Miracle-dz/UniFAR-FTUs huggingface dataset:
Disentangling the clinical data chaos: User-centered interface system design for trauma centers

This paper presents a year-long study of our project, aiming at (1) understanding the work practices of clinical staff in trauma intensive care units (TICUs) at a trauma center, with respect to their usage of clinical data interface systems, and (2) developing and evaluating an intuitive and user-centered clinical data interface system for their TICU environments. Based on a long-term field study in an urban trauma center that involved observation-, interview-, and survey-based studies to understand our target users and their working environment, we designed and implemented MediSenseView as a working prototype. MediSenseView is a clinical-data interface system, which was developed through the identification of three core challenges of existing interface system use in a trauma care unit—device separation, usage inefficiency, and system immobility—from the perspectives of three staff groups in our target environment (i.e., doctors, clinical nurses and research nurses), and through an iterative design study. The results from our pilot deployment of MediSenseView and a user study performed with 28 trauma center staff members highlight their work efficiency and satisfaction with MediSenseView compared to existing clinical data interface systems in the hospital.
High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages

High titers and low fucosylation of human anti–spike protein IgG promote alveolar macrophage activation and inflammation. Activating antibodies Excessive inflammation is a characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly in patients that are hospitalized with coronavirus disease 2019 (COVID-19). Here, Hoepel et al. investigated how human antibodies specific to SARS-CoV-2 spike protein may contribute to exacerbated inflammation. The authors found that spike protein–specific antibodies from patients with COVID-19 who were hospitalized had altered glycosylation, with an enrichment in low-fucosylated antibodies. These antibodies were able to activate human macrophages in vitro to secrete proinflammatory cytokines. Thus, altered antibody glycosylation may contribute to disease severity in COVID-19. Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein–specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19–associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG–activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.
Value of second-trimester uterine artery pulsatility index in pregnancies with systemic lupus erythematosus and/or antiphospholipid syndrome

Abstract Objective To assess the value of the second trimester mean pulsatility index of the uterine arteries (MPI-UtA) to predict adverse perinatal outcome (APO) in women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Pregnancies with either an SLE diagnosis or with primary APS controlled at our Hospital during a 10 years period were included. MPI-UtA was performed between 19–23 weeks' gestation. The MPI-UtA was defined as abnormal when it was >95th centile. APO was defined as the presence of: preeclampsia (PE), small for gestational age (SGA) newborn, preterm delivery, placental abruption and fetal or neonatal death. Results There were 39 ongoing pregnancies, 16 of them with SLE and 23 with primary APS. Nine patients had no previous pregnancy (23%). Globally, 35 live births were recorded, being the mean gestational age at delivery 38.1 ± 2.1 weeks and the mean birth weight 2835 ± 492 g. Abnormal MPI-UtA was found in 6 (15%) pregnancies, all of them (100%) had an APO: there were 4 fetal deaths and 2 further severe PE with live newborn. Normal MPI-UtA was shown in the remaining 33 (84.6%); of them, 6 (18%) had an APO: one late PE with a premature newborn, another one severe preterm baby and 4 SGA term newborns. No cases of perinatal death occurred in this group. Therefore, accuracy of MPI-UtA evaluation for APO was: sensitivity 50%, specificity 100%, PPV 100% and NPV 82%, respectively (p < .001). Conclusion Abnormal second-trimester uterine artery Doppler evaluation is highly predictive for adverse perinatal outcome in pregnancies affected by SLE or APS.
Radiocarbon in otoliths of tropical marine fishes: Reference Δ14C chronology for north Caribbean waters

