Miracle-dz/UniFAR-FTUs huggingface dataset:
On the prediction of neuronal microscale topology descriptors based on mesoscale recordings

The brain possesses structural and functional hierarchical architectures organized over multiple scales. Considering that functional recordings commonly focused on a single spatial level, and because multiple scales interact with one another, we explored the behaviour of in silico neuronal networks across different scales. We established ad hoc relations of several topological descriptors (average clustering coefficient, average path length, small‐world propensity, modularity, network degree, synchronizability and fraction of long‐term connections) between different scales upon application and empirical validation of a Euclidian renormalization approach. We tested a simple network (distance‐dependent model) as well as an artificial cortical network (Vertex; undirected and directed networks) finding the same qualitative power law relations of the parameters across levels: their quantitative nature is model dependent. Those findings were then organized in a workflow that can be used to predict, with approximation, microscale topologies from mesoscale recordings. The present manuscript not only presents a theoretical framework for the renormalization of biological neuronal network and their study across scales in light of the spatial features of the recording method but also proposes an applicable workflow to compare real functional networks across scales.
Central nervous system (CNS) involvement has an adverse impact on survival in newly diagnosed adult acute lymphoblastic leukemia (ALL) assessed by flow cytometry

Abstract The role of CNS involvement detected by flow cytometry (FCM) in patients with acute lymphoblastic leukemia has been discussed previously; however, its impact on survival has not been described enough. We analyzed a retrospective cohort of newly diagnosed ALL adult patients who had a cerebrospinal fluid (CSF) analysis by FCM and conventional cytology. We evaluated 81 patients; 19 (23.4%) were only positive by FCM, five (6.3%) were double-positive (DP) and 57 (70.4%) were double-negative (DN). The detection of CNS involvement was increased from 6% to 24%, employing FCM; In our final analysis, patients with FCM + had a lower survival of 7.01 months [95% CI (5.90–8.24)], compared with 11.71 months [IC95% (9.49–13.94)] in the DN group (p = 0.03).
Positive surgical margin is an independent predictor of overall survival of patients with vulvar squamous cell carcinoma

It is uncertain whether curative surgical treatment or a less radical surgery with adjuvant treatment should be provided to preserve function in patients with vulvar squamous cell carcinoma (SCC) that is adjacent to the urethra, anus, and vagina. The aim of this study was to investigate the surgical margin in patients with vulvar SCC with regard to local recurrence and overall survival.
Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma with IgG4-related ophthalmic disease

ABSTRACT Purpose To analyse the incidence and characteristics of ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD), and to compare with IgG4-negative OAML. Methods We enrolled 130 patients with pathology-confirmed OAML at a single tertiary medical centre. Patients were divided into IgG4-positive and IgG4-negative groups based on the pathologic criteria for IgG4-ROD. The data were reviewed and compared between the groups. Results IgG4-positive OAML was identified in 5.4% (7/130) of OAML and 13.5% (7/52) of non-conjunctival OAML. IgG4-positive group had a higher incidence of involvement of the lacrimal gland (7/7 vs. 18/123, p = .001), extraocular muscles (3/7 vs. 10/123, p = .022) and infraorbital nerve (2/7 vs. 0/123, p < .001), and had a lower incidence of involvement of the conjunctiva (0/7 vs. 84/123; p < .001) than IgG4-negative group. IgG4-positive group had higher T and N categories of the American Joint Committee on Cancer classification (T1:T2:T3:T4 ratio of 0:6:0:1 vs. 78:32:8:5, p < .001; and ≥N1 ratio of 2/7 vs. 7/123, p = .021). There were no differences in the response rate to initial treatment (5/6 vs. 39/41, p = .343) or the relapse rate (1/6 vs. 5/41, p = 1.000) between the groups. Conclusion IgG4-positive OAML showed clinical features similar to IgG4-ROD, such as predominant disease involvement of the lacrimal gland, extraocular muscles, infraorbital nerve and lymph nodes, but not the conjunctiva. However, treatment outcomes were favourable with or without background IgG4-ROD. Physicians should be aware that IgG4-ROD might undergo a malignant transformation and that thorough treatment and surveillance of IgG4-ROD are important.
Nurse Led Clinics; a Novel Model of Care for Compensated Liver Cirrhosis

