bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-Related Stigma Shapes Research Participation for Youth Living With HIV in Kenya
Authors: Gillette Emma , Naanyu Violet , Nyandiko Winstone , Chory Ashley , Scanlon Michael , Aluoch Josephine , Koros Hillary , Ashimosi Celestine , Beigon Whitney , Munyoro Dennis , Lidweye Janet , Nyagaya Jack , DeLong Allison , Kantor Rami , Vreeman Rachel
Published: April 2023

Introduction: HIV stigma affects medication adherence, psychosocial outcomes, and clinical management for youth living with HIV (YLWH). We explored the impact of HIV stigma on research participation, to inform the ethical engagement of this vulnerable group. Methods: We interviewed 40 YLWH, 20 caregivers, and 39 subject matter experts (SMEs); transcripts were analyzed by HK and EG, with emerging themes confirmed by JA and AC. Results: All categories of participants identified the impacts of stigma on YLWH research participation, suggesting implementing privacy protections, considering recruitment locations carefully, and developing supportive relationships with YLWH. SMEs suggested that YLWH experience uniquely high risks from stigma due to the compounding effects of developmental challenges and transitionary life period. Accidental HIV disclosure and subsequent stigma were identified as a risk of research participation; some viewed the creation of community through research as a benefit. Conclusion: Participants provided insights into stigma-related considerations for research with YLWH, which may guide engagement protocols.
Repair of Ramp Lesions of the Medial Meniscus With ACL Reconstruction Can Better Restore Knee Stability: A Cadaveric Study
Authors: Li Shuzhen , Qin Yu , Wang Hao , Qin Zhi , Jiang Lianjian , Zhu Shengwang , Zeng Feng , Sun Ke , Wen Jieming , Yin Dong
Published: April 2023

Background:

Ramp lesions of the medial meniscus have an impact on joint stability in anterior cruciate ligament (ACL)–deficient knees, but the impact of lesion length and repair is unclear.

Purpose/Hypothesis:

The purpose of this cadaveric study was to evaluate the effect of medial meniscal ramp lesion repair on the biomechanics of ACL-deficient knee joints. It was hypothesized that (1) ramp lesions will increase the anterior tibial translation (ATT), internal rotation (IR), and external rotation (ER) in ACL-deficient knee joints; (2) increasing the length of the ramp lesion will further increase the ATT, IR, and ER; and (3) repairing the ramp lesion will reduce the ATT, IR, and ER after ACL reconstruction.

Study Design:

Controlled laboratory study.

Methods:

Included were 9 fresh-frozen cadaveric specimens (4 left knees, 5 right knees; 6 males and 3 females; mean age, 60 years [range, 40-73 years]). The specimens were tested on a biomechanical rig. Two external loading conditions were applied: a 134-N anterior tibial load and 5-N·m internal/external tibial torque with the knee at full extension and at 15°, 30°, 60°, and 90° of flexion. ATT was tracked via a high-speed video camera. The following knee states were tested: intact; ACL-deficient; ACL-deficient combined with a 5-, 10-, 15-, or 20 mm–long ramp lesion of the medial meniscus; ACL reconstruction; and ACL reconstruction combined with ramp lesion repair. The ATT, IR, and ER at all knee angles were analyzed by 1-way analysis of variance.

Results:

The ATT, IR, and ER were significantly increased after cutting of the ACL ( P < .05). The ATT, IR, and ER continued to increase when ACL deficiency was combined with ramp lesions of 5 to 20 mm in length ( P < .05). The ATT, IR, and ER significantly decreased after ACL reconstruction and ACL reconstruction combined with ramp lesion repair ( P < .05).

Conclusion:

The laxity of knees with ACL deficiency combined with a ramp lesion of the medial meniscus increased more obviously as the ramp lesion increased in length. In a cadaveric model, ACL reconstruction combined with ramp repair improved knee joint stability.
Injuries and Use of Safety Equipment in River Surfing
Authors: Wende Christina , Lambert Christophe , Hoeher Juergen , Balke Maurice
Published: April 2023

Background:

River surfing (also called “rapid surfing”) involves surfing on stationary waves that are artificially created or placed in rivers and is gaining popularity, especially among surfers in landlocked areas but also among athletes without experience in ocean surfing. Different wave setups, types of boards, and types of fins, as well as the use of safety equipment, can lead to overuse and injuries.

Purpose:

To analyze the incidence, mechanisms, and risk factors of river surfing–related injuries for different types of waves and to evaluate the usage and appropriateness of safety equipment.

Study Design:

Descriptive epidemiology study.