Reef fishes support important fisheries throughout the Caribbean, but a combination of factors in the tropics makes otolith microstructure difficult to interpret for age estimation. Therefore, validation of ageing methods, via application of Δ14C is a major research priority. Utilizing known-age otolith material from north Caribbean fishes, we determined that a distinct regional Δ14C chronology exists, differing from coral-based chronologies compiled for ageing validation from a wide-ranging area of the Atlantic and from an otolith-based chronology from the Gulf of Mexico. Our north Caribbean Δ14C chronology established a decline series with narrow prediction intervals that proved successful in ageing validation of three economically important reef fish species. In examining why our north Caribbean Δ14C chronology differed from some of the coral-based Δ14C data reported from the region, we determined differences among study objectives and research design impact Δ14C temporal relationships. This resulted in establishing the first of three important considerations relevant to applying Δ14C chronologies for ageing validation: 1) evaluation of the applicability of original goal/objectives and study design of potential Δ14C reference studies. Next, we determined differences between our Δ14C chronology and those from Florida and the Gulf of Mexico were explained by differences in regional patterns of oceanic upwelling, resulting in the second consideration for future validation work: 2) evaluation of the applicability of Δ14C reference data to the region/location where fish samples were obtained. Lastly, we emphasize the application of our north Caribbean Δ14C chronology should be limited to ageing validation studies of fishes from this region known to inhabit shallow water coral habitat as juveniles. Thus, we note the final consideration to strengthen findings of future age validation studies: 3) use of Δ14C analysis for age validation should be limited to species whose juvenile habitat is known to reflect the regional Δ14C reference chronology.
Effects of multiple stressors on the dimensionality of ecological stability

Abstract Ecological stability is a multidimensional construct. Investigating multiple stability dimensions is key to understand how ecosystems respond to disturbance. Here, we evaluated the single and combined effects of common agricultural stressors (insecticide, herbicide and nutrients) on four dimensions of stability (resistance, resilience, recovery and invariability) and on the overall dimensionality of stability (DS) using the results of a freshwater mesocosm experiment. Functional recovery and resilience to pesticides were enhanced in nutrient‐enriched systems, whereas compositional recovery was generally not achieved. Pesticides did not affect compositional DS, whereas functional DS was significantly increased by the insecticide only in non‐enriched systems. Stressor interactions acted non‐additively on single stability dimensions as well as on functional DS. Moreover we demonstrate that pesticides can modify the correlation between functional and compositional aspects of stability. Our study shows that different disturbance types, and their interactions, require specific management actions to promote ecosystem stability.
Wedelolactone improves the renal injury induced by lipopolysaccharide in HK-2 cells by upregulation of protein tyrosine phosphatase non-receptor type 2

Objective To explore the effects of wedelolactone (WEL) on sepsis-induced renal injury in the human renal proximal tubular epithelial cell line HK-2. Methods HK-2 cells were stimulated by 1 µg/ml lipopolysaccharide (LPS) to trigger renal injury in vitro. HK-2 cells were pretreated with or without WEL (0.1, 1 and 10 µM) before LPS stimulation. Protein and mRNA analyses were performed using enzyme-linked immunosorbent assays, Western blot analysis and quantitative reverse transcription–polymerase chain reaction. The MTT assay and flow cytometry were used to measure cell viability and the rate of cell apoptosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) knockdown was induced by the transection of HK-2 cells with short hairpin RNA. Results Cell viability was significantly increased in a dose-dependent manner by WEL in LPS-induced HK-2 cells. WEL also decreased the levels of four inflammatory cytokines and cell apoptosis in LPS-induced HK-2 cells. The level of PTPN2 was increased after WEL treatment. PTPN2 knockdown partly abolished the inhibitory effects of WEL on cell apoptosis, the levels of inflammatory cytokines and on p38 mitogen-activated protein kinase/nuclear factor-kappaB signalling in LPS-induced HK-2 cells. Conclusion WEL improved renal injury by suppressing inflammation and cell apoptosis through upregulating PTPN2 in HK-2 cells. PTPN2 might be used as a potential therapeutic target for LPS-induced sepsis.
Incoming HIV Virion-Derived Gag Spacer Peptide 2 (p1) is a Target of Effective CD8+ T Cell Antiviral Responses

Persistence of HIV through integration into host DNA in CD4+ T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8+ T cells are triggered to kill infected CD4+ T cells through recognition of HLA class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with ‘beneficial’ HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtained proof of early presentation of a virion-derived HLA-A*02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag spacer peptide 2 (SP2). FH9-specific CD8+ T cell responses were detectable in individuals with primary HIV infection and eliminated HIV-infected CD4+ T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.
Uveitis in Tumor Patients Treated with Immunological Checkpoint- and Signal Transduction Pathway-Inhibitors

ABSTRACT Purpose New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient’s survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. Methods In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. Results Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. Conclusions Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient’s vision without cessation of the tumor treatment.
Biologics and small molecules in the management of psoriatic arthritis: Reproduction related issues in female and male patients

