bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping in caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation
Authors: Amonoo Hermioni L. , Johnson P. Connor , Nelson Ashley M. , Clay Madison A. , Daskalakis Elizabeth , Newcomb Richard A. , Deary Emma C. , Mattera Elizabeth F. , Yang Daniel , Cronin Katherine , Boateng Kofi , Lee Stephanie J. , LeBlanc Thomas W. , El-Jawahri Areej
Published: November 2022

Caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) must cope with substantial caregiving burden, high rates of psychological distress, and diminished quality of life (QOL). However, data describing coping strategies before HSCT and the association between coping, QOL, and psychological outcomes in this population are lacking. We conducted a secondary analysis of data collected during a multisite randomized clinical trial of a supportive care intervention in HSCT recipients and their caregivers. Caregivers completed the Brief COPE, Hospital Anxiety and Depression Scale, and the Caregiver Oncology Quality of Life Questionnaire to measure coping strategies, psychological distress, and QOL, respectively. We grouped coping into 2 higher-order domains: approach-oriented (ie, emotional support and active coping) and avoidant (ie, self-blame and denial). We used the median split method to describe the distribution of coping and multivariate linear regression models to assess the relationship between coping and caregiver outcomes. We enrolled 170 caregivers, with a median (range) age of 53 (47-64) years. Most were White (87%), non-Hispanic (96%), and female (77%). Approach-oriented coping was associated with less anxiety (β = −0.210, P = .003), depression symptoms (β = −0.160, P = .009), and better QOL (β = 0.526, P = .002). In contrast, avoidant coping was associated with more anxiety (β = 0.687, P<.001), depression symptoms (β = 0.579, P < .001), and worse QOL (β = −1.631, P < .001). Our findings suggest that coping is related to distress and QOL among caregivers of HSCT recipients even before transplant. Hence, caregivers of patients with hematologic malignancies undergoing HSCT may benefit from resources that facilitate adaptive coping with the demands of caregiving.
Transcriptional reprogramming of infiltrating neutrophils drives lung pathology in severe COVID-19 despite low viral load
Authors: Eddins Devon J. , Yang Junkai , Kosters Astrid , Giacalone Vincent D. , Pechuan-Jorge Ximo , Chandler Joshua D. , Eum Jinyoung , Babcock Benjamin R. , Dobosh Brian S. , Hernández Mindy R. , Abdulkhader Fathma , Collins Genoah L. , Orlova Darya Y. , Ramonell Richard P. , Sanz Ignacio , Moussion Christine , Eun-Hyung Lee F. , Tirouvanziam Rabindra M. , Ghosn Eliver E. B.
Published: November 2022

Troubling disparities in COVID-19–associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. However, targeted studies on this vulnerable population are scarce. Here, we applied multiomics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, leads to persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1β, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to acute respiratory distress syndrome in a well-defined patient population disproportionally affected by severe COVID-19.
Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy
Authors: Li ChangYan , Ma JingYuan , Mali Niroj , Zhang Le , Wei Tao , Shi LuYao , Liu Fang , WenXing Fan , Yang Jing
Published: November 2022

Background

A chronic inflammatory disease caused by disturbances in metabolism, diabetic nephropathy (DN) is a chronic inflammatory disease. Pyroptosis is a novel form of programmed cell death in many inflammation-related diseases, including DN. Therefore, pyroptosis could be a promising target for DN therapy.

Methods

To get the components and pharmacodynamic targets of Chuanxiong, we identified by searching TCMID, TCMSP, ETCM and HERB databases. Then, from the Molecular Signatures Database (MSigDB) and Gene Ontology (GO) database, pyroptosis genes were collected. Identification of critical genes in DN by bioinformatics analysis and then using the ConsensusClusterPlus package to divide the express data of diff genes into some subgroups with different levels of pyroptosis; the WGCNA machine algorithm was used to simulate the mechanism Chuanxiong improving DN.

