bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of shale oil production based on Prophet algorithm
Authors: Wan Xiaolong , Zou Yongling , Wang Juan , Wang Weina
Published: August 2021

The large-scale volume fracturing development of shale oil horizontal wells, and the production is affected by seasonal cycle and emergencies, resulting in the complexity of production prediction. Aiming at the problem of poor actual effect or heavy workload of shale oil production prediction by classical reservoir engineering, reservoir numerical simulation and other methods, a new shale oil production prediction method based on Prophet algorithm is proposed It is easier to find the inherent law from a small amount of data. In this paper, we use the production data of production wells in Huanjiang A reservoir in 2015 to predict the production, and compare the prediction results with long-term and short-term memory neural network (LSTM) and ARPS production decline model. The results show that the prediction accuracy of Prophet algorithm is higher, and it is more accurate for the production of complex shale oil.
Disposable enzyme-free glucose biosensor based on H-rGO-Pt@Pd NPs/Au NPs
Authors: Shi Xiaohang , Wang Tong , Wang Bo , Li Guiyin , Liang Jintao
Published: August 2021

In this study, we constructed a H-rGO-Pt@Pd NPs with the characteristics of glucose oxidase. Then, the H-rGO-Pt@Pd NPs and Au NPs was modified on the surface of screen printed electrode to form an enzyme-free glucose biosensor. Among them, H-rGO-Pt@Pd NPs/Au NPs has a strong ability to capture electrons and catalyze the hydrolysis of glucose, resulting in a current-time change. The i-t curve is used to record the current-time change under different glucose concentration. When the glucose concentration was in the range of 0.6-1.4 mg/mL, the sensor current response value (Y) showed a linear relationship with the glucose concentration (X). The linear regression equation was Y=4.8515X-9.9361, the correlation coefficient was 0.9844, and the minimum detection limit was 0.2 mg/mL. In addition, the sensor has good specificity and stability.
Research on On-line Identification of Equivalent Circuit Model Parameters and SOC Estimation for Lithium-ion Batteries
Authors: Feng Juqiang , Si Yuwen , Huang Kaifeng , Lu Jun , Zhang Xing
Published: August 2021

The online identification model parameters can reflect the real terminal voltage state of the battery in real time and provide accurate observation data for battery SOC estimation. BMS is an important part of new energy vehicles, which supervises and controls the working process of the battery. The core of BMS is SOC estimation, and the accuracy of its estimation is related to whether the battery works efficiently and safely. Based on Thevenin model, FFRLS-EKF and KF-EKF were used to estimate the SOC of ternary lithium battery under DST condition. The estimation results show that FFRLS-EKF has a maximum error of 0.0079, which can estimate the SOC of the battery well.
Highly electrically conductive silver-coated poly(p-phenylene terephthalamide) fiber prepared by poly(catechol/polyamine) surface modification
Authors: Hao Mingzheng , Zhou Yang , Tian Zejin , Li Zixuan , Song Wenqiang , Wang Jiazhen , Lyu Chao
Published: August 2021

In this work, poly(p-phenylene terephthalamide)(PPTA) fiber was modified by catechol and tetraethylenepentamine through Michael addition and Schiff base reaction. Then the silver-coated PPTA fiber was prepared by electroless plating. The SEM images showed that the phenolic hydroxyl group of catechol has a strong adhesion effect and a metal binding ability, which can make the silver particles tightly coated on the surface of PPTA fiber. The XPS and XRD results indicate that the Ag on the surface of the PPTA fiber is elemental silver, and there is no diffraction peaks of silver halide and silver oxide. The resistivity of the silver-coated PPTA fiber prepared with the deposition time of 2h has reached 0.1m^cm. This highly conductive PPTA/Ag fiber can be used in the field of flexible conductive materials and electromagnetic shielding clothing.
Age Differences in Multimodal Quantitative Sensory Testing and Associations With Brain Volume
Authors: Johnson Alisa J , Wilson Abigail T , Laffitte Nodarse Chavier , Montesino-Goicolea Soamy , Valdes-Hernandez Pedro A , Somerville Jessie , Peraza Julio A , Fillingim Roger B , Bialosky Joel , Cruz-Almeida Yenisel
Published: August 2021

Background and Objectives

Somatosensory function is critical for successful aging. Prior studies have shown declines in somatosensory function with age; however, this may be affected by testing site, modality, and biobehavioral factors. While somatosensory function declines are associated with peripheral nervous system degradation, little is known regarding correlates with the central nervous system and brain structure in particular. The objectives of this study were to examine age-related declines in somatosensory function using innocuous and noxious stimuli, across 2 anatomical testing sites, with considerations for affect and cognitive function, and associations between somatosensory function and brain structure in older adults.

Research Design and Methods

A cross-sectional analysis included 84 “younger” (n = 22, age range: 19–24 years) and “older” (n = 62, age range: 60–94 years) healthy adults who participated in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study. Participants were assessed on measures of somatosensory function (quantitative sensory testing), at 2 sites (metatarsal and thenar) using standardized procedures, and completed cognitive and psychological function measures and structural magnetic resonance imaging.

