bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing the global and local spatial associations of medical resources across Wuhan city using POI data
Authors: Chen Qiao , Cheng Jianquan , Tu Jianguang
Published: January 2023

Background

There is a sharp contradiction between the supply and demand of medical resources in the provincial capitals of China. Understanding the spatial patterns of medical resources and identifying their spatial association and heterogeneity is a prerequisite to ensuring that limited resources are allocated fairly and optimally, which, along with improvements to urban residents’ quality of life, is a key aim of healthy city planning. However, the existing studies on medical resources pattern mainly focus on their spatial distribution and evolution characteristics, and lack the analyses of the spatial co-location between medical resources from the global and local perspectives. It is worth noting that the research on the spatial relationship between medical resources is an important way to realize the spatial equity and operation efficiency of urban medical resources.

Methods

Localized colocation quotient (LCLQ) analysis has been used successfully to measure directional spatial associations and heterogeneity between categorical point data. Using point of interest (POI) data and the LCLQ method, this paper presents the first analysis of spatial patterns and directional spatial associations between six medical resources across Wuhan city.

Results

(1) Pharmacies, clinics and community hospitals show “multicentre + multicircle”, “centre + axis + dot” and “banded” distribution characteristics, respectively, but specialized hospitals and general hospitals present “single core” and “double core” modes. (2) Overall, medical resources show agglomeration characteristics. The degrees of spatial agglomeration of the five medical resources, are ranked from high to low as follows: pharmacy, clinic, community hospital, special hospital, general hospital and 3A hospital. (3) Although pharmacies, clinics, and community hospitals of basic medical resources are interdependent, specialized hospitals, general hospitals and 3A hospitals of professional medical resources are also interdependent; furthermore, basic medical resources and professional medical resources are mutually exclusive.

Conclusions

Government and urban planners should pay great attention to the spatial distribution characteristics and association intensity of medical resources when formulating relevant policies. The findings of this study contribute to health equity and health policy discussions around basic medical services and professional medical services.
Incidents related to safety in mental health facilities in Kenya
Authors: Kwobah Kamaru Edith , Kiptoo Sitienei Robert , Jaguga Florence , Wangechi Felicita , Chelagat Saina , Ogaro Francis , Aruasa WK
Published: January 2023

Background

Both patients and health care providers working in mental health facilities witness high rates of incidents that have the potential to jeopardize their safety. Despite this, there are few studies that have documented the kind of incidents that are experienced, or explored the potential contributors to these incidents, and solutions that would result in better safety. This study explored various types of safety related incidents occurring in mental facilities in Kenya, perceived contributing factors, and recommendations for improve.

Methods

This qualitative descriptive study was carried out between December 2019 – February 2020. It included 28 mental health staff across 14 mental health unit spread across the country.

Results

All the participants reported having personally experienced an incident that threatened their safety or that of the patients. Most of the respondents (24/26. 91.67%) admitted to have experienced verbal aggression while 54.17%, (n = 24) had experienced physical assault. Participating health care workers attributed the safety incidents to poor infrastructure, limited human resources, and inadequate medication to calm down agitated patients. Suggested solutions to improve patient safety included; improving surveillance systems, hiring more specialized healthcare workers, and provision of adequate supplies such as short-acting injectable psychotropic.

Conclusion

Incidents that threaten patient and staff safety are common in mental health facilities in Kenya. There is need to strengthen staff capacity and reporting mechanisms, as well as invest in infrastructural improvements, to safeguard patient and staff safety in mental health facilities in Kenya.
Risk factors for herpes zoster: should people with asthma or COPD be vaccinated?
Authors: Safonova Ekaterina , Yawn Barbara P. , Welte Tobias , Wang Chengbin
Published: January 2023

Without vaccination, an estimated 1 in 3 individuals will develop herpes zoster (HZ) in their lifetime. Increased risk of HZ is attributed to impaired cell-mediated immunity, as observed in age-related immunosenescence or in individuals immunocompromised due to disease or immunosuppressive treatments. Most vaccination guidelines recommend HZ vaccination in all adults ≥ 50 years of age, although Shingrix® was recently approved by the U.S. Food and Drug Administration for use in individuals aged ≥ 18 years who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy, followed by approval by the European Medicines Agency for use in immunocompromised individuals aged ≥ 18 years. Chronic respiratory diseases are also risk factors for HZ. A new meta-analysis reported 24% and 41% increased risks of HZ in those with asthma and chronic obstructive pulmonary disorder (COPD), respectively, compared with healthy controls. Asthma and COPD increase a person’s risk of HZ and associated complications at any age and may be further elevated in those receiving inhaled corticosteroids. Despite the increased risks, there is evidence that HZ vaccination uptake in those aged ≥ 50 years with COPD may be lower compared with the age-matched general population, potentially indicating a lack of awareness of HZ risk factors among clinicians and patients. The 2022 Global Initiative for Chronic Lung Disease report recognizes that Centers for Disease Control and Prevention recommended to vaccinate those aged ≥ 50 years against HZ, although health systems should consider the inclusion of all adults with asthma or COPD into their HZ vaccination programs. Further research into HZ vaccine efficacy/effectiveness and safety in younger populations is needed to inform vaccination guidelines.

