bluuebunny/crossref_metadata_2025 huggingface dataset:
Project Taking Charge: An Interprofessional Education Approach to Improve Health Outcomes
Authors: Eng Howard J , Tong Theodore G
Published: August 2022

Project Taking Charge (PTC) is an interprofessional community health education experience for medical, nursing, pharmacy, and public health students. PTC uses a patient/family center, inter-professional team-based approach to change project participants’ lifestyle and health practices that will improve their health status. The PTC employs the KAP-O health promotion strategy that increase Knowledge resulting in positive Attitudes changes that lead to desirable Practice changes of project participants. Positive health behavioral (practice) changes result to health Outcome improvements. Participants who attended more than one health promotional session decreased their risk factors as indicated by the screening results.
Evaluation of Advanced Medical Imaging Services at Government Hospitals-West Bank
Authors: Ahmad Muntaser S , Rjoub Bara’A , Abuelsamen Abdulsalam , Mohammad Hjouj
Published: August 2022

Background: Medical imaging services provided to patients in the CT and MRI unit are essential to reach the best results for assessing their health conditions. Objective: The aim of this study was to evaluate the client’s satisfaction and medical services of the CT and MRI at private centres and hospitals in the West Bank- Palestine. Methods: The study was based on triangulated design; checklist, interview and questionnaire. The checklist is made by researchers to evaluate CT and MRI units’ design. The researchers interviewed 100 patients who were imaged in CT and MRI units to assess their satisfaction with the provided medical service. The questionnaire was distributed to 28 radiologic technologists (RTs) to know their characteristics and to assess the extent of the RTs commitment to the medical services. Results: Findings revealed that from the client’s perspective: Inferential analysis shows that there was a statistically significant difference at the level of significant α≤0.05 in reception and waiting with respect to the residence. While there is no statistically significant difference at (α≤0.05) in the evaluating of reception and communication in the radiology department with respect to gender and employment status. Meanwhile, the results showed there is a relationship between satisfaction and the monthly income of participants. The study showed MRI units track the international standard system in structures and occupational safety while about 87.5% of CT units follow occupational safety and about 65% of the structures. Conclusion: Through the study, the shortage in the CT and MRI units, and RTs compared to other countries became clear. The deficiency was observed in radiological protection techniques presented to patients and RTs
Ophthalmic Zoster, A Rare Pathology in a Child
Authors: Mbodj Mohameth , Seck Ndiogou , Ndiaye Serigne Tawa , Bop Khadim , Sow Papa Souleye , Diagne Ibrahima
Published: August 2022

Herpes zoster in children is rare and particularly the ophthalmic form, which can be responsible for serious ocular complications. We report the case of a 6-year-old female patient with herpes zoster ophthalmicus. The patient was 6 years old and hospitalised with a painful rash. The examination revealed an infectious syndrome, a painful vesicular rash, in a cluster, resting on an erythematous background located on the forehead and the root of the nose with eyelid edema. Slit lamp examination came back normal. The diagnosis of herpes zoster ophthalmicus was made on the basis of clinical findings. The course was favourable on acyclovir with no ocular complications and no post-herpetic pain.
Prevalence of depression in patients with end-stage renal disease undergoing hemodialysis in Saudi Arabia: A cross-sectional study
Authors: Sallam Lujain , Alsharif Fatmah , Abaalalaa Sarah , Alakeely Rawan , Abdullah Zahraa , Alkhamis Zahra , Sindi Najla , Sharif Loujain S
Published: August 2022

