been introduced as a non-invasive, practical, safe, and low-cost technique to assess disease activity and complications. In our study we aim to assess the comparability of ultrasound to MRE in evaluation of patients with Crohn’s disease, and its complications.ResultsTwenty-five patients with 38 Crohn’s disease affected segments were evaluated by bowel ultrasound (BUS) and MRI enterography (MRE), where BUS and MRE showed equivalent diagnostic performance for disease detection and localization (97.4%, 100%), for sensitivity and specificity of both modalities. Peri-mural fluid (89.5%, 94.4%) and mural stratification loss (100%, 100%) showed high sensitivity and specificity by BUS compared to MRE, while for assessment of mural vascularity, BUS showed high sensitivity and specificity for high grade vascularity (100%, 83.3%), but low sensitivity and high specificity for low and moderate vascularity (0%–62.5%, 81.8%) compared to MRE. Complications including fistulae and abscessed were all correctly identified in BUS compared to MRE.ConclusionBUS showed comparable results to MRE for identification, localization, assessment of findings related to disease activity, and complications in cases of Crohn’s disease rendering it a viable alternative to MRE.

Potential Advantage of Magnetic Resonance Imaging in Detecting Thoracic Wall Infiltration in Pleural Mesothelioma. A Retrospective Single Center Analysis.

Abstract Background Thoracic wall infiltration in pleural mesothelioma (PM) can be an important prognostic factor when determining the extent of resection. Currently, standardized imaging for restaging after neoadjuvant systemic therapy comprises contrast enhanced Computed Tomography (CT) or Positron Emission Tomography (PET/CT) scan. Aims However, thoracic Magnetic Resonance Imaging (MRI) could be a better discriminator of chest wall infiltration prior to surgery. To increase the preoperative staging accuracy, we introduced a MRI protocol at our center. Methods A retrospective analysis of this prospective new imaging protocol was performed from 07/2018 to 08/2023, including descriptive analysis for patient`s sex, age, nicotine consumption, asbestos exposure, histological subtype, TNM-stage, RECIST criteria and number of neoadjuvant therapy cycles. Preoperative restaging included routine imaging and MRI. After histological diagnosis of PM, neoadjuvant therapy was conducted, followed by partial pleurectomy or extended pleurectomy/decortication, with intraoperative biopsies of suspicious chest wall lesions. The CT/MRI results were compared to the intraoperative biopsies. Sensitivity and specificity of both modalities were analyzed. Results Twenty-five patients (mean age 65.4, 12% female) with possible chest wall infiltration were included out of the 35 patients with PM treated during the observation period. Of the 10 patients with actual chest wall infiltration, 9 (90%) had a T-Stage of 3 or higher, 9 (90%) had PM of epithelioid histologic subtype and 4 (40%) a R2-Resection. The mean overall survival of all patients was 18.88 months (8-58). In our study, thoracic MRI showed a high sensitivity (90%) and specificity (100%) for the detection of chest wall infiltration, especially when compared to the CT scan (sensitivity of 10%). Conclusion With the adjunctive use of thoracic MRI we demonstrated a higher sensitivity for detection of chest wall infiltration compared to conventional imaging prior to surgery. This may facilitate the preoperative assessment of the extent of resection. Nevertheless, larger studies are required to confirm these results.

Cross-modal attention network for retinal disease classification based on multi-modal images.

Multi-modal eye disease screening improves diagnostic accuracy by providing lesion information from different sources. However, existing multi-modal automatic diagnosis methods tend to focus on the specificity of modalities and ignore the spatial correlation of images. This paper proposes a novel cross-modal retinal disease diagnosis network (CRD-Net) that digs out the relevant features from modal images aided for multiple retinal disease diagnosis. Specifically, our model introduces a cross-modal attention (CMA) module to query and adaptively pay attention to the relevant features of the lesion in the different modal images. In addition, we also propose multiple loss functions to fuse features with modality correlation and train a multi-modal retinal image classification network to achieve a more accurate diagnosis. Experimental evaluation on three publicly available datasets shows that our CRD-Net outperforms existing single-modal and multi-modal methods, demonstrating its superior performance.

