Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic performance of the ‘DICA’ endoscopic classification and the ‘CODA’ score in predicting clinical outcomes of diverticular disease: an international, multicentre, prospective cohort study

Objective To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA). Design A multicentre, prospective, international cohort study. Setting 43 gastroenterology and endoscopy centres located in Europe and South America. Participants 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications. Interventions A 3-year follow-up was performed. Main outcome measures To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score). Results The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981). Conclusions DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score. Trial registration number NCT02758860.
Intermodulation of gut-lung axis microbiome and the implications of biotics to combat COVID-19

Abstract The novel coronavirus disease pandemic caused by the COVID-19 virus has infected millions of people around the world with a surge in transmission and mortality rates. Although it is a respiratory viral infection that affects airway epithelial cells, a diverse set of complications, including cytokine storm, gastrointestinal disorders, neurological distress, and hyperactive immune responses have been reported. However, growing evidence indicates that the bidirectional crosstalk of the gut-lung axis can decipher the complexity of the disease. Though not much research has been focused on the gut-lung axis microbiome, there is a translocation of COVID-19 infection from the lung to the gut through the lymphatic system resulting in disruption of gut permeability and its integrity. It is believed that detailed elucidation of the gut-lung axis crosstalk and the role of microbiota can unravel the most significant insights on the discovery of diagnosis using microbiome-based-therapeutics for COVID-19. This review calls attention to relate the influence of dysbiosis caused by COVID-19 and the involvement of the gut-lung axis. It presents first of its kind details that concentrate on the momentousness of biotics in disease progression and restoration. Communicated by Ramaswamy H. Sarma Graphical Abstract
Comparative anatomy and genetic bases of fruit development in selected Rubiaceae (Gentianales)

Abstract Premise The Rubiaceae are ideal for studying the diversity of fruits that develop from flowers with inferior ovary. We aimed to identify morpho‐anatomical changes during fruit development that distinguish those derived from the carpel versus the extra‐carpellary tissues. In addition, we present the fruit genetic core regulatory network in selected Rubiaceae species and compare it in terms of copy number and expression patterns to model core eudicots in the Brassicaceae and the Solanaceae. Methods We used light microscopy to follow morphoanatomical changes in four selected species with different fruit types. We generated reference transcriptomes for seven selected Rubiaceae species and isolated homologs of major transcription factors involved in fruit development histogenesis, assessed their homology, identified conserved and new protein motifs, and evaluated their expression in three species with different fruit types. Results Our studies revealed ovary‐derived pericarp tissues versus floral‐cup‐derived epicarp tissues. Gene evolution analyses of FRUITFULL, SHATTERPROOF, ALCATRAZ, INDEHISCENT and REPLUMLESS homologs suggest that the gene complement in Rubiaceae is simpler compared to that in Brassicaceae or Solanaceae. Expression patterns of targeted genes vary in response to the fruit type and the developmental stage evaluated. Conclusions Morphologically similar fruits can have different anatomies as a result of convergent tissues developed from the epicarps covering the anatomical changes from the pericarps. Expression analyses suggest that the fruit patterning regulatory network established in model core eudicots cannot be extrapolated to asterids with inferior ovaries.
Baicalin suppresses autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage

ABSTRACT Early brain injury, characterized by massive cell apoptosis or death, is identified as a critical pathophysiological process during subarachnoid hemorrhage (SAH). Ferroptosis, a class of autophagy-dependent cell death discovered in 2012, is induced by iron-dependent lipid peroxidation accumulation. The present study was designed to study the role of baicalin in autophagy-dependent ferroptosis in early brain injury after SAH. Neurological scores and brain water content were measured to evaluate brain injury. Measurement of iron ion, malondialdehyde (MDA), lipid reactive oxygen species was conducted for ferroptosis evaluation. Immunofluorescence staining, western blotting, and flow cytometry analysis were used to evaluate autophagy and apoptosis. First, we observed that, compared with sham rats, SAH rats had lower neurobehavioral scores. Next, baicalin was proven to decrease the Fe2+, malondialdehyde, and ROS levels in the brain tissues of rats. Also, baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Finally, the effects of baicalin on brain injury in the SAH rats were verified. Overall, our results demonstrated that baicalin suppressed autophagy-dependent ferroptosis in EBI after SAH.
Risk factors for severe infections in secondary immunodeficiency: a retrospective US administrative claims study in patients with hematological malignancies

