bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study
Authors: Ballouz Tala , Menges Dominik , Anagnostopoulos Alexia , Domenghino Anja , Aschmann Hélène E , Frei Anja , Fehr Jan S , Puhan Milo A
Published: June 2023

Objective

To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection.

Design

Population based, longitudinal cohort.

Setting

General population of canton of Zurich, Switzerland.

Participants

1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection.

Main outcome measures

Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection.

Results

22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)).

Conclusions

Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials.

Study registration

Current Controlled Trials
ISRCTN14990068

Current Controlled Trials
ISRCTN18181860
Postneonatal under-5 mortality in peri-urban and rural Eastern Uganda, 2005–2015
Authors: Hirose Atsumi , Kajungu Dan , Tusubira Valerie , Waiswa Peter , Alfven Tobias , Hanson Claudia
Published: June 2023

Introduction

Community and individual sociodemographic characteristics play an important role in child survival. However, a question remains how urbanisation and demographic changes in sub-Saharan Africa affect community-level determinants for child survival.

Methods

Longitudinal data from the Iganga/Mayuge Health and Demographic Surveillance Site was used to obtain postneonatal under-5 mortality rates between March 2005 and February 2015 in periurban and rural areas separately. Multilevel survival analysis models were used to identify factors associated with mortality.

Results

There were 43 043 postneonatal under-5 children contributing to 116 385 person years of observation, among whom 1737 died. Average annual crude mortality incidence rate (IR) differed significantly between periurban and rural areas (9.0 (8.1 to 10.0) per 1000 person-years vs 18.1 (17.1 to 19.0), respectively). In periurban areas, there was evidence for decreasing mortality from IR=11.3 (7.7 to 16.6) in 2006 to IR=4.5 (3.0 to 6.9) in 2015. The mortality fluctuated with no evidence for reduction in rural areas (IR=19.0 (15.8 to 22.8) in 2006; IR=15.5 (13.0 to 18.6) in 2015). BCG vaccination was associated with reduced mortality in periurban and rural areas (adjusted rate ratio (aRR)=0.45; 95% CI 0.30 to 0.67 and aRR=0.56; 95% CI 0.41 to 0.76, respectively). Maternal education level within the community was associated with reduced mortality in both periurban and rural sites (aRR=0.83; 95% CI 0.70 to 0.99; aRR=0.90; 95% CI 0.81 to 0.99). The proportion of households in the poorest quintile within the community was associated with mortality in rural areas only (aRR=1.08; 95% CI 1.00 to 1.18). In rural areas, a large disparity existed between the least poor and the poorest (aRR=0.50; 95% CI 0.27 to 0.92).

Conclusion

We found evidence for a mortality decline in peri-urban but not rural areas. Investments in the known key health (eg, vaccination) and socio-economic interventions (education, and economic development) continue to be crucial for mortality declines. Focused strategies to eliminate the disparity between wealth quintiles are also warranted. There may be equitable access to health services in peri-urban areas but improved metrics of socioeconomic position suitable for peri-urban residents may be needed.
Effectiveness of a mental health stepped-care programme for healthcare workers with psychological distress in crisis settings: a multicentre randomised controlled trial
Authors: Mediavilla Roberto , Felez-Nobrega Mireia , McGreevy Kerry R , Monistrol-Mula Anna , Bravo-Ortiz María-Fe , Bayón Carmen , Giné-Vázquez Iago , Villaescusa Rut , Muñoz-Sanjosé Ainoa , Aguilar-Ortiz Salvatore , Figueiredo Natasha , Nicaise Pablo , Park A-La , Petri-Romão Papoula , Purgato Marianna , Witteveen Anke B , Underhill James , Barbui Corrado , Bryant Richard , Kalisch Raffael , Lorant Vincent , McDaid David , Melchior Maria , Sijbrandij Marit , Haro Josep Maria , Ayuso-Mateos Jose Luis
Published: June 2023

Background

Evidence-based mental health interventions to support healthcare workers (HCWs) in crisis settings are scarce.

Objective

To evaluate the capacity of a mental health intervention in reducing anxiety and depression symptoms in HCWs, relative to enhanced care as usual (eCAU), amidst the COVID-19 pandemic.

Methods

We conducted an analyst-blind, parallel, multicentre, randomised controlled trial. We recruited HCWs with psychological distress from Madrid and Catalonia (Spain). The intervention arm received a stepped-care programme consisting of two WHO-developed interventions adapted for HCWs: Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+). Each intervention lasted 5 weeks and was delivered remotely by non-specialist mental health providers. HCWs reporting psychological distress after DWM completion were invited to continue to PM+. The primary endpoint was self-reported anxiety/depression symptoms (Patient Health Questionnaire-Anxiety and Depression Scale) at week 21.

Findings

Between 3 November 2021 and 31 March 2022, 115 participants were randomised to stepped care and 117 to eCAU (86% women, mean age 37.5). The intervention showed a greater decrease in anxiety/depression symptoms compared with eCAU at the primary endpoint (baseline-adjusted difference 4.4, 95% CI 2.1 to 6.7; standardised effect size 0.8, 95% CI 0.4 to 1.2). No serious adverse events occurred.

