Miracle-dz/UniFAR-FTUs huggingface dataset:
Inter‐joint coordination variability is associated with pain severity and joint loading in persons with knee osteoarthritis

As the lower extremity is a linked‐joint system, the contribution of movements at the hip and ankle, in addition to the knee, to gait patterns should be considered for persons with knee osteoarthritis (OA). However, the relationships of joint coordination variability to OA symptoms, particularly knee pain, and joint loading is unknown. The purpose of this study was to determine the relationship of joint coordination variability to knee pain severity and joint loading in persons with knee OA. Thirty‐four participants with knee OA underwent gait analysis. Vector coding was used to assess coordination variability during the early, mid, and late stance phase. Hip–knee coupling angle variability (CAV) during midstance was associated with Knee Injury and Osteoarthritis Outcome Score (KOOS) pain (r = −0.50, p = 0.002) and Visual Analog Scale pain (r = 0.36, p = 0.04). Knee–ankle CAV during midstance was associated with KOOS pain (r = −0.34, p = 0.05). Hip–knee CAV during early and midstance were associated with knee flexion moment (KFM) impulses (r = −0.46, p = 0.01). Knee–ankle CAV during early and midstance were associated with peak KFM (r = −0.51, p < 0.01; r = −0.70, p < 0.01). Moreover, knee–ankle CAV during early, mid, and late stance phase were associated with KFM impulses (r = −0.53, p < 0.01; r = −0.70, p < 0.01; r = −0.54, p < 0.01). These findings suggest that joint coordination variability may be a factor that influences pain and knee joint loading in persons with knee OA. Statement of Clinical Significance: Movement coordination of the hip, knee, and ankle should be considered in the clinical management and future research related to knee OA.
Vessel Contour Detection in Intracoronary Images via Bilateral Cross-Domain Adaptation

Vessel contour detection (VCD) in intravascular images is important for the quantitative assessment of vessels. However, it is still a challenging task due to a high degree of morphology variability. Images from a single modality lack sufficient information on the vessel morphology due to the natural limitation of the imaging capability. Therefore, the single-modality VCD methods have difficulty extracting sufficient morphological information. Cross-modality methods have the potential to overcome morphology variability by extracting more information from different modalities. However, they still face the difficulty of the domain discrepancy, i.e., feature space discrepancy and label space inconsistency. In this paper, we aim to address the domain discrepancy for VCD. To overcome label space inconsistency, our method divides the label space into private label space and shared label space. It constructs subdomains for the private label space and the shared label space, and minimizes the task risk at the subdomain level. To overcome feature space discrepancy, it extracts domain-invariant features via domain adaptation between the subdomains. Finally, it uses the domain-invariant features as auxiliary information for each subdomain. Extensive experiments on 130 IVUS sequences (135663 images) and 124 OCT sequences (39857 images) show that our method is effective (e.g., the Dice index $\geqslant$ 0.949), and superior to the nineteen state-of-the-art VCD methods.
Cardiovascular organ damage in relation to hypertension status in patients with ankylosing spondylitis

