Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine profile and cytoskeletal changes after herpes simplex virus type 1 infection in human trabecular meshwork cells

Uveitis caused by herpes simplex virus (HSV)‐1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV‐1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)‐1 expression upon HSV‐1 infection in TM cells (p < 0.05). HSV‐1 infection led to downregulation of fibrogenic molecules (fibronectin, α‐smooth muscle actin, connective tissue growth factor and TGF‐β1). Notably, HSV‐1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF‐β1 and inhibited by treatment with the Rho‐kinase inhibitor, Y‐27632. TM cells treated with MCP‐1 exhibited a dose‐dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV‐1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP‐1 and TM cell contractile activity upon HSV‐1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV‐1 anterior uveitis.
Full Code to Do-Not-Resuscitate: Culturally Adapted Palliative Care Consultations and Code Status Change Among Seriously Ill Hispanic Patients

Background: Palliative care and hospice services are disproportionately underutilized by ethnic minority patients. Addressing barriers to utilization of these services is critical to reducing disparities. The purpose of this study was to assess the impact of a culturally adapted palliative care consultation service for Hispanics on end-of-life decisions, specifically likelihood of changing from full code to do-not-resuscitate (DNR) status during index admission for serious illness. Methods: A cross-sectional study design was applied to data extracted from electronic health records (EHR) of patients seen by a Geriatric Palliative Care service during inpatient stays between 2018 and 2019. The majority of referrals came from critical care sites. Culturally adapted palliative care consultations using the SPIKES tool featured a Spanish-speaking team member leading discussions, involvement of multiple and key family members, and a chaplain who is a Catholic Priest. Results: The analytic sample included 351 patients who were, on average, 72 years old. 54.42% were female, 59.54% were Hispanic, and of Hispanic patients, 47.37% spoke primarily Spanish. Culturally adapted consults resulted in higher rates of conversion to DNR status in palliative cases of the target population. Both primary language and ethnicity were associated with likelihood of change from full code to DNR status, such that Spanish speakers and those of Hispanic ethnicity were more likely to switch to DNR than non-Hispanics and English-Speakers. Conclusion: This study illustrates how culturally adapted palliative care consultations can help reduce barriers and improve end-of-life decision-making, and can be applied with similar populations of seriously ill Hispanic patients.
A Positively Selected MAGEE2 LoF Allele Is Associated with Sexual Dimorphism in Human Brain Size and Shows Similar Phenotypes in Magee2 Null Mice

Abstract A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation, and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10−6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of gray matter in males (P = 0.00094), and smaller volumes of gray (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behavior or cognition, but it might have been the driving force underlying the positive selection in humans.
Simple and efficient heterologous expression of necrosis‐inducing effectors using the model plant Nicotiana benthamiana

Abstract Plant fungal pathogens cause devastating diseases on cereal plants and threaten global food security. During infection, these pathogens secrete proteinaceous effectors that promote disease. Some of these effectors from necrotrophic plant pathogens induce a cell death response (necrosis), which facilitates pathogen growth in planta. Characterization of these effectors typically requires heterologous expression, and microbial expression systems such as bacteria and yeast are the predominantly used. However, microbial expression systems often require optimization for any given effector and are, in general, not suitable for effectors involving cysteine bridges and posttranslational modifications for activity. Here, we describe a simple and efficient method for expressing such effectors in the model plant Nicotiana benthamiana. Briefly, an effector protein is transiently expressed and secreted into the apoplast of N. benthamiana by Agrobacterium‐mediated infiltration. Two to three days subsequent to agroinfiltration, the apoplast from the infiltrated leaves is extracted and can be directly used for phenotyping on host plants. The efficacy of this approach was demonstrated by expressing the ToxA, Tox3, and Tox1 necrosis‐inducing effectors from Parastagonospora nodorum. All three effectors produced in N. benthamiana were capable of inducing necrosis in wheat lines, and two of three showed visible bands on Coomassie‐stained gel. These data suggest that N. benthamiana–agroinfiltration system is a feasible tool to obtain fungal effectors, especially those that require disulfide bonds and posttranslational modifications. Furthermore, due to the low number of proteins typically observed in the apoplast (compared with intracellular), this simple and high‐throughput approach circumvents the requirement to lyse cells and further purifies the target proteins that are required in other heterologous systems. Because of its simplicity and potential for high‐throughput, this method is highly amenable to the phenotyping of candidate protein effectors on host plants.
Fire Detection using Transformer Network

