bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender disparity and stigma experience of patients with chronic hepatitis B virus infection: A prospective cross-sectional study from a hospital in Nigeria
Authors: Adekanle Olusegun , Komolafe Akinwumi Oluwole , Ijarotimi Oluwasegun , Olowookere Anu Samuel , Ndububa Dennis A
Published: September 2022

Backgound

Hepatitis B virus (HBV) infected persons often suffer stigma. Stigma can come from the society or be self-induced. This study assessed the gender differences and stigma experience of patients with HBV.

Methods

Prospective cross-sectional design with a qualitative element using a pretested interviewer administered questionnaire and an in-depth oral interview of HBV infected patients. Quantitative data obtained were entered into SPSS version 20 and analyzed using simple descriptive and inferential statistics, while content analysis was used for the qualitative data.

Results

Total of 242 respondents answered the quantitative questionnaire. There were 142(58.7%) males and 100 (41.3%) females; age range was 18–72 years with mean (SD) of 35.4(10.7) years. Overall stigma rate was 23.1%. Stigma resulted from a positive HBsAg test, and the experience was unaffected by other markers of HBV infection. Stigma was higher in the domain of disease transmission for both single and married respondents and was particularly higher among males than females. Stigma among females affected pre-marital engagements and also caused marital disharmony among married respondents. In-depth oral interview of 23 HBV infected respondents revealed that many exhibited self-stigma, had wrong knowledge of HBV infection modes, complications, and interpretation of HBV internet information which aggravated stigma reactions.

Conclusions

Stigma of HBV is high and majorly in the domain of disease transmission. It is higher in males than females. Enlightenment campaign targeting singles and married couples and HBV infection modes is advocated.
Mechanistic Prediction of Chinese Herb Compound (Zhi Zhu Ma Ren Pill) in the Treatment of Constipation Using Network Pharmacology and Molecular Docking
Authors: Wen Yong , Zhan Yu , Tang Shiyu , Kang Jian , Wu Rong , Tang Xuegui
Published: September 2022

Background: Constipation is one of the most prevalent chronic gastrointestinal diseases. Notably, previous studies have demonstrated that Chinese herbal compounds may exert effects on constipation. The present study aimed to predict the mechanisms underlying the effects of Zhi Zhu Ma Ren Pill (ZZMRP), which includes Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, Fructus Cannabis, Paeonia lactiflora and Radix Asteris in the treatment of constipation, using network pharmacology and molecular docking. Methods: The components and target information of ZZMRP were accessed using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform, and the associated targets of constipation were obtained from the GeneCards, Disgenet, Online Mendelian Inheritance in Man, DrugBANK and Therapeutic Target Database databases. The major targets were subsequently selected using a Venn diagram and network topology analysis, which was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to authenticate the binding activity between active components and core targets. Results: A total of 44 active components, 249 targets of ZZMRP and 1501 targets associated with constipation were acquired. A total of 122 intersection targets were discovered between ZZMRP and constipation. Subsequently, 18 key targets were authenticated, including tumor protein 53, RAC-alpha serine/threonine-protein kinase, JUN and caspase-3. GO and KEGG pathway enrichment analysis indicated that mitogen-activated protein kinase, tumor necrosis factor, and phosphoinositide 3-kinase/protein kinase B signaling pathways may be involved in the treatment of constipation using ZZMRP. Molecular docking suggested that quercetin, kaempferol, and luteolin exhibited high binding affinities with several of the primary targets. Conclusions: The active components, core targets, and signaling pathways of ZZMRP in the treatment of constipation were predicted, which may be applicable to the development of treatments for constipation and application of ZZMRP.
Fertility desire of HIV-positive men and women in public health hospitals
Authors: Tilahun Wassie Semahegn , Marye Yimam Shimels , Birhanu Fentaw Tesfaye
Published: September 2022

Objective:

Despite the increased emphasis on antiretroviral therapy and other healthcare services for HIV-infected individuals, issues of fertility desire have received relatively little attention. In particular, little is known about actual fertility desire and determinants of fertility desires among HIV-infected women and men receiving antiretroviral therapy.

Methods:

A cross-sectional study was conducted among HIV-positive individuals in public health hospitals of Addis Ababa City from 1 October to 30 November 2021. A pretested structured questionnaire was used to collect the data with a consecutive sampling technique. EpiData 4.6.2 and SPSS 25 were used for data entry and analysis. Bivariate and multivariable logistic regression analyses were done to identify factors associated with fertility desire. An adjusted odds ratio with a 95% confidence interval was computed for data interpretation. A p value of ⩽0.05 was considered to be statistically significant.

