bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico studies of bacterial quorum sensing during population dynamics: simulations by using COMSOL Multiphysics
Authors: Maslovskaya A G , Kuttler Ch , Shuai Y
Published: June 2023

In the present study, computing techniques are designated and employed in order to analyze “quorum sensing” as a special case of cell-to-cell bacterial communication attributed to the Pseudomonas bacterial genus. One of the challenges consists in predicting the concentration of key substances characterizing the “quorum level” during bacterial population dynamics. To estimate relevant characteristics of bacterial communication, we applied a deterministic approach. The mathematical model is formalized as an initial-boundary value problem for a system of semilinear partial differential equations supplemented by the procedure to specify the multiphase dynamics of bacterial populations. The finite element solution of the problem is obtained by COMSOL Multiphysics. The comparative numerical analysis for various types of space approximation of bacterial density is performed. A series of computational experiments were conducted to estimate changes in concentrations of chemical compounds during the Pseudomonas putida population dynamics.
Semantic approach for solving the decision problem in natural language
Authors: Strübbe S , Sidorenko I , Grünwald A , Lampe R
Published: June 2023

Every language, whether formal or natural, has a corresponding decision problem, the problem of whether a statement is well-formed and a valid sentence of the language. While compilers usually solve the decision problem for a computer language during compilation, there is no mathematical method to solve the decision problem in natural language. Although a human can use natural language grammar to reason whether a sentence is correct, computers have problems with this because natural language grammar is not a closed theory. We show that the decision problem for the German language can not be solved entirely by phrase structure grammar, dependency parsing or grammar checkers and develop a parser for the German language, which solves the decision problem for that language using a new semantic approach.
Sensitivity analysis of the energy balance of dynamic soaring
Authors: Zwenig A , Hong H , Holzapfel F
Published: June 2023

Dynamic soaring is a periodic flying technique observed in large seabirds that enables the extraction of energy from wind and thereby facilitates covering large distances with minimum effort. It requires wind shears as seen close to the ocean surface or behind mountain ridges. At sufficiently strong winds it becomes feasible to extract at least the amount of energy required for overcoming the aircraft’s dissipation. This situation is often referred to as energy-neutral dynamic soaring and would theoretically enable an abiding effortless flight. An energy-neutral dynamic soaring cycle has already been formulated and solved as a parametric optimal control problem. Due to the inherent variability of the wind, the sensitivity of the energy balance of an open type dynamic soaring cycle to wind conditions will be investigated within this work. Of particular interest is the wind direction and the wind speed. To expose the parameters with the strongest influence for some given conditions, state sensitivities will be computed after the optimization by applying the sensitivity differential equation approach.
Development of low-cost digital gamma spectrometer using ARM Cortex-M Type Microcontroller Unit
Authors: Shaker Hesham H. , Kasban H. , Saleh A.A. , Dessouky M.
Published: June 2023

Recently, digital gamma spectrometers have replaced analog
ones due to their durability, flexibility, and compact size. The
main part of the digital gamma spectrometer is the digital pulse
processing (DPP) unit. The implementation of the DPP unit using the
ARM Cortex-M-based microcontroller units is a recent attractive
approach. This originates from their advanced features and low
cost. In this paper, we propose an implementation of the DPP unit
using the ARM Cortex-M3-based microcontroller unit. The targeted
detector with this implementation is the sodium iodide
detector. However, this implementation is based on less than 2 MS/s
sampling rate, it is guaranteed experimentally to cope with input
count rates up to 47 kC/s. This results from our specific proposed
methodology for extracting pulse height from the trapezoidal-shaped
pulses.
Design considerations and experimental investigations on fiber ball lens systems for optical metrology
Authors: Brueckner Hans Josef , Chai Lo Yat , Tiedeken Sabine , Braun Volker , Teubner Ulrich
Published: June 2023

Optical fibers play an important role in general and, in particular, in the field of sensors. As part of a sensor system, quite often fibers are coupled by a ball lens. For efficient usage, the fiber ball lens systems (FBLSs) have to be optimized. The present work presents analytic expressions for the design parameters of such systems. FBLSs comprise sections of a single-mode optical fiber, a coreless fiber (CLF) and a ball lens. Their geometric dimensions have to be optimized for their use in different applications in optical metrology. The derived expressions facilitate the optimum parameter choice, which is usually done by expensive numerical simulations. For comparison and validation of the results by experiments, FBLSs with different ball lens radii and CLF sections have been prepared by a fusion splicer technique. Their characteristics were investigated in the optical spectral ranges at 630 nm and 1550 nm. Experimental methods comprising far-field, near-field and reflection/transmission measurements with optical fibers validate the theoretical considerations. To our knowledge, this is the first time that simple analytic approaches have been applied to the fabrication of FBLSs. This facilitates and quickens their general design for different applications in optical metrology significantly.
Fixed points, local monodromy, and incompressibility of congruence covers
Authors: Brosnan Patrick , Fakhruddin Najmuddin
Published: June 2023

