bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducibility of high‐resolution manometry among healthy and constipated persons
Authors: Mishra Rahul , Gautam Misha , Oblizajek Nicholas R. , Bharucha Adil E.
Published: August 2022

Background and Aims

Although high‐resolution manometry (HR_ARM) is commonly used to diagnose defecatory disorders, its intraindividual day‐to‐day reproducibility is unknown. Since these measurements entail voluntary effort, this study aimed to evaluate the intraindividual day‐to‐day reproducibility of HR_ARM.

Methods

In 22 healthy women (35 years [14] mean [SD]) and 53 constipated patients (42 years [13], 46 women), the rectal balloon expulsion time (BET), and anorectal pressures were measured with HR_ARM on 2 days separated by a median (interquartile range) of 15 days (11–53) in healthy and 40 days (8–75) in constipated patients. Anorectal pressures were evaluated at rest (20 s), during squeeze, and during evacuation. Rectal sensation was also evaluated in constipated patients. The agreement between both measurements was evaluated with Lin's concordance correlation coefficient (CCC) and other tests.

Results

Among constipated patients, the anal resting (mean CCC [95%CI] 0.62 [0.43–0.76]) and squeeze pressures (CCC 0.65 [0.47–0.79]), rectoanal gradient during evacuation (CCC 0.42 [0.17–0.62]), and rectal sensory thresholds (CCC for urgency 0.72 [0.52–0.84]) were concordant. Between days 1 and 2, one or more outcomes, characterized as normal or abnormal, differed in 79% of constipated patients, i.e., anal resting and squeeze pressures, the gradient, and the rectal BET differed in, respectively, 25%, 19%, 36%, and 10% of constipated patients. The rectal BET was prolonged in three healthy persons (both days) and either on 1 day (six patients) or 2 days (33 patients) in constipated patients.

Conclusions

While HR_ARM variables and the BET are reproducible within healthy and constipated persons, the outcome on repeat testing differed in 79% of constipated patients.
Management of acne in transgender and gender diverse youth part 1: Gender affirming care and risk factors for the development of acne
Authors: Boos Markus D. , Hollingshead Nicole , Hodax Juanita K.
Published: August 2022

Acne vulgaris is among the most common skin disorders afflicting adolescents worldwide, and though well‐established guidelines of care exist for acne management, these guidelines do not uniformly consider or address the unique psychosocial and medical needs of transgender and gender diverse (TGD) youth. TGD youth may possess distinct goals of therapy when treating their acne; the use of medicines routinely employed to treat acne may also expose TGD adolescents receiving gender affirming medical therapy to greater risk of adverse events. Part 1 of this two‐part review provides dermatologists an understanding of gender affirming care and its timing, as well as its potential impacts on the development of acne in TGD youth.
Policy feedback via economic behavior: A model and experimental analysis of consumption behavior
Authors: Schober Gregory S.
Published: August 2022

This article examines policy feedback via economic behavior in the mass public, with a focus on consumption behavior. Do public policies affect the consumption behavior of mass publics and subsequent policymaking processes and outcomes? If so, how? I introduce a policy feedback model of consumption behavior in the mass public. Within this model, I advance a theoretical argument on the consequences of targeted cash assistance policies (TCAPs) for consumer spending behavior and government provision of basic utilities in developing countries. Using a randomized field experiment in Mexico and pre–post analysis, I find that TCAPs boost consumer spending on private access to basic utilities in the short term and reduce government provision of basic utilities in the medium term. The study pushes policy feedback theorists to think beyond the arena of mass politics, and the findings have important implications for social policy and human development in developing countries.
What did Didactic Literature Teach? Change‐Ringing Manuals, Printed Miscellanies and Forms of Active Reading☆
Authors: Hunt Katherine
Published: August 2022

This paper takes the practice of change‐ringing as a case study to examine the forms, transmission, and effects of early modern didactic literature. The novelty of change‐ringing, which was invented and very quickly spread in the seventeenth century, offers an opportunity to test out the contours of learning from printed books. Tracing the dissemination of its instructions in printed miscellanies of instructional literature, and comparing didactic miscellanies to poetic ones, I suggest that what might be most at stake in change‐ringing's written texts is the creation of an educated audience for, rather than practitioners of, the practice. I situate my argument among recent work on instructional literature to propose a renewed role for the literary techniques of textual analysis and bibliography in the study of early modern manuals.
Experimental Investigation on Debris Bed Quenching With Additional Non-Condensable Gas Injection
Authors: Petroff Markus , Kulenovic Rudi , Starflinger Jörg
Published: August 2022