Abstract Purpose Hypertension is a major cardiovascular (CV) risk factor in ankylosing spondylitis (AS) patients. Less is known about the prevalence of CV organ damage in relation to hypertension status in AS patients. Materials and Methods CV organ damage was assessed by echocardiography, carotid ultrasound and pulse wave velocity (PWV) by applanation tonometry in 126 AS patients (mean age 49 ± 12 years, 39% women) and 71 normotensive controls (mean age 47 ± 11 years, 52% women). CV organ damage was defined as presence of abnormal left ventricular (LV) geometry, LV diastolic dysfunction, left atrial (LA) dilatation, carotid plaque or high pulse wave velocity (PWV). Results Thirty-four percent of AS patients had hypertension. AS patients with hypertension were older and had higher C-reactive protein (CRP) levels compared to AS patients without hypertension and controls (p < 0.05). The prevalence of CV organ damage was 84% in AS patients with hypertension, 29% in AS patients without hypertension and 30% in controls (p < 0.001). In multivariable logistic regression analyses, having hypertension was associated with a fourfold increased risk of CV organ damage independent of age, presence of AS, gender, body mass index, CRP, and cholesterol (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.53 to 13.61, p = 0.006). In AS patients, presence of hypertension was the only covariable significantly associated with presence of CV organ damage (OR 4.40, 95% CI 1.40 to 13.84, p = 0.011). Conclusions CV organ damage in AS was strongly associated with hypertension, pointing to the importance of guideline-based hypertension management in AS patients. PLAIN LANGUAGE SUMMARY What is the context? Ankylosing spondylitis (AS) is an inflammatory disease primarily affecting the spine. Patients with AS have increased risk for cardiovascular disease. High blood pressure (hypertension) is both very common in AS patients, and a major risk factor for developing cardiovascular disease. Hypertension leads to structural and functional changes in the heart and arteries, referred to as cardiovascular organ damage. However, little is known about the prevalence of cardiovascular organ damage in AS patients with hypertension. What is new? Using ultrasound and tonometry, we assessed organ damage in the heart and arteries in AS patients with hypertension and compared them to AS patients with normal blood pressure as well as a group of healthy controls. We found that 84% of the AS patients with hypertension had cardiovascular organ damage, compared to 29% of AS patients with normal blood pressure and 30% of controls. Independent of other risk factors, hypertension was associated with a fourfold increased risk of cardiovascular organ damage in AS patients. What is the impact? These findings are important because cardiovascular organ damage is potentially reversible with treatment. Our results underline the significance of guideline-directed hypertension management in AS patients to reduce cardiovascular disease.
Explicit results on primes

Let p be a prime number. In this thesis we prove the following theorems. Theorem -1.0. 1. Let x0 ≥ 4·1018 be a fixed constant and let x > x0. Then there exists at least one prime p such that (1 −∆−1)x < p < x, where ∆ is a constant depending on x0 and is given in Table 2.2. Theorem -1.0. 1 improves on the 2003 paper of Ramaré and Saouter [67]. This work has been refereed and is to appear in the scholarly journal Integers [38]. Theorem -1.0. 1 allows one to deduce the following verification of the odd Goldbach conjecture: Corollary -1.0. 2. Every odd number larger than 5 and smaller than 1 966 196 911× 4 · 10 = 7.864 . · 10 is the sum of at most three primes. The second part of this thesis investigates the error term in the prime number theorem in arithmetic progressions. Let a and q be positive relatively prime integers. Let ψ(x; q, a) = ∑ n≤x n≡a(mod q) n=pk k≥1 log n and E(x; q, a) = ∣∣∣∣ψ(x; q, a)− x φ(q) x φ(q) ∣∣∣∣ , be the error term for the prime number theorem in arithmetic progressions. We prove Theorem -1.0. 3. For b a fixed positive constant and x ≥ 10b, there exists q,b > 0 such that E(x; q, a) ≤ q,b where q,b is given explicitly in Theorem 3.7. 8 and is computed in iii in Table 3.10. Theorem -1.0. 3 improves the 1996 work of Ramaré and Rumely [66], which was the article of reference for explicit bounds on E(x; q, a) for nearly 20 years.
A centre-based, ambulatory care concept for Hidradenitis suppurativa improves disease activity, burden, and patient satisfaction: results from the randomised controlled trial EsmAiL.

