bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of background EEG activity based on MRI findings in neonatal hypoxic-ischemic encephalopathy: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study
Authors: Kim Kwang Yeon , Lee Joo-Young , Moon Ja-Un , Eom Tae-Hoon , Kim Young-Hoon
Published: June 2022

Background

It is important to assess the degree of brain injury and predict long-term outcomes in neonates diagnosed with hypoxic-ischemic encephalopathy (HIE). However, routine studies, including magnetic resonance imaging (MRI) and conventional encephalography (EEG) or amplitude-integrated EEG (aEEG), have their own limitations in terms of availability and accuracy of evaluation. Recently, quantitative EEG (qEEG) has been shown to improve the predictive reliability of neonatal HIE and has been further refined with brain mapping techniques.

Methods

We investigated background EEG activities in 29 neonates with HIE who experienced therapeutic hypothermia, via qEEG using a distributed source model. MRI images were evaluated and classified into two groups (normal-to-mild injury vs moderate-to-severe injury), based on a scoring system. Non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the two groups.

Results

Electrical neuronal activities were significantly lower in the moderate-to-severe injury group compared with the normal-to-mild injury group. Background EEG activities in moderate-to-severe HIE were most significantly reduced in the temporal and parietal lobes. Quantitative EEG also revealed a decrease in background activity at all frequency bands, with a maximum in decrease in the delta component. The maximum difference in current density was found in the inferior parietal lobule of the right parietal lobe for the delta frequency band.

Conclusions

Our study demonstrated quantitative and topographical changes in EEG in moderate-to-severe neonatal HIE. They also suggest possible implementation and evaluation of conventional EEG and aEEG in neonatal HIE. The findings have implications as biomarkers in the assessment of neonatal HIE.
The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086)
Authors: Tropea Saveria , Del Fiore Paolo , Maurichi Andrea , Patuzzo Roberto , Santinami Mario , Ribero Simone , Quaglino Pietro , Caliendo Virginia , Borgognoni Lorenzo , Sestini Serena , Giudice Giuseppe , Nacchiero Eleonora , Caracò Corrado , Cordova Adriana , Solari Nicola , Piazzalunga Dario , Tauceri Francesca , Carcoforo Paolo , Lombardo Maurizio , Cavallari Sara , Mocellin Simone ,   Italian Melanoma Intergroup (IMI), Cespa Maddalena , Forcignanò Rosachiara , Moise Gianmichele , Fargnoli Maria Concetta , Ferreli Caterina , Grimaldi Maria , Zannetti Guido , Cinieri Saverio , Trevisan Giusto , Stanganelli Ignazio , Moretti Giovanna , Bruder Francesca , Bianchi Luca , Fierro Maria Teresa , Mascheroni Luigi , Asero Salvatore , Catricalà Caterina , Staibano Stefania , Rinaldi Gaetana , Pellicano Riccardo , Milesi Laura , Visini Marilena , Di Filippo Franco , Zichichi Leonardo , Pizzichetta Maria Antonietta , Iacono Carmelo , Guidoboni Massimo , Sanna Giovanni , Maio Michele , Del Vecchio Michele , Lospalluti Lucia , Vita Leonardi , Pollio Annamaria , Riberti Carlo
Published: June 2022

Background

The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients.

Methods

A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model.

Results

The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS.

Conclusion

The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.
Excess mortality associated with the COVID-19 pandemic in Latvia: a population-level analysis of all-cause and noncommunicable disease deaths in 2020
Authors: Gobiņa Inese , Avotiņš Andris , Kojalo Una , Strēle Ieva , Pildava Santa , Villeruša Anita , Briģis Ģirts
Published: June 2022

Background

Age-standardised noncommunicable disease (NCD) mortality and the proportion of the elderly population in Latvia are high, while public health and health care systems are underresourced. The emerging COVID-19 pandemic raised concerns about its detrimental impact on all-cause and noncommunicable disease mortality in Latvia. We estimated the timing and number of excess all-cause and cause-specific deaths in 2020 in Latvia due to COVID-19 and selected noncommunicable diseases.

