bluuebunny/crossref_metadata_2025 huggingface dataset:
Inductive process of moral distress development in viewpoints from surgical nurses: a mixed-method study
Authors: Hosseinpour Azam , Keshmiri Fatemeh
Published: March 2024

Background

Moral distress is a multifactorial and complex phenomenon influenced by various individual, cultural, and systemic factors. This study aimed to investigate the frequency and intensity of nurses’ moral distress, explore their experiences, and develop the conceptual model of risk factors of moral distress in surgical units and operating rooms.

Method

This is a sequential mixed-method study conducted at four teaching hospitals affiliated with the Qom University of Medical Sciences. In the first step, the moral distress of nurses in surgical units and operating rooms was investigated by a survey. The participants included nurses who worked in the operating room and surgical units. (n = 180). The data was collected by a Moral Distress Scale-Revised (MDS-R) questionnaire. In the second step, the experiences of nurses regarding risk factors of moral distress were explored using semi-structured interviews and analyzed using the conventional content analysis by Graneheim and Lundman’s approach.

Results

One hundred eighty nurses participated in this study. The mean total moral distress scores ranged from 12 to 221, with a mean (SD) of 116.8 (42.73). The causes of moral distress cited with the highest frequency and intensity related to the ‘role of healthcare providers’. The experiences of the participants in the theme ‘Inductive process of moral distress development’ were categorized into three categories: ‘Melting into the faulty system’, ‘Power and the system as distress promotors’, and ‘Perceived unpleasant consequences’.

Conclusion

The results indicated that the frequency of moral distress in operating rooms and surgical units was at a moderate level and the distress intensity of nurses was at a moderately high level. The results indicated that in the investigated system, the “inductive moral process of distress development” was continuously understood by the participants. This process was influenced by systemic and individual factors. Weak assertiveness, conservative compromise, and desensitization to unprofessionalism as individual factors were effective in causing distress. Risk factors at the systemic level led nurses to melt into the faulty system and created adverse outcomes at the individual level. The lack of systemic support and the stabilization of mobbing by powerful system members had a negative impact on the individual factors of distress development. Also, these factors directly cause negative consequences.
Assessment of preventive practices towards hepatitis B infection among nursing students in Bangladesh: role of knowledge, attitudes and sociodemographic factors
Authors: Tamanna Sumaiya Sultana , Paul Kallol Deb , Al Banna Md. Hasan , Zannat Zamia , Paul Anup Kumar , Sultana Sadia , Alshahrani Najim Z. , Talukder Sohan , Hassan Md. Nazmul
Published: March 2024

Background

Globally, hepatitis B infection (HBI) poses a substantial public health concern and healthcare workers, including nursing students, are at a higher risk of contracting this disease. Thus, the study aimed to assess how knowledge, attitudes, and sociodemographic factors are associated with HBI prevention among a sample of Bangladeshi nursing students.

Methods

A cross-sectional survey was performed among 737 nursing students from the nursing institutes of Khulna and Barishal divisions in Bangladesh from January to April 2023. The data were collected by providing questionnaires (structured questionnaire) in the classroom, following a stratified random sampling process. A model of multinomial logistic regression was used to evaluate the factors linked to HBI prevention practices.

Result

The mean (SD) scores were 11.42 (± 2.88) for knowledge, 4.33 (± 1.91) for attitude and 4.27 (± 2.056) for practice respectively. Participants’ low knowledge (adjusted odds ratio, aOR = 2.562, 95% CI: 1.29–5.07) and poor attitude (aOR = 5.730, 95% CI: 3.19–10.28) regarding HBI were significantly associated with higher likelihood of poor practice towards HBI prevention. Moreover, being 2nd year of nursing students (aOR = 2.147, 95% CI: 1.19–3.86), being aged 19–20 years (aOR = 3.038, 95% CI: 1.30–7.09), being married (aOR = 0.320, 95%CI: 0.13–0.82) and having a family history of HBI (aOR = 0.134, 95%CI: 0.05–0.36) were significantly associated with poor practices of HBI prevention among study participants.

