Miracle-dz/UniFAR-FTUs huggingface dataset:
Delayed skeletal muscle repair following inflammatory damage in simulated agent-based models of muscle regeneration

Healthy skeletal muscle undergoes repair in response to mechanically localised strains during activities such as exercise. The ability of cells to transduce the external stimuli into a cascade of cell signalling responses is important to the process of muscle repair and regeneration. In chronic myopathies such as Duchenne muscular dystrophy and inflammatory myopathies, muscle is often subject to chronic necrosis and inflammation that perturbs tissue homeostasis and leads to non-localised, widespread damage across the tissue. Here we present an agent-based model that simulates muscle repair in response to both localised eccentric contractions similar to what would be experienced during exercise, and non-localised widespread inflammatory damage that is present in chronic disease. Computational modelling of muscle repair allows for in silico exploration of phenomena related to muscle disease. In our model, widespread inflammation led to delayed clearance of tissue damage, and delayed repair for recovery of initial fibril counts at all damage levels. Macrophage recruitment was delayed and significantly higher in widespread compared to localised damage. At higher damage percentages of 10%, widespread damage led to impaired muscle regeneration and changes in muscle geometry that represented alterations commonly observed in chronic myopathies, such as fibrosis. This computational work offers insight into the progression and aetiology of inflammatory muscle diseases, and suggests a focus on the muscle regeneration cascade in understanding the progression of muscle damage in inflammatory myopathies.
Assessing the impact of single or short-term administration on a therapy’s cost-effectiveness: a hypothetical disease-agnostic model

Abstract Aims Assessing the value of single or short-term therapies (SSTs) within traditional cost-effectiveness analyses (CEAs) has been a topic of discussion as the number of SSTs increases, particularly regarding the effect of discounting on valuation. To quantify the impact of discounting in economic evaluations, a CEA of a hypothetical SST and equivalent chronic therapy was conducted using standard methods. Materials and methods A lifetime Markov model was developed for a hypothetical chronic, progressive disease that could be treated with an SST, chronic therapy, or no novel treatment, termed standard of care (SoC). Incremental cost-effectiveness ratios (ICERs) with quality-adjusted life years (QALYs) comparing SST vs. SoC and an equivalent chronic therapy vs. SoC were assessed from a payer perspective. Both treatments had equal benefits and undiscounted lifetime costs; 3% discounting was applied to costs/benefits in the base case, and the impact of discounting was assessed. Results In the base case example, both the SST and equivalent chronic therapy vs. SoC had ICERs of $86,000/QALY without discounting. With 3% discounting, the ICER for the SST increased by 116% ($186,000/QALY) while the ICER for the chronic therapy increased by 10% ($95,000/QALY) despite equal clinical benefit. In scenario analyses, the ICER of the SST was consistently higher than the equivalent chronic therapy across a range of assumptions/inputs. Varying the cost/benefit discount rates had a greater impact on the SST. Differences in the ICERs between the therapies increased with increasing life expectancy/time horizon. Limitations The simple model structure may not be reflective of acute or more complex diseases. Also, the scenario of perfect equivalency in efficacy and lifetime costs is hypothetical. Conclusions This quantitative assessment showed the extent to which SST CEAs are highly sensitive to discounting, resulting in worse value assessments for SSTs than equivalent chronic therapies.
When crisis hits: Bike-Sharing platforms amid the Covid-19 pandemic

In this work, we examine the changes in demand for bike-sharing platforms with the onset of the Covid-19 pandemic. Using the fixed-effects regression formulation of difference-in-differences, we evaluate how the demand for bike-sharing platforms changed after the first cases of Covid were discovered and after the first executive orders were implemented. Accounting for weather conditions, socio-economic characteristics, time trends, and fixed effects across cities, our findings indicate that there is an increase in daily bike-sharing trips by 22% on average after the first Covid-19 case diagnosis, and a decrease of 30% after the first executive order implementation in each municipality, using the data up to August 2020. Moreover, we observe a 22% increase in weekday-specific trip frequency after the first Covid-19 case diagnosis and a 28% decrease in weekend-specific trip frequency after the first executive order implementation. Finally, we find that there is an increase in the frequency of trips on bike-sharing platforms in more bike-friendly, transit-friendly, and pedestrian-friendly cities upon both the first Covid-19 case diagnosis and the first executive order implementation.
No(cebo) Vax: COVID-19 Vaccine Beliefs Are Important Determinants of Both Occurrence and Perceived Severity of Common Vaccines’ Adverse Effects

