bluuebunny/crossref_metadata_2025 huggingface dataset:
Land and the US Agrarian South
Authors: Ajl Max
Published: December 2021

This review essay summarizes and synthesizes three books on Black and Indigenous agrarian struggles in the modern-day territories of the USA. It discusses how they recount the centrality of land, national liberation, self-reliant development, food sovereignty and sustainable forms of agriculture and land management to Black and Indigenous radical struggle. It then suggests parallels and divergences between those struggles and those in the Third World’s agrarian south. It focusses on the anti-systemic dimensions of national liberation struggles in the core, especially those carried out historically by Black and Indigenous movements, and details how those movements historically looked out beyond the US landmass for solidarity and to build internationalist fronts. Finally, it reflects on their role in destabilizing settler-capitalism in the USA.
Downsizing Teaching: The Case for Seminars as the Backbone of Law Degrees
Authors: Vargiu Paolo
Published: December 2021

This article is aimed at contributing to the ongoing debate on the purpose of law school and the work of law teachers, calling for a scholarship-based approach to teaching, centred on culture, research and method and advocating for seminars to replace lectures as the core method of teaching delivery in law schools. The article addresses, under this perspective, the salient elements of legal education: the philosophy of a teacher, the function of lectures and seminars, the problem of the time necessary to gain the required preparation, the importance of reading and the role played by assessment in the economy of a law degree. It is argued that teaching delivery methods should be the subject of constant reflection, and that the drafting of law school curricula should aim at cultivating the intellectual abilities and curiosity of law students, focussing on their education rather than their mere instruction.
Gender, fraud opportunity, and rationalisation
Authors: Ameer Rashid , Othman Radiah
Published: December 2021

Framed by opportunity and gender theories, this study examines whether men and women who occupy similar organisational positions differ in the types of fraud committed and their rationalisations. Based on 261 published legal cases of convicted fraudsters in New Zealand, our results show that fraudster's position and rationalisation are important fraud predictors. Our multinomial regression results show that there is a significant difference in the fraud committed in a similar position. There is a relationship between female gambling and embezzlement fraud. A large percentage of fraudsters of both genders offered no rationalisation; those who did, claimed they were victims of circumstances (denial of responsibility) and morally justified their offending. The morally justified rationalisation was associated with lifestyles and pleasing others. Moreover, two rationalisation categories —appeal to higher loyalties and condemning the condemners—are significant in predicting the likelihood of obtaining by deception and embezzlement fraud in the New Zealand context. We also identify two distinct patterns of fraud offending: instrumental-opportunist and pathological-opportunist.
Tigecycline: Role in the Management of cIAI and cSSTI in the Indian Context
Authors: Swaminathan Subramanian , Kundu Prithwijit
Published: December 2021

The current millennium has witnessed an increased antimicrobial resistance which poses a mammoth challenge for public health management. This has resulted in an increase in morbidity and mortality, resulting in an increase in financial burden to the patients. A recent analysis from 10 hospitals in India reported that mortality rate increases by 1.57 times in patients suffering from multidrug resistance (MDR) bacterial infections as compared to patients infected with similar but susceptible infections. Due to the emergence of MDR and extensively drug-resistant (XDR) bacteria, most of the broad-spectrum antibiotics have been rendered ineffective. The mortality rate with Gram-negative strains is higher than with Gram-positive strains. Tigecycline is the first in class glycylcycline antibiotic with an expanded broad-spectrum activity. Tigecycline enters bacterial cells through energy-dependent pathways or via passive diffusion, to reversibly bind to the 30S ribosomal subunit. It has potent in vitro activity against Gram-negative carbapenemase producers, except Pseudomonas aeruginosa and Proteus spp. It also has good in vitro activity against Carbapenem-resistant Klebsiella pneumoniae strains. Hence, it is considered as a therapeutic option in XDR isolates. Recent meta-analyses have shown tigecycline to be as effective as its comparators with reducing mortality rates. Due to increased resistance reported in carbapenem-resistant isolates in Indian health-care settings, a colistin/polymyxin B-based combination therapy as a treatment option is being sought. A lower mortality rate has been reported with colistin-based combination therapy in Carbapenem-resistant Enterobacteriaceae-associated infections. Combinations with tigecycline, Fosfomycin, and chloramphenicol have shown to improve treatment outcomes. Tigecycline can be a good alternative in MDR and XDR complicated intra-abdominal and complicated skin and soft tissue infections. Appropriately designed clinical trials in Indian health-care setups will reinforce clinician’s confidence in using tigecycline in complex clinical situations.
An Adenylate Kinase OsAK3 Involves Brassinosteroid Signaling and Grain Length in Rice (Oryza sativa L.)
Authors: Zhang Jiaqi , Gao Xiuying , Cai Guang , Wang Yuji , Li Jianbo , Du Huaying , Wang Ruqin , Zhang Hongsheng , Huang Ji
Published: December 2021

