Miracle-dz/UniFAR-FTUs huggingface dataset:
Examining lysyl oxidase-like modulation of collagen architecture in 3D spheroid models of idiopathic pulmonary fibrosis via second-harmonic generation microscopy

Abstract. Significance: Idiopathic pulmonary fibrosis (IPF) patients have a poor prognosis with short lifespan following diagnosis as there are limited effective treatment options. Despite matrix stiffening being the hallmark of the disease there remains a lack of knowledge surrounding the underlying collagen alterations in the disease. Specifically, while increased collagen crosslinking has been implicated, the resulting effects on collagen macro/supramolecular changes have not been explored. Aim: We sought to determine if second-harmonic generation (SHG) microscopy could characterize differences in the collagen architecture in 3D spheroid models of IPF grown under different crosslinking modulation conditions (promotion and inhibition). Approach: We used SHG metrics based on the fiber morphology, relative SHG brightness, and macro/supramolecular structure by SHG polarization analyses to compare the structure of the IPF spheroids. Results: Comparison of the fiber morphology of the spheroids showed that the control group had the longest, straightest, and thickest fibers. The spheroids with crosslink enhancement and inhibition had the highest and lowest SHG conversion efficiencies, respectively, consistent with the resulting harmonophore density. SHG polarization analyses showed that the peptide pitch angle, alignment of collagen molecules, and overall chirality were altered upon crosslink modulation and were also consistent with reduced organization relative to the control group. Conclusions: While no single SHG signature is associated with crosslinking, we show that the suite of metrics used here is effective in delineating alterations across the collagen architecture sizescales. The results largely mirror those of human tissues and demonstrate that the combination of 3D spheroid models and SHG analysis is a powerful approach for hypothesis testing the roles of operative cellular and molecular factors in IPF.
Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015.

OBJECTIVE Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG. METHODS A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients. RESULTS In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010). CONCLUSIONS Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.
An unusual case of hip pain after total hip arthroplasty: A case report

Our goal is to draw attention to the inflammation of the iliopectineal bursa being a rare condition, which can cause lower limb swelling and anterior pain of the hip even years after total hip arthroplasty. A 67-year-old woman was admitted seven years after hip arthroplasty (cemented total endoprosthesis [TEP]) with swelling and feeling of excessive fullness of the lower extremity and with tolerable anterior hip pain. The physical examination and blood tests were non-specific for septic condition. Ultrasound showed a cystic mass in the inguinal region with a direct contact to the common femoral vein. Deep vein thrombosis was excluded. The single-photon emission computed tomography-computed tomography (SPECT-CT) was administered to decide the surgical plan, either making a bursa extirpation or making revision hip arthroplasty. The SPECT-CT excluded the possibility of aseptic loosening. Methylene blue was injected into the bursa intraoperatively which did not enter the strong pseudo-capsule of the joint and, therefore, we did not administer revision of the TEP, and the bursa was extirpated. Two weeks after the operation, the patient had no pain, was able to walk, and the swelling decreased. Four months after surgery, the pain and feeling of fullness disappeared, with minimal lower limb swelling. In conclusion, in case of increasing complaints of patients who left years behind without any problem following total hip arthroplasty, the pathogenic role of the iliopectineal bursa should be taken into account, after excluding more frequent causes such as aseptic loosening or periprosthetic joint infection. As long as we consider about a rare disease, we can find a solution to the patient’s complaint sooner.
EPSOL: sequence-based protein solubility prediction using multidimensional embedding

MOTIVATION The heterologous expression of recombinant protein requires host cells, such as Escherichia coli, and the solubility of protein greatly affects the protein yield. A novel and highly accurate solubility predictor that concurrently improves the production yield and minimizes production cost, and that forecasts protein solubility in an E. coli expression system before the actual experimental work is highly sought. RESULTS In this paper, EPSOL, a novel deep learning architecture for the prediction of protein solubility in an E. coli expression system, which automatically obtains comprehensive protein feature representations using multidimensional embedding, is presented. EPSOL outperformed all existing sequence-based solubility predictors and achieved 0.79 in accuracy and 0.58 in Matthew's correlation coefficient. The higher performance of EPSOL permits large-scale screening for sequence variants with enhanced manufacturability and predicts the solubility of new recombinant proteins in an E. coli expression system with greater reliability. AVAILABILITY AND IMPLEMENTATION EPSOL's best model and results can be downloaded from GitHub (https://github.com/LiangYu-Xidian/EPSOL). SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Competing Demands for a Complex System: Photosystem II Repair, Photoprotection and Quantum Yield