Results

In this study, we found DHCR24, ANXA1, HMOX1, CDH13, ALDH1A1, LTF, CHI3L1, CACNB2, and MTHFD2 interacted with the diff genes of DN. We used GSE96804 as a validation set to evaluate the changes of APIP, CASP6, CHMP2B, CYCS, DPP8, and TP53 in four different cell proapoptotic states. WGCNA analysis showed that DHCR24, CHI3L1, and CACNB2 had significant changes in different cell proapoptotic levels. In the experimental stage, we also confirmed that the active ingredients of Chuanxiong could improve the inflammatory state and the levels of pyroptosis under high glucose.

Conclusion

The improvement of DN by Chuanxiong is related to the change of pyroptosis.
Cost-effectively dissecting the genetic architecture of complex wool traits in rabbits by low-coverage sequencing
Authors: Wang Dan , Xie Kerui , Wang Yanyan , Hu Jiaqing , Li Wenqiang , Yang Aiguo , Zhang Qin , Ning Chao , Fan Xinzhong
Published: November 2022

Background

Rabbit wool traits are important in fiber production and for model organism research on hair growth, but their genetic architecture remains obscure. In this study, we focused on wool characteristics in Angora rabbits, a breed well-known for the quality of its wool. Considering the cost to generate population-scale sequence data and the biased detection of variants using chip data, developing an effective genotyping strategy using low-coverage whole-genome sequencing (LCS) data is necessary to conduct genetic analyses.

Results

Different genotype imputation strategies (BaseVar + STITCH, Bcftools + Beagle4, and GATK + Beagle5), sequencing coverages (0.1X, 0.5X, 1.0X, 1.5X, and 2.0X), and sample sizes (100, 200, 300, 400, 500, and 600) were compared. Our results showed that using BaseVar + STITCH at a sequencing depth of 1.0X with a sample size larger than 300 resulted in the highest genotyping accuracy, with a genotype concordance higher than 98.8% and genotype accuracy higher than 0.97. We performed multivariate genome-wide association studies (GWAS), followed by conditional GWAS and estimation of the confidence intervals of quantitative trait loci (QTL) to investigate the genetic architecture of wool traits. Six QTL were detected, which explained 0.4 to 7.5% of the phenotypic variation. Gene-level mapping identified the fibroblast growth factor 10 (FGF10) gene as associated with fiber growth and diameter, which agrees with previous results from functional data analyses on the FGF gene family in other species, and is relevant for wool rabbit breeding.

Conclusions

We suggest that LCS followed by imputation can be a cost-effective alternative to array and high-depth sequencing for assessing common variants. GWAS combined with LCS can identify new QTL and candidate genes that are associated with quantitative traits. This study provides a cost-effective and powerful method for investigating the genetic architecture of complex traits, which will be useful for genomic breeding applications.
Modeling the metabolic evolution of mixotrophic phytoplankton in response to rising ocean surface temperatures
Authors: Gonzalez Logan M. , Proulx Stephen R. , Moeller Holly V.
Published: November 2022

Background

Climate change is expected to lead to warming in ocean surface temperatures which will have unequal effects on the rates of photosynthesis and heterotrophy. As a result of this changing metabolic landscape, directional phenotypic evolution will occur, with implications that cascade up to the ecosystem level. While mixotrophic phytoplankton, organisms that combine photosynthesis and heterotrophy to meet their energetic and nutritional needs, are expected to become more heterotrophic with warmer temperatures due to heterotrophy increasing at a faster rate than photosynthesis, it is unclear how evolution will influence how these organisms respond to warmer temperatures. In this study, we used adaptive dynamics to model the consequences of temperature-mediated increases in metabolic rates for the evolution of mixotrophic phytoplankton, focusing specifically on phagotrophic mixotrophs.

