bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the role of Epac1‐SOCS3 signaling in the development of neonatal‐CRD‐induced visceral hypersensitivity in rats
Authors: Huang Si‐Ting , Chen Bin‐Bin , Song Zhi‐Jing , Tang Hui‐Li , Hua Rong , Zhang Yong‐Mei
Published: June 2022

Aims

Visceral hypersensitivity in irritable bowel syndrome (IBS) is widespread, but effective therapies for it remain elusive. As a canonical anti‐inflammatory protein, suppressor of cytokine signaling 3 (SOCS3) reportedly relays exchange protein 1 directly activated by cAMP (Epac1) signaling and inhibits the intracellular response to inflammatory cytokines. Despite the inhibitory effect of SOCS3 on the pro‐inflammatory response and neuroinflammation in PVN, the systematic investigation of Epac1‐SOCS3 signaling involved in visceral hypersensitivity remains unknown. This study aimed to explore Epac1‐SOCS3 signaling in the activity of hypothalamic paraventricular nucleus (PVN) corticotropin‐releasing factor (CRF) neurons and visceral hypersensitivity in adult rats experiencing neonatal colorectal distension (CRD).

Methods

Rats were subjected to neonatal CRD to simulate visceral hypersensitivity to investigate the effect of Epac1‐SOCS3 signaling on PVN CRF neurons. The expression and activity of Epac1 and SOCS3 in nociceptive hypersensitivity were determined by western blot, RT‐PCR, immunofluorescence, radioimmunoassay, electrophysiology, and pharmacology.

Results

In neonatal‐CRD‐induced visceral hypersensitivity model, Epac1 and SOCS3 expressions were downregulated and IL‐6 levels elevated in PVN. However, infusion of Epac agonist 8‐pCPT in PVN reduced CRF neuronal firing rates, and overexpression of SOCS3 in PVN by AAV‐SOCS3 inhibited the activation of PVN neurons, reduced visceral hypersensitivity, and precluded pain precipitation. Intervention with IL‐6 neutralizing antibody also alleviated the visceral hypersensitivity. In naïve rats, Epac antagonist ESI‐09 in PVN increased CRF neuronal firing. Consistently, genetic knockdown of Epac1 or SOCS3 in PVN potentiated the firing rate of CRF neurons, functionality of HPA axis, and sensitivity of visceral nociception. Moreover, pharmacological intervention with exogenous IL‐6 into PVN simulated the visceral hypersensitivity.

Conclusions

Inactivation of Epac1‐SOCS3 pathway contributed to the neuroinflammation accompanied by the sensitization of CRF neurons in PVN, precipitating visceral hypersensitivity and pain in rats experiencing neonatal CRD.
Spectrophotometry and colorimetry profiling of pure phenol red and cell culture medium on pH variation
Authors: Raffay Razemy , Husin Norfaiqah , Omar Ahmad Fairuz
Published: June 2022

The application of phenol red has been widely applied in cell culture media to enable monitoring of the pH value of cell growth. However, sometimes it is difficult for a human observer to identify the colour transformation using only the naked eye. Furthermore, different people will give different interpretations of colour transformation. Thus the current study was performed to provide the spectrophotometry and colorimetry profiling of pure phenol red and cell culture media to pH variation. Pure phenol red and cell culture media were used as samples. The pH values of both types of sample were manipulated using citric acid. Spectrophotometry analysis results show that the pH value of the pure phenol red samples could be well profiled by using the wavelengths in the green light region (in the range of 500‐600 nm). The pH value of the cell culture medium samples could also be well profiled, by using wavelengths in either the green or blue light region. Colorimetry analysis results conducted using CIELab colour space indicate that the colour transformation of both samples is linear, with a high value for the coefficient of determination. This profiling proves that phenol red can be used to quantify the pH values of the samples and shows good potential to be applied in the development of spectroscopy‐based and colorimetry‐based pH sensors.
Effect of metformin on arginine and dimethylarginines in patients with advanced type 2 diabetes: A post hoc analysis of a randomized trial
Authors: Top Wiebe M. C. , Lehert Philippe , Schalkwijk Casper G. , Stehouwer Coen D. A. , Kooy Adriaan
Published: June 2022

Aim

To study the effect of metformin on plasma levels of arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), indicators of the nitric oxide pathway.

Materials and Methods

In this post hoc analysis of the HOME trial, we analysed plasma levels of arginine, ADMA and SDMA during the 4.3‐year follow‐up (comparing the effects of metformin versus placebo on top of insulin therapy). Statistical analysis was performed with a mixed model approach, in which simultaneously constant treatment effects were estimated, as well as time‐dependent treatment effects.