Background

Grain size is one of the major determinants of cereal crop yield. As a class of plant polyhydroxysteroids, brassinosteroids (BRs) play essential roles in the regulation of grain size and plant architecture in rice. In a previous research, we cloned qGL3/OsPPKL1 encoding a protein phosphatase with Kelch-like repeat domains, which negatively regulates BR signaling and grain length in rice.

Results

Here, we screened qGL3-interacting proteins (GIPs) via yeast two-hybrid assay and analyzed the phenotypes of the T-DNA insertion mutants of GIPs. Among these mutants, mutant osak3 presents shorter grain length and dwarfing phenotype. OsAK3 encodes an adenylate kinase, which regulates grain size by controlling cell expansion of rice spikelet glume. Overexpression of OsAK3 resulted in longer grain length. OsAK3 interacts with qGL3 in vivo and in vitro. Lamina inclination, coleoptile elongation and root inhibition experiments showed that the osak3 mutant was less sensitive to exogenous brassinolide (BL) treatment. The transcriptional level of OsAK3 was up-regulated under BL induction. In addition, RNA-Seq data indicate that OsAK3 is involved in a variety of biological processes that regulate BR signaling and grain development in rice.

Conclusions

Our study reveals a novel BR signaling component OsAK3 in the regulation of grain length, and provides novel clues for uncovering the potential functions of OsAK3 in rice growth and development.
Platelet-to-hemoglobin ratio as a valuable predictor of long-term all-cause mortality in coronary artery disease patients with congestive heart failure
Authors: Bao Kunming , Huang Haozhang , Huang Guoyong , Wang Junjie , Liao Ying , Pan Yuxiong , Chen Weihua , Lu Jin , Yang Yanfang , Huang Zhidong , Chen Shiqun , Chen Kaihong , Chen Liling
Published: December 2021

Background

The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF.

Methods

Based on the registry at Guangdong Provincial People’s Hospital in China, we analyzed data of 2599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as ˂ 1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan–Meier method. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted.

Results

During a median follow-up of 5.2 (3.1–7.8) years, a total of 985 (37.9%) patients died. On the Kaplan–Meier analysis, patients in high PHR group had a worse prognosis than those in low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.13–1.52, p < 0.0001).

Conclusion

Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.
de Winter syndrome or inferior STEMI?
Authors: Wang Shijun , Shen Liang
Published: December 2021

Background

The de Winter electrocardiography (ECG) pattern is associated with acute total or subtotal occlusion of the left anterior descending coronary artery (LAD) characterized by upsloping ST-segment depression at the J point in leads V1–V6 without ST-segment elevation.

Case presentation

We report an atypical style case of the de Winter ECG pattern accompanied by ST elevation in inferior leads. The patient underwent emergency coronary angiography, which revealed total occlusion of the proximal LAD with no observable stenosis in the right coronary artery.

