bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming denominator problems in refugee settings with fragmented electronic records for health and immigration data: a prediction-based approach
Authors: Erdmann Stella , Jahn Rosa , Rohleder Sven , Bozorgmehr Kayvan
Published: July 2023

Background: Epidemiological studies in refugee settings are often challenged by the denominator problem, i.e. lack of population at risk data. We develop an empirical approach to address this problem by assessing relationships between occupancy data in refugee centres, number of refugee patients in walk-in clinics, and diseases of the digestive system.
Methods: Individual-level patient data from a primary care surveillance system (PriCarenet) was matched with occupancy data retrieved from immigration authorities. The three relationships were analysed using regression models, considering age, sex, and type of centre. Then predictions for the respective data category not available in each of the relationships were made. 21 German on-site health care facilities in state-level registration and reception centres participated in the study, covering the time period from November 2017 to July 2021.
Results: 445 observations (“centre-months”) for patient data (EHR, 230 mean walk-in clinics visiting refugee patients per month and centre; standard deviation sd: 202) of a total of 47.617 refugee patients were available, 215 for occupancy data (OCC, mean occupancy of 348 residents, sd: 287), 147 for both (matched), leaving 270 observations without occupancy (EHR-unmatched) and 40 without patient data (OCC-unmatched). The incidence of diseases of the digestive system, using patients as denominators in the different sub-data sets were 9.2 % (sd: 5.9) in EHR, 8.8 % (sd: 5.1) when matched, 9.6% (sd: 6.4) in EHR- and 12% (sd 2.9) in OCC-unmatched. Using the available or predicted occupancy as denominator yielded average incidence estimates (per centre and month) of 4.7% (sd: 3.2) in matched data, 4.8% (sd: 3.3) in EHR- and 7.5% (sd: 2.8) in OCC-unmatched.
Conclusions: By modelling the ratio between patient and occupancy numbers in refugee centres depending on sex and age, as well as on the total number of patients or occupancy, the denominator problem in health monitoring systems could be addressed. The approach helped to estimate the missing component of the denominator, and to compare disease frequency across time and refugee centres more accurately using an empirically grounded prediction of disease frequency based on demographic and centre typology. This avoided over-estimation of disease frequency as opposed to the use of patients as denominators.
Effective dose of remimazolam combined with different doses butorphanol inhibiting response to cervical dilation during artificial abortion: A randomized dose-finding clinical study
Authors: Chen Jinming , Li Xiaoling , Hu Zilan , Zheng Yuling , Mai Ying , Zhongqi Zhang
Published: July 2023

The purpose was to determine the effective dose of remimazolam (RMZ) combined with different doses butorphanol inhibiting response to cervical dilation during artificial abortion. This is a prospective, randomized, and double-blind study. Sixty-one female patients were randomly assigned to Group B10 (31 patients) and Group B15 (30 patients). All patients were given RMZ 5 min after an intravenous (IV) administration of butorphanol 10 μg/kg (Group B10) and 15 μg/kg (Group B15). According to the pre-experiment, the first dose of RMZ in the first patient was 0.35 mg/kg, and the adjacent geometric dose ratio was 0.9. The centered isotonic regression was performed to determine the ED50 and ED90 of RMZ and their corresponding 90% confidence interval (CI). The total RMZ dose administered, recovery time, and anesthesia-related adverse events were all recorded. The recovery time in Group B10 was significantly shorter than in Group B15. The incidence of post-operative nausea and vomiting (PONV) in the B10 and B15 groups was 3.2% and 16.7%, respectively. Therefore, to enhance the sedative effect of RMZ, the recommended dose of butorphanol is 10 μg/kg, and the ED50 and ED90 of the RMZ during painless artificial abortion were 0.263 and 0.331 mg/kg, respectively.
Does the setting of local government economic growth targets promote or hinder urban carbon emission performance?Evidence from China
Authors: Chen Mo , Zhang Jijian , Xu Zhe , Hu Xuhua , Hu Dianxi , Yang Guang
Published: July 2023

The management of growth targets drives China's rapid economic expansion and leads to potential carbon emission externalities. This paper empirically investigates the impact of economic growth target setting on carbon emission performance using panel data from 257 Chinese localities between 2004 and 2020. The analysis is conducted using 2SLS instrumental variable regression, cluster standard error regression, and the spatial Durbin model. The empirical findings indicate that local economic growth targets conditionally improve urban carbon emission performance, and moderate targets effectively enhance regional carbon emission performance, with moderate targets effectively enhancing regional carbon emission performance. However, aggressive economic growth targets do not contribute to the enhancement of regional carbon emission performance. The analysis of mechanisms shows that moderate economic growth targets enhance regional carbon performance by fostering innovation in green technology, while aggressive targets impede performance by encouraging increased investment in fixed assets and the growth of new cities. The analysis of heterogeneity indicates that cities in the eastern and western regions, characterized by larger populations and lower reliance on natural resources, have more effective economic development targets for enhancing local carbon performance. Additionally, the establishment of local economic development targets negatively affects the carbon emissions performance of neighboring regions, with the most significant negative spillovers observed at a spatial scale of 100 to 200 kilometers. This paper expands upon research concerning the environmental consequences of setting economic growth targets and the factors influencing carbon emission performance. It offers practical insights for achieving a balance between economic growth and carbon emission governance in emerging market countries.
12 Pulse Variable Frequency Drive and Impact of Input Voltage Sag and Unbalance on DC Link Inductor and Capacitor Stress
Authors: Rengamuni Govarthanan , Kaliannan Palanisamy , Shanmugam Paramasivam
Published: July 2023