Result:

Among 400 participants, 55% (95% confidence interval = 50%, 60%) have future fertility desire. Factors like age less than 35 years (adjusted odds ratio = 24.03, 95% confidence interval = 9.99, 57.83), a secondary education level (adjusted odds ratio = 2.78, 95% confidence interval = 1.21, 6.40), being married (adjusted odds ratio = 2.89, 95% confidence interval = 1.39, 5.99), being employed (adjusted odds ratio = 3.12, 95% confidence interval = 1.56, 6.24), being diagnosed with HIV in the past 1 year (adjusted odds ratio = 4.02, 95% confidence interval 2.07, 7.80) or past 2–4 years (adjusted odds ratio = 9.80, 95% confidence interval = 3.89, 26.02) have a significant association with future fertility desire. Respondents using contraceptives were 90.9% less likely to have future fertility desire (adjusted odds ratio = 0.09, 95% confidence interval = 0.05, 0.18).

Conclusion:

The magnitude of future fertility desire was founded high. Further research on this topic should include qualitative studies to provide a deeper understanding of people living with HIV fertility desires.
Subacute necrotizing fasciitis of the posterior neck disguised as a herpes zoster infection: A case report
Authors: Wright Samantha-Jo , Khedr Anwar , Bartlett Brian N , Jama Abbas B , Mushtaq Hisham , Wahab Abdul , Khan Syed Anjum
Published: September 2022

Necrotizing fasciitis is a rare soft tissue infection characterized by a rapidly spreading infection of the subcutaneous tissue. Early diagnosis is important as it requires immediate and complete debridement of infected tissues and antibiotic therapy. Necrotizing fasciitis usually involves the extremities, abdomen, and groin, but rarely involves the head and neck. Necrotizing fasciitis has an aggressive course; however, in rare cases, it can present in a subacute indolent form which can be misdiagnosed as other cutaneous diseases. Our case is a unique presentation of subacute necrotizing fasciitis of the posterior neck, which was initially diagnosed as a herpes zoster infection, in a patient with undiagnosed diabetes mellitus, which was complicated with diabetic ketoacidosis and sepsis.
Tunneled hemodialysis catheter insertion: Above, within, or below the right atrium—Where is the tip?
Authors: Auer Jonas , Braun Joachim , Lenk Julian , Gollrad Johannes , Ro Sa-Ra , Hamm Bernd , de Bucourt Maximilian
Published: September 2022

Background

One major challenge when inserting a tunneled, cuffed central venous catheter (CVC) for hemodialysis under fluoroscopy is to accurately place the catheter tip by assessing its position in relation to the cardiac silhouette to approximate the right atrium (RA).

Purpose

To investigate whether a weighted mean calculated from published results for two two-dimensional landmark reference distances may be useful in assessing CVC tip positions in relation to the RA.

Material and Methods

Central venous catheter tip positions attained under fluoroscopic imaging during insertion using the cardiac silhouette as approximation were retrospectively related to two reference distances (carina to cranial RA border and craniocaudal RA extent), which were used to group catheter tip locations above (1), within (2), or below (3) the RA (henceforth referred to as landmark technique approximation, LTA). The LTA-derived catheter tip locations were validated by correlation with postinterventional computed tomography (CT) datasets acquired shortly after implantation (if available).

Results

Based on LTA, 45 catheter tips (10.6%) were above, 179 (42.2%) within, and 200 (47.2%) below the RA. Postinterventional CT ( n = 57; 13.4%) visualized 26.3% above, 66.7% within, and 7.0% below the RA.

Conclusion

The LTA reference distances appear to lead to a rather low categorization of the CVC tips, or the tips have been placed rather low in the study population. Validation using postinterventional CT indicated an underestimation of the RA in the LTA. Patient characteristics with a higher risk of false estimation through LTA have been defined.
Management and Scheduling of Spine Surgery in a Level 1 Trauma Center in the Setting of the COVID-19 Pandemic: Feasibility and Considerations for Reimplementation of Elective Spine Surgery
Authors: Crawford Zachary , Elson Nora C. , Kanhere Arun , Thomson Cameron , Sabbagh Ramsey , Nasser Rani , Guanciale Anthony F.
Published: September 2022

Introduction

Determination of what constitutes necessary surgery in the setting of acute hospital resource strain during the COVID-19 pandemic is an unprecedented challenge for healthcare systems. Over the past two years during the COVID-19 pandemic, there have been many changes in reviews of medically necessary spine surgery. There continues to be no clear guidelines on recommendations and further discussion is necessary to continue to provide appropriate and high-level care during future pandemics.

Significance

This review critically appraises and evaluates current barriers to medically necessary spine surgery during the COVID-19 pandemic and evaluates future decision making to maintain spine surgery during future pandemics or limitations in medical care.

Results

Multiple studies included in this review have shown that while various orthopaedic surgeries may be considered elective, medically necessary spine surgery will need to continue during settings of limited medical care. This review discussed multiple methods and recommendations to limit transmission of virus from patients to providers and providers to patients.