Methods

A time series analysis of all-cause and cause-specific weekly mortality from COVID-19, circulatory diseases, malignant neoplasms, diabetes mellitus, and chronic lower respiratory diseases from the National Causes of Death Database from 2015 to 2020 was used by applying generalised additive modelling (GAM) and joinpoint regression analysis.

Results

Between weeks 14 and 52 (from 1 April to 29 December) of 2020, a total of 3111 excess deaths (95% PI 1339 – 4832) were estimated in Latvia, resulting in 163.77 excess deaths per 100 000. Since September 30, with the outbreak of the second COVID-19 wave, 55% of all excess deaths have occurred. Altogether, COVID-19-related deaths accounted for only 28% of the estimated all-cause excess deaths. A significant increase in excess mortality was estimated for circulatory diseases (68.91 excess deaths per 100 000). Ischemic heart disease and cerebrovascular disease were listed as the underlying cause in almost 60% of COVID-19-contributing deaths.

Conclusions

All-cause mortality and mortality from circulatory diseases significantly increased in Latvia during the first pandemic year. All-cause excess mortality substantially exceeded reported COVID-19-related deaths, implying COVID-19-related mortality during was significantly underestimated. Increasing mortality from circulatory diseases suggests a negative cumulative effect of COVID-19 exposure and reduced access to healthcare services for NCD patients.
A genetic correlation scan identifies blood proteins associated with bone mineral density
Authors: Xu Jiawen , Zhang Shaoyun , Si Haibo , Zeng Yi , Wu Yuangang , Liu Yuan , Li Mingyang , Wu Limin , Shen Bin
Published: June 2022

Background

Osteoporosis is a common metabolic bone disease that is characterized by low bone mass. However, limited efforts have been made to explore the functional relevance of the blood proteome to bone mineral density across different life stages.

Methods

Using genome-wide association study summary data of the blood proteome and two independent studies of bone mineral density, we conducted a genetic correlation scan of bone mineral density and the blood proteome. Linkage disequilibrium score regression analysis was conducted to assess genetic correlations between each of the 3283 plasma proteins and bone mineral density.

Results

Linkage disequilibrium score regression identified 18 plasma proteins showing genetic correlation signals with bone mineral density in the TB-BMD cohort, such as MYOM2 (coefficient = 0.3755, P value = 0.0328) among subjects aged 0 ~ 15, POSTN (coefficient = − 0.5694, P value = 0.0192) among subjects aged 30 ~ 45 and PARK7 (coefficient = − 0.3613, P value = 0.0052) among subjects aged over 60.

Conclusions

Our results identified multiple plasma proteins associated with bone mineral density and provided novel clues for revealing the functional relevance of plasma proteins to bone mineral density.
Clinical results following colonic resection for ulcerative colitis in elderly individuals (elderly-onset vs. nonelderly onset)
Authors: Kuwahara Ryuichi , Ikeuchi Hiroki , Bando Toshihiro , Goto Yoshiko , Horio Yuki , Minagawa Tomohiro , Uchino Motoi
Published: June 2022

Background

The incidence of ulcerative colitis (UC) is increasing, but there are few reports comparing elderly UC patients undergoing colectomy for elderly-onset UC (EO) and nonelderly-onset UC (NEO). The aim of this study was to analyze the differences between EO and NEO patients who underwent UC-related surgery.

Methods

We identified 1973 patients with UC who underwent colectomy at Hyogo College of Medicine between January 1, 1984, and December 31, 2018. Only patients aged 65 years old and older who underwent colectomy were enrolled in this study (n = 221, 11.2%), and their clinical records were retrospectively reviewed. Patients were divided into two groups according to their age at disease onset: those with onset at younger than 60 years old (NEO) and at 60 years old or older (EO).