Severe accidents of light water reactors with core degradation can lead to the formation of a, so-called, debris bed inside the reactor cavity. In the scenario of depleted residual water, the bed can partially melt and interact with the concrete underneath generating noncondensable gases (NCG) at the bottom of the particle bed, which will flow through the debris bed. The impact of additional gas on the quenching process can in principle be considered in thermal-hydraulic system codes such as ATHLET; however, there is still a need for experimental validation of respective models or verification of corresponding simulation results. Therefore, especially for the model validation of COCOMO-3D, which is implemented in ATHLET, a specific extension to the existing experimental database is required. Experimental results of the quenching behavior of a monodispersed particle bed at top-flooding cooling condition with additional NCG injection, utilizing the new built-up test facility FLOAT (flooding facility with gas injection), are presented.
Comparison of the Acoustic Performance of Wooden Violins and Carbon Fiber Reinforced Polymer Violins Through a Modal Study by Finite Elements Method and Effective Masses
Authors: Zambrano Marcos , Vergara Mary , Burgos José Luis , Trejo Jhonattan
Published: August 2022

Even though string musical instruments made of synthetic materials such as carbon fiber reinforced polymer (CFRP) have respected acoustic performance, but a short manufacturing cycle and low product cost, they do not become an alternative to replace high-quality string instruments made of sound woods. For CFRP violins to approach high acoustic performance wood violins, they must exhibit approximately the same bending stiffness. The CFRP is denser, stiffer, and isotropic compared to the orthotropy of wood. In this work, the acoustic behavior of CFRP violins with the same geometry as high-quality wood violins was compared. A numerical modal study was developed by finite element simulations, comparing two violin top plates, one in CFRP and the other in Picea abies (PA) wood. The simulations were developed in the ansys mechanical software, using the Block Lanczos method with a mesh of 38,216 finite volumes, finding modal patterns for both the CFRP model and the PA model. Mathematical models based on solid state physics such as effective masses and maximum vibration amplitude between models were outlined. Both models were validated against experimental studies developed by other authors. It is concluded that for instruments with the same geometry, a sonorous superiority of the wood over the CFRP was evidenced, which leads to further reinforce the unique, enigmatic, and mythical behavior of violins made of sonorous woods such as the Stradivarius violins.
A Stochastic and Bayesian Inference Toolchain for Uncertainty and Risk Quantification of Rare Autoignition Events in Dry Low-Emission Premixers
Authors: Yousefian Sajjad , Jella Sandeep , Versailles Philippe , Bourque Gilles , Monaghan Rory F. D.
Published: August 2022

Quantification of aleatoric uncertainties due to the inherent variabilities in operating conditions and fuel composition is essential for designing and improving premixers in dry low-emissions (DLE) combustion systems. Advanced stochastic simulation tools require a large number of evaluations in order to perform this type of uncertainty quantification (UQ) analysis. This task is computationally prohibitive using high-fidelity computational fluid dynamic (CFD) approaches such as large eddy simulation (LES). In this paper, we describe a novel and computationally efficient toolchain for stochastic modeling using minimal input from LES, to perform uncertainty and risk quantification of a DLE system. More specially, high-fidelity LES, chemical reactor network (CRN) model, beta mixture model, Bayesian inference and sequential Monte Carlo (SMC) are integrated into the toolchain. The methodology is applied to a practical premixer of low-emission combustion system with dimethyl ether (DME)/methane–air mixtures to simulate auto-ignition events at different engine conditions. First, the benchmark premixer is simulated using a set of LESs for a methane/air mixture at elevated pressure and temperature conditions. A partitioning approach is employed to generate a set of deterministic chemical reactor network (CRN) models from LES results. These CRN models are then solved at the volume-average conditions and validated by LES results. A mixture modeling approach using the expectation-method of moment (E-MM) is carried out to generate a set of beta mixture models and characterize uncertainties for LES-predicted temperature distributions. These beta mixture models and a normal distribution for DME volume fraction are used to simulate a set of stochastic CRN models. The Bayesian inference approach through SMC method is then implemented on the results of temperature distributions from stochastic CRN models to simulate the probability of auto-ignition in the benchmark premixer. The results present a very satisfactory performance for the stochastic toolchain to compute the auto-ignition propensity for a few events with a particular combination of inlet temperature and DME volume fraction. Characterization of these rare events is computationally prohibitive in the conventional deterministic methods such as high-fidelity LES.
Blisk With Small Geometry Mistuning and Blend Repair: As-Measured Finite Element Model and Experimental Verification
Authors: Zhou Biao , Zhao Jingchao , Ye Nan , Berruti Teresa M.
Published: August 2022

This paper presents an “As-Measured Model” (AMM) of a blended blisk, built upon the measurement of the true geometry of the blisk by the three-dimensional optical scanning technology. This high-fidelity model aims to account for the variances of blade frequencies and mode shapes within the real blisk in the presence of both the blend repair and inherent geometry mistuning due to manufacturing, etc. An improved mesh updating strategy is proposed to adapt a seed blisk finite element model (FEM) to the measured geometry. The resultant AMM is therefore able to accurately represent the measured blade-to-blade geometry variances. The classical blade detuning test (BDT) in combination with a novel “correction” procedure is employed to experimentally evaluate the “blade-alone” frequency mistuning pattern in the real blisk. Experimental verification of the AMM demonstrates that it is able to not only capture the blade-alone frequency and mode shape variations due to both the blend and intrinsic blade geometry variances, but also to reproduce the global dynamics of the blended blisk with acceptable accuracy.
A Nonlinear Rotordynamics Model for Automotive Turbochargers Coupled to a Physical Model for a (SEMI) Floating Ring Bearing System
Authors: Jung Wonbae , San Andres Luis , Kim Jungbae
Published: August 2022