This paper investigates the stresses, losses and the lifetime of the dc-link inductor and capacitors of 12-Pulse Variable Frequency Drives (VFD) due to Type A, Type B Sags and voltage unbalances. These parameters are mainly attributable to the rectifier’s transition into unbalance and single-phase operation, giving rise to low-order harmonic voltages (100Hz, 200Hz etc.,) at the DC Link. When one type of Sag is imposed in the primary of the 12 Pulse transformer, it will transform into another Sag type in its secondary windings based on the transformer configuration. The transformed Sag will be different between the secondary windings. So, the rectifiers will experience a different current profile, which will increase the low-order harmonics in dc-Link of the VFD. This variation in the low frequency components will affect the lifetime of dc-bus Capacitors. This will increase the ac-flux densities of the DC Choke which will lead to increased core loss and saturation. The analysis predicts the life of the DC capacitors and core loss of the DC-Link inductors under different types of Sags and unbalances. 12-Pulse VFDs are generally used for high-Power. But for the analysis, simulation and testing, a 12-Pulse 7.5kW VFD is used.
Physical Activity Measurement in Older Adults with Dementia in Long-term Care Facilities: A Scoping Review
Authors: Kim Yeongeun , Yoo Leeho , Kim Mijeong , Moon Changsun
Published: July 2023

Purpose
This scoping review systematically identifies methods of measuring physical activity in dementia patients, proposing strategies tailored to individual physical and cognitive statuses.
Methods
The methodological framework of Arksey and O’Malley was adopted, with studies identified via RISS, KISS, ScienceON, PubMed, PsychINFO, and CINAHL. Study with physical activity measurements used for dementia residents in long-term care facilities were selected. Each study was analyzed for publication features, participant characteristics, and measurement techniques.
Results
Out of the 30 studies reviewed, the majority were descriptive research in gerontology. Subjects, predominantly over 65, had their cognition and physical abilities assessed via the MMSE and Barthel Index, respectively. Physical activities were primarily measured using accelerometers, supplemented by caregiver observations. The choice of physical activity measurement correlated with cognitive function and levels of daily life dependency.
Conclusion
Although limited by the lack of literature, accelerometers proved effective in measuring physical activity in dementia patients with moderate to severe dependency, while surveys were utilized for those with total dependency. Future research should strive to offer more specific guidelines, ensuring measurement methods are effectively tailored to patients' cognitive and physical capacities.
Impact of Schistosoma sp., infection on biological, behavioral, physiological, histological, and genotoxicological aspects of Biomphalaria alexandrina and Bulinus truncatus snails
Authors: Dokmak Heba , hamam olfat , ibrahim amina
Published: July 2023

Trematodes infection of genus Schistosoma can lead to physiological and behavioral changes in intermediate snail hosts. This is because the parasite consumes essential resources required for the host's survival, but the hosts can adaptively modify their behavior to ensure some level of fitness before parasite-induced mortality. The present study examined the reproductive and biochemical parameters of Biomphalaria alexandrina and Bulinus truncatus during the shedding stage of infection with Schistosoma mansoni and haematobium, respectively. The study found that the infection rate with S. mansoni was 34.7% and 30.4% with S. haematobium. In B.alexandrina infected with S. mansoni, a survival rate of 65.2% was recorded, along with a mean duration of shedding of 32.8 ± 5.5 days, a mean prepatent period of 37.5 ± 1.15 days, and a mean life span of 57.0 ± 1.21 days. Meanwhile, in B. truncatus infected with S. haematobium, a survival rate of 56.4% was recorded, with a mean duration of shedding of 42.6 ± 2.6 days, a mean prepatent period of 46.7 ± 2.3 days, and a mean life span of 65.9 ± 1.6 days. The feeding behavior was increased in the two infected species snail, while the net reproductive rate (Ro) of the infected species snails was reduced. Total antioxidant (TAO) and lipid peroxidation activity were increased in the two infected snails during shedding, while Glutathione-S-transferase was reduced. Lipid peroxidase (LPO) activity and nitrogen oxide (NO) levels decreased significantly in infected B. alexandrina and increased in infected Bulinus. Steroid hormone measurements were increased in the infected Biomphalaria, while they were reduced in infected Bulinus. Comet assay parameters were increased in the two infected genera after infection than control snails, and histopathological damage occurred. These observations demonstrated that infection initiates diverse biochemical, hormonal, genotoxic, and histopathological change to the tissues responsible for fecundity and reproduction in B. alexandrina and B. truncatus.
Unemployment and opioid overdose death patterns in the United States from 2017 to 2019
Authors: Khafagy Rana , Naraentheraraja Saranya , Sathiyamoorthy Aranee
Published: July 2023