Results

In the 221 UC patients who underwent colectomy at 65 years old or older, there were 155 cases of EO and 66 cases of NEO. The main surgical indication in NEO patients was colitis-associated cancer/dysplasia (32/66, 47%). In contrast, refractory to medical treatment was the leading cause of surgery in EO patients (80/155, 52%). The distributions of surgical indications were different between the two groups (p < 0.01). The preoperative daily dose of steroids was significantly higher in the EO group than in the NEOgroup (0 mg vs. 10 mg, p < 0.01). The rates of immunosuppressant, infliximab (IFX) and adalimumab use did not differ significantly between the groups. Significantly more patients underwent emergency surgery in the EO group than in the NEO group (14% vs. 35%, p < 0.01). The proportions of patients with postoperative morbidity (Clavien-Dindo grade III or higher) were 17.4% (27/155) in the EO group and 13.6% (9/66) in the NEO group. There was no significant difference between the two groups (p = 0.48). The prognosis of the EO patients who underwent UC-related emergency surgery was worse than that of the NEO patients (p < 0.01). In the EO group, 8 (14.8%) of 54 patients died within 30 postoperative days, while there were no deaths in the NEO group.

Conclusion

Among elderly UC patients undergoing UC-related surgery, EO patients undergoing emergency surgery had very poor outcomes, and the mortality rate was 14.8%. In such cases, it is important for physicians and surgeons to begin communication at an early stage so that the optimal surgical timeframe is not missed.
Child marriage and risky health behaviors: an analysis of tobacco use among early adult and early middle-aged women in India
Authors: Datta Biplab K. , Tiwari Ashwini , Fazlul Ishtiaque
Published: June 2022

Background

Though the harmful impacts of child marriage have been evaluated across several domains, evidence on the relationship between child marriage and health behaviors over the life course is limited. In this paper, we examined whether getting married as a child is associated with one of the most common risky health behaviors, tobacco use, in adulthood.

Methods

Using nationally representative data from India, we compared the odds in favor of tobacco use among early adult (age 22–34) and early middle-aged (age 35–44) women who were married before age 18 with that of those who were married as youths (age 18–21). We estimated univariate and multivariable logistic regressions to obtain odds ratios in favor of any tobacco-use and relative risk ratios in favor of mutually exclusive types of tobacco use (smoking-only, smokeless-only, and dual-use). We also explored the intensive margin of the relationship by assessing if the odds of tobacco use in adulthood were affected by how early (13 or less, 14–15, or 16–17) a child bride was married.

Results

We find that the adjusted odds of tobacco use for those who were married as a child were 1.3 and 1.2 times that of those who were married as a youth among early adult and early middle-aged women, respectively. The younger was the child bride when married, the higher were the odds of tobacco use as an adult. The relative risks of different types of tobacco use were also higher for child brides than their peers.

Conclusions

These results are the first evidence of the association between child marriage and a major risky health behavior, tobacco use, over the life course. These findings will inform policies to strengthen child marriage prevention efforts and targeted tobacco control initiatives in the low-and-middle income countries.
Learning on the run – a qualitative, longitudinal study of pharmacy educators’ experiences implementing a hospital pharmacy residency program
Authors: Wang Chih Yuan , Clavarino Alexandra , Winckel Karl , Stacey Sonya , Luetsch Karen
Published: June 2022

Background

A hospital pharmacy foundation residency training program has been introduced in Australia, modelled on residency programs established in other countries. The program aims to support the professional development of early-career hospital pharmacists, in both clinical and non-clinical roles. Pharmacy educators are usually tasked with the implementation and maintenance of this program. This qualitative, longitudinal study aimed to investigate hospital pharmacy educators’ expectations, perceptions and experiences with implementing and developing their residency program.

Methods

Qualitative data were collected at two timepoints, approximately 24 months apart, using either focus groups or interviews with pharmacy educators who were directly involved in the implementation of the residency program at their respective hospitals. During the early phases of implementation, and approximately 24 months later, participants were asked about their experiences and expectations of the residency program as well as any changes that had occurred within the residency program over time.

