Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of femoral head coverage from articulated statistical shape models of patients with developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is commonly described as reduced femoral head coverage due to anterolateral acetabular deficiency. Although reduced coverage is the defining trait of DDH, more subtle and localized anatomic features of the joint are also thought to contribute to symptom development and degeneration. These features are challenging to identify using conventional approaches. Herein, we assessed the morphology of the full femur and hemi‐pelvis using an articulated statistical shape model (SSM). The model determined the morphological and pose‐based variations associated with DDH in a population of Japanese females and established which of these variations predict coverage. Computed tomography (CT) images of 83 hips from 47 patients were segmented for input into a correspondence‐based SSM. The dominant modes of variation in the model initially represented scale and pose. After removal of these factors through individual bone alignment, femoral version and neck‐shaft angle, pelvic curvature, and acetabular version dominated the observed variation. Femoral head oblateness and prominence of the acetabular rim and various muscle attachment sites of the femur and hemi‐pelvis were found to predict 3D CT‐based coverage measurements (R2 = 0.5–0.7 for the full bones, R2 = 0.9 for the joint). Statement of Clinical Significance: Currently, clinical measurements of DDH only consider the morphology of the acetabulum. However, the results of this study demonstrated that variability in femoral head shape and several muscle attachment sites were predictive of femoral head coverage. These morphological differences may provide insight into improved clinical diagnosis and surgical planning based on functional adaptations of patients with DDH.
Identification of ClpP Dual Isoform Disruption as an Antisporulation Strategy for Clostridioides difficile

Due to diverse roles of ClpP and the reliance of pathogens upon this system for infection, it has emerged as a target for antimicrobial development. Biology regulated by ClpP is organism dependent and has not been defined in Clostridioides difficile. ABSTRACT The Gram-positive bacterium Clostridioides difficile is a primary cause of hospital-acquired diarrhea, threatening both immunocompromised and healthy individuals. An important aspect of defining mechanisms that drive C. difficile persistence and virulence relies on developing a more complete understanding of sporulation. C. difficile sporulation is the single determinant of transmission and complicates treatment and prevention due to the chemical and physical resilience of spores. By extension, the identification of druggable targets that significantly attenuate sporulation would have a significant impact on thwarting C. difficile infection. By use of a new CRISPR-Cas9 nickase genome editing methodology, stop codons were inserted early in the coding sequence for clpP1 and clpP2 to generate C. difficile mutants that no longer produced the corresponding isoforms of caseinolytic protease P (ClpP). The data show that genetic ablation of ClpP isoforms leads to altered sporulation phenotypes with the clpP1/clpP2 double mutant exhibiting asporogenic behavior. A small screen of known ClpP inhibitors in a fluorescence-based biochemical assay identified bortezomib as an inhibitor of C. difficile ClpP that produces dose-dependent inhibition of purified ClpP. Incubation of C. difficile cultures in the presence of bortezomib reveals antisporulation effects approaching that observed in the clpP1/clpP2 double mutant. This work identifies ClpP as a key contributor to C. difficile sporulation and provides compelling support for the pursuit of small-molecule ClpP inhibitors as C. difficile antisporulating agents. IMPORTANCE Due to diverse roles of ClpP and the reliance of pathogens upon this system for infection, it has emerged as a target for antimicrobial development. Biology regulated by ClpP is organism dependent and has not been defined in Clostridioides difficile. This work identifies ClpP as a key contributor to C. difficile sporulation and provides compelling support for the pursuit of small-molecule ClpP inhibitors as antisporulating agents. The identification of new approaches and/or drug targets that reduce C. difficile sporulation would be transformative and are expected to find high utility in prophylaxis, transmission attenuation, and relapse prevention. Discovery of the ClpP system as a major driver to sporulation also provides a new avenue of inquiry for advancing the understanding of sporulation.
COVID‐19: Using high‐throughput flow cytometry to dissect clinical heterogeneity

Here we consider how high‐content flow cytometric methodology at appropriate scale and throughput rapidly provided meaningful biological data in our recent studies of COVID‐19, which we discuss in the context of other similar investigations. In our work, high‐throughput flow cytometry was instrumental to identify a consensus immune signature in COVID‐19 patients, and to investigate the impact of SARS‐CoV‐2 exposure on patients with either solid or hematological cancers. We provide here some examples of our ‘holistic’ approach, in which flow cytometry data generated by lymphocyte and myelomonocyte panels were integrated with other analytical metrics, including SARS‐CoV‐2‐specific serum antibody titers, plasma cytokine/chemokine levels, and in‐depth clinical annotation. We report how selective differences between T cell subsets were revealed by a newly described flow cytometric TDS assay to distinguish actively cycling T cells in the peripheral blood. By such approaches, our and others' high‐content flow cytometry studies collectively identified overt abnormalities and subtle but critical changes that discriminate the immuno‐signature of COVID‐19 patients from those of healthy donors and patients with non‐COVID respiratory infections. Thereby, these studies offered several meaningful biomarkers of COVID‐19 severity that have the potential to improve the management of patients and of hospital resources. In sum, flow cytometry provides an important means for rapidly obtaining data that can guide clinical decision‐making without requiring highly expensive, sophisticated equipment, and/or “‐omics” capabilities. We consider how this approach might be further developed.
Magneto-electric monopole antenna for terminal multiband applications