Conclusion

Continued medically necessary spine surgery in the setting of the COVID-19 pandemic and future pandemics should continue while limiting risk of transmission to continue providing high-level medical care and allowing hospitals to maintain financial responsibility.
Job Insecurity, Financial Threat, and Mental Health in the COVID-19 Context: The Moderating Role of the Support Network
Authors: Alcover Carlos-María , Salgado Sergio , Nazar Gabriela , Ramírez-Vielma Raúl , González-Suhr Carolina
Published: September 2022

The aim of this study is two-fold. Firstly, to analyze the relations between the perceptions of job insecurity and financial threat and general mental health during the early stage of the COVID-19 pandemic. And secondly, to identify the potential moderating effect of the support network. We carried out a cross-sectional study on a non-probabilistic sample aimed at a general Chilean adult population to analyze this. The results show that both job insecurity ( β = −.183; p < .001) and financial threat ( β = −.309; p < .001) are associated with a decline in general mental health. Likewise, the results indicated a positive relationship between support network and general mental health in the two models analyzed ( βs = 0.322 and 0.182; ps < 0.001 and = 0.012, respectively), as well as a moderating effect of support network on the relationship between job insecurity and decreased general mental health ( β = .232; p < .001). The theoretical and applied scope of these findings are analyzed, and their challenges and limitations are discussed.
Minimal Pain Tumescent Local Anesthesia Injection for Wide Awake Modified Radical Mastectomy
Authors: Pandya Sameer M. , Njuguna Tabitha , Maina Carol , Jani Pankaj , Lalonde Donald
Published: September 2022

The advent of minimal pain tumescent local anesthesia injection has improved patient safety by eliminating the need for sedation for many wide awake operations, especially in patients with significant medical comorbidities. Modified radical mastectomy (MRM) for breast cancer is commonly performed under general anesthesia as it requires the dissection of the entire breast and an ipsilateral axillary lymph node dissection (ALND). General anesthesia has been shown to have a high risk in patients with severe medical comorbidities. We present a case of a 78-year-old male patient who was diagnosed with invasive ductal breast carcinoma, cardiac failure, and other metabolic abnormalities. Taking his comorbidities into account, we performed a wide awake MRM and ALND after tumescent minimal pain local anesthesia injection. The patient experienced the successful procedure safely with minimal discomfort.
The Role of Circulating Aβ Seeds in the Progression of Cerebral Amyloidosis
Authors: Gamez Nazaret , Morales Rodrigo
Published: September 2022

While understudied, it is suspected that peripheral Aβ peptides affect Alzheimer’s disease (AD)-associated pathological changes in the brain. The peripheral sink hypothesis postulates that the central and peripheral pools of Aβ co-exist in equilibrium. As such, cerebral amyloid levels may be modulated by intervening circulating Aβ. In this commentary, we discuss relevant literature supporting the potential role of peripheral Aβ in exacerbating brain amyloidosis in both humans and mouse models of AD. Moreover, we highlight the need to further understand the mechanisms by which circulating Aβ peptides may reach the brain and contribute to neuropathology. Finally, we discuss the implications of targeting peripheral Aβ as a therapeutic approach in treating AD.
Introduction to a How I Treat series on management of high-risk patients following allogeneic transplant
Authors: Zeiser Robert
Published: September 2022

Edited by Associate Editor Robert Zeiser, this How I Treat series focuses on post–allogeneic transplant management of high-risk patients. These patients are at risk for relapse of malignancy and severe graft-versus-host disease (GVHD). Two articles in the series discuss adoptive cellular immunotherapy and maintenance therapy to preempt relapse of acute myeloid leukemia. The third article addresses the state of the art for preventing GVHD in this subset of stem cell transplant recipients.
Driving Environment Uncertainty-Aware Motion Planning for Autonomous Vehicles
Authors: Tang Xiaolin , Yang Kai , Wang Hong , Yu Wenhao , Yang Xin , Liu Teng , Li Jun
Published: September 2022

Autonomous vehicles require safe motion planning in uncertain environments, which are largely caused by surrounding vehicles. In this paper, a driving environment uncertainty-aware motion planning framework is proposed to lower the risk of position uncertainty of surrounding vehicles with considering the risk of rollover. First, a 4-degree of freedom vehicle dynamics model, and a rollover risk index are introduced. Besides, the uncertainty of surrounding vehicles' position is processed and propagated based on the Extended Kalman Filter method. Then, the uncertainty potential field is established to handle the position uncertainty of autonomous vehicles. In addition, the model predictive controller is designed as the motion planning framework which accounts for the rollover risk, the position uncertainty of the surrounding vehicles, and vehicle dynamic constraints of autonomous vehicles. Furthermore, two edge cases, the cut-in scenario, and merging scenario are designed. Finally, the safety, effectiveness, and real-time performance of the proposed motion planning framework are demonstrated by employing a hardware-in-the-loop experiment bench.
Exploring the relationship between age and prognosis in glioma: rethinking current age stratification
Authors: Jia Zetian , Li Xiaohui , Yan Yaqi , Shen Xuxuan , Wang Jiuxin , Yang He , Liu Shuo , Han Chengxi , Hu Yuhua
Published: September 2022

Background

The age of glioma plays a unique role in prognosis. We hypothesized that age is not positively correlated with survival prognosis and explored its exact relationship.