Results

Significant age × test site interaction effects were observed for warmth detection (p = .018, ηp2= 0.10) and heat pain thresholds (p = .014, ηp2= 0.12). Main age effects were observed for mechanical, vibratory, cold, and warmth detection thresholds (ps < .05), with older adults displaying a loss of sensory function. Significant associations between somatosensory function and brain gray matter structure emerged in the right occipital region, the right temporal region, and the left pericallosum.

Discussion and Implications

Our findings indicate healthy older adults display alterations in sensory responses to innocuous and noxious stimuli compared to younger adults and, furthermore, these alterations are uniquely affected by anatomical site. These findings suggest a nonuniform decline in somatosensation in older adults, which may represent peripheral and central nervous system alterations part of aging processes.
Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn’s Disease: The OPERA II Study
Authors: D’Haens Geert R , Reinisch Walter , Lee Scott D , Tarabar Dino , Louis Edouard , Kłopocka Maria , Klaus Jochen , Schreiber Stefan , Il Park Dong , Hébuterne Xavier , Nagy Peter , Cataldi Fabio , Martin Steven W , Nayak Satyaprakash , Banerjee Anindita , Gorelick Kenneth J , Sandborn William J
Published: August 2021

Background

Patients with Crohn’s disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD.

Methods

Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0–72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator’s discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods.

Results

Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn’s Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually.

Conclusions

Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks.

ClinicalTrials.gov ID: NCT01298492.
CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69–Myl9 system
Authors: Nakayama Toshinori , Hirahara Kiyoshi , Kimura Motoko Y , Iwamura Chiaki , Kiuchi Masahiro , Kokubo Kota , Onodera Atsushi , Hashimoto Kahoko , Motohashi Shinichiro
Published: August 2021

CD4+ T cells not only direct immune responses against infectious micro-organisms but are also involved in the pathogenesis of inflammatory diseases. In the last two to three decades, various researchers have identified and characterized several functional CD4+ T-cell subsets, including T-helper 1 (Th1), Th2, Th9 and Th17 cells and regulatory T (Treg) cells. In this mini-review, we introduce the concept of pathogenic Th cells that induce inflammatory diseases with a model of disease induction by a population of pathogenic Th cells: the ‘pathogenic Th population disease-induction model’. We will focus on Th2 cells that induce allergic airway inflammation—pathogenic Th2 cells (Tpath2 cells)—and discuss the nature of Tpath2 cells that shape the pathology of chronic inflammatory diseases. Various Tpath2-cell subsets have been identified and their unique features are summarized in mouse and human systems. Second, we will discuss how Th cells migrate and are maintained in chronic inflammatory lesions. We propose a model known as the ‘CD69–Myl9 system’. CD69 is a cell surface molecule expressed on activated T cells and interaction with its ligand myosin light chain 9 (Myl9) is required for the induction of inflammatory diseases. Myl9 molecules in the small vessels of inflamed lungs may play a crucial role in the migration of activated T cells into inflammatory lesions. Emerging evidence may provide new insight into the pathogenesis of chronic inflammatory diseases and contribute to the development of new therapeutic strategies for intractable inflammatory disorders.
Impact of four fiber-rich supplements on nutrient digestibility, colostrum production, and farrowing performance in sows
Authors: Feyera Takele , Hu Liang , Eskildsen Maria , Bruun Thomas S , Theil Peter K
Published: August 2021

This study aimed to investigate the impact of dietary fiber (DF) sources on sow and litter performance, and apparent total tract digestibility (ATTD) of gross energy (GE) and nutrients. A total of 48 sows were stratified for body weight at mating and randomly assigned to one of four DF sources (mixed fiber [MF], palm kernel expellers [PKE], sugar beet pulp [SBP], or soy hulls [SH]) and fed the diet from mating until farrowing. Within DF treatments, sows were supplemented with one of two extra energy sources (glycerol or sugar dissolved in water), whereas a third group (control) received water from day 108 of gestation until farrowing. The number of total born, live-born, and stillborn pigs; birth time and birth weight of the pigs; farrowing duration; and farrowing assistance (FA) were recorded. Live-born pigs were weighed again at 12 and 24 h after birth to record weight gain, which was used to estimate intake and yield of colostrum. Blood samples were collected once daily from day −3 relative to farrowing until day 1 after farrowing in sows and once from selected pigs right after birth. Fecal samples were collected on day 114 of gestation and colostrum at 0, 12, 24, and 36 h after onset of farrowing. Intake of soluble and insoluble nonstarch polysaccharides (NSP) was greater for SBP (P < 0.001) and PKE (P < 0.001) supplemented sows, respectively, when compared with other groups. Farrowing duration and stillbirth rate were not affected by DF sources, but PKE and SH supplemented sows had greater FA than SBP and MF supplemented sows (P < 0.001). Extra energy supplement did not improve the farrowing performance. Concentration (P = 0.02) and output (P = 0.04) of dry matter in colostrum, and ATTD of GE (P < 0.001) and crude protein (CP; P < 0.001) were lower for PKE supplemented sows than in sows from the remaining groups. Intake of insoluble NSP correlated negatively with ATTD of GE (P < 0.001) and CP (P < 0.001). Concentrations of glucose (P < 0.001), lactate (P < 0.001), CO2 (P < 0.001), and HCO3 (P < 0.001) in sows blood were increased with time progress relative to farrowing. Newborn pigs from PKE supplemented sows had greater concentration of lactate (P = 0.02) and lower blood pH (P = 0.02) than the remaining treatments. In conclusion, PKE supplement reduced ATTD of GE and CP, and concentration and output of dry matter in colostrum but increased FA. Results of this experiment indicated that the use of PKE as a fiber source for late gestating sows should be avoided.
Association of Female Genital Schistosomiasis With the Cervicovaginal Microbiota and Sexually Transmitted Infections in Zambian Women
Authors: Sturt Amy S , Webb Emily L , Himschoot Lisa , Phiri Comfort R , Mapani Joyce , Mudenda Maina , Kjetland Eyrun F , Mweene Tobias , Levecke Bruno , van Dam Govert J , Corstjens Paul L A M , Ayles Helen , Hayes Richard J , van Lieshout Lisette , Hansingo Isaiah , Francis Suzanna C , Cools Piet , Bustinduy Amaya L
Published: August 2021