Automotive turbochargers (TCs) use an engine oil lubricated bearing system to produce acceptable performance (as per the engine volumetric efficiency) and proven reliability. However, the bearings also cause TC rotordynamic responses that are rich in subsynchronous whirl motions through reaching stable limit cycles. The paper describes the lubrication model for a finite length semi-floating ring bearing (SFRB) system and its coupling to the rotor and ring structure models for prediction of both linear and nonlinear system responses and their characterization in terms of motion amplitudes and whirl frequency content. The SFRB model includes a thermal energy transport network for the inner and outer films in both radial bearings and the thrust bearings located on the end sides of the ring. The large temperature difference between the hot shaft and a cold housing induces a three-dimensional thermal gradient in the fluid films and the floating ring, further exacerbated by the heat generated from drag power losses in the inner films adjacent to the rotor. The temperature gradients affect the lubricant viscosity and the bearing system operating clearances. The integration of the rotor and bearing system (RBS) equations of motion accounts for the SFRB nonlinear forces and starts from static equilibrium position, if existing. The model predictions of nonlinear behavior are accurate when benchmarked to a set of measurements procured in a gas stand test rig. The analysis also investigates the influence of the bearing inner clearance and rotor mass imbalance distribution on the onset, persistence and severity of SSV.
A Three-Dimensional Non-Newtonian Magnetic Fluid Flow Induced Due to Stretching of the Flat Surface With Chemical Reaction
Authors: Punith Gowda R. J. , Sarris Ioannis E. , Naveen Kumar R. , Kumar Raman , Prasannakumara B. C.
Published: August 2022

Three-dimensional (3D) flow of non-Newtonian liquid is studied in this analysis. Also, this paper is mainly focused on an incompressible magnetic liquid with low Curie temperature and moderate saturation magnetization. An extremely long, straight wire delivering an electric current generates a magnetic field that affects the fluid. Thermal radiation and chemical reaction impacts are considered to study heat and mass transport characteristics. Appropriate transformations are used to reduce pertinent flow expressions into ordinary differential equations (ODEs). The obtained ODEs are solved by means of a numerical method (Runge–Kutta–Fehlberg's fourth–fifth order method (RKF-45) algorithm with shooting technique). The effect of pertinent parameters like chemical reaction rate parameter (between 0.1 and 1.5), ferromagnetic interaction parameter (between 0.01 and 1.0), viscous dissipation parameter (between 0.1 and 1.0), radiation parameter (between 0.1 and 1.0), Deborah number (between 0.1 and 1.0) and Schmidt number (between 1.0 and 2.0) on Maxwell liquid flow, heat and mass transport is illustrated via graphs. Furthermore, from the analysis, the heat transfer rate increases about 30%–40% for the increasing values of the ferromagnetic interaction parameter. Also, the mass transfer rate increases about 4%–6% for the increasing values of the chemical reaction rate parameter.
Asymmetric Nugget Growth in Aluminum Resistance Spot Welding With Multi-Ring Domed Electrodes: An Experimental Study
Authors: Deng Lin , Lv Tianle , Li Yongbing , Cai Wayne , Haselhuhn Amberlee S. , Carlson Blair E. , Balogh Michael P. , Haddad Daad
Published: August 2022

Resistance spot welding of aluminum alloys (Al RSW) is known to be very challenging, in part due to the undesirable and hard-to-predict asymmetric growth of the weld nugget. In this paper, two 1.2 mm thick AA6022-T4 aluminum alloy sheets were joined by RSW using multi-ring domed (MRD) electrodes to experimentally investigate the effect of sheet surface condition, electrode surface morphology, electrode material, weld schedule, and electrode tip condition on asymmetric nugget growth, as well as the resulting weld microstructure and coach peel strength. It was found that asymmetric nugget growth was most strongly influenced by sheet surface conditions and electrode materials at the positive polarity electrode side. The asymmetric nuggets exhibited a smaller nugget angle in relation to the faying surface and a wider partially melted zone (PMZ) in the sheet adjacent to the negative electrode which reduced weld mechanical strength and toughness. In addition, the asymmetric nugget growth also caused asymmetric electrode/workpiece interaction.
A Fourier Approach to Kinematic Acquisition of Geometric Constraints of Planar Motion for Practical Mechanism Design
Authors: Li Xiangyun , Lv Hao , Zhao Ping , Lu Qi
Published: August 2022