Background: A hemodialysis is a treatment option for patients with End-Stage Renal Disease (ESRD). However, patients undergoing hemodialysis three times per week may experience psychological issues, including depression, which are highly prevalent among patients. Unfortunately, most healthcare providers fail to recognize the symptoms of depression due to overlap with other somatic symptoms; thus, depression remains undiagnosed.
Objective: This study aimed to estimate the prevalence of depression and compare the differences in depression symptoms according to the sociodemographic characteristics of patients with ESRD undergoing hemodialysis.
Method: A descriptive, cross-sectional study was conducted from August to October 2021 with a total of 132 hemodialysis patients using the Beck Depression Inventory (BDI II) questionnaire to examine symptoms of depression at multiple health centers in Jeddah. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, Post-hoc analysis using Conover tests were used for data analysis.
Results: The prevalence of depression in hemodialysis patients was 51.5%, 25.8%, 15.9%, and 6.8%, with minimal, mild, moderate, and severe symptoms, respectively. Depression exhibited a significant relationship with sex (p = 0.034), with females showing higher mean depression scores than males. Additionally, depression scores were statistically significant across the different levels of education (p = 0.019), with the mean depression scores significantly highest in subjects who had only primary school level of education. Furthermore, the most common symptoms associated with depression were found to be energy loss and fatigue.
Conclusion: Depression prevalence was relatively low among patients with ESRD undergoing hemodialysis, and a loss of energy and fatigue were the most common symptoms correlated with depression. Hence, nurses should be trained on how to routinely use psychological screening scales among patients with ESRD undergoing hemodialysis.
Developing, validating, and pre-testing of a diabetic care self-management mobile health application: A technology-based intervention for patients with diabetes in Malaysia
Authors: Firdaus Mohd Khairul Zul Hasymi , Jittanoon Piyanuch , Boonyasopun Umaporn
Published: August 2022

Background: Technology-based intervention showed a promising approach to health promotion strategies. There had been limited knowledge of the existing program for technology-based intervention in promoting foot care and dietary behavior modification. Thus, a mobile app was developed as an alternative strategy for promoting foot care and dietary behavior modification.
Objective: This paper aims to elaborate on the process of developing, validating, and examining the Diabetic Care Self-Management Mobile Health Application (Diabetic Care).
Methods: There are two phases conducted. The first phase is the process of developing and validating Diabetic Care. Intervention Mapping (IM) Framework was used to guide the process of developing Diabetic Care, while in assessing validity, guidance from Kassam-Adams et al. was used. A team of experts was appointed to validate the mobile app developed. Next, the usability of Diabetic Care was conducted among ten conveniently chosen patients with diabetes in a governmental primary care clinic.
Results: The process of developing Diabetic Care was clearly explained. The Diabetic Care app showed a good I-CVI score (1.00) and general CVI score (1.00) after the expert team assessed. During the trial, two drawbacks were identified and explored to find solutions.
Conclusion: The Diabetic Care app is proven appropriate to be employed in the study. Even though there were two drawbacks encountered, however, possible solutions were able to be explored in addressing the issues. Further research should be conducted to examine the effectiveness of this mobile app in modifying foot care behavior and dietary behavior. Hence, it will assist in the translation of advanced technology in nursing care.
Factors influencing nursing students’ continued success in a baccalaureate nursing program in Indonesia
Authors: Sommers Christine L. , Houghty Grace Solely , Purbojo Rijanto , Bernarto Innocentius
Published: August 2022

Background: Holistic admission processes are needed to promote diversity in nursing students. Previous research had identified different variables related to the average grade point at the end of the first semester. There is a need to examine if those variables are associated with ongoing student success.
Objective: The purpose of this study was to analyze experience, attributes, and academic variables for an association with nursing student success. Student success was defined as being an active student at the end of the first year and at the end of the second year of a baccalaureate nursing program in Indonesia.
Methods: Binary logistic regression analysis was used to determine what relationship, if any, the variables had with student success, measured at the end of the first and second academic years. The data of 341 nursing students enrolled in August 2018 was analyzed.
Results: The variables accounted for 40.3% of the variance at the end of the first year and 24.3% of the variance at the end of the second year. There was a significant (p < .05) relationship between being enrolled at the end of the first year and 1) academic variables of first semester grade point average and the admission score of Raven’s Advanced Progressive Matrices, and 2) attribute variables of reason for entering nursing and brief calling presence scale. A significant relationship was found between being enrolled at the end of the second year and the attribute variable of grit score. No variables had a strong correlation with other variables.
Conclusion: Holistic admission processes and promoting student success can create the future of the nursing workforce. Improving the diversity in admitted nursing students will enhance the diversity in the nursing workforce. To promote the success of all students, a variety of support interventions will need to be developed. As students’ calling and grit may play a role in student success, a better understanding is needed. In addition, more research is needed to explore how developing calling and grit throughout the nursing program can impact student success.
Changes in Acoustic Quality in Dynamic Microphones according to Distance and Angle of Use
Authors:   The Korean Society of Culture and Convergence, Jung Hyun , Chung Jaeyoun
Published: August 2022