Results

Four focus groups and three semi-structured interviews were held with pharmacy educators and senior pharmacists from different hospital settings. These were audio recorded and transcribed verbatim. Transcripts were inductively analysed via thematic analysis. Fifteen hospital pharmacy educators and senior hospital pharmacists participated in the initial focus groups and interviews, and seven educators were retained for follow-up. Four main themes were established from the discussions: participants had great expectations of a positive impact of the residency on their workplace and residents’ professional development; substantial effort, support and resources were needed to implement and maintain a residency program; self-motivation and engagement is needed by residents to succeed and experience timely completion and career acceleration; and lastly a balance between standardisation, consistency and flexibility in delivering the residency needs to be found. The role of educators changed with the implementation of a residency, with the addition of more managerial and supervisory aspects.

Conclusion

The Australian hospital pharmacy foundation residency program is a complex workplace training program with multiple factors and prerequisites influencing its implementation, development and outcomes. Pharmacy educators are central to the successful implementation and ongoing sustainability of a residency program. They may benefit from formal training and qualifications to support their role.
Organizational logics in time of crises: How physicians narrate the healthcare response to the Covid-19 pandemic in Swedish hospitals
Authors: Jacobsson Maritha , Härgestam Maria , Bååthe Fredrik , Hagqvist Emma
Published: June 2022

Background

The COVID-19 pandemic has challenged healthcare organizations and puts focus on risk management in many ways. Both medical staff and leaders at various levels have been forced to find solutions to problems they had not previously encountered. This study aimed to explore how physicians in Sweden narrated the changes in organizational logic in response to the Covid-19 pandemic using neo-institutional theory and discursive psychology. In specific, we aimed to explore how physicians articulated their understanding of if and, in that case, how the organizational logic has changed during this crisis response.

Methods

The empirical material stems from interviews with 29 physicians in Sweden in the summer and autumn of 2020. They were asked to reflect on the organizational response to the pandemic focusing on leadership, support, working conditions, and patient care.

Results

The analysis revealed that the organizational logic in Swedish healthcare changed and that the physicians came in troubled positions as leaders. With management, workload, and risk repertoires, the physicians expressed that the organizational logic, to a large extent, was changed based on local contextual circumstances in the 21 self-governing regions. The organizational logic was being altered based upon how the two powerbases (physicians and managers) were interacting over time.

Conclusions

Given that healthcare probably will deal with future unforeseen crises, it seems essential that healthcare leaders discuss what can be a sustainable organizational logic. There should be more explicit regulatory elements about who is responsible for what in similar situations. The normative elements have probably been stretched during the ongoing crisis, given that physicians have gained practical experience and that there is now also, at least some evidence-based knowledge about this particular pandemic. But the question is what knowledge they need in their education when it comes to dealing with new unknown risks.
Associations of handgrip strength with morbidity and all-cause mortality of cardiometabolic multimorbidity
Authors: Lu Yanqiang , Li Guochen , Ferrari Pietro , Freisling Heinz , Qiao Yanan , Wu Luying , Shao Liping , Ke Chaofu
Published: June 2022

Background

Cardiometabolic multimorbidity (CM) is an increasing public health and clinical concern. However, predictors for the development and prognosis of CM are poorly understood. The aims of this study were to investigate the relation between handgrip strength (HGS) and the risk of CM and to examine the association of HGS with all-cause mortality risk among patients with CM.

Methods

This prospective cohort study involved 493,774 participants from the UK Biobank. CM was defined as the simultaneous occurrence of two or more of the following conditions: type 2 diabetes, stroke, and coronary heart disease (CHD). Cox proportional hazards models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

During a median follow-up of 12.1 years, 4701 incident CM cases were documented among participants with none cardiometabolic disease at baseline. Compared with the fourth quartile (Q4), the multivariable adjusted HR (95% CI) value of Q1 of HGS for developing CM was 1.46 (1.34–1.60). In participants with one cardiometabolic disease at baseline, participants in Q1 of HGS also possessed higher risk of CM than those in Q4, with HRs (95% CIs) being 1.35 (1.23–1.49) in patients with type 2 diabetes, 1.23 (1.04–1.46) in patients with stroke, and 1.23 (1.11–1.36) in patients with CHD. For participants with CM at recruitment, HGS was also associated with the risk of all-cause mortality (Q1 vs. Q4 HR: 1.57, 95% CI: 1.36–1.80).