This paper studies the problem of geometric constraint acquisition from a given planar motion task using Fourier descriptor. In the previous work, we established a computational geometric framework for simultaneous type and dimensional synthesis of planar dyads by extracting line or circle constraints from a sequence of task poses. In cases where six or more poses are specified as the desired movement, the resulting optimal constraint may be nowhere in the accuracy neighborhood to be viewed as an approximate line or circle. The approach herein enhances the framework by exploiting Fourier transform to capture the feasible constraint of a continuous motion with a large set of poses. Theoretically, any arbitrary point trajectory on the task motion can be transformed to an array of harmonics and used as a constraint; on a practical level, only those with low number of harmonics could allow accurate realization by simple planar mechanisms suitable for real applications, e.g., four- and six-bar linkages, cams, and coupled serial chains. Therefore, the practical goal is to find the simple Fourier constraint defined with the least number of harmonics. Two examples of designing assistive mechanisms for upper- and lower-limb rehabilitation are provided in the end to illustrate the effectiveness of our approach.
Analysis of Anomalies in Water Hammer Experiments With Partially Open Valves
Authors: Xu Tingyu , Zhang Lei , Ni Weixiang , Zhang Xiaoying , Yu Xiaodong , Zhang Jian
Published: August 2022

This study investigated the water hammer pressure due to the sudden closure of the partially open valve experimentally and analytically. Because the partially open valve could produce local nonuniform flow, a supplementary Joukowsky's water hammer equation was derived based on the assumption of the local nonuniform flow and the kinetic energy equation. A physical model was set up to measure the maximum water hammer pressure of the first positive wave due to the sudden closure of the partially open valve under different conditions, including various water heads, flow velocities, pipe diameters, and valve types. The results showed that Joukowsky's equation obtained by the momentum theorem in the uniform flow field was applicable to the uniform flow field with the valve fully open. The experimental results of the partially open valve-closure water hammer pressures were 3.5–21% larger than Joukowsky's equation, which consisted of the theoretical analysis of the supplementary Joukowsky's water hammer equation. This phenomenon had repeatability and was unrelated to the water head, the inlet flow velocity, the pipe diameter, and the valve type. This study could guide water hammer protection in hydropower and pump stations.
Fan Stability Enhancement With Partial Casing Treatments
Authors: Oldfield Matthew K. , Castillo Pardo Alejandro , Hall Cesare A.
Published: August 2022

Casing treatments are used to extend the stability margin of fans or compressors. These typically have an axisymmetric arrangement, but for a fan exposed to non-axisymmetric distortion, a casing treatment applied to a fraction of the annulus is of interest to target a particular distortion feature. In this paper, a partial casing treatment has been designed with axial-skewed slots, and an experimental investigation has been carried out to determine the effects of the treatment extent and position. Three inlet conditions were tested for each extent of casing treatment: clean, radial tip-low distortion, and half-annulus tip-low distortion. For axisymmetric inlet conditions, the stall margin and efficiency penalty increased approximately linearly with casing treatment extent. However, for half-annulus tip-low distortion, there was a strong dependence between the position of the casing treatment relative to the distorted sector and the stall margin improvement. If the casing treatment is positioned where the rotor enters the distorted sector, unsteady disturbances in the rotor tip flow are minimized. However, if the rotor meets the casing treatment later in the distorted sector, the disturbances are able to grow, leading to earlier stall inception. Overall, this shows that partial casing treatments can target a distorted flow to give a disproportionately positive impact compared to a full annulus casing treatment. For example, it was found that a 72 deg casing treatment extent could be positioned to achieve over 50% of the full annulus casing treatment stall margin improvement with only 20% of the efficiency penalty.
The Effect of Gas and Surface Temperature on Cold-Side and Hot-Side Turbine Deposition
Authors: Bons Jeffrey P. , Lo Chihsiu , Nied Eric , Han Jiaxuan
Published: August 2022

Deposition studies were conducted using two impingement jet facilities: a 60 m/s cold jet (830–950 K) impinging on a heated Hastelloy-X surface (1033–1255 K) and a 215 m/s hot jet (1450–1625 K) impinging on an uncooled ceramic target or a cooled thermal barrier coated (TBC) surface (1090–1400 K). These can be considered analogs for an internal impingement cooling jet flow and an external nozzle guide vane leading edge flow respectively. Airflows were seeded with 0–10 µm Arizona road dust and deposition accumulated over a period of 5–10 min. Selected tests were completed with other size distributions. Studies were conducted by varying flow temperature at constant surface temperature and vice-versa. For both hot and cold impingement jets, the sensitivity of capture efficiency to fluid (and thus particle) temperature was found to be roughly double the sensitivity to surface temperature. Hot jet tests with three different size distributions of dust (0–5, 0–10, and 5–10 µm) allowed particle size sensitivity to be evaluated. For both target types (ceramic and cooled TBC), the 0–10 µm test dust produced the highest deposition rate of the three size distributions. Possible explanations for the observed behavior are proposed. Companion CFD studies modeling both impinging jets with particle deposition demonstrate that temperature induced variations in particle trajectories alone are not sufficient to explain observed deposition trends with temperature. Implications for the development of a universal sticking model relevant to gas turbine deposition are discussed.
Effect of Temperature and Velocity on Microparticle Erosion/Deposition into Environmental-Barrier-Coated Ceramic Matrix Composite for Aeroengines
Authors: Okita Yoji , Suzuki Masaya , Yamane Takashi , Hasegawa Jun , Mizokami Yosuke , Nakamura Takeshi
Published: August 2022