Results

We found that metformin compared with placebo did not affect ADMA or SDMA plasma levels but rapidly decreased arginine plasma levels and hence the arginine to ADMA ratio. The constant treatment effect on ADMA was 0.99 (95% CI 0.97, 1.00) relative to placebo and the time‐dependent treatment effect was 1.00 (95% CI 1.00, 1.01). By contrast, the constant treatment effect on arginine was 0.86 (95% CI 0.84, 0.88), with only a minimal time‐dependent change of 1.01 (95% CI 1.00, 1.01).

Conclusions

The potential benefits of metformin on endothelial function cannot be explained by a decrease in ADMA or by improved global arginine availability. The clinical significance of the decreased arginine plasma levels is not clear and can be harmful or beneficial, depending on the mechanism involved. However, a potential effect of metformin on the nitric oxide pathway is not restricted to the studied metabolites.
The impact of wildfire and mammal carcasses on beetle emergence from heathland soils
Authors: Feng Lanya , Lysakowski Bartosz , Eisenschmidt Jenny , Birkhofer Klaus
Published: June 2022

Wildfires alter the composition of insect communities due to fire‐induced mortality, and the post‐fire vegetation and soil conditions also affect the initial re‐colonisation and subsequent local emergence of adults from burnt soils. However, the impact of wildfires on re‐colonisation and emergence of carrion‐associated scavenging species from soils has previously been neglected.

We established an experiment in an unmanaged heathland area that was affected by a severe wildfire in 2017 by adding wild boar carcasses to burnt and unburnt areas 204 days after the wildfire. Adult beetles were then collected with emergence tents at paired sites with and without carcasses and in burnt and unburnt areas from 27 April to 10 August 2018.

The wildfire did not significantly affect the diversity or abundance of soil‐emerging beetles. Community composition in the burnt area differed significantly from the unburnt area with higher numbers of Staphylinidae and lower numbers of phytophagous beetle families (Curculionidae and Elateridae) emerging from soils, probably reflecting the structurally simpler vegetation and reduced litter one year after the wildfire.

Scavenging beetles generally colonise mammal carcasses in burnt areas to the same extent as in unburnt areas, but the post‐fire conditions favoured some species with very specialised habitat preferences. A few rare species of conservation concern almost exclusively occurred in the burnt area and in most cases in combination with the presence of a carcass. This result highlights the joint importance of heathland wildfires and carcass resources for species conservation in beetle communities.
Effects of quantity and rheological properties of glutenin macropolymer on the physical properties of extruded noodles made from flour mill streams
Authors: Hu Chongxue , Zhang Yingquan , Don Clyde , Zhang Bo , Guo Boli
Published: June 2022

Four extruded noodles with same variety wheat flour mill streams (FMS) from the centre to the outer layer of the endosperm and 1 round or 3 rounds of extrusion have different quantity and rheological properties of glutenin macropolymer (GMP). The results showed that the GMP content and the G' plateau value of GMP‐gel of the extruded noodles were 0.074 ~ 0.093 [g/(g noodle)] and 575 ~ 1895 Pa, respectively. Meanwhile, the freezing water content, the cooking loss, the textural hardness and the springiness of the extruded noodles were 11.4 ~ 19.5 [g/(100 g water)], 1.7 ~ 2.0 [g/(100 g water‐insoluble noodle)], 5378 ~ 6112 g and 83.4 ~ 90.8%, respectively. Compared to 1 round, extruded noodle with 3 rounds extrusions had slowly decreasing G' with strain increasing, a significantly low freezing water content and cooking loss (P < 0.05) and high hardness. Extruded noodle with high G' in GMP‐gel had relatively high springiness.
Overtime or fragmentation? Family transactions and working time during the COVID‐19 pandemic
Authors: CLOUET Hadrien
Published: June 2022

What changes affected the working time of employees required to work from home by the 2020 French health measures? Drawing on a qualitative survey of a municipal water company, based on interviews, direct observations, and questionnaires, the author shows how telework prompted by the COVID‐19 pandemic restructured working time and redistributed the power of regulation. During lockdown periods, working hours were extended and work rhythms changed, with considerable variation depending on the family configuration: confinement with family was not conducive to extended working hours, instead tending to fragment them, whereas isolated teleworkers experienced the opposite effect.
Deconvoluting interrelationships between low‐energy vibrational modes and elastic properties in CaO–Al2O3 glasses
Authors: Nasikas Nektarios K. , Kalampounias Angelos G.
Published: June 2022