We prove a fixed point theorem for the action of certain local monodromy groups on étale covers and use it to deduce lower bounds on essential dimension. In particular, we give more geometric proofs of some of the results of a paper of Farb, Kisin and Wolfson, which uses arithmetic methods to prove incompressibility results for Shimura varieties and moduli spaces of curves. Our method allows us to prove new results for exceptional groups, applies also to the reduction modulo good primes of congruence covers of Shimura varieties and moduli spaces of curves, and also to certain “quantum” covers of moduli spaces of curves arising from a certain TQFT.
GJB2 p.V37I Mutation Associated With Moderate Nonsyndromic Hearing Loss in an Adult Taiwanese Population
Authors: Yen Ting-Ting , Chen I-Chieh , Cho Sudi , Chang Ting-Gang , Shih Kai-Hsiang , Hua Men-Wei , Li Jui-Lin , Hsu Chiann-Yi , Hsiao Tzu-Hung , Chen Yi-Ming
Published: June 2023

Background:

Gap junction protein beta 2 (GJB2) p.V37I mutations are the most important hereditary cause of sensorineural hearing loss (SNHL) in Taiwan. Hearing outcomes are associated with hearing levels at baseline and the duration of follow-up. However, the audiological features of GJB2 p.V37I mutations in the adult population are unknown. The objectives of the present study were to investigate the audiological features, progression rate, and allele frequency of GJB2 p.V37I mutations among an adult Taiwanese population.

Methods:

Subjects of this case–control study were chosen from 13,580 participants of the Taiwan Precision Medicine Initiative. The genetic variations of GJB2 p.V37I were determined by polymerase chain reaction. We analyzed existing pure-tone threshold data from 38 individuals who were homozygous or compound heterozygotes for GJB2 p.V37I, 129 who were heterozygotes, and 602 individuals who were wild-type. Phenome-wide association studies (PheWAS) analysis was also performed to identify phenotypes associated with GJB2 p.V37I.

Results:

The minor allele frequency of GJB2 p.V37I was 0.92% in our study population. The mean hearing level of participants with a p.V37I mutation indicated moderate to severe hearing loss with 38.2% ± 22.3% binaural hearing impairment. GJB2 p.V37I was associated with an increased risk of hearing disability (odds ratio: 21.46, 95% confidence interval: 8.62 to 53.44, p < 0.001) in an autosomal recessive pattern. In addition, PheWAS discovered a significant association between GJB2 p.V37I and fracture of the humerus. GJB2 p.V37I is a pathogenic and prevalent variant of SNHL among the adult population.

Conclusions:

The present study recommends patients with known GJB2 p.V37I mutations receive regular audiometric evaluation and genetic counseling. Early assistive listening device intervention is suggested to improve the quality of hearing.
Honoring Grief Journeys Following the Death of a Loved One
Authors: Hooten Phyllis Ann , Leschber Tiffany
Published: June 2023

Nurses, regardless of the healthcare setting, have numerous opportunities for interacting with those who are grieving. The purpose of this article is to help honor and support those who are on a grief journey following the death of a loved one. Caring for the grieving involves offering the ministry of presence, awareness of both established and individualized grief responses, planning interventions for loneliness and isolation, and navigating through special occasions. Praying and sharing Scripture and encouraging time alone in God's presence can be integral in helping the bereaved meet spiritual needs.
A Testimony of Christian Drug Rehabilitation
Authors: Yeh Pi-Ming
Published: June 2023

Drug addiction is at crisis level in the United States. Nurses caring for persons affected by substance use disorder (SUD) have a resource in Mr. Ming Ho Liu's testimony on Good TV (Taiwan)—translated and summarized in this article—of his addiction experiences and successful treatment at Operation Dawn, a Christian drug rehabilitation center. Recovery from SUD is possible by God's power. In Mr. Liu's case, his recovery was accomplished without medication.
Vasoprotective effects of NOX4 are mediated via polymerase and transient receptor potential melastatin 2 cation channels in endothelial cells
Authors: Alves-Lopes Rheure , Lacchini Silvia , Neves Karla B. , Harvey Adam , Montezano Augusto C. , Touyz Rhian M.
Published: June 2023

Background:

NOX4 activation has been implicated to have vasoprotective and blood pressure (BP)-lowering effects. Molecular mechanisms underlying this are unclear, but NOX4-induced regulation of the redox-sensitive Ca2+ channel TRPM2 and effects on endothelial nitric oxide synthase (eNOS)-nitric oxide signalling may be important.

Method:

Wild-type and LinA3, renin-expressing hypertensive mice, were crossed with NOX4 knockout mice. Vascular function was measured by myography. Generation of superoxide (O2
-) and hydrogen peroxide (H2O2) were assessed by lucigenin and amplex red, respectively, and Ca2+ influx by Cal-520 fluorescence in rat aortic endothelial cells (RAEC).

Results:

BP was increased in NOX4KO, LinA3 and LinA3/NOX4KO mice. This was associated with endothelial dysfunction and vascular remodelling, with exaggerated effects in NOX4KO groups. The TRPM2 activator, ADPR, improved vascular relaxation in LinA3/NOX4KO mice, an effect recapitulated by H2O2. Inhibition of PARP and TRPM2 with olaparib and 2-APB, respectively, recapitulated endothelial dysfunction in NOX4KO. In endothelial cells, Ang II increased H2O2 generation and Ca2+ influx, effects reduced by TRPM2 siRNA, TRPM2 inhibitors (8-br-cADPR, 2-APB), olaparib and GKT137831 (NOX4 inhibitor). Ang II-induced eNOS activation was blocked by NOX4 and TRPM2 siRNA, GKT137831, PEG-catalase and 8-br-cADPR.