Role of Ga68 Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography in Prostate Cancer Imaging

AbstractThe introduction of prostate-specific membrane antigen (PSMA) in clinical practice has revolutionized the evaluation of biochemical recurrence (BCR) of prostate cancer after curative-intent treatment. The high expression of this glycoprotein in prostate cancer cells makes PSMA imaging superior to the current conventional staging methods, namely bone scanning and computed tomography. The high capability of PSMA imaging for identifying very small previously undetected lesions has been widely demonstrated in the literature, leading to a rethinking of patient management by treating physicians. The usual and predictable patterns of spread in prostate cancer are still more prevalent, such as spread to pelvic lymph nodes and bone metastasis, but different patterns of disease spread are becoming more commonly recognized with higher reliability because PSMA imaging allows the detection of more usual and unusual lesions than conventional imaging. The expanding use of PSMA positron emission tomography (PET) has also revealed PSMA ligand uptake in diverse nonprostatic diseases, which raised questions about the specificity of this imaging modality. It is important for the reading physician to recognize and understand the usual disease spread, the most prevalent unusual sites of relapse, and the nonprostatic conditions which are PSMA avid not only to heighten the relevancy of reports but also to improve imaging consultancy in multispecialty oncologic practice. This article aims to brief the role of PSMA PET in the initial staging of multitude of clinical scenarios, BCR, castration-resistant prostate cancer, usual and unusual patterns of recurrence and metastatic spread diagnosed with PSMA PET, normal variants, pitfalls, and nonprostatic disorders showing PSMA expression.

Modal specificity of Russian verbs of "thinking" and "to think" with the prefix y-

The article examines the verbs included in the structure of the semantic field of thinking, namely the basic verbs to think and thinking, complicated by the prefix y-, based on the material of Russian texts of different genres. The subject of the study is the following values of situational modality (the so–called semantic X) - the invariant value of desirability, as well as the value of the opportunity realized by derivatives to conceive, to think in the process of communication. The purpose of the work is to reveal the specifics and conditions of the modal functioning of these verbs. Achieving this goal is facilitated by solving the following tasks: 1) to identify the modal meanings realized by the considered derivatives; 2) to determine the conditions of their modal functioning within the framework of the utterance; 3) to identify the role of the nominatively independent word-formation with formant y- in the process of creating the modal, modal-evaluative meanings of the corresponding derivatives. The goals and objectives of this work determined the choice of a comprehensive research methodology, including the following methods: functional-semantic, descriptive, contextual. The scientific novelty of the article is determined by the subject of the study. As a result of the conducted research, it is concluded that the verbs of thinking, to think with the formant y- are able to realize the modal meanings of possibility, desirability (which is a condition for the realization of opportunity), associated mainly with intentions that contradict the moral, ethical, social norms of society. The analysis of the texts made it possible to determine the lexical and grammatical basis of the modal functioning of the verbs of thinking, complicated by the prefix y-, in the semantics of which the modal component is implicitly contained, to establish syntactic conditions for the realization of the meanings of situational modality, i.e. the presence of a dependent subject semantically unlimited infinitive in the verb. The reinforcing role of the service formant is determined for the formation of the modal meaning of the derivatives to think, to conceive as an independent (autonomous) significant unit, in the meaning of which the seme "bringing to an undesirable state" is explicitly expressed, as well as the pejorative seme "to commit something bad, criminal, reprehensible (to the detriment of someone)". The materials of the article can be used at seminars and practical classes of the university on topical issues of the category of linguistic modality.