Due to various factors, dynamic microphones, which are mainly used in performances, demonstrate differences in their usage according to each singer. Accordingly, the purpose of this study is to find reasonable criteria for the use of the microphone in the acoustic aspect by examining the differences in acoustic characteristics and acoustic quality according to the differentiated distances and angles between the microphone and the singers. As a result, changes in acoustic characteristics and acoustic quality were found depending on the distance and angle between each singer and the dynamic microphone. In particular, in the experimental environment set up in this study, it was confirmed that the acoustic quality degraded more when the non-recommended distance was applied than when the nonrecommended angle was applied. This study is meaningful in that it contributes to controlling the quality of performances by uncovering the methods for reasonable acoustic quality control as the importance placed on sound, in comparison with various other elements pursued by popular music performances, is not small.
How has the COVID-19 Pandemic Affected Diabetes Self-Management in People With Diabetes? - A One-Year Follow-Up Study
Authors: Olesen Kasper , Joensen Lene Eide , Madsen Kristoffer Panduro , Willaing Ingrid
Published: August 2022

Background and Aim

In Denmark, the COVID-19 pandemic resulted in two lockdowns, one from March to May 2020 and another from December 2020 to April 2021, which had severe impact on everyday life. The aim of this study was to explore changes in diabetes self-management behaviors during the pandemic and to examine how specific population characteristics were associated with changes in diabetes management.

Methods and Participants

In a cohort study from March 2020 to April 2021, two online questionnaires were collected from a total of 760 people with diabetes. Descriptive statistics were used to assess the proportion of participants experiencing improvements, deterioration, and status quo in diabetes self-management during the pandemic. Using logistic regressions, baseline characteristics were explored as potential predictors of change.

Results

Approximately half of the participants reported that they experienced lower physical activity in April 2021 compared to before the pandemic, approximately one fifth reported diabetes self-management to be more difficult than prior to the pandemic, and one fifth reported eating more unhealthily than before the pandemic. Some participants reported higher frequency of high blood glucose levels (28%), low blood glucose levels (13%) and more frequent blood glucose variability (33%) compared to before. Easier diabetes self-management was reported by relatively few participants, however, 15% reported eating more healthily, and 20% reported being more physically active. We were largely unable to identify predictors of change in exercise activities. The few baseline characteristics identified as predictors of difficulties in diabetes self-management and adverse blood glucose levels due to the pandemic were sub-optimal psychological health, including high diabetes distress levels.

Conclusion

Findings indicate that many people with diabetes changed diabetes self-management behaviors during the pandemic, mostly in a negative direction. Particularly high diabetes distress levels in the beginning of the pandemic was a predictor of both positive and negative change in diabetes self-management, indicating that people with high diabetes distress levels could potentially benefit from increased support in diabetes care during a period of crisis.
Gearing up for battle: Harnessing adaptive T cell immunity against gram-negative pneumonia
Authors: Gao Catherine A. , Morales-Nebreda Luisa , Pickens Chiagozie I.
Published: August 2022

Pneumonia is one of the leading causes of morbidity and mortality worldwide and Gram-negative bacteria are a major cause of severe pneumonia. Despite advances in diagnosis and treatment, the rise of multidrug-resistant organisms and hypervirulent strains demonstrates that there will continue to be challenges with traditional treatment strategies using antibiotics. Hence, an alternative approach is to focus on the disease tolerance components that mediate immune resistance and enhance tissue resilience. Adaptive immunity plays a pivotal role in modulating these processes, thus affecting the incidence and severity of pneumonia. In this review, we focus on the adaptive T cell responses to pneumonia induced by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We highlight key factors in these responses that have potential for therapeutic targeting, as well as the gaps in current knowledge to be focused on in future work.
Case report: Mitral valve replacement for Libman-Sacks endocarditis and cerebral embolism of primary antiphospholipid syndrome
Authors: Liang Huili , Ma Chunyan , Chen Xin
Published: August 2022