Conclusion

The knowledge, attitude and practice scores of the nursing students on HBI prevention were suboptimal. We advocate for implementing regular HBI prevention education and policies, free or subsidized services, skill development, proper HBI prevention enforcement and strict professional ethics within nursing colleges. Such efforts should predominantly focus on second-year, aged 19–20 and unmarried nursing students.
Healthcare worker burnout: exploring the experiences of doctors working in a maternity unit in Namibia
Authors: Brückner Tanya Y. , Heemelaar S. , Endjala T. , van den Akker T.
Published: March 2024

Background

Globally, healthcare workers (HCWs) in maternity units are at high risk of developing burnout. Burnout can lead to multiple harmful impacts on HCWs, their patients, and the broader healthcare system. Little is known about the burden of burnout among sub-Saharan African HCWs. Although evidence suggests that maternity unit doctors in a hospital complex in Namibia are at risk of developing burnout, no studies have been conducted on doctors in this department yet.

Methods

Through participant observation and a mixed-methods needs assessment, this study aimed to explore the drivers, experiences, and impact of burnout symptoms among doctors in this department, and current support mechanisms in place. Survey data was collected from 18 participants and seven in-depth interviews were conducted. Burnout risk was assessed using the Burnout Assessment Tool.

Results

Seven out of 18 participants were at very high risk for burnout and three were at risk, showing a high prevalence of burnout risk. Burnout risk remained similar between levels of staff, while gender qualitatively impacted burnout-related experiences. Drivers of burnout were identified at personal, occupational, and systemic levels.

Conclusions

Over half of participants were at risk or at very high risk of burnout. Results highlighted a need for support and identified areas for intervention and further research. Such areas include blame culture, lack of trust between colleagues, and systemic drivers of burnout. This study contributes to the understanding of burnout among HCWs in sub-Saharan Africa.
CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib
Authors: Li Haosheng , Feng Haoran , Zhang Tao , Wu Junwei , Shen Xiaonan , Xu Shuiyu , Xu Lianghui , Wang Shaodong , Zhang Yaqi , Jia Wenqing , Ji Xiaopin , Cheng Xi , Zhao Ren
Published: March 2024

Background

Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure.

Methods

The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335).

Results

Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels.

Conclusions

CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.
ECM stiffness affects cargo sorting into MSC-EVs to regulate their secretion and uptake behaviors
Authors: Liu Zhixiao , Liu Yingying , Li Yu , Xu Sha , Wang Yang , Zhu Yuruchen , Jiang Chu , Wang Kaizhe , Zhang Yinan , Wang Yue
Published: March 2024

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered extensive attention as natural product-based nanomedicines and potential drug delivery vehicles. However, the specific mechanism for regulating MSC-EVs secretion and delivery remains unclear. Here, we demonstrate that extracellular matrix (ECM) stiffness regulates the secretion and delivery of EVs by affecting MSCs' cargo sorting mechanically. Using multi-omics analysis, we found that a decrease in ECM stiffness impeded the sorting of vesicular transport-related proteins and autophagy-related lipids into MSC-EVs, impairing their secretion and subsequent uptake by macrophages. Hence, MSC-EVs with different secretion and uptake behaviors can be produced by changing the stiffness of culture substrates. This study provides new insights into MSC-EV biology and establishes a connection between MSC-EV behaviors and ECM from a biophysical perspective, providing a basis for the rational design of biomedical materials.

Graphical Abstract
AURKB promotes bladder cancer progression by deregulating the p53 DNA damage response pathway via MAD2L2
Authors: Li Linzhi , Jiang Pengcheng , Hu Weimin , Zou Fan , Li Ming , Rao Ting , Ruan Yuan , Yu Weimin , Ning Jinzhuo , Cheng Fan
Published: March 2024

Background

Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway.

Methods

Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR.