Graphical Abstract
Comparison of static and dynamic exposures to air pollution, noise, and greenness among seniors living in compact-city environments
Authors: Marquet Oriol , Tello-Barsocchini Jose , Couto-Trigo Daniel , Gómez-Varo Irene , Maciejewska Monika
Published: January 2023

GPS technology and tracking study designs have gained popularity as a tool to go beyond the limitations of static exposure assessments based on the subject's residence. These dynamic exposure assessment methods offer high potential upside in terms of accuracy but also disadvantages in terms of cost, sample sizes, and types of data generated. Because of that, with our study we aim to understand in which cases researchers need to use GPS-based methods to guarantee the necessary accuracy in exposure assessment. With a sample of 113 seniors living in Barcelona (Spain) we compare their estimated daily exposures to air pollution (PM2.5, PM10, NO2), noise (dB), and greenness (NDVI) using static and dynamic exposure assessment techniques. Results indicate that significant differences between static and dynamic exposure assessments are only present in selected exposures, and would thus suggest that static assessments using the place of residence would provide accurate-enough values across a number of exposures in the case of seniors. Our models for Barcelona’s seniors suggest that dynamic exposure would only be required in the case of exposure to smaller particulate matter (PM2.5) and exposure to noise levels. The study signals to the need to consider both the mobility patterns and the built environment context when deciding between static or dynamic measures of exposure assessment.
Lipid biomarkers that reflect postoperative recurrence risk in lung cancer patients who smoke: a case–control study
Authors: Takanashi Yusuke , Kahyo Tomoaki , Hayakawa Takamitsu , Sekihara Keigo , Kawase Akikazu , Kondo Minako , Kitamoto Takuya , Takahashi Yutaka , Sato Tomohito , Sugimura Haruhiko , Shiiya Norihiko , Setou Mitsutoshi , Funai Kazuhito
Published: January 2023

Background

The risk of postoperative recurrence is higher in lung cancer patients who smoke than non-smokers. However, objective evaluation of the postoperative recurrence risk is difficult using conventional pathological prognostic factors because of their lack of reproducibility. Consequently, novel objective biomarkers that reflect postoperative risk in lung cancer patients who smoke must be identified. Because cigarette smoking and oncogenesis alter lipid metabolism in lung tissue, we hypothesized that the lipid profiles in lung cancer tissues are influenced by cigarette smoking and can reflect the postoperative recurrence risk in smoking lung cancer patients. This study aimed to identify lipid biomarkers that reflect the smoking status and the postoperative recurrence risk.

Methods

Primary tumor tissues of lung adenocarcinoma (ADC) (n = 26) and squamous cell carcinoma (SQCC) (n = 18) obtained from surgery were assigned to subgroups according to the patient’s smoking status. The ADC cohort was divided into never smoker and smoker groups, while the SQCC cohort was divided into moderate smoker and heavy smoker groups. Extracted lipids from the tumor tissues were subjected to liquid chromatography-tandem mass spectrometry analysis. Lipids that were influenced by smoking status and reflected postoperative recurrence and pathological prognostic factors were screened.

Results

Two and 12 lipid peaks in the ADC and SQCC cohorts showed a significant positive correlation with the Brinkman index, respectively. Among them, in the ADC cohort, a higher lipid level consisted of three phosphatidylcholine (PC) isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), was associated with a shorter recurrence free period (RFP) and a greater likelihoods of progressed T-factor (≥ pT2) and pleural invasion. In the SQCC cohort, a lower m/z 736.5276 level was associated with shorter RFP and greater likelihood of recurrence.