Background

The cervicovaginal microbiota, including sexually transmitted infections (STIs), have not been well described in female genital schistosomiasis (FGS).

Methods

Women (aged 18–31, sexually active, nonpregnant) were invited to participate at the final follow-up of the HPTN 071 (PopART) Population Cohort in January–August 2018. We measured key species of the cervicovaginal microbiota (Lactobacillus crispatus, L. iners, Gardnerella vaginalis, Atopobium vaginae, and Candida) and STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) using quantitative PCR (qPCR). We evaluated associations of the microbiota and STI presence and concentration with FGS (qPCR-detected Schistosoma DNA in any of 3 genital specimens).

Results

The presence and concentration of key cervicovaginal species did not differ between participants with (n = 30) or without FGS (n = 158). A higher proportion of participants with FGS had T. vaginalis compared with FGS-negative women (P = .08), with further analysis showing that T. vaginalis was more prevalent among women with ≥2 Schistosoma qPCR-positive genital specimens (50.0%, 8/16) than among FGS-negative women (21.5%, 34/158; P = .01).

Conclusions

We found weak evidence of an association between the presence of T. vaginalis and FGS, with a stronger association in women with a higher-burden FGS infection. Additional research is needed on potential between-parasite interactions, especially regarding HIV-1 vulnerability.
The Clinical Pause: An Augmented Approach to Simulation Debriefing in Nursing Education
Authors: Kacalek Cathy , Krautscheid Lorretta , Walkley Vanessa
Published: August 2021

Debriefing after simulation, a form of reflection-on-action, is widely practiced in nursing education. A lesser used alternative is a faculty-facilitated clinical pause. During natural breaks within an unfolding simulation scenario, faculty incorporated Caputi’s thinking skills to facilitate clinical reasoning, reflection-in-action, and timely feedback. The clinical pause enabled well-timed validation of correct thinking, resolution of erroneous thinking, and deliberate practice opportunities to construct contextual meaning. Written student comments, obtained after the simulation, suggest the clinical pause teaching innovation enhanced learning and clinical reasoning. Combining the clinical pause with end-of-simulation debriefing can provide a powerful one-two punch that maximizes clinical judgment.
Update on omalizumab in allergen immunotherapy
Authors: Dantzer Jennifer A. , Wood Robert A.
Published: August 2021

Purpose of review

To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy.

Recent findings

Omalizumab has been used in combination with inhalant, venom, and food allergen immunotherapy. These studies suggest that omalizumab can decrease the time required to reach maintenance dosing and adverse events. However, severe adverse events do still occur. Limited long-term data suggests that there is a risk for increased reactivity after stopping omalizumab.

Omalizumab in conjunction with immunotherapy has shown promising results for the treatment of allergic rhinitis, venom hypersensitivity, and food allergy, especially in the reduction of adverse events. Larger randomized, placebo-controlled trials are needed to better understand optimal dosing and duration, cost-–benefit analysis, ideal patients, and long-term benefits. This combination therapy has the potential to improve treatment, particularly for high–risk patients.
Transcranial direct current and transcranial magnetic stimulations for chronic pain
Authors: Sorkpor Setor K. , Ahn Hyochol
Published: August 2021

Purpose of review

Chronic pain is debilitating and difficult to treat with pharmacotherapeutics alone. Consequently, exploring alternative treatment methods for chronic pain is essential. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are increasingly being investigated for their neuropharmacological effects in the treatment of chronic pain. This review aims to examine and evaluate the present state of evidence regarding the use of tDCS and TMS in the treatment of chronic pain.

