bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel natural inhibitors targeting KRAS G12C by computational study
Authors: Jiang Yuting , Chen Wanting , Wang Xinhui , Zhou Baolin , Xie Haoqun , Hou Yuanyuan , Guo Zhen , Yu Bo , Zhong Sheng , Su Xing
Published: August 2022

Ideal leading and nominee compounds with inhibiting effects on KRAS G12C were selected from the ZINC database, laying a cornerstone for the progress of anticancer drugs. A variety of computational virtual screening methods were utilized to screen possible inhibitors of KRAS G12C. LibDock was utilized to estimate 17 930 compounds and the top 20 were nominated for additional study, which was absorption, distribution, metabolism, and excretion and harmfulness prediction. Molecule docking was employed to prove the binding connection between certain ligands and KRAS G12C. Natural novel compounds ZINC000012494057 and ZINC000003789195 were selected to bind stably with KRAS G12C. In addition, they had lower scores in Ames mutagenicity, rodent carcinogenicity, cytochrome P450 2D6(CYP2D6) tolerance, and non-developmental toxicity potential. Molecular dynamic simulations demonstrate that the combination of ZINC000012494057 and ZINC000003789195 with KRAS G12C has more favorable potential energy, which provides conditions for their stable existence in the natural environment. Natural compounds ZINC000012494057 and ZINC000003789195 were identified as KRAS G12C potential inhibitors. These two compounds have been verified to have enormous importance for the progress of anticancer medicines.
Serial Circulating Tumor DNA in Monitoring the Effect of Neoadjuvant and Adjuvant Immunotherapy in Patients With Colon Cancer: Case Series and Review of the Literature
Authors: Qin Qiyuan , Yang Keli , Ma Tenghui , Wang Huaiming , Yu Pengli , Yuan Mingming , Chen Yuefang , Wang Hui
Published: August 2022

Although programmed death 1 blockade has significantly improved the survival of advanced colorectal cancer patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H), clinical data in neoadjuvant and adjuvant setting are limited. The role of circulating tumor DNA (ctDNA) in precision oncology is promising, but its clinical significance in immunotherapy needs to be validated. We report a case series of 3 colon patients who received neoadjuvant and adjuvant immunotherapy and serial ctDNA analysis. This report summarizes clinical and molecular details for 3 patients with locally advanced or recurrent dMMR/MSI-H/polymerase epsilon (POLE) mutation-positive tumors treated with neoadjuvant/adjuvant immunotherapy. One stage IV recurrent colon cancer patient diagnosed with Lynch syndrome received adjuvant sintilimab monotherapy and had a progression-free survival (PFS) over 16 months, one stage Ⅲc colon cancer patient with MSI-H/high tumor mutation burden received neoadjuvant toripalimab monotherapy, was assessed as clinical complete response before surgery, continued with adjuvant sintilimab monotherapy and had a PFS over 17 months, one stage Ⅱ colon cancer patient with POLE P286R also received adjuvant sintilimab monotherapy and had a PFS over 17 months. All patients had detectable ctDNA after radical surgery and clearance of ctDNA during adjuvant immunotherapy. All 3 patients are free of tumor disease at the time of this report. Further studies are warranted to evaluate the long-term efficacy of neoadjuvant and adjuvant programmed death 1 blockade in locally advanced and metastasis in dMMR/MSI-H/POLE mutated colorectal cancer and the role of ctDNA monitoring.
Using an Institute Model to Reduce the Incidence of Venous Thromboembolism Within a Large Hospital System
Authors: Leininger Susan , Rinaldi John , Hite Philip Frances , Birdsong Edward L.
Published: August 2022

Internal benchmarking showed that the Orthopedic Institute had an above average rate of venous thromboembolism (VTE) along with other institutes. The Orthopedic VTE Quality Team was assigned to investigate opportunities for improvement to share with other institutes. To investigate the issues and barriers to the administration of chemical and mechanical VTE prophylaxis, data collection included real-time point prevalence study, physician and nursing surveys, and electronic medical record audits. The results of the data collection indicated inconsistencies in nursing and patient care. Therefore a VTE policy and VTE educational poster was developed. In conjunction, nursing education will be completed to describe the best practice for sequential compression devices and anticoagulant therapies and documentation. The physician will be notified for refusals on either mechanical or chemical prophylaxis.
Air-Assisted Technology
Authors: Stoddart Cathy
Published: August 2022

Continuous quality improvement using Lean methodology engages and values the expertise of the staff close to the patient and the everyday work of caring for them. The patients are not safe if the staff is not safe. Finding the appropriate methodology, where the problem is deeply investigated, respect is visible in the process, and evidence-based decision-making takes place to find safe patient handling solutions for moving lifting and transferring patients was a key objective in this Lean process improvement effort. This article describes the journey taken, the collaboration of 2-unit based councils, and the successful implementation of an air-assisted moving, lifting, and transferring system at a large level 1 quaternary tertiary intercity hospital.
The Future of Assessing Frailty in the Patient With Advanced Heart Failure
Authors: Leininger Susan , Davis Micco Renee N.
Published: August 2022