Conclusions

From our data, we propose three PC isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), and a lipid peak of m/z 736.5276 as novel candidate biomarkers for postoperative recurrence risk in lung ADC and SQCC patients who are smokers.
Berberin sustained-release nanoparticles were enriched in infarcted rat myocardium and resolved inflammation
Authors: Zhu Ke , Yao Yu , Wang Kun , Shao Fuqiang , Zhu Ziyang , Song Yangmeihui , Zhou Zhangyongxue , Jiang Dawei , Lan Xiaoli , Qin Chunxia
Published: January 2023

Inflammatory regulation induced by macrophage polarization is essential for cardiac repair after myocardial infarction (MI). Berberin (BBR) is an isoquinoline tetrasystemic alkaloid extracted from plants. This study analyzes the most likely mechanism of BBR in MI treatment determined via network pharmacology, showing that BBR acts mainly through inflammatory responses. Because platelets (PLTs) can be enriched in the infarcted myocardium, PLT membrane-coated polylactic-co-glycolic acid (PLGA) nanoparticles (BBR@PLGA@PLT NPs) are used, which show enrichment in the infarcted myocardium to deliver BBR sustainably. Compared with PLGA nanoparticles, BBR@PLGA@PLT NPs are more enriched in the infarcted myocardium and exhibit less uptake in the liver. On day three after MI, BBR@PLGA@PLT NPs administration significantly increases the number of repaired macrophages and decreases the number of inflammatory macrophages and apoptotic cells in infarcted rat myocardium. On the 28th day after MI, the BBR@PLGA@PLT group exhibits a protective effect on cardiac function, reduced cardiac collagen deposition, improved scar tissue stiffness, and an excellent angiogenesis effect. In addition, BBR@PLGA@PLT group has no significant impact on major organs either histologically or enzymologically. In summary, the therapeutic effect of BBR@PLGA@PLT NPs on MI is presented in detail from the perspective of the resolution of inflammation, and a new solution for MI treatment is proposed.

Graphical Abstract
Cognitive functioning in women with breast cancer: psychometric properties of the Arabic version of the Functional Assessment of Cancer Therapy-Cognitive Function Tool
Authors: Hassan Mariam , Barakat Zainab , Fares Youssef , Abou-Abbas Linda
Published: January 2023

Background

The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) evaluates perceived cognitive functioning and their impact on quality of life. This study was designed to evaluate the factors associated with cognitive functioning in a sample of women with breast cancer (BC) in Lebanon. We also sought to explore the psychometric properties of the FACT-Cog Arabic version.

Methods

A cross-sectional study was carried out between March and August 2020 among women with BC. Socio-demographic and clinical characteristics were collected. In addition, patients were asked to complete the FACT-Cog Arabic version as well as the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30, the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7). The internal consistency of the FACT-Cog tool was evaluated using Cronbach’s alpha. Content, convergent, and known group validity of the FACT-Cog Arabic version were also evaluated. All statistical analyses were performed using SPSS version 23.0.

Results

A sample of 134 women with BC was collected. Internal consistencies of the FACT-cog total scale and its subscales were high (Cronbach’s α between 0.83 and 0.95). The convergent validity of the FACT-Cog Arabic version was supported by the positive correlation with the EORTC-cognitive functioning subscale. Moreover, negative correlations were found between FACT-Cog scale and fatigue, pain, anxiety, as well as depression. Known-group validity was supported by the statistically significant mean differences of the FACT-Cog total scale between patients in early (I &II) and late (III & IV) BC stages. Unmarried BC patients as well as those having higher depressive symptoms and a lower quality of life were found to be at higher risk of cognitive impairment.

Conclusion

The FACT-Cog Lebanese Arabic version is a valid and reliable tool for assessing perceived cognitive functioning in BC women. Higher level of depression and impaired quality of life were associated with a decline in cognitive functioning.
The involvement and therapeutic potential of lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway in arsenic trioxide-induced cardiotoxicity
Authors: Shen Xiuyun , Zhi Fengnan , Shi Chunpeng , Xu Jincheng , Chao Yuqiu , Xu Juan , Jiang Yanan , Bai Yunlong , Yang Baofeng
Published: January 2023

Background/Aims

Arsenic trioxide (ATO) is the first-line therapeutic drug for acute promyelocytic leukemia. However, the cardiotoxicity of ATO limits its clinical application. This study aims to explore the long noncoding RNA (lncRNA) involved molecular mechanism in ATO-induced cardiotoxicity and to identify available prevention strategies.

Methods

ATO was administered to mice or primary cultured mouse cardiomyocytes. Small interfering RNA targeting lncRNA Kcnq1ot1 (si-Kcnq1ot1) was used to knockdown lncRNA Kcnq1ot1. MiR-34a-5p mimic and antisense morpholino oligonucleotide targeting miR-34a-5p (AMO-34a-5p) were used to upregulate and downregulate the expression of miR-34a-5p, respectively. TUNEL staining was conducted to detect cell DNA damage. Flow cytometry assay was used to detect cell apoptosis. Western blot was conducted to detect Bcl-2, Bax and Sirt1 protein expression. Real-time PCR was used to detect lncRNA Kcnq1ot1, miR-34a-5p, and Sirt1 mRNA expression. Dual-luciferase reporter assay was performed to validate the predicted binding site.