Recent findings

Despite conflicting evidence in the early literature, evidence from recent rigorous research supports the use of tDCS and TMS in treating chronic pain conditions. For both tDCS and TMS, standardized stimulation parameters have been identified with the recommendation for repeated maintenance stimulation to ensure that the analgesic effect is sustained beyond discontinuation of therapy.

Due to a lack of defined stimulation protocols, early findings on the efficacy of tDCS and TMS are mixed. Although the application of tDCS and TMS as pain relief approaches is still in its early stages, the introduction of standardized stimulation protocols is paving the way for more robust and informed research.
The Prospective Prognostic Value of Biopsychosocial Indices of Sensitivity to Physical Activity Among People With Back Pain
Authors: Woznowski-Vu Arthur , Aternali Andrea , Gervais Alexandre , Pavilanis Antonina D.S. , Nijs Jo , Sullivan Michael J.L. , Wideman Timothy H.
Published: August 2021

Objectives:

Many people living with musculoskeletal pain conditions experience a range of negative biopsychosocial responses to physical activity, referred to as increased sensitivity to physical activity (SPA), that may undermine successful rehabilitation. This exploratory study aims to provide the first prospective analysis of the potential prognostic value of 3 biopsychosocial indices of SPA in relation to rehabilitation outcomes. This study also aimed to shed light on the cross-sectional interrelationships between these 3 biopsychosocial indices of SPA.

Materials and Methods:

Adults with back pain were evaluated upon starting physical therapy and then again 3 months later. The initial testing session consisted of self-reported pain-related questionnaires and assessment of activity-related changes in pressure pain thresholds (SPA-Sensory), pain intensity ratings (SPA-Pain), and situational catastrophizing (SPA-Psych). The 3-month follow-up consisted of self-reported disability and pain questionnaires. Correlational and hierarchical linear regression analyses were conducted.

Results:

A total of 97 participants completed both the initial visit and 3-month follow-up. The SPA-Pain index and the SPA-Psych index were significantly intercorrelated, but neither were correlated with the SPA-Sensory index. The SPA-Sensory index was not correlated with outcomes. The SPA-Pain index was correlated only with cross-sectional disability and pain outcomes. The SPA-Psych index was the only SPA index significantly correlated with outcomes both cross-sectionally and at 3-month follow-up. After controlling for baseline pain/disability and pain catastrophizing, SPA-Psych was no longer a significant prognostic factor for pain, but remained a significant prognostic factor for disability at 3-month follow-up (β=0.272, t=2.674, P=0.008, R
2 Δ=5.60%).

Discussion:

This study highlights the importance of conceptualizing and measuring SPA as a biopsychosocial (rather than unidimensional) construct and points toward the added prognostic value of this construct. Implications for future research and practice are discussed.
Risk and Resilience Predictors of Recovery After Spinal Fusion Surgery in Adolescents
Authors: Beeckman Melanie , Hughes Sean , Van der Kaap-Deeder Jolene , Plasschaert Frank , Michielsen Jozef , Moens Pierre , Schelfaut Sebastiaan , Goubert Liesbet
Published: August 2021

Objective:

This prospective study examined risk and resilience predictors of pain and functional recovery in the first 6 months after spinal fusion surgery in adolescents.

Methods:

Adolescents with adolescent idiopathic scoliosis undergoing spinal fusion surgery (n=100, aged 12 to 18 y, 77% girls) completed assessments before surgery and at 3 weeks, 6 weeks, and 6 months after surgery. Recovery trajectories in pain, health-related quality of life (HRQOL), and objectively registered physical activity were identified. Presurgical pain catastrophizing and pain intensity (risk), and psychological flexibility, and postsurgical pain acceptance (resilience) were examined as predictors of recovery.

Results:

Latent growth class analyses revealed 4 distinct pain recovery trajectories (ie, Severe-Moderate [11%, n=9], Mild-No [58%, n=49], Moderate-Mild [24%, n=20], and Moderate-Severe [7%, n=6] pain trajectory), 2 HRQOL recovery trajectories; 2 trajectories characterizing recovery in average daily physical activity at moderate-to-vigorous intensity (MVPA); and 3 trajectories characterizing recovery in total physical activity volume characterized by the average daily number of steps. Subsequent multivariate analyses of variance revealed that presurgical pain intensity (partial η2=0.21, P<0.001) and pain catastrophizing (partial η2=0.13, P<0.01) were both predictive of poorer recovery in HRQOL, and pain catastrophizing additionally predicted poorer pain recovery (partial η2=0.15, P<0.05). Psychological flexibility (partial η2=0.25, P<0.001) and postsurgical pain acceptance (partial η2=0.07, P<0.05) were predictive of more favorable recovery trajectories in HRQOL, and psychological flexibility additionally predicted more favorable recovery trajectories in postsurgical pain (partial η2=0.15, P<0.05). Daily MVPA trajectories were not significantly predicted by any of the hypothesized factors, while presurgical pain catastrophizing levels were predictive of a delayed recovery trajectory in the daily amount of steps (partial η2=0.17 P<0.01).