Results

We find that mixotrophs tend to evolve to become more reliant on phagotrophy as temperatures rise, leading to reduced prey abundance through higher grazing rates. However, if prey abundance becomes too low, evolution favors greater reliance on photosynthesis. These responses depend upon the trade-off that mixotrophs experience between investing in photosynthesis and phagotrophy. Mixotrophs with a convex trade-off maintain mixotrophy over the greatest range of temperatures; evolution in these “generalist” mixotrophs was found to exacerbate carbon cycle impacts, with evolving mixotrophs exhibiting increased sensitivity to rising temperature.

Conclusions

Our results show that mixotrophs may respond more strongly to climate change than predicted by phenotypic plasticity alone due to evolutionary shifts in metabolic investment. However, the type of metabolic trade-off experienced by mixotrophs as well as ecological feedback on prey abundance may ultimately limit the extent of evolutionary change along the heterotrophy-phototrophy spectrum.
“The problem is that our culture is just so messed up about aging.” Recruiting older men who have sex with men (MSM) into research studies: an example from a study of aging, HIV, and anal HPV.
Authors: Hernandez Alexandra L. , Weatherly Christopher Scott , Burrowes Sahai , Jimenez Jessica Lopez , Gonzalez Ryan , Palefsky Joel M.
Published: November 2022

Background

Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research.

Methods

We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50–75.

Results

We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered “older” in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care.

Conclusion

Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.
Cultural adaptation of the savvy caregiver program for Korean Americans with limited English proficiency: a feasibility and acceptability study
Authors: Jang Yuri , Hepburn Kenneth , Park Juyoung , Haley William E. , Kim Miyong T.
Published: November 2022

Background

Limited English proficiency (LEP) of dementia caregivers poses a critical barrier to these caregivers’ access to evidence-based interventions. In an effort to make such interventions available and accessible to dementia caregivers with LEP, in the present study we use Barrera and colleagues’ (2011) three-step model of cultural adaptation: (1) information gathering, (2) preliminary adaptation, and (3) full adaptation. Selecting Korean Americans as a target group and the Savvy Caregiver Program (SCP) as a target intervention, we demonstrate the sequential process of cultural adaption and report the outcomes on feasibility and acceptability.

Methods

Preliminary adaptation with linguistic attunement was conducted by translating the SCP manual into Korean and certifying two lay individuals who were bilingual in English and Korean as Savvy trainers. The 6-week online SCP program was delivered by the two trainers in Korean with six to seven caregiver participants per trainer (N = 13). Feasibility and acceptability of the SCP for both caregiver participants and trainers were assessed using mixed methods, and their data then informed full adaptation.

Results

Findings not only showed the initial efficacy of the linguistically attuned SCP but also suggested areas for further modification. Data-driven assessment yielded a list of recommended changes for full adaptation, which was reviewed by the SCP developer to ensure fidelity and by community and research partners to confirm contextual and cultural relevance.

Conclusions

The adopted changes are broadly summarized as representing logistical, technical, and cultural issues. Given our refined set of educational materials and implementation guidelines, we discuss future directions for research and development.
Knowledge, attitude, and determinants of exclusive breastfeeding during COVID-19 pandemic among lactating mothers in Mekelle, Tigrai: a cross sectional study
Authors: Gebretsadik Gebretsadkan Gebremedhin , Tadesse Zuriash , Mamo Liya , Adhanu Amaha Kahsay , Mulugeta Afework
Published: November 2022

Background

Due to the nutritive and immunologic benefits of breastmilk, children should be exclusively breastfed for the first 6 months of life, even during the corona virus pandemic. However, fear of transmission risk and pandemic-related restrictions could undermine the practice of breastfeeding. This study aimed to assess the knowledge, attitude, and determinants of exclusive breastfeeding (EBF) during COVID-19 among lactating mothers in Mekelle, Tigrai, Ethiopia.

Methods

A community based cross-sectional study was conducted among 621 lactating mothers living in Mekelle city, Tigrai, from April to June, 2021. Data were collected using an adapted form of a standard KAP questionnaire. Binary logistic regression was used to determine the independent determinants of EBF at a statistical significance of p < 0.05. The strength of the association was measured by odds ratio and 95% confidence interval.