Ceramic matrix composites (CMCs), especially SiC/SiC, have garnered significant attention owing to their remarkable mechanical properties at higher temperatures. For the protection of the substrate from oxidation, the SiC/SiC CMCs inherently require environmental barrier coating (EBC). Because aeroengines must function under a wide range of conditions and environments, the coated CMC must be sufficiently resistant to various damage modes. Among these, the effect of microparticles is one of the limiting factors for the durability and performance of components, particularly when the engine is operated in dusty areas. The main goal of this experimental research is to investigate and determine the surface damage behavior of the coated CMC caused by micro-sand particles. The data were surveyed across a fairly broad range of exposed temperatures and velocities, and covered conditions relevant to advanced hot section designs. In the experiments, silica or alumina sand entrained in the gas stream was jet-blasted from the nozzle and then impinged on the target CMC + EBC coupon. Owing to the broad testing range, the damage mode and extent of damage varied considerably by condition. The obtained data were then reorganized and compared with several previously proposed particle impact models. This is to first understand and obtain a complete picture of all the probable consequences in the expected design and off-design conditions and, second, to determine the validity of, and deviations from the conventional modeling with the present CMC + EBC material, which will be useful in the next component design phase.
A bubble-based demonstration of free-fall weightlessness
Authors: Slisko Josip , Garduño Ricardo del Rosal
Published: August 2022

According to the equivalence principle, there is no local gravity field inside free-falling systems. Consequently, all gravity-related forces disappear. Among them is the buoyant force. The absence of the buoyant force in free-falling systems was previously shown in various published demonstrations.
Interdependence of the First and Second Laws of
Thermodynamics
Authors: Kaufman Richard , Leff Harvey
Published: August 2022

Historically, classical thermodynamics was developed during attempts to improve the efficiency of steam engines. Those investigations led to the well-known zeroth, first, and second laws of thermodynamics. Although these laws are presented independently, linkages between the zeroth and second laws have been pointed out in the physics teaching literature. In our 2020 paper, “What if Energy Flowed from Cold to Hot? Counterfactual Thought Experiments,” we imagined a universe in which energy spontaneously flowed from colder to hotter objects. That paper inspired us to explore the connections between the first law and the Clausius statement of the second law in the present paper.
Parametrically enhanced interactions and nonreciprocal bath dynamics in a photon-pressure Kerr amplifier
Authors: Rodrigues Ines Corveira , Steele Gary Alexander , Bothner Daniel
Published: August 2022

Photon-pressure coupling between two superconducting circuits is a promising platform for investigating radiation-pressure coupling in distinct parameter regimes and for the development of radio-frequency (RF) quantum photonics and quantum-limited RF sensing. Here, we implement photon-pressure coupling between two superconducting circuits, one of which can be operated as a parametric amplifier. We demonstrate a Kerr-based enhancement of the photon-pressure single-photon coupling rate and an increase of the cooperativity by one order of magnitude in the amplifier regime. In addition, we observe that the intracavity amplification reduces the measurement imprecision of RF signal detection. Last, we demonstrate that RF mode sideband cooling is unexpectedly not limited to the effective amplifier mode temperature arising from quantum noise amplification, which we interpret in the context of nonreciprocal heat transfer between the two circuits. Our results demonstrate how Kerr amplification can be used as resource for enhanced photon-pressure systems and Kerr cavity optomechanics.
CD39
+
tissue-resident memory CD8
+
T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer
Authors: Lee Yong Joon , Kim Jee Ye , Jeon Seung Hyuck , Nam Heejin , Jung Jae Hyung , Jeon Minwoo , Kim Eui-Soon , Bae Soong June , Ahn Juneyoung , Yoo Tae-Kyung , Sun Woo Young , Ahn Sung Gwe , Jeong Joon , Park Su-Hyung , Park Woo Chan , Kim Seung Il , Shin Eui-Cheol
Published: August 2022

Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8
+
T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer (
n
 = 131). Among tissue-resident memory CD8
+
T (T
RM
) cells, including virus- and tumor-specific CD8
+
T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39
+
T
RM
cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39
+
T
RM
cells clonally overlapped with CD39
−
T
RM
and non-T
RM
cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39
+
T
RM
clonotypes were frequently detected among effector memory CD8
+
T cells in peripheral blood, suggesting a systemic clonal overlap. CD39
+
T
RM
cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39
+
T
RM
cells and enhanced cytokine production by CD8
+
T cells from tumors or mLNs, particularly in the presence of CD39
+
T
RM
enrichment. This suggests that CD39
+
T
RM
cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39
+
T
RM
cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.
Vanishing enteric duplication cyst presenting with melaena
Authors: Cave Joshua J , Chaudhary Ahsan , Tsigka Alexia , Tan Yew-Wei
Published: August 2022