This study highlights the role of psychological influences in triggering and amplifying the adverse effects of the COVID-19 vaccine (i.e., nocebo effects). Fear, beliefs, and expectations about the COVID-19 vaccine, trust in health and scientific institutions, and stable personality traits were measured in 315 adult Italian citizens (145 men) during the 15-min waiting time after vaccination. The occurrence and severity of 10 potential adverse effects were assessed 24 hr later. Nonpharmacological variables predicted nearly 30% of the severity of the vaccine’s adverse effects. Expectations are important determinants of adverse effects from vaccines, and the results of the path analyses show that these expectations stem primarily from people’s vaccine beliefs and attitudes, which can be changed. Implications for increasing vaccine acceptability and limiting the nocebo effect are discussed.
Ocular conjunctival microbiome profiling in dry eye disease: A case control pilot study

Purpose: Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is a multifactorial disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. A pilot study was undertaken to determine if there were any major substantial differences in the ocular microbiome in DED patients versus healthy controls. Methods: The bacterial communities residing in the conjunctiva of patients with DED (n = 4) and healthy controls (n = 4) were assessed by 16S ribosomal RNA (rRNA) gene sequencing of the V4–V5 region. Results: The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were most dominant and accounted for 97% and 94.5% of all bacterial sequences in patients and controls, respectively. At the genus level, 27 bacterial genera were found with more than two-fold difference between patients and controls. Four of these – Acinetobacter, Corynebacterium, Lactobacillus, and Pseudomonas spp. – dominated the ocular microbiome of all subjects, but were proportionately lower in DED (16.5%) compared to controls (37.7%). Several bacterial genera were found to be unique in DED (34) and controls (24). Conclusion: This pilot study is an attempt to profile the ocular microbiome in patients with DED that demonstrated a higher concentration of microbial DNA compared to controls, with Firmicutes phyla dominating the bacterial population in patients with DED.
GRAB-Net: Graph-Based Boundary-Aware Network for Medical Point Cloud Segmentation

Point cloud segmentation is fundamental in many medical applications, such as aneurysm clipping and orthodontic planning. Recent methods mainly focus on designing powerful local feature extractors and generally overlook the segmentation around the boundaries between objects, which is extremely harmful to the clinical practice and degenerates the overall segmentation performance. To remedy this problem, we propose a GRAph-based Boundary-aware Network (GRAB-Net) with three paradigms, Graph-based Boundary-perception Module (GBM), Outer-boundary Context-assignment Module (OCM), and Inner-boundary Feature-rectification Module (IFM), for medical point cloud segmentation. Aiming to improve the segmentation performance around boundaries, GBM is designed to detect boundaries and interchange complementary information inside semantic and boundary features in the graph domain, where semantics-boundary correlations are modelled globally and informative clues are exchanged by graph reasoning. Furthermore, to reduce the context confusion that degenerates the segmentation performance outside the boundaries, OCM is proposed to construct the contextual graph, where dissimilar contexts are assigned to points of different categories guided by geometrical landmarks. In addition, we advance IFM to distinguish ambiguous features inside boundaries in a contrastive manner, where boundary-aware contrast strategies are proposed to facilitate the discriminative representation learning. Extensive experiments on two public datasets, IntrA and 3DTeethSeg, demonstrate the superiority of our method over state-of-the-art methods.
Direct and inverse low‐frequency acoustic excitation of a layered sphere by an arbitrarily positioned point source

A layered sphere is excited by an acoustic point source arbitrarily located inside or outside the sphere. First, the direct scattering problem is solved analytically by developing a transitions matrix methodology. Then, approximations of the acoustic far‐field in the low‐frequency regime are derived, by using asymptotic techniques, and are subsequently utilized in inverse scattering algorithms concerning either the determination of the sphere's characteristics or the parameters of an internal point source. Copyright © 2016 John Wiley & Sons, Ltd.
Management of corneal perforations in dry eye disease: Preferred practice pattern guidelines