Results

Four hundred (64.4%) mothers exclusively breastfed their children. Infants from female-headed households had twice (AOR 2.21; 95% CI 1.31, 3.71) higher odds of EBF. Higher educational status was associated with higher odds of EBF practice. A unit increase in parity was associated with a 23% increase in the odds of EBF. Mothers who received breastfeeding information had a 73% (AOR 1.73; 95% CI 1.17, 2.56) higher odds of EBF. Moreover, mothers with high knowledge score and positive attitude showed a 74% higher (AOR 1.74; 95% CI 1.20, 2.51) and more than double (AOR 2.35; 95% CI 1.50, 3.70) odds of EBF, respectively.

Conclusion

About two-thirds of the mothers practiced EBF. Household head, maternal educational, parity, breastfeeding information, knowledge of breastfeeding, and attitude towards EBF were significant determinants of EBF. Our study findings highlighted that programs that enhance women’s participation in education and decision-making could improve EBF practice. Besides, during the COVID-19 pandemic, providing lactating mothers with adequate and up-to-date breastfeeding information could be significant in improving EBF practice.
The usefulness of the total metabolic tumor volume for predicting the postoperative recurrence of thoracic esophageal squamous cell carcinoma
Authors: Kaida Hayato , Yasuda Takushi , Shiraishi Osamu , Kato Hiroaki , Kimura Yutaka , Hanaoka Kohei , Yamada Minoru , Matsukubo Yuko , Tsurusaki Masakatsu , Kitajima Kazuhiro , Hattori Satoshi , Ishii Kazunari
Published: November 2022

Background

Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC.

Methods

We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34–82] years) treated at our hospital in 2007–2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test.

Results

The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0–1 or pN0–1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0–1, p < 0.001; TMTV pN0–1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011).

Conclusions

The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.
Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes
Authors: Sun Hui , Wang Xin , Zhang Xiaoyan , Wang Xu , Tan Cong , Weng Weiwei , Zhang Meng , Ni Shujuan , Wang Lei , Huang Dan , Xu Midie , Sheng Weiqi
Published: November 2022

Background

The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples.

Methods

Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed.

Results

FAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively.

Conclusions

These results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs.
Prescreening of tumor samples for tumor-centric transcriptome analyses of lung adenocarcinoma
Authors: Kim Nayoung , Jeong Dasom , Jo Areum , Eum Hye Hyeon , Lee Hae-Ock
Published: November 2022

Background

Single-cell RNA sequencing (scRNA-seq) enables the systemic assessment of intratumoral heterogeneity within tumor cell populations and in diverse stromal cells of the tumor microenvironment. Gain of treatment resistance during tumor progression or drug treatment are important subjects of tumor-centric scRNA-seq analyses, which are hampered by scarce tumor cell portions. To guarantee the inclusion of tumor cells in the data analysis, we developed a prescreening strategy for lung adenocarcinoma.

Methods

We obtained candidate genes that were differentially expressed between normal and tumor cells, excluding stromal cells, from the scRNA-seq data. Tumor cell-specific expression of the candidate genes was assessed via real-time reverse transcription-polymerase chain reaction (RT-PCR) using lung cancer cell lines, normal vs. lung cancer tissues, and lymph node biopsy samples with or without metastasis.

Results

We found that CEA cell adhesion molecule 5 (CEACAM5) and high mobility group box 3 (HMGB3) were reliable markers for RT-PCR-based prescreening of tumor cells in lung adenocarcinoma.

Conclusions

The prescreening strategy using CEACAM5 and HMGB3 expression facilitates tumor-centric scRNA-seq analyses of lung adenocarcinoma.
Ocular surface disorders affect quality of life in patients with autoimmune blistering skin diseases: a cross-sectional study
Authors: Kang Huanmin , Wu Mengbo , Feng Jianing , Ren Yuerong , Liu Yingyi , Shi Wen , Peng Yingqian , Tan Yixin , Wu Ruifang , Zhang Guiying , He Yan
Published: November 2022

Background

Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases.