Photosynthesis in general is a key biological process on Earth and Photo system II (PSII) is an important component of this process. PSII is the only enzyme capable of oxidizing water and is largely responsible for the primordial build-up and present maintenance of the oxygen in the atmosphere. This thesis endeavoured to understand the link between structure and function in PSII with special focus on primary photochemistry, repair/photodamage and spectral characteristics. The deletion of the PsbU subunit ofPSII in cyanobacteria caused a decoupling of the Phycobilisomes (PBS) from PSII, likely as a result of increased rates of PSII photodamage with the PBS decoupling acting as a measure to protect PSII from further damage. Isolated fractions of spinach thylakoid membranes were utilized to characterize the heterogeneity present in the various compartments of the thylakoid membrane. It was found that the pooled PSIILHCII pigment populations were connected in the grana stack and there was also a progressive decrease in the reaction rates of primary photochemistry and antennae size of PSII as the sample origin moved from grana to stroma. The results were consistent with PSII complexes becoming damaged in the grana and being sent to the stroma for repair. The dramatic quenching of variable fluorescence and overall fluorescent yield of PSII in desiccated lichens was also studied in order to investigate the mechanism by which the quenching operated. It was determined that the source of the quenching was a novel long wavelength emitting external quencher. Point mutations to amino acids acting as ligands to chromophores of interest in PSII were utilized in cyanobacteria to determine the role of specific chromophores in energy transfer and primary photochemistry. These results indicated that the Hl14 ligated chlorophyll acts as the 'trap' chlorophyll in CP47 at low temperature and that the Q130E mutation imparts considerable changes to PSII electron transfer kinetics, essentially protecting the complex via increased non-radiative charge
An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.
Evaluating the safety of two human experimental intestinal ischemia reperfusion models: A retrospective observational study

Background We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR. Methods A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR. Secondary outcome parameters were operative time, blood loss, 90-day mortality and length of hospital stay. Results Following pancreatic surgery, 63% of the patients experienced one or more postoperative complications. There was no significant difference in incidence or severity of complications between patients undergoing pancreatic surgery with (70%) or without (60%, P = 0.7) jejunal IR. Following colorectal surgery, 60% of the patients experienced one or more postoperative complication. Complication rate and severity were similar in patients with (50%) and without (65%, P = 0.46) colonic IR. Operative time, amount of blood loss, postoperative C-reactive protein, length of hospital stay or mortality were equal in both intervention and control groups for jejunal and colon IR. Conclusion This study showed that human experimental intestinal IR models are safe in patients undergoing pancreatic or colorectal surgery.
Multilayer Sparsity-Based Tensor Decomposition for Low-Rank Tensor Completion

Existing methods for tensor completion (TC) have limited ability for characterizing low-rank (LR) structures. To depict the complex hierarchical knowledge with implicit sparsity attributes hidden in a tensor, we propose a new multilayer sparsity-based tensor decomposition (MLSTD) for the low-rank tensor completion (LRTC). The method encodes the structured sparsity of a tensor by the multiple-layer representation. Specifically, we use the CANDECOMP/PARAFAC (CP) model to decompose a tensor into an ensemble of the sum of rank-1 tensors, and the number of rank-1 components is easily interpreted as the first-layer sparsity measure. Presumably, the factor matrices are smooth since local piecewise property exists in within-mode correlation. In subspace, the local smoothness can be regarded as the second-layer sparsity. To describe the refined structures of factor/subspace sparsity, we introduce a new sparsity insight of subspace smoothness: a self-adaptive low-rank matrix factorization (LRMF) scheme, called the third-layer sparsity. By the progressive description of the sparsity structure, we formulate an MLSTD model and embed it into the LRTC problem. Then, an effective alternating direction method of multipliers (ADMM) algorithm is designed for the MLSTD minimization problem. Various experiments in RGB images, hyperspectral images (HSIs), and videos substantiate that the proposed LRTC methods are superior to state-of-the-art methods.
Protective function and durability of mouse lymph node-resident memory CD8+ T cells

Protective lung tissue-resident memory CD8+T cells (Trm) form after influenza A virus (IAV) infection. We show that IAV infection of mice generates CD69+CD103+and other memory CD8+T cell populations in lung-draining mediastinal lymph nodes (mLNs) from circulating naive or memory CD8+T cells. Repeated antigen exposure, mimicking seasonal IAV infections, generates quaternary memory (4M) CD8+T cells that protect mLN from viral infection better than 1M CD8+T cells. Better protection by 4M CD8+T cells associates with enhanced granzyme A/B expression and stable maintenance of mLN CD69+CD103+4M CD8+T cells, vs the steady decline of CD69+CD103+1M CD8+T cells, paralleling the durability of protective CD69+CD103+4M vs 1M in the lung after IAV infection. Coordinated upregulation in canonical Trm-associated genes occurs in circulating 4M vs 1M populations without the enrichment of canonical downregulated Trm genes. Thus, repeated antigen exposure arms circulating memory CD8+T cells with enhanced capacity to form long-lived populations of Trm that enhance control of viral infections of the mLN.
Orchestrating multiplexity in polychromatic science through OMIPs: A decade‐old resource to empower biomedical research