Corneal perforations in eyes with dry eye disease (DED) are difficult to manage due to the interplay of several factors such as the unstable tear film, surface inflammation, and the underlying systemic disease affecting the wound healing process, and the eventual outcome. A careful preoperative examination is required to identify the underlying pathology, and status of ocular surface and adnexa, rule out microbial keratitis, and order appropriate systemic workup in addition to assessing the perforation itself. Several surgical options are available, which include tissue adhesives, multilayered amniotic membrane grafting (AMT), tenon patch graft (TPG), corneal patch graft (CPG), and penetrating keratoplasty (PK). The choice of procedure depends upon the size, location, and configuration of the perforation. In eyes with smaller perforations, tissue adhesives are effective treatment modalities, whereas AMT, TPG, and CPG are viable options in moderate-sized perforations. AMT and TPG are also preferable in cases where the placement of a bandage contact lens may be a challenge. Large perforations require a PK, with additional procedures such as tarsorrhaphy to protect the eyes from the associated epithelial healing issues. Conjunctival flaps are considered in eyes with poor visual potential. The management of the acute condition is carried out in conjunction with measures to improve the tear volume bearing in mind the chances of delayed epithelialization and re-perforation in these cases. Administration of topical and systemic immunosuppression, when indicated, helps improve the outcome. This review aims to facilitate clinicians in instituting a synchronized multifaceted therapy for the successful management of corneal perforations in the setting of DED.
Microglia actively remove NR1 autoantibody‐bound NMDA receptors and associated post‐synaptic proteins in neuron microglia co‐cultures

Autoantibodies against the NR1 subunit of NMDA receptors (NMDARs) have been shown to promote crosslinking and internalization of bound receptors in NMDAR encephalitis (NMDARE). This internalization‐mediated loss of NMDARs is thought to be the major mechanism leading to pathogenic outcomes in patients. However, the role of bound autoantibody in engaging the resident immune cells, microglia, remains poorly understood. Here, using a patient‐derived monoclonal NR1 autoantibody (hNR1‐mAb) and a co‐culture system of microglia and neurons, we could show that hNR1‐mAb bound to hippocampal neurons led to microglia‐mediated removal of hNR1‐mAb bound NMDARs. These complexes were found to accumulate inside endo‐lysosomal compartments of microglia. Utilizing another patient isolated monoclonal autoantibody, against the α1‐subunit of GABAA receptors (α1‐GABAA‐mAb), such removal of receptors was found to be specific to the antibody‐bound receptor targets. Interestingly, along with receptor removal, we also observed a reduction in synapse number, more specifically in the numbers of post‐synaptic proteins like PSD95 and Homer 1, when microglia were present in the culture. Importantly, mutations in the Fc region of hNR1‐mAb, blocking its Fcγ receptor (FcγR) and complement binding, attenuated hNR1‐mAb driven loss of NMDARs and synapses, indicating that microglia engagement by bound hNR1‐mAb is critical for receptor and synapse loss. Our data argues for an active involvement of microglia in removal of NMDARs and other receptors in individuals with autoimmune encephalitis, thereby contributing to the etiology of these diseases.
Factors affecting the quality of laparoscopic D2 lymph node dissection for gastric cancer: a cohort study from two randomized controlled trials