STRACT Background: Psoriatic arthritis (PsA) is the musculoskeletal manifestation of psoriatic disease, an inflammatory systemic disease with a high incidence in the reproductive years. Biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) as well as ‘small molecules’, are increasingly used to treat subtypes of PsA. Safety concerns exist in the field of fertility for PsA patients since the literature shows discordant results toward the influence of anti-psoriatic drugs. Areas covered: This comprehensive review critically reviews the available data on the safety of biologics and small molecules in PsA including pregnancy and lactation and men who want to father a child. TNF inhibitors (TNFi) are best studied in relation to reproduction. For other biologics and small molecules, no prospective, controlled studies are available. Expert opinion: No contraindications appear for TNFi in pregnancy, lactation, and paternal exposure. For biologics other than TNFi and small molecules, prospective controlled studies on outcomes after exposure in early and late pregnancy are urgently needed. Potential effects of all biologics on immune function, infection rates, and vaccine responses in prenatally exposed children need to be expanded. Until more data become available, small molecules should be avoided during pregnancy and breastfeeding. More reproduction-related data are expected from various national and international registries in the future
Assessing the Causal Relationships Between Insulin Resistance and Hyperuricemia and Gout Using Bidirectional Mendelian Randomization

Hyperuricemia is closely associated with insulin resistance syndrome (and its many cardiometabolic sequelae); however, whether they are causally related has long been debated. We undertook this study to investigate the potential causal nature and direction between insulin resistance and hyperuricemia, along with gout, by using bidirectional Mendelian randomization (MR) analyses.
Radiological changes in sagittal parameters after C1-C2 arthrodesis and their clinical correlation: is there a difference between traumatic and non-traumatic causes?

Abstract Background Compensatory changes in cervical sagittal alignment after C1-C2 arthrodesis have been reported in a few studies. No studies have explored the differences in these compensatory changes between traumatic and non-traumatic pathologies. Conflicting reports exist on the correlation between cervical sagittal parameters and neck pain or function. Methodology Medical records of 81 consecutive patients [Jan 2010–Dec 2018] who underwent Harms arthrodesis were retrospectively reviewed. 53 patients were included in the final analysis. Radiological parameters [C0-C1, C1-C2, C2-C7 angles and T1 slope] and clinical parameters [VAS (Visual analogue scale) and NDI (Neck disability index)] were compared between the two groups, Group A (traumatic) and Group B (non-traumatic). Results The 53 patients [Group A (n = 24,) and Group B (n = 29)] had a mean age of 49.98 ± 21.82 years (42 males, 11 females). Mean follow up duration was 48.9 months. Δ C1-C2 angle is significantly correlated with ΔC2-C7 angle (Group A, p = 0.004; Group B, p = 0.015) but not with ΔC0-C1 angle (Group A, p = 0.315; Group B, p = 0.938). Though significant improvement in the clinical parameters (VAS/NDI) has been noted in both groups, Group A showed a greater improvement in VAS scores [Group A, (p < 0.001); Group B, (p < 0.023)]. Conclusions The sub-axial sagittal profile was strongly correlated with the ΔC1-C2 angle in both groups. Group B showed greater changes in sagittal parameters after Harms fixation and Group A showed greater improvement in long-term functional outcomes. The final functional outcomes were not related to the initial or final radiological sagittal profile in both groups.
Seroprevalence of antibodies to SARS-CoV-2 and predictors of seropositivity among employees of a teaching hospital in New Delhi, India

Objectives Healthcare workers (HCWs) are at a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to the increased likelihood of clinical exposure during patient management. The study objective was to determine the seroprevalence of antibodies to SARS-CoV-2 and its predictors among hospital employees. Methods The cross-sectional study was conducted at a teaching hospital from August 2020 to September 2020 among 1,401 employees, including 1,217 HCWs, in New Delhi, India. The serum samples were examined for immunoglobulin G (IgG) antibodies to SARS-CoV-2 using the COVID Kavach-Anti-SARS-CoV-2 IgG Antibody Detection enzyme-linked immunosorbent assay kit. Data were collected electronically using the EpiCollect mobile platform. A p < 0.05 was considered to indicate statistical significance. Results A total of 169 participants (12.1%) had detectable IgG antibodies to SARS-CoV-2. The highest seropositivity rate was observed in the administrative staff (20.1%), while it was lowest among medical doctors (5.5%, p < 0.001). Male sex and ever having lived in a containment zone were independently associated with past infection with SARS-CoV-2. Conclusion The seroprevalence of SARS-CoV-2 infection in health workers may be lower than in the general population in New Delhi. However, nonpharmaceutical interventions were not associated with a reduction in the risk of acquisition of SARS-CoV-2.
Structural Vulnerability and Occupational Injury Among Latinx Child Farmworkers in North Carolina