Methods

Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated.

Results

92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales.

Conclusions

AIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.
Higher dietary acid load is associated with hyperuricemia in Chinese adults: a case-control study
Authors: Shao Si-si , Lin Chong-ze , Zhu Yong-fu , Chen Chun , Wu Qian-jia , Chen Ruo-ru
Published: November 2022

Background

This study aims to explore the association between dietary acid load and hyperuricemia in Chinese adults.

Methods

A case-control study was conducted. Adult participants with hyperuricemia were recruited as the cases and those without hyperuricemia were as the controls. Food consumption was evaluated by food frequency questionnaire (FFQ). Dietary acid load was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Dietary acid load was divided into four levels: the first quartile (Q1), the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4). Logistic regression model was applied for exploring the association between dietary acid load (PRAL and NEAP) and hyperuricemia. Odds ratio (OR) and its correspondence confidence interval (CI) were computed.

Results

A total of 290 participants were eligible in this study, in which there were 143 individuals in case group and 147 in control group. A higher level of PRAL was found to be associated with odds of hyperuricemia. ORs of hyperuricemia for Q2, Q3 and Q4 of PRAL were 2.74 (95%CI: 1.94 ~ 3.88, p-value: 0.004), 2.90 (95%CI: 2.05 ~ 4.10, p-value: 0.002) and 3.14 (95%CI: 2.22 ~ 4.45, p-value: 0.001), respectively. There was a positive association between elevated NEAP and hyperuricemia. OR of hyperuricemia for Q2 was not material significance (OR:1.54, 95%CI: 0.93 ~ 2.53, p-value: 0.210), however, ORs of hyperuricemia for Q3 (OR: 2.40, 95%CI: 1.70 ~ 3.38, p-value: 0.011) and Q4 (OR: 3.27, 95%CI: 2.31 ~ 4.62, p-value: 0.001) were statistically significant.

Conclusion

Higher level of dietary acid load was found to be associated with hyperuricemia in Chinese adults, indicative of advocation of a well-balanced diet in this population.
Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence
Authors: Falck Johanna , Rolander Bo , Nygårdh Annette , Jonasson Lise-Lotte , Mårtensson Jan
Published: November 2022

Background

Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema.

Methods

We conducted a national cross-sectional study using an online survey assessing sociodemographic data, lipoedema characteristics, symptom severity, comorbidities, HRQOL (RAND-36), and SOC (SOC-13). In total, 245 women with lipoedema, recruited from all Lipoedema Association groups in Sweden, participated. Data were compiled with descriptive statistics, and mean differences between groups were analysed by using parametric and non-parametric tests.

Results

Moderate and severe leg heaviness, pain, numbness, cold skin, feeling cold, easy bruising, and sleep problems were found to occur in all lipoedema stages. Moreover, almost all participants reported having comorbidities. Worse physical health and most substantial limitations in daily life were reported among women with the most progressive lipoedema (i.e., stage 3). Social and emotional functioning and SOC were found to be, on the other hand, primarily related to respondents’ sociodemographic data and their ages at lipoedema onset. Even though approximately 70% of the women had experienced lipoedema onset before age 30, only three (1.6%) had been diagnosed by a healthcare professional before that age.

Conclusion

Having lipoedema is associated with several health problems and a lower HRQOL. In addition, the extent of delay in diagnosis within this sample indicates that many women with lipoedema are often underdiagnosed and are left without support from healthcare. These findings call for the need for greater attention on lipoedema. Moreover, further studies on how women with lipoedema manage their health and symptoms, as well as on their experiences of healthcare services and lipoedema treatments, are needed.
Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway
Authors: Baig Nida , Sultan Rabia , Qureshi Shamim Akhtar
Published: November 2022