By employing a nonconventional melting technique, namely, the aerodynamic levitation combined with CO2 laser melting, we have been able to synthesize a series of glasses in the binary system xCaO − (1 − x)Al2O3, (x = 0.45, 0.50, 0.55, 0.60, 0.65, 0.70, 0.75, and 0.80). Utilizing Raman spectroscopy, we have systematically followed the compositionally induced spectral changes in the low‐frequency regime of the spectra, the so‐called Boson Peak (BP) region, and unraveled interesting interrelationships between the low‐energy vibrational modes and the elastic properties of calcium aluminate (CA) glasses. It was found that the BP frequency is not only systematically dependent on altering CaO content by exhibiting a minimum close to the eutectic composition. Interestingly, the above‐mentioned compositional dependence of the BP, which is exhibited in the shift of the BP frequency versus the altering CaO content, is also strongly correlated with its elastic properties and seems to follow similar patterns for the binary CA glassy system. The above observations point toward the estimation that the eutectic point can serve as a strong indicator for various physicochemical phenomena taking place in the solid–liquid transition and thus provide new insights in an effort to deconvolute the ambiguous interrelationships occurring in the low vibrational frequency regime of these glasses.
HbA1c measurement may save COVID‐19 inpatients from overlooked diabetes
Authors: Yoroidaka Ayaka , Kurita Seiichiro , Kita Toshiyuki
Published: June 2022

Aims/Introduction

To investigate overlooked diabetes in patients with coronavirus disease 2019 (COVID‐19).

Materials and Methods

In total, 462 COVID‐19 inpatients were included in this retrospective study. The presence of diabetes before COVID‐19 admission, and the HbA1c and blood glucose levels at admission were examined.

Results

Of the 462 patients, 116 had diabetes. Seventy‐six patients had been diagnosed with diabetes before COVID‐19 admission, and 40 patients were diagnosed for the first time. Of the patients with diabetes 72% required insulin. Patients with diabetes were significantly (P < 0.05) older, more likely to be male, heavier, and showed a lower eGFR. Patients with overlooked diabetes showed a lower HbA1c (average 7.1% vs 7.5%), a lower casual blood glucose (average 157 vs 179 mg/dL), and they used less insulin per day during hospitalization (average 16.0 units vs 34.5 units) than patients with previously diagnosed diabetes. Patients with overlooked diabetes tended to have more severe COVID‐19 than those with pre‐diagnosed diabetes. Multivariable logistic regression analyses showed that the increased odds ratios (ORs) of aggravation in all patients with COVID‐19 were associated with age [OR 1.04], BMI [OR 1.05], and diabetes [OR 2.15]. The risk factors for aggravation in patients with COVID‐19 and diabetes were age [OR 1.05] and HbA1c [OR 1.45].

Conclusions

Diabetes is a predictor of COVID‐19 aggravation. Furthermore, in COVID‐19 patients with diabetes, high HbA1c levels are a risk factor for severe COVID‐19. A total of 8.7% of COVID‐19 inpatients were diagnosed with diabetes after HbA1c was measured on admission. Therefore, it is important to measure HbA1c in COVID‐19 patients.
Plasma protein biomarkers for the detection of pancreatic neuroendocrine tumors and differentiation from small intestinal neuroendocrine tumors
Authors: Thiis‐Evensen Espen , Kjellman Magnus , Knigge Ulrich , Gronbaek Henning , Schalin‐Jäntti Camilla , Welin Staffan , Sorbye Halfdan , del Pilar Schneider Maria , Belusa Roger ,   The Nordic NET Biomarker Group
Published: June 2022

There is an unmet need for novel biomarkers to diagnose and monitor patients with neuroendocrine neoplasms. The EXPLAIN study explores a multi‐plasma protein and supervised machine learning strategy to improve the diagnosis of pancreatic neuroendocrine tumors (PanNET) and differentiate them from small intestinal neuroendocrine tumors (SI‐NET). At time of diagnosis, blood samples were collected and analyzed from 39 patients with PanNET, 135 with SI‐NET (World Health Organization Grade 1–2) and 144 controls. Exclusion criteria were other malignant diseases, chronic inflammatory diseases, reduced kidney or liver function. Prosed Oncology‐II (i.e., OLink) was used to measure 92 cancer related plasma proteins. Chromogranin A was analyzed separately. Median age in all groups was 65–67 years and with a similar sex distribution (females: PanNET, 51%; SI‐NET, 42%; controls, 42%). Tumor grade (G1/G2): PanNET, 39/61%; SI‐NET, 46/54%. Patients with liver metastases: PanNET, 78%; SI‐NET, 63%. The classification model of PanNET versus controls provided a sensitivity (SEN) of 0.84, specificity (SPE) 0.98, positive predictive value (PPV) of 0.92 and negative predictive value (NPV) of 0.95, and area under the receiver operating characteristic curve (AUROC) of 0.99; the model for the discrimination of PanNET versus SI‐NET providing a SEN 0.61, SPE 0.96, PPV 0.83, NPV 0.90 and AUROC 0.98. These results suggest that a multi‐plasma protein strategy can significantly improve diagnostic accuracy of PanNET and SI‐NET.
Commodity Financialization and Information Transmission
Authors: GOLDSTEIN ITAY , YANG LIYAN
Published: June 2022