Conclusion:

Our findings indicate that NOX4-induced H2O2 production activates PARP/TRPM2, Ca2+ influx, eNOS activation and nitric oxide release in endothelial cells. NOX4 deficiency impairs Ca2+ homeostasis leading to endothelial dysfunction, an effect exacerbated in hypertension. We define a novel pathway linking endothelial NOX4/H2O2 to eNOS/nitric oxide through PARP/TRPM2/Ca2+. This vasoprotective pathway is perturbed when NOX4 is downregulated and may have significance in conditions associated with endothelial dysfunction, including hypertension.
Nursing Implications for Tianeptine Use and Misuse
Authors: Hargett Jennifer L. , Lowry Presly F. , Lee Keyshawnna N.
Published: June 2023

Tianeptine is an atypical antidepressant that is not approved for use in the United States and has a significant potential for abuse. In recent years, illicit use and misuse of tianeptine have become increasingly common. Symptoms caused by illicit use and withdrawal from tianeptine have become an emerging public health concern. Nurses should be aware of serious or even fatal opiate-like intoxication or withdrawal symptoms, which may present in the absence of a positive urine drug screen or in cases where withdrawal does not follow expected patterns. The associated health effects of tianeptine exposure and misuse include neurologic, cardiovascular, and gastrointestinal symptoms, which manifest in a similar manner to opioid toxicity and opioid withdrawal syndrome. People who illicitly use or misuse tianeptine should be educated regarding the risks associated with this drug. In addition, nurses should promote screening, intervention, and referral to treatment for this and other substance use disorders. Nurses should also support efforts to control access to products containing tianeptine.
Efficacy and safety of preoperative immunotherapy alone followed by surgery in the treatment of advanced gastric cancer with MSI-H/dMMR or EBV-positive
Authors: Lei Xiaokang , Wang Yinkui , Shan Fei , Li Shuangxi , Jia Yongning , Miao Rulin , Xue Kan , Li Zhemin , Ji Jiafu , Li Ziyu
Published: June 2023

Background:

At present, there is no consensus on whether preoperative immunotherapy (PIT) without chemotherapy followed by surgery could benefit patients with advanced gastric cancer (AGC). Here, we report a six-case series study to describe the safety and efficacy of PIT plus gastrectomy in patients with AGC.

Methods:

This study involved six patients with AGC who received PIT and surgery at our center between January 2019 and July 2021. Demographic characteristics, preoperative gastroscope biopsy pathology, surgical tissue pathology, radicalness of tumor resection, surgical safety, and recovery parameters were reported.

Results:

Six patients, including four patients with Epstein-Barr virus (EBV)-positive gastric cancer (GC) and two patients with microsatellite instability-high (MSI-H)/expression deficiency of mismatch repair (dMMR) protein GC, were enrolled in this study. Four patients experienced immunotherapy-related adverse events (irAEs), without severe adverse events (SAEs). Five patients underwent R0 resection, and one patient underwent palliative gastrectomy due to liver and hilar lymph node metastasis. Pathologic responses from the surgical tissue were observed in all patients, including two pathological complete response (pCR). No operative complications or postoperative deaths occurred. Three patients (50%) experienced mild or moderate postoperative complications without severe postoperative complications. All six patients eventually recovered and were discharged.

Conclusion:

This study indicated that PIT was effective and tolerant in some patients with MSI-H/dMMR and/or EBV-positive AGC. PIT followed by gastrectomy might be an alternative treatment option for these selected patients.
Value of Using a Structured Improvement Approach: A Dedicated Education Unit Exemplar
Authors: Polancich Shea , Byrd Elizabeth , Miltner Rebecca S. , Eagerton Greg , Talley Michele , Moneyham Linda , Stewart Jill , White-Williams Connie
Published: June 2023

Using a structured approach to improvement that integrates methodological frameworks and commonly used improvement tools and techniques allows an improvement team to systematically implement and evaluate an intervention. Authors from one academic medical center will describe our four-step structured improvement approach in the design of a dedicated education unit (DEU) pilot to potentially meet a critical post-COVID-19 workforce need. Using our structured improvement approach, we successfully piloted a DEU with a unit-based clinical educator and 16 nursing students over 26 clinical days and received 13 preintervention surveys from participants. Although the DEU pilot was small with limited data, the structured improvement approach resulted in an organized and systematic way of designing, implementing, and evaluating improvement.
Role of 18F-FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus
Authors: Sarswat Sulochana , Khan Dikhra , Sagar Sambit , Kumar Rakesh
Published: June 2023

Purpose

Hypercoagulable state is a complication of various infections, and inflammatory processes and is a common scenario in cancer patients also. Timely diagnosis and treatment are essential to reduce further complications in such patients. The present study aimed to assess the role of FDG PET/CT in the diagnosis of benign vs. malignant tumor thrombus and to determine cut-off SUVmax to differentiate them.