Results

ATO induced apoptosis in cardiomyocytes both in vivo and in vitro. Simultaneously, the expression of lncRNA Kcnq1ot1 and Sirt1 was downregulated, and miR-34a-5p was upregulated. MiR-34a-5p has binding sites with lncRNA Kcnq1ot1 and Sirt1. Knockdown of lncRNA Kcnq1ot1 induced apoptosis of cardiomyocytes, with increased miR-34a-5p and decreased Sirt1 expression. Inhibition of miR-34a-5p attenuated si-Kcnq1ot1-induced apoptosis in cardiomyocytes. Therefore, the lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 signaling pathway is involved in ATO-induced cardiotoxicity. Propranolol alleviated ATO-induced apoptosis in cardiomyocytes both in vivo and in vitro, which was related to the lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 signaling pathway.

Conclusion

The lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway is involved in ATO-induced cardiotoxicity. Propranolol can attenuate ATO-induced cardiotoxicity at least partially through the lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway. Combined administration with propranolol may be a new strategy for alleviating the cardiotoxicity of ATO.
Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression
Authors: Gao Xinyi , Zhou Shiqi , Qin Zhaofu , Li Dechuan , Zhu Yuping , Ma Dening
Published: January 2023

Background

Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC.

Methods

Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors.

Results

Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation.

Conclusions

The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.
Child maltreatment exposure and adolescent nonsuicidal self-injury: the mediating roles of difficulty in emotion regulation and depressive symptoms
Authors: Hu Changchun , Huang Jialing , Shang Yushan , Huang Tingting , Jiang Wenhao , Yuan Yonggui
Published: January 2023

Background

Although child maltreatment (CM) experiences are recognized risk factors for nonsuicidal self-injury (NSSI), the mechanisms underlying this relationship remain unclear. The purpose of this study was to examine whether difficulty in emotion regulation (DER) and depressive symptoms mediate the relationship between child maltreatment experiences and NSSI severity, adjusting for demographic variables.

Methods

The participants were 224 adolescent inpatients recruited from a hospital in China (mean age 15.30 years, SD = 1.83; 78.6% females). Study measures included the Clinician-Rated Severity of Nonsuicidal Self-Injury (CRSNSSI), Childhood Trauma Questionnaire (CTQ-SF), Difficulties in Emotion Regulation Scale (DERS), and Patient Health Questionnaire-9 (PHQ-9). The hypothesized chain mediation model was tested using the structural equation model.

Results

A total of 146 (65.18%) adolescents reported engaging in NSSI during the past 12 months, and 103 (45.98%) participants met the DSM-5 diagnostic criteria for NSSI. Emotional neglect (48.1%) and emotional abuse (46.1%) had the highest prevalence, followed by physical neglect (43.1%) and physical abuse (24.1%), whereas sexual abuse (12.5%) was the least prevalent form of CM. Separately, both DER and depressive symptoms significantly mediated the association between CM and NSSI, with DER being the strongest mediator, with an indirect effect of 49.40% (p = 0.014). At the same time, we also proved a potential chain-mediated pathway of DER and depression in the relationship between CM and NSSI.

Conclusion

Child maltreatment seems to play a role in the aetiology of NSSI. DER and depressive symptoms both have a mediating role in the relationship between CM and NSSI. Importantly, DER seems to be a mediator with a stronger indirect effect compared to depressive symptoms.
Pre-hospital analgesia in pediatric trauma and critically ill patients: An analysis of a German air rescue service
Authors: Eimer Christine , Reifferscheid Florian , Jung Philipp , Rudolph Marcus , Terboven Tom , Hoffmann Florian , Lorenzen Ulf , Köser Andrea , Seewald Stephan
Published: January 2023

Background

Pain management in the pre-hospital setting remains a particular challenge for paramedics and emergency physicians, especially in children. This study evaluates the pre-hospital use and effect of analgesics in children with trauma or pain due to other reasons.

Methods

This study is a retrospective analysis of the database of a German air rescue service and was conducted over a period of 9 years (2012–2020) to assess pain in general and whether patients with trauma pain due to other reasons received treatment with analgesics. We included all patients in the registry under the age of 16 years. Patients with a Glasgow Coma Scale of 3 at hospital admission and incomplete records were excluded. The intensity of pain was determined by the emergency physician on scene at arrival and hospital admission in a ten-point rating scale (0 = no pain). Effective pain reduction was analyzed.