We provide a model to understand the effects of commodity futures financialization on various market variables. We distinguish between financial speculators and financial hedgers and study their separate and combined effects on the informativeness of futures prices, the futures price bias, the comovement of futures prices with other markets, and the predictiveness of financial trading. We capture the interactions between commodity futures financialization and the real economy through spot prices and production decisions. A dynamic extension illustrates how key variables change over time in a period of acute financialization in a way that is consistent with observed empirical patterns.
Raising the minimum age of criminal responsibility to 14 years
Authors: Haysom Leigh
Published: June 2022

At 10 years of age, Australia and New Zealand have one of the lowest ages for criminal responsibility across the developed world. Evidence shows that children under 14 years of age are not mature enough to be considered criminally responsible people. Children of this age do not have the ability to advocate for themselves within the criminal justice system, which is systematically biased in how it deals with the youngest offenders. The over‐representation of Indigenous youth within the justice system is seen at its most extreme in the 10–14 years age group, and contact with the criminal justice system at this age is strongly associated with re‐offending, and is considered ‘criminogenic’. Raising the minimum age of criminal responsibility is likely to decrease overall rates of youth offending, and reduce the over‐representation of Indigenous children at all points of contact with the criminal justice system.
Polycythemia in dogs with chronic hypoxic pulmonary disease
Authors: Holopainen Saila , Laurila Henna P. , Lappalainen Anu K. , Rajamäki Minna M. , Viitanen Sanna J.
Published: June 2022

Background

Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis.

Objective

To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs.

Animals

Forty‐seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls.

Methods

Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO2] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis.

Results

Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0‐17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13‐38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0‐14) dogs. No marked polycythemia (Hct ≥65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO2: Erytr, r = −.14; Hb, r = −.21; Hct, r = −.14; P > .05 for all).

Conclusions and Clinical Importance

Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.
Effect of station format on the psychometric properties of Multiple Mini Interviews
Authors: Renaud Jean‐Sébastien , Bourget Martine , St‐Onge Christina , Eva Kevin W. , Tavares Walter , Salvador Loye Alexis , Leduc Jean‐Michel , Homer Matt
Published: June 2022

Background

Given the widespread use of Multiple Mini Interviews (MMIs), their impact on the selection of candidates and the considerable resources invested in preparing and administering them, it is essential to ensure their quality. Given the variety of station formats used and the degree to which that factor resides in the control of training programmes that we know so little about, format's effect on MMI quality is a considerable oversight. This study assessed the effect of two popular station formats (interview vs. role‐play) on the psychometric properties of MMIs.

Methods

We analysed candidate data from the first 8 years of the Integrated French MMIs (IF‐MMI) (2010–2017, n = 11 761 applicants), an MMI organised yearly by three francophone universities and administered at four testing sites located in two Canadian provinces. There were 84 role‐play and 96 interview stations administered, totalling 180 stations. Mixed design analyses of variance (ANOVAs) were used to test the effect of station format on candidates' scores and stations' discrimination. Cronbach's alpha coefficients for interview and role‐play stations were also compared. Predictive validity of both station formats was estimated with a mixed multiple linear regression model testing the relation between interview and role‐play scores with average clerkship performance for those who gained entry to medical school (n = 462).

Results

Role‐play stations (M = 20.67, standard deviation [SD] = 3.38) had a slightly lower mean score than interview stations (M = 21.36, SD = 3.08), p < 0.01, Cohen's d = 0.2. The correlation between role‐play and interview stations scores was r = 0.5 (p < 0.01). Discrimination coefficients, Cronbach's alpha and predictive validity statistics did not vary by station format.

Conclusion

Interview and role‐play stations have comparable psychometric properties, suggesting format to be interchangeable. Programmes should select station format based on match to the personal qualities for which they are trying to select.
FOXM1‐mediated NUF2 expression confers temozolomide resistance to human glioma cells by regulating autophagy via the PI3K/AKT/mTOR signaling pathway
Authors: Guo Liang , Wu Zhangyi
Published: June 2022

Glioma is the most common malignant tumor in the central nervous system and has a high mortality rate. Temozolomide (TMZ) is a widely used chemotherapeutic drug for glioma. NDC80 kinetochore complex (NUF2) is suggested to play a regulatory role in different cancers, but its specific function and mechanism in glioblastoma TMZ resistance remain unknown. NUF2, assessed by reverse transcription quantitative polymerase chain reaction (RT‐qPCR), was highly expressed in glioma cell lines. TMZ was used to treat cells to establish a TMZ‐resistant cell line. The potential functions of NUF2 in glioma were assessed using cell counting kit‐8 (CCK‐8) assays, colony formation assays, 5‐Ethynyl‐2'‐deoxyuridine (EdU) assays, flow cytometry, Western blotting, and a tumor xenograft model. The results showed that NUF2 knockdown attenuated malignant phenotypes of TMZ‐resistant cells and prevented tumor growth. Mechanistically, as luciferase reporter assays and chromatin immunoprecipitation (ChIP) as showed, Fox transcription factor M1 (FOXM1) had binding sites on the NUF2 promoter. Rescue assays demonstrated that FOXM1 upregulation counteracted the inhibitory effects of NUF2 depletion on the malignancies of TMZ‐resistant cells. This study demonstrates that FOXM1‐activated NUF2 promotes TMZ to human glioma cells by regulating proliferation, apoptosis, and autophagy.
Seasonal changes in testis size, testosterone levels and sperm production quality in meat rams
Authors: Aibazov Magomet , Trukhachev Vladimir , Selionova Marina , Malorodov Viktor
Published: June 2022