Conclusions

Our study provided novel evidence that HGS could be an independent predictor of morbidity and all-cause mortality of CM.
Simultaneous and enantiospecific quantification of primaquine and carboxyprimaquine in human plasma using liquid chromatography-tandem mass spectrometry
Authors: Hanpithakpong Warunee , Day Nicholas P. J. , White Nicholas J. , Tarning Joel
Published: June 2022

Background

The enantiomers of the 8-aminoquinoline anti-malarial primaquine have different pharmacological properties. Development of an analytical method for simultaneous quantification of the enantiomers of primaquine and its metabolite, carboxyprimaquine, will support clinical pharmacometric assessments.

Methods

A simple and sensitive method consisting of liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) was developed for simultaneous and enantiospecific determination of primaquine and its metabolite, carboxyprimaquine, in human plasma. Stable isotopes were used as internal standards to compensate for potential interference and matrix effects. Plasma samples (100 µL) were precipitated with 1% formic acid in acetonitrile followed by phospholipid removal solid phase extraction. Primaquine and carboxyprimaquine enantiomers were separated on a Chiralcel OD-3R (150 mm × 4.6 mm; I.D. 3 μm) column using a LC gradient mode. For separation of racemic primaquine and carboxyprimaquine, the LC method was modified and validated using a reverse phase column (Hypersil Gold 100 mm × 4.6 mm; I.D. 3 µm) and a mobile phase composed of 10 mM ammonium acetate buffer, pH 3.5 and acetonitrile in the isocratic mode. Method validation was performed according to regulatory guidelines.

Results

The calibration range was set to 0.571–260 ng/mL and 2.44–2,500 ng/mL for primaquine and carboxyprimaquine enantiomers, respectively, resulting in a correlation coefficient (r2) ≥ 0.0998 for all calibration curves. The intra- and inter-day assay precisions were < 10% and the accuracy was between 94.7 to 103% for all enantiomers of primaquine and carboxyprimaquine. The enantiospecific method was also modified and validated to quantify racemic primaquine and carboxyprimaquine, reducing the total run time from 30 to 8 min. The inter-, intra-day assay precision of the racemic quantification method was < 15%. The absolute recoveries of primaquine and carboxyprimaquine were between 70 and 80%. Stability was demonstrated for up to 2 years in − 80 °C. Both the enantiomeric and racemic LC–MS/MS methods were successfully implemented in pharmacokinetic studies in healthy volunteers.

Conclusions

Simple, sensitive and accurate LC–MS/MS methods for the quantification of enantiomeric and racemic primaquine and carboxyprimaquine in human plasma were validated successfully and implemented in clinical routine drug analysis.
Tregs biomimetic nanoparticle to reprogram inflammatory and redox microenvironment in infarct tissue to treat myocardial ischemia reperfusion injury in mice
Authors: Li Fangyuan , Liu Daozhou , Liu Miao , Ji Qifeng , Zhang Bangle , Mei Qibing , Cheng Ying , Zhou Siyuan
Published: June 2022

Background

At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI). There lacks effectively method to treat MI/RI in clinic. For the treatment of MI/RI, it is still a bottleneck to effectively deliver drug to ischemic myocardium. In this paper, a regulatory T cells (Tregs) biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging nanoparticle with platelet membrane.

Results

CsA@PPTK actively accumulated in ischemic myocardium of MI/RI mice. CsA@PPTK significantly scavenged reactive oxygen species (ROS) and increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Moreover, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. CsA@PPTK markedly decreased the protein expression of MMP-9 and increased the protein expression of CX43 in ischemic myocardium tissue. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of MI/RI mice was markedly improved.

Conclusion

CsA@PPTK showed significant therapeutic effect on MI/RI, and it has great potential application in the treatment of MI/RI.

Graphical Abstract
Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy
Authors: Wang Yao , Jia Ming , Zheng Xiu , Wang Chenglong , Zhou Yun , Pan Hong , Liu Yan , Lu Ji , Mei Zhiqiang , Li Chunhong
Published: June 2022

Background

Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects.