Methods:

An online survey was distributed via social media to river surfers in German-speaking countries to collect information on demographics, injury history for the previous 12 months, wave site attended, use of (safety) equipment, and health issues. The survey was accessible between November 2021 and February 2022.

Results:

A total of 213 participants completed the survey: 195 participants from Germany, 10 from Austria, 6 from Switzerland, and 2 from other countries. The mean age was 36 years (range, 11-73 years), 72% (n = 153) were male, and 10% (n = 22) took part in competitions. Overall, 60% (n = 128) of surfers experienced 741 surfing-related injuries over the previous 12 months. The most common mechanisms of injury were contact with the bottom of the pool/river (n = 75 [35%]), with the board (n = 65 [30%]), and with the fins (n = 57 [27%]). The most frequent injury types were contusions/bruises (n = 256), cuts/lacerations (n = 159), abrasions (n = 152), and overuse (n = 58). Injuries affected mainly the feet/toes (n = 90), head/face (n = 67), hand/fingers (n = 51), knee (n = 49), lower back (n = 49), and thighs (n = 45). Earplugs were used by 50 (24%) participants, and a helmet was used regularly by 38 (18%) participants and never by 175 (82%) participants.

Conclusion:

The most frequent types of injury in river surfers were contusions/bruises, cuts/lacerations, and abrasions. The main mechanisms of injury were contact with the bottom of the pool/river, with the board, or with the fins. The feet/toes were more prone to injuries, followed by the head/face and hand/fingers.
Intensive receptor blockade and plasma exchange to treat refractory scleroderma renal crisis in patients with agonistic autoantibodies targeting the angiotensin II type 1 and endothelin-1 type A receptors
Authors: Hegner Björn , Callaghan Julia , Schindler Ralf , Heidecke Harald , Riemekasten Gabriela , Philippe Aurélie , Catar Rusan
Published: May 2023

Scleroderma renal crisis is a rare complication of systemic sclerosis characterized by a rapid decline in kidney function due to acute renal vascular injury. Recently, activating autoantibodies targeting the angiotensin II type 1 receptor and the endothelin-1 type A receptor have been implicated in the pathophysiology of scleroderma renal crisis by sensitizing the angiotensin II type 1 receptor and endothelin-1 type A receptor in renal resistance arteries to their natural ligands. Here, we describe a cohort of 10 patients with scleroderma renal crisis refractory to standard treatment, including blockade of the renin-angiotensin system. Multimodal therapy was initiated, targeting at the removal of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies by plasma exchange and the reduction of vasoconstrictive activity. Further treatment options included angiotensin II type 1 receptor and endothelin-1 type A receptor blockade, iloprost, intravenous immunoglobulins, and immunosuppression. Six patients were hypertensive. On kidney biopsy, concentric intimal sclerosis was present in all patients, whereas acute vascular injury was evident in eight. Levels of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies were significantly reduced by multimodal treatment. Kidney function improved in three patients with histological signs of severe acute renal vascular damage. This report demonstrates that intensive multimodal therapy taking account of potentially pathogenic anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies in concert with other vasodilatory interventions provides a salvage option for patients with refractory scleroderma renal crisis.
Neurological Adverse Effects Following Administration of COVID-19 Vaccination: A Meta-Analysis
Authors: Ahmad Shwan A. , Abbas Yadgar N. , Ahmed Jaafar O. , Mahmood Zana H. , Kakamad Fahmi H. , Baba Hiwa O. , Salih Karzan M. , Karim Sanaa O. , Mohammed Shvan H. , Hassan Marwan N. , Salih Rawezh Q. , Kakamad Suhaib H.
Published: April 2023

Introduction

During the previous year, a variety of serious neurological problems associated with the COVID-19 vaccination have been documented, including encephalopathy, Guillain-Barré syndrome, transverse myelitis, and Bell’s palsy.

Objective

In the current study, neurological complications reported post-COVID-19 vaccination were systematically reviewed. The current meta-analysis aims to provide clinicians with a comprehensive understanding of this uncommon adverse event.

Method

Web of Science, MEDLINE on OVID, PubMed, and Google Scholar were searched for English-language papers published after January 1, 2020.

Result

Thirty articles were included in this study (21 case series and 9 cohort studies). The studies comprised 22,780 patients who got COVID-19 vaccinations and had at least 1 neurological adverse event. Across the majority of event types, females (54%) reported more adverse events than males (40%). The median duration from vaccination to the development of neurological symptoms was 12 days (0-41 days) in case series studies and 10 days (0-30 days) in cohort studies. Stroke is by far the most common neurological side effect of SARS-CoV-2 vaccines, followed by Bell’s palsy and seizures.