Conclusions

Brief stepped-care psychological interventions reduce anxiety and depression during a period of stress among HCWs.

Clinical implications

Our results can inform policies and actions to protect the mental health of HCWs during major health crises and are potentially rapidly replicable in other settings where workers are affected by global emergencies.

Trial registration number

NCT04980326.
Rubella seroprevalence among pregnant women in the region of Rabat, Morocco: a cross-sectional study
Authors: Lamrani Alaoui Hafsa , Seffar Myriam , Kassouati Jalal , Zouaki Amal , Kabbaj Hakima
Published: June 2023

Objectives

The aim of the present research is to update data on the seroprevalence of rubella and to identify the associated risk factors among pregnant women in the Rabat region of Morocco in order to take immediate action to monitor the virus.

Design

A cross-sectional study.

Setting

The study was conducted at Ibn Sina University Hospital and at referral healthcare centres in the region of Rabat.

Participants

A total of 502 pregnant women (mean age 29.7±6.3 years, range 17–44 years) attending the maternity department during 8 months were selected for serological testing.

Outcome measures

A structured questionnaire was used to obtain sociodemographic, reproductive and clinical characteristics after obtaining written informed consent. Venous blood samples were collected to determine rubella-specific IgG antibodies using an automated chemiluminescent microparticle immunoassay (ARCHITECT i1000SR and i2000SR, Abbott Diagnostics).

Results

Antirubella IgG antibodies (≥10 IU/mL) were found in 408 (85.9%) pregnant women examined. The rate of susceptibility to rubella virus infection among pregnant women was found to be 14.1%. These protective rates were found to differ significantly between uneducated pregnant women (80.9%) and those with university-level education (95.5%) (p=0.02). Pregnant women in the 17–24, 25–34 and 35–44 years age groups accounted for 92.5%, 85.2% and 82.8%, respectively (p=0.015). Also, IgG seropositivity status was found to differ significantly between multiparous (83.3%) and primiparous (92.5%) pregnant women (p=0.01). None of the other characteristics was significantly associated with rubella infections.

Conclusion

Vaccination programmes need to be updated to ensure that campaigns reach their specified goals. Thus, implementing an effective, large-scale screening programme for congenital rubella infection in different regions of Morocco is highly recommended. On the other hand, seronegative pregnant women should be given special preventive care and health education about rubella transmission and congenital rubella syndrome sequelae.
Barriers and facilitators of family doctor contract services in caring for disabled older adults in Beijing, China: a mixed methods study
Authors: Zhang Zhiying , Zhang Ruyi , Peng Yingchun , Zhai Shaoqi , Zhang Jiaying , Jin Qilin , Zhou Jiaojiao , Li Hanlin , Chen Jingjing
Published: June 2023

Objective

To evaluate the current state of family doctor contract services (FDCS) in Beijing, identify the roles of family doctors who have worked with disabled older adults and investigate the barriers and facilitators faced by family doctors in providing care for them.

Design

A convergent mixed methods study was carried out from October 2020 to January 2021 to collect and analyse both quantitative and qualitative data. The integration strategies in this study were connecting the results of the quantitative phase to data collection of the qualitative phase.

Setting

A multi-stage sampling strategy was used to select 15 community health centres (CHCs) in four districts of Beijing. Of the four districts, two were from urban areas and two were from rural areas.

Participants

The inclusion criteria for participants were (1) family doctors, (2) contracted with disabled older adults, (3) engaged in related work for disabled older adults more than 6 months.

Methods

A cluster sampling of 283 family doctors was used in the questionnaire. A purposive sample of 30 family doctors from the same CHCs was selected during the same period. Frequency and rank, rank-sum test, Kruskal-Wallis test were conducted in qualitative data analysis, the views of the interviewees were analysed through the thematic framework method.

Results

Currently, family doctors provided various services to satisfy the health needs of disabled older adults, while the usage of FDCS for disabled older adults is affected by many factors. The differences of the importance of family doctors’ role (p<0.001) and service satisfaction (p=0.004) were significant among four districts. Compared with contracted health senior citizens, this study has identified five unique roles of family doctors, including ‘psychological consultant’, ‘rehabilitation physiotherapist’, ‘health educator’, ‘health manager’ and ‘family health guardian’. Moreover, family doctors are confronted with a myriad of barriers (including high risks in the process of home visits, a lack of supervisory and incentive mechanisms, insufficiency of time and energy, etc) and facilitators (including establishing a doctor–patient trust relationship, developing humanistic care services, etc) in the FDCS for disabled older adults.