Patients and methods

We retrospectively reviewed all FDG PET/CT scans of patients done in our department from January 2017 to March 2022. All scans were reviewed by two experienced nuclear medicine physicians. A total of 135 patients who had venous or arterial thrombus in FDG PET/CT scans were included. All the FDG PET/CT scans of 135 patients were analyzed for primary tumor site and/or site of thrombus. Additional clinical data were collected for patients with benign conditions in the form of ESR and CRP if available and doubtful cases were followed up by HPE reports and/or CEMRI. The SUV max of the primary tumor(in cancer patients), thrombus, and background (aorta) were calculated.

Results

A total of 135 patients (108 cancer patients and 27 with benign thrombus) were included with an age range of 3 to 86 years (median 50 years). There were 91 males and 44 females. Of 108 cancer patients, the most common cancers were hepatocellular cancer – 38 (35.18%), renal cell cancer – 28(25.92%), and carcinoma of the thyroid – 6 (5.55%). Of 108 cancer patients, 36 (33.33%) had tumor thrombosis in inferior vena cava, 31 (28.70%) in the portal vein, and 41 (37.96%) in other vessels (renal vein, jugular vein, etc.). Of 27 patients with benign conditions,13 had venous thrombi, 11 had arterial thrombus and three had atrial thrombus and the most common thrombus sites were thoraco-abdominal aorta in seven (25.92%) and right atrium in three (11.11%) patients. In the subgroup of 108 oncological patients, the mean SUV max of the primary tumors was 17.67 (range 2.1–91.0; median 10.82), thrombi were 17.61 (range 2.14–90.11; median 14.56) and background was 5.29 (range 0.29–25.00; median 3.12). Of 27 patients with benign conditions, the mean SUV max of the thrombi was 11.09 (range 1.98–31; median 8.10) and the background was 9.80 (range 1.46–24.50; median 10.20) The ESR was raised in 13 of 26 patients (mean 35.84, range 10.98–62.00, median 35.00) and CRP was raised 22 of 26 patients (mean11.46, range 3.45–24.50, median 20.40). Upon plotting the receiver operating curve, a cutoff SUV max of 12.7 with a sensitivity of 62.96% and specificity of 77.77% was produced to demarcate tumor thrombus from benign thrombus.

Conclusion

FDG PET/CT plays a significant role in the detection of thrombo-embolic disease and can differentiate benign thrombus from tumor thrombus.
A Current State Assessment on Nursing Work Activities
Authors: Perpetua Zachary , Lennon Jennifer , Shovel Judith A. , Appell Katherine E. , Patterson Leah , Martin Susan C. , Minnier Tamra E. , Sackrowitz Rachel , Zapf Rachel L. , Kip Paula L. , McLaughlin Maribeth
Published: June 2023

Background:

Nationwide nursing shortages have led to higher patient-to-nurse ratios, nursing burnout, and decreased quality of care.

Local Problem:

Staffing challenges and nursing burnout were becoming growing concerns and success was contingent upon efficient use of existing resources.

Methods:

Direct observation current state assessment was completed on medical-surgical specialty units to better understand work activities of registered nurses (RNs) and unlicensed assistive personnel (UAPs).

Results:

RNs spent more time performing indirect care (eg, documentation) than direct patient care. Interruptions and problems consumed 17.4% and 5.6% of their time, respectively. UAPs performed more direct patient care but had a higher proportion of downtime. RNs underdelegated nonclinical tasks.

Conclusions:

Direct observation current state assessment offers a better understanding of workflow and workload inefficiencies. This information is critical to provide informed, evidence-based recommendations to develop future patient care models with more capacity to deliver high-quality care with greater efficiency and lessen nursing burden and burnout during the nursing shortage crisis.
Ruptured Appendicitis Within an Intussusception on Point-of-Care Ultrasound
Authors: Wu Amy
Published: June 2023

This case describes a 21-month-old girl who was transferred to our pediatric emergency department with daily fevers for 9 days and concern for intussusception on an ultrasound obtained at the outside hospital. Her examination was notable for diffuse tenderness to palpation with no rebound or guarding. Point-of-care-ultrasound (POCUS) revealed a noncompressible, target-shaped structure in the right midabdomen, which appeared to contain a dilated loop of bowel surrounded by a hypoechoic fluid collection. This was confirmed by radiology-performed ultrasound and computed tomography scan, which showed an ileocolic intussusception containing a dilated echogenic loop of bowel consistent with perforated acute appendicitis and associated abscess with surrounding inflammatory changes. To our knowledge, this is the first reported case of perforated appendicitis within an intussusception identified on POCUS in a pediatric patient. This case demonstrates the utility of POCUS in facilitating the recognition of an atypical diagnosis of a perforated appendicitis contained within an intussusception and helping to guide further evaluation and management.
Risk factors for acquiring Acinetobacter baumannii infection in the intensive care unit: experience from a Moroccan hospital.
Authors: BENAISSA ELMOSTAFA , Belouad Elmehdi , Maleb Adil , Elouennass Mostafa
Published: June 2023