Results

Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~ 70%) and EE (~ 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications.

Conclusions

This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment.

Graphical Abstract
The group-based law enforcement mistrust scale: psychometric properties of an adapted scale and implications for public health and harm reduction research
Authors: Johnson Laura M. , Devereux Paul G. , Wagner Karla D.
Published: June 2022

Background

Negative encounters with law enforcement—direct and vicarious—fuel mistrust. When considered as part of the ‘risk environment’ in public health and harm reduction research, law enforcement mistrust may have broad implications. For example, fearing arrest may prevent someone from calling 911 when witnessing an overdose or lead to syringe-sharing and community spread of HIV. For people in the US who identify as Black or African American, these effects may compound, given the ways in which communities of color have been overpoliced. The purpose of this study is to investigate the psychometrics of an adapted scale of law enforcement mistrust—the Group-Based Law Enforcement Mistrust Scale (GBLEMS)—and evaluate its associations with racial and ethnic identity and experiences with law enforcement.

Methods

This cross-sectional survey took place in a small city in the Western United States where only 3% of the population is Black or African American. The sample included Black or African American and Hispanic and Latina women at risk of HIV, and members of their social networks, yielding a diverse sample across racial, ethnic, and gender identities (N = 219). The GBLEMS is a 12-item scale adapted from the Group-Based Medical Mistrust Scale (GBMMS; Thompson et al. 2004). The current analysis evaluated the psychometric properties of the GBLEMS (reliability, exploratory factor analysis) and its associations with demographics, other race-based constructs, and experiences with law enforcement.

Results

The GBLEMS demonstrated strong reliability (Cronbach’s alpha = 0.92) and exploratory factor analysis indicated that items loaded onto two factors—mistrust and disparities in treatment. There was also support for the scale’s construct validity. As hypothesized, GBLEMS scores were higher among respondents who identify as Black or African American, and among those who reported other experiences of racial discrimination, medical mistrust, and negative encounters with law enforcement.

Conclusions

This study yielded support for the reliability and validity of the GBLEMS as a multi-item, two-factor scale measuring group-based law enforcement mistrust. When framing public health and harm reduction research in terms of the risk environment, law enforcement mistrust may be important to measure as part of a comprehensive approach that addresses persistent racial disparities.
The study of feasibility and acceptability of using HIV self-tests in high-risk Iranian populations (FSWs, MSM, and TGs): a cross-sectional study
Authors: Moradi Ghobad , Amini Elnaz Ezzati , Valipour Azam , Tayeri Katayoon , Kazerooni Parvin Afsar , Molaeipour Leila , Moradi Yousef
Published: June 2022

Background

This study aimed to evaluate the feasibility of using the HIV self-test in high-risk Iranian groups (MSM, FSWs, and TGs).

Methods

This study was a mixed study designed as a quantitative–qualitative study conducted between October 1, 2020, and June 22, 2021, in Tehran and Karaj, Iran. The sample size needed for this study generally was 1000 people, including FSWs, MSM, and transgender individuals. Convenience and snowball sampling methods were used to collect the samples.

Results

A total of 930 eligible respondents were enrolled in the study, of whom 456 (49%) were female and 49 (5.3%) were transgender (98% of TGs were male to female), and their mean age was 33.63 years (10.54 SD). The feasibility of using HIV self-tests in Iranian high-risk groups was significantly high. The majority of participants (97%) did not have any confidentiality problems while preparing or performing the test. In general, feasibility was assessed based on five questions. The overall feasibility score was 6.33 (0.824 SD). Taking tests, reading HIV test results, finding a safe place to do the test, and accessing HIV self-tests showed a high average.

Conclusion

HIV self-testing was highly acceptable and feasible among high-risk populations, so routine HIV testing was efficiently possible.
Uptake of COVID-19 vaccination among people who inject drugs
Authors: Iversen Jenny , Wand Handan , Kemp Robert , Bevan Jude , Briggs Myf , Patten Kate , Heard Sue , Maher Lisa
Published: June 2022

Background

People who inject drugs (PWID) may be at elevated risk of adverse outcomes from SARS-CoV-2 infection; however, data on COVID-19 vaccine uptake among PWID are scarce. This study aimed to determine COVID-19 vaccine uptake among PWID, identify factors associated with sub-optimal uptake, and compare uptake to the general population.