Conclusion

Concerns regarding the safety of COVID-19 vaccinations are being backed up by a growing number of studies that demonstrate neurological side effects.
A Brief Review of New Neoclassical Synthesis of Monetary Policy
Authors: Ajaz Taufeeq
Published: May 2023

This article reviews the central tenants of the New Neoclassical Synthesis of monetary policy. Starting with the optimising behaviour of central banks, this article reviews different theoretical developments like the role of expectations, the Taylor Principle, time-inconsistency, central bank independence and the importance of financial markets for monetary policy. The article concludes by highlighting the challenges faced by policymakers.
CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-β1/p38 MAPK activation and mitochondrial apoptotic pathways
Authors: Zhang Peiyao , Bai Liting , Tong Yuanyuan , Guo Shengwen , Lu Wenlong , Yuan Yue , Wang Wenting , Jin Yu , Gao Peng , Liu Jinping
Published: May 2023

Background

The ischemia–reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms.

Methods

Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen–glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments.

Results

We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-β1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-β1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo.

Conclusion

Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.
Guillain–Barre syndrome after myocardial infarction: a case report and literature review
Authors: Wen Pu-yuan , Chen Xian-wen , Zhang Min , Chu Wen-zheng , Wu Hong-liang , Ren Chao
Published: May 2023

Background

Guillain–Barre syndrome after myocardial infarction occurs infrequently, and its occurrence following percutaneous coronary intervention is extremely rare. Due to the high mortality rate of myocardial infarction and the disability of Guillain–Barre syndrome, early identification of Guillain–Barre syndrome after myocardial infarction and early intervention can decrease the mortality rate, lead to early recovery, and provide a better outcome.

Case presentation

Herein, we reported a rare case of Guillain–Barre syndrome after myocardial infarction treated with percutaneous coronary intervention. The patient was a 75-year-old woman from China who was admitted to hospital due to sudden loss of consciousness. Electrocardiography showed acute myocardial infarction in the right ventricle and inferior and posterior walls. The patient underwent emergency percutaneous intervention of the posterior collateral artery of the right coronary artery. Soon after, her condition worsened resulting in limb weakness and numbness. Unfortunately, she continued to develop respiratory failure, and treated with intravenous immunoglobulin and ventilator-assisted breathing. A physical examination showed hypotonia of all four limbs, complete quadriplegia, bulbar palsy, dysarthria, and tendon areflexia. Serum immunoglobulin (Ig) G anti-ganglioside antibody analysis was positive with anti-GT1a antibodies (+ +), anti-GM1 antibodies ( +), anti-GM2 antibodies ( +), and anti-GM4 antibodies ( +), and he was diagnosed with Guillain–Barre syndrome after myocardial infarction. She was discharged due to poor response to treatment. The patient died two days after being discharged.

Conclusions

Myocardial infarction and/or percutaneous coronary intervention may activate immune-mediated response and cause severe complications. Clinician should be alert to Guillain–Barre syndrome after myocardial infarction and/or percutaneous coronary intervention.
CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3
Authors: Zhao Chongru , Zeng Ning , Zhou Xiaomei , Tan Yufang , Wang Yichen , Zhang Jun , Wu Yiping , Zhang Qi
Published: May 2023

Background

Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression.

Methods

Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression.

Results

CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages.

Conclusions

Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.
Depression literacy and misconceptions scale (DepSter): a new two-factorial tool for measuring beliefs about depression
Authors: Kulwicka Katarzyna , Gasiorowska Agata
Published: May 2023

Background

Depression literacy has received extensive attention within mental health research. It has been studied by different social groups and professions in Western and non-Western cultures. The importance of this topic stems from the fact that depression literacy is strongly related to attitudes toward people who are diagnosed with depression, the tendency to stigmatize this mental disorder, and to the propensity to undertake help-seeking behaviors. Therefore, understanding and promoting depression literacy is crucial in contemporary mental health prevention and promotion. We propose a new two-factorial tool measuring beliefs about depression. This 14-item self-report measure captures how people vary across two dimensions of beliefs about depression—depression literacy and misconceptions about depression.