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arteriovenous thrombosis and/or morbid pregnancy. Valve involvement is the most common cardiac manifestation of APS, with lesions characterized by valve thickening and vegetations known as Libman-Sacks endocarditis (LSE). This report discussed a rare case of a 26-year-old young woman diagnosed with primary APS with multiple cerebral infarctions and right middle cerebral artery occlusion that occured 3 years ago. During the investigation, transthoracic echocardiography (TTE) revealed vegetations on both leaflets of the mitral valve with mild to moderate mitral regurgitation. One year following corticosteroid and anticoagulant treatment, mitral valve fibrosis and moderate to severe regurgitation were noted, after which mitral mechanical valve replacement was finally performed. Accordingly, this report suggests that LSE occurrence should be alerted during the examination of APS patients especially in those with cerebrovascular disease. Furthermore, establishing an early diagnosis and conducting close follow-ups are necessary for its timely intervention and treatment.
HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study
Authors: Shao Yingbo , Luo Zhifen , Yu Yang , Chen Qi , He Yaning , Liu Chaojun , Nie Bing , Zhu Fangyuan , Liu Hui
Published: August 2022

Background

There is accumulating evidence support human epidermal growth factor receptor 2 (HER2)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether HER2-low expression will affect the clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitor for patients with hormone receptor (HR)-positive, HER-2 negative metastatic breast cancer.

Methods

Patients with HR+/HER2- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. HER2-zero was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/fluorescence in situ hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety.

Results

45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 HER-2-zero and 21 HER-2-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between HER-2-zero and HER-2-low patients. And simultaneously, HER2-zero and HER2-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively.

Conclusions

HER2-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating HER2-low into systemic therapy decisions for patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitor.
The relationships between the gut microbiota and its metabolites with thyroid diseases
Authors: Jiang Wen , Lu Ganghua , Gao Dingwei , Lv Zhongwei , Li Dan
Published: August 2022

Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis.
Epileptic seizures during Non-Ketotic Hyperglycemia (NKH) in French Guiana: A retrospective study
Authors: Baltyde Dimitri , De Toffol Bertrand , Nacher Mathieu , Sabbah Nadia
Published: August 2022

Introduction

Epileptic seizures during non-ketotic hyperglycemia (NKH) represent a rare complication of uncontrolled diabetes mellitus. The definition associates a blood sugar level > 200mg/dL (11mmol/L), hyperosmolality, absence of ketosis, dehydration and seizure control after normalization of blood sugar levels.

Material and methods

This retrospective observational study included patients hospitalized for epileptic seizures and NKH in the Cayenne Hospital Center between January 2010 and June 2020. The clinical, biological, and radiological results were collected.

Results

18 out of 228 (7.9%) patients with both diabetes and epileptic seizures had NKH. The mean age of the 12 women and 6 men was 64.8 years. In 8 patients, brain imaging did not show acute lesions and the seizures disappeared with control of hyperglycemia by hydration and insulin. In 6 patients, the seizures revealed a stroke, hemorrhagic in 4 cases, ischemic in 2 cases. 4 patients had a seizure in a context of known vascular epilepsy. The epileptic seizures were mainly focal seizures with motor symptoms that could be repeated, focal to bilateral tonic-clonic or focal status.

Conclusion

Seizures in NKH are symptomatic of an acute brain lesion or vascular epilepsy more than 1 in 2 times. However, isolated NKH can cause seizures with a suggestive brain MRI.
Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome
Authors: Suntharalingham Jenifer P. , Ishida Miho , Del Valle Ignacio , Stalman Susanne E. , Solanky Nita , Wakeling Emma , Moore Gudrun E. , Achermann John C. , Buonocore Federica
Published: August 2022

Background

Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. The range of additional clinical associations is expanding and includes disrupted placental development, poor post-natal growth and endocrine features. Increasingly, milder phenotypic features such as hypospadias in small for gestational age (SGA) boys and normal adrenal function are reported. Some children present with isolated myelodysplastic syndrome (MDS/monosomy 7) without MIRAGE features.

Objective

We aimed to investigate: 1) the range of reported SAMD9 variants, clinical features, and possible genotype-phenotype correlations; 2) whether SAMD9 disruption affects placental function and leads to pregnancy loss/recurrent miscarriage (RM); 3) and if pathogenic variants are associated with isolated fetal growth restriction (FGR).