Background: Laparoscopic D2 lymph node dissection (LND) for gastric cancer has a wide range and high difficulty. In the past, the quality of surgery was often judged by the time of the operation or the amount of blood loss, but the analysis based on surgical video was rarely reported. The purpose of this study was to analyze the relationship between the quality of laparoscopic D2 LND for gastric cancer and postoperative complications. Methods: The surgical video and clinicopathological data of 610 patients in two randomized controlled trials in our center from 2013 to 2016 were retrospectively analyzed. Klass-02-QC LND scale and general error score tool were used to quantitatively evaluate the intraoperative performance of D2 LND. Logistic regression was used to analyze the influencing factors of postoperative complications. Results: The overall incidence of complications (CD classification≥2) was 20.6%; the incidence of surgical complications was 6.9%. According to whether the LND score reached 44, patients were divided into a qualified group (73%) and a not-qualified group (27%). Event score (ES) by quartile was divided into grade 1 (21.7%), grade 2 (26%), grade 3 (28%), and grade 4 (24.3%) from low to high. Univariate logistic regression analysis showed that ES greater than or equal to 3, tumor size greater than or equal to 35 mm, and cTNM >II were independent risk factors for not-qualified LND. Male,tumor size greater than or equal to 35 mm and cTNM >II were independent risk factors for grade 4 ES. Not-qualified LND (OR=1.62, 95% CI: 1.16–3.89, P=0.021), grade 4 ES (OR=3.21, 95% CI: 1.52–3.90, P=0.035), and cTNM >II (OR=1.74, 95% CI: 1.39–7.33, P=0.041) were independent risk factors for postoperative surgical complications. Conclusions: The qualification of LND and intraoperative events based on surgical video are the independent influencing factors of postoperative complications of laparoscopic gastric cancer surgery. Specialist training and teaching based on surgical video may help to improve the surgical skills of specialists and improve the postoperative outcome of patients.
Prospective association between depressive symptoms and blood-pressure related outcomes in Kosovo

Kosovo has the lowest life expectancy in the Western Balkans, where cardiovascular disease (CVD) accounts for over half of all deaths. Depression also contributes to disability in the country, with a prevalence of moderate to severe symptoms reported as high as 42% in the general population. Although the mechanisms are not yet well understood, evidence suggests that depression is an independent risk factor for CVD. Our study assessed the prospective association between depressive symptoms and blood pressure (BP)-related outcomes among primary healthcare users in Kosovo to understand the role of BP in the relationship between depression and CVD. We included 648 primary healthcare users from the KOSCO study. The presence of depressive symptoms was defined as moderate to very severe depressive symptoms (DASS-21 depressive symptoms score ≥14). Multivariable censored regression models assessed prospective associations between baseline depressive symptoms and changes in systolic and diastolic BP while taking hypertension treatment into consideration. Multivariable logistic regression models assessed prospective associations between baseline depressive symptoms and hypertension diagnosis among normotensive patients (n = 226) as well as uncontrolled hypertension in hypertensive patients (n = 422) at follow-up. Depressive symptoms were associated with attenuated diastolic BP (β = -2.84, 95%-CI -4.64 to -1.05, p = 0.002) over a year of follow-up in our fully adjusted model, although the association with systolic BP (β = -1.98, 95%-CI -5.48 to 1.28, p = 0.23) did not meet statistical significance. We found no statistically significant association of depressive symptoms with hypertension diagnosis among initially normotensive people (OR = 1.68, 95%-CI 0.41 to 6.98, p = 0.48), nor with hypertension control among initially hypertensive people (OR = 0.69, 95%-CI 0.34 to 1.41, p = 0.31). Our findings are not consistent with increased BP as an underlying mechanism between depression and elevated CVD risk and contribute valuable evidence to cardiovascular epidemiology, where the mechanisms between depression, hypertension and CVD are yet to be elucidated.
Salivary aquaporin-3 as a screening biomarker for xerostomia in patients with periodontal disease and the effects of xerostomia on oral health-related quality of life