Methods

In ten studies with a total sample of over 4,600 participants from three countries, we demonstrated the two-factorial structure of the Depression Literacy and Misconceptions Scale (DepSter) in Polish (Studies 1 and 2), American (Study 4), and British (Study 5) samples. We showed measurement equivalence for the Polish and English versions of the scale (Study 3). Furthermore, we tested the discriminant meaning of the two dimensions of beliefs about depression analyzing its association with health literacy, mental health literacy, and prejudice toward people with mental illness (Study 4), depression literacy and depression stigma (Study 5), empathetic concerns (Study 7), social dominance orientation (Study 8), and the Big Five personality traits (Study 9). We also investigated whether individuals with formal education in psychology and direct or indirect experience with depression demonstrate a higher level of depression literacy and a lower level of misconceptions about depression (Study 6). Our measure showed high stability for two dimensions of beliefs about depression (Study 10), in both its Polish and English versions, with the measurement conducted after three weeks and three months.

Discussion

We conclude that the proposed approach to beliefs about depression capturing both depression literacy and misconceptions about depression measured with the DepSter scale can easily be applied in clinical and social settings, especially in studies concerning the perception of those diagnosed with depression.
Severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis
Authors: Huang Shuihua , Zhang Shengxin , Yuan Lin , Zhuo Zhiqiang , Wu Xingdong
Published: May 2023

Background

This study aimed to analyze the clinical characteristics of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis.

Methods

We retrospectively analyzed the clinical data of five children clinically diagnosed with severe adenoviral pneumonia combined with invasive pulmonary aspergillosis at Xiamen Children’s Hospital.

Results

These five children included one boy and four girls, with ages of onset ranging from 8 months and 15 days to 2 years and 2 months. All of them had fever with a mean duration of 11–35 days and cough. Pulmonary imaging was performed, which revealed solid pulmonary opacification in all five children, pleural effusion in two children, and emphysema and multiple small cavity formations in one child. Multiple microbiological tests were performed on the 5 children, and adenovirus was positive in the alveolar lavage fluid for the first time, and aspergillus culture was positive in the second test. On tracheoscopy, the bronchial mucosa was seen to be congested and edematous or pale and eroded; white moss-like material was seen adhering to the tracheal wall or even blocking the airway. The five children were treated with a combination of two or more broad-spectrum antimicrobials, glucocorticoids, and gamma globulins and underwent bronchoscopy. Voriconazole was added in the treatment regimen after the diagnosis of aspergillosis (28–34 days of treatment). Four of the children were discharged in good condition with a mean total length of hospital stay of 17–47 days. The other child leave against medical advice. Follow-up 3–5 months after discharge showed that one child had been cured; two children had developed obliterative bronchiolitis; one child had developed bronchiectasis; and the remaining child who had been discharged spontaneously was not contactable via telephone.

Conclusions

Immune disorders and antibiotic and steroid treatments for adenovirus infection are high-risk factors for secondary invasive pulmonary aspergillosis in children. Prolonged fever and cough are the main manifestations, but which lack specificity, and bronchoscopic mucosal-specific injury evaluation and alveolar lavage fluid culture are helpful in the diagnosis of aspergillosis. The long-term prognosis of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis maybe poor.
Evaluation of the simulation based training quality assurance tool (SBT-QA10) as a measure of learners’ perceptions during the action phase of simulation
Authors: Ekelund Kim , O’Regan Stephanie , Dieckmann Peter , Østergaard Doris , Watterson Leonie
Published: May 2023

Background

In an earlier interview-based study the authors identified that learners experience one or more of eight explicit perceptual responses during the active phase of simulation-based training (SBT) comprising a sense: of belonging to instructor and group, of being under surveillance, of having autonomy and responsibility for patient management, of realism, of an understanding of the scenario in context, of conscious mental effort, of control of attention, and of engagement with task. These were adapted into a ten-item questionnaire: the Simulation Based Training Quality Assurance Tool (SBT-QA10) to allow monitoring of modifiable factors that may impact upon learners’ experiences. This study assessed the construct validity evidence of the interpretation of the results when using SBT-QAT10.

Materials and methods

Recently graduated doctors and nurses participating in a SBT course on the topic of the deteriorating patient completed the SBT-QAT10 immediately following their participation in the scenarios. The primary outcome measure was internal consistency of the questionnaire items and their correlation to learners’ satisfaction scores. A secondary outcome measure compared the impact of allocation to active versus observer role.

Results

A total of 349 questionnaires were returned by 96 course learners. The median of the total score for the ten perception items (TPS) was 39 (out of 50), with no significant difference between the scenarios. We identified fair and positive correlations between nine of the 10 items and the SBT-QA10-TPS, the exception being “mental effort”. Compared to observers, active learners reported significantly more positive perceptions related to belonging to the team and interaction with the instructor, their sense of acting independently, and being focused. The questionnaire items were poorly correlated with the two measures of global satisfaction.