Presented is a multiband terminal antenna providing two wide bands for covering seven-band LTE/GSM/UMTS operation. This new antenna comprises an electric monopole with parasitic shorted strip and two back-to-back slot monopoles, which can be seen as magnetic monopoles. The two slot monopoles are excited by the coupling of two microstrip stubs on the back side, and the electric monopole is connected to the microstrip feeding line directly. A prototype has been constructed and tested. Simulated and measured results are given.
Oligodendrocyte progenitor proliferation is disinhibited following traumatic brain injury in leukemia inhibitory factor heterozygous mice

Traumatic brain injury (TBI) is a significant problem that affects over 800,000 children each year. As cell proliferation is disturbed by injury and required for normal brain development, we investigated how a pediatric closed head injury (CHI) would affect the progenitors of the subventricular zone (SVZ). Additionally, we evaluated the contribution of leukemia inhibitory factor (LIF) using germline LIF heterozygous mice (LIF Het), as LIF is an injury‐induced cytokine, known to influence neurogenesis and gliogenesis. CHIs were performed on P20 LIF Het and wild‐type (WT) mice. Ki‐67 immunostaining and stereology revealed that cell proliferation increased ~250% in injured LIF Het mice compared to the 30% increase observed in injured WT mice at 48‐hr post‐CHI. OLIG2+ cell proliferation increased in the SVZ and white matter of LIF Het injured mice at 48‐hr recovery. Using an 8‐color flow cytometry panel, the proliferation of three distinct multipotential progenitors and early oligodendrocyte progenitor cell proliferation was significantly increased in LIF Het injured mice compared to WT injured mice. Supporting its cytostatic function, LIF decreased neurosphere progenitor and oligodendrocyte progenitor cell proliferation compared to controls. In highly enriched mouse oligodendrocyte progenitor cell cultures, LIF increased phospho‐protein kinase B after 20 min and increased phospho‐S6 ribosomal protein at 20 and 40 min of exposure, which are downstream targets of the mammalian target of rapamycin pathway. Altogether, our data provide new insights into the regulatory role of LIF in suppressing neural progenitor cell proliferation and, in particular, oligodendrocyte progenitor cell proliferation after a mild TBI.
Comparison of confirmed and probable COVID-19 patients in the intensive care unit during the normalization period

The decrease in social distance together with the normalization period as of June 1, 2020, in our country caused an increase in the number of coronavirus disease 2019 (COVID-19) patients. Our aim was to compare the demographic features, clinical courses, and outcomes of confirmed and probable COVID-19 patients admitted to our intensive care unit (ICU) during the normalization period. Critically ill 128 COVID-19 patients between June 1, 2020, and December 2, 2020, were analyzed retrospectively. The mean age was 69.7 ± 15.5 y (61.7% male). Sixty-one patients (47.7%) were confirmed. Dyspnea (75.0%) was the most common symptom and hypertension (71.1%) was the most common comorbidity. The mean Acute Physiology and Chronic Health Evaluation System (APACHE II) score; Glasgow Coma Score; Sequential Organ Failure Assessment scores on ICU admission were 17.4 ± 8.2, 12.3 ± 3.9, and 5.9 ± 3.4, respectively. One hundred and one patients (78.1%) received low-flow oxygen, 48 had high-flow oxygen therapy (37.5%), and 59 (46.1%) had invasive mechanical ventilation. Fifty-three patients (41.4%) had vasopressor therapy and 30 (23.4%) patients had renal replacement therapy due to acute kidney injury (AKI). Confirmed patients were more tachypneic (p = 0.005) and more hypoxemic than probable patients (p < 0.001). Acute respiratory distress syndrome and AKI were more common in confirmed patients than probable (both p < 0.001). Confirmed patients had higher values of hemoglobin, C- reactive protein, fibrinogen, and D-dimer than probables (respectively, p = 0.028, 0.006, 0.000, and 0.019). The overall mortality was higher in confirmed patients (p = 0.209, 52.6% vs. 47.4%). Complications are more common among confirmed COVID-19 patients admitted to ICU. The mortality rate of confirmed COVID-19 patients admitted to the ICU was found to be higher than probable patients. Mortality of confirmed cases was higher than prediction of APACHE-II scoring system.
Mental health and initiation of antiretroviral treatment at enrolment into HIV care in Cameroon under a national “treat all” policy: a cross‐sectional analysis