BACKGROUND Hidradenitis suppurativa is an inflammatory disease of the inverse skin regions that occurs particularly in young women and affects approximately 1% of the population. Outpatient care is often inadequate and usually cannot prevent progression. OBJECTIVE The aim of the EsmAiL trial was to evaluate whether an innovative care concept can decrease disease activity and burden, as well as improve patient satisfaction. METHODS EsmAiL was conducted as a two-arm, multicentre, prospective randomised controlled trial including 553 adults with HS. Inclusion criteria were a minimum of three inflammatory lesions and at least moderate impact of the disease on the quality of life. The control group (CG) remained in standard care, whereas the intervention group (IG) was treated according to a trial-specific, multimodal concept. Primary endpoint was the absolute change in the International Hidradenitis Suppurativa Severity Score System (IHS4). RESULTS 279 patients were randomised to the IG and 274 to the CG. Of those, 377 attended final assessment after 12-month of intervention. Participants in the IG (n=203) achieved a mean improvement in the IHS4 of 9.3 points while the average decrease in the CG patients (n=174) amounted to 5.7 points (p=0.003). Patients receiving the new care concept also reported a significantly (p<0.001) higher decrease in pain, DLQI and HADS compared to changes in the CG. Patient satisfaction was also significantly higher in the IG than in the CG (p<0.001). CONCLUSION The establishment of standardised treatment algorithms in so-called "acne inversa centres (AiZ)" in the ambulatory setting has a substantial, positive impact on the course of the disease and significantly improves patient satisfaction.
Pressured cytotoxic T cell epitope strength among SARS‐CoV‐2 variants correlates with COVID‐19 severity

Heterogeneity in susceptibility among individuals to COVID‐19 has been evident through the pandemic worldwide. Cytotoxic T lymphocyte (CTL) responses generated against pathogens in certain individuals are known to impose selection pressure on the pathogen, thus driving emergence of new variants. In this study, we probe the role played by host genetic heterogeneity in terms of HLA‐genotypes in determining differential COVID‐19 severity in patients. We use bioinformatic tools for CTL epitope prediction to identify epitopes under immune pressure. Using HLA‐genotype data of COVID‐19 patients from a local cohort, we observe that the recognition of pressured epitopes from the parent strain Wuhan‐Hu‐1 correlates with COVID‐19 severity. We also identify and rank list HLA‐alleles and epitopes that offer protectivity against severe disease in infected individuals. Finally, we shortlist a set of 6 pressured and protective epitopes that represent regions in the viral proteome that are under high immune pressure across SARS‐CoV‐2 variants. Identification of such epitopes, defined by the distribution of HLA‐genotypes among members of a population, could potentially aid in prediction of indigenous variants of SARS‐CoV‐2 and other pathogens.
Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub‐Saharan Africa: A scoping review of interventions in the era of universal treatment

Men in sub‐Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented.
Toward Human-Like Grasp: Functional Grasp by Dexterous Robotic Hand Via Object-Hand Semantic Representation

Intelligent robotic manipulation is a challenging study of machine intelligence. Although many dexterous robotic hands have been designed to assist or replace human hands in executing various tasks, how to teach them to perform dexterous operations like human hands is still a challenge. This motivates us to conduct an in-depth analysis of human behavior in manipulating objects and propose an object-hand manipulation representation. This representation provides an intuitive and clear semantic indication of how the dexterous hand should touch and manipulate an object based on the object's own functional areas. At the same time, we propose a functional grasp synthesis framework, which does not require real grasp label supervision, but relies on the guidance of our object-hand manipulation representation. In addition, in order to obtain better functional grasp synthesis results, we propose a network pre-training method that can make full use of easily obtained stable grasp data, and a network training strategy to coordinate the loss functions. We conduct object manipulation experiments on a real robot platform, and evaluate the performance and generalization of our object-hand manipulation representation and grasp synthesis framework.
Facile Synthesis of Highly Stretchable, Tough, and Photodegradable Hydrogels