Conclusion

ECG-related changes in acute total LAD occlusion can present with the de Winter pattern and ST elevation in inferior leads. Recognizing this atypical ECG pattern is critical for immediate reperfusion therapy.
Maternal-fetal bonding during the COVID-19 pandemic
Authors: Koire Amanda , Mittal Leena , Erdei Carmina , Liu Cindy H.
Published: December 2021

Background

The pregnant population experienced unique COVID-19 physical and psychosocial stressors such as direct health concerns related to the virus and loss of access to resources since the COVID-19 emerged as a global pandemic in early 2020. Despite these COVID-19-related stress and concerns, the maternal experience of bonding with their unborn children has not been well studied. This work aimed to study the association between mental health history, current mental health symptoms, psychological factors, COVID-19-related worries, and self-reported maternal-fetal bonding of pregnant women.

Methods

This online, survey-based cross-sectional study focused on women pregnant during the pandemic and assessed 686 women using data collected from May 19, 2020 to October 3, 2020. Enrolled respondents completed assessments in which they self-reported maternal-fetal bonding, mental health symptomatology, psychological factors, and COVID-19-related worries regarding health, pregnancy, and resources.

Results

Depressive symptoms in pregnant women were associated with lower quality maternal-fetal bonding, while a higher level of anxiety was positively associated with bonding; however, past history of depression or generalized anxiety diagnosis did not appear to be as relevant as active symptomatology. Maternal resilience, but not distress tolerance, appeared to be a protective factor resulting in improved bonding. Higher levels of worry regarding impact of COVID-19 on health were significantly associated with improved bonding, while worries regarding the impact of COVID-19 on the pregnancy or resources were not significantly associated with bonding. The study also found associations between different sociodemographic variables and bonding, including a strong positive association between first time motherhood and bonding and a negative association between higher education and income and bonding.

Conclusions

This study was the first to report potential protective and risk factors to the maternal-fetal bonding process in women pregnant during the COVID-19 pandemic. Unique COVID-19 concerns exist; however, anxiety and COVID-19 concerns do not appear to undermine maternal-fetal bonding while active depressive symptomatology may negatively influence bonding; interventions increasing maternal resilience may be particularly valuable.
Psychological impacts of the COVID-19 pandemic on one-month postpartum mothers in a metropolitan area of Japan
Authors: Takubo Youji , Tsujino Naohisa , Aikawa Yuri , Fukiya Kazuyo , Iwai Momoko , Uchino Takashi , Ito Megumu , Akiba Yasuo , Mizuno Masafumi , Nemoto Takahiro
Published: December 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic has recently become the most important issue in the world. Very few reports in Japan have examined the impact of the COVID-19 pandemic on peripartum mental health. We examined the status of postpartum mental health before and during COVID-19 pandemic from a consecutive database in a metropolitan area of Japan.

Methods

The subjects were women who had completed a maternity health check-up at a core regional hospital in Yokohama during the period from April 1, 2017, to December 31, 2020. We collected the subjects’ scores for the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-to-Infant Bonding Scale (MIBS) at 1 month postpartum. The subjects were divided into four groups (three Before COVID-19 groups and a During COVID-19 group). MANOVA and post-hoc tests were used to determine mental health changes in the postpartum period among the four groups.

Results

The Before and During COVID-19 groups contained 2844 and 1095 mothers, respectively. There were no significant difference in the total scores of the EPDS and MIBS among the four groups. However, the EPDS items related to anxiety factors were significantly higher and the EPDS items related to anhedonia and depression factors (excluding thoughts of self-harm) were significantly lower in the During COVID-19 group.

Conclusion

The EPDS scores changed in connection with the COVID-19 pandemic. Anxiety, which represent hypervigilance, was significantly higher and anhedonia and depression were significantly lower in the During COVID-19 group. Our results may reflect COVID-19-related health concerns and a lack of social support caused by the COVID-19 pandemic.
Risk factors and prognostic significance of lateral pelvic lymph node dissection after neoadjuvant chemoradiotherapy for rectal patients with clinically suspected lateral lymph node metastasis
Authors: Zhou Sicheng , Jiang Yujuan , Pei Wei , Liang Jianwei , Zhou Zhixiang
Published: December 2021

Aim

It is still controversial whether the addition of lateral pelvic lymph node (LPN) dissection (LPND) to total mesorectal excision (TME) can provide a survival benefit after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients with pathological lateral lymph node metastasis (LPNM).