Conclusions

Family doctors play a pivotal role in the FDCS for disabled older adults, while the effect and quality of FDCS in China needs to be improved. It is suggested that further research needs to focus on solving existing barriers of FDCS to optimise the health of disabled older adults and improve the quality of their lives.
Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank
Authors: Cannings-John Rebecca , Schoenbuchner Simon , Jones Hywel , Lugg-Widger Fiona V , Akbari Ashley , Brookes-Howell Lucy , Hood Kerenza , John Ann , Thomas Daniel Rh , Prout Hayley , Robling Michael
Published: June 2023

Objectives

To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic.

Design

A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment.

Setting

Registered DCW population in Wales.

Participants

Records for all linked DCWs from 1 March 2020 to 30 November 2021.

Primary and secondary outcome measures

Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality.

Results

Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15–64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate.

Conclusions

While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector’s workforce.
Implementation of early warning system in the clinical teaching unit to reduce unexpected deaths
Authors: Swami Tara , Shams Ali , Mittelstadt Matthew , Guenther Catherine , Tse Tiffanie , Noor Hifsa , Shahid Rabia
Published: June 2023

Background

Early detection of patients with clinical deterioration admitted to the hospital is critical. The early warning system (EWS) is developed to identify early clinical deterioration. Using individual patient’s vital sign records, this bedside score can identify early clinical deterioration, triggering a communication algorithm between nurses and physicians, thereby facilitating early patient intervention. Although various models have been developed and implemented in emergency rooms and paediatric units, data remain sparse on the utility of the EWS in patients admitted to general internal medicine wards and the processes and challenges encountered during the implementation.

Local problem

There is a lack of standardised tools to recognise early deterioration of patient condition.

Methods

This was a quality improvement project piloted in the clinical teaching unit of a tertiary care hospital. Data were collected 24 weeks pre-EWS and 55 weeks post-EWS implementation. A series of Plan, Do, Study, Act cycles were conducted to identify the root cause, develop a driver diagram to understand the drivers of unexpected deaths, run a sham test trial run of the EWS, educate and obtained feedback of clinical care teams involved, assess adherence to the EWS during the pilot project (6 weeks pre-EWS and 6 weeks post-EWS implementation), evaluate outcomes by extending the duration to 24 weeks pre-EWS and 55 weeks post-EWS implementation, and retrospectively review the uptake of the EWS.

Interventions

Implementation of a standardised protocol to detect deterioration in patient condition.

Results

During the pre-EWS implementation phase (24 weeks), there were 4.4 events per week (1.2 septic workups, 1.9 observation unit transfers, 0.7 critical care transfers, 0.13 cardiac arrests and 0.46 per week unexpected deaths). In the post-EWS implementation phase (55 weeks), there were 4.2 events per week (1.0 septic workup, 1.9 observation unit transfers, 0.82 critical care transfers, 0.25 cardiac arrests and 0.25 unexpected deaths).

Conclusion

The EWS can improve patient care; however, more engagement of stakeholders and electronic vital sign documentation may improve the uptake of the system.
Phase I trial of KN046, a novel bispecific antibody targeting PD-L1 and CTLA-4 in patients with advanced solid tumors
Authors: Ma Yuxiang , Xue Jinhui , Zhao Yuanyuan , Zhang Yang , Huang Yan , Yang Yunpeng , Fang Wenfeng , Guo Ye , Li Qun , Ge Xiaoxiao , Sun Jie , Zhang Bangyong , Zhang Yuhan , Xiao Jinyuan , Zhang Li , Zhao Hongyun
Published: June 2023

Background

KN046 is a novel bispecific antibody targeting programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This multicenter phase I trial investigated the safety, tolerability, pharmacokinetics (PK), and efficacy of KN046 in patients with advanced solid tumors.

Methods

Patients who failed standard treatment were included. KN046 was administered at doses of 1, 3, and 5 mg/kg every 2 weeks (Q2W), 5 mg/kg every 3 weeks (Q3W), and 300 mg Q3W based on the modified toxicity probability interval method in the dose-escalation phase; the recommended dose was used in the expansion phase. Primary objectives were maximum tolerated dose (MTD) and recommended phase II dose (RP2D) in escalation and preliminary efficacy in expansion. Secondary objectives included PK, pharmacodynamics, safety, and tolerability of KN046. We also explored biomarkers based on PD-L1 expression, multiplex immunofluorescence (mIF) staining, and RNAseq-derived nCounter platform.

Results

Totally, 100 eligible patients were enrolled, including 59 with nasopharyngeal carcinoma (NPC), 36 with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), and those with other advanced solid tumors. The most common treatment-related adverse events (TRAEs) were rash (33.0%), pruritus (31.0%), and fatigue (20.0%). Grade ≥3 TRAEs were observed in 14.0% of participants. No dose-limiting toxicity occurred in the dose-escalation phase, and the MTD was not reached. The RP2D was determined as 5 mg/kg Q2W according to the pharmacokinetic–pharmacodynamic model, the preliminary exposure–response analysis, and the overall safety profile. Among 88 efficacy-evaluable participants, the objective response rate (ORR) was 12.5%, and the median duration of response was 16.6 months. In the NPC subgroup, the ORR was 15.4%, and the median overall survival (OS) was 24.7 (95% CI 16.3 to not estimable) months. In the EGFR-mutant NSCLC subgroup, the ORR was 6.3%. mIF analysis results showed patients with high CD8 expression showed longer median OS (27.1 vs 9.2 months, p=0.02); better prognosis was observed in patients with high CD8 and PD-L1 expression.