The aim of the present study was to evaluate seasonal changes in testes size, serum testosterone (T) levels and sperm production characteristics of 24 adult (2–3 years old) rams of meat breeds: Charollais (n = 6), Ile de France (n = 6), Dorset (Polled) (n = 5) and Dorper (Dorper, n = 7). Semen was collected with artificial vagina using a female in spontaneous oestrus (September–November, breeding season, BS) or a female with induced oestrus (March–July, non‐breeding season, NBS). A total of 672 ejaculates were examined. Jugular vein blood was collected to determine testosterone levels during BS and NBS, and serum was extracted. Results of the present study indicate that there was no significant change in parameters such as body weight (kg) and testes length, both right and left, during BS and NBS, irrespective of the breed. The remaining metrics of testes differ in varying degrees between breeds of rams (with the exception of the Dorper breed) between BS and NBS. No significant variation in these parameters was found in Dorper rams. For all breeds, season had a statistically significant effect on important parameters such as total sperm count and progressive sperm motility after thawing. There was also significant seasonal variation in ejaculate volume across the three breeds, excluding il‐de‐France rams. The most constant was the sperm concentration, which was unchanged in BS and NBS in the three breeds, excluding Dorset rams, which showed a slightly significant decrease in this indicator in the non‐breeding season. The serum content of the major male hormone testosterone (T) in rams of all breeds showed significant changes between BS and NBS, decreasing by a highly significant amount in the non‐breeding season.
All-optical graph representation learning using integrated diffractive photonic computing units
Authors: Yan Tao , Yang Rui , Zheng Ziyang , Lin Xing , Xiong Hongkai , Dai Qionghai
Published: June 2022

Photonic neural networks perform brain-inspired computations using photons instead of electrons to achieve substantially improved computing performance. However, existing architectures can only handle data with regular structures but fail to generalize to graph-structured data beyond Euclidean space. Here, we propose the diffractive graph neural network (DGNN), an all-optical graph representation learning architecture based on the diffractive photonic computing units (DPUs) and on-chip optical devices to address this limitation. Specifically, the graph node attributes are encoded into strip optical waveguides, transformed by DPUs, and aggregated by optical couplers to extract their feature representations. DGNN captures complex dependencies among node neighborhoods during the light-speed optical message passing over graph structures. We demonstrate the applications of DGNN for node and graph-level classification tasks with benchmark databases and achieve superior performance. Our work opens up a new direction for designing application-specific integrated photonic circuits for high-efficiency processing large-scale graph data structures using deep learning.
CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy
Authors: Chen Ping-Min , Katsuyama Eri , Satyam Abhigyan , Li Hao , Rubio Jose , Jung Sungwook , Andrzejewski Sylvia , Becherer J. David , Tsokos Maria G. , Abdi Reza , Tsokos George C.
Published: June 2022

Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD
+
, is up-regulated in CD8
+
T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8
+
T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8
+
T cell–targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.
Draft Genome Sequences of
Flavobacterium covae
Strains LSU-066-04 and LV-359-01
Authors: Churchman Emily M. , Parello Gianni , Lange Miles D. , Farmer Bradley D. , LaFrentz Benjamin R. , Beck Benjamin H. , Liles Mark R.
Published: June 2022

Flavobacterium covae
is one of four
Flavobacterium
spp. that cause columnaris disease in teleost fish. Here, we report the draft genomes of two isolates, LSU-066-04 and LV-359-01, and their predicted virulence factors.
Fifteen-minute consultation: An overview of major incidents
Authors: Widya Stefani , Hewitson Rebecca , Patel Tulsi , Roland Damian , Dadnam Christopher
Published: June 2022

Major incidents are rare but require a large amount of preparation, co-ordination and communication across different emergency services and specialities. This ensures that casualties are efficiently managed within the constraints of limited clinical resources. This article aims to provide a brief understanding of what constitutes as a major incident, how it is declared and the chain of command in communication and action, focusing specifically on the paediatric process. It also aims to highlight important considerations that could potentially be missed (eg, the mental health impact, forensic evidence and so on).
Antenatal Doppler screening for fetuses at risk of adverse outcomes: a multicountry cohort study of the prevalence of abnormal resistance index in low-risk pregnant women
Authors: Vannevel Valerie , Vogel Joshua P , Pattinson Robert C , Adanu Richard , Charantimath Umesh , Goudar Shivaprasad S , Gwako George , Kavi Avinash , Maya Ernest , Osoti Alfred , Pujar Yeshita , Qureshi Zahida P , Rulisa Stephen , Botha Tanita , Oladapo Olufemi T
Published: June 2022

Introduction

Few interventions exist to address the high burden of stillbirths in apparently healthy pregnant women in low- and middle-income countries (LMICs). To establish whether a trial on the impact of routine Doppler screening in a low-risk obstetric population is warranted, we determined the prevalence of abnormal fetal umbilical artery resistance indices among low-risk pregnant women using a low-cost Doppler device in five LMICs.