High-resolution diffusion-weighted MRI plus mammography for detecting clinically occult breast cancers in women with dense breasts

PurposeTo compare the performance of mammography, high-resolution DW-MRI, DCE-MRI, and their combinations in detecting clinically occult breast cancer in women with dense breasts. Method544 breasts from 281 consecutive asymptomatic women with dense breasts were retrospectively identified. They underwent breast MRI for preoperative evaluation of breast cancers (n = 214) or as supplemental screening (n = 67) including DCE-MRI and DW-MRI (b values, 0 and 1000 sec/mm2; in-plane resolution, 1.1 × 1.1 mm2 and 1.3 × 1.3 mm2; section thickness, 3 mm), in addition to mammography. Three readers independently reviewed each examination on a per-breast basis. Histopathology and at least two year of imaging follow-up served as the gold standard. The sensitivities and specificities of different imaging modalities were compared using McNemar test. Results230 of 544 breasts (42 %) had malignant lesions. The sensitivity of DW-MRI was higher than that of mammography (77.0 % vs 57.9 %; adjusted p < 0.001), but lower than that of DCE-MRI (84.8 %; adjusted p = 0.014). The specificity of DW-MRI was comparable to those of mammography (98.1 % vs 99.1 %; adjusted p > 0.999) and DCE-MRI (97.1 %; adjusted p > 0.999). DW-MRI plus mammography had a comparable sensitivity and specificity to those of DCE-MRI plus mammography (88.6 % vs 90.9 % and 97.1 % vs 96.2 %; adjusted p > 0.999 for both). ConclusionsHigh-resolution DW-MRI had a sensitivity higher than mammography and lower than DCE-MRI. Nevertheless, DW-MRI plus mammography showed a comparable sensitivity and specificity to DCE-MRI plus mammography for detecting clinically occult cancers in women with dense breasts.

Interpersonal Metafunctional Analysis of Marital Conflictual Discourse in Sofola’s the Sweet Trap and Soyinka’s Trials of Brother Jero

This research examines language choices employed by the spouses during their conflictual interactivity as depicted in the select Nigerian plays. The analysis is anchored on Modality aspect of Interpersonal Metafunction theoretical Framework of Michael Halliday, 1960. Its modality specificity is because it is a grammatical resource for making interpersonal meaning. The analysis focuses on the provocative language usages of the spouses during their dialogical interactivity in the plays. The analysis is of qualitative research design, and thesampling technique for data collection is purposive. Twenty-five (25) data excerpts are used for the analysis. The result shows dominance of Modulation Obligation modals, followed by Modulation Inclination, and a minor detect of high Probability Modalization. The prevalence of the Modulation modality is as a result that the spouses’ relations revolves around proposal, a form of speech function that expresses either offer or command. Command aspects of it is found prevalent within the conflictual discourse of the male spouse, who expects obeisance of the commands from his female counterpart.The research reveals to the reader the use of variants modals and gives clue to understanding the negative implication of inappropriate application of high sounding types in cordial relationship like marriage.

Intraoperative Assessment of Resection Margin in Oral Cancer: The Potential Role of Spectroscopy.

In parallel with the increasing number of oncological cases, the need for faster and more efficient diagnostic tools has also appeared. Different diagnostic approaches are available, such as radiological imaging or histological staining methods, but these do not provide adequate information regarding the resection margin, intraoperatively, or are time consuming. The purpose of this review is to summarize the current knowledge on spectrometric diagnostic modalities suitable for intraoperative use, with an emphasis on their relevance in the management of oral cancer. The literature agrees on the sensitivity, specificity, and accuracy of spectrometric diagnostic modalities, but further long-term prospective, multicentric clinical studies are needed, which may standardize the intraoperative assessment of the resection margin and the use of real-time spectroscopic approaches.

The role of the left ventral occipitotemporal cortex in speech processing-The influence of visual deprivation.