Conclusions:

Presurgical screening could include assessment of pain intensity, pain catastrophizing, psychological flexibility, and pain acceptance to identify adolescents who are at risk for poorer recovery. These are potentially modifiable factors that can be targeted in presurgical interventions to prevent poor and foster adaptive outcomes after major surgery in adolescents.
Quality of Life Related to Functional Disability in Migraine Patients
Authors: Soni Prashant , Chawla Evanka
Published: August 2021

Objective:

The aim of this study was to conduct a systematic review and network meta-analysis of all randomized trials investigating effect of anti-calcitonin gene-related peptide monoclonal antibodies on disability related to migraine in adult patients.

Materials and Methods:

Medline, Embase, and Cochrane Central Register of Controlled Trials searched from inception to July 2020 with an additional review of clinical trial registries. Disability evaluated using change in patient reported Migraine Disability Assessment scores from baseline were considered for the final analysis. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects.

Results:

Overall 41 studies (7095 migraineurs in 9 randomized trials) were included with treatment course of at least 12 weeks. Subcutaneous injections of fremanezumab 675+225+225 mg QM and 225+225+225 mg QM were more effective in reducing disability in chronic and episodic migraine patients, respectively, with higher median difference in Migraine Disability Assessment score from baseline compared with other treatments including erenumab (70 mg QM; 140 mg QM), galcanezumab (120 mg QM; 240 mg QM), and low doses of fremanezumab (225 mg single dose; 675 mg single dose).

Discussion:

For short-term prevention of migraine, fremanezumab demonstrated slightly better improvement in disability compared with other anti-calcitonin gene-related peptide monoclonal antibodies in adult patients with migraine.
Preliminary Validation of the Pain Burden Inventory in a Pediatric Chronic Pain Population
Authors: Santos Melissa , Santanelli James P. , Zempsky William T.
Published: August 2021

Objective:

To determine the preliminary reliability and validity of the Pain Burden Inventory-Youth (PBI-Y), a 7-item measure of the impact of chronic pain in adolescents with chronic pain that was, initially validated in youth with sickle cell disease.

Materials and Methods:

A retrospective chart review of 130 patients presenting to an interdisciplinary pain clinic were examined with 98 (mean age=14.49; 66% female) comprising the final sample. Demographic information as well as adolescent and parent self-reported measures were examined.

Results:

Youth reported a variety of pains including abdominal pain, headaches, back pain, and amplified musculoskeletal pain. The PBI-Y demonstrated strong internal reliability (α=0.792) and strong cross-informant concordance (r=0.822; P=0.000). Good construct validity was seen where higher scores on the PBI-Y were correlated with higher scores of (1) functional disability (r=0.689; P=0.000), (2) pain catastrophizing (r=0.494; P=0.000), (3) pain frequency days (r=0.526; P=0.000), (4) usual pain intensity (r=0.467; P=0.000), and (5) the worst pain intensity (r=0.485; P=0.000). Similar results were seen with caregiver assessments. Neither caregiver nor youth reports differed based on the sex or age of the child.

Discussion:

The results support the psychometric properties of a brief self-report measure of pain impact in a pediatric chronic pain population. This measure may have great utility for clinicians caring for youth with chronic pain.
Raynaud's phenomenon and digital ulcers: advances in evaluation and management
Authors: Herrick Ariane L.
Published: August 2021

Purpose of review

The aim of this review is to give an update on advances in evaluation and management of systemic sclerosis (SSc)-related Raynaud's phenomenon and digital ulceration, focusing on reports from the last 18 months. The increasing recognition of the huge impact of Raynaud's phenomenon and of digital ulceration on the everyday lives of patients with SSc has sparked enthusiasm internationally to develop better outcome measures and better treatments, and so a review is timely.

Recent findings

There have been recent advances in the development of patient reported outcome instruments [e.g. the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) instrument] and also in noninvasive imaging techniques, including thermography and laser Doppler methods. Improved outcome measures will facilitate future clinical trials, both early phase proof-of-concept and later phase trials. New insights have been gained into mechanisms of action and methods of administration of ‘conventional’ therapies, for example phosphodiesterase inhibitors and intravenous prostanoids. New treatment approaches are being investigated, including topical and procedural therapies.

Clinicians can look forward to seeing these advances translating into clinical benefit over the next 5 years. To help ensure this, they should strive whenever possible to recruit patients with SSc-related digital vasculopathy into observational studies and clinical trials.
Use of Digital Tomosynthesis in Assessing Accurate Medial Epicondyle Fracture Displacement as Compared With Conventional Radiography and Computed Tomography
Authors: Livingston Kristin S. , Edwards Emily A. , Griffin Michael , MacKenzie John D. , Zapala Matthew A.
Published: August 2021

Introduction:

Medial epicondyle fracture displacement is notoriously difficult to determine on conventional radiography, and follow-up computed tomography (CT) is often obtained to measure precise displacement. Another option for fracture characterization is digital tomosynthesis (DT), a technology providing high in-plane resolution of bony anatomy by acquiring multiple low-dose images in a linear arc. Advantages of DT include lower radiation exposure and lower cost than CT, rapid image acquisition, and a similar patient experience to conventional radiography. The digital application of tomosynthesis is relatively new and is integrated as an add-on feature with modern radiography equipment. This study compares DT, CT and conventional radiography for measurement accuracy in medial epicondyle fractures with the goal of determining relative accuracy in measuring medial epicondyle fracture displacement.