Methods

Glioma was identified from the SEER database (between 2000 and 2018). A multivariate Cox proportional regression model and restricted cubic spline (RCS) plot were used to assess the relationship between age and prognosis.

Results

A total of 66465 patients with glioma were included. Hazard ratios (HR) for ten-year by age: 0–9 years, HR 1.06 (0.93–1.20); 10–19 years: reference; 20–29 years, HR 0.90 (0.82–1.00); 30–39 years, HR 1.14 (1.04–1.25); 40–49 years, HR 2.09 (1.91–2.28); 50–59 years, HR 3.48 (3.19–3.79); 60–69 years, HR 4.91 (4.51–5.35);70–79 years, HR 7.95 (7.29–8.66); 80–84 years, HR 12.85 (11.74–14.06). After adjusting for covariates, the prognosis was not positively correlated with age. The smooth curve of RCS revealed this non-linear relationship: HR increased to 10 years first, decreased to 23 years, reached its lowest point, and became J-shaped.

Conclusion

The relationship between age and glioma prognosis is non-linear. These results challenge the applicability of current age groupings for gliomas and advocate the consideration of individualized treatment guided by precise age.
Effectiveness of combined extracorporeal shock-wave therapy and hyaluronic acid injections for patients with shoulder pain due to rotator cuff tendinopathy: a person-centered approach with a focus on gender differences to treatment response
Authors: Pellegrino Raffaello , Di Iorio Angelo , Brindisino Fabrizio , Paolucci Teresa , Moretti Antimo , Iolascon Giovanni
Published: September 2022

Background

Rotator cuff (RC) tendinopathy is a common shoulder pain condition. Extracorporeal shockwave therapy (ESWT) and hyaluronic acid peritendinous injection are viable treatment options for RC tendinopathy.

The aim of this study is to evaluate the response in two different therapeutic rehabilitative approaches, the combined treatment ESWT plus hyaluronic acid injections (E + Hy) compared to ESWT alone (ESWT-al), in a cohort of patients with RC tendinopathy according to gender differences.

Methods

This is a retrospective longitudinal cohort study of patients with painful RC tendinopathy. Patients that had received a clinical evaluation, a shoulder ultra sound examination, as well as the Shoulder Pain and Disability Index (SPADI) questionnaire, and the Numerical Rating Scale (NRS) for pain at baseline, 1-month (T1) and 2-month follow-ups (T2) were included.

Results

Medical records of 53 patients were analyzed. In the comparison between baseline to T1 and similarly from baseline to T2, a statistically significant reduction has been reported in the NRS (p < 0.001) and in the SPADI (p < 0.001) in the entire study group. At T1, patients in the E + Hy compared to ESWT-al group, showed a slight but statistically significant reductions in both NRS and SPADI score, while these changes were more evident at T2 (p < 0.001). Interestingly, a gender dimorphism in NRS and in SPADI was found, with female patients that apparently responded better to the combined E + Hy compared to ESWT-al approach.

Conclusion

This retrospective cohort study suggests that the combination of ESWT plus HyA injections seems to be more effective than ESWT alone in RC tendinopathy in both genders. Moreover, in ESWT alone treatment, male patients reported better outcomes compared to females. However, further randomized controlled trials should be structured to confirm and enforce these conclusions.
Clinical, metabolic, and immunological characterisation of adult Ugandan patients with new-onset diabetes and low vitamin D status
Authors: Kibirige Davis , Sekitoleko Isaac , Balungi Priscilla , Kyosiimire-Lugemwa Jacqueline , Lumu William
Published: September 2022

Background

Low vitamin D concentrations are associated with metabolic derangements, notably insulin resistance and pancreatic beta-cell dysfunction in Caucasian populations. Studies on its association with the clinical, metabolic, and immunologic characteristics in black African adult populations with new-onset diabetes are limited. This study aimed to describe the clinical, metabolic, and immunologic characteristics of a black Ugandan adult population with recently diagnosed diabetes and hypovitaminosis D.

Methods

Serum vitamin D concentrations were measured in 327 participants with recently diagnosed diabetes. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were defined as serum 25 hydroxyvitamin D levels of < 20 ng/ml, 21–29 ng/ml, and ≥ 30 ng/ml, respectively.

Results

The median (IQR) age, glycated haemoglobin, and serum vitamin D concentration of the participants were 48 years (39–58), 11% (8–13) or 96 mmol/mol (67–115), and 24 ng/ml (18–30), respectively. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were noted in 105 participants (32.1%), 140 participants (42.8%), and 82 participants (25.1%), respectively.

Compared with those having normal serum vitamin D levels, participants with vitamin D deficiency and insufficiency had higher circulating concentrations of interleukin (IL) 6 (29 [16–45] pg/ml, 23 [14–40] pg/ml vs 18 [14–32] pg/ml, p = 0.01), and IL-8 (24 [86–655] pg/ml, 207 [81–853] pg/ml vs 98 [67–224], p = 0.03). No statistically significant differences were noted in the markers of body adiposity, insulin resistance, and pancreatic beta-cell function between both groups.