Results

AURKB was highly expressed and associated with prognosis in patients with BC. AURKB expression was positively correlated with MAD2L2 expression. We confirmed that AURKB interacts with, and modulates the expression of, MAD2L2 in BC cells. AURKB knockdown suppressed the proliferation, migration, and invasion abilities of, and cell cycle progression in, BC cells, inducing senescence in these cells. The effects of AURKB knockdown were rescued by MAD2L2 overexpression in vitro and in vivo. The effects of MAD2L2 knockdown were similar to those of AURKB knockdown. Furthermore, p53 ablation rescued the MAD2L2 knockdown-induced suppression of BC cell proliferation and cell cycle arrest and senescence in BC cells.

Conclusions

AURKB activates MAD2L2 expression to downregulate the p53 DDR pathway, thereby promoting BC progression. Thus, AURKB may serve as a potential molecular marker and a novel anticancer therapeutic target for BC.
Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia–reperfusion injury
Authors: Chen Shuang , Pan Jingrui , Gong Zhe , Wu Meiling , Zhang Xiaoni , Chen Hansen , Yang Dan , Qi Suhua , Peng Ying , Shen Jiangang
Published: March 2024

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.
Mechanism of self-recovery of hydrophobicity after surface damage of lotus leaf
Authors: Wang Li , Shu Lichun , Hu Qin , Jiang Xingliang , Yang Hang , Wang Huan , Rao Lipeng
Published: March 2024

The surfaces of lotus leaves with micro- and nano-waxy cuticle structures are superhydrophobic and possess a self-healing ability to regain hydrophobicity after damage. Inspired by this phenomenon, the problem of water-repellent coatings used in natural environments failing to perform after damage can be solved if these coatings are endowed with rapid self-repair and self-growth functions. However, there has been almost no exploration into the hydrophobicity self-repair process in lotus leaves. The changes in surface morphology during the hydrophobicity recovery process are not understood. There is a lack of research on the hydrophobicity recovery in lotus leaves. In this study, the damage and recovery experiments on lotus leaf surfaces were carried out in an artificial climate chamber, and the water repellency recovery process and typical water repellency roughness parameters regained time were obtained. Upon analyzing the differences in the recovery process of different damage types, the recovery mechanism after lotus leaf surface damage was obtained. Finally, it was found that the microscopic roughness determined the static contact angle (WCA) of the lotus leaf surface, and the nanoscopic roughness determined the rolling angle (SA). The dual factors of the recovery of the extruded epidermal tissue and the regeneration of the epidermal wax crystals determined the hydrophobicity recovery process in damaged lotus leaves.
Exploring the support needs of Australian parents of young children with Usher syndrome: a qualitative thematic analysis
Authors: Johansen L. , O’Hare F. , Shepard E. R. , Ayton L. N. , Pelentsov L. J. , Kearns L. S. , Galvin K. L.
Published: March 2024

Background

Advancements in genetic testing have led to Usher syndrome now being diagnosed at a much earlier age than in the past, enabling the provision of early intervention and support to children and families. Despite these developments, anecdotal reports suggest there are substantial gaps in the services and supports provided to parents of children with Usher syndrome. The current study investigated the support needs of parents of children with Usher syndrome Type 1 when their child was aged 0 to 5 years.

Method

Purposive sampling was used, and six semi-structured interviews were conducted with Australian parents of children with Usher syndrome, Type 1. Data was analysed using modified reflexive thematic analysis.

Results

Four key themes were identified as being central to the support needs of parents of children with Usher syndrome aged 0 to 5 years. (1) Social Needs referred to parents’ need for various sources of social support, (2) Informational Needs described the lack of information parents received regarding Usher syndrome from treating professionals, (3) Practical Needs included supports needed to assist parents in managing the day-to-day tasks of caring for a child with a disability, and (4) Emotional Needs represented the emotional support (both formal and informal) that parents needed to be a positive support to their child.