A toddler presented with melaena on a background of a possible enteric duplication cyst, diagnosed in the neonatal period which ‘vanished’. What was later confirmed to be a small bowel duplication cyst was not seen on follow-up ultrasounds and thus the patient was managed expectantly until presentation as an emergency. Our case highlights the challenges faced in managing cystic abdominal structures in infancy and the potential consequences of expectant management. We discuss whether cross-sectional imaging or diagnostic laparoscopy should be advocated when duplications cysts are considered amongst the differentials of a lesion on ultrasound.
Clinical procedures used to diagnose inflammatory bowel disease: real-world evidence from a Danish nationwide population-based study
Authors: Rasmussen Nathalie Fogh , Green Anders , Allin Kristine Højgaard , Iversen Aske T , Madsen Gunvor Iben , Pedersen Andreas Kristian , Wolff Donna Lykke , Jess Tine , Andersen Vibeke
Published: August 2022

Objective

Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting.

Design

Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age.

Results

The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn’s disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn’s disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001).

Conclusion

For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD.
To identify the association between dietary vitamin D intake and serum levels and risk or prognostic factors for melanoma-systematic review and meta-analysis
Authors: Song Yadong , Lu Hongyan , Cheng Yan
Published: August 2022

Objective

To evaluate the association of serum vitamin D levels and dietary intake with melanoma risk and prognostic factors.

Methods

Two independent investigators systematically searched PubMed, Embase and ISI Web of Knowledge (Thomson Scientific Technical Support, New York) databases for eligible studies published between January 1992 and September 2020 using the following combinations of search terms: (vitamin D, or 25-hydroxyvitamin D) AND (melanoma, malignant melanoma, cutaneous melanoma, or cutaneous malignant melanoma). Articles not written in English but with English titles and abstracts were also checked. We obtained the full text of all potentially eligible articles, and reference lists of all studies retrieved at the ﬁrst stage were also checked to identify other eligible papers. Review articles not reporting original data were excluded, but their reference lists were inspected.

Results

Six studies including 212 723 cases reported the association between dietary intake of 25(OH) D serum levels and melanoma risk. The total relative risk for the comparison between the highest and lowest quantiles of the distribution of vitamin D intake was 1.10 (95% CI 0.96 to 1.26) withI2=56%. Another six studies including 12 297 cases evaluated the association between serum vitamin D levels and melanoma risk. The total relative risk for the comparison of serum vitamin D levels between the highest and lowest quantiles was 1.12 (95% CI 0.53 to 2.35) withI2=91%. Four studies with 2105 cases investigated the association between serum 25(OH)D (nmol/L) and Breslow thickness, three of which found an inverse association between serum 25(OH)D (nmol/L) and melanoma thickness.

Conclusions

Vitamin D intake and serum 25(OH)D levels were not closely related with melanoma risk, but an inverse association between serum 25(OH)D levels with melanoma thickness was discovered. As the positive correlation between melanoma thickness and melanoma mortality has been recognised, hence it is concluded that a moderate dietary vitamin D supplement to avoid the serum 25(OH)D deficient might be beneficial to the long-term survival of patients with melanoma.
General practice database on mortality in adults on methylphenidate: cohort study
Authors: Stricker Bruno , Cheung Kiki , Verhamme Katia
Published: August 2022

Objectives

Methylphenidate is a ‘prescription only’ drug against attention disorders which is increasingly used by adults. We investigated whether methylphenidate in adults was associated with an increased risk of psychiatric events such as depression, and suicide attempt and overall mortality.

Design

A population-based matched cohort design.

Setting

The Integrated Primary Care Information system, a general practitioners (GP) database in the Netherlands with a source population of 2.5 million inhabitants.

Participants

During the study period between 1 June 1996 and 1 January 2018, 8905 adults started methylphenidate and were matched to 10 non-users on sex, age, GP practice and ad prescription date. The total study population consisted of 97 198 participants.

Main outcome measures

Serious psychiatric events such as depression and suicide attempts, and overall mortality.

Analyses

Risks of development of each event during the use of methylphenidate were expressed as HR with 95% CI, adjusted for relevant confounders with methylphenidate as a time-dependent determinant. Additional adjustment was performed for the intervention (‘intention-to-treat’).

Results

Although during follow-up, the unadjusted risks of depression and suicide attempt were strongly increased in users, depression and psychosis became non-significant after adjustment for alcohol-abuse and substance-abuse and psychiatric disease in the medical history and after adjustment for ‘intention-to-treat’. However, the risk of suicide attempts remained significantly increased after full adjustment (HR 2.0; 95% CI 1.1 to 3.6), and was highest in women and in participants within the age-group of 18–40 years. The unadjusted risk of overall mortality was strongly increased, but this lowered to a significant 30% risk increase (HR 1.3; 95% CI 1.1 to 1.6) after full adjustment.