Background

Type 2 diabetes mellitus (T2DM) approximately constitutes 90% of the reported cases. 30-40% of diabetics eventually develop diabetic nephropathy (DN); accounting for one of the major causes of morbidity and mortality. Increased glucose autoxidation and non-enzymatic glycation of proteins in diabetic kidneys lead to the excessive generation of reactive oxygen species (ROS) that results in lipid peroxidation and activation of inflammatory mediators which overwhelms the scavenging capacity of the antioxidant defense system (Nrf2/Keap1/HO-1). Centratherum anthelminticum commonly called as kali zeeri (bitter cumin) and its seeds are well known for culinary purposes in Asia (Pakistan). It has reported anti-inflammatory, antioxidant, and anti-diabetic activities. The present study has attempted to explore the in-vivo anti-inflammatory, antioxidant and antihyperglycemic potential of the C. anthelminticum seed’s fixed oil (FO) and its fractions in high fat-high fructose-streptozotocin (HF-HFr-STZ) induced T2DM rat model.

Methods

The T2DM rat model was developed by giving a high-fat and high-fructose diet followed by a single intraperitoneal injection of streptozotocin (STZ 60 mg/kg) on 28th day of the trial. After 72 hours of this injection, rats showing fasting blood glucose (FBG) levels≥230 mg/dL were recruited into six groups. These groups were orally administered distilled water (1 mL/kg), Gliclazide (200 mg/kg), Centratherum anthelminticum seed (FO) and its hexane (HF), chloroform (CF) and ethanol (EF) soluble fractions (200 mg/kg each), respectively for 4 weeks (i.e. 28 days). Blood, serum, and kidney tissue samples of euthanized animals were used for biochemical, pro-inflammatory, and antioxidant markers (ELISA, qRT-PCR, and spectrophotometric assays) and histology, respectively.

Results

C. anthelminticum FO and its fractions reduced the lipid peroxidation, and improved the antioxidant parameters: enzymatic (SOD, CAT, and GPx), non-enzymatic (GSH), and mRNA expression of anti-inflammatory markers (Nrf-2, keap1, and HO-1). mRNA expression of inflammatory and apoptotic markers (TNF-α, IL-1β, COX-1, NF-κB, Bax, and Bcl-2) were attenuated along with improved kidney architecture.

Conclusion

C. anthelminticum can mitigate inflammation and oxidative stress in early DN. The anti-nephropathic effect can be attributed to its ability to down-regulate NF-κB and by bringing the Nrf-2 expression levels to near normal.
Ascorbic acid 6-palmitate modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated BV-2 cells via PERK/elF2α mediated endoplasmic reticulum stress
Authors: Li Qian , Wu Yao , Chen Xue-shen , Zeng Tao , Liu Lin-ling , Feng Zi-qi , Liu Dan-yang , Zhu Ling , Wan Li-hong
Published: November 2022

Background

Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells.

Methods

Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK).

Results

L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation.

Conclusion

Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.
Consumption of coffee and tea with all-cause and cause-specific mortality: a prospective cohort study
Authors: Chen Yanchun , Zhang Yuan , Zhang Mengnan , Yang Hongxi , Wang Yaogang
Published: November 2022

Background

Previous studies suggested that moderate coffee and tea consumption are associated with lower risk of mortality. However, the association between the combination of coffee and tea consumption with the risk of mortality remains unclear. This study aimed to evaluate the separate and combined associations of coffee and tea consumption with all-cause and cause-specific mortality.