A nurse-led cirrhosis clinic model for management of stable, compensated cirrhotic patients is practised in our unit since 2013, wherein these patients are reviewed every six months by specialist nurses in community clinics under remote supervision of hepatologists. We evaluated the experiences of patients and healthcare providers involved in the model to understand the acceptability, strengths, and limitations of the model and obtain suggestions to improve. A qualitative design using in-depth interviews was employed, followed by thematic analysis of eight patients, one attending physician both nurse and hospital clinics, four hepatologists, and three experienced specialist nurses running the nurse-led cirrhosis clinic. Patients expressed satisfaction and a good understanding of the nurse-led cirrhosis clinic, preferring it to hospital clinics for better accessibility and the unique nurse–patient relationship. Upskilling and provision of professional care in a holistic manner were appreciated by specialist nurses. The hepatologists expressed confidence and satisfaction, although they acknowledged the difference between the medical training of specialist nurses and hepatologists. The greater availability of hospital clinic time for sick patients was welcomed. Increased specialist nurse staffing, regular forums to promote specialist nurse learning, and formalization of the referral process were suggested. No adverse experiences were reported by patients or staff. The nurse-led cirrhosis clinic model for compensated liver cirrhosis was well received by patients, hepatologists, and specialist nurses. Wider implementation of the model could be considered after further investigations in other settings.
Evaluating the benefit of hearing aids with motion-based beamformer adaptation in a real-world setup

Abstract Objective Conventional directional hearing aid microphone technology may obstruct listening intentions when the talker and listener walk side by side. The purpose of the current study was to evaluate hearing aids that use a motion sensor to address listening needs during walking. Design Each participant completed two walks in randomised order, one walk with each of two hearing aid programs: (1) conventional beamformer adaptation that activated an adaptive, multiband beamformer in loud environments and (2) motion-based beamformer adaptation that activated a pinna-mimicking microphone setting when walking was detected. Participants walked along a pre-defined track and completed tasks assessing speech understanding and environmental awareness. Study Sample Participants were 22 older adults with moderate-to-severe hearing loss and experience using hearing aids. Results More participants preferred the motion-based than conventional beamformer adaptation for speech understanding, environmental awareness, overall listening, and sound quality (p < 0.05). Measures of speech understanding (p < 0.01) and localisation of sound stimuli (p < 0.05) were significantly better with motion-based than conventional beamformer adaptation. Conclusions The results suggest that hearing aid users can benefit from beamforming that uses motion sensor input to adapt the signal processing according to the user’s activity. The real-world setup of this study had limitations.
Halogenases: a palette of emerging opportunities for synthetic biology–synthetic chemistry and C–H functionalisation

The enzymatic generation of carbon–halogen bonds is a powerful strategy used by both nature and synthetic chemists to tune the bioactivity, bioavailability and reactivity of compounds, opening up the opportunity for selective C–H functionalisation. Genes encoding halogenase enzymes have recently been shown to transcend all kingdoms of life. These enzymes install halogen atoms into aromatic and less activated aliphatic substrates, achieving selectivities that are often challenging to accomplish using synthetic methodologies. Significant advances in both halogenase discovery and engineering have provided a toolbox of enzymes, enabling the ready use of these catalysts in biotransformations, synthetic biology, and in combination with chemical catalysis to enable late stage C–H functionalisation. With a focus on substrate scope, this review outlines the mechanisms employed by the major classes of halogenases, while in parallel, it highlights key advances in the utilisation of the combination of enzymatic halogenation and chemical catalysis for C–H activation and diversification.
Efficacy of Acotiamide on Postprandial Distress Syndrome and Epigastric Pain Syndrome Depending on the Estimated Gastric Acid Secretion Level