Conclusions

KN046 was well tolerated and showed promising antitumor efficacy in advanced solid tumors, especially in patients with NPC. The combination of both CD8 and PD-L1 expression improved the prediction of KN046 response.

Trial registration numbers

NCT03733951.
Storing paediatric genomic data for sequential interrogation across the lifespan
Authors: Gyngell Christopher , Lynch Fiona , Vears Danya , Bowman-Smart Hilary , Savulescu Julian , Christodoulou John
Published: June 2023

Genomic sequencing (GS) is increasingly used in paediatric medicine to aid in screening, research and treatment. Some health systems are trialling GS as a first-line test in newborn screening programmes. Questions about what to do with genomic data after it has been generated are becoming more pertinent. While other research has outlined the ethical reasons for storing deidentified genomic data to be used in research, the ethical case for storing data for future clinical use has not been explicated. In this paper, we examine the ethical case for storing genomic data with the intention of using it as a lifetime health resource. In this model, genomic data would be stored with the intention of reanalysis at certain points through one’s life. We argue this could benefit individuals and create an important public resource. However, several ethical challenges must first be met to achieve these benefits. We explore issues related to privacy, consent, justice and equality. We conclude by arguing that health systems should be moving towards futures that allow for the sequential interrogation of genomic data throughout the lifespan.
Evoked mid-frontal activity predicts cognitive dysfunction in Parkinson’s disease
Authors: Singh Arun , Cole Rachel C , Espinoza Arturo I , Wessel Jan R , Cavanagh James F , Narayanan Nandakumar S
Published: June 2023

Background

Cognitive dysfunction is a major feature of Parkinson’s disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that mid-frontal delta/theta rhythms predict cognitive dysfunction in PD.

Method

We recruited 100 patients with PD and 49 demographically similar control participants who completed a series of cognitive control tasks, including the Simon, oddball and interval-timing tasks. We focused on cue-evoked delta (1–4 Hz) and theta (4–7 Hz) rhythms from a single mid-frontal EEG electrode (cranial vertex (Cz)) in patients with PD who were either cognitively normal, with mild-cognitive impairments (Parkinson’s disease with mild-cognitive impairment) or had dementia (Parkinson’s disease dementia).

Results

We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased mid-frontal delta power across all tasks. Within patients with PD, the first principal component of evoked electroencephalography features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment score (r=0.34) and with National Institutes of Health Toolbox Executive Function score (r=0.46).

Conclusions

These data demonstrate that cue-evoked mid-frontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.
The dietary inflammatory index is positively associated with insulin resistance in underweight and healthy weight adults
Authors: Mi Zhendong , Wang Xuhan , Ma Liying , Liu Honglin , Zhang Yidan , Ding Ziji , Wang Ling , Sun Mengzi , Li Bo
Published: June 2023

The aim of this study was to explore the relationship between dietary inflammatory index (DII) and insulin resistance (IR) in underweight and healthy weight adults. This cross-sectional study involved 3205 participants from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. All dietary data used to calculate the DII were obtained based on the average of two 24-h dietary recall interviews. Participants were divided into an anti-inflammatory diet group and a pro-inflammatory diet group based on DII < 0 and DII ≥ 0, respectively. Fasting blood glucose and fasting insulin data used to calculate IR index (HOMA-IR) were from laboratory data in the NHANES database. According to the linear regression analysis results of DII and HOMA-IR, we found that there was a positive relationship between DII and IR. A positive association between DII and HOMA-IR was seen in the following groups after stratification: by age in 20–39-year olds, by sex in males, by race in Non-Hispanic Whites, by family history of diabetes in those without a family history of diabetes, by education level in those with high school education, by smoking status in current smokers and non-smokers, by hypertension in those with hypertension, by BMI in those with a BMI of 18.5–24.99, by hypertriglyceridemia (HTG) in those without HTG, by poverty impact ratio (PIR) in those with PIR ≤ 1.3 and >1.3, and by physical activity in those with moderate recreational activities. In conclusion, in underweight and healthy weight adults, DII was positively correlated with the risk of IR.
Saliva insulin tracks plasma insulin across the day following high-carbohydrate and low-carbohydrate meals
Authors: Rafiei Hossein , Omidian Kosar , Chang Courtney Rochelle , Little Jonathan Peter
Published: June 2023