Frailty is becoming an important component of health care outcomes in patients with a diagnosis of heart failure. A literature search was completed to determine whether a best practice guideline existed to assess frailty in patients who were considering ventricular assist device placement. The literature search revealed that best practice guidelines did not exist. A second comprehensive literature search was completed specifically for frailty including the definition, criteria, assessment, and outcomes. The studies revealed that there were challenges with defining frailty, the age of frailty, assessments tools, and study designs. Cardiologists are primarily interested in screening for frailty, but other physician specialty practices are interested in a frailty screening tool as well. This article discusses the inconsistent research studies and the need for a valid and reliable tool to assess for frailty. It is important that nurse leaders and those working with heart failure patients determine the best practice guidelines for assessing frailty.
Efficacy of a Novel Zigzag Application Pattern for Micropulse Transscleral Cyclophotocoagulation for the Management of Glaucoma
Authors: Sami Ahmed , Aboulnasr Tarek T. , El-Shahed Ahmed F.
Published: August 2022

Précis:

A zigzag mode of application effectively lowered IOP in glaucoma patients at 6 months with a low incidence of complications despite the longer application time. Comparative studies to assess the potential advantages of treating a larger area of ciliary body with this approach are needed.

Purpose:

The purpose of this study is to evaluate the clinical outcome of micropulse transscleral laser cyclophotocoagulation with zigzag mode of application in adult glaucomatous patients.

Subjects and Methods:

A prospective single-arm clinical trial included a series of 34 eyes of 30 consecutive patients who underwent micropulse transscleral cyclophotocoagulation (MP-TSCPC) with zigzag technique at a private ophthalmology center. The trial was conducted from March 16, 2021 to April 12, 2021. Patients who had at least 6 months of follow-up were included. MP-TSCPC probe was moved for 2 mm perpendicular to a line 3 mm parallel to the cornea. This aims to cover the largest circumference of the area supposed to hinder the cilliary body. The probe is moved over 3 quadrants for 90 seconds for each quadrant (total 270 s). Defined as an intraocular pressure (IOP) of 6 to 21 mm Hg or a reduction of IOP by 30%. Failure was defined as an inability to meet the criteria for success or need for retreatment.

Results:

The mean age of involved patients was 52.9 (±SD: 3.9) years old. The mean IOP before MP-TSCPC was 37.47 (±SD: 11.08) mm Hg, which was significantly reduced to 17.7 (±SD: 7.4) mm Hg in the last follow-up visit at 6 months. Number of medications showed significant reduction from mean 3.44 (±SD: 0.99) to 1.91 (±SD: 1.26) in the last follow-up. Success rate was found to be 88% (30 out of 34 eyes) at the final follow-up, where 9 cases showed complete success (26.5%), whereas 21 (61.8%) cases showed qualified success. Despite the relatively higher parameters used in our study, no cases reported postoperative complications apart from only 1 case of reduced visual acuity by 1 line.

Conclusions:

A zigzag mode of application effectively lowered IOP in glaucoma patients at 6 months with a low incidence of complications despite the longer application time. Comparative studies to assess the potential advantages of treating a larger area of ciliary body with this approach are needed.
Risk Factors for Trabeculotomy Failure in Primary Congenital Glaucoma
Authors: Aktas Zeynep , Ucgul Ahmet Y. , Boluk Ceyda E. , Atalay Hatice T.
Published: August 2022

Précis:

This study demonstrates that a baseline corneal diameter >12.25, initial age <4 months at diagnosis, higher baseline IOP than 24 mm Hg, bilaterality, or inability to perform circumferential trabeculotomy, increases the risk of surgical failure of trabeculotomy in patients with primary congenital glaucoma (PCG).

Purpose:

The aim of this study was to identify clinical predictive factors for surgical failure and to evaluate potential prognostic factors affecting surgical success in patients with PCG who underwent trabeculotomy.

Patients and Methods:

The medical charts of 123 eyes of 75 patients who underwent trabeculotomy surgery for the treatment of PCG were retrospectively reviewed. At baseline and each visit, intraocular pressure (IOP), corneal diameter, cup to disc ratio, axial length, number of medications, and need for further glaucoma surgery were noted. Surgical success was defined as an IOP ≤18 mm Hg and 20% IOP reduction from baseline with (qualified) or without (complete) medication and without any further IOP-lowering surgery.

Results:

The mean age at surgery was 4.2±6.6 months and the mean follow-up time was 60.0±37.6 months. The receiver operating characteristic curve showed 4 following best cutoff values to predict surgical failure: the first for age at surgery was 4.5 months; the second baseline IOP was 24.0 mm Hg; the third for baseline cup to disc ratio was 0.4; and the fourth for baseline corneal diameter was 12.25 mm. Multivariate logistic regression analysis revealed that baseline IOP more than 24 mm Hg increased the risk of surgical failure by 2 times, baseline mean corneal diameter >12.25 mm did by 4.2 times, younger age than 4 months did by 2.5 times, bilaterality did by 1.5 times.

Conclusions:

A higher baseline IOP, younger age, larger corneal diameter, and bilaterality were identified as risk factors for trabeculotomy failure in congenital glaucoma. The presence of one or more of these should be considered in the decision-making process when considering surgical options to manage glaucoma in these patients.
Association of Ultra-Short-Term Intraocular Pressure Fluctuation With Disease Progression in Primary Angle Closure Glaucoma: The CUPAL Study
Authors: Tan Shaoying , Yu Marco , Baig Nafees , Chan Poemen P. , Tang Fang Yao , Cheung Carol Y. , Tham Clement C.Y.
Published: August 2022

Précis:

This study demonstrated significant differences in ultra-short-term IOP fluctuations, measured by a contact lens sensor between progressive and stable PACG eyes, during the first one hour after falling asleep.