Conclusion

Vitamin D deficiency and insufficiency were highly prevalent in our study population and were associated with increased circulating concentrations of pro-inflammatory cytokines. The absence of an association between pancreatic beta-cell function, insulin resistance, and low vitamin D status may indicate that the latter does not play a significant role in the pathogenesis of type 2 diabetes in our adult Ugandan population.
Practicing traditional Chinese medicine in the COVID-19 pandemic in Switzerland – an exploratory study
Authors: Bourqui Angélique , Rodondi Pierre-Yves , El May Emna , Dubois Julie
Published: September 2022

Background

To curb the spread of the first wave of the COVID-19 pandemic, the Swiss government declared a state of health emergency and ordered a legal restriction concerning the opening of healthcare institutions. In this study, we aimed to assess the proportion of traditional Chinese medicine (TCM) physicians and therapists who consulted patients regarding COVID-19 during the first wave of the pandemic in 2020 in Switzerland, as well as the extent to which COVID-19 affected their practices during the same period.

Methods

A retrospective study was performed by using a questionnaire from January to April 2021 among a random sample of TCM physicians and therapists based in Switzerland. The survey included questions on demographic characteristics, opening status of practices, channels of communication used for the medical encounter, and experience in managing the prevention, acute, and recovery stages of COVID-19 infection.

Results

Among the 320 participants, 76% consulted a patient regarding COVID-19 at least once. Overall, physicians and therapists consulted more patients during recovery (76.3%) and prevention (67.8%) than during the acute stage (19.8%) of the disease. Acupuncture was the most frequently used technique among TCM therapists and physicians consulting for prevention (80.4%) and recovery (92.5%), whereas Chinese pharmacopeia was the most used technique among those consulting for the acute stage (59.3%). Of those who closed their practices from March to April 2020 but kept consulting, telephone (30.4%) and home visits (29.9%) were the two principal methods of consultation.

Conclusions

The restriction concerning the opening of practices induced a loss of the health workforce, especially among TCM therapists. Nonetheless, TCM therapists and physicians consulted patients regarding COVID-19, especially during the recovery stage. As there is a demand for the use of TCM in the context of COVID-19, it raises the need for a better consideration of TCM in the Swiss health care system.
Design and validation of recombinant protein standards for quantitative Western blot analysis of cannabinoid CB1 receptor density in cell membranes: an alternative to radioligand binding methods
Authors: Saumell-Esnaola Miquel , Elejaga-Jimeno Ainhoa , Echeazarra Leyre , Borrega-Román Leire , Barrondo Sergio , López de Jesús Maider , González-Burguera Imanol , Gómez-Caballero Alberto , Goicolea María Aranzazu , Sallés Joan , García del Caño Gontzal
Published: September 2022

Background

Replacement of radioligand binding assays with antibody-antigen interaction-based approaches for quantitative analysis of G protein-coupled receptor (GPCR) levels requires the use of purified protein standards containing the antigen. GPCRs in general and cannabinoid CB1receptor in particular show a progressive tendency to aggregate and precipitate in aqueous solution outside of their biological context due to the low solubility that the hydrophobic nature imprinted by their seven transmembrane domains. This renders full-length recombinant GPCRs useless for analytical purposes, a problem that can be overcome by engineering soluble recombinant fragments of the receptor containing the antigen.

Results

Here we generated highly soluble and stable recombinant protein constructs GST-CB1414–472and GST-CB1414-442containing much of the human CB1receptor C-terminal tail for use as standard and negative control, respectively, in quantitative Western blot analysis of CB1receptor expression on crude synaptosomes of the adult rat brain cortex. To this end we used three different antibodies, all raised against a peptide comprising the C-terminal residues 443–473 of the mouse CB1receptor that corresponds to residues 442–472 in the human homolog. Estimated values of CB1receptor density obtained by quantitative Western blot were of the same order of magnitude but slightly higher than values obtained by the radioligand saturation binding assay.

Conclusions

Collectively, here we provide a suitable Western blot-based design as a simple, cost-effective and radioactivity-free alternative for the quantitative analysis of CB1receptor expression, and potentially of any GPCR, in a variety of biological samples. The discrepancies between the results obtained by quantitative Western blot and radioligand saturation binding techniques are discussed in the context of their particular theoretical bases and methodological constraints.
Strategies for efficient production of recombinant proteins in Escherichia coli: alleviating the host burden and enhancing protein activity
Authors: Zhang Zi-Xu , Nong Fang-Tong , Wang Yu-Zhou , Yan Chun-Xiao , Gu Yang , Song Ping , Sun Xiao-Man
Published: September 2022

Escherichia coli, one of the most efficient expression hosts for recombinant proteins (RPs), is widely used in chemical, medical, food and other industries. However, conventional expression strains are unable to effectively express proteins with complex structures or toxicity. The key to solving this problem is to alleviate the host burden associated with protein overproduction and to enhance the ability to accurately fold and modify RPs at high expression levels. Here, we summarize the recently developed optimization strategies for the high-level production of RPs from the two aspects of host burden and protein activity. The aim is to maximize the ability of researchers to quickly select an appropriate optimization strategy for improving the production of RPs.
A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment
Authors: Xie Xiaoting , Wei Jiemao , Zhang Bin , Xiong Wei , He Zhiyi , Zhang Yayun , Gao Chenghao , Zhao Yuandi , Liu Bo
Published: September 2022

Background

Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment.