Methods:

Medial epicondyle fractures were created in 5 cadaveric elbow specimens. Each specimen was imaged with conventional radiography, DT, and CT. True displacement measured by digital calipers was compared with “measured” displacement for each image acquisition. CT images included axial, sagittal, and coronal reformats. DT images of the elbow included anteroposterior (AP) longitudinal and transverse, lateral longitudinal and transverse, and axial longitudinal and transverse. Conventional radiographs included AP, lateral, and axial distal humerus images. Four physicians reviewed all images 3 months later. Each reviewer independently measured maximum apparent fracture displacement to the nearest 0.1 mm. Measurement accuracy was calculated as percent difference [(measured displacement−actual displacement)/actual displacement] for each acquisition. Mean, median, and SD for measurement accuracy were calculated. Two-tailed paired t tests were performed on each acquisition to compare the measurement accuracy.

Results:

Compared with conventional radiographs, accuracy of DT was superior in AP longitudinal (P=0.03), AP transverse (P=0.01), axial longitudinal (P=0.0001), and axial transverse projections (P=0.001). Accuracy of CT was superior to conventional radiography in the AP projection (P=0.03), but was equivalent in the axial projection (P=0.9). Accuracy of CT was similar to DT in AP longitudinal (P=0.6), AP transverse (P=0.5), and axial longitudinal projections (P=0.07). Accuracy of DT in the axial transverse projection was superior to CT (P=0.03).

Conclusion:

DT is more accurate than conventional radiography (both AP and axial views) and as accurate as CT in assessing millimeters of displacement of medial epicondyle fracture fragments.

Level of Evidence:

Level IV—diagnostic study.
Too Loud for Comfort: A Simulated Evaluation of Cast Saw Noise
Authors: Shaw K. Aaron , Bailey Virginia , O’Brien Fred
Published: August 2021

Background:

Orthopaedic cast saws are an integral component to a pediatric orthopaedic practice but can also be associated with patient anxiety and noise exposure for patient. Although previous studies have deemed the noise generation from orthopaedic cast saws to be within safe occupational exposure levels, no study to date has compared the noise generation from a cast saw used in various exam room settings.

Methods:

A simulated fiberglass cast model was used. Noise generation was assessed using calibrated sound level meters with measurements performed at 18 inches, 36 inches, and 6 ft measured from the cast saw. Measurements were performed in 1 of 2 clinical settings: (1) an open bay setting and (2) an enclosed exam room. In the enclosed exam room, the 6-foot measurement was performed behind the closed exam door. An orthopaedic cast saw with built-in vacuum was used to continuously cut the fiberglass model for 1 minute with measurements of peak and mean sound generation, recorded in decibels (dB), a logarithmic scale. Three measurements were recorded at each distance. Between group comparisons were performed with statistical significance set at P=0.05.

Results:

Baseline sound levels were similar between cohorts with progressive decreases in mean sound with increasing distance from the saw. Mean sound levels were significantly higher in the enclosed room setting at 18 inches (92.8 dB, 95% confidence interval (CI): 91.72-93.88 vs. 90.6 dB, 95% CI: 89.91-91.29; P=0.043] and 36 inches (90.3 dB, 95% CI: 89.9-90.7 vs. 86.0 dB, 95% CI: 85.18-86.82; P=0.017). At 6-ft distance, however, the enclosed room demonstrated a 13.8-fold sound reduction compared with the open bay (72.0 dB, 95% CI: 71.59-72.4 vs. 83.4 dB, 83.14-83.72; P<0.001).

Conclusion:

By closing the exam door, a 13-fold reduction in noise exposure can be achieved for adjacent patients and personnel. Consideration should be given for using orthopaedic cast saws in an enclosed exam room to prevent unnecessary noise exposure with hearing protection of cast saw operators and treated patients.

Clinical Relevance:

Orthopaedic cast removal.
Core Decompression and Bone Marrow Aspirate Concentrate in the Treatment of Femoral Head Avascular Necrosis in Pediatric Sickle Cell Disease: Can We Improve Natural History?
Authors: Griffith Matthew S. , Shaw Kenneth A. , Hattaway Joshua K. , Schrader Timothy
Published: August 2021

Introduction:

Femoral head avascular necrosis (AVN) affects between 10% and 41% of children with sickle cell disease (SCD), resulting in the development of proximal femoral deformity and residual hip pain in the majority of patients without treatment. There have been multiple adult studies published on the outcomes of core decompression with and without the use of bone marrow aspirate concentrate (BMAC) injection both in idiopathic and SCD-related AVN with promising results, however, few studies have reported on outcomes in skeletally immature patients.