Background
Unemployment has been linked to increased opioid-related harms such as opioid overdose deaths. Identifying hotspots and coldspots across the United States (US), specifically concerning opioid overdose deaths, can be crucial to understanding health resources and leveraging strategies, policies and programs to reduce the burden of opioid-related harms.
Methods
Using data from the US Bureau of Labour Statistics and the Center for Disease Control from 2017 to 2019, we describe how unemployment correlates with opioid overdose deaths in the US. Spatial clustering analyses were carried out to generate Moran’s global I values and create hotspot maps leveraging Moran’s local I to identify clusters and trends over time.
Results
There was an autocorrelation of opioid overdose death rates with surrounding states, particularly in the Midwest, Northeast and Southeast in 2017 and 2019. In contrast, only certain states in the Northeast showed greater clustering in 2018. A Poisson regression model showed a positive association between unemployment and opioid overdose deaths for the years 2017 and 2019. However, a protective effect of unemployment was seen in 2018. Overall, 2018 did not follow similar patterns seen in 2017 and 2019 in terms of the correlation between unemployment and opioid overdose rates.
Conclusion
Opioid-related deaths appear to be associated with unemployment rates in the US during 2017 and 2019, but less so in 2018. The Midwest, Northeast and Southeast were highly positively correlated with each other. Future studies which incorporate potential confounders such as age, sex, and race/ethnicity are needed to better understand the true association between unemployment and opioid overdose deaths.
BCL-XL inhibitors enhance the apoptotic efficacy of BRAF inhibitors in BRAFV600E colorectal cancer
Authors: Mariadason John , Jenkins Laura , Luk Ian , Chionh Fiona , Tan Tao , Needham Kristen , Vukelic Natalia , Sieber Oliver , Mouradov Dmitri , Gibbs Peter , Williams David , Tebbutt Niall , Desai Jayesh , Hollande Frederic , Dhillon Amardeep , Lee Erinna , Merino Delphine , Fairlie Walter
Published: July 2023

Metastatic BRAFV600E colorectal cancer (CRC) carries an extremely poor prognosis and is in urgent need of effective new treatments. While the BRAFV600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. We have found that a limitation of Enc+Cet treatment is the failure to efficiently induce apoptosis in BRAFV600E CRCs, despite inducing expression of the pro-apoptotic protein BIM and repressing expression of the pro-survival protein MCL-1. Here, we show that BRAFV600E CRCs express high basal levels of the pro-survival proteins MCL-1 and BCL-XL, and that combining encorafenib with a BCL-XL inhibitor significantly enhances apoptosis in BRAFV600E CRC cell lines. This effect was directly dependent on the induction of BIM as BIM deletion markedly attenuated BRAF plus BCL-XL inhibitor-induced apoptosis. As thrombocytopenia is an established on-target toxicity of BCL-XL inhibition, we also examined the effect of combining encorafenib with the BCL-XL targeting PROTAC DT2216, and the novel BCL-2/BCL-XL inhibitor dendrimer conjugate AZD0466. Combining encorafenib with DT2216 significantly increased the induction of apoptosis in vitro, while combining encorafenib with AZD0466 was well tolerated in mice and further reduced growth of BRAFV600E CRC xenografts compared to either agent alone. Collectively, these findings demonstrate that combined BRAF and BCL-XL inhibition significantly enhances apoptosis in pre-clinical models of BRAFV600E CRC and is a combination regimen worthy of clinical investigation to improve outcomes for these patients.
Exploring the potential common genetic characteristics and molecular mechanisms between inflammatory bowel disease and atherosclerosis using bioinformatics analysis and machine learning
Authors: xuezhu wang , zhai zihan , Rong Zhen , Wei Tingting , Yu Xuefang , Bian Bo
Published: July 2023