Methods

We conducted a multicentre, prospective cohort study in Ghana, India, Kenya, Rwanda and South Africa. Trained nurses or midwives performed a single, continuous-wave Doppler screening using the Umbiflow device for low-risk pregnant women (according to local guidelines) between 28 and 34 weeks’ gestation. We assessed the prevalence of abnormal (raised) resistance index (RI), including absent end diastolic flow (AEDF), and compared pregnancy and health service utilisation outcomes between women with abnormal RI versus those with normal RI.

Results

Of 7151 women screened, 495 (6.9%) had an abnormal RI, including 14 (0.2%) with AEDF. Caesarean section (40.8% vs 28.1%), labour induction (20.5% vs 9.0%) and low birth weight (<2500 g) (15.0% vs 6.8%) were significantly more frequent among women with abnormal RI compared with women with normal RI. Abnormal RI was associated with lower birth weights across all weight centiles. Stillbirth and perinatal mortality rates were similar between women with normal and abnormal RI.

Conclusion

A single Doppler screening of low-risk pregnant women in LMICs using the Umbiflow device can detect a large number of fetuses at risk of growth restriction and consequent adverse perinatal outcomes. Many perinatal deaths could potentially be averted with appropriate intervention strategies.

Trial registration number

CTRI/2018/07/01486.
Impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients: a prospective cohort study
Authors: Saleem Shahzadi Sidra , Khan Amjad , Aman Rubina , Saleem Shahzadi Sadia , Bibi Ayesha , Ahmad Nafees , Mushtaq Saima , Mehsud Saifullah , Green Ivan R , Rashid Sheikh Abdur , Khan Ahmad , Shah Kifayat Ullah
Published: June 2022

Objectives

Poor control of asthma in the majority of patients could be partly due to their lack of knowledge concerning disease management, its triggering agents and when to seek advice from the healthcare provider. This study aims to assess the impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients.

Design

A pre–post cohort study.

Setting

Outpatient department of a tertiary care hospital affiliated with Quaid-i-Azam University, Pakistan.

Participants

Approximately 265 adult asthmatic patients selected through a spirometry process, aged ≥18 years, were approached. 240 patients gave consent to participate in the study and were divided into control and treatment groups.

Interventions

The educational intervention consisted of individual patient counselling using educational material with time varied according to each patient’s comprehension and previous knowledge.

Primary and secondary outcome measures

Assessment consisted of a 14-item Asthma Self-Management Knowledge Questionnaire (ASMQ) quantifying a patient’s self-management knowledge through an ASMQ score and its change following an educational intervention.

Results

Disease self-management knowledge was low with an average raw ASMQ score of 4.1 (max 14); which equates to a transformed score of 29.34 (max 100) and the proportion of patients who correctly answered more than 50% of questions were 16.7% preintervention. More than half of the participants (55%) did not know that asthma cannot be cured. The administration of educational intervention protocols resulted in significantly improved level of knowledge of asthma self-management (<0.001) in the treatment group (mean ASMQ score improved from 4.20 to 9.77).

Conclusion

On baseline visit, patients possessed a poor knowledge about asthma self-management. Educational intervention protocols had a positive impact on improving patients’ knowledge about disease self-management. This would suggest that education and self-management skills should be seen as an integral component of asthma management and should be incorporated in structured patient care to achieve optimal asthma control.
Can incentives improve antipsychotic adherence in major mental illness? A mixed-methods systematic review
Authors: Hodson Nathan , Majid Madiha , Vlaev Ivo , Singh Swaran Preet
Published: June 2022

Objectives

Incentives have been effectively used in several healthcare contexts. This systematic review aimed to ascertain whether incentives can improve antipsychotic adherence, what ethical and practical issues arise and whether existing evidence resolves these issues.

Design

Systematic review of MEDLINE, EMBASE and PsycINFO. Searches on 13 January 2021 (no start date) found papers on incentives for antipsychotics. Randomised controlled trials (RCTs), cohort studies, qualitative research and ethical analyses were included. Papers measuring impact on adherence were synthesised, then a typology of ethical and policy issues was compiled, finally the empirical literature was compared with this typology to describe current evidence and identify remaining research questions.

Results

26 papers were included. 2 RCTs used contingent financial incentives for long-acting injectable antipsychotic preparations. Over 12 months, there were significantly larger increases in adherence among the intervention groups versus control groups in both RCTs. There were no consistently positive secondary outcomes. 39 ethical and practical issues were identified. 12 of these are amenable to empirical study but have not been researched and for 7 the current evidence is mixed.