Purpose:

To identify the most sensitive period for detecting significant ultra-short-term intraocular pressure (IOP) fluctuation associated with disease progression in primary angle closure glaucoma (PACG).

Materials and Methods:

PACG eyes, which had been followed up for over 2 years under the CUHK PACG Longitudinal (CUPAL) Study, were recruited. Eyes with or without functional or structural glaucomatous progression were classified into ‘progressive’ or ‘stable’ groups on the basis of serial visual field and retinal nerve fiber layer (RNFL) thickness documentations, respectively. Ultra-short-term IOP fluctuations were recorded by Sensimed Triggerfish sensors (Sensimed AG, Lausanne, Switzerland) with 288 readings over 30 seconds, at 5-minute intervals, over a 24-hour period. In each of 7 activity-related 1-hour periods during the examining day, the mean value of the amplitude-frequency profiles of the signal fluctuations in twelve 30-second intervals was calculated by semivariogram/semi-variance. The ‘progressive’ and ‘stable’ groups were compared by permutation tests on functional t-statistics.

Results:

Among the 25 recruited PACG eyes, 16 eyes were classified as RNFL ‘progressive’ group (the mean rate of change in global RNFL thickness: -0.199 ±0.128 μm/mo). Higher signal fluctuations, in terms of amplitude-frequency, were found during the first 1-hour period of sleeping in the RNFL ‘progressive’ group compared with the RNFL ‘stable’ group (P=0.028).

Conclusions:

Between RNFL ‘progressive’ and ‘stable’ PACG eyes, significant differences in ultra-short-term IOP fluctuation at the 1-hour period after falling asleep were identified. The first hour of sleeping may be the most sensitive period for detecting significant ultra-short-term IOP fluctuation in PACG eyes.
Patterns of Optical Coherence Tomography Imaging in Preperimetric Open Angle Glaucoma: A Comparative Study With Young-Age-Onset and Old-Age-Onset Eyes
Authors: Bak Eunoo , Sun Sukkyu , Wy Seoyoung , Kim Yong Woo , Kim Young Kook , Park Ki Ho , Kim Hee Chan , Jeoung Jin Wook
Published: August 2022

Précis:

Optic coherence tomography imaging in preperimetric open angle glaucoma (OAG) differed between young-age-onset and old-age-onset eyes. Inferior and superior quadrants were thinner in young and old-age-onset eyes, respectively. Understanding the specific patterns of early glaucomatous damage based on age-at-onset may improve glaucoma diagnosis and monitoring.

Purpose:

To investigate the patterns of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning in preperimetric OAG by optical coherence tomography based on age at onset (“young-age onset (<40 y)” vs. “old-age onset (≥40 y)”.

Materials and Methods:

The RNFL and GCIPL deviation images were acquired by Cirrus HD-optical coherence tomography, and overlaid, thus converted to a “deviation frequency map”, respectively. The topographic thinning patterns and parameters of RNFL and GCIPL thickness measurements were compared.

Results:

A total of 194 eyes of 194 patients with preperimetric OAG and 97 eyes of 97 age-matched normal subjects were analyzed. Young-age-onset eyes of preperimetric OAG mainly had RNFL defects inferotemporally (264–296 degrees) with GCIPL defects in the inferior region (213–357 degrees). Old-age-onset preperimetric OAG eyes had RNFL defects inferotemporally (266–294°) and superotemporally (33–67 degrees), with GCIPL defects in the inferior and superior regions (206–360 degrees, 0–22 degrees). The inferior quadrant of RNFL and GCIPL thicknesses were significantly thinner in young-age-onset eyes compared with old-age-onset eyes (P=0.012, 0.016), while the superior quadrant of those were significantly thinner in the old-age-onset eyes (P=0.003, 0.005).

Conclusion:

Young-age-onset and old-age-onset eyes of preperimetric OAG present different specific patterns of RNFL and GCIPL thinning.
Healthcare-associated Infections in Very Low Birth–weight Infants in a South African Neonatal Unit: Disease Burden, Associated Factors and Short-term Outcomes
Authors: Lloyd Lizel Georgi , Bekker Adrie , Van Weissenbruch Mirjam M. , Dramowski Angela
Published: August 2022

Background:

Infection is a leading cause of death among very low birth–weight (VLBW) infants in resource-limited settings.

Methods:

We performed a retrospective review of healthcare-associated infection (HAI) episodes among VLBW infants from January 1, 2016, to December 31, 2017. The epidemiology, causative organisms and short-term outcomes were analyzed. Logistic regression was used to investigate for factors associated with development of HAI.

Results:

During the study period, 715 VLBW infants with suspected HAI were investigated, including 162/715 (22.7%) proven and 158/715 (22.1%) presumed HAI. Of the proven infections, 99/162 (61.1%) contained at least one Gram-negative organism per blood culture; 84/162 (51.9%) single Gram-negative organisms and 15/162 (9.3%) polymicrobial growth. Independent factors associated with development of any HAI included low gestational age, small for gestational age, indwelling central venous catheter and invasive ventilation. Compared with infants in whom HAI had been excluded, infants with HAI were more likely to be diagnosed with necrotizing enterocolitis (5.6% vs. 23.1%; P < 0.001) and bronchopulmonary dysplasia (1.0% vs. 4.4%; P = 0.007). Infants with any HAI also had a longer hospital stay [44 (25–65) vs. 38 (26–53) days; P < 0.001] and increased mortality [90/320 (28.1%) vs. 21/395 (5.3%); P < 0.001] compared with infants who did not develop HAI episodes.