Background
The prevalence of inflammatory bowel disease (IBD) is increasing worldwide. According to recent research, IBD is a separate risk element for atherosclerosis (AS),however the cause of IBD combined with AS is still not clear. Through a thorough bioinformatics analysis, this study investigated the potential mechanisms of AS in conjunction with IBD and aimed to pinpoint biomarkers for patients with IBD and AS complications.
Methods
From two microarray datasets, we obtained differentially expressed genes(DEGs) for AS and IBD using the "Limma" package. The CDEGs underwent enrichment analysis, leading to the construction of a network for protein-protein interaction (PPI). Afterward, two algorithms based on machine learning were utilized to search for hub genes. A diagnostic nomogram was created using the Hub genes. To assess the dependability of the nomogram, the ROC curve was employed.qPCR was used to analyze the expression of hub genes in animal models. The AS dataset underwent immune infiltration analysis and consensus clustering analysis in the end.
Results
A total of 51 CDEGs were obtained. Further screening yielded three hub genes (LCP2, MMP9, and NCF2). The nomogram demonstrated good diagnostic performance. The disease group exhibited markedly elevated expression levels of hub genes compared to the control group, as revealed by the qPCR findings.In AS, the analysis of immune infiltration showed irregularity in the infiltration of immune cell. Two molecular subtypes were identified through consensus clustering analysis, with subtype B exhibiting higher expression levels of hub genes and immune checkpoint genes compared to subtype A.
Conclusion
Our study revealed the common inflammatory immune pathways in IBD and AS and constructed a nomogram with good diagnostic performance based on hub genes.
A mixed-method randomised controlled feasibility trial of digital CBT and emotion regulation skills training for employees in the workplace (REST)
Authors: Moukhtarian Talar R. , Fletcher Sophie , Walasek Lukasz , Kershaw Charlotte , Patel Krishane , Hurley-Wallace Anna L. , Russell Sean , Daly Guy , Tang Nicole , Toro Carla , Meyer Caroline
Published: July 2023

Background and aim:
Digital interventions for depression and anxiety can be as effective as face-to-face therapy. In a bid to tackle findings that one in six workers experience some form of mental health problems, a potential avenue to deliver mental health interventions as stepped care models is through the workplace. This study aims to assess the acceptability, feasibility, and preliminary efficacy of a digital cognitive behavioural therapy (dCBT) for depression and anxiety for employees in the workplace.
Methods: Mixed-methods evaluation of employees allocated to dCBT (n=25) or a waitlist control group (n=27) assessed against five feasibility objectives related to recruitment of employers and employees, engagement, study procedure and preliminary efficacy of the intervention. Quantitative outcome measures and qualitative interviews at 8 weeks post-randomisation were used. Quantitative outcomes were also assessed within subject at 3-, 6-, and 12-month follow-up. Qualitative data was assessed using thematic and framework analysis in Nvivo, whilst quantitative outcomes were analysed using mixed effect linear models between and within subject in R and SPSS.
Results: 33 businesses agreed to facilitate the delivery of three trials run by the University of Warwick in their workplaces. 52 participants consented into the REST trial. Adherence/usage of participants of the treatment platform was just over 50% across the whole sample. There was a reduction in depression and anxiety symptoms post-intervention and at follow-up timepoints across all participants and over time although there was no statistically significant between group differences. High acceptability and satisfaction were reported by participants with the intervention based on qualitative interview data at post-intervention.
Conclusions: Results from this feasibility study suggests that the dCBT programme (REST) was acceptable and shows preliminary treatment efficacy for depression and anxiety. Recruitment of participants and engagement with the intervention made the feasibility of the delivery somewhat challenging. With better operational infrastructure in place to promote recruitment and engagement, as well as implementing the learnings from the feasibility trial, a fully powered study will inform the efficacy of the REST intervention.
Trial registration number:ISRCTN31161020 (registered on 08/06/2021).
ED50 of Ciprofol Combined with Sufentanil for Fiber Bronchoscopy of Different Patient Populations with Pulmonary Tuberculosis
Authors: Pan Min , Liu Weidong , Zhang Zhixin , Li Tong , Xie Weibin
Published: July 2023

Backgroud: Ciprofol is a promising sedative. At present, there were few clinical studies on the median effective dose (ED50) of ciprofol. The aim of this study was to compare the ED50 of ciprofol for fiberoptic bronchoscopy in pulmonary tuberculosis (TB) patients of different genders and ages.
Methods：TB patients who underwent bronchoscopy examination and treatment at The Third People’s Hospital of Changzhou between May 2023 and June 2023 were selected, and divided into four groups according to stratified random method: Group N1 (non-elderly male patients), Group N2 (non-elderly female patients), Group N3 (elderly male patients), and Group N4 (elderly female patients). All patients received intravenous injection of 0.15 μg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Fiberoptic bronchoscopy was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups of TB patients was 0.4 mg/kg, and the ratio of adjacent doses was 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy process. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups.
Results: The ED50 of ciprofol combined with 0.15 μg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. The ED50 of ciprofol in the Group N1 was significantly higher compared with the Group N2 and Group N3 (p<0.05). The ED50 of ciprofol in the Group N4 was significantly lower compared with the Group N2 and Group N3 (p<0.05).
Conclusions: The ED50 of ciprofol used for fiber bronchoscopy in patients with TB of different genders and ages was different.
Trial registration: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.
WITHDRAWN: Does Green Finance Boost Carbon-Neutral Performance? -- Evidence from China
Authors: Hou Hui , Qu Pengsheng , Zhang Minglang
Published: July 2023