Recently, highly stretchable and tough hydrogels that are photodegradable on‐demand have been reported. Unfortunately, the preparation procedure is complex due to the hydrophobic nature of the photocrosslinkers. Herein, a simple method is reported to prepare photodegradable double‐network (DN) hydrogels that exhibit high stretchability, toughness, and biocompatibility. Hydrophilic ortho‐nitrobenzyl (ONB) crosslinkers incorporating different poly(ethylene glycol) (PEG) backbones (600, 1000, and 2000 g mol−1) are synthesized. These photodegradable DN hydrogels are prepared by the irreversible crosslinking of chains by using such ONB crosslinkers, and the reversible ionic crosslinking between sodium alginate and divalent cations (Ca2+). Remarkable mechanical properties are obtained by combining ionic and covalent crosslinking and their synergistic effect, and by reducing the length of the PEG backbone. The rapid on‐demand degradation of these hydrogels is also demonstrated by using cytocompatible light wavelength (λ = 365 nm) that degrades the photosensitive ONB units. The authors have successfully used these hydrogels as skin‐worn sensors for monitoring human respiration and physical activities. A combination of excellent mechanical properties, facile fabrication, and on‐demand degradation holds promise for their application as the next generation of substrates or active sensors eco‐friendly for bioelectronics, biosensors, wearable computing, and stretchable electronics.
CDK4/6 and autophagy inhibitors synergize to suppress the growth of human head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) accounts for over 10,000 deaths in the United States annually. Approximately 80% of HNSCC are human papillomavirus (HPV)‐negative which have an overall poorer prognosis compared to the HPV‐positive disease. Treatment options are mainly nontargeted chemotherapy, radiation, and surgery. The cyclin‐d‐CDK4/6‐RB pathway, which regulates cell cycle progression, is often deregulated in HNSCC, making it an attractive therapeutic target. In the current study, we investigated the therapeutic effects of cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors in preclinical models of HNSCCs. Our results show that the specific CDK4/6 inhibitor, abemaciclib, inhibited cell growth, and induced apoptosis in HNSCC cell lines. We also demonstrated that both the pro‐survival autophagy pathway and the ERK pathway in HNSCC cells were activated with abemaciclib treatment through the generation of reactive oxygen species (ROS). Coinhibition of CDK4/6 and autophagy synergistically decreased cell viability, induced apoptosis, and inhibited tumor growth in both in vitro and in vivo preclinical HNSCC models. These results reveal a potential therapeutic strategy that supports the rationale for further clinical development of a combination of CDK4/6 and autophagy inhibitors in HNSCC.
Assignment strategies modulate students’ academic performance in an online learning environment during the first and second COVID-19 related school closures

A growing number of studies seek to evaluate the impact of school closures during the ongoing COVID-19 pandemic. While most studies reported severe learning losses in students, some studies found positive effects of school closures on academic performance. However, it is still unclear which factors contribute to the differential effects observed in these studies. In this article, we examine the impact of assignment strategies for problem sets on the academic performance of students (n ≈ 16,000 from grades 4–10 who calculated ≈ 170,000 problem sets) in an online learning environment for mathematics, during the first and second period of pandemic-related school closures in Germany. We observed that, if teachers repeatedly assigned single problem sets (i.e., a small chunk of on average eight mathematical problems) to their class, students’ performance increased significantly during both periods of school closures compared to the same periods in the previous year (without school closures). In contrast, our analyses also indicated that, if teachers assigned bundles of problem sets (i.e., large chunks) or when students self-selected problem sets, students’ performance did not increase significantly. Moreover, students’ performance was generally higher when single problem sets were assigned, compared to the other two assignment types. Taken together, our results imply that teachers’ way of assigning problem sets in online learning environments can have a positive effect on students’ performance in mathematics.
Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain

Pleiotropic consequences of deletion of SERF in mice reveals biological functions in cell growth and development and supports the existence of biological modifiers of amyloid polymorphisms in the brain. In age-related neurodegenerative diseases, like Alzheimer’s and Parkinson’s, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated conditional Serf2 knockout mice and found that full-body deletion of Serf2 delayed embryonic development, causing premature birth and perinatal lethality. Brain-specific Serf2 knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-β aggregation, brain depletion of Serf2 altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest that Serf2 depletion changed the structure of amyloid deposits, which was further supported by scanning transmission electron microscopy, but further study will be required to confirm this observation. Altogether, our data reveal the pleiotropic functions of SERF2 in embryonic development and in the brain and support the existence of modifying factors of amyloid deposition in mammalian brain, which offer possibilities for polymorphism-based interventions.
Pathological imaging‐assisted cancer gene–environment interaction analysis