As the optimized multicolor immunofluorescence panel (OMIP) platform entered its 10th anniversary since its launch, the multicolor flow cytometry landscape has changed significantly. Likewise, OMIPs have continuously evolved to cover larger panel sizes, increasing number of subpopulations profiled in a single panel, and new species. After a decade of contributions to the OMIP platform, a review of this collection, summarizing its content and purpose for the research community, is timely and due. This review provides an overview of OMIPs and a presentation of the depth and diversity of this collection of validated panels, with the expectation that readers will take advantage of them to empower and accelerate their research.
Lack of association between MMP13 (rs3819089), ADAM12 (rs3740199-rs1871054) and ADAMTS14 (rs4747096) genotypes and advanced-stage knee osteoarthritis

Objectives The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). Patients and methods A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the Kellgren- Lawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample. Results The most common nucleotides in both the control and patient groups were CG for rs3740199 and CT for rs1871054 in the ADAM12 gene, and the most common nucleotides in alleles were GG for MMP13 rs3819089 and AA for ADAMTS14 rs4747096. No statistically significant relationship was detected between the gene polymorphisms and advanced OA. Conclusion The study results suggest that ADAM12 rs3740199 and rs1871054, MMP13 rs3819089, and ADAMTS14 rs4747096 polymorphisms have no relationship with knee OA susceptibility in the Turkish population. However, as this is the first study to investigate the relationship between the SNPs of ADAM12, ADAMTS14, and MMP13 genes and the development of OA in the Turkish population, it would contribute to our understanding of the molecular bases of OA.
Sparrows and supergenes: Ecological epigenetics in action

Despite the promise of ecological epigenetics, there remain few cases that clearly link epigenetic variation in wild animal populations to evolutionary change. In this issue of Molecular Ecology, Sun et al. provide such an example in white‐throated sparrows—a fascinating system in which a large chromosomal rearrangement generates a “supergene” polymorphism linked to plumage colour, aggression and parenting behaviour. By combining whole genome bisulphite sequencing with RNA‐sequencing and chromatin accessibility data, they show that the two alleles of this chromosomal polymorphism also exhibit substantial differences in DNA methylation levels, with implications for gene expression and transposable element activity. Their results provide a compelling case study for how genetic and epigenetic evolution proceed in concert. They also demonstrate the importance of integrating multiple types of genomic information to understand how gene regulation evolves, providing a model for future work in nonmodel species.
Transient Bipartite Synchronization for Cooperative-Antagonistic Multiagent Systems With Switching Topologies

This article aims at addressing the transient bipartite synchronization problem for cooperative-antagonistic multiagent systems with switching topologies. A distributed iterative learning control protocol is presented for agents by resorting to the local information from their neighbor agents. Through learning from other agents, the control input of each agent is updated iteratively such that the transient bipartite synchronization can be achieved over the targeted finite horizon under the simultaneously structurally balanced signed digraph. To be specific, all agents finally have the same output moduli at each time instant over the desired finite-time interval, which overcomes the influences caused by the antagonisms among agents and topology nonrepetitiveness along the iteration axis. As a counterpart, it is revealed that the stability can be achieved over the targeted finite horizon in the presence of a constantly structurally unbalanced signed digraph. Simulation examples are carried out to demonstrate the effectiveness of the distributed learning results developed among multiple agents.
Inter-hospital transfer of polytrauma and severe traumatic brain injury patients: Retrospective nationwide cohort study using data from the Swiss Trauma Register

Introduction Polytrauma and traumatic brain injury (TBI) patients are among the most vulnerable patients in trauma care and exhibit increased morbidity and mortality. Timely care is essential for their outcome. Severe TBI with initially high scores on the Glasgow Coma (GCS) scores is difficult to recognise on scene and referral to a Major Trauma Center (MTC) might be delayed. Therefore, we examined current referral practice, injury patterns and mortality in these patients. Materials and methods Retrospective, nationwide cohort study with Swiss Trauma Register (STR) data between 01/012015 and 31/12/2018. STR includes patients ≥16 years with an Injury Severity Score (ISS) >15 and/or an Abbreviated Injury Scale (AIS) for head >2. We performed Cox proportional hazard models with injury type as the primary outcome and mortality as the dependent variable. Secondary outcomes were inter-hospital transfer and age. Results 9,595 patients were included. Mortality was 12%. 2,800 patients suffered from isolated TBI. 69% were men. Median age was 61 years and median ISS 21. Two thirds of TBI patients had a GCS of 13–15 on admission to the Emergency Department (ED). 26% of patients were secondarily transferred to an MTC. Patients with isolated TBI and those aged ≥65 years were transferred more often. Crude analysis showed a significantly elevated hazard for death of 1.48 (95%CI 1.28–1.70) for polytrauma patients with severe TBI and a hazard ratio (HR) of 1.82 (95%CI 1.58–2.09) for isolated severe TBI, compared to polytrauma patients without TBI. Patients directly admitted to the MTC had a significantly elevated HR for death of 1.63 (95%CI 1.40–1.89), compared to those with secondary transfer. Conclusions A high initial GCS does not exclude the presence of severe TBI and triage to an MTC should be seriously considered for elderly TBI patients.