Conclusions:

Proven and presumed HAI are a major contributor to neonatal morbidity and mortality; further research is urgently needed to better understand potential targets for prevention and treatment of HAI in resource-limited neonatal units.
Comparing and Contrasting Quality Frameworks Using Research on High-Probability Requests With Young Children
Authors: Hardy Jessica K. , McLeod Ragan H. , Sweigart Chris A. , Landrum Timothy
Published: August 2022

The purpose of this study was to compare and contrast frameworks for evaluating methodological rigor in single case research. Specifically, research on high-probability requests to increase compliance in young children was evaluated. Ten studies were identified and were coded using 4 frameworks. These frameworks were the Council for Exceptional Children Standards for Evidence-based Practices, What Works Clearinghouse, Risk of Bias Assessment for Single Subject Experimental Designs, and Single Case Analysis and Review Framework. Significant differences were found across frameworks, both in the rating of rigor and the study effects. Implications for determining high-quality research and effective practices are discussed.
A novel F13A1 gene mutation (Arg208Pro) in a Chinese patient with factor XIII deficiency
Authors: Xie Haixiao , Wang Mingshan , Jin Yanhui , Li Xiaolong , Jiang Shuting , Yang Lihong
Published: August 2022

The objective of the study was to analyse a novel F13A1 gene mutation in a Chinese patient with factor XIII (FXIII) deficiency and explore the molecular mechanism. Pedigree investigation, clinical diagnosis, phenotypic and genetic analysis were conducted. The F13A1 gene was amplified by PCR and directly sequenced. Online bioinformatics software was needed to analyse the mutation. A novel mutation c.515G>C (p.Arg208Pro) in exon 4 was found in the proband. Protein Arg208 is conserved highly among homologous species. Bioinformatics software showed that Arg208Pro mutation might affect the protein function. We preliminarily believed the mutation Arg208Pro was responsible for the decrease FXIII level. We reported a novel mutation in the F13A1 gene, which can flesh out the mutant library.
The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis
Authors: Wang Huan , Reddy Srinivasa T. , Fogelman Alan M.
Published: August 2022

Purpose of review

This review explores mechanisms by which gut-derived bacterial

lipopolysaccharide (LPS) and oxidized phospholipids contribute to chronic systemic inflammation and atherosclerosis.

Recent findings

Gut-derived LPS enters through the small intestine via two distinct pathways that involve high density lipoproteins (HDL) and chylomicrons. Gut-derived LPS can bind to the LPS-binding protein (LBP) and to HDL3 in the small intestine and travel through the portal vein to the liver where it does not elicit an inflammatory reaction, and is inactivated or it can bind to HDL2 and travel through the portal vein to the liver where it elicits an inflammatory reaction. Alternatively, in the small intestine, LPS can bind to LBP and chylomicrons and travel through the lymphatics to the systemic circulation and enhance inflammatory processes including atherosclerosis. Oxidized phospholipids formed in the small intestine regulate the levels and uptake of LPS in small intestine by regulating antimicrobial proteins such as intestinal alkaline phosphatase. Gut-derived LPS and oxidized phospholipids may be responsible for the persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels.

By targeting gut-derived oxidized phospholipids, the uptake of gut-derived LPS may be reduced to decrease systemic inflammation and atherosclerosis.
Prognostic Value of Regular Nutritional Treatment in Patients With Amyotrophic Lateral Sclerosis
Authors: Altinkaynak Mustafa , Gok Gokhan Kerim , Ozmen Bahar , Buyukdemir Serpil , Akpinar Timur Selcuk , Erten Sebile Nilgun , Saka Bulent
Published: August 2022

Background:

Malnutrition adversely affects the prognosis of amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate the effect of regular nutrition treatment and follow-up in clinical nutrition outpatient clinic (CNOC) on survival in ALS patients.

Materials and Methods:

The study included 55 ALS patients who were admitted and followed up in CNOC. Malnutrition was diagnosed using ESPEN criteria and nutrition treatment was planned according to needs of each patient. Nutritional status was followed up by body mass index (BMI), bioelectrical impedence analysis, and serum albumin. During the follow-up, survivors and nonsurvivors were compared according to their nutrition treatment success and changes in the anthropometric and laboratory measurements.

Results:

Body weight, BMI, and fat free mass were decreased during the follow-up in both survivors and nonsurvivors (P<0.01). The decrease in the serum albumin and BMI were significantly higher in nonsurvivors (P<0.01). Mortality rate was lower in those with higher adherence to nutrition treatment (P<0.01) and patients with lower adherence to nutrition treatment showed more significant decrease in serum albumin levels (P<0.01).