Introduction : Acinetobacter spp is a non-fermenting and ubiquitous Gram-negative coccobacillus, which is in recent years the leading cause of healthcare-associated infections worldwide. Our objective is to study the epidemiology and risk factors associated with Acinetobacter baumannii infections in the intensive care units.
Methods: 
This retrospective case-control study was conducted collaboratively between the Medical Bacteriology Department and the two Intensive Care Units of the Military Hospital of Instruction Mohammed V-Rabat over a 3-month period.
Results: We included 180 patients, out of which 60 had Acinetobacter baumannii infection. We observed a male predominance in both matched groups, with a sex ratio of 1.6. The median age was 67 years IQR [59.5-77]. The median length of stay in the intensive care units before infection was 8.5days IQR [5-14]. Multi-variate logistic regression analysis identified the risk factors statistically associated with Acinetobacter baumannii infection at the intensive care units level as follows: duration of invasive procedures˃ 7days(OR=1. 02), parenteral nutrition(OR=3.514), mechanical ventilation (OR=3.024), imipenem (OR=18.72), colistin(OR=5.645), probabilistic antibiotic therapy ˃4days (OR=9.063) and neoplastic pathology(OR=5.727).
Conclusion: 
Based on our results, it can be inferred that shortening the duration of stay in the resuscitation setting, implementing rational use of medical devices, and optimizing antibiotic therapy could decrease the incidence of these infections.
Genetic and environmental determinants of surface adaptations in Pseudomonas aeruginosa
Authors: Ambreetha Sakthivel , Singh Varsha
Published: June 2023

Pseudomonas aeruginosa

is a well-studied Gram-negative opportunistic bacterium that thrives in markedly varied environments. It is a nutritionally versatile microbe that can colonize a host as well as exist in the environment. Unicellular, planktonic cells of

P. aeruginosa

can come together to perform a coordinated swarming movement or turn into a sessile, surface-adhered population called biofilm. These collective behaviours produce strikingly different outcomes. While swarming motility rapidly disseminates the bacterial population, biofilm collectively protects the population from environmental stresses such as heat, drought, toxic chemicals, grazing by predators, and attack by host immune cells and antibiotics. The ubiquitous nature of

P. aeruginosa

is likely to be supported by the timely transition between planktonic, swarming and biofilm lifestyles. The social behaviours of this bacteria viz biofilm and swarm modes are controlled by signals from quorum-sensing networks, LasI-LasR, RhlI-RhlR and PQS-MvfR, and several other sensory kinases and response regulators. A combination of environmental and genetic cues regulates the transition of the

P. aeruginosa

population to specific states. The current review is aimed at discussing key factors that promote physiologically distinct transitioning of the

P. aeruginosa

population.
Algorithm Refinement in the Non-Invasive Detection of Blood Glucose via Bio-RFID™ Technology1
Authors: Klyve Dominic , Currie Kaptain , Anderson James H. , Ward Carl , Schwarz David , Shelton Barry
Published: June 2023

Diabetes Mellitus (DM) is a highly prevalent and increasingly common disorder that can have dire health consequences if not properly managed. Managing DM involves monitoring blood glucose levels, which can be cumbersome and invasive, and adherence to this practice is poor. We present a validation for a novel sensor designed to measure blood glucose (BG) non-invasively using Radio Frequency (RF) waves. In this n=5 study, we trained a Light Gradient-Boosting Machine (lightGBM) model to predict BG values using 1,555 observations from over 130 hours of data collection from five participants, where an observation is defined as data collected from 13 Bio-RFID sensor sweeps paired with a single Dexcom G6® value. Using this model, we predicted BG in the test set with a Mean Absolute Relative Difference (MARD) of 12.7% in the normoglycemic range and 14.0% in the hyperglycemic range. Overall, 70.7% of the estimates fell within 15% of the reference value, and 79.1% fell within 20% of the reference value. While this is a small participant sample, these strong initial results indicate the efficacy of this technique, and that with further refinement and more data, there is promise to achieve a clinically relevant level of accuracy.
Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression
Authors: Bell Alexander J. , Pal Ravi , Labaki Wassim W. , Hoff Benjamin A. , Wang Jennifer M. , Murray Susan , Kazerooni Ella A. , Galban Stefanie , Lynch David A. , Humphries Stephen M. , Martinez Fernando J. , Hatt Charles R. , Han MeiLan K. , Ram Sundaresh , Galban Craig J.
Published: June 2023

Objectives

Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.

Materials and Methods

PRM metrics of normal lung (PRMNorm) and functional SAD (PRMfSAD) were generated from CT scans collected as part of the COPDGene study (n=8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRMNormand PRMfSAD. Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV1decline using a machine learning model.

Results

Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRMfSADand PRMNormwere independently associated with the amount of emphysema. Readouts χfSAD(β of 0.106, p<0.001) and VfSAD(β of 0.065, p=0.004) were also independently associated with FEV1% predicted. The machine learning model using PRM topologies as inputs predicted FEV1decline over five years with an AUC of 0.69.