Technological breakthroughs in computing have empowered vision-based surveillance systems to detect fire using transformers framework. Over the last few decades, convolutional neural networks (CNNs) have been broadly applied for many computer vision-related problems and provided satisfactory results. However, due to the inductive prejudices embedded in convolutional operations, it cannot comprehend long-range dependencies. Vision transformers (ViT) has recently become an alternative to CNN for a vision problem by factoring an image as a patches sequence and leverage intra-attention between pixels. This paper shows that ViT is a viable tool for automated fire detection by aggregating features from the whole spatial context. The proposed method is tested on benchmark fire datasets to reveal the framework's strength and effectiveness.
Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

PURPOSE Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL. METHODS Patients age ≥ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years. RESULTS Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease–negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4%-84.4%) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up. CONCLUSION AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL. Low toxicity & high durability CD19CAR T without allo-SCT offers new possibility for refractory adult B-ALL
Comparing Coupled and Decoupled Steering Interface Designs for Emergency Obstacle Evasion

Automatic evasive steering maneuvers can outperform human-initiated steering maneuvers in emergency situations. A steering interface that decouples the steering wheel from the tires may enhance the efficiency of automatic steering maneuvers by providing full authority to the automation system. Yet, an alternative interface in which the steering wheel remains coupled to the tires has the advantages of enabling the driver to intervene in the event of an automation failure and preventing the human factors issues associated with decoupling the driver. In this paper, we present a driving simulator study with 64 participants where we compared four steering interface design schemes in their ability to enable successful obstacle evasion in emergency scenarios. The steering wheel was either decoupled from the tires and the automation was given full authority, or the steering wheel was coupled to the tires and the automation was provided high, low or no authority. The automation was designed to avoid all obstacles, except for the last one when it failed unexpectedly. Results uncovered a design tradeoff: as the authority of an agent (driver or automation) increases, the protection against the agent’s faults (provided by the other agent) reduces. The results also show that decoupled driving reduced driver’s vigilance and mode awareness and deprived the drivers of the authority required to intervene during automation faults. Coupled driving alleviated these issues but caused driver discomfort when designed with high automation authority and resulted in a larger number of collisions during perfect automation operation when designed with low automation authority.
Cognitive Function and Sleep in Caregivers of Persons Living with Dementia

Poor sleep is prevalent among caregivers of persons living with dementia and increases their risk for cognitive impairment and decline. In this cross-sectional, correlational study, we compared the cognitive function scores of caregivers with poor sleep with the demographically adjusted normed scores of the National Institutes of Health Toolbox Cognition Battery. Caregivers completed a 14-day sleep diary. On average, caregivers (n = 28) were 65.14 (±10.08) years, female, and White. Their average crystallized cognitive function composite score was significantly higher and their average fluid cognitive function composite score was significantly lower than the normative scores. Caregivers performed significantly worse on the processing speed domain measure. Poor sleep may affect how caregivers, including highly educated caregivers, process and respond to information, thus can influence how they safely perform complex caregiving tasks. Health care providers should consistently assess caregivers’ sleep and cognitive abilities to promptly identify changes and provide timely interventions.
Experience of patients with COVID‐19 in hospital isolation in Taiwan