Methods

Patients with clinically suspected LPNM who underwent nCRT followed by TME + LPND were systematically reviewed and divided into the positive LPN group (n = 15) and the negative LPN group (n = 58). Baseline characteristics, clinicopathological data and survival outcomes were collected and analysed.

Results

Of the 73 patients undergoing TME + LPND after nCRT, the pathological LPNM rate was 20.5% (15/73). Multivariate analysis showed that a post-nCRT LPN short diameter ≥ 7 mm (OR 49.65; 95% CI 3.98–619.1; P = 0.002) and lymphatic invasion (OR 9.23; 95% CI 1.28–66.35; P = 0.027) were independent risk factors for pathological LPNM. The overall recurrence rate of patients with LPNM was significantly higher than that of patients without LPNM (60.0% vs 27.6%, P = 0.018). Multivariate regression analysis identified that LPNM was an independent risk factor not only for overall survival (OS) (HR 3.82; 95% CI 1.19–12.25; P = 0.024) but also for disease-free survival (DFS) (HR 2.33; 95% CI 1.02–5.14; P = 0.044). Moreover, N1-N2 stage was another independent risk factor for OS (HR 7.41; 95% CI 1.63–33.75; P = 0.010).

Conclusions

Post-nCRT LPN short diameter ≥ 7 mm and lymphatic invasion were risk factors for pathological LPNM after nCRT. Furthermore, patients with pathological LPNM still show an elevated overall recurrence rate and poor prognosis after TME + LPND. Strict patient selection and intensive perioperative chemotherapy are crucial factors to ensure the efficacy of LPND.
One-stop clinic for patients with suspected ovarian cancer: results from a retrospective outcome study of the referral pathway
Authors: Ashmore Ayisha A. , Gnanachandran Chellappah , Luqman Iqra , Horrocks Kathryn
Published: December 2021

Background

Women with abdominal pain and bloating frequently have their Ca-125 levels investigated for suspected ovarian cancer and this has led to a significant increase in referrals to the ovarian cancer service. We have conducted this study to help improve the efficiency in which these patients are investigated and to improve future pathways within the referral service.

Methods

This was a retrospective observational outcome study. Data were collected from electronic documents of patients’ referrals, assessments, and clinical correspondences over 48 months. The study was conducted in a secondary gynaecology cancer centre with direct referrals from primary care. The pelvic mass clinic was set up to include a consultation and an ultrasound scan with support available for patients if required. All patients included were referred directly from primary care for suspected ovarian cancer with Ca-125 result over a period of 2 years.

Results

286 were referred from primary care according to the NICE guidelines of ‘2-week wait for ovarian cancer’. Only 223 patients who had a Ca-125 result reported at the time of their referral were included in the analysis. Out of the 223 patients, 126 patients were discharged with or without a repeat Ca-125 after the initial assessment. 18 patients were diagnosed with cancer following the referral, but only 12 of them had a primary ovarian malignancy. The malignancy rate in women under 50 years of age was 22% (4/18) and 78% (14/18) in women aged 50 or above.

Conclusion

One-stop focused gynaecology ultrasound clinics where clinicians may assess patients and perform ultrasound scans for suspected cancer, may be better for managing this patient population due to improved efficiencies in waiting times, same day diagnosis and a reduction in waiting times to first appointment. Secondly, the majority of the patients with Ca-125 of more than 35 U/mL, who were referred through this pathway, did not have cancer. This review queries the future value of using Ca-125 as the basis for referrals from primary care for suspected ovarian malignancy. Further studies are required to assess whether a higher Ca-125 cut off may be used as the basis of referrals for premenopausal women.
Level of exclusive breastfeeding and its enabling factors among lactating women who delivered in health facilities of Asosa town, Ethiopia: a cross sectional study
Authors: Kumera Megersa , Haidar Jemal
Published: December 2021

Background

Despite the enormous benefit of exclusive breastfeeding (EBF) to mothers and infants, the practice of exclusive breastfeeding is globally low. In sub-Saharan Africa and Ethiopia, the prevalence of EBF stands at 35% and 59%, respectively. The low EBF practice in Ethiopia as well as in the studied region calls for further study and thus we studied the EBF practice in the study area since little is known about its current magnitude and factors influencing its practice for some programmatic improvements.