Conclusions

We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRMfSADand PRMNormmay show promise as an early indicator of emphysema onset and COPD progression.
Similarity and diversity of genetic architecture for complex traits between East Asian and European populations
Authors: Zhang Jinhui , Zhang Shuo , Qiao Jiahao , Wang Ting , Zeng Ping
Published: June 2023

Background:Genome-wide association studies have detected a large number of single-nucleotide polymorphisms (SNPs) associated with complex traits in diverse ancestral groups. However, the trans-ethnic similarity and diversity of genetic architecture is not well understood currently.

Results:By leveraging summary statistics of 37 traits from East Asian (Nmax=254,373) or European (Nmax=693,529) populations, we first evaluated the trans-ethnic genetic correlation (ρg) and found substantial evidence of shared genetic overlap underlying these traits between the two populations, withranging from 0.53 (se=0.11) for adult-onset asthma to 0.98 (se=0.17) for hemoglobin A1c. However, 88.9% of the genetic correlation estimates were significantly less than one, indicating potential heterogeneity in genetic effect across populations. We next identified common associated SNPs using the conjunction conditional false discovery rate method and observed 21.7% of trait-associated SNPs can be identified simultaneously in both populations. Among these shared associated SNPs, 20.8% showed heterogeneous influence on traits between the two ancestral populations. Moreover, we demonstrated that population-common associated SNPs often exhibited more consistent linkage disequilibrium and allele frequency pattern across ancestral groups compared to population-specific or null ones. We also revealed population-specific associated SNPs were much likely to undergo natural selection compared to population-common associated SNPs.

Conclusions:Our study provides an in-depth understanding of similarity and diversity regarding genetic architecture for complex traits across diverse populations, and can assist in trans-ethnic association analysis, genetic risk prediction, and causal variant fine mapping.
Syndromic surveillance during 2022 Uganda martyrs’ commemoration
Authors: Ninsiima Mackline , Wanyana Mercy W. , Kiggundu Thomas , King Patrick , Lubwama Bernard , Migisha Richard , Bulage Lilian , Kadobera Daniel , Ario Alex Riolexus
Published: June 2023

Mass gatherings frequently include close, prolonged interactions between people, which presents opportunities for infectious disease transmission. Over 20,000 pilgrims gathered at Namugongo Catholic and Protestant shrines to commemorate 2022 Uganda Martyr’s Day. We described syndromes suggestive of key priority diseases particularly COVID–19 and viral hemorrhagic fever (VHF) among visiting pilgrims during May 25−June 5, 2022. A suspected COVID–19 case was defined as ≥2 signs or symptoms of: fever >37.50C, flu, cough, and difficulty in breathing whereas a suspected VHF case was defined as fever >37.50C and unexplained bleeding among pilgrims who visited Namugongo Catholic and Protestant shrines from May 25 to June 5, 2022. Pilgrims were sampled systematically at entrances and demarcated zonal areas to participate in the survey. Additionally, we extracted secondary data on pilgrims who sought emergency medical services from Health Management Information System registers. Descriptive analysis was conducted to identify syndromes suggestive of key priority diseases based on signs and symptoms. Among 1,350 pilgrims interviewed, 767 (57%) were female. The mean age was 37.9 (±17.9) years. Nearly all pilgrims 1,331 (98.6%) were Ugandans. A total of 236 (18%) reported ≥1 case definition symptom and 25 (2%) reported ≥2 symptoms. Twenty-two (1.6%) were suspected COVID–19 cases and three (0.2%) were suspected VHF cases from different regions of Uganda. Among 5,582 pilgrims who sought medical care from tents, 538 (9.6%) had suspected COVID–19 and one had suspected VHF. Almost one in fifty pilgrims at the 2022 Uganda Martyrs’ commemoration had at least one symptom of COVID–19 or VHF. Overall, we identified 4 Viral Hemorrhagic Fever and 560 COVID-19 suspected cases during the 2022 Uganda Martyrs’ commemoration. Intensified syndromic surveillance and planned laboratory testing capacity at mass gatherings is important for early detection of public health emergencies that could stem from such events.
Arg4810Lys Mutation inRNF213among Eastern Indian Non-MMD Ischemic Stroke Patients: A Genotype-Phenotype Correlation
Authors: Sadhukhan Dipanwita , Mitra Parama , Mishra Smriti , Roy Arunima , Podder Gargi , Ray Biman Kanti , Biswas Atanu , Hui Subhra Prakash , Banerjee Tapas Kumar , Biswas Arindam
Published: June 2023

Introduction

RNF213mutations have been reported mostly in Moyamoya Disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset Ischemic Stroke is still not well explored.

Aims & Objectives

This present study thus aims to screen the most commonRNF213variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD Ischemic Stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analysed for this variant using PCR-RFLP and confirmed using Sanger sequencing method.

Result & Conclusion

We have identified Arg4810Lys variant among eleven young-onset familial Ischemic Stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age-at-onset (P = 0.002), history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213- a pathogenic variant for young-onset familial Ischemic Stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.
Data-driven hypothesis generation among inexperienced clinical researchers: A comparison of secondary data analyses with visualization (VIADS) and other tools
Authors: Jing Xia , Cimino James J. , Patel Vimla L. , Zhou Yuchun , Shubrook Jay H. , De Lacalle Sonsoles , Draghi Brooke N. , Ernst Mytchell A. , Weaver Aneesa , Sekar Shriram , Liu Chang
Published: June 2023

Objectives

To compare how clinical researchers generate data-driven hypotheses with a visual interactive analytic tool (VIADS, avisual interactiveanalysis tool for filtering and summarizing largedatasets coded with hierarchical terminologies) or other tools.