Conclusions

Findings provide rich information for relevant support groups, policy makers, individual healthcare professionals, and professional governing bodies regarding the education of stakeholders and the development and implementation of best-practice treatment guidelines.
Effect of an entry-to-care intervention on diabetes distress in individuals with newly diagnosed type 2 diabetes: a study protocol for a cluster-randomized trial
Authors: Hansen Steffan Holst , Jensen Troels Mygind , Petersen Gitte Stentebjerg , Pouwer Francois , Larrabee Sonderlund Anders , Søndergaard Jens
Published: March 2024

Background

Diabetes distress (DD) affects at least 36% of T2DM patients and is often associated with insufficient support and care. This study examines an intervention that targets DD through enhanced cross-sectoral collaboration and treatment during the first 3 months following diagnosis. The intervention aims to improve care and self-management and to reduce DD.

Methods and intervention

The study is designed as a cluster-randomized trial with the intervention focusing on four key elements of diabetes care: effective cross-sectoral communication and information sharing, systematic care, a “one-stop-shop” health screening and start-up conversation at the municipality, and improving patient insights into own care.

This study requires 32 clusters (16/arm) to achieve 80% power and a 5% significance cut-off, with 270 patients required. GP recruitment occurred from May to Dec 2022. Patient recruitment is ongoing from May 2022 to Aug 2023. GPs were randomized 1:1 using computer-generated blocks of six.

Participating GPs are located in Southern Denmark and are not participating in other trials. Patients must be 18 + years of age, have a T2DM diagnosis, and be fluent in spoken and written Danish. DD is the primary outcome and will be measured at baseline, at four months, and again at a 12-month follow-up. Secondary outcomes include quality of care, self-management, quality of life, and clinical factors. Tertiary outcomes comprise depression, stress, resilience, sleep quality, and social network quality.

Conclusion

This study is among the first clinical trials exploring the development of DD from diagnosis to 12 months post-diagnosis. Many previous interventions did not directly target DD as the primary outcome. This research provides new insights into DD progression in patients newly diagnosed with T2DM and examines an intervention designed to lower DD in early diabetes stages, contributing to a better understanding of the development of DD and how this intervention affects patient well-being.

Trial registration

ClinicalTrial.gov NCT05571306. Registered on 07 October 2022.
Structural insights into curdlan degradation via a glycoside hydrolase containing a disruptive carbohydrate-binding module
Authors: Lv Tianhang , Feng Juanjuan , Jia Xiaoyu , Wang Cheng , Li Fudong , Peng Hui , Xiao Yazhong , Liu Lin , He Chao
Published: March 2024

Background

Degradation via enzymatic processes for the production of valuable β-1,3-glucooligosaccharides (GOS) from curdlan has attracted considerable interest. CBM6E functions as a curdlan-specific β-1,3-endoglucanase, composed of a glycoside hydrolase family 128 (GH128) module and a carbohydrate-binding module (CBM) derived from family CBM6.

Results

Crystallographic analyses were conducted to comprehend the substrate specificity mechanism of CBM6E. This unveiled structures of both apo CBM6E and its GOS-complexed form. The GH128 and CBM6 modules constitute a cohesive unit, binding nine glucoside moieties within the catalytic groove in a singular helical conformation. By extending the substrate-binding groove, we engineered CBM6E variants with heightened hydrolytic activities, generating diverse GOS profiles from curdlan. Molecular docking, followed by mutation validation, unveiled the cooperative recognition of triple-helical β-1,3-glucan by the GH128 and CBM6 modules, along with the identification of a novel sugar-binding residue situated within the CBM6 module. Interestingly, supplementing the CBM6 module into curdlan gel disrupted the gel’s network structure, enhancing the hydrolysis of curdlan by specific β-1,3-glucanases.