Conclusion

There is an increased risk of suicide attempts in adults up to 40 years of age after starting methylphenidate and this risk should be carefully considered before prescribing to this group.
Subjective assessments of research domain criteria constructs in addiction and compulsive disorders: a scoping review protocol
Authors: Ribeiro Ana Paula , Piquet-Pessôa Marcelo , Félix-da-Silva Carina , Mühlbauer Julia Fernandes Eigenheer , de-Salles-Andrade Juliana B , Fontenelle Leonardo F
Published: August 2022

Introduction

Obsessive-compulsive and related disorders (OCRDs) and disorders due to addictive behaviours (DABs) are prevalent conditions that share behavioural and neurobiological characteristics. The Research Domain Criteria lists a series of constructs whose dysfunctions may be present in both groups of disorders. The present study will describe the research protocol of a scoping review of the literature on self-report scales and questionnaires that tap dysfunctional constructs that underlie OCRDs and DABs.

Methods and analysis

This protocol outlines a scoping review on self-report tools and questionnaires that assess OCRDs and DABs-related constructs. The scoping review will select sources in MEDLINE, EMBASE, PsychINFO and Web of Science databases. Inclusion and exclusion criteria will be designed according to the Population, Concept, Context, Types of source framework. Two reviewers will screen independently titles, abstracts and full texts to determine the eligibility of articles. A methodological framework including six stages steps ((1) identifying a research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarising and reporting the result) will be used, and the findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Information extracted will be collated, and quantitative results will be presented using descriptive statistics such as percentages, tables, charts and flow diagrams as appropriate.

Ethics and dissemination

Ethical approval for conducting this scoping review is not required, as this study will involve secondary analysis of existing literature. The researchers will disseminate the study results via conference presentations and publication in a peer-reviewed journal.

Scoping review protocol registration

DOI 10.17605/OSF.IO/UJ7G5.
Pathogenic genetic variants identified in Australian families with paediatric cataract
Authors: Jones Johanna L , McComish Bennet J , Staffieri Sandra E , Souzeau Emmanuelle , Kearns Lisa S , Elder James E , Charlesworth Jac C , Mackey David A , Ruddle Jonathan B , Taranath Deepa , Pater John , Casey Theresa , Craig Jamie E , Burdon Kathryn P
Published: August 2022

Objective

Paediatric (childhood or congenital) cataract is an opacification of the normally clear lens of the eye and has a genetic basis in at least 18% of cases in Australia. This study aimed to replicate clinical gene screening to identify variants likely to be causative of disease in an Australian patient cohort.

Methods and analysis

Sixty-three reported isolated cataract genes were screened for rare coding variants in 37 Australian families using genome sequencing.

Results

Disease-causing variants were confirmed in eight families with variant classification as ‘likely pathogenic’. This included novel variantsPITX3p.(Ter303LeuextTer100),BFSP1p.(Glu375GlyfsTer2), andGJA8p.(Pro189Ser), as well as, previously described variants identified in genesGJA3, GJA8, CRYAA, BFSP1, PITX3, COL4A1andHSF4. Additionally, eight variants of uncertain significance with evidence towards pathogenicity were identified in genes:GJA3, GJA8, LEMD2, PRX, CRYBB1, BFSP2,andMIP.

Conclusion

These findings expand the genotype–phenotype correlations of both pathogenic and benign variation in cataract-associated genes. They further emphasise the need to develop additional evidence such as functional assays and variant classification criteria specific to paediatric cataract genes to improve interpretation of variants and molecular diagnosis in patients.
Self-report of chronic diseases in old-aged individuals: extent of agreement with general practitioner medical records in the German AugUR study
Authors: Steinkirchner Anna B , Zimmermann Martina E , Donhauser Ferdinand J , Dietl Alexander , Brandl Caroline , Koller Michael , Loss Julika , Heid Iris M , Stark Klaus J
Published: August 2022

Background

To estimate prevalence and incidence of diseases through self-reports in observational studies, it is important to understand the accuracy of participant reports. We aimed to quantify the agreement of self-reported and general practitioner-reported diseases in an old-aged population and to identify socio-demographic determinants of agreement.

Methods

This analysis was conducted as part of the AugUR study (n=2449), a prospective population-based cohort study in individuals aged 70–95 years, including 2321 participants with consent to contact physicians. Self-reported chronic diseases of participants were compared with medical data provided by their respective general practitioners (n=589, response rate=25.4%). We derived overall agreement, over-reporting/under-reporting, and Cohen’s kappa and used logistic regression to evaluate the dependency of agreement on participants’ sociodemographic characteristics.

Results

Among the 589 participants (53.1% women), 96.9% reported at least one of the evaluated chronic diseases. Overall agreement was >80% for hypertension, diabetes, myocardial infarction, stroke, cancer, asthma, bronchitis/chronic obstructive pulmonary disease and rheumatoid arthritis, but lower for heart failure, kidney disease and arthrosis. Cohen’s kappa was highest for diabetes and cancer and lowest for heart failure, musculoskeletal, kidney and lung diseases. Sex was the primary determinant of agreement on stroke, kidney disease, cancer and rheumatoid arthritis. Agreement for myocardial infarction and stroke was most compromised by older age and for cancer by lower educational level.