Purpose:

This study sought to report on a single surgeon’s outcomes for core decompression with BMAC injection in pediatric patients with AVN of the femoral head secondary to underlying SCD.

Methods:

A single-center, retrospective review was performed for pediatric patients undergoing core decompression with BMAC injection for femoral head AVN in patients with SCD with a minimum of 12-month follow-up. Demographic, radiographic, and clinical variable were collected. Patients were subdivided based upon presence of open femoral physes at the time of surgery. Successful treatment was defined as the ability to return to activities without limitations.

Results:

A total of 13 patients (average age 14.1±2.8 y, 84.6% male, 6 skeletally immature and 7 skeletally mature) with 18 affected extremities were identified. Open physes were present in 50% of operative extremities. Skeletally immature patient demonstrated reconstitution of the femoral head in 78% of cases and 89% demonstrated regression of at least 1 Steinberg grade and none had progression. Skeletally immature patients were significantly more likely to return to activities (100% vs. 55.6%, P=0.023) and achieve a final Tonnis grade <2 (89% vs. 44%, P=0.046).

Conclusion:

Core decompression appears to alter the natural history of AVN in skeletally immature patients with SCD. Skeletal immaturity was a positive prognostic factor for the ability to return to activities without pain and achieve a lower Tonnis grade at final follow-up.
VALD-3 inhibits proliferation and induces apoptosis of colorectal cancer cells via upregulating tumor suppressor activity of p53 to inhibit Wnt/β-catenin signal pathway
Authors: Li Hongling , Meng Yuna , Ma Shuping , Dang Chunyan , Xue Li
Published: August 2021

Colorectal cancer is the third most common malignant tumor and a leading cause of cancer death. Currently lacks effective therapies available to improve the prognosis. In the present study, VALD-3, an important Schiff base ligand from o-vanillin derivatives was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The effect of VALD-3 on colorectal cancer cells proliferation was assessed using MTT assay and the cell migration was evaluated using wound healing scratch assay. The appearance of apoptotic colorectal cancer cells was detected by flowcytometry analysis. Morphological changes caused by VALD-3 induced apoptosis were also observed by Hoechst 33258 staining. The flow cytometry assay was also used to measure cell cycle arrest. The expression levels of TP53 and Bad were analyzed using quantitative real-time PCR. Protein expression of P53, Wnt/β-catenin signaling pathway proteins, apoptosis proteins and cell cycle-related protein were viewed by Western blotting. In addition, HT-29 cells xenograft tumor model was used for the study in vivo. Immunohistochemistry (IHC) staining was employed to detect the P53 protein expression. The results showed that VALD-3 obviously inhibited the proliferation and migration for colorectal cancer cells. In addition, flow cytometry analysis demonstrated that VALD-3 markedly increased early and late apoptosis on colorectal cancer cells, respectively. VALD-3 induced cell cycle arrest at the G0/G1 phase. Most importantly, tumor growth in HT-29 xenograft mice was suppressed by VALD-3, but no significant change in body weight. As confirmed by IHC staining from tumor tissue, the P53 proteins expression increased. These results suggested that VALD-3 represses cell proliferation and induces apoptosis associated with upregulating tumor suppressor activity of p53 to inhibit Wnt/β-catenin signal pathway, and it is a potential anticancer agent for colorectal cancer.
Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1
Authors: He Xiaoqiong , Yao Qian , Hall Duane D , Song Zhongyu , Fan Dan , You Yutong , Lian Wenjing , Zhou Zhangping , Duan Ling , Chen Biyi
Published: August 2021

One cost-effective way for identifying novel cancer therapeutics is in the repositioning of available drugs for which current therapies are inadequate. Levofloxacin prevents DNA duplication in bacteria by inhibiting the activity of DNA helicase. As eukaryotic cells have similar intracellular biologic characteristics as prokaryotic cells, we speculate that antibiotics inhibiting DNA duplication in bacteria may also affect the survival of cancer cells. Here we report that levofloxacin significantly inhibited the proliferation and clone formation of cancer cells and xenograft tumor growth through cell cycle arrest at G2/M and by enhancing apoptosis. Levofloxacin significantly altered gene expression in a direction favoring anticancer activity. THBS1 and LAPTM5 were dose-dependently upregulated whereas SRD5A3, MFAP5 and P4HA1 were downregulated. Pathway analysis revealed that levofloxacin significantly regulated canonical oncogenic pathways. Specific network enrichment included a MAPK/apoptosis/cytokine–cytokine receptor interaction pathway network that associates with cell growth, differentiation, cell death, angiogenesis and development and repair processes and a bladder cancer/P53 signaling pathway network mediating the inhibition of angiogenesis and metastasis. THBS1 overlapped in 16 of the 22 enriched apoptotic pathways and the 2 pathways in the bladder cancer/P53 signaling pathway network. P4HA1 enriched in 7 of the top 10 molecular functions regulated by differential downregulated genes. Our results indicate that levofloxacin has broad-spectrum anticancer activity with the potential to benefit cancer patients already treated or requiring prophylaxis for an infectious syndrome. The efficacy we find with levofloxacin may provide insight into the discovery and the design of novel less toxic anticancer drugs.
Asynchrony of primary tumor and mediastinal lymph nodes response after neoadjuvant immunotherapy plus chemotherapy in a patient with stage IIIA non–small-cell lung cancer: a case report
Authors: Liu Yunpeng , Gao Zhiru , Zhang Chengbin , Liu Xing , Liu Zihao , Lin Xingyu , Qian Benxin , Jin Fukang , Shao Guoguang , Yang Zhiguang
Published: August 2021