Conclusions

This study offers new insights into the recognition mechanism of glycoside hydrolases toward triple-helical β-1,3-glucans, presenting an effective method to enhance endoglucanase activity and manipulate its product profile. Furthermore, it discovered a CBM module capable of disrupting the quaternary structures of curdlan, thereby boosting the hydrolytic activity of curdlan gel when co-incubated with β-1,3-glucanases. These findings hold relevance for developing future enzyme and CBM cocktails useful in GOS production from curdlan degradation.
Attributes of Anopheles gambiae swarms in South Central Uganda
Authors: Birungi Krystal , Mabuka Danspaid P. , Balyesima Victor , Tripet Frederic , Kayondo Jonathan K.
Published: March 2024

Background

Anopheles gambiae continues to be widespread and an important malaria vector species complex in Uganda. New approaches to malaria vector control are being explored including population suppression through swarm reductions and genetic modification involving gene drives. Designing and evaluating these new interventions require good understanding of the biology of the target vectors. Anopheles mosquito swarms have historically been hard to locate in Uganda and therefore have remained poorly characterized. In this study we sought to identify and characterize An. gambiae s.l mosquito swarms in three study sites of high An. gambiae s.l prevalence within Central Uganda.

Methods

Nine sampling visits were made to three villages over a 2-year period. Sampling targeted both wet and dry seasons and was done for 2 days per village during each trip, using sweep nets. All swarm data were analysed using the JMP 14 software (SAS Institute, Inc., Cary, NC, USA), parametrically or non-parametrically as appropriate.

Results

Most of the An. gambiae s.s. swarms sampled during this study were single-species swarms. However, some mixed An. gambiae s.s. and Culex spp. mosquito swarms were also observed. Swarms were larger in the wet season than in the dry season. Mean swarm height ranged from 2.16 m to 3.13 m off the ground and only varied between villages but not by season. Anopheles gambiae mosquitoes were present in all three villages, preferred to swarm over bare ground markers, and could be effectively sampled by field samplers.

Conclusions

This study demonstrated that An. gambiae s.l swarms could be effectively located and sampled in South Central Uganda and provided in-depth descriptions of hitherto poorly understood aspects of An. gambiae local swarm characteristics. Swarms were found close to inhabited households and were greater in size and number during the rainy season. Anopheles gambiae s.s swarms were significantly associated with bare ground markers and were sometimes at heights over 4 m above the ground, showing a necessity to develop tools suitable for swarm sampling at these heights. While mixed species swarms have been reported before elsewhere, this is the first documented instance of mixed genus swarms found in Uganda and should be studied further as it could have implications for swarm sampling explorations where multiple species of mosquitoes exist.

Graphical Abstract
Correlation between time in range and serum uric acid in Chinese patients with type-2 diabetes: an observational cross-sectional study
Authors: Liu Yan , Peng Xiaoren , Qiu Chunjian , Shao Jiaqing
Published: March 2024

Background

At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM).

Methods

A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5–306.0 µmol/L), Q3 (306.0–385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point.

Results

TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, β was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05).

Conclusions

There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control.
Comment on "Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update"
Authors: Bai Yan , Zhang Fan
Published: March 2024

In the study published by Sun et al., a systematic review and meta-analysis illustrated the advantageous of stem cell therapy in diabetic foot and can improve the quality of life of patients. Nevertheless, the authors had a lack of knowledge regarding the methodology of the meta-analysis, which had four main aspects: (1) The textual report is inconsistent with the forest plot results, i.e., the authors have insufficient knowledge of RevMan. (2) The "zero event" needs to be corrected for summary analysis. (3) Lack of aesthetics in the forest plots. (4) Registration is recommended for systematic reviews and meta-analyses.
Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery
Authors: Shen Lingling , Fang Jian , Liu Lulu , Yang Fei , Jenkins Jeremy L. , Kutchukian Peter S. , Wang He
Published: March 2024

We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.
Therapeutic and immunomodulatory potentials of mesenchymal stromal/stem cells and immune checkpoints related molecules
Authors: Hazrati Ali , Malekpour Kosar , Khorramdelazad Hossein , Rajaei Samira , Hashemi Seyed Mahmoud
Published: March 2024