Conclusion

Self-reports may be an effective tool to assess diabetes and cancer in observational studies in the old and very old aged. In contrast, self-reports on heart failure, musculoskeletal, kidney or lung diseases may be substantially imprecise.
Chemical priming of natural killer cells with branched polyethylenimine for cancer immunotherapy
Authors: Choi Seung Hee , Kim Hye Jin , Park Joo Dong , Ko Eun-Su , Lee Minwook , Lee Dae-Keum , Choi Jin-Ho , Jang Hye Jung , Kim Isaac , Jung Hae-Yun , Park Keun-Hong , Park Kyung-Soon
Published: August 2022

Background

Due to their powerful immune surveillance activity and ability to kill and clear cancer cells, natural killer (NK) cells are an emerging anticancer immunotherapeutic agent. Therefore, there is much interest in developing efficient technologies that further enhance the therapeutic antitumor efficacy of NK cells.

Methods

To produce chemically primed NK cells, we screened polymers with various electric charges and examined their ability to enhance the cytotoxicity of NK cells. The effect of primary amine and electric charges of 25 kDa branched polyethylenimine (25KbPEI) was investigated by fluorination of the chemical. The role of 25KbPEI in determining the major priming mechanism was investigated in terms of calcium influx into NK cells. In vivo therapeutic efficacy of chemically primed NK cells was evaluated against solid tumor mouse model of triple negative breast and ovarian cancers.

Results

Chem_NK that was produced by the priming activity of 25KbPEI showed potent antitumor activity to various cancer cells. Chem_NK showed an activated phenotype, which manifests as increased expression of activating/adhesion/chemokine receptors and perforin accumulation, leading to enhanced migration ability and antitumor activity. Chem_NK display potent therapeutic efficacy against in vivo mouse model of triple negative breast and ovarian cancers. Fluorination of the primary amine group reduces the activity of 25KbPEI to prime NK cells, indicating that the cationic charge on the chemical plays a critical role in NK cell activation. A major priming mechanism was 25KbPEI-mediated calcium influx into NK cells, which occurred mainly via the Ca2+-permeable non-selective cation channel transient receptor potential melastatin 2.

Conclusions

NK cells can be chemically primed with 25KbPEI to express potent antitumor activity as well as enhanced migration ability. Because PEI is a biocompatible and Food and Drug Administration-approved chemical for biomedical use, these results suggest a cost-effective and simple method of producing therapeutic NK cells.
Higher- and lower-load resistance exercise training induce load-specific local muscle endurance changes in young women: a randomised trial
Authors: Fliss Matthew D. , Stevenson Jordan , Mardan-Dezfouli Sobhan , Li Donna C.W. , Mitchell Cameron J.
Published: August 2022

The effect of resistance training with higher- and lower-loads on muscle mass and strength has been extensively studied, while changes in muscle endurance have received less attention. This trial aimed to assess the effect of training load on absolute muscle endurance (AME) and relative muscle endurance (RME). Sixteen untrained women (22.7 ± 3.3 yr: mean ± SD) had one arm and leg randomly assigned to train with higher loads (HL; 80–90% 1RM), and the contralateral limbs trained with lower loads (LL; 30–50% 1RM) thrice weekly to volitional fatigue for 10 weeks. Heavy and light load AME and RME, strength, and muscle mass were assessed pre- and post-training. Strength increased more in the HL compared to LL leg ( P < 0.01), but similar increases in strength were observed between upper body conditions ( P = 0.46). Lower body heavy and light load AME improved in both conditions, but HL training induced a larger improvement in heavy load AME (HL: 9.3 ± 4.3 vs. LL: 7.5 ± 7.1 repetitions, time × limb P < 0.01) and LL training induced a larger improvement in light load AME (LL: 24.7 ± 22.2 vs. HL: 15.2 ± 16.7 repetitions, time × limb P = 0.04). In the upper body, HL and LL training induced similar increases in both heavy (time × limb P = 0.99), and light load (time × limb P = 0.16) AME. Dual-energy X-ray absorptiometry showed no change in leg fat-and-bone-free mass (FBFM) for either condition, and an increase in only LL arm FBFM. AME improved in a manner specific to the training loads used. ClinicalTrials.gov (NCT04547972).
The Minmax Regret Reverse 1-Median Problem on Trees with Uncertain Vertex Weights
Authors: Nhan Tran Hoai Ngoc , Nguyen Kien Trung , Nguyen-Thu Huong
Published: August 2022

The classical reverse 1-median problem on trees is to adjust the edge lengths within a budget so as to reduce the 1-median function at a predetermined vertex as much as possible. This paper concerns the corresponding problem with uncertain vertex weights presented by linear functions. Moreover, we use the minmax regret criterion to measure the maximum loss of a feasible solution with respect to the worst-case scenario. The regarding problem is called the minmax regret reverse 1-median problem on trees. We first partition the set of scenarios into parts such that the optimal solution of the corresponding reverse 1-median problem does not change in each part. Then the problem can be reformulated as the minimization of a quadratic number of affine linear functions. We finally develop a greedy algorithm that solves the problem in [Formula: see text] time where n is the number of vertices in the underlying tree.