Methods

This prospective cohort study included 498,158 participants (37–73 years) from the UK Biobank between 2006 and 2010. Coffee and tea consumption were assessed at baseline using a self-reported questionnaire. All-cause and cause-specific mortalities, including cardiovascular disease (CVD), respiratory disease, and digestive disease mortality, were obtained from the national death registries. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After a median follow-up of 12.1 years, 34,699 deaths were identified. The associations of coffee and tea consumption with all-cause and cause-specific mortality attributable to CVD, respiratory disease, and digestive disease were nonlinear (all P nonlinear < 0.001). The association between separate coffee consumption and the risk of all-cause mortality was J-shaped, whereas that of separate tea consumption was reverse J-shaped. Drinking one cup of coffee or three cups of tea per day seemed to link with the lowest risk of mortality. In joint analyses, compared to neither coffee nor tea consumption, the combination of < 1–2 cups/day of coffee and 2–4 cups/day of tea had lower mortality risks for all-cause (HR, 0.78; 95% CI: 0.73–0.85), CVD (HR, 0.76; 95% CI: 0.64–0.91), and respiratory disease (HR, 0.69; 95% CI: 0.57–0.83) mortality. Nevertheless, the lowest HR (95% CI) of drinking both < 1–2 cup/day of coffee and ≥ 5 cups/day of tea for digestive disease mortality was 0.42 (0.34–0.53).

Conclusions

In this large prospective study, separate and combined coffee and tea consumption were inversely associated with all-cause and cause-specific mortality.
The use of routine health facility data for micro-stratification of malaria risk in mainland Tanzania
Authors: Thawer Sumaiyya G. , Golumbeanu Monica , Munisi Khalifa , Aaron Sijenunu , Chacky Frank , Lazaro Samwel , Mohamed Ally , Kisoka Noela , Lengeler Christian , Molteni Fabrizio , Ross Amanda , Snow Robert W. , Pothin Emilie
Published: November 2022

Background

Current efforts to estimate the spatially diverse malaria burden in malaria-endemic countries largely involve the use of epidemiological modelling methods for describing temporal and spatial heterogeneity using sparse interpolated prevalence data from periodic cross-sectional surveys. However, more malaria-endemic countries are beginning to consider local routine data for this purpose. Nevertheless, routine information from health facilities (HFs) remains widely under-utilized despite improved data quality, including increased access to diagnostic testing and the adoption of the electronic District Health Information System (DHIS2). This paper describes the process undertaken in mainland Tanzania using routine data to develop a high-resolution, micro-stratification risk map to guide future malaria control efforts.

Methods

Combinations of various routine malariometric indicators collected from 7098 HFs were assembled across 3065 wards of mainland Tanzania for the period 2017–2019. The reported council-level prevalence classification in school children aged 5–16 years (PfPR5–16) was used as a benchmark to define four malaria risk groups. These groups were subsequently used to derive cut-offs for the routine indicators by minimizing misclassifications and maximizing overall agreement. The derived-cutoffs were converted into numbered scores and summed across the three indicators to allocate wards into their overall risk stratum.

Results

Of 3065 wards, 353 were assigned to the very low strata (10.5% of the total ward population), 717 to the low strata (28.6% of the population), 525 to the moderate strata (16.2% of the population), and 1470 to the high strata (39.8% of the population). The resulting micro-stratification revealed malaria risk heterogeneity within 80 councils and identified wards that would benefit from community-level focal interventions, such as community-case management, indoor residual spraying and larviciding.

Conclusion

The micro-stratification approach employed is simple and pragmatic, with potential to be easily adopted by the malaria programme in Tanzania. It makes use of available routine data that are rich in spatial resolution and that can be readily accessed allowing for a stratification of malaria risk below the council level. Such a framework is optimal for supporting evidence-based, decentralized malaria control planning, thereby improving the effectiveness and allocation efficiency of malaria control interventions.
Protein arginine deiminase 2 (PAD2) modulates the polarization of THP-1 macrophages to the anti-inflammatory M2 phenotype
Authors: Stachowicz Aneta , Pandey Rakhi , Sundararaman Niveda , Venkatraman Vidya , Van Eyk Jennifer E. , Fert-Bober Justyna
Published: November 2022

Background

Macrophages are effector cells of the innate immune system that undergo phenotypical changes in response to organ injury and repair. These cells are most often classified as proinflammatory M1 and anti-inflammatory M2 macrophages. Protein arginine deiminase (PAD), which catalyses the irreversible conversion of protein-bound arginine into citrulline, is expressed in macrophages. However, the substrates of PAD and its role in immune cells remain unclear. This study aimed to investigate the role of PAD in THP-1 macrophage polarization to the M1 and M2 phenotypes and identify the citrullinated proteins and modified arginines that are associated with this biological switch using mass spectrometry.