Abstract Real-world data are lacking to identify patients with secondary immunodeficiency (SID) who may benefit most from anti-infective interventions. This retrospective analysis used the IQVIA PharMetrics® Plus database to assess baseline characteristics associated with risk of severe infections post-SID diagnosis in patients with hematological malignancies. In 4066 patients included, the mean number of any and severe infections per patient in the one-year pre-SID diagnosis period was 9.5 and 0.7, respectively. Post-SID diagnosis, the mean annualized number of any and severe infections was 19.1 and 1.5, respectively. Receiver operating characteristic curve analysis identified a threshold (cutoff) of three bacterial infections at baseline as optimally predictive of severe infections post-SID diagnosis. Multivariate analysis indicated that hospitalizations, infections (≥3), or antibiotic use pre-SID diagnosis were predictive of severe infections post-SID diagnosis. Evaluation of these risk factors could inform clinical decisions regarding which patients may benefit from prophylactic anti-infective treatment, including immunoglobulin replacement if warranted.
Remembering spatial words: Sensorimotor simulation affects verbal recognition memory

Previous evidence shows that words with implicit spatial meaning or metaphorical spatial associations are perceptually simulated and can guide attention to associated locations (e.g., bird—upward location). In turn, simulated representations interfere with visual perception at an associated location. The present study investigates the effect of spatial associations on short-term verbal recognition memory to disambiguate between modal and amodal accounts of spatial interference effects across two experiments. Participants in both experiments encoded words presented in congruent and incongruent locations. Congruent and incongruent locations were based on an independent norming task. In Experiment 1, an auditorily presented word probed participants’ memory as they were visually cued to either the original location of the probe word or a diagonal location at retrieval. In Experiment 2, there was no cue at retrieval but a neutral encoding condition in which words normed to central locations were shown. Results show that spatial associations affected memory performance although spatial information was neither relevant nor necessary for successful retrieval: Words in Experiment 1 were retrieved more accurately when there was a visual cue in the congruent location at retrieval but only if they were encoded in a non-canonical position. A visual cue in the congruent location slowed down memory performance when retrieving highly imageable words. With no cue at retrieval (Experiment 2), participants were better at remembering spatially congruent words as opposed to neutral words. Results provide evidence in support of sensorimotor simulation in verbal memory and a perceptual competition account of spatial interference effect.
The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
Iron deficiency and early childhood caries: a systematic review and meta-analysis

Supplemental Digital Content is available in the text Abstract Backgrounds: Previous surveys have found that children with iron deficiency (ID) were likely to suffer from early childhood caries (ECC). We aimed to assess the scientific evidence about whether ID is intrinsically related to ECC. Methods: The medical subject headings (MeSH) terms and free words were searched on PubMed, Web of Science, Cochrane, China National Knowledge Infrastructure, Wanfang, and the Database for Chinese Technical Periodicals from March 2020 to September 2020. Two researchers independently screened the articles. Data extraction and cross-checking were performed for the studies that met the inclusion criteria. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.3 software. Results: After excluding duplication and irrelevant literature, 12 case-control studies were included in the study. The meta-analysis demonstrated that children with ECC were more likely to have ID (odds ratio [OR] = 2.63, 95% confidence interval [CI]: [1.85, 3.73], P < 0.001). There was no statistically significant association found between the level of serum ferritin and ECC (weighted mean difference (WMD) = −5.80, 95% CI: [−11.97, 0.37], P = 0.07). Children with ECC were more likely to have iron-deficiency anemia (OR = 2.74, 95% CI: [2.41,3.11], P < 0.001). The hemoglobin (HGB) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = −9.96, 95% CI: [−15.45, −4.46], P = 0.0004). The mean corpuscular volume (MCV) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = −3.72, 95% CI: [−6.65, −0.79], P = 0.01). Conclusions: ID was more prevalent in children with ECC, and the markers of iron status in the ECC group, such as serum ferritin, HGB, and MCV, were relatively lower than the ECC-free group.
Assessment of heavy metals in wild and farmed tilapia (Oreochromis niloticus) on Lake Kariba, Zambia: implications for human and fish health