Mesenchymal stromal/stem cells (MSCs) are used in many studies due to their therapeutic potential, including their differentiative ability and immunomodulatory properties. These cells perform their therapeutic functions by using various mechanisms, such as the production of anti-inflammatory cytokines, growth factors, direct cell-to-cell contact, extracellular vesicles (EVs) production, and mitochondrial transfer. However, mechanisms related to immune checkpoints (ICPs) and their effect on the immunomodulatory ability of MSCs are less discussed. The main function of ICPs is to prevent the initiation of unwanted responses and to regulate the immune system responses to maintain the homeostasis of these responses. ICPs are produced by various types of immune system regulatory cells, and defects in their expression and function may be associated with excessive responses that can ultimately lead to autoimmunity. Also, by expressing different types of ICPs and their ligands (ICPLs), tumor cells prevent the formation and durability of immune responses, which leads to tumors' immune escape. ICPs and ICPLs can be produced by MSCs and affect immune cell responses both through their secretion into the microenvironment or direct cell-to-cell interaction. Pre-treatment of MSCs in inflammatory conditions leads to an increase in their therapeutic potential. In addition to the effect that inflammatory environments have on the production of anti-inflammatory cytokines by MSCs, they can increase the expression of various types of ICPLs. In this review, we discuss different types of ICPLs and ICPs expressed by MSCs and their effect on their immunomodulatory and therapeutic potential.
Sensitive and reliable miRNA analysis based on cyclic reverse transcription and CRISPR-Cas12a-assisted signal cycle
Authors: Yang Xiaoqing , Gao Jie
Published: March 2024

MicroRNAs (miRNAs), a category of small molecules that possess significant regulatory capabilities, have been extensively employed as biomarkers in the domain of biosensing to facilitate the early detection of diverse ailments. However, sensitive and accurate miRNA detection remains a huge challenge due to the high similarity between the homologous sequences and low abundance. Therefore, it is essential to develop methods with high sensitivity and specificity for miRNA detection. In this study, we present the development of a signal cycle-based platform that utilizes cyclic reverse transcription (CRT) and CRISPR-Cas12a to enable the precise and sensitive detection of microRNAs. The CRT mechanism facilitates precise target recognition in the presence of target miRNA, thereby converting miRNA signals to DNA signals. The trans-cleavage activity of the Cas12a protein is triggered by the formation of complete hairpin-shaped CRT products; this results in the cleavage of the DNA section contained in the H probe, while the RNA section (“4”@MBs) remains loaded onto the surface of magnetic beads (MB). By binding with the “reporter” sensor, the “4” sequences create an RNA/DNA duplex that the duplex-specific nuclease (DSN) can recognize. The “reporter” probe is thus metabolized, leading to the reappearance of the fluorescence signal. By capitalizing on the exceptional fidelity and selectivity of CRISPR/Cas12a, as well as the substantial impact of triggered enzymatic cycle amplification, this approach demonstrated remarkable sensitivity and specificity in miRNA detection, even in a complex environment containing 10% fetal bovine serum (FBS) and a serum sample. In contrast, a detection limit of 3.2 fM is conceivable. Furthermore, this approach maintained a notable degree of stability, which was anticipated to result in the detection of miRNAs in an effective and sensitive manner.
Direct and indirect instruction in educational robotics: a comparative study of task performance per cognitive level and student perception
Authors: Anđić Branko , Maričić Mirjana , Mumcu Filiz , Prodromou Theodosia , Leoste Janika , Saimon Musa , Lavicza Zsolt
Published: March 2024