Using Chinese provincial sample data from 2011–2021, the paper uses a Durbin spatial model and a threshold panel model to test hypotheses on the relationship between green finance and carbon-neutral performance. The study found that (1) green finance development would promote carbon-neutral performance; (2) there are notable spatial characteristics of green finance and carbon neutrality performance, with local carbon neutrality performance being influenced by local and neighboring green finance; (3) green finance impacts carbon-neutral performance at a single threshold, and different levels of green finance development affect carbon-neutral performance differently. In the eastern, central, and western regions, the contribution of green finance to carbon-neutral performance gradually decreases. Thus, Chinese authorities should strengthen the green sustainable financing system, promote regional green finance, and enhance the carbon-neutral performance of green finance.
Baicalin Target Protein, Annexin A2, is a Target of New Antitumor Drugs
Authors: Kusakabe Yoshio , Matsumoto Kazuya , Tsuyuki Takahiro , Hayashi Yasuhiro , Watanabe Hideaki
Published: July 2023

Baicalin is a flavonoid extracted from Scutellaria baicalensis Georgi. As it has significant antitumor and apoptosis-inducing effects, baicalin may be useful in new antitumor drug development. However, as the pharmacological actions of baicalin have yet to be elucidated, we isolated its target protein, which was successfully identified as Annexin A2. Annexin A2 forms a heterotetramer with S100A10 protein, which plays an important role in the plasminogen activator system. The heterotetramer bound to tissue plasminogen activator (tPA) activates the conversion of plasminogen to plasmin and promotes the expression of STAT-3 and NF-κB, which are target genes involved in the development of cancer. Moreover, NF-κB and STAT-3 induce the expression of cell inhibitors of apoptotic proteins (cIAPs) and inhibit apoptosis. To examine whether these antitumor and apoptosis-inducing effects of baicalin are mediated by Annexin A2, we prepared Annexin A2 knockdown HepG2 cells. We compared mRNA expression by RT-qPCR and apoptosis by caspase-3 activity assays in Annexin A2 knockdown HepG2 cells. The results showed that the antitumor and apoptosis-inducing effects of baicalin are mediated by Annexin A2. The results of this study suggest that agents capable of inhibiting Annexin A2 may be useful candidates for the development of novel antitumor agents.
Risk factors for stoma-and-incision-related complications in children with very early-onset inflammatory bowel disease: A prospective cohort study
Authors: Xu Xiaofeng , Zhou Yiwen , Tan Zhixing , Huang Ying , Dong Kuiran , Gu Ying , Chen Jie , Huang Yuyan , Gou Zhaoyang , Yu Zhuowen
Published: July 2023

Objective
To describe the incidence of postoperative complications of enterostomy and explore the related risk factors in children with very early-onset inflammatory bowel disease (VEO-IBD).
Methods
Forty-three children with VEO-IBD who underwent enterostomy from January 2015 to December 2021 were included. Patients were divided into two groups according to whether they had complications after the enterostomy. The T-test and the Chi-square test were used to analyze the influencing factors of two groups of enterostomy complications. Factors screened out by univariate analysis were included in binary logistic regression.
Results
There were 23(53.5%) VEO-IBD patients who had ostomy complications, 16(37.2%) patients who had peristomal complications, and 15 (34.9%) patients who had incision complications after enterostomy. Univariate analysis showed that there were significant differences in Weight-for-Age Z Score (WAZ), Height-for-Age Z Score (HAZ), and weighted Pediatric Crohn's Disease Activity Index (wPCDAI) among groups with and without complications (P < 0.05). Further multivariate logistic regression analysis showed that wPCDAI was an independent risk factor for stoma-and-incision complications after enterostomy in children with VEO-IBD (P = 0.02, OR = 1.13, 95%CI = 1.02–1.25).
Conclusion
wPCDAI score should be fully considered before the enterostomy procedure in children with VEO-IBD.
Interstitial carbon in an active RuO2 catalyst and its stabilization under low temperature CO2 methanation reaction conditions
Authors: Concepcion PATRICIA , Tébar-Soler Carmen , Diaconescu Vlad Martin , Simonelli Laura , Missyul Alexander , Perez-Dieste Virginia , Villar-Garcia Ignacio , Brubach Jean Blaise , Roy Pascale , Corma Avelino
Published: July 2023

The authors have requested that this preprint be removed from Research Square.
The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA).
Authors: Albers Elaine , Kieffer J.M. , Schagen S.B.
Published: July 2023