Abstract The COVID‐19 pandemic has significantly impacted everyone's lives, challenging us in ways that can be frustrating, daunting, and intensely emotive. This qualitative study explored the isolation experiences of patients with COVID‐19 in a hospital in northern Taiwan. We collected data from nine patients in June–July 2020, conducting semi‐structured, virtual face‐to‐face, in‐depth interviews to gather input on two topics: (1) the psychological effect of hospital isolation on patients, including the psychological burden, stress response, support, disease stigma, and fear of returning to society; and (2) the patients' cognition and behaviors, which included tracking epidemic information, monitoring disease progression, soliciting suggestions about hospital isolation, and gauging comprehension after recovery. The results confirmed that hospital isolation significantly impacts patients physically, psychologically, spiritually, and socially. Thus, the isolated patients faced the dual challenges of fighting, adapting to, and recovering from the disease itself and struggling in isolation to maintain positive beliefs, independently assess their condition, and gain strength from the knowledge of continuing social support.
Predicting Chronic Wound Healing Time Using Machine Learning

Objective: Chronic wounds have risen to epidemic proportions in the United States and can have an emotional, physical, and financial toll on patients. By leveraging data within the electronic health record (EHR), machine learning models offer the opportunity to facilitate earlier identification of wounds at risk of not healing or healing after an abnormally long time, which may improve treatment decisions and patient outcomes. Machine learning models in this study were built to predict chronic wound healing time. Approach: Machine learning models were developed using EHR data to predict patients at risk of having wounds not heal within 4, 8, and 12 weeks from the start of treatment. The models were trained on three data sets of 1,220,576 wounds, including 187 covariates describing patient demographics, comorbidities, and wound characteristics. The area under the receiver operating characteristic curve (AUC) was used to assess the accuracy of the models. Shapley Additive Explanations (SHAP) were used to analyze variable importance in predictions and enhance clinical interpretations. Results: The 4-, 8-, and 12-week gradient-boosted decision tree models achieved AUC's of 0.854, 0.855, and 0.853, respectively. Days in treatment, wound depth and location, and wound area were the most influential predictors of wounds at risk of not healing. Innovation: Machine learning models can accurately predict chronic wound healing time using EHR data. SHAP values can give insight into how patient-specific variables influenced predictions. Conclusion: Accurate models identifying patients with chronic wounds at risk of non or slow healing are feasible and can be incorporated into routine wound care.
Effect of Esophageal Pressure-Guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-Based and Mechanistic Reanalysis of the EPVent-2 Trial.

RATIONALE In acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension. OBJECTIVE To evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect in EPVent-2, a multicenter trial of esophageal pressure (PES)-guided PEEP versus empirical high PEEP in moderate-to-severe ARDS. METHODS This post-hoc reanalysis of EPVent-2 evaluated for heterogeneity of treatment effect on mortality by baseline multiorgan dysfunction, determined via Acute Physiology and Chronic Health Evaluation-II (APACHE-II). It also evaluated whether PEEP titrated to end-expiratory transpulmonary pressure near 0 cmH2O was associated with survival. MEASUREMENTS AND MAIN RESULTS All 200 trial participants were included. Treatment effect on 60-day mortality differed by multiorgan dysfunction severity (p=0.03 for interaction). PES-guided PEEP was associated with lower mortality among patients with lower APACHE-II (HR 0.43, 95% CI 0.20-0.92 for APACHE-II less than median) and may have had the opposite effect in patients with higher APACHE-II (HR 1.69; 95% CI 0.93-3.05). Independent of treatment group or multiorgan dysfunction severity, mortality was lowest when PEEP titration achieved end-expiratory transpulmonary pressure near 0 cmH2O. CONCLUSIONS The effect on survival of PES-guided PEEP, compared to empirical high PEEP, differed by multiorgan dysfunction severity. Independent of multiorgan dysfunction, PEEP titrated to end-expiratory transpulmonary pressure closer to 0 cmH2O was associated with greater survival than more positive or negative values. These findings warrant prospective testing in a future trial.
Assessing Patient Needs During Natural Disasters: Mixed Methods Analysis of Portal Messages Sent During Hurricane Harvey