Background/Aims Gastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide. Methods Dyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale. Results Of the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046). Conclusion Although acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hyper-secretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable.
Effect of azithromycin and hydroxychloroquine in patients hospitalized with COVID‐19: Network meta‐analysis of randomized controlled trials

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID‐19) infection. The network meta‐analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID‐19 infection. The outcomes of interest were all‐cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random‐effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168–1.887]), AZ alone (OR = 0.965 [95% CI: 0.865–1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995–1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ2 = 0; I2 = 0% [95% CI: 0%–0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID‐19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID‐19.
Erythema gyratum repens following COVID‐19 infection

Erythema gyratum repens following COVID-19 infection Dear Editor, Erythema gyratum repens (EGR) is a rare figurate erythema, which presents as annular, erythematous concentric bands resembling wood grain. The diagnosis of EGR is based on clinical findings, supported by histologic findings. Though EGR has been originally reported as a paraneoplastic syndrome, in up to 20–30% of cases, it is associated with nonneoplastic causes, of which 1% are related to infection. We report on a 71-year-old previously healthy (non-smoking) male with the sudden onset of inferior limb pain and paresthesia followed by progressive itchy, erythematous, annular, concentric, slightly scaly patches on the thighs, lower abdomen, and buttocks (Figs. 1 and 2), which started 30 days after a moderately severe COVID-19 infection. Histopathology revealed perivascular lymphocytic infiltrate on the superficial and intermediate dermis, with slight erythrocyte extravasation and eosinophils (Fig. 3).
Reported Signs, Symptoms, and Diagnostic Tests Before Cardiotoxicity Among Women With Breast Cancer: A Pilot Study

Background Cardiotoxicity after cancer treatment is a potentially preventable life-threatening complication among women with breast cancer. There is no algorithm to identify women with breast cancer at risk of cardiotoxicity. Objectives We quantified signs and symptoms as well as selected laboratory values among women with breast cancer who developed cardiotoxicity. Methods The clinical characteristics (n = 15) were collected from electronic health records. Spearman correlation coefficients and a nonparametric statistical test were used to analyze data. Results Significant statistical differences were detected in the laboratory values comparing the first and second half of 6 months before cardiotoxicity including alanine aminotransferase (U/L) (30.67 ± 26.27 and 42.31 ± 35.65, respectively; P = .03, Cohen’s d = 0.37). A negative correlation was found between estimated glomerular filtration rate and new onset of more than 1 sign or symptom (Spearman's ρ = −0.5, P = .06). Conclusions Investigating clinical characteristics before cardiotoxicity may determine the mechanism(s) and identify high-risk patients.
Long-term association between diet quality and characteristics of the gut microbiome in the multiethnic cohort study

Abstract As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993–1996), 5280 at follow-up (Q3, 2003–2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013–2016). All participants provided a stool sample in 2013–2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.
Poor adherence to guideline-directed anticoagulation in elderly Chinese patients with atrial fibrillation: a report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry

Abstract Aims Adherence to guideline-directed oral anticoagulation (OAC) in patients with atrial fibrillation (AF) improves outcomes, but limited data are available from China. We evaluated the adherence to guideline-directed anticoagulation and its impact on clinical outcomes in a high-risk cohort of elderly Chinese patients. Methods and results The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre study conducted from October 2014 to December 2018. Endpoints of interest were all-cause death, thromboembolic (TE) events and major bleedings in patients with a guideline-directed indication for OACs (CHA2DS2-VASc ≥1 if male or ≥2 if female). The eligible cohort consisted of 5742 patients, of whom 2567 (44.7%) patients were treated with an OAC. Seven independent predictors of OAC undertreatment were identified: age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.03–1.05; P < 0.001], first diagnosed AF (OR: 1.71; 95%CI: 1.44–2.03; P < 0.001), chronic kidney disease (OR: 1.67; 95%CI: 1.36–2.06; P < 0.001), liver disease (OR: 1.69; 95%CI: 1.19–2.41; P = 0.003), dementia (OR: 1.67; 95%CI: 1.06–2.64; P = 0.026), prior extracranial bleeding (OR: 1.89; 95%CI: 1.35–2.64; P < 0.001), and the use of antiplatelet drug (OR: 6.97; 95%CI: 5.89–8.23; P < 0.001). On multivariate analysis, OAC undertreatment was significantly associated with a higher risk all-cause death (OR: 3.79; 95%CI: 2.61–5.53; P < 0.001) and TE events (OR: 2.28; 95%CI: 1.39–3.72; P = 0.001), and a similar risk of major bleeding as compared with guideline-directed OAC therapy. Conclusion Only 44.7% of all eligible patients were prescribed OAC in accordance with guideline recommendations. The independent predictors for OAC undertreatment were age, first diagnosed AF, chronic kidney disease, chronic obstructive pulmonary disease, prior extracranial bleeding, and the use of the antiplatelet drugs. Guideline-adherent thromboprophylaxis was safe and may be associated with improved survival and less TE among elderly Chinese patients with AF.
Intrahepatic Cholestasis Is a Clinically Significant Feature Associated with Natural History of X-Linked Myotubular Myopathy (XLMTM): A Case Series and Biopsy Report

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.
Cost-effectiveness of a telemonitoring program (telEPOC program) in frequently admitted chronic obstructive pulmonary disease patients

Chronic obstructive pulmonary disease is a typical disease among chronic and respiratory diseases. The costs associated with chronic disease care are rising dramatically, and this makes it necessary to redesign care processes, including new tools which allow the health system to be more sustainable without compromising on the quality of the care, compared to that currently provided. One approach may be to use information and communication technologies. In this context, we explored the cost-effectiveness of applying a telemonitoring system to a cohort of chronic obstructive pulmonary disease patients with frequent readmissions (the telEPOC programme). We conducted an intervention study with a control group. The inclusion criteria used were having chronic obstructive pulmonary disease (forced expiratory volume in the first second/forced vital capacity < 70%) and having been hospitalised for exacerbation at least twice in the last year or three times in the last 2 years. We estimated the costs incurred by patients in each group and calculated the quality-adjusted life years and incremental cost-effectiveness ratio. Overall, 77 patients were included in the control group and 86 in the intervention group. The raw cost-effectiveness analysis showed that the cost of the telEPOC intervention was significantly lower than that of usual care, while there were no significant differences between the groups in effectiveness. The incremental cost-effectiveness ratio for the intervention was €175,719.71 per quality-adjusted life-year gained. There were no differences between the intervention group (telemonitoring) and the control group (standard care) from the cost-effectiveness point of view. On the other hand, the intervention programme (telEPOC) was less expensive than routine clinical practice.
Direct Comparison of N-Glycans and Their Isomers Derived from Spike Glycoprotein 1 of MERS-CoV, SARS-CoV-1, and SARS-CoV-2

The emergence of COVID-19 pandemic has engaged the scientific community around the globe in the rapid development of effective therapeutics and vaccines. Owing to its crucial role in the invasion of the host cell, spike (S) glycoprotein is one of the major targets in these studies. The S1 subunit of the S protein (S1 protein) accommodates the receptor-binding domain, which enables the initial binding of the virus to the host cell. Being a heavily glycosylated protein, numerous studies have investigated its glycan composition. However, none of the studies have explored the isomeric glycan distribution of this protein. Furthermore, this isomeric glycan distribution has never been compared to that in S1 proteins of other coronaviruses, severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, which were responsible for past epidemics. This study explores the uncharted territory of the isomeric glycan distribution in the coronaviruses’ S1 protein using liquid chromatography coupled to tandem mass spectrometry. We believe that our data would facilitate future investigations to study the role of isomeric glycans in coronavirus viral pathogenesis.