Methods

In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility.

Results

The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery.

Conclusion

This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.

Graphical Abstract
Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis
Authors: Xiao Xiaoxiong , Chen Min , Zhang Yuchen , Li Liang , Peng Ying , Li Junyu , Zhou Wenhu
Published: September 2022

Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H2O2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.
Circ_0136666 aggravates osteosarcoma development through mediating miR-1244/CEP55 axis
Authors: Gao Xiang , Xu Nanwei , Miao Kaisong , Huang Gao , Huang Yong
Published: September 2022

Background

Accumulating articles demonstrate that circular RNAs play pivotal functions in tumorigenesis. However, the working mechanism of circ_0136666 in osteosarcoma (OS) progression remains to be further clarified.

Methods

Real time-quantitative polymerase chain reaction and western blot assay were applied to determine RNA and protein expression, respectively. Cell proliferation was assessed by 5-Ethynyl-2′-deoxyuridine assay and colony formation assay. Transwell assays were carried out to assess cell migration and invasion abilities. Flow cytometry was performed to analyze cell apoptosis. Cell glycolysis was evaluated by analyzing the uptake of glucose and the production of lactate using the corresponding kits. Dual-luciferase reporter assay and biotinylated RNA-pull down assay were performed to confirm the target interaction between microRNA-1244 (miR-1244) and circ_0136666 or centrosomal protein 55 (CEP55). Xenograft tumor model was utilized to explore the role of circ_0136666 in tumor growth in vivo.

Results

Circ_0136666 expression was prominently elevated in OS tissues and cell lines. Circ_0136666 absence restrained the proliferation, migration, invasion and glycolytic metabolism and promoted the apoptosis of OS cells. Circ_0136666 negatively regulated miR-1244 expression by binding to it in OS cells. MiR-1244 overexpression suppressed the malignant behaviors of OS cells. CEP55 was a target of miR-1244 in OS cells. Circ_0136666 positively regulated CEP55 expression partly by sequestering miR-1244 in OS cells. CEP55 overexpression largely reversed circ_0136666 silencing-mediated influences in OS cells. Circ_0136666 silencing significantly suppressed tumor growth in vivo.

Conclusion

Circ_0136666 silencing inhibited OS progression partly by targeting miR-1244/CEP55 signaling. Silencing circ_0136666 and CEP55 or restoring miR-1244 level might be a potential therapeutic strategy for OS.
A pregnant women with history of hashimoto's thyroiditis diagnosed with Kikuchi-Fujimoto disease: the first case report
Authors: Bazkke Bashar , Osman Joli , Shahrour Mohammad , Ziadeh Mohammad , Haji Mohamad Aya , Mouhandes Mohamed Imad Eddin , Niazi Ammar
Published: September 2022

Background

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting disorder characterized by regional lymphadenopathy. Clinical symptoms range from mild fever and tenderness to upper respiratory syndrome. A few cases have been observed during pregnancy or Hashimoto's disease. What we describe here is the first observed case of KFD in a pregnant woman with a history of Hashimoto's thyroiditis.

Case presentation

A 36-year-old woman presented to Aleppo University Hospital during the 13th week of gestation with a painful cervical node on the right side of her neck. The patient's previous medical history confirmed Hashimoto's thyroiditis for several years. After histopathological examinations and radiological investigations, she was diagnosed with Kikuchi-Fujimoto disease and treated with corticosteroids. Although the patient did not adhere to the treatment very well due to her concerns for the fetus, the clinical picture improved after delivery. The patient now is on follow-up and continuing the current treatment with corticosteroids.

Conclusions

Further investigations need to be conducted to understand the possible autoimmune etiology of KFD when it is associated with Hashimoto's thyroiditis disease. It is also necessary to understand the relationship between this disease and pregnancy.
RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma
Authors: Tu Qiu , Liu Xiuyun , Yao Xiaoqing , Li Ruixue , Liu Gaojing , Jiang Honglv , Li Kaiqin , Chen Qiongfang , Huang Xiaoyan , Chang Qing , Xu Guoqiang , Zhu Hong , Shi Peng , Zhao Bo
Published: September 2022

Background

Severe hypoxia is a prominent character of pancreatic ductal adenocarcinoma (PDAC) microenvironment. In the process of gemcitabine based chemotherapy, PDAC cells are insulted from replication stresses co-induced by hypoxia and gemcitabine. However, PDAC cells get outstanding abilities to resist to such harsh conditions and keep proliferating, causing a major obstacle for current therapy. RETSAT (Retinol Saturase) is defined as a hypoxia convergent gene recently, with high expression in PDAC hypoxic sectors. This study aimed to explore the roles of RETSAT in replication stress resistance and hypoxia adaptation in PDAC cells, and decipher the underlying mechanism.