Conclusion:

A personalized nutrition treatment combined with increased nutritional adherence in CNOC can decrease mortality in ALS patients.
TSC/MTOR-associated Eosinophilic Renal Tumors Exhibit a Heterogeneous Clinicopathologic Spectrum
Authors: Xia Qiu-yuan , Wang Xiao-tong , Zhao Ming , He Hui-ying , Fang Ru , Ye Sheng-bing , Li Rui , Wang Xuan , Zhang Ru-song , Lu Zhen-feng , Ma Heng-hui , Wang Zi-yu , Rao Qiu
Published: August 2022

Background:

Several TSC1/2- or MTOR-mutated eosinophilic renal tumor subsets are emerging, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumors (EVTs) and low-grade oncocytic tumors (LOTs). “Unclassified renal tumors with TSC/MTOR mutations” (TSC-mt RCC-NOS) do not meet the criteria for other histomolecular subtypes. Whether these tumors represent a continuum of 1 TSC/MTOR-mutation-associated disease is unknown.

Design:

We evaluated the clinicopathologic and IHC profiles of 39 eosinophilic renal tumors with targeted DNA sequencing-confirmed TSC/MTOR mutations. Twenty-eight of these, plus 6 ChRCC, 5 RO, 5 ccRCC, 7 MiT RCC and 6 normal renal tissues, were profiled transcriptionally by RNA-seq.

Results:

The 39 cases were reclassified based on morphological and IHC features as ESC RCC (12), EVT (9), LOT, (8) and TSC-mt RCC-NOS (10). The mutation profiles demonstrated consistency; ESC RCCs (12/12) had TSC mutations, and most LOTs (7/8) had MTOR mutations. Ten TSC-mt RCC-NOSs exhibited heterogeneous morphology, arising a differential diagnosis with other renal tumors, including MiT RCC, PRCC and epithelioid PEComa. RNA sequencing-based clustering segregated ESC RCC, EVT and LOT from each other and other renal tumors, indicating expression profile-level differences. Most TSC-mt RCC-NOSs (6/7) formed a mixed cluster with ESC RCC, indicating similar expression signatures; one TSC-mt RCC-NOS with unusual biphasic morphology clustered with EVT.

Conclusions:

We expanded the TSC/MTOR-associated eosinophilic renal tumor morphologic spectrum, identified gene mutation characteristics, and highlighted differential diagnosis challenges, especially with MiT RCC. ESC RCC, EVT, and LOT having distinct expression profiles. TSC-mt RCC-NOS may cluster with recognized TSC/MTOR-associated entities.
Characteristics of a Pediatric Emergency Psychiatric Telephone Triage Service
Authors: Cancilliere Mary Kathryn , Ramanathan Amrita , Hoffman Pamela , Jencks Jennifer , Spirito Anthony , Donise Kathleen
Published: August 2022

Objectives

Caregivers of youth in psychiatric crisis often seek treatment from hospital emergency departments (EDs) as their first point of entry into the mental health system. Emergency departments have struggled over the last decade with growing numbers and now, because of the pandemic, have experienced a deluge of mental health crises. As one approach to divert unnecessary ED admissions, pediatric emergency psychiatric telephone triage services have been created. This study aimed to define the characteristics and utilization of a pediatric triage service and to examine clinician documentation of calls to identify the assessment of risk and disposition.

Methods

This study included 517 youth (2–18 years; mean, 12.42 years; SD, 3.40 years) who received triage services in the winter of 2 consecutive years. Triage calls were received from caregivers (>75%), schools (17.0%), and providers (6.6%) regarding concerns, including suicidal ideation (28.6%), school issues (28.6%), and physical aggression (23.4%).

Results

Dispositions were for acute, same-day evaluation (9.7%), direct care service (28.8%), further evaluation (within 48–72 hours, 40.0%), and resource/service update information (21.5%). Findings revealed that most clinical concerns were referred for further evaluation. Both adolescent females and males were referred for emergency evaluations at high rates.

Conclusions

A dearth of information on pediatric crisis telephone triage services exists; thus, developing an evidence base is an important area for future work. This information assists not only in our understanding of which, why, and how many youths are diverted from the ED but allows us to extrapolate significant costs that have been saved because of the utilization of the triage service.
Willingness to use nonpharmacologic treatments for musculoskeletal pain in the emergency department: a cross-sectional study
Authors: Eucker Stephanie A. , Foley Shawna , Peskoe Sarah , Gordee Alexander , Risoli Thomas , Morales Frances , George Steven Z.
Published: August 2022

Objectives:

Pain is an individual experience that should incorporate patient-centered care. This study seeks to incorporate patient perspectives toward expanding nonpharmacologic treatment options for pain from the emergency department (ED).

Methods:

In this cross-sectional study of adult patients in ED with musculoskeletal neck, back, or extremity pain, patient-reported outcomes were collected including willingness to try and prior use of various nonpharmacologic pain treatments, sociodemographics, clinical characteristics, functional outcomes, psychological distress, and nonmusculoskeletal symptoms. Least absolute shrinkage and selection operator regression identified variables associated with (1) willingness to try and (2) having previously tried nonpharmacologic treatments.

Results:

Responses were analyzed from 206 adults, with a mean age of 45.4 (SD 16.4) years. The majority (90.3%) of patients in ED were willing to try at least one form of nonpharmacologic pain treatment, with 70.4%, 81.6%, and 70.9% willing to try respective subcategories of active (eg, exercise), passive (eg, heat), and psychosocial (eg, prayer) modalities. Only 56.3% of patients had previously tried any, with 35.0%, 52.4%, and 41.3% having tried active, passive, and psychosocial modalities, respectively. Patient-level factors associated with willingness included pain in upper back, more severe pain-related symptoms, and functional impairments. The factor most consistently associated with treatment use was health care provider encouragement to do so.