Educational Robotics (ER) has emerged as one of the tools to improve STEM learning in primary education if students are properly instructed. However, there is a lack of studies that guide teachers on which type of instruction should be used for ER in STEM between direct (DI) and indirect instruction (II). As a result, the present study aims to compare the two types of instructions in terms of their effect on learning outcomes, students’ perceptions, and students’ gender differences. We adopted a quasi-experiment comparative research design involving 100 ninth-grade students (13–14 years old). We collected data through achievement tests and perception questionnaires and analyzed them using Cochran’s Q-test, Mann–Whitney U-test, and independent samples t-test. Results show that the group in which II was used performed better than those from the group where DI was used. Also, the results show that girls performed better with DI than boys. Furthermore, students perceived ER as useful for developing collaboration and interest in STEM. Therefore, teachers should be supported in learning how to use II and DI strategically in ER to enhance STEM learning.
A blueprint for patient and public involvement in the development of a reporting guideline for systematic reviews of outcome measurement instruments: PRISMA-COSMIN for OMIs 2024
Authors: Elsman Ellen B. M. , Smith Maureen , Hofstetter Catherine , Gavin Frank , Jobson Estelle , Markham Sarah , Ricketts Juanna , Baba Ami , Butcher Nancy J. , Offringa Martin
Published: March 2024

Background

In recent years, projects to develop reporting guidelines have attempted to integrate the perspectives of patients and public members. Best practices for patient and public involvement (PPI) in such projects have not yet been established. We recently developed an extension of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), to be used for systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) for OMIs 2024. Patients and public members formed a small but impactful stakeholder group. We critically evaluated the PPI component in this project and developed recommendations for conducting PPI when developing reporting guidelines.

Main text

A patient partner was an integral research team member at the project development and grant application stage. Once the project started, five patient and public contributors (PPCs) were recruited to participate in the Delphi study; three PPCs contributed to subsequent steps. We collected quantitative feedback through surveys; qualitative feedback was garnered through a focus group discussion after the Delphi study and through debrief meetings after subsequent project activities. Feedback was thematically combined with reflections from the research team, and was predominantly positive. The following themes emerged: importance of PPI partnership, number of PPCs involved, onboarding, design of Delphi surveys, flexibility in the process, complexity of PPI in methodological research, and power imbalances. Impacts of PPI on the content and presentation of the reporting guideline were evident, and reciprocal learning between PPCs and the research team occurred throughout the project. Lessons learned were translated into 17 recommendations for future projects.

Conclusion

Integrating PPI in the development of PRISMA-COSMIN for OMIs 2024 was feasible and considered valuable by PPCs and the research team. Our approach can be applied by others wishing to integrate PPI in developing reporting guidelines.
Joint application of plant immunity-inducing elicitors and fungicides to control Phytophthora diseases
Authors: Chen Rubin , Ma Dicheng , Bao Yazhou , Wang Weijie , Du Dandan , Chen Xujun , Dou Daolong , Liang Xiangxiu
Published: March 2024

Phytophthora are destructive plant pathogens that pose a serious threat to crop production. Traditional control methods rely heavily on chemical fungicides, which are harmful to the environment and human health. Currently, effective green prevention and control methods for Phytophthora pathogens are lacking. Plants rely primarily on their innate immune system to resist pathogens. Plant cells perceive pathogen invasion and activate immune responses by recognizing specific pathogen-derived molecules, called elicitors, which mainly include pathogen-associated molecular patterns (PAMPs) and microbial effector proteins. PAMPs, which are conserved molecular features of microbes and recognized by plant cell surface-localized pattern-recognition receptors (PRRs), activate mild and broad-spectrum disease resistance. However, there are few reports on elicitor proteins that induce broad resistance against Phytophthora pathogens. In this study, we identified BcIEB1, a fungal-derived PAMP, which activated plant immune responses in a BAK1- and SOBIR1-dependent manner. BcIEB1 could induce plant resistance to various Phytophthora pathogens, including P. capsici, P. infestans, and P. parasitica. We further found that the combination of lower concentrations of BcIEB1 with fungicides, such as pyraclostrobin, azoxystrobin, and metalaxyl-M, could enhance the effect on Phytophthora disease control while reducing the dependence on fungicides, thereby reducing environmental pollution. This study identified a novel, less toxic strategy for controlling Phytophthora diseases.
Tailoring IPM plans to fight a cloaked pest: helping smallholder farmers combat the sweetpotato weevil in sub-Saharan Africa
Authors: Keyser Chad A. , Walters Frederick S. , Turner Haley , Armstrong Elka , Davis Jeff , Bissinger Brooke , Johnson Brant , Alajo Agnes , Musana Paul , Odongo Joseph , Yada Benard , Otema Milton A.
Published: March 2024