Conclusion

Except for the item for mental effort, the QA10-TPS measures learners’ experiences during the active phase of simulation scenarios that are associated with a positive learning experience. The tool may have utility to learners, instructors, and course providers by informing subsequent debriefing and reflection upon practice for learners and faculty. The relationship between these perceptions and commonly used measures of satisfaction remains poorly understood raising questions about the value of the latter.
The case for citizen science in public health policy and practice: a mixed methods study of policymaker and practitioner perspectives and experiences
Authors: Marks Leah , Smith Ben J. , Mitchell Jo , Laird Yvonne , Rowbotham Samantha
Published: May 2023

Background

Citizen science (CS) is increasingly being utilised to involve the public in public health research, but little is known about whether and how CS can address the needs of policy and practice stakeholders in health promotion and chronic disease prevention.

Methods

Using a mixed methods approach we conducted an online survey (n = 83) and semi-structured interviews (n = 21) with policy and practice stakeholders across Australia to explore how CS approaches are perceived and applied in chronic disease prevention, how CS aligns with existing approaches to community engagement, and how the uptake of CS can be supported within policy and practice settings.

Results

Most participants had heard of CS, and while few had experience of using CS, there was widespread support for this approach, with many seeing it as complementary to other community engagement approaches. CS was seen as providing: (a) a robust framework for engagement; (b) access to rich data; (c) opportunities for more meaningful engagement; and (d) a mutually beneficial approach for stakeholders and community members. However, stakeholders identified a need to weigh benefits against potential risks and challenges including competing organisational priorities, resourcing and expertise, data quality and rigour, governance, and engagement.

Conclusions

To expand the use of CS, stakeholders identified the need for increased awareness, acceptance, and capacity for CS within public health organisations, greater access to supporting tools and technology, and evidence on processes, feasibility and impacts to enhance the visibility and legitimacy of CS approaches.
Phenolic compounds as Nrf2 inhibitors: potential applications in cancer therapy
Authors: Sharifi-Rad Javad , Seidel Veronique , Izabela Michalak , Monserrat-Mequida Margalida , Sureda Antoni , Ormazabal Valeska , Zuniga Felipe A. , Mangalpady Shivaprasad Shetty , Pezzani Raffaele , Ydyrys Alibek , Tussupbekova Gulmira , Martorell Miquel , Calina Daniela , Cho William C.
Published: May 2023

Cancer is a leading cause of death worldwide and involves an oxidative stress mechanism. The transcription factor Nrf2 has a crucial role in cytoprotective response against oxidative stress, including cancer growth and progression and therapy resistance. For this reason, inhibitors of Nrf2 are new targets to be studied. Traditional plant-based remedies rich in phytochemicals have been used against human cancers and phenolic compounds are known for their chemopreventive properties. This comprehensive review offers an updated review of the role of phenolic compounds as anticancer agents due to their action on Nrf2 inhibition. In addition, the role of naturally-occurring bioactive anticancer agents are covered in the clinical applications of polyphenols as Nrf2 inhibitors.
Socioeconomic position and the influence of food portion size on daily energy intake in adult females: two randomized controlled trials
Authors: Langfield Tess , Clarke Katie , Marty Lucile , Jones Andrew , Robinson Eric
Published: April 2023

Background

Reducing portion sizes of commercially available foods could be an effective public health strategy to reduce population energy intake, but recent research suggests that the effect portion size has on energy intake may differ based on socioeconomic position (SEP).

Objective

We tested whether the effect of reducing food portion sizes on daily energy intake differed based on SEP.

Methods

Participants were served either smaller or larger portions of food at lunch and evening meals (N = 50; Study 1) and breakfast, lunch and evening meals (N = 46; Study 2) in the laboratory on two separate days, in repeated-measures designs. The primary outcome was total daily energy intake (kcal). Participant recruitment was stratified by primary indicators of SEP; highest educational qualification (Study 1) and subjective social status (Study 2), and randomisation to the order portion sizes were served was stratified by SEP. Secondary indicators of SEP in both studies included household income, self-reported childhood financial hardship and a measure accounting for total years in education.

Results

In both studies, smaller (vs larger) meal portions led to a reduction in daily energy intake (ps < .02). Smaller portions resulted in a reduction of 235 kcal per day (95% CI: 134, 336) in Study 1 and 143 kcal per day (95% CI: 24, 263) in Study 2. There was no evidence in either study that effects of portion size on energy intake differed by SEP. Results were consistent when examining effects on portion-manipulated meal (as opposed to daily) energy intake.