Conclusions:

Patients in ED report high willingness to try nonpharmacologic treatments for pain. Higher pain severity and interference may indicate greater willingness, while health care provider encouragement correlated with treatment use. These findings may inform future strategies to increase the introduction of nonpharmacologic treatments from the ED.
Associations of Polypharmacy With Clinical Parameters, Function, and Health-Related Quality of Life in Psoriatic Arthritis
Authors: Erdem Gürsoy Didem , Gezer Halise Hande , Acer Kasman Sevtap , Duruöz Mehmet Tuncay
Published: August 2022

Objective

The aim of this study was to assess predictors of polypharmacy and its effect on health-related quality of life in patients with psoriatic arthritis (PsA).

Methods

This cross-sectional study was performed between February and December 2019. The number of medications was grouped into minor (2–4) and major (≥5) polypharmacy. Functional status and quality of life were assessed using the Health Assessment Questionnaire and Short-Form 36, respectively. Clinical and demographic characteristics, physical function, and quality of life of the polypharmacy group were compared. Predictive factors for major polypharmacy were evaluated using a logistic regression analysis.

Results

The mean age of the 100 patients (70 females and 30 males) with PsA was 48.43 ± 12.94 years. The proportion of patients with major polypharmacy was 19%. The physical function subscale of Short-Form 36 was lower in the major polypharmacy group (p = 0.009). Univariable analysis revealed that sex, body mass index, disease duration, disease activity, psoriasis severity, dactylitis, enthesitis, PsA subtypes, smoking, and Health Assessment Questionnaire were not associated with major polypharmacy (p > 0.10). In the multivariable model, the number of comorbidities (odds ratio, 3.151; 95% confidence interval, 1.828–5.429; p < 0.001) and age ≥60 years (odds ratio, 4.864; 95% confidence interval, 1.159–20.418; p = 0.031) were significantly associated with major polypharmacy.

Conclusions

The number of comorbid diseases and age ≥60 years were the factors associated with major polypharmacy in patients with PsA. Although physical function was not associated with polypharmacy, patients with major polypharmacy had poorer quality of life.
Does Cancer Masquerade as Sarcoidosis?
Authors: Albert Daniel
Published: August 2022

Background/Objective

Sarcoidosis is a granulomatous disorder. Rarely, malignancy is accompanied by a granulomatous reaction. This retrospective study addressed whether cancer can masquerade as sarcoidosis.

Methods

TriNetX identified 1029 newly diagnosed cases of sarcoidosis between October 2015 and September 2020, of whom 50 had a subsequent diagnosis of malignancy.

Results

In 36 cases, the malignancy was unrelated to sarcoidosis. In 7 cases, the diagnosis of sarcoidosis delayed the eventual cancer diagnosis by a range of 1 month to 2 years. In 7 cases, the subsequent diagnosis of cancer might have been related to the therapy for sarcoid.

Conclusions

Cancer masquerading as sarcoidosis is very rare occurring in 7 (0.7%) of our 1029 cases. In no case was lung cancer masquerading as sarcoidosis. Searching for occult malignancy in patients with a known diagnosis of sarcoidosis is rarely indicated.
Understanding Local Hemodynamic Changes After Liver Transplant: Different Entities or Simply Different Sides to the Same Coin?
Authors: Calderon Novoa Francisco , Mattera Juan , de Santibañes Martín , Ardiles Victoria , Gadano Adrian , D’Agostino Daniel E , Fratantoni Eugenia , De Santibañes Eduardo , Pekolj Juan
Published: August 2022

Liver transplantation is an extremely complex procedure performed in an extremely complex patient. With a successful technique and acceptable long-term survival, a new challenge arose: overcoming donor shortage. Thus, living donor liver transplant and other techniques were developed. Aiming for donor safety, many liver transplant units attempted to push the viable limits in terms of size, retrieving smaller and smaller grafts for adult recipients. With these smaller grafts came numerous problems, concepts, and definitions. The spotlight is now aimed at the mirage of hemodynamic changes derived from the recipients prior alterations. This article focuses on the numerous hemodynamic syndromes, their definitions, causes, and management and interconnection with each other. The aim is to aid the physician in their recognition and treatment to improve liver transplantation success.
Uptake of Sotrovimab for prevention of severe COVID-19 and its safety in the community in England
Authors: Patone Martina , Snelling Andrew JHL , Tibble Holly , Coupland Carol AC , Sheikh Aziz , Hippisley-Cox Julia
Published: August 2022

Sotrovimab is a neutralising monoclonal antibody (nMAB), currently administrated in England to treat extremely clinically vulnerable COVID-19 patients. Trials have shown it to have mild or moderate side effects, however safety in real-world settings has not been yet evaluated. We used national databases to investigate its uptake and safety in community patients across England. We used a cohort study to describe uptake and a self-controlled case series design to evaluate the risks of 49 pre-specified suspected adverse events in the 2-28 days post-treatment. Between December 11, 2021 and May 24, 2022, there were 172,860 COVID-19 patients eligible for treatment. Of the 22,815 people who received Sotrovimab, 21,487 (94.2%) had a positive SARS-CoV-2 test and 5,999 (26.3%) were not on the eligible list. Between treated and untreated eligible individuals, the mean age (54.6, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) were similar. There were marked variations in uptake between ethnic groups, which was higher amongst Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), White (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We found no increased risk of any of the suspected adverse events in the overall period of 2-28 days post-treatment, but an increased risk of rheumatoid arthritis (IRR 3.08, 95% CI 1.44, 6.58) and of systematic lupus erythematosus (IRR 5.15, 95% CI 1.60, 16.60) in the 2-3 days post-treatment, when we narrowed the risk period.