Methods

We recruited clinical researchers and separated them into “experienced” and “inexperienced” groups. Participants were randomly assigned to a VIADS or control group within the groups. Each participant conducted a remote 2-hour study session for hypothesis generation with the same study facilitator on the same datasets by following a think-aloud protocol. Screen activities and audio were recorded, transcribed, coded, and analyzed. Hypotheses were evaluated by seven experts on their validity, significance, and feasibility. We conducted multilevel random effect modeling for statistical tests.

Results

Eighteen participants generated 227 hypotheses, of which 147 (65%) were valid. The VIADS and control groups generated a similar number of hypotheses. The VIADS group took a significantly shorter time to generate one hypothesis (e.g., among inexperienced clinical researchers, 258 seconds versus 379 seconds,p= 0.046, power = 0.437, ICC = 0.15). The VIADS group received significantly lower ratings than the control group on feasibility and the combination rating of validity, significance, and feasibility.

Conclusion

The role of VIADS in hypothesis generation seems inconclusive. The VIADS group took a significantly shorter time to generate each hypothesis. However, the combined validity, significance, and feasibility ratings of their hypotheses were significantly lower. Further characterization of hypotheses, including specifics on how they might be improved, could guide future tool development.
Age classes stratified by risk and adaptive behavior during epidemics
Authors: Arthur Ronan F. , Levin May , Labrogere Alexandre , Feldman Marcus W.
Published: June 2023

Heterogeneity in contact patterns, mortality rates, and transmissibility among and between different age classes can have significant effects on epidemic outcomes. Adaptive behavior in response to the spread of an infectious pathogen may give rise to complex epidemiological dynamics. Here we model an infectious disease in which adaptive behavior incentives, and mortality rates, can vary between three age classes. The model indicates that age-dependent variability in infection aversion can produce more complex epidemic dynamics at lower levels of pathogen transmissibility.
Using Explainable AI to understand frailty indicators
Authors: Mohsen Attayeb , Yamamoto Masaki , Martin-Morales Agustin , Watanabe Daiki , Nishi Nobuo , Nakagata Takashi , Yoshida Tsukasa , Miyachi Motohiko , Mizuguchi Kenji , Araki Michihiro
Published: June 2023

Introduction

The prevalence of frailty is on the rise with the aging population and increasing life expectancy, which often is accompanied by comorbidities. Frailty can be effectively detected using Frailty index such as KCL index. Early detection of frailty allows applying measures that reduce the conversion rate to frail, and improve the quality of life in the frail people. Therefore, to facilitate the screening of frailty status at the primary care level, we suggest to produce a shorter version of the KCL questionnaire.

Aim

To understand the importance of KCL components in the decision making process for frailty and use machine learning approach to shorten the Questionnaire while maintaining reasonable accuracy, making it easier to screen for frailty in primary care.

Methods

We developed an automated framework of three steps: Feature importance determination using Shap values, testing models with Cross-validation with increased addition of selected features. Moreover, we validated the reliability of KCL to detect frailty by comparing the results of KCL criteria with the unsupervised clustering of the data.

Results

Our approach allowed us to identify the most important questions in the KCL questionnaire and demonstrate its performance using a short version with only four questions (4) Do you visit homes of friends?, (6) Are you able to go upstairs without using handrails or the wall for support? (10) Do you feel anxious about falling when you walk?, and (25) (In the past two weeks) Have you felt exhausted for no apparent reason?). We also showed that the data clustering corresponds well with the results of KCL criteria.

Discussion and Conclusion

While it is difficult to predict pre-frail status using shorter KCL questionnaire, it was shown to be fairly accurate in predicting frail status using only four questions.
Human Rhinoviruses: a novel class of oncolytic virus
Authors: Burnett William J , Cluff Amber , Reeves Melissa , Parkman Gennie L , Hart Chase , Ramstead Andrew , Holmen Sheri , Williams Matthew A , VanBrocklin Matthew W
Published: June 2023

While continuing to develop new and improved OVs, researchers have been vigilant in optimizing their ability to safely infect, replicate, and induce an immune response within tumors. There are currently two crucial limitations in OV development, however: modification of viruses often negatively impact their ability to infect, and induction of strong immune responses also promotes rapid viral clearance. In this study, we investigate wild-type HRVs as a novel class of OV. Multiple HRV serotypes were propagated in human melanoma cell lines to produce highly oncolytic populations of virus. A large panel of cancer types were infected, with cytotoxicity evaluated using flow cytometry and real time live imaging. Pro-inflammatory signaling was assessed by cytokine multiplexing. Tumor responses to HRV were assessed in human xenograft and in syngeneic, immune-competent mouse tumor models. We find that HRVs are capable of infecting and killing a wide variety of human cancer cell linesin vitroandin vivo, inducing pro-inflammatory responses and, ultimately, tumor regression. We propose that the natural safety profile of these viruses, coupled with their anti-tumor efficacy and multivalent potential seen in our preclinical model systems, make HRVs ideal candidates for development as oncolytic viruses for clinical testing.