Conclusions

Reducing meal portion sizes could be an effective way to reduce overall daily energy intake and contrary to other suggestions it may be a socioeconomically equitable approach to improving diet.

Trial registration

These trials were registered at www.clinicaltrials.gov as NCT05173376 and NCT05399836.
Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells
Authors: Tsai Ming-Han C. , Caswell Sarah J. , Morris Elizabeth R. , Mann Melanie C. , Pennell Simon , Kelly Geoff , Groom Harriet C. T. , Taylor Ian A. , Bishop Kate N.
Published: May 2023

Background

SAMHD1 is a deoxynucleotide triphosphohydrolase that restricts replication of HIV-1 in differentiated leucocytes. HIV-1 is not restricted in cycling cells and it has been proposed that this is due to phosphorylation of SAMHD1 at T592 in these cells inactivating the enzymatic activity. To distinguish between theories for how SAMHD1 restricts HIV-1 in differentiated but not cycling cells, we analysed the effects of substitutions at T592 on restriction and dNTP levels in both cycling and differentiated cells as well as tetramer stability and enzymatic activity in vitro.

Results

We first showed that HIV-1 restriction was not due to SAMHD1 nuclease activity. We then characterised a panel of SAMHD1 T592 mutants and divided them into three classes. We found that a subset of mutants lost their ability to restrict HIV-1 in differentiated cells which generally corresponded with a decrease in triphosphohydrolase activity and/or tetramer stability in vitro. Interestingly, no T592 mutants were able to restrict WT HIV-1 in cycling cells, despite not being regulated by phosphorylation and retaining their ability to hydrolyse dNTPs. Lowering dNTP levels by addition of hydroxyurea did not give rise to restriction. Compellingly however, HIV-1 RT mutants with reduced affinity for dNTPs were significantly restricted by wild-type and T592 mutant SAMHD1 in both cycling U937 cells and Jurkat T-cells. Restriction correlated with reverse transcription levels.

Conclusions

Altogether, we found that the amino acid at residue 592 has a strong effect on tetramer formation and, although this is not a simple “on/off” switch, this does correlate with the ability of SAMHD1 to restrict HIV-1 replication in differentiated cells. However, preventing phosphorylation of SAMHD1 and/or lowering dNTP levels by adding hydroxyurea was not enough to restore restriction in cycling cells. Nonetheless, lowering the affinity of HIV-1 RT for dNTPs, showed that restriction is mediated by dNTP levels and we were able to observe for the first time that SAMHD1 is active and capable of inhibiting HIV-1 replication in cycling cells, if the affinity of RT for dNTPs is reduced. This suggests that the very high affinity of HIV-1 RT for dNTPs prevents HIV-1 restriction by SAMHD1 in cycling cells.
The interactions between PML nuclear bodies and small and medium size DNA viruses
Authors: Ryabchenko Boris , Šroller Vojtěch , Horníková Lenka , Lovtsov Alexey , Forstová Jitka , Huérfano Sandra
Published: May 2023

Promyelocytic leukemia nuclear bodies (PM NBs), often referred to as membraneless organelles, are dynamic macromolecular protein complexes composed of a PML protein core and other transient or permanent components. PML NBs have been shown to play a role in a wide variety of cellular processes. This review describes in detail the diverse and complex interactions between small and medium size DNA viruses and PML NBs that have been described to date. The PML NB components that interact with small and medium size DNA viruses include PML protein isoforms, ATRX/Daxx, Sp100, Sp110, HP1, and p53, among others. Interaction between viruses and components of these NBs can result in different outcomes, such as influencing viral genome expression and/or replication or impacting IFN-mediated or apoptotic cell responses to viral infection. We discuss how PML NB components abrogate the ability of adenoviruses or Hepatitis B virus to transcribe and/or replicate their genomes and how papillomaviruses use PML NBs and their components to promote their propagation. Interactions between polyomaviruses and PML NBs that are poorly understood but nevertheless suggest that the NBs can serve as scaffolds for viral replication or assembly are also presented. Furthermore, complex interactions between the HBx protein of hepadnaviruses and several PML NBs-associated proteins are also described. Finally, current but scarce information regarding the interactions of VP3/apoptin of the avian anellovirus with PML NBs is provided. Despite the considerable number of studies that have investigated the functions of the PML NBs in the context of viral infection, gaps in our understanding of the fine interactions between viruses and the very dynamic PML NBs remain. The complexity of the bodies is undoubtedly a great challenge that needs to be further addressed.
Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract
Authors: Brown James S. , Diamond Gary L.
Published: April 2023

Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between the rate of particle clearance from a region and their solubility in respiratory solvents. Dissolution is a function of particle surface area divided by particle volume or mass (i.e., dissolution is inversely proportional to the physical diameter of particles). As a conservative approach, investigators commonly assume the complete and instantaneous dissolution of metals from particles depositing in the alveolar region of the respiratory tract. We derived first-order dissolution rate constants to facilitate biokinetic modeling of particle clearance, dissolution, and absorption into the blood. We then modeled pulmonary burden and total dissolution of particles over time as a function of particle size, density, and solubility. We show that assuming poorly soluble particle forms will enter the blood as quickly as highly soluble forms causes an overestimation of concentrations of the compound of interest in blood and other extrapulmonary tissues while also underestimating its pulmonary burden. We conclude that, in addition to modeling dose rates for particle deposition into the lung, physiologically based pharmacokinetic modeling of pulmonary and extrapulmonary tissues concentrations of moderately and poorly soluble materials can be improved by including estimates of lung burden and particle dissolution over time.
Non-spherical gold nanoparticles enhanced fluorescence of carbon dots for norovirus-like particles detection
Authors: Alzahrani Abdulhakeem , Alsulami Tawfiq , Salamatullah Ahmad Mohammad , Ahmed Syed Rahin
Published: April 2023

Background

Norovirus is a common pathogen that causes foodborne outbreaks every year and the increasing number of deaths caused by it has become a substantial concern in both developed and underdeveloped countries. To date, no vaccines or drugs are able to control the outbreak, highlighting the importance of finding specific, and sensitive detection tools for the viral pathogen. Current diagnostic tests are limited to public health laboratories and/or clinical laboratories and are time-consuming. Hence, a rapid and on-site monitoring strategy for this disease is urgently needed to control, prevent and raise awareness among the general public.

Results

The present study focuses on a nanohybridization technique to build a higher sensitivity and faster detection response to norovirus-like particles (NLPs). Firstly, the wet chemical-based green synthesis of fluorescent carbon quantum dots and gold nanoparticles (Au NPs) has been reported. Then, a series of characterization studies were conducted on the synthesized carbon dots and Au NPs, for example, high-resolution transmission emission microscopy, fluorescence spectroscopy, fluorescence life-lime measurement, UV–visible spectroscopy, and X-ray diffraction (XRD). The fluorescence emission of the as-synthesized carbon dots and the absorption of Au NPs were located at 440 nm and 590 nm, respectively. Then, the plasmonic properties of Au NPs were utilized to enhance the fluorescence emission of carbon dots in the presence of NLPs in human serum. Here, the enhanced fluorescence response was linearly correlated up to 1 μg mL−1. A limit of detection (LOD) value was calculated to be 80.3 pg mL−1 demonstrating that the sensitivity of the proposed study is 10 times greater than that of the commercial diagnostic kits.

Conclusions

The proposed exciton-plasmon interaction-based NLPs-sensing strategy was highly sensitive, specific, and suitable for controlling upcoming outbreaks. Most importantly, the overall finding in the article will take the technology a step further to applicable point-of-care (POC) devices.
TRAF3 suppression encourages B cell recruitment and prolongs survival of microbiome-intact mice with ovarian cancer
Authors: Zorea Jonathan , Motro Yair , Mazor Roei D. , Carmi Yifat Koren , Shulman Ziv , Mahajna Jamal , Moran-Gilad Jacob , Elkabets Moshe
Published: May 2023

Background

Ovarian cancer (OC) is known for exhibiting low response rates to immune checkpoint inhibitors that activate T cells. However, immunotherapies that activate B cells have not yet been extensively explored and may be a potential target, as B cells that secrete immunoglobulins have been associated with better outcomes in OC. Although the secretion of immunoglobulins is often mediated by the microbiome, it is still unclear what role they play in limiting the progression of OC.

Methods

We conducted an in-vivo CRISPR screen of immunodeficient (NSG) and immune-intact wild type (WT) C57/BL6 mice to identify tumor-derived immune-escape mechanisms in a BRAC1- and TP53-deficient murine ID8 OC cell line (designated ITB1). To confirm gene expression and signaling pathway activation in ITB1 cells, we employed western blot, qPCR, immunofluorescent staining, and flow cytometry. Flow cytometry was also used to identify immune cell populations in the peritoneum of ITB1-bearing mice. To determine the presence of IgA-coated bacteria in the peritoneum of ITB1-bearing mice and the ascites of OC patients, we employed 16S sequencing. Testing for differences was done by using Deseq2 test and two-way ANOVA test. Sequence variants (ASVs) were produced in Qiime2 and analyzed by microeco and phyloseq R packages.