Rapid antiretroviral treatment (ART) initiation reduces time from HIV infection to viral suppression, decreasing HIV transmission risk. Mental health symptoms may influence timing of ART initiation. This study estimated the prevalence of ART initiation at enrolment into HIV care and the relationship between mental health and ART initiation at enrolment into HIV care.
Enhancing Predicted Shear Strength for the Assessment of Existing Concrete Bridges

Abstract This paper presents a method of calculating the enhanced shear capacity of concrete T-beams that arises from the increased concrete contribution provided by the flange overhangs of reinforced concrete (RC) T-beams in positive bending or sagging. The method applies recognised provisions in the Australian Concrete Bridge Design Code AS5100–5:2004 to enhance the prediction of shear strength of concrete T-beams based on failure mechanisms reported in published experimental work. The method is applied to specimens reported in previous experimental studies that report shear failure in RC T-beams in positive bending or sagging. It is shown to yield conservative estimates of shear strength enhancement that arise in a T-beam giving consideration to the flange overhangs. A discussion is provided to outline the application of this method for calculating shear strength of concrete highway bridge decks where T-shaped cross-sections resist an applied shear. The paper discusses the variability that arises in the prediction of shear strength from applying the method. The variability observed in the application is consistent with that observed in shear strength tests used as a basis for code-based formulations. All international codes use a lower value of strength reduction for shear than pure flexure to cater for this. It is recommended that confidence in the method be increased by applying the method to more testing targeted at isolating the flange proportions on the shear strength of RC T-beams in sagging.
An integrated framework utilising software agent reasoning and ontology models for sensor based building monitoring

Smart building monitoring demands a new software infrastructure that can elaborate building domain knowledge in order to provide advanced and intelligent functionalities. Conventional facility management (FM) software tools lack semantically rich components, and that limits the capability of supporting software for automatic information sharing, resource negotiation and to assist in timely decision making. Recent hardware innovation on compact ZigBee sensor devices, software developments on ontology and intelligent software agent paradigms provide a good opportunity to develop tools that can further improve current FM practices. This paper introduces an integrated framework which includes a ZigBee based sensor network and underlying multi-agent software (MAS) components. Several different types of sensors were integrated with the ZigBee host devices to produce compact multi-functional sensor units. The MAS framework incorporates the belief-desire-intention (BDI) abstraction with ontology support (provided via explicit knowledge bases). The different software agent types have been developed to work with sensor hardware to conduct resource negotiation, to optimize battery utilization, to monitor building space in a non-intrusive way and to reason about its usage through real time ontology model queries. The deployed sensor network shows promising intelligent characteristics, and it has been applied in several on-going research projects as an underlying decision making service. More applications and larger deployments have been planned for future work.
Using Natural Language Processing to Extract Drug-Drug Interaction Information from Package Inserts

The package insert (aka drug product label) is the only publicly-available source of information on drug-drug interactions (DDIs) for some drugs, especially newer ones. Thus, an automated method for identifying DDIs in drug package inserts would be a potentially important complement to methods for identifying DDIs from other sources such as the scientific literature. To develop such an algorithm, we created a corpus of Federal Drug Administration approved drug package insert statements that have been manually annotated for pharmacokinetic DDIs by a pharmacist and a drug information expert. We then evaluated three different machine learning algorithms for their ability to 1) identify pharmacokinetic DDIs in the package insert corpus and 2) classify pharmacokinetic DDI statements by their modality (i.e., whether they report a DDI or no interaction between drug pairs). Experiments found that a support vector machine algorithm performed best on both tasks with an F-measure of 0.859 for pharmacokinetic DDI identification and 0.949 for modality assignment. We also found that the use of syntactic information is very helpful for addressing the problem of sentences containing both interacting and non-interacting pairs of drugs.
PQN-59 antagonizes microRNA-mediated repression during post-embryonic temporal patterning and modulates translation and stress granule formation in C. elegans