Methods

The Australian Needle Syringe Program Survey is an annual sentinel surveillance project, comprising a self-completed questionnaire and provision of a dried blood sample for HIV and HCV testing. In 2021, respondents provided information on their COVID-19 vaccination status. Multivariate logistic regression models identified correlates of vaccine uptake.

Results

Among 1166 respondents, 49% had been vaccinated and in most states and territories, vaccine uptake was significantly lower than among the general population. Independent predictors of vaccine uptake were longer duration of vaccine eligibility (AOR 3.42, 95% CI 2.65, 4.41); prior SARS-CoV-2 diagnostic testing (AOR 2.90, 95% CI 2.22, 3.79); injection of opioids (AOR 1.91, 95% CI 1.20, 3.05); and current opioid agonist therapy (AOR 1.70, 95% CI 1.23, 2.33). Women (AOR 0.70, 95% CI 0.54, 0.92) and those who reported daily or more frequent injection (AOR 0.75, 95% CI 0.57, 1.00) were significantly less likely to be vaccinated.

Conclusions

In most Australian states and territories, uptake of COVID-19 vaccine among PWID lagged uptake among the general population. Increased efforts are required to ensure PWID have equitable access to vaccination. Vaccination programmes within harm reduction services and via outreach, coupled with increased support for peers to act as vaccine champions, are likely to reduce barriers and improve COVID-19 vaccine uptake in this population.
Differences in clinical outcomes according to the time interval between the bridge to surgery stenting and surgery for left-sided malignant colorectal obstruction
Authors: Oh Hyung-Hoon , Hong Ji-Yun , Kim Dong-Hyun , Myung Dae-Seong , Cho Sung-Bum , Lee Wan-Sik , Kim Hyun-Soo , Joo Young-Eun
Published: June 2022

Background

Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO.

Methods

Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2–3 weeks), and group 3 (interval >3 weeks).

Results

Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival.

Conclusions

A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.
Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells
Authors: Ma Liang , Zhang Liwen , Zhuang Yun , Ding Yanbo , Chen Jianping
Published: June 2022

Background

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH.

Methods

Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin–eosin staining to determine the role of gut microbiota on AIH.

Results

Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner.

Conclusion

Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH.
Anastasis: cell recovery mechanisms and potential role in cancer
Authors: Mohammed Rebar N. , Khosravi Mohsen , Rahman Heshu Sulaiman , Adili Ali , Kamali Navid , Soloshenkov Pavel Petrovich , Thangavelu Lakshmi , Saeedi Hossein , Shomali Navid , Tamjidifar Rozita , Isazadeh Alireza , Aslaminabad Ramin , Akbari Morteza
Published: June 2022

Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance.
Bayesian analysis of dynamic phosphoproteomic data identifies protein kinases mediating GPCR responses
Authors: Leo Kirby T. , Chou Chung-Lin , Yang Chin-Rang , Park Euijung , Raghuram Viswanathan , Knepper Mark A.
Published: June 2022

Background

A major goal in the discovery of cellular signaling networks is to identify regulated phosphorylation sites (“phosphosites”) and map them to the responsible protein kinases. The V2 vasopressin receptor is a G-protein coupled receptor (GPCR) that is responsible for regulation of renal water excretion through control of aquaporin-2-mediated osmotic water transport in kidney collecting duct cells. Genome editing experiments have demonstrated that virtually all vasopressin-triggered phosphorylation changes are dependent on protein kinase A (PKA), but events downstream from PKA are still obscure.

Methods

Here, we used: 1) Tandem mass tag-based quantitative phosphoproteomics to experimentally track phosphorylation changes over time in native collecting ducts isolated from rat kidneys; 2) a clustering algorithm to classify time course data based on abundance changes and the amino acid sequences surrounding the phosphosites; and 3) Bayes’ Theorem to integrate the dynamic phosphorylation data with multiple prior “omic” data sets covering expression, subcellular location, known kinase activity, and characteristic surrounding sequences to identify a set of protein kinases that are regulated secondary to PKA activation.