Simple Summary

The idea of utilizing viruses to combat cancer has been around for over a century, yet in practice has seen relatively modest therapeutic success following decades of strategic design to improve safety, efficacy, and tumor selectivity. Engagement of an immune response is critical to have lasting tumor regression upon treatment, but many patients are unable to mount a sufficient response to standard-of-care immunotherapy alone. Oncolytic viruses (OVs) have been shown to synergize with such therapies to accomplish this goal to varying degrees. The purpose of this study is to investigate human rhinoviruses (HRVs) to establish their efficacy as a novel class of anti-cancer agents. We aim to use HRVs to promote longer lasting and more effective immune responses to tumors by fostering viral persistence and immune evasion, in addition to developing multivalent treatment strategies that enhance tumor regression by preventing tumor escape from viral infection.
High-resolution Dynamic Human Brain Neural Activity Recording Using 3T MRI
Authors: Zhang Yifei , Sun Kaibao , Ren Jianxun , Hu Qingyu , Wang Yezhe , Li Shiyi , Chen Tienzheng , Xu Na , Guo Ning , Fu Xiaoxuan , Liu Xuan , Cao Zhenen , Gao Jia-hong , Liu Hesheng
Published: June 2023

Despite extensive research over decades, a non-invasive technique capable of capturing neural activities in the human brain with high spatiotemporal resolution is still lacking. The recently proposed direct imaging of neuronal activity (DIANA) using ultrahigh-field magnetic resonance imaging (MRI) has shown promise, but the translation from anesthetized mice to awake humans poses a significant challenge. Here we present Time Resolved ImaGing of Global Electroneurophysiological Record (TRIGGER), a novel technique that enables the direct detection of neural activity in the awake human brain using 3T MRI. In 18 participants, visual responses were captured at 5-mm spatial resolution and 1.4-ms temporal resolution. Importantly, the delay in stimulus presentation reliably corresponded to the latency of neural responses on a millisecond scale. Furthermore, when stimuli were presented to one visual field, the responses in two hemispheres exhibited the expected time difference. This non-invasive mapping approach holds the potential to elucidate neural dynamics underlying human brain function and disorders.
GeneToCN: an alignment-free method for gene copy number estimation directly from next-generation sequencing reads
Authors: Pajuste Fanny-Dhelia , Remm Maido
Published: June 2023

Genomes exhibit large regions with segmental copy number variation, many of which include entire genes and are multiallelic. We have developed a computational method GeneToCN that counts the frequencies of gene-specifick-mers in FASTQ files and uses this information to infer copy number of the gene. We validated the copy number predictions for amylase genes (AMY1, AMY2A, AMY2B) using experimental data from digital droplet PCR (ddPCR) on 39 individuals and observed a strong correlation (R=0.99) between GeneToCN predictions and experimentally determined copy numbers. We further tested the method on three different genomic regions (SMN, NPY4R, and LPA Kringle IV-2 domain). Predicted copy number distributions of these genes in a set of 500 individuals from the Estonian Biobank were in good agreement with the previously published studies. In addition, we investigated the possibility to use GeneToCN on sequencing data generated by different technologies by comparing copy number predictions from Illumina, PacBio, and Oxford Nanopore data of the same sample. Despite the differences in variability ofk-mer frequencies, all three sequencing technologies give similar predictions with GeneToCN.
Chronotate: An open-source tool for manual timestamping and quantification of animal behavior
Authors: Philipsberg Paul A. , Christenson Wick Zoé , Diego Keziah S. , Vaughan Nick , Galas Angelina , Jurkowski Albert , Feng Yu , Vetere Lauren M. , Chen Lingxuan , Cai Denise J. , Shuman Tristan
Published: June 2023

A core necessity to behavioral neuroscience research is the ability to accurately measure performance on behavioral assays, such as the novel object location and novel object recognition tasks. These tasks are widely used in neuroscience research and measure a rodent’s instinct for investigating novel features as a proxy to test their memory of a previous experience. Automated tools for scoring behavioral videos can be cost prohibitive and often have difficulty distinguishing between active investigation of an object and simply being in close proximity to an object. As such, many experimenters continue to rely on hand scoring interactions using stopwatches which makes it difficult to review scoring after-the-fact and results in the loss of temporal information. Here, we introduce Chronotate, a free, open-source tool to aid in manually scoring novel object behavior videos. The software consists of an interactive video player with keyboard integration for marking timestamps of behavioral events during video playback, making it simple to quickly score and review bouts of rodent-object interaction. In addition, Chronotate outputs detailed interaction bout data, allowing for nuanced behavioral performance analyses. Using this detailed temporal information, we demonstrate that novel object location performance peaks within the first 3 seconds of interaction time and preference for the novel location becomes reduced across the test session. Thus, Chronotate can be used to determine the temporal structure of interactions on this task and can provide new insight into the memory processes that drive this behavior. Chronotate is available for download at:https://github.com/ShumanLab/Chronotate.