Xerostomia is a subjective condition of dryness of the oral cavity that may lead to several oral problems deteriorating oral health-related quality of life. This study aimed to (1) determine the prevalence of xerostomia, (2) compare the general health status, unstimulated salivary flow rate, and oral health-related quality of life in xerostomics and non-xerostomics, and (3) investigate the potential of salivary aquaporin-3 (AQP-3) as a screening biomarker for xerostomia in patients with periodontal disease. Demographics and systemic health data were collected from 109 healthy participants, 20 to 55 years old, with Community Periodontal Index (CPI) score ≥ 3. For subjective assessment of xerostomia, Shortened Xerostomia Inventory (SXI) was used. For objective assessment of xerostomia, unstimulated salivary flow rate was measured. Shortened Oral Health Impact Profile (S-OHIP) was utilized for oral health-related quality of life assessment. The collected saliva samples were processed and stored at −80°C. Quantification of salivary AQP-3 protein was done with enzyme-linked immunosorbent assay. Xerostomia was reported in 78% of the subjects based on SXI score. Median concentration of AQP-3 was significantly higher in xerostomics compared to non-xerostomics, p = 0.001. Moreover, oral health-related quality of life was significantly poor in xerostomics compared to non-xerostomics, p = 0.002. Furthermore, there were significant correlations between AQP-3 and SXI (r = 0.21, p = 0.025), AQP-3 and S-OHIP (r = 0.2, p = 0.042), S-OHIP and SXI (r = 0.37, p < 0.001), unstimulated salivary flow rate and random blood glucose level (r = 0.32, p = 0.001), and body mass index and mean arterial pressure (r = 0.44, p < 0.001). Regression analysis showed that body mass index, CPI score 3, and salivary AQP-3 were suitable predictors for presence of xerostomia. AQP-3 could be a potential screening biomarker for xerostomia in patients with periodontal disease for its early identification may help improve oral health-related quality of life of the individuals.
Optimization and evaluation of tear protein elution from Schirmer’s strips in dry eye disease

Purpose: Extraction of tear protein from Schirmer's strip is a prerequisite for the proper identification and screening of biomarkers in dry eye disease. The study compares different methods of extraction of tear proteins from the Schirmer's strip. Methods: Reflex tear was collected from healthy controls (HC; n = 12), Stevens–Johnson syndrome (SJS; n = 3) and dry eye disease (DED; n = 3) patients using capillary tube. This tear was used to measure the volume absorbed by Schirmer's strip per microliter. Different buffers (6) were used to compare the protein yield from the Schirmer's strip in four different conditions. The tear proteins extracted using the highest protein yield buffer were analyzed by mass spectrometry. Results: A linear relationship between the tear volume and wetting length was observed (r = 0.0.997, n = 6). The highest yield was observed after incubation of the Schirmer's strip in 100 mM ammonium bicarbonate (ABC) with 0.25% Nonidet P-40(NP-40) at 4°C for an hour (P < 0.00005). The in-solution digestion of tear eluted in the above condition 100 Mm ABC + 0.25% NP-40 with one-hour incubation yielded a total of 2119 proteins in HC, SJS, and DED. The unique protein observed in SJS and DED was 0.6% and 17.9%, respectively. The significantly expressed proteins are associated with innate immune response, proteolysis, wound healing, and defense response. Conclusion: A method for extraction of protein from Schirmer's strip was optimized for increase in protein yield from the tear sample. SJS and DED tear samples have unique protein signature. The study will aid in better design of tear protein-based experimental study.
Does migrant workers’ subjective social status affect their mental health? Job satisfaction as a longitudinal mediator

Background: Prior studies on migrant workers have explored the effect of their subjective social status and job satisfaction on their mental health, respectively or combined, as well as how their subjective social status affects their job satisfaction. Nonetheless, few have accounted straightforwardly and holistically for the mechanism of interaction between subjective social status, job satisfaction and mental health amongst migrant workers. Aims: Taking migrant workers in China as the object of study, we intended to probe the longitudinal links between their subjective social status, job satisfaction and mental health, in particular, their job satisfaction as a longitudinal mediator therein. Method: Using the three-wave data from the 2014, 2016 and 2018 China Labour-force Dynamics Survey, we defined migrant workers as labourers aged 15 to 64 with agricultural hukou and engaged in non-agricultural work in urban areas. The final valid sample comprised 2,035 individuals. Latent growth models (LGMs) were applied to test the hypothesised relationships. Results: The LGMs based on bootstrapping showed that amongst migrant workers the subjective social status, job satisfaction and mental health tended overall to grow linearly and that the job satisfaction longitudinally mediated between the subjective social status and mental health. Conclusions: The findings may enlighten policymaking to elevate migrant workers mentally and inform future studies on theoretical and practical fronts.