Non-invasive monitoring of insulin could hold promise to identify those with, or at risk for developing, insulin resistance. We aimed to examine saliva insulin responses across the day following high- and low-carbohydrate meals and evaluate whether changes in saliva insulin might accurately reflect changes in plasma insulin. In two randomized crossover studies, young normal weight men (NW; n = 8; Study 1) and adults with overweight/obesity (OO; n = 8; Study 2) completed two 9-h experimental trials in which the participants consumed isocaloric mixed high-carbohydrate (HC) or low-carbohydrate (LC) meals at 0, 3, and 6 h. Plasma and saliva samples were collected at fasted baseline and every 30 min for a total of 19 samples across 9 h. Overall, findings revealed a similar trend for postprandial saliva and plasma insulin responses regardless of the time of the day with a ∼30–45 min lag between saliva and plasma insulin responses. In both NW and OO groups, saliva and plasma insulin area under the curve (AUC) and incremental AUC were significantly higher in HC condition as compared to LC condition (all P ≤ 0.002). Nine-hour plasma and saliva insulin total AUCs were strongly and very strongly correlated in both HC ( r = 0.68; P = 0.007) and LC ( r = 0.84, P < 0.001) conditions, respectively. Saliva insulin is proportionate to and appears to reasonably track plasma insulin across the day with a ∼30–45 min delay. Saliva insulin shows promise as a non-invasive method to discern between low and high plasma insulin and may have utility in predicting the degree of insulin resistance (NCT03374436).
Born–Infeld corrections to holographic transport coefficients with spatially modulated chemical potential
Authors: Srivastav Ankur , Gangopadhyay Sunandan , Saha Ashis
Published: June 2023

In this work, we have analytically computed the holographic transport coefficients for $$(2+1)$$

(
2
+
1
)

-dimensional strongly coupled field theories, placed in a spatially modulated chemical potential along the x-direction, in the presence of Born–Infeld electrodynamics. We have obtained these coefficients in terms of the black hole horizon data only. We have observed that the Born–Infeld parameter affects these coefficients in a non-trivial way. We have, then, used these results to further study a holographic model for ultra-clean graphene near Dirac point. This is a two current model with an inhomogeneous holographic lattice.
Charged Higgs induced 5 and 6 lepton signatures from heavy neutrinos at the LHC
Authors: Das Arindam , Kanemura Shinya , Sanyal Prasenjit
Published: June 2023

We propose an anomaly free gauged U(1) extension of the SM where three right handed heavy neutrinos, being charged under the general U(1) gauge group, are introduced to explain the origin of the tiny neutrino mass through the seesaw mechanism after the general U(1) symmetry is broken. Due to the breaking of the general U(1) symmetry a neutral beyond the standard model gauge boson $$Z^\prime $$

Z
′

acquires mass. There are two Higgs doublets in this model where one interacts with the SM fermions and the other one interacts with the right handed heavy neutrinos and charged leptons. The charged multiplet of the second Higgs can completely decay into the heavy neutrinos and charged lepton in the neutrinophilic limit of the model parameters. The charged Higgs pair production can be influenced due to presence of the $$Z^\prime $$

Z
′

boson at the High Luminosity LHC (HL-LHC) in addition to the neutral SM gauge bosons. The pair produced charged Higgs bosons decay into SM charged leptons and heavy neutrinos. Following the leading decay modes of the heavy neutrinos into charged leptons and W boson we study the 5 and 6 lepton final states after the leptonic and hadronic decay of the W bosons considering solely muons and electrons in the final state. Combining the electron and muon final states we estimate the significance of the 5 and 6 charged lepton processes in the $$m_{H^\pm }-m_N$$

m

H
±

-

m
N

plane for different benchmark points of $$m_{Z^\prime }$$

m

Z
′

. It is found that the 5 (6) charged lepton processes could be probed at the High Luminosity LHC (HL-LHC) with at least 5 (3) $$\sigma $$
σ
significance and there are parameter regions where the significance could be larger.
Minimization of Makespan and Total Completion Time for Hybrid Job Shop Scheduling Problem Using Genetic Approaches
Authors: Abdelhak Seifeddine , Nouaouri Issam , Krichen Saoussen , Goncalves Gilles
Published: June 2023

This paper deals with two different versions of Hybrid Job Shop Scheduling Problems (HJSP); the minimization of the maximum completion time (makespan) and the minimization of the total completion time. State of the art shows that the literature on HJSP is rather scarce and that the majority of works concern the general problem called Flexible Job Shop Scheduling Problem (FJSP) in which parallel machines of a stage may have different speeds or yields. We propose the use of a genetic algorithm (GA) and a hybrid version of a GA (HGA) that applies a stochastic local search with two operators, specifically adapted to the HJSP. To conduct a clear statistical study based on the GA, HGA, and other state-of-the-art approaches, we extended our testbed to cover many existing benchmarks. The results of our experimental study show that our proposed algorithms improve the best-known results on a large set of benchmarks found in the literature. The scalability study shows that the proposed algorithm scales better and can deal with larger instances in the literature.
A note on Rivin’s interpretation of McShane’s identity as identities for closed geodesics with one self-intersection
Authors: Lei Da , Zhang Ying
Published: June 2023