microRNAs (miRNAs) are potent regulators of gene expression that function in a variety of developmental and physiological processes by dampening the expression of their target genes at a post-transcriptional level. In many gene regulatory networks (GRNs), miRNAs function in a switch-like manner whereby their expression and activity elicit a transition from one stable pattern of gene expression to a distinct, equally stable pattern required to define a nascent cell fate. While the importance of miRNAs that function in this capacity are clear, we have less of an understanding of the cellular factors and mechanisms that ensure the robustness of this form of regulatory bistability. In a screen to identify suppressors of temporal patterning phenotypes that result from ineffective miRNA-mediated target repression, we identified pqn-59, an ortholog of human UBAP2L, as a novel factor that antagonizes the activities of multiple heterochronic miRNAs. Specifically, we find that depletion of pqn-59 can restore normal development in animals with reduced lin-4 and let-7-family miRNA activity. Importantly, inactivation of pqn-59 is not sufficient to bypass the requirement of these regulatory RNAs within the heterochronic GRN. The pqn-59 gene encodes an abundant, cytoplasmically-localized, unstructured protein that harbors three essential “prion-like” domains. These domains exhibit LLPS properties in vitro and normally function to limit PQN-59 diffusion in the cytoplasm in vivo. Like human UBAP2L, PQN-59’s localization becomes highly dynamic during stress conditions where it re-distributes to cytoplasmic stress granules and is important for their formation. Proteomic analysis of PQN-59 complexes from embryonic extracts indicates that PQN-59 and human UBAP2L interact with orthologous cellular components involved in RNA metabolism and promoting protein translation and that PQN-59 additionally interacts with proteins involved in transcription and intracellular transport. Finally, we demonstrate that pqn-59 depletion reduces protein translation and also results in the stabilization of several mature miRNAs (including those involved in temporal patterning). These data suggest that PQN-59 may ensure the bistability of some GRNs that require miRNA functions by promoting miRNA turnover and, like UBAP2L, enhancing protein translation.
An Analytical Study on the Seismic Vulnerability of Masonry Buildings in India

Two analytical models for unreinforced masonry (URM) buildings are proposed with the aim to simulate their seismic response and to estimate corresponding vulnerability functions. The proposed models are implemented in SAP 2000 nonlinear software to obtain capacity curve parameters for representative Indian URM buildings, based on a field survey and statistical analysis. Vulnerability functions are estimated using the obtained capacity curves. Damage Probability Matrices (DPMs) are obtained using the approximate PGA-intensity correlation relationship as per Indian seismic building code and are compared with the commonly used intensity scales and empirical damage data observed after the 2001 Bhuj earthquake.
Induction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging

Somatopause refers to the gradual declines in growth hormone (GH) and insulin‐like growth factor‐1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning of the cortices, which compromised bone strength. We report progressive declines in osteocyte lacunar number, and increases in lacunar volume, in iGHRKO males, and reductions in lacunar number accompanied by ~20% loss of overall canalicular connectivity in iGHRKO females by 30 months of age. Induced somatopause did not affect mineral/matrix ratio assessed by Raman microspectroscopy. We found significant increases in bone marrow adiposity and high levels of sclerostin, a negative regulator of bone formation in iGHRKO mice. Surprisingly, however, despite compromised bone morphology, osteocyte senescence was reduced in the iGHRKO mice. In this study, we avoided the confounded effects of constitutive deficiency in the GH/IGF‐1 axis on the skeleton during growth, and specifically dissected its effects on the aging skeleton. We show here, for the first time, that induced somatopause compromises bone morphology and the bone marrow environment.
Protection of Coastal Infrastructure under Rising Flood Risk

Thanks are due to Professor Kerry Emanuel for his guidance in the application of his hurricane analysis. Any errors in its application are attributable to the authors. The authors gratefully acknowledge the ﬁnancial support for this work provided by the MIT Joint Program on the Science and Policy of Global Change through a consortium of industrial sponsors and Federal grants with special support from the U.S. Department of Energy (DE-FE02-94ER61937). N. L. was supported by the NOAA Climate and Global Change Postdoctoral Fellowship Program, administered by the University Corporation for Atmospheric Research.
Temporal Patterns of Spontaneous Fixational Eye Movements: The Influence of Basal Ganglia

Background: Spontaneity is a unique feature of the nervous system. One of the fundamentally critical and recognized forms of spontaneous motor activity is witnessed in the visuomotor system. Microsaccades, the miniature spontaneous eye movements, are critical for the visual perception. We hypothesized that microsaccades follow specific temporal patterns that are modulated by the basal ganglia output. Methods: We used high-resolution video-oculography to capture microsaccades in 48 subjects (31 healthy and 17 with Parkinson's disease) when subjects were asked to hold their gaze on a straight-ahead target projected on white background. We analyzed spontaneous discharge patterns of microsaccades. Results: The first analysis considering coefficient of variation in intersaccadic interval distribution demonstrated that microsaccades in Parkinson's disease are more dispersed than the control group. The second analysis scrutinized microsaccades' temporal variability and revealed 3 distinct occurrence patterns: regular rhythmic, clustered, and randomly occurring following a Poisson-like process. The regular pattern was relatively more common in Parkinson's disease. Subthalamic DBS modulated this temporal pattern. The amount of change in the temporal variability depended on the DBS-induced volume of tissue activation and its overlap with the subthalamic nucleus. The third analysis determined the autocorrelations of microsaccades within 2-second time windows. We found that Parkinson's disease altered local temporal organization in microsaccade generation, and DBS had a modulatory effect. Conclusion: The microsaccades occur in 3 temporal patterns. The basal ganglia are one of the modulators of the microsaccade spontaneity.