Methods

A facility based cross-sectional study linked to a community was conducted from June-July 2019 among 412 mothers who had antenatal follow-up and delivered in health facilities of Asosa town over a period of one year prior to the study. Data on socio demographic characteristics and other important variables were collected through face to face interview while gestational age in weeks was recorded from their medical chart by trained health extension workers in accordance with relevant ethical guidelines and regulations. The collected data were then cleaned and entered into Epi-data software version 3.02. Analysis was done by SPSS version 20. Binary and multivariate logistic regression were performed to identify the contributing factors. P-value of less than 0.05 and 95% confidence interval was considered to determine statistical significance.

Results

Of the 412 respondents, the majority (88.1%) were multi-gravida and above. Slightly higher than a quarter (26.0%) and over half (55.4%) had neither received antenatal nor postnatal care. The proportion of mothers who exclusively breastfed their children was 76.0% and the overall aggregated good practice of EBF score was 64.1%. Mothers who completed primary school [AOR = 4.5; 95% CI = 1.1,18.2], had four or more ANC [AOR = 1.8;95CI = 0.79–0.98], and postnatal follow-up [AOR = 0.21;95% CI = 0.07–0.67], and had male infants [AOR = 2.3; 95% CI = 1.0–4.95] were among the factors influencing the exclusive breastfeeding practice score.

Conclusion

While three in four mothers exclusively breastfed their newborns and about two-thirds had good EBF score, the observed women’s retention on the continuum of the maternal care pathway is low with one in four had no antenatal and over half had no postnatal care which are important derivers for EBF practice. To improve the EBF score and narrow the observed maternal and child health disparities, it is essential to promote maternal education and increase the recomended coverage of antenatal and postnatal care for mothers.
A study on women’s health information needs in menopausal age
Authors: Hajesmaeel-Gohari Sadrieh , Shafiei Elaheh , Ghasemi Fatemeh , Bahaadinbeigy Kambiz
Published: December 2021

Menopause is a natural event experienced by women in middle age. To help women manage this event, it is important to identify their health information needs. A study specific questionnaire was used to identify menopausal women’s health information needs and the resources and challenges related to finding information about menopause. A total of 301 women aged 48–55 years completed the questionnaire. Data were analysed using negative binomial regression and chi-square tests. The most frequently sought information was that related to breast cancer (n = 209, 69.5%), hot flushes (n = 200, 66.5%), cervical cancer (n = 194, 64.5%), non-hormonal therapies for menopausal symptoms (n = 192, 64%), laboratory tests (n = 189, 63%) and joint and muscle pain (n = 188, 62.5%). The main sources of information were audiovisual media (n = 171, 57%), obstetricians (n = 165, 55%), friends (n = 157, 52%), family (n = 157, 52%) and the internet (n = 153, 51%). The two main challenges were not knowing how to correctly access information (n = 115, 38%) and not being aware of reliable sources of information (n = 108, 36%). Therefore, it is essential for policymakers and decision-makers to provide reliable and accurate information to increase awareness and reduce anxiety of women experiencing menopause.
HuR drives lung fibroblast differentiation but not metabolic reprogramming in response to TGF-β and hypoxia
Authors: Trivlidis Joshua , Aloufi Noof , Al-Habeeb Fatmah , Nair Parameswaran , Azuelos Ilan , Eidelman David H. , Baglole Carolyn J.
Published: December 2021

Background

Pulmonary fibrosis is thought to be driven by recurrent alveolar epithelial injury which leads to the differentiation of fibroblasts into α-smooth muscle actin (α-SMA)-expressing myofibroblasts and subsequent deposition of extracellular matrix (ECM). Transforming growth factor beta-1 (TGF-β1) plays a key role in fibroblast differentiation, which we have recently shown involves human antigen R (HuR). HuR is an RNA binding protein that also increases the translation of hypoxia inducible factor (HIF-1α) mRNA, a transcription factor critical for inducing a metabolic shift from oxidative phosphorylation towards glycolysis. This metabolic shift may cause fibroblast differentiation. We hypothesized that under hypoxic conditions, HuR controls myofibroblast differentiation and glycolytic reprogramming in human lung fibroblasts (HLFs).