Funding

National Institute of Health Research (Grant reference 135561)
An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors
Authors: Singh Raminder , Rossini Valerio , Stockdale Stephen R. , Saiz-Gonzalo Gonzalo , Hanrahan Naomi , D’ Souza Tanya , Clooney Adam , Draper Lorraine A. , Hill Colin , Nally Ken , Shanahan Fergus , Andersson-Engels Stefan , Melgar Silvia
Published: August 2022

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesise that the heterogeneous prevalence of pathobionts [e.g., adherent-invasiveEscherichiacoli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. UsingIL10-/-mice, we show aggravation of colitis in AIEC-colonised animals fed NSAID. This is accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis and pyroptosis; features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers and activated T-cells and macrophages, improved histology and increased abundance ofClostridiumcluster XIVa species. Our findings provide mechanistic insights into how NSAID and an opportunistic gut-pathobiont can synergise to worsen IBD symptoms. Thus, targeting the NLRP3 inflammasome and Caspase-8 could be a potential therapeutic strategy in patients with NSAID-worsened inflammation.
Distinct roles of forward and backward alpha-band waves in spatial visual attention
Authors: Alamia Andrea , Terral Lucie , D’ambra Malo Renaud , VanRullen Rufin
Published: August 2022

Previous research has associated alpha-band [8-12Hz] oscillations with inhibitory functions (Klimesch et al., 2007; Jensen and Mazaheri, 2010): for instance, several studies showed that visual attention increases alpha-band power in the hemisphere ipsilateral to the attended location (Thut et al., 2006; Händel et al., 2011). However, other studies demonstrated that alpha oscillations positively correlate with visual perception (Busch et al., 2009; Vanrullen and MacDonald, 2012), hinting at different processes underlying their dynamics. Here, using an approach based on traveling waves, we demonstrate that there are two functionally distinct alpha-band oscillations propagating in different directions. We analyzed EEG recordings from two datasets of human participants (N=32, both genders) performing a covert visual attention task. Participants were instructed to detect a brief target by covertly attending to the screen’s left or right side. Our analysis reveals two distinct processes: allocating attention to one hemifield increases top-down alpha-band waves propagating from frontal to occipital regions ipsilateral to the attended location, both with or without visual stimulation. These top-down oscillatory waves correlate positively with alpha-band power in frontal and occipital regions. Yet, different alpha-band waves propagate from occipital to frontal regions and contralateral to the attended location. Crucially, these forward waves were present only during visual stimulation, suggesting a separate mechanism related to visual processing. Together, these results reveal two distinct processes reflected by different propagation directions, demonstrating the importance of considering oscillations as traveling waves when characterizing their functional role.
Crystal structure of an indium–salicylhydroximate complex cation: [In4(H2shi)8(H2O)6](NO3)4·8.57H2O
Authors: Aziz Ozha A. , Zeller Matthias , Zaleski Curtis M.
Published: August 2022

The synthesis and crystal structure for the title compound, hexaaquahexakis(μ-2-hydroxybenzenecarbohydroxamato)bis(2-hydroxybenzenecarbohydroxamato)tetraindium(III) tetranitrate 8.57-hydrate + unknown solvent, [In4(H2shi)8(H2O)6](NO3)4·8.57H2O·solvent, where H2shi− is salicylhydroximate (C7H5NO3), are reported. The complex cation of the structure, [In4(H2shi)8(H2O)6]4+, is a dimer with a step-like topology and possesses an inversion center that relates each [In2(H2shi)4(H2O)3]2+ side of the complex cation. Each InIII ion is seven-coordinate with a pentagonal–bipyramidal geometry, and the salicylhydroximate ligands have a 1− charge as only the oxime oxygen of the ligand is deprotonated. Four interstitial nitrate anions maintain the charge balance of the compound. One of the nitrate anions (and its symmetry equivalent) is disordered over two different orientations with an occupancy ratio of 0.557 (7) to 0.443 (7). The interstitial solvent water molecules show substantial disorder. Approximately 8.57 water molecules per formula unit were refined as disordered and partially occupied, while a suitable model could not be devised for the other extensively disordered solvent molecules (water and possibly methanol as this was the synthesis solvent). Thus, these latter solvent molecules were instead treated with the SQUEEZE routine [Spek (2015). Acta Cryst. C71, 9–18.] as implemented in the program PLATON, and the procedure corrected for 151 electrons within solvent-accessible voids of 367 Å3.
Evaluation of the performance of the multi-objective scalarization methods for the aircraft sequencing and scheduling problem using multi-criteria decision-making
Authors: Dönmez Kadir
Published: August 2022

Purpose

This study aims to evaluate the performance of the most popular multi-objective programming scalarization methods in the literature for the aircraft sequencing and scheduling problem (ASSP). These methods are the weighted sum method, weighted goal programming, the ε-constraint method, the elastic constraint method, weighted Tchebycheff and augmented weighted Tchebycheff.