ABSTRACT The aim of this study was to assess the levels of heavy metals in both wild and farmed tilapia on Lake Kariba in Zambia and to evaluate the impact of intensive fish farming on wild tilapia. Three sites for wild fish (2 distant and 1 proximal to fish farms) and two fish farms were selected. One hundred fish (52 from distant sites; 20 near fish farms; 28 farmed fish) were sampled and muscle tissues excised for analysis of heavy metals (Mg, Fe, Zn, Al, Cu, Se, Co, Mo, As, Cr, V, Ni, Hg, Pb, Li, Cd, and Ag) by acid (HNO3) digestion and ICP-MS. All metals were found to be below the maximum limits (MLs) set by WHO/EU. Essential metals were higher in farmed tilapia, whereas non-essential metals were higher in wild tilapia. Significantly higher levels of essential metals were found in wild fish near the fish farms than those distant from the farms. Estimated weekly intake (EWI) for all metals were less than the provisional tolerable weekly intakes (PTWI). Target hazard quotients (THQ) and Hazard Indices (HI) were <1, indicating no health risks from a lifetime of fish consumption. Selenium Health Benefit Value (HBVSe) was positive for all locations, indicating protective effects of selenium against mercury in fish. Total cancer risk (CR) due to As, Cr, Cd, Ni and Pb was less than 1 × 10−4, indicating less than 1 in 10,000 carcinogenic risk from a lifetime consumption of tilapia from Lake Kariba. Hg levels (0.021 mg/kg) in wild tilapia at site 1 were higher than the Environmental quality standard (EQS = 0.020 mg/kg) set by EU, indicating possible risk of adverse effects to fish. Except for Hg, levels of metals in fish were safe for human consumption and had no adverse effects on fish. Graphical abstract
Endovascular treatment of vertebrobasilar system aneurysms - long term results.

INTRODUCTION Microsurgical treatment of VBSA is complex and challenging due to the deep location of the vessels and the proximity of important structures. Therefore, minimally invasive endovascular techniques have been introduced to the treatment of VBSA. The aim of this study was to present long-term results and technical aspects of VBSA embolisation. In this manuscript, we describe our experience in the treatment of VBSA with long-term results. Furthermore, we discuss the advantages and disadvantages of this treatment modality, paying special attention to the technical aspects. We believe that this is an important contribution to this topic because the number of previous reports is limited. It adds to a population that can be compared to patients treated using different methods. MATERIALS AND METHODS We analysed the medical records of patients with aneurysms of vertebral and basilar arteries referred for endovascular treatment between 2015 and 2020. RESULTS A total of 44 patients were selected for the study. From this group, 10 patients (22.7%) were admitted with SAH caused by ruptured VBSA. The median age of the patients was 58 years (31-80), with 27 (61.4%) females and 17 (38.6%) males. The majority of the VBSAs (35, 79.5%) were located on the basilar artery. Complete occlusion was achieved in 39 patients (88.6%). Procedural complications occurred in three cases (6.8%). In long-term follow-up, complete embolisation was achieved in 81.8% (36 of 44 patients). In 18.2% (eight patients), recurrence of VBSA was observed. Two patients were qualified for recoiling. Clinical follow-up was uneventful in 37 (84%) patients. Four patients (9%) reported mild headaches. Three (7%) patients required assistance for daily living. CONCLUSIONS Endovascular embolisation of VBSA is feasible and provides an excellent rate of complete occlusion and a high rate of favourable long-term outcomes, which support using this technique as a first-line treatment. A relatively high rate of recurrence remains the major drawback, especially in cases of wide-neck VBSA.
Deficient Chaperone-Mediated Autophagy Promotes Inflammation and Atherosclerosis