Purpose
Breast cancer patients receiving chemotherapy can develop cognitive impairment. There is no gold standard for defining cognitive impairment. We applied the National Institute on Aging- Alzheimer’s Association (NIA-AA) criteria for mild cognitive impairment (MCI) to determine its prevalence in breast cancer patients receiving adjuvant chemotherapy and examine differences between patients with and without MCI.
Methods
Existing cognitive data of 240 breast cancer patients who received adjuvant conventional (n = 154) or high-dose chemotherapy (n = 86) on 5 neuropsychological test outcomes measuring verbal memory, processing speed, executive functioning and verbal fluency was used. Testing occurred 6 or 12 months post-chemotherapy and results were compared to 66 women without cancer. MCI was defined by; i) presence of concern regarding a change in cognition, ii) impairment in one or more cognitive tests (1.5 Standard Deviation below a normative mean), iii) preservation of independence in functional abilities, and iv) no dementia.
Results
20% (n = 49) of breast cancer patients who received chemotherapy (conventional therapy n = 29 (12%), high-dose therapy = 20 (8.3%)) met criteria for MCI, compared to 7.6% (n = 5) of controls. Prevalence was significantly different between the groups (P = 0.020) and corrected for IQ (P < 0.001). Patients with MCI had significant lower education levels (P < 0.002) and premorbid IQ (P = 0.001) compared to patients without MCI.
Conclusion
20% of breast cancer patients treated with chemotherapy met NIA-AA criteria for MCI, compared to 7.6% of the controls. These criteria, which include formal test performance as well as a person's symptoms and functional status, can be useful in clinical practice and scientific research.
Integrated Magnetless Passive Broadband Faraday Isolator
Authors: Lapointe Jerome , Coia Cedrik , Vallée Réal
Published: July 2023

Optical isolation based on a non-reciprocal effect is crucial for proper operation of several high-performance photonic devices such as LiDAR and quantum platforms. The magneto-optical Faraday rotation is the most commonly used non-reciprocal effect as it offers unique advantages, including broadband operation, wide input optical power range, low insertion losses and high optical isolation, but it is currently not conducive to miniaturization. Two major impediments hinder the direct integration of Faraday isolators into photonic integrated circuits (PICs): the need for bulky external magnets, and the challenging fabrication of low-loss waveguides that would eliminate the need for free-space coupling optics. We have addressed both challenges using a first-of-its-kind femtosecond laser writing technique to create waveguides within the bulk of latched bismuth-doped iron garnet (BIG) slabs without altering its magneto-optic functionality. As a result, we have achieved a magnetless Faraday rotator waveguide exhibiting <0.15 dB insertion loss with a record high figure of merit of 346° dB-1. By interposing this Faraday rotator between two 30 μm-thick polarizers, we further demonstrate an integrated magnetless optical isolator with >25 dB isolation ratio and <1.5 dB insertion loss over the entire optical telecom C-band.
Universal Eye Screening: Perinatal Risk Factors & Ocular Pathologies in 1795 Newborns Not Meeting Retinopathy of Prematurity Criteria
Authors: Khanna Rohit , Nayak Sameera , Padhy Tapas , Mettla Asha Latha
Published: July 2023

Objectives: This prospective cohort study aimed to investigate the ocular outcomes of universal eye screening in newborns and assess the relationship between different perinatal risk factors and various ocular pathologies in infants who do not meet the criteria for retinopathy of prematurity (ROP) screening.
Methods: A universal eye screening questionnaire was utilised to screen newborn babies who did not meet the ROP screening criteria within 72 hours of birth at a public and private hospital between June 2016 to April 2018. The questionnaire covered demographic characteristics, neonatal history, and eye examination findings. A trained retina specialist conducted comprehensive anterior and posterior segment examinations utilising a binocular indirect ophthalmoscope.
Results: Out of the 1795 newborns screened, 55.2% were male, and 44.8% were female. The most prevalent ocular pathology observed was retinal haemorrhage (RH), with a prevalence of 10.64% (95% CI: 9.25% – 12.16%). The prevalence of non-RH pathology was 7.5% (95% CI: 6.34% – 8.84%). Multivariable analysis revealed that RH was associated with normal vaginal deliveries (OR: 10.1; 95% CI: 6.9-15), while non-RH pathologies were associated with preterm birth (OR: 5.6; 95% CI: 3.5-9.0), consanguinity (OR: 2.3; 95% CI: 1.3-4.1), low birth weight (OR: 8.8; 95% CI: 5.1-15.1), and systemic abnormalities (OR: 3.3; 95% CI: 2.0-5.3).
Conclusions: Sight-threatening ocular pathology in newborns may be linked to perinatal risk factors such as preterm birth, low birth weight, consanguinity, and systemic abnormalities. Therefore, targeted eye screening for newborns in this high-risk group is warranted.
Synthesis, anticancer evaluation and docking studies of novel adamantanyl-1,3,4-oxadiazol hybrid compounds as Aurora-A kinase inhibitors
Authors: Jaber Areej Majed , Al-Mahadeen Mohammed M , Al-Qawasmeh Raed A , Taha Mutasem O
Published: July 2023

Cancer is a devastating disease, but advancements in cancer treatment offer hope for the future. Aurora Kinases are a family of serine/threonine kinases that play critical roles in cell cycle control and mitosis. There are three members of the Aurora kinase family in humans: Aurora-A kinase, Aurora-B kinase, and Aurora-C kinase. This study focuses on the synthesis of hybrid compounds combining adamantane and 1,3,4-oxadiazole as potential inhibitors of Aurora-A kinase. A series of novel 4-((5-((3r,5r,7r)-adamantan-1-yl)-1,3,4-oxadiazol-2-yl)thio)-N,N-2-yn-1-amine were synthesized and evaluated against Aurora-A kinase. The most potent derivatives were 6a and 6k with IC50 values 36.6 and 38.8 μM, respectively. Docking studies probed the binding interactions of these compounds within the active site of the kinase. The findings contribute to the development of novel cancer therapeutics and offer promise for more effective and targeted treatments in the future.
Implementing the time-to-event continualreassessment method in the presence of partial orders in a phase I head and neck cancer trial.
Authors: Patel Amit , Brock Kristian , Slade Daniel , Billingham Lucinda , Gaunt Piers , Gaunt Claire , Kong Anthony , Mehanna Hisham
Published: July 2023