Rivin interpreted McShane’s identity as an identity for closed geodesics with one self-intersection on a one-cusped hyperbolic torus (cf. [I. Rivin, Geodesics with one self-intersection, and other stories, Adv. Math. 231 (2012) 2391–2412, Theorem 3.2]). In this note we point out that only those geodesics of non-hyperelliptic type are included in the interpreted identity, while those of hyperelliptic type are missing, and we give the desired identity for the closed geodesics with one self-intersection of hyperelliptic type. We also remark that the interpretation in [I. Rivin, Geodesics with one self-intersection, and other stories, Adv. Math. 231 (2012) 2391–2412, Theorem 3.7] of generalized McShane’s identity for a one-coned hyperbolic torus with cone angle [Formula: see text] is only partly valid because closed curves with one minimal self-intersection of non-hyperelliptic type are realizable as closed geodesics on the torus if and only if [Formula: see text].
Enhancing the Performance of 1–3 Lead-Free Piezoelectric Composites Using a CNT-Doped Matrix
Authors: Cañamero Francisco J. , Buroni Federico C. , Aliabadi Ferri M. H. , Rodríguez-Tembleque Luis
Published: June 2023

This work presents a computational study on the impact of carbon nanotube (CNT) enriched matrix on the performance of 1–3 lead-free piezoelectric periodic composites. Specifically, we investigate a piezoelectric composite system consisting of [Formula: see text] parallel aligned fibers of polycrystalline barium titanate (BaTiO3) embedded in a polydimethylsiloxane (PDMS) matrix doped with multiwalled CNT. The effective properties and several figures of merit have been obtained to evaluate the performance of this composite system as is typically done for these materials used for sensing, actuating, or harvesting applications. The results reveal that, in lead-free BaTiO3/PDMS piezocomposites, the addition of CNTs in the PDMS matrix should be [Formula: see text] “being [Formula: see text] the percolation threshold”, but not higher. In another case, we will only improve the performance of the lead-free piezocomposite for sensing or actuating, but not for energy harvesting applications. This study provides insights into the use of multiwalled CNTs in lead-free piezocomposites and suggests the optimal concentration of CNTs to enhance their performance. The findings have potential implications for the development of new piezoelectric materials and devices for sensing and harvesting applications.
Thomson Effect on an Electro-Magneto-Thermoelastic Medium under Dual-Phase-Lag Model
Authors: Eraki Ebtesam E. M. , Fathy Rania A. , Othman Mohamed I. A.
Published: June 2023

In this paper, the plane wave propagation, in a homogeneous, isotropic thermoelastic solid in the presence of Thomson effect is studied. The problem is solved in the context of the dual-phase-lag model and Lord and Shulman theory. The heat conduction equation is influenced by the Thomson coefficient. The analytical solution of the problem is acquired by using the normal mode method to obtain the stress components, the temperature and the displacement components. The variations of the field quantities have been depicted graphically in the dual-phase-lag model and Lord and Shulman theory for an insulated boundary. From numerical calculations, the effect of Thomson parameter on a homogeneous, isotropic, electro-magneto-thermoelastic material is revealed and discussed.
“Biped” Janus Fe3O4@nSiO2@TiO2−x&mSiO2 Nanoparticles for Drug Delivery and Microwave-Triggered Drug Release
Authors: Liu Ye , Hui Zhuang , Zhan Zewei , Cui Lili , Liu Xueru , Cui Bin
Published: June 2023

In this work, we constructed the “Biped” Janus Fe3O4@[Formula: see text]SiO2@TiO[Formula: see text]&[Formula: see text]SiO2 nanoparticles as drug carriers to improve the performance of microwave-controlled releasing drugs. The SEM and TEM characterization confirmed the successful synthesis of the “Biped” Janus nanoparticles. The Fe3O4@[Formula: see text]SiO2@TiO[Formula: see text] core-shell nanosphere showed stable nanoparticles of consistent and desirable diameter of about 250[Formula: see text]nm. The length and the diameter of the rod-shaped [Formula: see text]SiO2 were about 420[Formula: see text]nm and 310[Formula: see text]nm, respectively. The cumulative loading rate of doxorubicin hydrochloride (DOX) reached 43[Formula: see text]wt% after 240[Formula: see text]min, equivalent to 100.18[Formula: see text]mg g[Formula: see text]. It was found that the “Biped” Janus nanoparticles had dual-triggering properties of pH and microwave. At pH 7.0, 5.0 and 3.0, the drug release rate was as high as 55.91[Formula: see text]wt%, 73.78[Formula: see text]wt% and 77.81[Formula: see text]wt% at 210[Formula: see text]min, respectively. Under the microwave stimulation of pH 7.0, the drug release rate was significantly increased from 55.91[Formula: see text]wt% to 83.86[Formula: see text]wt% compared with nonmicrowave irradiation. The “Biped” Janus Fe3O4@[Formula: see text]SiO2@TiO[Formula: see text]&[Formula: see text]SiO2 have high drug loading and release efficiency, and shown good biocompatibility. Therefore, the biped Janus-shaped nanoparticles have huge potential in targeted therapy.
The Role of Explainable AI in the Research Field of AI Ethics
Authors: Vainio-Pekka Heidi , Agbese Mamia Ori-Otse , Jantunen Marianna , Vakkuri Ville , Mikkonen Tommi , Rousi Rebekah , Abrahamsson Pekka
Published: June 2023