Africa accounts for a significant portion of the world’s sweetpotato production where it is widely grown as a staple crop. In sub-Saharan Africa (SSA), sweetpotato serves as an important year-round source of calories and nutrition, a form of income for smallholder and pre-commercial farmers, and is increasingly used as silage for animal feed. However, yield per hectare is considerably lower in SSA than from other regions primarily due to sweetpotato weevils (SPW,
Cylas
spp., Coleoptera: Brentidae). Weevil feeding causes physical damage to the root and can induce chemical responses that give the storage root a bitter taste, both of which make them unmarketable. Commercial growers in many developed countries rely on frequent chemical treatments and strict quarantine regulations to control SPW, however, this approach is currently not practical for many areas of SSA. In this paper we, (1) outline factors that contribute to SPW infestation; (2) review available strategies and ongoing research for control of SPW, including chemical pesticides, biological control (macro-organismal as well as microbial control), cultural practices, selective breeding, and biotechnology; and (3) discuss the potential for implementing an integrated pest management (IPM) approach that leverages a combination of techniques. We rationalize that a multifaceted strategy for SPW control will improve both the quantity and quality of sweetpotato production in Africa.
RETRACTED ARTICLE: Current design of rectangular steel silos: limitations and improvement
Authors: Abdelbarr Mohamed H. , Ramadan Osman M. O. , Hilal AlHussein , Sanad A. M. , Abdalla Hany A.
Published: March 2024

This study proposes a modification for the current design approach for square and rectangular silos that accounts for silos’ wall flexibility. First, the authors investigated the effect of wall stiffness symbolized by the wall width-to-thickness ratio (a/t) and silo’s dimensions, on the wall-filling pressure using a recently validated 3D finite element model (FEM). The model was then employed to predict the pressures acting on silos’ walls accounting for the stress state in stored granular materials. Most design formulas and guidelines assume silos’ walls to be rigid. This assumption is acceptable for the case of rigid wall concrete silos; however, it is questionable for semi-rigid, flexible wall metal silos. Consequentially, it is crucial to determine the minimum wall stiffness necessary to secure the applicability of the current design rigid wall assumptions and to propose a way to deal with semi-rigid and flexible walls. To this end, several wall pressure distributions that correspond to filling steel silos with varied wall thicknesses were studied. A new adjustment to the Janssen technique was proposed for a better estimate of the wall-filling pressures for square and rectangular silos. In the case of prismatic silos, the Eurocode uses the Janssen equation together with an equivalent radius of a corresponding circular silo (with the same hydraulic radius) to determine the wall pressure. This method predicts pressure values that are practically accurate for rigid-wall silos, but its accuracy decreases for semi-rigid and flexible-wall silos. As an enhancement, the Janssen equation was modified in this research to generate more accurate pressure estimates based on the equivalent volume concept. The finite element results of several developed models with the same granular material were compared to the estimations of the newly established approach to verify the broad range of its applicability.
Assessing the Global Impact of Ambient Air Pollution on Cancer Incidence and Mortality: A Comprehensive Meta-Analysis
Authors: Ramamoorthy Thilagavathi , Nath Anita , Singh Shubhra , Mathew Stany , Pant Apourv , Sheela Samvedana , Kaur Gurpreet , Sathishkumar Krishnan , Mathur Prashant
Published: March 2024

PURPOSE

This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers.

METHODS

This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software.

RESULTS

The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I2, 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I2, 68.52%) and nitrogen dioxide (NO2) (RR, 1.03 [95% CI, 1.01 to 1.05]; I2, 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I2, 94.77%; P < .001). Among the four pollutants, PM2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I2, 95.33%) and NO2 (RR, 1.05 [95% CI, 1.02 to 1.08]; I2, 89.98%) were associated with lung cancer mortality.

CONCLUSION

The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.