Supplemental Digital Content is available in the text. Rationale: The NLRP3 (NLR [NOD-like receptor] family, pyrin domain containing 3) inflammasome is an important driver of atherosclerosis. Our previous study shows that chaperone-mediated autophagy (CMA), one of the main lysosomal degradative process, has a regulatory role in lipid metabolism of macrophages. However, whether the NLRP3 inflammasome is regulated by CMA, and the role of CMA in atherosclerosis remains unclear. Objective: To determine the role of CMA in the regulation of NLRP3 inflammasome and atherosclerosis. Methods and Results: The expression of CMA marker, LAMP-2A (lysosome-associated membrane protein type 2A), was first analyzed in ApoE−/− mouse aortas and human coronary atherosclerotic plaques, and a significant downregulation of LAMP-2A in advanced atherosclerosis in both mice and humans was observed. To selectively block CMA, we generated macrophage-specific conditional LAMP-2A knockout mouse strains in C57BL/6 mice and ApoE−/− mice. Deletion of macrophage LAMP-2A accelerated atherosclerotic lesion formation in the aortic root and the whole aorta in ApoE−/− mice. Mechanistically, LAMP-2A deficiency promoted NLRP3 inflammasome activation and subsequent release of mature IL (interleukin)-1β in macrophages and atherosclerotic plaques. Furthermore, gain-of-function studies verified that restoration of LAMP-2A levels in LAMP-2A–deficient macrophages greatly attenuated NLRP3 inflammasome activation. Importantly, we identified the NLRP3 protein as a CMA substrate and demonstrated that LAMP-2A deficiency did not affect the NLRP3 mRNA levels but hindered degradation of the NLRP3 protein through CMA pathway. Conclusions: CMA function becomes impaired during the progression of atherosclerosis, which increases NLRP3 inflammasome activation and secretion of IL-1β, promoting vascular inflammation and atherosclerosis progression. Our study unveils a new mechanism by which NLRP3 inflammasome is regulated in macrophages and atherosclerosis, thus providing a new insight into the role of autophagy-lysosomal pathway in atherosclerosis. Pharmacological activation of CMA may provide a novel therapeutic strategy for atherosclerosis and other NLRP3 inflammasome/IL-1β–driven diseases.
The National Cancer Database: Survival Between Head and Neck Melanoma and Melanoma of Other Regions

Objective Primary site is considered an important prognostic factor for cutaneous malignant melanoma (CMM); however, opinions vary regarding its influence on survival. This study compares overall survival between head and neck melanoma (HNM) and melanoma of other regions (MOR), as well as between melanoma of the scalp and neck (MSN) and melanoma of other head regions (MOHR). Study Design Level III retrospective cohort study. Setting Patients from Commission on Cancer–accredited cancer programs affiliated to the National Cancer Database (NCDB). Methods Patients with HNM (MSN and MOHR included) and MOR, stages I to IV (n = 39,754), and their linked survival data using the NCDB were identified. Survival was analyzed using propensity score matching methods. Results After matching using propensity scores, allowing this observational study to mimic a randomized controlled trial, subjects with HNM showed a 22% increased mortality when compared to MOR (P < .01). Among those with HNM, hazard was not proportional over time. Overall, subjects with MSN in the first 3.5 years of follow-up (75% of subjects) showed a 15% increased mortality when compared to MOHR (P < .01); however, after 3.5 years, no difference in survival was noted (P = .5). Conclusion Patients with HNM showed a higher mortality when compared to MOR. The risk of death of primary sites within the head and neck varies over time, showing a higher risk of mortality for scalp and neck during the first 3.5 years of follow-up. This increased risk was not evident after the 3.5-year threshold. Further research is needed to evaluate additional patient factors or differences in treatment approaches.
Discovery, preclinical development, and clinical application of pralsetinib in the treatment of thyroid cancer

ABSTRACT Introduction The use of targeted drug therapies has substantially increased in the treatment of RET-mutated thyroid and other solid cancers over the last decade. Multi-Kinase Inhibitors (MKI) have been approved by FDA, but limited efficacies and side effects make them uneasy to tolerate. Pralsetinib is an oral highly selective RET inhibitor drug that has been generated and clinically validated to have higher potency and less toxicity. Areas covered The present paper offers a brief summary of RET-related thyroid cancer genetics, an overview of the preclinical development of pralsetinib and reviews its clinical validation in the treatment of thyroid cancer. Expert opinion Pralsetinib is a new generation oral treatment that has been approved by the FDA for patients with RET-mutated thyroid cancer. Pralsetinib showed a safer toxicity profile compared to previously approved MKI, probably due to lower inhibition of other tyrosine kinases, especially VEGFR. The approval study ARROW trial showed that patients with RET-mutant medullary thyroid cancer had a better overall response rate to pralsetinib compared to standard-of-care treatments. Additional clinical trials or data enrichment of existing databases are desirable in order to verify and further describe the clinical benefit of pralsetinib in such patients to fully understand its pharmacological profile.