Results

We identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a tumor-derived immune suppressive mediator in ITB1 cells. Knockout of TRAF3 (TRAF3KO) activated the type-I interferon pathway and increased MHC-I expression. TRAF3KO tumors exhibited a growth delay in WT mice vs. NSG mice, which was correlated with increased B cell infiltration and activation compared to ITB1 tumors. B cells were found to be involved in the progression of TRAF3KO tumors, and B-cell surface-bound and secreted IgA levels were significantly higher in the ascites of TRAF3KO tumors compared to ITB1. The presence of commensal microbiota was necessary for B-cell activation and for delaying the progression of TRAF3KO tumors in WT mice. Lastly, we observed unique profiles of IgA-coated bacteria in the ascites of OC-bearing mice or the ascites of OC patients.

Conclusions

TRAF3 is a tumor-derived immune-suppressive modulator that influences B-cell infiltration and activation, making it a potential target for enhancing anti-tumor B-cell responses in OC.
The efficacy and safety of fluconazole in preventing invasive fungal infection in very low birth weight infants: a systematic review and meta-analysis
Authors: Xie Jinghong , Zeng Jiayue , Zheng Shouyan
Published: April 2023

This meta-analysis aimed to assess the efficacy and safety of fluconazole for the prevention of invasive fungal infections (IFI) in very low birth weight infants (VLBWI) and to provide a basis for the clinical use. A detailed search of Pubmed, Embase, Cochrane Library and other databases was performed to carefully screen eligible randomized controlled clinical studies to assess the safety and efficacy of fluconazole in very low birth weight infants in terms of the incidence of invasive fungal infections, fungal colonization rate, and mortality. Our research indicated that the application of fluconazole did not result in intolerable adverse reactions in patients. Fluconazole is effective in preventing invasive fungal infections in very low birth weight infants without serious adverse effects. The dose and frequency of fluconazole in very low birth weight infants still needs to be evaluated in consequent studies.
Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial
Authors: Le Meur Yannick , Nowak Emmanuel , Barrou Benoit , Thierry Antoine , Badet Lionel , Buchler Matthias , Rerolle Jean-Philippe , Golbin Leonard , Duveau Agnès , Dantal Jacques , Merville Pierre , Kamar Nassim , Demini Leïla , Zal Franck
Published: May 2023

Background

Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts.

Methods

OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation.

Discussion

The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation.

Trial registration

ClinicalTrials.gov, ID: NCT04181710. registered on November 29, 2019.
Exploring implementation outcomes in the clinical trial context: a qualitative study of physician trial stakeholders
Authors: Stensland Kristian D. , Sales Anne E. , Vedapudi Varsha K. , Damschroder Laura J. , Skolarus Ted A.
Published: April 2023

Introduction

Cancer clinical trials can be considered evidence-based interventions with substantial benefits, but suffer from poor implementation leading to low enrollment and frequent failure. Applying implementation science approaches such as outcomes frameworks to the trial context could aid in contextualizing and evaluating trial improvement strategies. However, the acceptability and appropriateness of these adapted outcomes to trial stakeholders are unclear. For these reasons, we interviewed cancer clinical trial physician stakeholders to explore how they perceive and address clinical trial implementation outcomes.

Methods

We purposively selected 15 cancer clinical trial physician stakeholders from our institution representing different specialties, trial roles, and trial sponsor types. We performed semi-structured interviews to explore a previous adaptation of Proctor’s Implementation Outcomes Framework to the clinical trial context. Emergent themes from each outcome were developed.

Results

The implementation outcomes were well understood and applicable (i.e., appropriate and acceptable) to clinical trial stakeholders. We describe cancer clinical trial physician stakeholder understanding of these outcomes and current application of these concepts. Trial feasibility and implementation cost were felt to be most critical to trial design and implementation. Trial penetration was most difficult to measure, primarily due to eligible patient identification. In general, we found that formal methods for trial improvement and trial implementation evaluation were poorly developed. Cancer clinical trial physician stakeholders referred to some design and implementation techniques used to improve trials, but these were infrequently formally evaluated or theory-based.

Conclusion

Implementation outcomes adapted to the trial context were acceptable and appropriate to cancer clinical trial physician stakeholders. Use of these outcomes could facilitate the evaluation and design of clinical trial improvement interventions. Additionally, these outcomes highlight potential areas for the development of new tools, for example informatics solutions, to improve the evaluation and implementation of clinical trials.