Methods

Primary HLFs were cultured in the presence (or absence) of TGF-β1 (5 ng/ml) under hypoxic (1% O2) or normoxic (21% O2) conditions. Evaluation included mRNA and protein expression of glycolytic and myofibroblast/ECM markers by qRT-PCR and western blot. Metabolic profiling was done by proton nuclear magnetic resonance (1H- NMR). Separate experiments were conducted to evaluate the effect of HuR on metabolic reprogramming using siRNA-mediated knock-down.

Results

Hypoxia alone had no significant effect on fibroblast differentiation or metabolic reprogramming. While hypoxia- together with TGFβ1- increased mRNA levels of differentiation and glycolysis genes, such as ACTA2, LDHA, and HK2, protein levels of α-SMA and collagen 1 were significantly reduced. Hypoxia induced cytoplasmic translocation of HuR. Knockdown of HuR reduced features of fibroblast differentiation in response to TGF-β1 with and without hypoxia, including α-SMA and the ECM marker collagen I, but had no effect on lactate secretion.

Conclusions

Hypoxia reduced myofibroblasts differentiation and lactate secretion in conjunction with TGF-β. HuR is an important protein in the regulation of myofibroblast differentiation but does not control glycolysis in HLFs in response to hypoxia. More research is needed to understand the functional implications of HuR in IPF pathogenesis.
Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer
Authors: Jang Hye Jin , Choi Ji Yeon , Kim Kangjoon , Yong Seung Hyun , Kim Yeon Wook , Kim Song Yee , Kim Eun Young , Jung Ji Ye , Kang Young Ae , Park Moo Suk , Kim Young Sam , Cho Young-Jae , Lee Sang Hoon
Published: December 2021

Background

Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer.

Methods

16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses.

Results

In total, 84 patients were prospectively analyzed, of which 59 showed low (< 10%), and 25 showed high (≥ 10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group.

Conclusion

The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.
The opposing trends of body mass index and blood pressure during 1977–2020; nationwide registry of 2.8 million male and female adolescents
Authors: Fishman Boris , Zloof Yair , Orr Omri , Tsur Avishai M. , Furer Ariel , Omer Gilon Ma’ayan , Chodick Gabriel , Leiba Adi , Derazne Estela , Tzur Dorit , Afek Arnon , Grossman Ehud , Twig Gilad
Published: December 2021

Background

Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10–20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity.

Methods

This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index.

Results

During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend  < 0.001 in both sexes). The mean diastolic blood pressure decreased by 3.6 mmHg in males and by 2.9 mmHg in females (P  < 0.001 in both sexes). The mean systolic blood pressure increased by 1.6 mmHg in males and decreased by 1.9 mmHg in females. These trends were also consistent when blood pressure values were adjusted to body mass index.

Conclusion

Despite the increase in body mass index over the last four decades, diastolic blood pressure decreased in both sexes while systolic blood pressure increased slightly in males and decreased in females.
The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors
Authors: Lin Hao , Guo Qingqing , Wen Zhiyong , Tan Songlin , Chen Jie , Lin Lijian , Chen Pengcheng , He Jianquan , Wen Jianbo , Chen Ye
Published: December 2021

Background

Anxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient’s feces and serum and continued the metagenomic analysis of the microorganisms in the patient’s feces.

Results

The results showed that the patient’s anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were “bacterial chemotaxis, “flagellar assembly”, “glycine, serine and threonine metabolism”, “apoptosis”, and “bacterial invasion of epithelial cells”.