Ethics of Artificial Intelligence (AI) is a growing research field that has emerged in response to the challenges related to AI. Transparency poses a key challenge for implementing AI ethics in practice. One solution to transparency issues is AI systems that can explain their decisions. Explainable AI (XAI) refers to AI systems that are interpretable or understandable to humans. The research fields of AI ethics and XAI lack a common framework and conceptualization. There is no clarity of the field’s depth and versatility. A systematic approach to understanding the corpus is needed. A systematic review offers an opportunity to detect research gaps and focus points. This article presents the results of a systematic mapping study (SMS) of the research field of the Ethics of AI. The focus is on understanding the role of XAI and how the topic has been studied empirically. An SMS is a tool for performing a repeatable and continuable literature search. This article contributes to the research field with a Systematic Map that visualizes what, how, when, and why XAI has been studied empirically in the field of AI ethics. The mapping reveals research gaps in the area. Empirical contributions are drawn from the analysis. The contributions are reflected on in regards to theoretical and practical implications. As the scope of the SMS is a broader research area of AI ethics, the collected dataset opens possibilities to continue the mapping process in other directions.
An End-to-end Trust Management Framework for Crowdsourced IoT Services
Authors: Bahutair Mohammed , Bouguettaya Athman
Published: June 2023

We propose a novel end-to-end trust management framework for crowdsourced Internet of Things (IoT) services. The framework targets three main aspects:trust assessment,trust information credibility and accuracy, andtrust information storage. We harness theusage patternsof IoT consumers to offer a trust assessment thatadaptsto IoT consumers’ uses. Additionally, our framework ascertains thecredibilityandaccuracyof trust-related information before trust assessment. This is achieved by validating the data collected by IoT consumers and providers. In addition, our framework ensures thecontextual fairnessbetween IoT services and trust information. Moreover, we propose a blockchain-based trust information storage approach. Our proposed storage solution preserves theintegrityandavailabilityof trust information.
We used to get money to teach students, now we teach students to get money: medical education has become a market with credentials not knowledge the commodity!
Authors: Lujan Heidi L. , DiCarlo Stephen E.
Published: June 2023

We should be preparing future physicians to deliver the care we want to receive as patients. This requires training in communication, collaboration, inquiry, discovery, and innovation while developing the habits of the mind and heart that advance the practice of medicine and the health of the public. However, the current “corporatization” of medical education is failing to accomplish this outcome. Specifically, medical schools are adopting corporate models, cutting costs, and seeking profit-making opportunities without improving what goes on in the classroom. Our hope is that we will reconnect to the greater purpose and value of learning.
Effect and Safety of Pioglitazone-Metformin Tablets in the Treatment of Newly Diagnosed Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease in Shaanxi Province: A Randomized, Double-Blinded, Double-Simulated Multicenter Study
Authors: Jianfang Fu , Wanxia Xiao , Xiling Gao , Jing Xu , Wenjuan Yang , Jianrong Liu , Qingzhen He , Kaiyan Ma , Jingxuan Lian , Taixiong Chen , Qian Xu , Mengying Li , Jie Ming , Qiuhe Ji
Published: June 2023

Objective. The aim of study was to evaluate the effect and safety of pioglitazone-metformin combined treatment in the newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease. Methods. A total of 120 newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease from 8 centers were randomly divided into the control group (metformin hydrochloride) and the test group (pioglitazone hydrochloride and metformin hydrochloride). Results. Compared to the control group, after treatment, the proportion of people with mild and moderate fatty liver increased, and the proportion of people with severe fatty liver decreased, and this change was more obvious in the population with moderate and severe fatty liver. The level of γ-GT decreased in both groups before and after treatment, which was statistically significant, and there was also a statistically significant difference in the level of γ-GT between the two groups after 24 weeks. There were no significant statistically differences in blood lipid, body weight, and waist circumference between the test group and the control group. Logistic regression analysis found that BMI is one of the risk factors for fatty liver. There was also no significant difference in the incidence of serious adverse events between the two groups (control group: 10.00% and test group: 6.67%,

P
=
0.74

). Conclusion. Combined treatment with pioglitazone-metformin can effectively reduce liver fat content and gamma-GT level in newly diagnosed diabetic patients with nonalcoholic fatty liver disease, and adverse events do not increase compared with the control group, showing good safety and tolerance. This trial is registered with ClinicalTrials.gov NCT03796975.
The Addition of the Geriatric Nutritional Risk Index to the Prognostic Scoring Systems Did Not Improve Mortality Prediction in Trauma Patients in the Intensive Care Unit
Authors: Rau Cheng-Shyuan , Tsai Ching-Hua , Chou Sheng-En , Su Wei-Ti , Hsu Shiun-Yuan , Hsieh Ching-Hua
Published: June 2023