Methods

Published data were analyzed, particularly reviewing position/type of variant, pregnancy, growth data, and associated endocrine features. Genetic analysis of SAMD9 was performed in products of conception (POC, n=26), RM couples, (couples n=48; individuals n=96), children with FGR (n=44), SGA (n=20), and clinical Silver-Russell Syndrome (SRS, n=8), (total n=194).

Results

To date, SAMD9 variants are reported in 116 individuals [MDS/monosomy 7, 64 (55.2%); MIRAGE, 52 (44.8%)]. Children with MIRAGE features are increasingly reported without an adrenal phenotype (11/52, 21.2%). Infants without adrenal dysfunction were heavier at birth (median 1515 g versus 1020 g; P < 0.05) and born later (median 34.5 weeks versus 31.0; P < 0.05) compared to those with adrenal insufficiency. In MIRAGE patients, hypospadias is a common feature. Additional endocrinopathies include hypothyroidism, hypo- and hyper-glycemia, short stature and panhypopituitarism. Despite this increasing range of phenotypes, genetic analysis did not reveal any likely pathogenic variants/enrichment of specific variants in SAMD9 in the pregnancy loss/growth restriction cohorts studied.

Conclusion

MIRAGE syndrome is more phenotypically diverse than originally reported and includes growth restriction and multisystem features, but without adrenal insufficiency. Endocrinopathies might be overlooked or develop gradually, and may be underreported. As clinical features including FGR, severe infections, anemia and lung problems can be non-specific and are often seen in neonatal medicine, SAMD9-associated conditions may be underdiagnosed. Reaching a specific diagnosis of MIRAGE syndrome is critical for personalized management.
FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007-2012
Authors: Lang Xueyan , Li Yilan , Zhang Dandan , Zhang Yuheng , Wu Nilian , Zhang Yao
Published: August 2022

Background

Thyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population.

Methods

This retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.

Results

During a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results.

Conclusions

FT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population.
Guidance for high-dose vitamin D supplementation for prolonging the honeymoon phase in children and adolescents with new-onset type 1 diabetes
Authors: Nwosu Benjamin Udoka
Published: August 2022

The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the β-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo. The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL. If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.
The relationship between exposure to phthalate metabolites and adult-onset hypogonadism
Authors: Liu Zheng-Huan , Yang Lu-Chen , Song Pan , Chen Jun-Hao , Peng Zhu-Feng , Dong Qiang
Published: August 2022

Objective

Adult-onset hypogonadism (AOH) is a common disease for males >40 years old and is closely associated with age-related comorbidities. Phthalates are compounds widely used in a number of products with endocrine-disrupting effects. However, little is known about the association between exposure to phthalates and the risk of AOH. Thus, we conducted this study to explore the potential association using the 2013-2016 National Health and Nutrition Examination Survey (NHANES) data.

Method

Data on AOH and urinary phthalate metabolites were collected, and univariable and multivariable logistic regression analyses were adapted to evaluate the association. The concentrations of each metabolite were calculated and grouped according to their quartiles for the final analysis.

Result

Finally, we found that the odds ratio (OR) increased with increased concentrations of di-(2-ethylhexyl) phthalate (DEHP) metabolites, including mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). Simultaneously, a significant dose-dependent effect was also observed. The OR for the fourth quartile was highest among all three groups. Specifically, the ORs for the third quartile and fourth quartile were 1.774 and 1.858, respectively, in the MECPP group. For the MEHHP group, the OR increased from 1.580 for the second quartile to 1.814 for the fourth quartile. Similarly, the OR for the higher three quartiles varied from 1.424 to 1.715 in the MEOHP group.

Conclusion

This study first revealed that there was a positive association between exposure to DEHP metabolites and the risk of AOH. These findings add limited evidence to study this topic, while further studies are needed to explain the potential molecular mechanisms.
Population genetics of the naked mole-rat Heterocephalus glaber: The role of rivers in shaping genetic structure
Authors: Hess Jon , Braude Stan , Ingram Colleen , Templeton Alan
Published: August 2022