Results

Out of 227,458 cases, a total of 22,025 emergency cases involved pediatric patients aged 0–16 years. 20,405 cases were included in the study. 12,000 (58.8%) children had suffered a trauma, 8108 (39.7%) had pain due to other reasons and 297 (1.5%) had both. In total, 4,608 (38.4%) of the children with trauma were assessed having a numerical rating scale (NRS) > 4 at EMS arrival. These patients received mainly ketamine (34.5%) and the opioids fentanyl (38.7%) and piritramide (19.1%). The value on the NRS was significantly lower at admission to hospital (mean 1.9) compared with the EMS arrival (mean 6.9). In 4.9% the NRS at hospital admission was still > 4. 282 patients within the non-trauma group had a pre-hospital NRS of > 4. The pain therapy consisted of opioids (35.8%) and ketamine (2.8%). 28.4% patients in the non-trauma group received no pain medication. In 16.0% the NRS at hospital admission was still > 4.

Conclusions

German emergency physicians achieved a sufficient pain therapy in pediatric patients with a NRS > 4 after trauma. In case of non-trauma, the pain management by the emergency physicians is restrained and less successful. The most common analgesic medications administered were ketamine and fentanyl, followed by piritramide.

Trial registration: The study has been retrospectively registered at DRKS (DRKS00026222).
The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma
Authors: Wang Xiaonan , Zhu Wancui , Long Qian , Chen Enni , Sun Haohui , Li Xiaodi , Xu Hailin , Li Weizhao , Dong Pei , He Liru , Chen Miao , Deng Wuguo
Published: January 2023

Background

Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood.

Results

We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues.

Conclusions

We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.
A phase 1 clinical trial of the repurposable acetyllysine mimetic, n-methyl-2-pyrrolidone (NMP), in relapsed or refractory multiple myeloma
Authors: Jake Shortt  , Galettis Peter , Cheah Chan Y. , Davis Joanne , Ludford-Menting Mandy , Link Emma K. , Martin Jennifer H. , Koldej Rachel , Ritchie David
Published: January 2023

Background

N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR–MM). Secondary endpoints were safety, pharmacokinetics (PK), overall response rate and immunological biomarkers of activity.

Results

Thirteen patients received NMP at starting doses between 50 and 400 mg daily. Intra-patient dose escalation occurred in five patients, with one attaining the ceiling protocolised dose of 1 g daily. Median number of monthly cycles commenced was three (range 1–20). Grade 3–4 adverse events (AEs) were reported in seven (54%; 95% CI 25–81%) patients. Most common AEs (> 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200 mg NMP (overall DLT rate 8%; 95% CI 0–36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29–539) days and 33 (95% CI 9.7– > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39–91%). PK analysis demonstrated proportional dose–concentrations up to 400 mg daily, with a more linear relationship above 500 mg. Maximum plasma concentrations (Cmax) of 16.7 mg/L at the 800 mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12 months.

Conclusions

NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR–MM; an MTD was not determined up to a maximum dose of 1 g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.
An assessment of out of pocket payments in public sector health facilities under the free maternal healthcare policy in Ghana
Authors: Kumbeni Maxwell Tii , Afaya Agani , Apanga Paschal Awingura
Published: January 2023

Background

The free maternal healthcare policy was introduced in Ghana in 2008 under the national health insurance scheme as a social intervention to improve access to maternal health services. This study investigated the prevalence of out of pocket (OOP) payment among pregnant women with valid national health insurance who sought skilled delivery services at public sector health facilities in Ghana. The study also assessed the health system factors associated with OOP payment.

Methods

We used data from the Ghana Maternal Health Survey (GMHS), which was conducted in 2017. The study comprised 7681 women who delivered at a public sector health facility and had valid national health insurance at the time of delivery. We used multivariable logistic regression analysis to assess factors associated with OOP payment, whiles accounting for clustering, stratification, and sampling weights.

Results

The prevalence of OOP payment for skilled delivery services was 19.0%. After adjustment at multivariable level, hospital delivery services (adjusted Odds Ratio [aOR] = 1.23, 95% Confidence Interval [CI] = 1.00, 1.52), caesarean section (aOR = 1.73, 95% CI = 1.36, 2.20), and receiving intravenous infusion during delivery (aOR = 1.31, 95% CI = 1.08, 1.60) were associated with higher odds of OOP payment. Women who were discharged home 2 to 7 days after delivery had 19% lower odds of OOP payment compared to those who were discharged within 24 hours after delivery.