Conclusions

FMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients’ symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission.

Trial registration ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676.
A novel protein fusion partner, carbohydrate-binding module family 66, to enhance heterologous protein expression in Escherichia coli
Authors: Ko Hyunjun , Kang Minsik , Kim Mi-Jin , Yi Jiyeon , Kang Jin , Bae Jung-Hoon , Sohn Jung-Hoon , Sung Bong Hyun
Published: December 2021

Background

Proteins with novel functions or advanced activities developed by various protein engineering techniques must have sufficient solubility to retain their bioactivity. However, inactive protein aggregates are frequently produced during heterologous protein expression in Escherichia coli. To prevent the formation of inclusion bodies, fusion tag technology has been commonly employed, owing to its good performance in soluble expression of target proteins, ease of application, and purification feasibility. Thus, researchers have continuously developed novel fusion tags to expand the expression capacity of high-value proteins in E. coli.

Results

A novel fusion tag comprising carbohydrate-binding module 66 (CBM66) was developed for the soluble expression of heterologous proteins in E. coli. The target protein solubilization capacity of the CBM66 tag was verified using seven proteins that are poorly expressed or form inclusion bodies in E. coli: four human-derived signaling polypeptides and three microbial enzymes. Compared to native proteins, CBM66-fused proteins exhibited improved solubility and high production titer. The protein-solubilizing effect of the CBM66 tag was compared with that of two commercial tags, maltose-binding protein and glutathione-S-transferase, using poly(ethylene terephthalate) hydrolase (PETase) as a model protein; CBM66 fusion resulted in a 3.7-fold higher expression amount of soluble PETase (approximately 370 mg/L) compared to fusion with the other commercial tags. The intact PETase was purified from the fusion protein upon serial treatment with enterokinase and affinity chromatography using levan-agarose resin. The bioactivity of the three proteins assessed was maintained even when the CBM66 tag was fused.

Conclusions

The use of the CBM66 tag to improve soluble protein expression facilitates the easy and economic production of high-value proteins in E. coli.
Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo
Authors: Zhang Zhe-Ao , Xin Xin , Liu Chao , Liu Yan-hong , Duan Hong-Xia , Qi Ling-ling , Zhang Ying-Ying , Zhao He-ming , Chen Li-Qing , Jin Ming-Ji , Gao Zhong-Gao , Huang Wei
Published: December 2021

Background

The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery.

Methods

PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied.

Results

The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona.

Conclusions

The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery.

Graphical Abstract
Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy
Authors: Huang Chunyu , Liu Zeming , Chen Mingzhu , Du Liang , Liu Chunping , Wang Shuntao , Zheng Yongfa , Liu Wei
Published: December 2021

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Graphical Abstract
Preparation, toxicity reduction and radiation therapy application of gold nanorods
Authors: Xie Lina , Zhang Xujia , Chu Chengchao , Dong Yingqi , Zhang Tianzi , Li Xinyue , Liu Gang , Cai Wen , Han Suxia
Published: December 2021

Gold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy.

Graphical Abstract
Development of a knowledge broker group to support evidence-informed policy: lessons learned from Myanmar
Authors: Paing Pyone Yadanar , Kyaw Zarni Lynn , Schojan Matthew , Traill Tom , Thura Si , Tin Nilar , Sein Than-Tun , Myint Hnin Hnin Tha , Bolton Paul , Lee Catherine
Published: December 2021

Background

Globally, policy-makers face challenges to using evidence in health decision-making, particularly lack of interaction between research and policy. Knowledge-brokering mechanisms can fill research–policy gaps and facilitate evidence-informed policy-making. In Myanmar, the need to promote evidence-informed policy is significant, and thus a mechanism was set up for this purpose. This paper discusses lessons learned from the development of the Knowledge Broker Group–Myanmar (KBG-M), supported by the Johns Hopkins Bloomberg School of Public Health’s Applied Mental Health Research Group (JHU) and Community Partners International (CPI).