Methods

The expression of RETSAT was examined in TCGA (The Cancer Genome Atlas), human pancreatic cancer microarray, clinical specimens and cell lines. Functions of RETSAT were studied by means of DNA fiber assay and comet assay in monolayer cultured PDAC cell lines, three dimensional spheroids, patient derived organoids and cell derived xenograft mouse models. Mechanism was investigated by using iPOND (isolate proteins on nascent DNA) combined with mass spectrometry, immunoprecipitation and immunoblotting.

Results

First, we found the converse relationship of RETSAT expression and PDAC chemotherapy. That is, PDAC patients with high RETSAT expression correlated with poor survival, while ones holding low RETSAT expression were benefitted more in Gemcitabine based chemotherapy. Second, we identified RETSAT as a novel replication fork associated protein. HIF-1α signaling promotes RETSAT expression under hypoxia. Functionally, RETSAT promoted fork restarting under replication stress and maintained genomic stability. Third, we uncovered the interaction of RETSAT and R-loop unwinding helicase DDX39B. RETSAT detained DDX39B on forks to resolve R-loops, through which avoided fork damage and CHK1 initiated apoptosis. Targeting DDX39B using chemical CCT018159 sensitized PDAC cells and organoids to gemcitabine induced apoptosis, highlighting the synergetic application of CCT018159 and gemcitabine in PDAC chemotherapy.

Conclusions

This study identified RETSAT as a novel replication fork protein, which functions through interacting with DDX39B mediated R-loop clearance to promote fork restarting, leading to cellular resistance to replication stresses co-induced by tumor environmental hypoxia and gemcitabine in pancreatic ductal adenocarcinoma.
Efficacy of bednets with dual insecticide-treated netting (Interceptor® G2) on side and roof panels against Anopheles arabiensis in north-eastern Tanzania
Authors: Mbewe Njelembo J. , Rowland Mark W. , Snetselaar Janneke , Azizi Salum , Small Graham , Nimmo Derric D. , Mosha Franklin W.
Published: September 2022

Background

Optimising insecticide use and managing insecticide resistance are important to sustain gains against malaria using long-lasting insecticidal nets (LLINs). Restricting insecticides to where mosquitoes are most likely to make multiple contacts could reduce the quantity of insecticide needed to treat the nets. Previous studies have shown that nets partially treated with a pyrethroid insecticide had equivalent mortality compared to a fully treated net. This study compared the efficacy of: (i) whole Interceptor® G2 nets (IG2; a dual-active LLIN containing alpha-cypermethrin and chlorfenapyr), (ii) nets with roof panels made of IG2 netting, (iii) nets with side panels made of IG2 netting and (iv) whole untreated nets as test nets.

Methods

The study was conducted in cow-baited experimental huts, Moshi Tanzania, using a four-arm Latin square design. Test nets had 30 holes cut in panels to simulate a typical net after 2–3 year use. The trial data were analysed using generalized linear models with mortality, blood-feeding, exophily and deterrence against wild free-flying Anopheles arabiensis as outcomes and test nets as predictors.

Results

Mortality was significantly higher in the nets with roof IG2 [27%, P = 0.001, odds ratio (OR) = 51.0, 95% CI = 4.8–546.2), side IG2 (44%, P < 0.001, OR = 137.6, 95% CI = 12.2–1553.2] and whole IG2 (53%, P < 0.001, OR = 223.0, 95% CI = 19.07–2606.0) nettings than the untreated (1%) nets. Mortality was also significantly higher in the whole IG2 net compared to the net with roof IG2 netting (P = 0.009, OR = 4.4, 95% CI = 1.4–13.3). Blood feeding was 22% in untreated, 10% in roof IG2, 14% in side IG2 and 19% in whole IG2 nets. Exiting was 92% in untreated, 89% in roof IG2, 97% in side IG2 and 94% whole IG2 nets.

Conclusion

The results show that although the roof-treated IG2 net induced greater mortality compared to untreated nets, its efficacy was reduced compared to whole IG2 nets. Therefore, there was no benefit to be gained from restricting dual-active ingredient IG2 netting to the roof of nets.

Graphical Abstract
A longitudinal study on quality of life along the spectrum of Alzheimer’s disease
Authors: Mank Arenda , Rijnhart Judith J. M. , van Maurik Ingrid S. , Jönsson Linus , Handels Ron , Bakker Els D. , Teunissen Charlotte E. , van Berckel Bart N. M. , van Harten Argonde C. , Berkhof Johannes , van der Flier Wiesje M.
Published: September 2022

Background

Quality of life (QoL) is an important outcome from the perspective of patients and their caregivers, in both dementia and pre-dementia stages. Yet, little is known about the long-term changes in QoL over time. We aimed to compare the trajectories of QoL between amyloid-positive and amyloid-negative SCD or MCI patients and to evaluate QoL trajectories along the Alzheimer’s disease (AD) continuum of cognitively normal to dementia.