We used nested clade phylogeographic analysis (NCPA) of mitochondrial DNA sequence data to examine the processes contributing to population structure in naked mole-rats. We examined sequence variation in the (1097 bp) control region D-loop of the mitochondrial genome in 303 individuals from 174 colonies of naked mole-rats (Heterocephalus glaber) located mainly within an 870 km2area in Meru National Park, Kenya. Four rivers were found to be correlated to a significant fragmentation inference in the NCPA. The largest pairwise divergence between haplotypes from populations separated by rivers was 2.74%, which was well over half of the divergence reported between the extremes of the distribution from southern Ethiopia to southern Kenya (4.6%). However, the size of the river (measured in current discharge) was not a good predictor of the amount of sequence divergence between populations separated by a river. It appears that a large-scale historical fragmentation event may have conflated fragmentation patterns on a smaller scale, when recent colonization and range expansion brought two old lineages together at a location with a relatively small river separating them.
Secretory co-factors in next-generation cellular therapies for cancer
Authors: Okuma Atsushi , Ishida Yoshihito , Kawara Taketo , Hisada Shoji , Araki Shinsuke
Published: August 2022

Since chimeric antigen receptor (CAR) T-cell therapies for hematologic malignancies were approved by the U.S. Food and Drug Administration, numerous “next-generation” CAR T cells have been developed to improve their safety, efficacy, and applicability. Although some of these novel therapeutic strategies are promising, it remains difficult to apply these therapies to solid tumors and to control adverse effects, such as cytokine release syndrome and neurotoxicity. CAR T cells are generated using highly scalable genetic engineering techniques. One of the major strategies for producing next-generation CAR T cells involves the integration of useful co-factor(s) into the artificial genetic design of the CAR gene, resulting in next-generation CAR T cells that express both CAR and the co-factor(s). Many soluble co-factors have been reported for CAR T cells and their therapeutic effects and toxicity have been tested by systemic injection; therefore, CAR T cells harnessing secretory co-factors could be close to clinical application. Here, we review the various secretory co-factors that have been reported to improve the therapeutic efficacy of CAR T cells and ameliorate adverse events. In addition, we discuss the different co-factor expression systems that have been used to optimize their beneficial effects. Altogether, we demonstrate that combining CAR T cells with secretory co-factors will lead to next-generation CAR T-cell therapies that can be used against broader types of cancers and might provide advanced tools for more complicated synthetic immunotherapies.
Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study
Authors: Idda Maria Laura , Pitzalis Maristella , Lodde Valeria , Loizedda Annalisa , Frau Jessica , Lobina Monia , Zoledziewska Magdalena , Virdis Francesca , Delogu Giuseppe , Marini Maria Giuseppina , Mingoia Maura , Masala Marco , Lorefice Lorena , Fronza Marzia , Carmagnini Daniele , Carta Elisa , Pilotto Silvy , Castiglia Paolo , Chessa Paola , Uzzau Sergio , Farina Gabriele , Solla Paolo , Steri Maristella , Devoto Marcella , Fiorillo Edoardo , Floris Matteo , Zarbo Roberto Ignazio , Cocco Eleonora , Cucca Francesco
Published: August 2022

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.
Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis
Authors: Chilunda Vanessa , Weiselberg Jessica , Martinez-Meza Samuel , Mhamilawa Lwidiko E. , Cheney Laura , Berman Joan W.
Published: August 2022

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages, thus contributing to viral reservoirs and chronic neuroinflammation. Substance use disorders in PWH, including the use of methamphetamine (meth), can exacerbate HIV neuropathogenesis. We characterized the effects of meth on the transcriptional profile of HIV-infected mature monocytes using RNA-sequencing. We found that meth mediated an upregulation of gene transcripts related to viral infection, cell adhesion, cytoskeletal arrangement, and extracellular matrix remodeling. We also identified downregulation of several gene transcripts involved in pathogen recognition, antigen presentation, and oxidative phosphorylation pathways. These transcriptomic changes suggest that meth increases the infiltration of mature monocytes that have a migratory phenotype into the CNS, contributing to dysregulated inflammatory responses and viral reservoir establishment and persistence, both of which contribute to neuronal damage. Overall, our results highlight potential molecules that may be targeted for therapy to limit the effects of meth on HIV neuropathogenesis.
A platform technology for generating subunit vaccines against diverse viral pathogens
Authors: Young Andrew , Isaacs Ariel , Scott Connor A. P. , Modhiran Naphak , McMillan Christopher L. D. , Cheung Stacey T. M. , Barr Jennifer , Marsh Glenn , Thakur Nazia , Bailey Dalan , Li Kenneth S. M. , Luk Hayes K. H. , Kok Kin-Hang , Lau Susanna K. P. , Woo Patrick C. Y. , Furuyama Wakako , Marzi Andrea , Young Paul R. , Chappell Keith J. , Watterson Daniel
Published: August 2022