Results

Phosphoproteomic studies revealed 185 phosphosites regulated by vasopressin over 15 min. The resulting groups from the cluster algorithm were integrated with Bayes’ Theorem to produce corresponding ranked lists of kinases likely responsible for each group. The top kinases establish three PKA-dependent protein kinase modules whose regulation mediate the physiological effects of vasopressin at a cellular level. The three modules are 1) a pathway involving several Rho/Rac/Cdc42-dependent protein kinases that control actin cytoskeleton dynamics; 2) mitogen-activated protein kinase and cyclin-dependent kinase pathways that control cell proliferation; and 3) calcium/calmodulin-dependent signaling.

Conclusions

Our findings identify a novel set of downstream small GTPase effectors and calcium/calmodulin-dependent kinases with potential roles in the regulation of water permeability through actin cytoskeleton rearrangement and aquaporin-2 trafficking. The proposed signaling network provides a stronger hypothesis for the kinases mediating V2 vasopressin receptor responses, encouraging future targeted examination via reductionist approaches. Furthermore, the Bayesian analysis described here provides a template for investigating signaling via other biological systems and GPCRs.
Single-cell sequencing analysis reveals gastric cancer microenvironment cells respond vastly different to oxidative stress
Authors: Yu Weihua , Chen Guojun , Yan Jiafei , Wang Xianfa , Zhu Yiping , Zhu Linghua
Published: June 2022

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients’ survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.
CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice
Authors: Thomas Aline M. , Yang Ethan , Smith Matthew D. , Chu Chengyan , Calabresi Peter A. , Glunde Kristine , van Zijl Peter C. M. , Bulte Jeff W. M.
Published: June 2022

Background

Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs.

Methods and results

We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine.

Conclusions

Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.
DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation
Authors: Zhang Long-Qing , Gao Shao-Jie , Sun Jia , Li Dan-Yang , Wu Jia-Yi , Song Fan-He , Liu Dai-Qiang , Zhou Ya-Qun , Mei Wei
Published: June 2022

Background

Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Microglial activation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. However, the mechanisms underlying spinal microglial activation during neuropathic pain remain incompletely understood. Here, we investigated the role of Dickkopf (DKK) 3 and its interplay with microglial activation in the spinal cord in neuropathic pain.

Methods

In this study, we investigated the effects of intrathecal injection of recombinant DKK3 (rDKK3) on mechanical allodynia and microglial activation in the spinal cord after spared nerve injury (SNI) in rats by western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA).

Results

We found that SNI induced a significant decrease in the levels of DKK3, Kremen-1 and Dishevelled-1 (DVL-1) and up-regulated the expression of phosphorylated apoptosis signal-regulating kinase 1 (p-ASK1), phosphorylated c-JUN N-terminal kinase (p-JNK), phosphorylated p38 (p-p38) in the spinal cord. Moreover, our results showed that exogenous intrathecal administration of rDKK3 inhibited expression of p-ASK1, p-JNK, p-p38, promoted the transformation of microglia from M1 type to M2 type, and decreased the production of pro-inflammatory cytokines compared to the rats of SNI + Vehicle. However, these effects were reversed by intrathecal administration of Kremen-1 siRNA or Dishevelled-1 (DVL-1) siRNA.

Conclusions

These results suggest that DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation, at least partly, by the Kremen-1 and DVL-1 pathways.
Origin and evolution analysis and genetic characteristics of echovirus 9 in China
Authors: Si Fenfen , Ji Tianjiao , Wang Dongyan , Zhang Yong , Zhu Shuangli , Li Junhan , Xu Wenbo , Yan Dongmei
Published: June 2022

Background

Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9.

Method

A total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9.

Results

The estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10−3 substitutions per site per year (95% confidence interval [CI], 3.822 × 10−3/site/year to 4.710 × 10−3/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9–79.6% nucleotide identity and 95.3–95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity.

Conclusion

This study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9.