Conclusions

In keeping with other areas of healthcare, antipsychotic adherence can be increased with financial incentives. Payments of 2.5 times minimum wage changed behaviour. The typology of issues reported in this systematic review provides a template for future policy and ethical analysis. The persistence of the effect and the impact of incentives on intrinsic motivation require further research.

PROSPERO registration number

CRD42020222702.
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases
Authors: Sullivan Kevin M , Jiang Xiuyun , Guha Prajna , Lausted Christopher , Carter Jason A , Hsu Cynthia , Labadie Kevin P , Kohli Karan , Kenerson Heidi L , Daniel Sara K , Yan Xiaowei , Meng Changting , Abbasi Arezou , Chan Marina , Seo Y David , Park James O , Crispe Ian Nicholas , Yeung Raymond S , Kim Teresa S , Gujral Taranjit S , Tian Qiang , Katz Steven C , Pillarisetty Venu G
Published: June 2022

Objective

Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures.

Design

We created organotypic slice cultures from human CRLM (n=38 patients’ tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy.

Results

αIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8+T cells without exhaustion transcription changes, and increased human leukocyte antigen - DR isotype (HLA-DR) expression of macrophages. The antitumour effects of αIL-10 were reversed by major histocompatibility complex class I or II (MHC-I or MHC-II) blockade, confirming the essential role of antigen presenting cells. Interrupting IL-10 signalling also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 increased CEA-specific CAR-T cell activation and CAR-T cell-mediated cytotoxicity, with nearly 70% carcinoma cell apoptosis across multiple human tumours. Pretreatment with an IL-10 receptor blocking antibody also potentiated CAR-T function.

Conclusion

Neutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.
Escape from cell-cell and cell-matrix adhesion dependence underscores disease progression in gastric cancer organoid models
Authors: Tong Yin , Cheng Priscilla S W , Or Chung Sze , Yue Sarah S K , Siu Hoi Cheong , Ho Siu Lun , Law Simon Y K , Tsui Wai Yin , Chan Dessy , Ma Stephanie , Lee Siu Po , Chan Annie S Y , Chan April S , Yun Shui Wa , Hui Ho Sang , Yuen Siu Tsan , Leung Suet Yi , Yan Helen H N
Published: June 2022

Objective

Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells.

Design

We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix or both to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers:ARHGAPfusions,RHOAandCDH1,in modulating CC (CCi) or CM (CMi) adhesion independence.

Results

97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to three public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling viaRHOAmutation orARHGAPfusions. Inducible knockout ofARHGAPfusions in CCi/CMi tumour organoids led to resensitisation to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype and inhibited xenograft formation. Normal gastric organoids engineered withCDH1orRHOAmutations became CMi or CCi, respectively.

Conclusions

The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.
Principles and methods of global legal epidemiology
Authors: Poirier Mathieu J P , Viens A M , Penney Tarra L , Rogers Van Katwyk Susan , Astbury Chloe C , Lin Gigi , Nanyangwe-Moyo Tina , Hoffman Steven J
Published: June 2022

Although the theory and methods of legal epidemiology—the scientific study and deployment of law as a factor in the cause, distribution, and prevention of disease and injury in a population—have been well developed in the context of domestic law, the challenges posed by shifting the frame of analysis to the global legal space have not yet been fully explored. While legal epidemiology rests on the foundational principles that law acts as an intervention, that law can be an object of scientific study and that law has impacts that should be evaluated, its application to the global level requires the recognition that international laws, policies and norms can cause effects independently from their legal implementation within countries. The global legal space blurs distinctions between ‘hard’ and ‘soft’ law, often operating through pathways of global agenda setting, legal language, political pressures, social mobilisation and trade pressures to have direct impacts on people, places and products. Despite these complexities, international law has been overwhelmingly studied as operating solely through national policy change, with only one global quasi-experimental evaluation of an international law’s impact on health published to date. To promote greater adoption of global legal epidemiology, we expand on an existing typology of public health law studies with examples of policymaking, mapping, implementation, intervention and mechanism studies. Global legal epidemiology holds great promise as a way to produce rigorous and impactful research on the international laws, policies and norms that shape our collective health, equity and well-being.
Measuring CP nature of $$h\tau {{\bar{\tau }}}$$ coupling at $$e^-p$$ collider
Authors: Dutta Sukanta , Goyal Ashok , Kumar Mukesh , Swain Abhaya Kumar
Published: June 2022

The proposed future $$e^- p$$

e
-

p

collider provides sufficient energies to produce the Standard Model Higgs Boson (h) through $$W^\pm $$