The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge.
The Hippo-YAP pathway in various cardiovascular diseases: Focusing on the inflammatory response
Authors: Zheng Ancheng , Chen Qishan , Zhang Li
Published: August 2022

The Hippo pathway was initially discovered in Drosophila melanogaster and mammals as a key regulator of tissue growth both in physiological and pathological states. Numerous studies depict the vital role of the Hippo pathway in cardiovascular development, heart regeneration, organ size and vascular remodeling through the regulation of YAP (yes-associated protein) translocation. Recently, an increasing number of studies have focused on the Hippo-YAP pathway in inflammation and immunology. Although the Hippo-YAP pathway has been revealed to play controversial roles in different contexts and cell types in the cardiovascular system, the mechanisms regulating tissue inflammation and the immune response remain to be clarified. In this review, we summarize findings from the past decade on the function and mechanism of the Hippo-YAP pathway in CVDs (cardiovascular diseases) such as myocardial infarction, cardiomyopathy and atherosclerosis. In particular, we emphasize the role of the Hippo-YAP pathway in regulating inflammatory cell infiltration and inflammatory cytokine activation.
MX2: Identification and systematic mechanistic analysis of a novel immune-related biomarker for systemic lupus erythematosus
Authors: Meng Xiang-Wen , Cheng Zhi-Luo , Lu Zhi-Yuan , Tan Ya-Nan , Jia Xiao-Yi , Zhang Min
Published: August 2022

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs. However, the current SLE-related biomarkers still lack sufficient sensitivity, specificity and predictive power for clinical application. Thus, it is significant to explore new immune-related biomarkers for SLE diagnosis and development.

Methods

We obtained seven SLE gene expression profile microarrays (GSE121239/11907/81622/65391/100163/45291/49454) from the GEO database. First, differentially expressed genes (DEGs) were screened using GEO2R, and SLE biomarkers were screened by performing WGCNA, Random Forest, SVM-REF, correlation with SLEDAI and differential gene analysis. Receiver operating characteristic curves (ROCs) and AUC values were used to determine the clinical value. The expression level of the biomarker was verified by RT‒qPCR. Subsequently, functional enrichment analysis was utilized to identify biomarker-associated pathways. ssGSEA, CIBERSORT, xCell and ImmuCellAI algorithms were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Finally, the transcriptional regulatory network of the biomarker was constructed, and the corresponding therapeutic drugs were predicted.

Results

Multiple algorithms were screened together for a unique marker gene, MX2, and expression analysis of multiple datasets revealed that MX2 was highly expressed in SLE compared to the normal group (all P < 0.05), with the same trend validated by RT‒qPCR (P = 0.026). Functional enrichment analysis identified the main pathway of MX2 promotion in SLE as the NOD-like receptor signaling pathway (NES=2.492, P < 0.001, etc.). Immuno-infiltration analysis showed that MX2 was closely associated with neutrophils, and single-cell and transcriptomic data revealed that MX2 was specifically expressed in neutrophils. The NOD-like receptor signaling pathway was also remarkably correlated with neutrophils (r >0.3, P < 0.001, etc.). Most of the MX2-related interacting proteins were associated with SLE, and potential transcription factors of MX2 and its related genes were also significantly associated with the immune response.

Conclusion

Our study found that MX2 can serve as an immune-related biomarker for predicting the diagnosis and disease activity of SLE. It activates the NOD-like receptor signaling pathway and promotes neutrophil infiltration to aggravate SLE.
Neuroimaging and clinicopathological differences between tumefactive demyelinating lesions and sentinel lesions of primary central nervous system lymphoma
Authors: Sun Chenjing , Han Jinming , Lin Ye , Qi Xiaokun , Li Changqing , Liu Jianguo , Qiu Feng
Published: August 2022

Objective

It is still a challenge to distinguish sentinel lesions of primary central nervous system lymphoma (PCNSL) from atypical tumefactive demyelinating lesions (TDLs) in clinical practice. We aimed to investigate potential differences of clinical features, neuroimaging findings and pathological characteristics between PCNSL and TDLs, improving early accurate diagnosis.