Conclusion

This study provides evidence of high prevalence of OOP payment among women who had skilled delivery services in public sector health facilities although such women had valid national health insurance. Government may need to institute measures to reduce OOP payment in public sector facilities especially at the hospitals and for women undergoing caesarean sections.
13C analysis of cow tail hair and farm slurry can be used to implicitly distinguish between different dairy production systems
Authors: Sieve Friederike , Isselstein Johannes , Kayser Manfred
Published: January 2023

Background

Public interest in the way food is produced on the farm and processed along the food-production chain is increasing. The analysis of isotopic signatures (13C) in cow tail hair provides a method to reconstruct the dietary proportion of maize in cow diets. Based on this, we further investigated whether there is a relationship between isotopic signatures in cow tail hair or farm slurry and the proportion of maize of the total utilized agricultural area per farm [%]. We did an on-farm survey on 17 dairy farms in coastal Northwest Germany and collected cow tail hair from dairy cows and slurry samples on each farm. The farms differed in their feeding regime (C3 vs. C4 plants), their site conditions (sandy soil = ‘Geestland’; organic soil = ‘Peatland’; clayey soil = ‘Marshland’), and in the area cultivated with maize as a proportion of the total utilized agricultural area per farm.

Results

We found a positive relationship between δ13C values in both cow tail hair and slurry and the annual dietary proportion of maize (R2 = 0.67; and R2 = 0.63). Furthermore, we confirmed that there was a relationship between δ13C values in cow tail hair and area of maize as a proportion of the total utilized agricultural area per farm (R2 = 0.69).

Conclusion

Our findings suggest a general applicability of using isotopic signatures (13C) along a wide gradient of site conditions and productions systems in practice.
Life expectancy and healthy life expectancy of patients with advanced schistosomiasis in Hunan Province, China
Authors: Jiang Honglin , Zhou Jie , Xia Meng , Li Guangping , Di Jie , Mao Feng , Yu Liangqing , Cai Yu , Wang Zhengzhong , Xiong Ying , Tong Yixin , Yin Jiangfan , Chen Yue , Jiang Qingwu , Zhou Yibiao
Published: January 2023

Background

Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality.

Methods

We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga’s decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap.

Results

The estimated LE for advanced schistosomiasis patients aged 15–19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80–84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE < 0). For advanced schistosomiasis patients, the gender gap in LE was largely attributed to the difference in mortality among those under the age of 55; the age-specific mortality in women exerted positive influence on the gap at age 25–64 and 75–79 years, with the contribution rate ranging from 0.59% to 57.02%, and made the negative contribution at other age groups.

Conclusions

The LE of advanced schistosomiasis patients was still much lower compared with general population. Strengthened prevention strategies and targeted treatments are needed to reduce morbidity and mortality due to advanced schistosomiasis, especially for younger population and elderly female patients.
Use of a “tablet pole” for the administration of ivermectin for strongyloidiasis in a field study in Ecuador
Authors: Buonfrate Dora , Anselmi Mariella , Prandi Rosanna , Marquez Monica , Mazzi Cristina , Montresor Antonio
Published: January 2023

Background

Establishment of efficient control programs for strongyloidiasis, the infection by Strongyloides stercoralis, is among the World Health Organization (WHO) targets for 2030. Ivermectin is a drug of choice for strongyloidiasis, but its weight-based administration can be unfeasible in remote areas. We evaluated a WHO tablet pole for administration of ivermectin in school-age children living in remote villages in Ecuador.

Methods

Children were enrolled in 16 villages in Esmeraldas Province of Ecuador, between July 2021 and June 2022. The pole identified four height intervals corresponding to ivermectin doses going from one to four tablets. For each child, we calculated the dose (µg/kg) administered with both weight-based and pole-based administration. Results were classified as follows: optimal dose, acceptable, overdose, underdose. Agreement between the two methods for estimating the number of tablets was assessed with Cohen’s kappa coefficient. Estimations were reported with 95% confidence intervals (CIs).

Results

Total of 778 children (47.3% female) were enrolled, with median age of 9.59 years (interquartile range: 7.42‒11.22). Optimal dose was achieved for a higher proportion of children when assessed with weight (37.9%) than with pole (25.7%). Underdose and overdose were more frequent with the pole (8.3% and 19.2% children, respectively) than with the weight-based (3.7% and 6.0%, respectively) administration. Agreement between weight-based and pole-based administration was moderate: 0.56 (95% CI 0.51, 0.61). The two methods indicated the same number of tablets in 71.6% (95% CI 0.684, 0.748) cases.