Design/methodology/approach

First, the ASSP for a single runway case was modeled using mixed-integer programming considering the safety and operational constraints and the objectives of the minimization of total delay and total flight time for a sample airport. The objectives were then combined by using the multi-objective programming scalarization methods and various expected times of arrival–departure samples were run for the mathematical models. Finally, the methods were evaluated in terms of the number of nondominated solutions, superior nondominated solution and the average solution time using the Measurement of Alternatives and Ranking according to Compromise Solution method, which is a popular multi-criteria decision-making method.

Findings

Augmented Weighted Tchebycheff was found to be the most effective approach to ASSP in terms of the evaluation criteria followed by Weighted Tchebycheff and then weighted sum method.

Practical implications

The methodology presented in this study could provide more efficient air traffic management in terminal maneuvering areas when multiple objectives need to be optimized.

Originality/value

Although there are studies including the comparison of several scalarization methods for other problems, the comparison of the methods for ASSP has not yet been handled in the literature. As there are several stakeholders in the air traffic system, ASSP includes several objectives, and as a result, this problem can benefit from analyses using this comparison.
Reducing perseverative requesting and other problem behavior in a young girl with autism: a sequentially implemented intervention package
Authors: Chen Mo , Kreibich Shelley
Published: August 2022

Purpose

This study aims to use a sequentially implemented intervention package to reduce the occurrence of perseverative requesting and other problem behavior in a young girl with autism spectrum disorder (ASD).

Design/methodology/approach

In this single-case study, subsequent to a functional analysis and a preference assessment, an intervention package consisting of three components (i.e. a tolerance for delay to reinforcement, choice-making and visual schedule) was implemented sequentially to address perseverative requesting and other problem behavior maintained by access to preferred items/activities in a young girl with ASD.

Findings

Via the intervention package, the girl demonstrated higher self-control skills (i.e. delaying access to preferred items/activities, choosing more preferred items/activities with delayed access over less preferred ones with immediate access, completing tasks before having access to preferred items/activities) with a reduction of perseverative requesting or other problem behavior.

Originality/value

The current case study presents concrete steps that could be applied to address tangible-maintained perseverative requesting using more natural and educationally relevant signals while improving the child’s appropriate skills (e.g. delay to reinforcement, self-control and task engagement).
Drivers for SMEs participation in entrepreneurial ecosystems: evidence from health tech ecosystem in Northern Finland
Authors: Mohammadparast Tabas Abdollah , Kansheba Jonathan Mukiza Peter , Komulainen Hanna
Published: August 2022

Purpose

The entrepreneurial ecosystem (EE) literature is dominated by conceptual studies with insufficient theoretical foundations and empirical evidence on the micro-level. This study aims to explore the largely overlooked question of what the drivers that motivate small and medium-sized enterprises (SMEs) to participate in an ecosystem are.

Design/methodology/approach

The study adopts a qualitative exploratory approach. The empirical data consists of 19 semi-structured interviews with top management of SMEs in the health tech ecosystem in Finland. The data were analyzed using a thematic content analysis.

Findings

This study reveals a typology of drivers that motivate SMEs to participate in an ecosystem. These include social drivers (networking and cooperation and communication and knowledge sharing), resource drivers (access to resources, formal and informal support and market access) and cognitive drivers (shared goals and common values).

Research limitations/implications

The study contributes to the EE research by highlighting the drivers that motivate health tech SMEs to become members of the local ecosystem. It suggests that managers and entrepreneurs need to be aware of the factors related to social, resource and cognitive drivers to ensure the future success of their business.

Originality/value

The study draws evidence from a micro-level perspective which enriches the understanding of the EE phenomenon. It also explores an increasingly relevant but under-researched field, the health tech ecosystem.
Foreign ownership and liquidity: evidence from a frontier market
Authors: Bousnina Amina , Gana Marjène Rabah , Dakhlaoui Mejda
Published: August 2022

Purpose

This study aims to provide empirical evidence on the impact of foreign share ownership on the liquidity of the Tunisian Stock Exchange (TSE).

Design/methodology/approach

The authors hypothesize in the first strand that stock liquidity could be positively affected by foreign ownership based on the real friction channel. The authors then hypothesize in the second strand, based on the information friction channel, that foreign ownership's impact on stock liquidity could be insignificant or negative and that foreign investors raise the level of information asymmetry. A sample of 318 firm-year observations from Tunisia over the 2012–2017 period and a random-effects estimation were used. Moreover, using the 2SLS estimator, a robustness check framework was applied in order to address any potential reverse causality concerns.

Findings

The authors find strong evidence that higher foreign ownership improves stock liquidity. More specifically, firms with higher foreign ownership engender a lower bid-ask spread, a better stock ability to absorb a large amount of trading volume, and a larger depth. These findings are still valid when reverse causality concerns are addressed through the use of the 2SLS estimator.

Originality/value

The paper contributes to the existing literature by focusing on the ownership–liquidity relationship on a frontier market. It provides further empirical support that higher corporate governance quality reduces the information asymmetry problem and enhances stock market liquidity.