Background. Malnutrition is prevalent among critically ill patients and has been associated with a poor prognosis. This study sought to determine whether the addition of a nutritional indicator to the various variables of prognostic scoring models can improve the prediction of mortality among trauma patients in the intensive care unit (ICU). Methods. This study’s cohort included 1,126 trauma patients hospitalized in the ICU between January 1, 2018, and December 31, 2021. Two nutritional indicators, the prognostic nutrition index (PNI), a calculation based on the serum albumin concentration and peripheral blood lymphocyte count, and the geriatric nutritional risk index (GNRI), a calculation based on the serum albumin concentration and the ratio of current body weight to ideal body weight, were examined for their association with the mortality outcome. The significant nutritional indicator was served as an additional variable in prognostic scoring models of the Trauma and Injury Severity Score (TRISS), the Acute Physiology and Chronic Health Evaluation (APACHE II), and the mortality prediction models (MPM II) at admission, 24, 48, and 72 h in the mortality outcome prediction. The predictive performance was determined by the area under the receiver operating characteristic curve. Results. Multivariate logistic regression revealed that GNRI (OR, 0.97; 95% CI, 0.96–0.99;

p
=
0.007

), but not PNI (OR, 0.99; 95% CI, 0.97–1.02;

p
=
0.518

), was independent risk factor for mortality. However, none of these predictive scoring models showed a significant improvement in prediction when the GNRI variable is incorporated. Conclusions. The addition of GNRI as a variable to the prognostic scoring models did not significantly enhance the performance of the predictors.
Application of Nanoprecipitation Technique to Develop Poloxamer-407 Facilitated Solid Lipid Nanoparticles for the Controlled Delivery of Tacrolimus
Authors: Zaman Muhammad , Iqbal Asma , Sarwar Hafiz Shoaib , Butt Muhammad Hammad , Iqbal Muhammad Omer , Nissar Naveed , Mumtaz Asma , Nazeer Hafiza Yusra , Alshammari Abdulrahman , Riaz Muhammad Shahid
Published: June 2023

Currently, the solid lipid nanoparticles (SLNs) are utilized as a novel approach for the controlled drug delivery system (CDDS). Tacrolimus (TCM), a lipophilic drug, can easily be encapsulated in the hydrophobic core of these SLNs using nanoprecipitation technique. The current aim was to develop the controlled release Poloxamer (PLX) facilitated TCM loaded SLNs (PLX/TCM-SLNs), followed by their physicochemical evaluations, including chemical compatibility, particle size, surface charge, surface morphology, nature of SLNs, loading efficiency (LE), entrapment efficiency (EE), in vitro drug release studies, release kinetic modeling, and statistical evaluation. Here we also evaluate physicochemical properties of TCM and investigate solubility profile for improvement and dissolution rate of PLX/TCM-SLNs. PLX was used in the process as a polymer due to its low toxicity and weak immunogenic properties. The prepared formulation was characterized by scanning electron microscopy (SEM) images, and Fourier transform infrared spectroscopy (FTIR) has confirmed the compatibility of the selected ingredients, whereas particle size analysis showed that prepared PLX/TCM-SLNs were of nanosized (

120.6
±
9

 nm) having zeta potential of −21.3 Mv. On the other hand, SEM had revealed the smooth and uniform surface of the particle, while X-ray diffraction (XRD) confirmed the uniform surface as crystalline structure of TCM in PLX/TCM-SLNs masked. A satisfactory level of EE (

94.5
±
2.74

%) has also been noticed. Furthermore, in vitro drug release studies have explored the controlled release of drug during 8 hours, following zero order release kinetics and diffusion type of release mechanism. Outcomes of the studies have advocated the successful preparation of SLNs, as controlled release PLX/TCM-SLNs have been prepared efficiently.
Antioxidant and Hepatoprotective Effects of Fig Fruit Extract with Olive Oil and Date-Palm Fruit Extract on Hepatic Toxicity of Oral Subchronic Exposure to Some Nanoparticles in Wistar Rats
Authors: Fathy Abdallah H. , Naji Riyadh Musaed , Bashandy Mohamed A.
Published: June 2023

The aim is to study the possible protection of fig fruit extract with olive oil and date-palm fruit extract (FOD) as natural antioxidants in decreasing the subchronic toxicity hazards of SiO2NPs, Al2O3NPs, or ZnONPs in male rats treated for 75 days. We used 80 male Wistar rats distributed into eight groups according to the treatment. The FOD antioxidant treatments were used at their recommended antioxidant doses. All nanoparticles (100 mg/kg) were given orally and daily for 75 days. Compared with the control, the oral administration of different NPs alone led to dramatic oxidative stress, liver function parameters, histopathological, p53, and inflammatory markers (TNF-α and IL-6). The FOD-NPs-treated groups recorded significantly reduced hepatotoxicity effects compared to those treated with NPs alone. In conclusion, the FOD supplementations to the rats ameliorate the NP’s hepatotoxicity.