With the rapid development of immunotherapy, the efficacy and feasibility of neoadjuvant immunotherapy for early resectable non–small-cell lung cancer (NSCLC) has been demonstrated. However, there are still difficulties and controversies in evaluating the efficacy of neoadjuvant immunotherapy. In our report, we described a 43-year-old female patient who was diagnosed with stage IIIA (cT1N2M0) pulmonary adenocarcinoma. After two cycles of neoadjuvant immunotherapy (sintilimab) combined with chemotherapy, according to imaging evaluation, the efficacy of the primary lesion was evaluated as stable disease and the mediastinal lymph nodes were evaluated as partial response. However, the postoperative pathological evaluation showed the primary lesion was pathological complete response and the mediastinal lymph nodes were major pathological response. This indicated that neoadjuvant chemo-immunotherapy was effective for both primary and mediastinal lymph nodes, but regression of the lesions was not synchronous. This study provided a complete process of neoadjuvant treatment, illustrating the effectiveness and safety of neoadjuvant chemo-immunotherapy to a certain extent. It is also suggested that the evaluation of neoadjuvant immunotherapy should be combined with imaging and pathology, and the primary tumor and lymph nodes should be evaluated, respectively.
Anticancer properties of novel zinc oxide quantum dot nanoparticles against breast cancer stem-like cells
Authors: Fakhroueian Zahra , Rajabi Sadegh , Salehi Niloufar , Tavirani Mostafa Rezaei , Noori Shokoofe , Nourbakhsh Mitra
Published: August 2021

Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, β-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity.
Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma
Authors: He Wei , Zhu Xingyang , Tang Xueyan , Xiang Xianhui , Yu Jian , Sun Huirong
Published: August 2021

Hepatitis B virus (HBV) infection is the main trigger of hepatocellular carcinoma (HCC). Circular RNA plays an indispensable role in cancer development, and this study aimed to disclose the function and mechanism of circ_0027089 in HBV-related HCC. The expression levels of circ_0027089, miR-136-5p and nucleus accumbens associated protein 1 (NACC1) mRNA were measured by quantitative real-time PCR, and the protein level of NACC1 was detected by western blot. For functional analyses, cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry assay, and cell apoptosis was also assessed by caspase 3/7 activity. The capacities of migration and invasion were evaluated by wound healing assay and transwell assay, respectively. The predicted relationship between miR-136-5p and circ_0027089 or NACC1 was validated by dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay. Animal experiments were performed in nude mice to explore the role of circ_0027089 in vivo. Circ_0027089 expression and NACC1 expression were elevated, while miR-136-5p expression was decreased in HBV-related HCC tissues and cells. In function, circ_0027089 knockdown inhibited HepG2.2.15 and HepAD38 (tet-off) cell proliferation, migration and invasion but induced cell cycle arrest and apoptosis, while circ_0027089 overexpression played the reversed effects. For mechanism exploration, miR-136-5p was a target of circ_0027089, and miR-136-5p deficiency could reverse the role of circ_0027089 knockdown. Circ_0027089 functioned as an oncogene to promote the development of HBV-related HCC by regulating NACC1 via competitively targeting miR-136-5p.
Refractory hypokalemia caused by cetuximab with advanced colorectal cancer patients: the case series and literature review
Authors: Chen Yun-Wang , Yang Min , Wang Ming-Xing , Jiang Jia-Hong , Jiang Ding-Yi , Chen Zhe-Ling , Yang Liu
Published: August 2021

Cetuximab is the first-line treatment for advanced metastatic colon cancer. But cetuximab can cause electrolyte disturbances, including hypomagnesemia and hypokalemia. Among them, hypokalemia is often caused by hypomagnesemia, not directly caused by cetuximab. This article reports two cases of refractory hypokalemia caused by cetuximab without hypomagnesemia. The two patients had no abnormalities in serum potassium before cetuximab treatment. The occurrence of hypokalemia was clearly correlated with the cetuximab, and they were significantly improved after stopping or reducing the dose. At the same time, the appearance of hypokalemia is significantly related to the efficacy of cetuximab. They have received 37 and 35 cycles of cetuximab-related therapy, with condition stable periods of 12.8 and 15.1 months, respectively. Obviously, our report refutes the above view. In our opinion, hypokalemia, a side effect of cetuximab, may be directly caused by it, rather than secondary to hypomagnesemia. Similar to hypomagnesemia, the appearance of hypokalemia often indicates a better curative effect of cetuximab.