Methods

Sixteen stakeholders were interviewed to explore challenges in formulating evidence-informed policy. Two workshops were held: the first to further understand the needs of policy-makers and discuss knowledge-brokering approaches, and the second to co-create the KBG-M structure and process. The KBG-M was then envisioned as an independent body, with former officials of the Ministry of Health and Sports (MoHS) and representatives from the nongovernmental sector actively engaging in the health sector, with an official collaboration with the MoHS.

Results

A development task force that served as an advisory committee was established. Then, steps were taken to establish the KBG-M and obtain official recognition from the MoHS. Finally, when the technical agreement with the MoHS was nearly complete, the process stopped because of the military coup on 1 February 2021, and is now on hold indefinitely.

Conclusions

Learning from this process may be helpful for future or current knowledge-brokering efforts, particularly in fragile, conflict-affected settings. Experienced and committed advisory committee members enhanced stakeholder relationships. Responsive coordination mechanisms allowed for adjustments to a changing bureaucratic landscape. Coordination with similar initiatives avoided overlap and identified areas needing technical support. Recommendations to continue the work of the KBG-M itself or similar platforms include the following: increase resilience to contextual changes by ensuring diverse partnerships, maintain advisory committee members experienced and influential in the policy-making process, ensure strong organizational and funding support for effective functioning and sustainability, have budget and timeline flexibility to allow sufficient time and resources for establishment, organize ongoing needs assessments to identify areas needing technical support and to develop responsive corrective approaches, and conduct information sharing and collaboration between stakeholders to ensure alignment.
Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study
Authors: Qu Heshuang , Sundberg Erik , Aulin Cecilia , Neog Manoj , Palmblad Karin , Horne Anna Carin , Granath Fredrik , Ek Alexandra , Melén Erik , Olsson Mia , Harris Helena Erlandsson
Published: December 2021

Background

This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms.

Methods

Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA).

Results

The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA.

Conclusions

We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
Astrocytic C–X–C motif chemokine ligand-1 mediates β-amyloid-induced synaptotoxicity
Authors: Perez-Nievas Beatriz G. , Johnson Louisa , Beltran-Lobo Paula , Hughes Martina M. , Gammallieri Luciana , Tarsitano Francesca , Myszczynska Monika A. , Vazquez-Villasenor Irina , Jimenez-Sanchez Maria , Troakes Claire , Wharton Stephen B. , Ferraiuolo Laura , Noble Wendy
Published: December 2021

Background

Pathological interactions between β-amyloid (Aβ) and tau drive synapse loss and cognitive decline in Alzheimer’s disease (AD). Reactive astrocytes, displaying altered functions, are also a prominent feature of AD brain. This large and heterogeneous population of cells are increasingly recognised as contributing to early phases of disease. However, the contribution of astrocytes to Aβ-induced synaptotoxicity in AD is not well understood.

Methods

We stimulated mouse and human astrocytes with conditioned medium containing concentrations and species of human Aβ that mimic those in human AD brain. Medium from stimulated astrocytes was collected and immunodepleted of Aβ before being added to naïve rodent or human neuron cultures. A cytokine, identified in unbiased screens of stimulated astrocyte media and in postmortem human AD brain lysates was also applied to neurons, including those pre-treated with a chemokine receptor antagonist. Tau mislocalisation, synaptic markers and dendritic spine numbers were measured in cultured neurons and organotypic brain slice cultures.

Results

We found that conditioned medium from stimulated astrocytes induces exaggerated synaptotoxicity that is recapitulated following spiking of neuron culture medium with recombinant C–X–C motif chemokine ligand-1 (CXCL1), a chemokine upregulated in AD brain. Antagonism of neuronal C–X–C motif chemokine receptor 2 (CXCR2) prevented synaptotoxicity in response to CXCL1 and Aβ-stimulated astrocyte secretions.

Conclusions

Our data indicate that astrocytes exacerbate the synaptotoxic effects of Aβ via interactions of astrocytic CXCL1 and neuronal CXCR2 receptors, highlighting this chemokine–receptor pair as a novel target for therapeutic intervention in AD.