Gene–environment (G–E) interactions have important implications for cancer outcomes and phenotypes beyond the main G and E effects. Compared to main‐effect‐only analysis, G–E interaction analysis more seriously suffers from a lack of information caused by higher dimensionality, weaker signals, and other factors. It is also uniquely challenged by the “main effects, interactions” variable selection hierarchy. Effort has been made to bring in additional information to assist cancer G–E interaction analysis. In this study, we take a strategy different from the existing literature and borrow information from pathological imaging data. Such data are a “byproduct” of biopsy, enjoys broad availability and low cost, and has been shown as informative for modeling prognosis and other cancer outcomes/phenotypes in recent studies. Building on penalization, we develop an assisted estimation and variable selection approach for G–E interaction analysis. The approach is intuitive, can be effectively realized, and has competitive performance in simulation. We further analyze The Cancer Genome Atlas (TCGA) data on lung adenocarcinoma (LUAD). The outcome of interest is overall survival, and for G variables, we analyze gene expressions. Assisted by pathological imaging data, our G–E interaction analysis leads to different findings with competitive prediction performance and stability.
Modulating the Perceived Softness of Real Objects Through Wearable Haptics

In vision, Augmented Reality (AR) allows the superposition of digital content on real-world visual information, relying on the well-established See-through paradigm. In the haptic domain, a putative Feel-through wearable device should allow to modify the tactile sensation without masking the actual cutaneous perception of the physical objects. To the best of our knowledge, a similar technology is still far to be effectively implemented. In this work, we present an approach that allows, for the first time, to modulate the perceived softness of real objects using a Feel-through wearable that uses a thin fabric as interaction surface. During the interaction with real objects, the device can modulate the growth of the contact area over the fingerpad without affecting the force experienced by the user, thus modulating the perceived softness. To this aim, the lifting mechanism of our system warps the fabric around the fingerpad in a way proportional to the force exerted on the specimen under exploration. At the same time, the stretching state of the fabric is controlled to keep a loose contact with the fingerpad. We demonstrated that different softness perceptions for the same specimens can be elicited, by suitably controlling the lifting mechanism of the system.
LeadinCare: A Qualitative Informed Digital Training Platform Development to Increase Physicians’ Soft Communication Skills After COVID-19

ABSTRACT The post-COVID-19 pandemic era has placed new demands on physicians. One of these demands is the need to use targeted knowledge and soft communication skills, to address the psychosocial problems (e.g. vaccine hesitancy, fears) of individuals with Chronic Physical Illnesses (CPIs). Focusing on training physicians in targeted soft communication skills can help health care systems to address psychosocial-type problems. Yet, such training programs are rarely implemented, effectively. This study aimed to (a) understand physicians’ implementation challenges when using soft communication skills during the COVID-19 pandemic; (b) identify beliefs, barriers, and facilitators that can influence physicians’ behaviours to use soft communication skills; and (c) inform the content of the LeadinCare; a new digital training platform, designed to improve physicians’ soft communication skills, by leveraging the TDF Theoretical Domain Framework (TDF). We conducted 14 in-depth semi-structured interviews with physicians in Greece, supporting non-COVID-19 cases with CPIs. We analyzed their data using inductive and deductive approaches. Physicians highlighted time, inability to see patients in person, absence of space for non-COVID-19 cases, and poor organizational procedures as barriers to using soft communication skills. Five TDF domains (beliefs) were identified as the most salient to inform the LeadinCare platform: (1) practical and well-organized knowledge; (2) skills that support patients and their relatives; (3) physicians’ beliefs about capabilities to use the skills; (4) beliefs about consequences of using the skills (job satisfaction); and (5) the use of digital, interactive, and on-demand platforms (environmental context & resources). We mapped the domains in six narrative-based practices that informed the content of the LeadinCare. Physicians need skills that go beyond talking and towards cultivating resilience and flexibility.