Conclusions

In our setting, the tablet pole could be a valid alternative. The tool needs further evaluation in different populations.

Graphical Abstract
Spatio-temporal trends of malaria incidence from 2011 to 2017 and environmental predictors of malaria transmission in Myanmar
Authors: Zhao Yan , Aung Pyae Linn , Ruan Shishao , Win Kyawt Mon , Wu Zifang , Soe Than Naing , Soe Myat Thu , Cao Yaming , Sattabongkot Jetsumon , Kyaw Myat Phone , Cui Liwang , Menezes Lynette , Parker Daniel M.
Published: January 2023

Background

Myanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar.

Methods

Monthly reports of malaria cases at primary health centers during 2011–2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively.

Results

From 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P < 0.05). Areas with higher malaria incidence were concentrated along international borders. Primary clusters of P. falciparum persisted in western townships, while clusters of P. vivax shifted geographically over the study period. The primary cluster was detected from January 2011 to December 2013 and covered two states (Sagaing and Kachin). Annual malaria incidence was highest in townships with a mean elevation of 500‒600 m and a high variance in elevation (states with both high and low elevation). There was an apparent linear relationship between the mean normalized difference vegetative index and annual P. falciparum incidence (P < 0.05).

Conclusion

The decreasing trends reflect the significant achievement of malaria control efforts in Myanmar. Prioritizing the allocation of resources to high-risk areas identified in this study can achieve effective disease control.

Graphical Abstract
A scoping review of community-based post-opioid overdose intervention programs: implications of program structure and outcomes
Authors: Bailey Amelia , Harrington Calla , Evans Elizabeth A.
Published: January 2023

Background

An emergent intervention to address the opioid epidemic is the use of multidisciplinary outreach teams which connect an individual in the community to healthcare resources after the experience of an opioid overdose. While these interventions are receiving federal funding, less is known empirically to inform future interventions. Understanding the process and outcomes of these interventions is advisable due to the novel partnerships of public health and law enforcement agencies who sometimes hold divergent goals. The objective of the present review was to describe program structure and evaluated outcomes of community-based post-overdose interventions.

Results

A search of PubMed, PsycInfo, and Web of Science yielded 5 peer-reviewed articles that detail the implementation and outcomes of interventions delivered in the United States published from 2001 to July 2021. Most interventions used a multidisciplinary outreach team and referenced first responder data to contact individuals who recently experienced an overdose at their residence. Services offered often included referral to substance use treatment, recovery coaches, and social services. Method of outreach, evaluation measures, and outcomes varied. From the available literature, facilitators of program engagement included communication, information sharing, and leadership buy-in among multidisciplinary partners.

Conclusions

Future studies could benefit from exploration of service provision in rural areas, for family affected by overdose, and for minoritized populations. Community-based post-overdose interventions utilizing a law enforcement partnership are emergent with promising yet limited examples in empirical literature.
Validation of the Arabic version of the 35-item TEMPS-M in a community sample of adults
Authors: Fekih-Romdhane Feten , Yakın Ecem , Bitar Zeinab , Malaeb Diana , Sawma Toni , Obeid Sahar , Hallit Souheil
Published: January 2023

Background

To our knowledge, no brief version of the Temperament Evaluation in Memphis Pisa and San Diego (TEMPS-M) is available so far in the Arabic language, which might have resulted in limited research in this field from Arab countries. We aimed through this study to validate the 35-item TEMPS-M into the Arabic language in a sample of non-clinical Lebanese adults.

Methods

We used an online cross-sectional survey targeting non-clinical Lebanese adults from the general population. A confirmatory factor analysis was conducted to test the factorial structure of the TEMPS-M.

Results

All five temperament subscales achieved good/very good internal consistencies in the present study (depressive: α = 0.78, cyclothymic: α = 0.86, hyperthymic: α = 0.83, irritable: α = 0.87, and anxious: α = 0.87). The five-factor solution of the TEMPS-M displayed a good CFI of 0.94, TLI of .94 and a GFI of .95, but a poor RMSEA of .10 [90% CI .10, .11]. The five affective temperaments showed positive correlations with personality dysfunction domains, thus attesting for convergent validity. In addition, positive correlations between all affective temperament dimensions and anxiety/depression scores were found. We also tested for gender invariance, and found that configural, metric, and scalar invariance were supported across gender.