Children as young as ten-years-old can legally work as hired farm labor in the United States. In North Carolina, many hired children are part of the Latinx farmworker community. Agriculture is a hazardous industry, and child workers experience high rates of injury, illness, and mortality. As part of a community-based participatory research study, we draw from thirty in-depth interviews with Latinx child farmworkers aged ten to seventeen to describe their experiences of personal and observed workplace injury and close calls. Nearly all child workers had experienced or observed some form of injury, with several reporting close calls that could have resulted in severe injury or fatality. Overall, children reported a reactive approach to injury prevention and normalized pain as part of the job. Highlighting Latinx child farmworkers’ structural “vulnerability, this analysis contextualizes understanding of workplace injury among this largely hidden population. We offer policy recommendations to protect and support these vulnerable workers.
SPOT-1D-Single: improving the single-sequence-based prediction of protein secondary structure, backbone angles, solvent accessibility and half-sphere exposures using a large training set and ensembled deep learning

MOTIVATION Knowing protein secondary and other one-dimensional structural properties are essential for accurate protein structure and function prediction. As a result, many methods have been developed for predicting these one-dimensional structural properties. However, most methods relied on evolutionary information that may not exist for many proteins due to a lack of sequence homologs. Moreover, it is computationally intensive for obtaining evolutionary information as the library of protein sequences continues to expand exponentially. Here we developed a new single-sequence method called SPOT-1D-Single based on a large training dataset of 39120 proteins deposited prior to 2016 and an ensemble of hybrid Long-Short-Term-Memory bidirectional neural network and convolutional neural network. RESULTS We showed that SPOT-1D-Single consistently improves over SPIDER3-Single and ProteinUnet for secondary structure, solvent accessibility, contact number, and backbone angles prediction for all seven independent test sets (TEST2018, SPOT-2016, SPOT-2016-HQ, SPOT-2018, SPOT-2018-HQ, CASP12, and CASP13 free-modeling targets). For example, the predicted three-state secondary structure's accuracy ranges from 72.12-74.28% by SPOT-1D-Single, compared to 69.1-72.6% by SPIDER3-Single and 70.6-73% by ProteinUnet. SPOT-1D-Single also predicts SS3 and SS8 with 6.24% and 6.98% better accuracy than SPOT-1D on SPOT-2018 proteins with no homologs (Neff=1), respectively. The new method's improvement over existing techniques is due to a larger training set combined with ensembled learning. AVAILABILITY Standalone-version of SPOT-1D-Single is available at https://github.com/jas-preet/SPOT-1D-Single. Direct prediction can also be made at https://sparks-lab.org/server/spot-1d-single. The datasets used in this research can also be downloaded from GitHub.
Forced into an ecological corner: Round-the-clock deep foraging on small prey by elephant seals

It is not easy to get fat: Seals’ extreme foraging suggests evolutionary trade-off of large body size in marine mammals. Small mesopelagic fishes dominate the world’s total fish biomass, yet their ecological importance as prey for large marine animals is poorly understood. To reveal the little-known ecosystem dynamics, we identified prey, measured feeding events, and quantified the daily energy balance of 48 deep-diving elephant seals throughout their oceanic migrations by leveraging innovative technologies: animal-borne smart accelerometers and video cameras. Seals only attained positive energy balance after feeding 1000 to 2000 times per day on small fishes, which required continuous deep diving (80 to 100% of each day). Interspecies allometry suggests that female elephant seals have exceptional diving abilities relative to their body size, enabling them to exploit a unique foraging niche on small but abundant mesopelagic fish. This unique foraging niche requires extreme round-the-clock deep diving, limiting the behavioral plasticity of elephant seals to a changing mesopelagic ecosystem.