Background: In this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maxi­mum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.
Methods: The PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the pres­ence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known.
Results: We arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to deter­mine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial.
Conclusions: Whilst being a very efficient design we highlight some of the dif­ficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investiga­tions of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders.
Trial registration: ADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.
Investigation of the expression of Long non-coding RNA in Parkinson's disease
Authors: Mazdeh Mehrdokht , Farsani Mohesn Khosravi , Komaki Ali Rezae , Eftkharin Mohammad Mehadi
Published: July 2023

Background and aim
Parkinson's disease is the second chronic age-related neurodegenerative disease after Alzheimer's. Pathogenic factors in Parkinson's include inflammation and oxidative stress, which lead to dopaminergic cell apoptosis. The case-control study aims to determine the expression level of long non-coding RNAs (lncRNAs) of the apoptosis pathway in Parkinson's patients with healthy individuals.
Methods
In the case-control study, 50 patients with Parkinson's disease were examined, with 50 healthy individuals matched in age and sex. In both groups, the expression of long non-coding RNAs includes taurine up-regulated 1(TUG1), metastasis associated lung adenocarcinoma transcript 1(MALAT1) ،nuclear enriched abundant transcript 1(NEAT1), and Growth Arrest Specific 5(GAS5) were compared using Real-time polymerase chain reaction (PCR.)
Results
MALAT1, NEAT1, and TUG1 gene expression ratio in the case group was statistically significantly higher than in healthy individuals. The ratio of GAS5 gene expression in people with Parkinson's disease was lower, with a statistically significant difference. The ratio of HULC gene expression was higher in the case group, but it did not show a statistically significant difference with the control group.
Conclusion
The involvement of long lncRNAs that increase apoptosis may play a role in the pathogenesis of the disease, which may be used for identification and therapeutic purposes.
Dietary bile acids improve breast muscle growth in chickens through FXR/IGF2 pathway
Authors: Chen Liang , Shi Yanghong , Li Jinbao , Ma Shuai , Shen Chao , Shao Caimei , Zhao Ruqian
Published: July 2023

Background
Fast-growing broiler chickens are commonly fed diets with high-fat content, particularly in integrated farms in Northeast China. Therefore, the efficiency of fat digestion, absorption, and utilization is critical for broiler meat production. Bile acids (BA) promote fat digestion and absorption, yet whether and how BA affects muscle growth in broiler chickens remain unclear.
Results
In this study, one-day-old broiler chickens were fed diets of low, medium, and high levels of crude fat with or without BA supplementation, for 42 days (d). Chickens fed BA-supplemented high-fat diet had significantly (P < 0.05) higher body weight (BW) at 21 d and average daily gain (ADG) from 1 to 21 d, compared to all the other groups. Feed conversion rate (FCR) was significantly (P < 0.05) lower in high-fat group, which was further decreased (P < 0.05) with BA supplementation. The improved growth performance in BA-supplemented high-fat group was associated with significantly (P < 0.05) increased lipase activity in the chyme of small intestine, a trend of decrease (P = 0.06) in abdominal fat ratio, and significantly (P < 0.05) higher breast muscle mass. Further histological analysis revealed significant (P < 0.05) increases in myofiber diameter, cross-sectional area, as well as RNA and DNA content in the breast muscle of BA-supplemented broiler chickens on high-fat diet. Accordantly, genes related to muscle growth, including mTOR, MYH1B, and PAX7, are significantly (P < 0.05) upregulated. These changes were accompanied by significantly (P < 0.05) increased concentration of insulin-like growth factor 2 (IGF2) in serum, liver and breast muscle. The upregulation of IGF2 gene in the breast muscle of broiler chickens fed BA-supplemented high-fat diet was associated with significantly (P < 0.05) increased FXR protein content and FXR binding to IGF2 gene promoter.
Conclusions
These results suggest that dietary BA supplementation improves FCR and breast muscle growth through FXR-mediated IGF2 pathway in broiler chickens fed high-fat diet.
A fuzzy overlapping project resource optimization model in the project construction industry, using a fractal method
Authors: Zohrehvandi Shakib , Knapčíková Lucia
Published: July 2023