Conclusion

Our data suggest that the psychometric properties of the Arabic TEMPS-M are good. Making this scale available in Arabic will hopefully encourage Arab researchers to investigate this under-explored topic in their countries, and advance knowledge on how culture impacts the prevalence, development and course of temperament.
Forex market forecasting using machine learning: Systematic Literature Review and meta-analysis
Authors: Ayitey Junior Michael , Appiahene Peter , Appiah Obed , Bombie Christopher Ninfaakang
Published: January 2023

Background

When you make a forex transaction, you sell one currency and buy another. If the currency you buy increases against the currency you sell, you profit, and you do this through a broker as a retail trader on the internet using a platform known as meta trader. Only 2% of retail traders can successfully predict currency movement in the forex market, making it one of the most challenging tasks. Machine learning and its derivatives or hybrid models are becoming increasingly popular in market forecasting, which is a rapidly developing field.

Objective

While the research community has looked into the methodologies used by researchers to forecast the forex market, there is still a need to look into how machine learning and artificial intelligence approaches have been used to predict the forex market and whether there are any areas that can be improved to allow for better predictions. Our objective is to give an overview of machine learning models and their application in the FX market.

Method

This study provides a Systematic Literature Review (SLR) of machine learning algorithms for FX market forecasting. Our research looks at publications that were published between 2010 and 2021. A total of 60 papers are taken into consideration. We looked at them from two angles: I the design of the evaluation techniques, and (ii) a meta-analysis of the performance of machine learning models utilizing evaluation metrics thus far.

Results

The results of the analysis suggest that the most commonly utilized assessment metrics are MAE, RMSE, MAPE, and MSE, with EURUSD being the most traded pair on the planet. LSTM and Artificial Neural Network are the most commonly used machine learning algorithms for FX market prediction. The findings also point to many unresolved concerns and difficulties that the scientific community should address in the future.

Conclusion

Based on our findings, we believe that machine learning approaches in the area of currency prediction still have room for development. Researchers interested in creating more advanced strategies might use the open concerns raised in this work as input.
Smoothing target encoding and class center-based firefly algorithm for handling missing values in categorical variable
Authors: Nugroho Heru , Utama Nugraha Priya , Surendro Kridanto
Published: January 2023

One of the most common causes of incompleteness is missing data, which occurs when no data value for the variables in observation is stored. An adaptive approach model outperforming other numerical methods in the classification problem was developed using the class center-based Firefly algorithm by incorporating attribute correlations into the imputation process (C3FA). However, this model has not been tested on categorical data, which is essential in the preprocessing stage. Encoding is used to convert text or Boolean values in categorical data into numeric parameters, and the target encoding method is often utilized. This method uses target variable information to encode categorical data and it carries the risk of overfitting and inaccuracy within the infrequent categories. This study aims to use the smoothing target encoding (STE) method to perform the imputation process by combining C3FA and standard deviation (STD) and compare by several imputation methods. The results on the tic tac toe dataset showed that the proposed method (C3FA-STD) produced AUC, CA, F1-Score, precision, and recall values of 0.939, 0.882, 0.881, 0.881, and 0.882, respectively, based on the evaluation using the kNN classifier.
What shapes implementation of a school-based makerspace? Teachers as multilevel actors in STEM reforms
Authors: Gravel Brian E. , Puckett Cassidy
Published: January 2023

Background

We investigate the factors that shape teachers’ implementation of a school STEM reform—the creation of a high-school makerspace. Educational reformers have increasing interest in making and makerspaces in schools. Prior research shows how factors shape reform at the classroom, school (organizational), and institutional levels, as well as across levels. However, most research on teachers tends to focus on classroom-level effects, which may not capture the full complexity of how they navigate multilevel reforms. We consider teachers’ decision-making from an ecological perspective to investigate what shapes their implementation efforts, using observational and interview data collected over 2 years in a large comprehensive high school.

Results

We find teachers’ efforts are shaped by four “distances”—or spaces teachers traversed, physically and conceptually—related to skillsets and distributed expertise, physical space, disciplinary learning, and structural factors. The distances operate as a constellation of factors—independently identifiable, co-operatively manifesting—to shape implementation. We position teacher deliberations and decision-making as portals into the forms of organizational and institutional supports offered in multilevel reforms.

Conclusions

The paper contributes insights into makerspace implementation in schools, adding to the emerging literature on how making can transform STEM learning experiences for students. We conclude that teachers’ decision-making around multilevel implementations can inform our understanding of how makerspaces are implemented and their impact on students’ experiences, as well as how seeing teachers as multilevel actors can offer new insights into reform dynamics writ large. We offer implications for makerspaces in schools, as well as methodological and theoretical considerations for how organizations and institutions can better support teachers as agents of STEM reform.