Methods

It was a retrospective study involving 116 patients with TDLs and 150 patients with PCNSLs. All cases were pathologically confirmed. Clinical features, neuroimaging findings and pathological characteristics between two groups were analyzed.

Results

The onset age was 37 ± 14 years in TDLs and 58 ± 13 years in PCNSL(p=0.000). Main onset symptom was headache in TDLs, while cognitive impairment was frequently noted in PCNSL. CT brain scan image showed hypodense lesions in most cases of TDL (110/116, 94.8%), while approximately 80% patients (120/150) with PCNSL had hyperdense lesions. Furthermore, we found that the presence of Creutzfeldt-Peters cells (might be misdiagnosed as tumor cells) may serve as an important feature in TDLs.

Conclusions

Onset age of patients with TDLs was younger than PCNSL. Neuroimaging features on brain CT scan might provide clues to make a differential diagnosis. Pathological features of PCNSL with sentinel lesions or following steroids therapy might mimic TDLs. Dynamic neuroimaging pathological and follow-up information were essential for an accurate diagnosis.
Grid batch-dependent tuning of glow discharge parameters
Authors: Kazan Ramy , Bourgeois Gabrielle , Carisetti Dominique , Florea Ileana , Larquet Eric , Maurice Jean-Luc , Mechulam Yves , Ozanam François , Schmitt Emmanuelle , Coureux Pierre-Damien
Published: August 2022

Sample preparation on cryo-EM grids can give various results, from very thin ice and homogeneous particle distribution (ideal case) to unwanted behavior such as particles around the “holes” or complexes that do not entirely correspond to the one in solution (real life). We recently run into such a case and finally found out that variations in the 3D reconstructions were systematically correlated with the grid batches that were used. We report the use of several techniques to investigate the grids' characteristics, namely TEM, SEM, Auger spectroscopy and Infrared Interferometry. This allowed us to diagnose the origin of grid preparation problems and to adjust glow discharge parameters. The methods used for each approach are described and the results obtained on a common specific case are reported.
Accelerated aging-related transcriptome alterations in neurovascular unit cells in the brain of Alzheimer’s disease
Authors: Zhao Yan , Xie Yong-Zhi , Liu You-Shuo
Published: August 2022

Alzheimer’s disease (AD) is the most common cause of dementia with no effective therapies. Aging is a dominant risk factor for AD. The neurovascular unit (NVU) plays an important role in maintaining homeostasis of the brain microenvironment. The accelerated aging of NVU cells may directly impair NVU function and contribute to AD pathogenesis. However, the expression patterns of aging-related genes (AGs) in NVU cells of AD remain unclear. In this study, we performed single-nucleus transcriptome analysis of 61,768 nuclei from prefrontal cortical samples of patients with AD and normal control (NC) subjects. Eight main cell types were identified, including astrocytes, microglia, excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, pericytes, and endothelial cells. Transcriptomic analysis identified the expression patterns of AGs in NVU cells of AD. Gene set enrichment analysis confirmed the key aging-associated cellular pathways enriched in microglia and oligodendrocytes. These aging-related transcriptomic changes in NVU were cross-validated using bulk transcriptome data. The least absolute shrinkage and selection operator regression method was used to select the crucial AGs most associated with AD: IGF1R, MXI1, RB1, PPARA, NFE2L2, STAT5B, FOS, PRKCD, YWHAZ, HTT, MAPK9, HSPA9, SDHC, PRKDC, and PDPK1. This 15-gene model performed well in discriminating AD from NC samples. Among them, IGF1R, MXI1, PPARA, YWHAZ, and MAPK9 strongly correlated with pathologic progression in AD, were identified as critical regulators of AD. Although most AGs showed similar trends of expression changes in different types of NVU cells in AD, certain AGs were expressed in a cell-specific manner. Our comprehensive analysis of brain NVU from patients with AD reveals previously unknown molecular changes associated with aging that may underlie the functional dysregulation of NVU, providing important insights for exploring potential cell-specific therapeutic targets to restore brain homeostasis in AD.