When the number of projects in a company increases, it becomes very important to choose the right strategy to supply resources and raw materials in profit and loss and finish the work according to the schedule. This study presents a new mathematical model using the fractal method to optimize the resource planning system in project-oriented construction and industrial companies, and the results are analyzed. In the model proposed in this research, a fuzzy method and an overlapping method are used. Using the method of Pentagonal fuzzy numbers in determining the appropriate number of resources for project activities, as well as using a method of overlapping activities to determine the appropriate time of overlapping activities will lead to optimal use of project resources. This article aims to introduce a fuzzy overlapping project resource optimization (FOPRO) model in project-oriented construction and industrial companies by providing a fractal framework to minimize resource costs and the smooth flow of materials between projects to meet the existing demand. Assuming three levels of headquarters, regions, and projects, each of them in the collection is a self-similar structure defined as a fractal. The study was carried out in one of the contracting companies in the industrial and construction fields, which operates as a project-oriented project in different regions of the country. To evaluate the proposed model, the obtained results were compared with the results of previous models. The results showed that the model presented in this research was able to create optimization in terms of sending machines, material and manpower between different centers.
Investigating the effect of Zinc supplementation on the metabolic profile and expression of Nrf2, PPARγ and IL-10 genes in patients undergoing Methadone Maintenance Treatment: A Randomized, Double-Blind, Placebo- Controlled Trial
Authors: Ghaseminejad Azam , Ghaderi Amir , Ghotloo Somayyeh , Akbari Hossein , Bahmani Fereshteh , Aghadavood Esmat , Banafsheh Hamid Reza , Aboutalebian Hadis , Research Nejat Kheiripour.
Published: July 2023

Background: Methadone maintenance treatment (MMT) is associated with immunity dysfunction, increased inflammation, oxidative stress, and DNA damage. Zinc has various effects, including antioxidant and anti-inflammatory effects. In addition, zinc-finger proteins act as transcription factors regulating the expression of genes. In this study, we investigated the effect of Zinc supplement on the metabolic, and oxidative stress profiles, and expression of IL-10, NRF2, and PPARγ genes in heroin patients under MMT.
Methods: Randomized double-blind placebo-controlled clinical trial was carried out on 60 patients under MMT to receive 30 mg/day Zinc supplement (n=30) or placebo (n=30). Fasting blood samples were collected at the baseline and 12 weeks after intervention to quantify related markers, including metabolic, oxidative stress, and gene expression.
Results: At the end of the intervention, Zinc levels was significantly elevated in the intervention group in comparison with the placebo group (p=0.03). In addition, consuming Zink significantly changed the levels of HDL (p=0.04), insulin (p=0.01) and HOMA-IR (p=0.01). As well as the concentration of NO (p=0.02), GSH (p=0.01), TAC (p=0.04) were statistically significant between two groups. Taking Zink upregulated NRF2 gene expression (p< 0.05) in peripheral blood mononuclear cells of patients under MMT.
Conclusion: Results of this study indicated that, Zinc supplement can be recommended as an adjunct to MMT which may have beneficial effects on metabolic profile, oxidative stress, and gene expression and decrease methadone side effects.
Risk-Controlled Student Prescription Trees
Authors: Lentini Maria R. , Thayasivam Umashanger
Published: July 2023

Student Prescription Trees (SPTs) are interpretable policy trees which utilize a blackbox “teacher” model to predict counterfactuals on the basis of observed covariates and a interpretable decision tree (DT) “student” model which sorts datapoints into axis aligned partitions such that the sum over predicted coun-terfactuals outcome variables within each partition is optimized greedly. In this paper, we maintain this basic framework but experiment with a Bayesian hierarchical binomial regression model as the teacher, and require all gains acquired from DT splits to be statistically significant given the posterior distributions over outcome variables from any two disjoint partitions of the data when compared to their unity. This setup allows us to control the uncertainty (i.e., “risk”) associated with a deepening of the complexity (i.e., “depth”) of the student policy, and gives us natural tree growth stopping criteria. In general, fewer datapoints or greater variation are viewed as containing more uncertainty, and therefore greater uncertainty will result result in shallower tree policies, and vice versa.
Analysis of the driving effect of urban compactness on urban innovation capacity
Authors: Li Qingwen , Zhao Peihong , Yang Zhichen
Published: July 2023

Theoretically, we analyzed the mechanism of urban compactness affecting urban innovation capacity, and empirically analyzed the relationship between urban compactness and urban innovation capacity and its driving effects based on the measurement of compactness in 31 large and medium-sized cities. The findings of the study demonstrate that urban compactness plays a crucial role in promoting urban innovation capacity. Specifically, there are notable variations in the impact based on regional and city size heterogeneity. In terms of regional heterogeneity, the compact development of central and western cities leads to a significant enhancement of urban innovation compared to their eastern counterparts. Moreover, regarding city size heterogeneity, increased compactness in larger cities exhibits a positive influence on urban innovation capacity, while the compact development mode of megacities does not significantly impact innovation development. Furthermore, the influence mechanism of urban compactness on urban innovation capacity operates through multiple pathways, including the direct effect, knowledge spillover effect of human capital, agglomeration economy effect of industrial diversity, and the time-space compression effect of transportation access.