The role of the left ventral occipitotemporal cortex (vOT) in reading is well-established in both sighted and blind readers. Its role in speech processing remains only partially understood. Here, we test the involvement of the left vOT in phonological processing of spoken language in the blind (N = 50, age: 6.76-60.32) and in the sighted (N = 54, age: 6.79-59.83) by means of whole-brain and region-of-interest (including individually identified) fMRI analyses. We confirm that the left vOT is sensitive to phonological processing (shows greater involvement in rhyming compared to control spoken language task) in both blind and sighted participants. However, in the sighted, the activation was observed only during the rhyming task and in the speech-specific region of the left vOT, pointing to task and modality specificity. In contrast, in the blind group, the left vOT was active during speech processing irrespective of task and in both speech and reading-specific vOT regions. Only in the blind, the left vOT presented a higher degree of sensitivity to phonological processing than other language nodes in the left inferior frontal and superior temporal cortex. Our results suggest a changed development of the left vOT sensitivity to spoken language, resulting from visual deprivation.

The Diagnostic and Predictive Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Laryngeal Squamous Cell Carcinoma.

This retrospective study examines the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and neck magnetic resonance imaging (MRI) in detecting nodal metastasis for patients with laryngeal squamous cell carcinoma (LSCC) and assesses the predictive values of metabolic and structural features derived from 18F-FDG PET/CT. By involving 66 patients from 2014 to 2021, the sensitivity and specificity of both modalities were calculated. 18F-FDG PET/CT outperforms neck MRI for nodal disease detection, with 89% sensitivity, 65% specificity, and 77% accuracy for nodal metastasis (p = 0.03). On the other hand, neck MRI had 66% sensitivity, 62% specificity, and 64% accuracy. Approximately 11% of patients witnessed a change in their therapy intent when relying on 18F-FDG PET/CT nodal staging results. Analyzing the cohort for PET-derived metabolic and morphological parameters, a total of 167 lymph nodes (LN) were visualized. Parameters such as the LN maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN size were computed. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Among the 167 identified cervical LNs, 111 were histopathologically confirmed as positive. ROC analysis revealed the highest area under the curve for LN MTV (0.89; p < 0.01), followed by LN size (0.87; p < 0.01). Both MTV and LN size independently predicted LN metastasis through multivariate analysis. In addition, LN MTV can reliably predict false-positive LNs in preoperative staging, offering a promising imaging-based approach for further exploration.

NIMG-15. COMBINED ADVANCED IMAGING AND MGMT STATUS FOR DISTINCTION BETWEEN EARLY TUMOR PROGRESSION AND PSEUDOPROGRESSION IN GLIOBLASTOMA

Abstract BACKGROUND Within 3-6 months of completing initial chemoradiotherapy, up to 50% of glioblastomas (GBM) develop worsening contrast enhancement on surveillance imaging, which could represent early progression (EP) or pseudoprogression (PsP). Reports suggest EP is more common in MGMT unmethylated (uMGMT) cases. While multiple advanced imaging studies have tried to address this issue (including magnetic resonance with perfusion [MRP], with spectroscopy [MRS], and FDG-PET), no non-invasive test reliably differentiates EP from PsP, yet the distinction is critical for subsequent management. We aimed to develop a multiparametric score including advanced imaging and MGMT status to improve interpretation. METHODS We retrospectively reviewed records of patients diagnosed with GBM from 2016-2022 who had changes on anatomic imaging concerning for EP vs. PsP ≤6 months after chemoradiotherapy and underwent ≥ 2 advanced imaging sequences (MRP, MRS, FDG-PET); definitive distinction between EP and PsP was made by either histology from surgical resampling or subsequent clinico-radiographic evolution. Associations between clinical factors and EP were investigated with logistic regression. Sensitivity and specificity of each imaging modality and of a composite score (1 point each for MRP consistent with EP, MRS consistent with EP, and uMGMT) were calculated. RESULTS 46 evaluable patients (57% male; median age 58.5 years, range 31-80) were included; outcome (EP in 29 [63%], PsP in 17 [37%]) was determined histologically and clinically in 15 (33%) and 31 (67%) of cases, respectively. In multivariate analysis, uMGMT was predictive of EP (OR=2.63, 95% CI=1.29-37.55, p&amp;lt; 0.05). Sensitivity/specificity to predict EP were 78%/77% for uMGMT, 76%/29% for MRP, 85%/67% for MRS, 86%/0% for FDG-PET (8 patients) and 88%/75% for composite score of 2-3 (vs. 0-1). CONCLUSION Combining MRS, MRP and MGMT results can improve accuracy in distinguishing EP from PsP in GBM. MGMT status should be incorporated in the interpretation of advanced imaging to distinguish EP from PsP.