Results

Our study showed that PAD2 and, to a lesser extent, PAD1 and PAD4 were predominantly expressed in M1 macrophages. We showed that inhibiting PAD expression with BB-Cl-amidine decreased macrophage polarization to the M1 phenotype (TNF-α, IL-6) and increased macrophage polarization to the M2 phenotype (MRC1, ALOX15). This process was mediated by the downregulation of proteins involved in the NF-κβ pathway. Silencing PAD2 confirmed the activation of M2 macrophages by increasing the antiviral innate immune response and interferon signalling. A total of 192 novel citrullination sites associated with inflammation, cell death and DNA/RNA processing pathways were identified in M1 and M2 macrophages.

Conclusions

We showed that inhibiting PAD activity using a pharmacological inhibitor or silencing PAD2 with PAD2 siRNA shifted the activation of macrophages towards the M2 phenotype, which can be crucial for designing novel macrophage-mediated therapeutic strategies. We revealed a major citrullinated proteome and its rearrangement following macrophage polarization, which after further validation could lead to significant clinical benefits for the treatment of inflammation and autoimmune diseases.
Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment
Authors: Liu Faying , Tian Lifeng , Tan Jun , Li Zengming , Qin Haiyan , Xu Dingfei , Huang Zhihui , Wu Xingwu , Chen Ge , Wu Qiongfang , Zou Yang
Published: November 2022

Background

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5–10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.

Objective

To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.

Methods

Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.

Result(s)

During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.

Conclusion(s)

We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.
Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics
Authors: Bhat Ajaz A. , Nisar Sabah , Mukherjee Soumi , Saha Nirmalya , Yarravarapu Nageswari , Lone Saife N. , Masoodi Tariq , Chauhan Ravi , Maacha Selma , Bagga Puneet , Dhawan Punita , Akil Ammira Al-Shabeeb , El-Rifai Wael , Uddin Shahab , Reddy Ravinder , Singh Mayank , Macha Muzafar A. , Haris Mohammad
Published: November 2022

Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system’s pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.
Clinical electives in China: trends, experiences, barriers
Authors: Storz Maximilian Andreas
Published: November 2022

In recent decades, China has quickly transformed itself into a modern, urban, technological and economic powerhouse. China’s medical education system is internationalizing and attracting a considerable number of foreign students seeking medical degrees and other clinical experience, such as observerships, in China. Although the majority of international students in China come from low- and middle income countries, China’s rise towards the world’s largest medical education system also offers new opportunities for stronger cooperation with European countries. Both sides maintain tight economic ties, and China’s rise is also attracting more and more medial students for short-term clinical electives from the German-speaking countries. Such clinical electives are pertinent to global health education in a globalized world, and allow students to immerse in foreign healthcare systems for a short period. Notably, reasons for (and barriers to) electives in China are largely unexplored. To address this gap, we reviewed 4 popular German elective report databases and extrapolated key characteristics of electives in China undertaken by German-speaking medical student. N = 40 elective testimonies were analyzed with regard to students’ elective experience, elective barriers and organizational aspects. The vast majority of students reported an elective in Shanghai (n = 29, 72.50%). More than 70% of students applied directly to an elective program for foreign students, whereas less than 25% applied through a bilateral exchange program. Frequently cited positive aspects of electives in China included the Chinese hospitality and the regular high-quality teaching in English for international students. Notably, almost half of student reported some kind of difficulties during their elective (n = 18, 45%), including language barriers (n = 6), administrative issues (n = 5) and visa problems (n = 2). Our data suggest that international electives in China were overall well-rated by German-speaking students. The combination of structured clinical elective programs with English supervision and the opportunity to learn more about the Chinese culture apparently attracted said students in the past 2 decades.