Background Patient portals play an important role in connecting patients with their medical care team, which improves patient engagement in treatment plans, decreases unnecessary visits, and reduces costs. During natural disasters, patients’ needs increase, whereas available resources, specifically access to care, become limited. Objective This study aims to examine patients’ health needs during a natural crisis by analyzing the electronic messages sent during Hurricane Harvey to guide future disaster planning efforts. Methods We explored patient portal use data from a large Greater Houston area health care system focusing on the initial week of the Hurricane Harvey disaster, beginning with the date of landfall, August 25, 2017, to August 31, 2017. A mixed methods approach was used to assess patients’ immediate health needs and concerns during the disruption of access to routine and emergent medical care. Quantitative analysis used logistic regression models to assess the predictive characteristics of patients using the portal during Hurricane Harvey. This study also included encounters by type (emergency, inpatient, observation, outpatient, and outpatient surgery) and time (before, during, and after Hurricane Harvey). For qualitative analysis, the content of these messages was examined using the constant comparative method to identify emerging themes found within the message texts. Results Out of a total of 557,024 patients, 4079 (0.73%) sent a message during Hurricane Harvey, whereas 31,737 (5.69%) used the portal. Age, sex, race, and ethnicity were predictive factors for using the portal and sending a message during the natural disaster. We found that prior use of the patient portal increased the likelihood of portal use during Hurricane Harvey (odds ratio 13.688, 95% CI 12.929-14.491) and of sending a portal message during the disaster (odds ratio 14.172, 95% CI 11.879-16.907). Having an encounter 4 weeks before or after Hurricane Harvey was positively associated with increased use of the portal and sending a portal message. Patients with encounters during the main Hurricane Harvey week had a higher increased likelihood of portal use across all five encounter types. Qualitative themes included: access, prescription requests, medical advice (chronic conditions, acute care, urgent needs, and Hurricane Harvey–related injuries), mental health, technical difficulties, and provider constraints. Conclusions The patient portal can be a useful tool for communication between patients and providers to address the urgent needs and concerns of patients as a natural disaster unfolds. This was the first known study to include encounter data to understand portal use compared with care provisioning. Prior use was predictive of both portal use and message sending during Hurricane Harvey. These findings could inform the types of demands that may arise in future disaster situations and can serve as the first step in intentionally optimizing patient portal usability for emergency health care management during natural disasters.
Clinical characteristics differ between patients with non-traumatic neck pain, patients with whiplash-associated disorders, and pain-free individuals

ABSTRACT Background Evidence is lacking to what extent patients with Whiplash-Associated Disorders (WAD), those with non-traumatic neck pain (NTNP), and pain-free individuals differ regarding type and severity of impairments, disability, and psychological factors. Objective To compare clinical characteristics between patients with WAD, with NTNP, and pain-free individuals in primary care physiotherapy. Additionally, differences between patient groups for both acute and chronic symptoms were assessed. Method A cross-sectional study was conducted including 168 patients with WAD, 336 matched patients with NTNP, and 336 pain-free individuals. Differences and prevalence rates were calculated for pain intensity, pain distribution, cervical range of motion, neck flexor muscle endurance, self-reported disability, and psychological factors. Results Patients with WAD had higher pain intensity (median 6/10 vs. 5/10 p<.01), had a wider distribution of their neck pain (p=.02), more restricted cervical flexion-extension (-11.9°) and rotation (-12.4°), less muscle endurance (-5.5 seconds), and more disability (+14.0%), compared to patients with NTNP. More patients with WAD reported low back pain (+9.5%) and headache (+12.2%) as musculoskeletal comorbidities. Regarding anxiety, depression, and stress, most patients (>83%) scored in the normal range. No significant differences between the patient groups were observed (p>.16). Both patient groups scored significantly worse than pain-free individuals on all characteristics. Patients with WAD and NTNP experienced different types of activity limitations and participation restrictions. Conclusion WAD is a more severe condition than NTNP and should be considered a separate subgroup. A different approach in clinical practice and research is required for WAD and NTNP.