W
±

and Z-Boson fusion in charged and neutral current modes, respectively and to measure its properties. We take this opportunity to investigate the prospect of measuring the CP properties of h through $$h \rightarrow \tau ^{+} \tau ^{-}$$

h
→

τ
+

τ
-

, where $$\tau ^{-}\,\left( \tau ^{+}\right) $$

τ
-

τ
+

decays to a charged pion $$\pi ^-\,\left( \pi ^+\right) $$

π
-

π
+

and a neutral pion $$\pi ^0$$

π
0

in association with neutrino (anti-neutrino). An interesting CP sensitive angular observable $$\alpha _{\mathrm{CP}}$$

α
CP

between the two $$\tau $$
τ
-leptons decay plane in the $$\pi ^+\pi ^-$$

π
+

π
-

centre of mass frame is proposed and investigated in this work. For fixed electron energy of 150 GeV along with 7 (50) TeV of proton energy, the CP phase can be measured approximately to $$25^\circ $$

25
∘

($$14^\circ $$

14
∘

) at integrated luminosity of 1 ab$$^{-1}$$

-
1

for −80% polarised electron at 95% confidence level.
Bilinear forms, N-soliton solutions, breathers and lumps for a (2+1)-dimensional generalized breaking soliton system
Authors: Hu Lei , Gao Yi-Tian , Jia Ting-Ting , Deng Gao-Fu , Su Jing-Jing
Published: June 2022

In this paper, a ([Formula: see text])-dimensional generalized breaking soliton system, for the interactions of the Riemann wave with a long wave, is investigated. Via the Hirota method, bilinear forms different from those in the existing literatures are derived. [Formula: see text]-soliton solutions are constructed via the Wronskian technique. Solitons with the crest curves being curvilineal are constructed, whose shape changes with the propagation. Parallel solitons have been obtained. Directions of the soliton propagation change, and speeds of the solitons are different: The higher the amplitude of the soliton is, the faster the soliton propagates. Breathers are constructed. Solutions consisting of a lump and two solitons are derived: Two solitons propagate in the same direction and the lump occurs in the region of the interaction between the two solitons.
Phase characterization and new optical solitons of a pulse passing through nonlinear dispersive media
Authors: Raza Nauman , Arshed Saima , Salman Farwa , Gómez-Aguilar J. F. , Torres-Jiménez J.
Published: June 2022

In this paper, modified equal width Burgers’ equation has been investigated with the aid of unified method and bifurcation. This model has many applications in long wave transmission with dispersion and dissipation in nonlinear medium. The applied technique is efficient to retrieve exact solutions and their dynamic behaviors. The obtained solutions are polynomial and rational function solutions. The behavior of dynamical planer system has been analyzed by assigning different values to the parameters, also each possible case has been shown as phase portraits in this research paper. The estimated solutions demonstrate that the proposed approaches are simple, practical, and promising for investigating further equal width equation’s soliton wave solutions and phase portraits.
COVID-19 and information coevolution in post-epidemic era
Authors: Diao Hongyuan , Nian Fuzhong
Published: June 2022

In this paper, a two-layer network on various immunization strategies in the post-epidemic era is constructed and an improved symbiotic evolutionary model of COVID-19 and information collaboration is proposed. The dynamic transformation probability is introduced to influence the virus information transmission coevolutionary process. The dynamic transformation probability is influenced by the immunization strategies and vertex characteristics. We quantify the effects of immunization strategy, node properties, global temperature, and collaborative information dissemination on new crown outbreaks. We simulated our model in a scale-free network to analyze the propagation. The evolutionary phenomenon of the network during propagation was investigated. We simulated the proven epidemic information coevolutionary model in a two-layer network, validated it with real data comparisons by proving that our proposed model fits the real situation.
Productivity Growth and Technology Gaps of the National Systems of Entrepreneurship: Is There a Convergence Pattern between Efficiency-Driven and Innovation-Driven Countries?
Authors: Mitropoulos Panagiotis , Mitropoulos Alexandros
Published: June 2022

Entrepreneurship is an essential component to national economies, and a formidable engine of economic growth. Recognizing that success in entrepreneurship depends to a large extent on national context and local conditions our aim is to develop a framework to analyze national ecosystems and benchmark them with other countries to gain insights into the success or failure of entrepreneurial policies. This study uses a metafrontier framework with consideration to gauge the entrepreneurial ecosystem productivity across countries that operate under different technologies. Based on the metafrontier Malmquist productivity index, this paper analyzes the national entrepreneurial productivity of 30 countries over the period 2016–2018. By classifying the sample countries according to their level of economic development, we obtain that the efficiency-driven countries are the technology leaders in entrepreneurship, and innovation-driven countries are the followers. During the study period, the efficiency-driven countries have exhibited productivity growth of 0.5% which is mainly attributed by technological progress. Whereas, the innovation-driven countries have deteriorated their productivity by 0.7% which caused by their technological regress. Meanwhile the innovation-driven countries cached-up the world best practice technology at a faster rate than the efficiency-driven countries which indicate there was some convergence between the two groups over time.