Predicting executive functioning from brain networks: modality specificity and age effects.

Healthy aging is associated with structural and functional network changes in the brain, which have been linked to deterioration in executive functioning (EF), while their neural implementation at the individual level remains unclear. As the biomarker potential of individual resting-state functional connectivity (RSFC) patterns has been questioned, we investigated to what degree individual EF abilities can be predicted from the gray-matter volume (GMV), regional homogeneity, fractional amplitude of low-frequency fluctuations (fALFF), and RSFC within EF-related, perceptuo-motor, and whole-brain networks in young and old adults. We examined whether the differences in out-of-sample prediction accuracy were modality-specific and depended on age or task-demand levels. Both uni- and multivariate analysis frameworks revealed overall low prediction accuracies and moderate-to-weak brain-behavior associations (R2< 0.07, r< 0.28), further challenging the idea of finding meaningful markers for individual EF performance with the metrics used. Regional GMV, well linked to overall atrophy, carried the strongest information about individual EF differences in older adults, whereas fALFF, measuring functional variability, did so for younger adults. Our study calls for future research analyzing more global properties of the brain, different task-states and applying adaptive behavioral testing to result in sensitive predictors for young and older adults, respectively.

Sensitivity and specificity of diagnostic modalities in pouchitis: a systematic review and meta-analysis.

Restorative proctocolectomy (RPC) is the most common surgical procedure to restore gastrointestinal continuity after surgical resection of the colon and rectum. Pouchitis is a common complication with several different modalities that can be used to aid diagnosis. This systematic review and meta-analysis aimed at exploring the sensitivity and specificity these diagnostic modalities. The medical literature was searched using MEDLINE, EMBASE and EMBASE classic and PubMed from 1978 to June 2022. We calculated descriptive statistics using sensitivity, specificity, and false-positive rate of the primary studies and also their positive and negative likelihood ratios, and their diagnostic odds ratios. The screen found 5477 records with 13 studies being included. Faecal lactoferrin was found to have the highest pooled sensitivity and specificity of 98% and 88% respectively with imaging modalities coming in second and faecal calprotectin third with pooled sensitivities and specificities of 87% and 79% and 74% and 81% respectively. Faecal biomarkers particularly lactoferrin and imaging modalities may have an important role to play in diagnosing pouchitis. Importantly due to delays in availability of pouchoscopy, our data supports early ordering of these tests to help delineate from other causes. Further studies are required with larger cohort sizes to further validate these tests.

Biliary papillomatosis.

Biliary papillomatosis (BP) is a rare disorder of the biliary tract characterized by the presence of multiple papillary adenomas spread along the biliary tree. Although benign, it carries a significant risk of malignant transformation. Due to low sensitivity and specificity of conventional radiologic modalities, the diagnosis as well as estimation of disease extent is difficult. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreaticography (ERCP) are superior although direct peroral cholangioscopy (POC) is currently the most accurate diagnostic method. Mainly because it provides more detailed information and makes targeted histological diagnosis possible. The treatment of biliary papillomatosis consists of surgical resection, liver transplantation (LT) or a combination of both. Unfortunately, the recurrence rate after radical surgery without LT remains high due to the diffuse distribution of the disease.

A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep

A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund’s adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.