Methods

We included longitudinal data of 447 subjective cognitive decline (SCD), 276 mild cognitive impairment (MCI), and 417 AD dementia patients from the Amsterdam Dementia Cohort. We compared QoL trajectories (EQ-5D and visual analog scale (VAS)) between (1) amyloid-positive and amyloid-negative SCD or MCI patients and (2) amyloid-positive SCD, MCI, and dementia patients with linear mixed-effect models. The models were adjusted for age, sex, Charlson Comorbidity Index (CCI), education, and EQ-5D scale (3 or 5 level).

Results

In SCD, amyloid-positive participants had a higher VAS at baseline but showed a steeper decline over time in EQ-5D and VAS than amyloid-negative participants. Also, in MCI, amyloid-positive patients had higher QoL at baseline but subsequently showed a steeper decline in QoL over time compared to amyloid-negative patients. When we compared amyloid-positive patients along the Alzheimer continuum, we found no difference between SCD, MCI, or dementia in baseline QoL, but QoL decreased at a faster rate in the dementia stage compared with the of SCD and MCI stages.

Conclusions

QoL decreased at a faster rate over time in amyloid-positive SCD or MCI patients than amyloid-negative patients. QoL decreases over time along the entire AD continuum of SCD, MCI and dementia, with the strongest decrease in dementia patients. Knowledge of QoL trajectories is essential for the future evaluation of treatments in AD.
Patterns and drivers of tree carbon stocks in Kashmir Himalayan forests: implications for climate change mitigation
Authors: Dar Ashaq Ahmad , Parthasarathy Narayanaswamy
Published: September 2022

Background

Temperate forests are major carbon sinks because of their high storage potential and low decomposition processes. We quantified tree carbon (TC) storage from 143 plots distributed across three major forest types of Kashmir Himalaya, relative to differences in ecological factors. Combined regression and Random Forest (RF) analysis were used to examine the distribution of TC stock along ecological gradients and recognize the role of driving factors on TC stocks.

Results

Among the three forest types, sub-alpine (SA) forest was the primary TC sink, accounting for 228.73 t ha−1 of carbon, followed by mixed conifer (MC; 181.29 t C ha−1) and blue pine (BP; 133.04 t C ha−1) forests. The distribution of TC stocks among the three forest types differed significantly (χ2 = 18.87;P = 0.000). Relative carbon stock analysis demonstrated thatAbies pindrowandPinus wallichianaaccounted 91% of TC stocks across the landscape. Basal area, mean diameter at breast height (DBH), elevation, disturbance and precipitation had significant effects on TC stocks in bivariate regression models. The RF model explained 86% of the variation; basal area interpreted 30.15%, followed by mean DBH (17.96%), disturbance complex (10.64%), precipitation (8.00%) and elevation (7.34%).

Conclusions

Kashmir Himalayan forests are significant carbon sinks as they store a substantial quantum of carbon in trees. Forest carbon, an essential climatic indicator, is determined by a complex interaction of other ecological variables, particularly stand structural features. The study provides insights into the role of these natural forests in climate change mitigation and in REDD+/national commitments to offset the carbon.
Can information and communication technology and institutional quality help mitigate climate change in E7 economies? An environmental Kuznets curve extension
Authors: Gyamfi Bright Akwasi , Ampomah Asiedu B. , Bekun Festus V. , Asongu Simplice A.
Published: September 2022

Understanding the role of information communication and technology (ICT) in environmental issues stemming from extensive energy consumption and carbon dioxide emission in the process of economic development is worthwhile both from policy and scholarly fronts. Motivated on this premise, the study contributes to the rising studies associated with the roles of economic growth, institutional quality and information and communication technology (ICT) have on CO2 emission in the framework of the 21st Conference of the Parties (COP21) on climate convention in Paris. Obtaining data from the emerging industrialized seven (E7) economies (China, India, Indonesia, Russia, Mexico, Brazil and Turkey) covering annual frequency from 1995 to 2016 for our analysis achieved significant outcome. From the empirical analysis, economic globalization and renewable energy consumption both reduce CO2 emissions while ICT, institutional quality and fossil fuel contribute to the degradation of the environment. This study affirms the presence of an environmental Kuznets curve (EKC) phenomenon which shows an invented U-shaped curve within the E7 economies. On the causality front, both income and its square have a feedback causal relationship with carbon emissions while economic globalization, institutional quality, ICT and clean energy all have a one-way directional causal relationship with CO2 emissions. Conclusively, the need to reduce environmental degradation activities should be pursued by the blocs such as tree planting activities to mitigate the effect of deforestation. Furthermore, the bloc should shift from the use of fossil-fuel and leverage on ICT to enhance the use of clean energy which is environmentally friendly.