bluuebunny/crossref_metadata_2025 huggingface dataset:
Distal Clavicular Resection Worsens Outcomes in Rotator Cuff Repair: A National Database Study
Authors: Wiener Joshua M , Sanghvi Parshva A , Smith Kira A , Moyal Andrew , Piper Molly M , Calcei Jacob G
Published: May 2024

Introduction

Distal clavicular resection (DCR) is a procedure used to alleviate acromioclavicular joint (ACJ) pain, often done alongside rotator cuff repair (RCR). This investigation explored the relationships between DCR and RCR, outcomes of DCR during RCR, and complication rates of DCR.

Methods

This retrospective study used electronic medical record data from the TriNetX database. Cohorts were subdivided based on the timeline of DCR in comparison to RCR, as well as comparing RCR with DCR against RCR without DCR.

Results

In total 46 534 patients underwent RCR with 14.8% (6898) of these patients also undergoing DCR. And 72.8% (5021) had DCR during RCR, and 10.7% (740) had DCR after RCR. Less than 5% (<10) of patients with preexisting ACJ pain required DCR 3 years postoperatively, and 0.002% (78) patients without ACJ pain developed ACJ pain within 3 years. Less that 20 patients underwent DCR within 3 years of being diagnosed with ACJ pain. Patients who had RCR with DCR were more likely to have chronic pain postoperatively ( P < .0001).

Conclusion

Patients undergoing RCR do not require subsequent DCR. Performing DCR does not offer significant benefit when compared to performing isolated RCR without DCR in patients with preexisting ACJ pain, but increases risk for ACJ instability and chronic pain.
Towards an understanding of the embedded nature of everyday ethical reasoning in paramedic education and practice
Authors: Campbell Iain , Hill Lawrence , Copson Joe
Published: May 2024

Paramedicine is increasingly complex in affective, behavioural, and cognitive domains of practice. The ability to navigate this complexity is essential for paramedics who are required to simultaneously practice assertively, dynamically, sensitively, and professionally. Although these may seem to be superficially incongruent ways of practising, through insightful and reflexive practice underpinned by appropriate ethical approaches, paramedics can navigate the complexity inherent in paramedic work whether care episodes are routine or extreme. In what follows, we discuss the potential of virtue ethics as a way of navigating complexity in paramedic practice and preparing clinicians for the varied work they manage as paramedics. We do this by first describing some of the issues faced by the modern paramedic, outlining ethical approaches to practice, then working through a vignette showing how a deeper understanding of ethics and utilising a virtue ethics approach may have helped the clinicians navigate a typical ethical dilemma found in practice.
Sleeping soundly? Testing the links between sleep quality and neurodevelopmental characteristics
Authors: Bettencourt Madalena V. , Mareva Silvana ,   The CALM team, Astle Duncan E.
Published: May 2024

Sleep plays a major role in child development and sleep problems have been implicated in several neurodevelopmental conditions. However, its exact role in these conditions remains unknown. Co-occurrence is a core challenge of the existing diagnostic framework, with many advocating for a transdiagnostic approach to studying neurodevelopment. In this exploratory investigation, we look at a transdiagnostic sample of 299 children to (1) identify and compare data-driven sleep profiles and explore their links to behaviour, cognition and learning and (2) use a network approach to simultaneously characterise the relationship between sleep and symptoms of behaviour, communication and mental health. Cluster analysis identified two sleep profiles – regular sleepers and poor sleepers. Between-group comparisons showed that poor sleepers disproportionately experienced poorer emotion regulation, peer relationships and structural language. The network analysis suggested that after statistically accounting for the overlap between symptoms of behaviour, communication and mental health, sleep remained directly linked to multiple symptoms, with a particularly strong relationship with emotion regulation. These findings advance our knowledge of the role of sleep in neurodevelopmental conditions, highlighting its importance as a transdiagnostic process and priority in neurodevelopmental research.

Lay abstract

Sleep quality and quantity are essential in children’s development. Children diagnosed with neurodevelopmental conditions tend to present more sleep problems. However, the exact interaction between sleep and these conditions is still under discussion. Here, novel statistical approaches were used to explore the relationship between sleep and aspects of children’s behaviour, communication, and mental health. These methods identified two groups of children based on their sleep quality: poor sleepers and regular sleepers. The two groups were compared across a broad set of measures including neurodevelopmental difficulties, learning outcomes and mental health. The regular sleepers performed better than those with sleep problems on all measures, with poor sleepers presenting crucial difficulties in emotion regulation, peer relationships and structural language. Using network models, an explorative global analysis of all the participants together reiterated the influence of structural language on other behaviours and uncovered a strong connection between sleep and emotion regulation. Overall, this study improves our knowledge of the role of sleep in conditions affecting brain development and its relationship with behaviour, communication and mental health.
Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib
Authors: Woyach Jennifer A. , Jones Daniel , Jurczak Wojciech , Robak Tadeusz , Illés Árpád , Kater Arnon P. , Ghia Paolo , Byrd John C. , Seymour John F. , Long Susan , Mohamed Nehad , Benrashid Samon , Lai Tzung-Huei , De Jesus Gary , Lai Richard , de Bruin Gerjan , Rule Simon , Munugalavadla Veerendra
Published: May 2024

Chronic lymphocytic leukemia (CLL) progression during Bruton tyrosine kinase (BTK) inhibitor treatment is typically characterized by emergent B-cell receptor pathway mutations. Using peripheral blood samples from patients with relapsed/refractory CLL in ELEVATE-RR (NCT02477696; median 2 prior therapies), we report clonal evolution data for patients progressing on acalabrutinib or ibrutinib (median follow-up, 41 months). Paired (baseline and progression) samples were available for 47 (excluding 1 Richter) acalabrutinib-treated and 30 (excluding 6 Richter) ibrutinib-treated patients. At progression, emergent BTK mutations were observed in 31 acalabrutinib-treated (66%) and 11 ibrutinib-treated patients (37%; median variant allele fraction [VAF], 16.1% vs 15.6%, respectively). BTK C481S mutations were most common in both groups; T474I (n = 9; 8 co-occurring with C481) and the novel E41V mutation within the pleckstrin homology domain of BTK (n = 1) occurred with acalabrutinib, whereas neither mutation occurred with ibrutinib. L528W and A428D comutations presented in 1 ibrutinib-treated patient. Preexisting TP53 mutations were present in 25 acalabrutinib-treated (53.2%) and 16 ibrutinib-treated patients (53.3%) at screening. Emergent TP53 mutations occurred with acalabrutinib and ibrutinib (13% vs 7%; median VAF, 6.0% vs 37.3%, respectively). Six acalabrutinib-treated patients and 1 ibrutinib-treated patient had emergent TP53/BTK comutations. Emergent PLCG2 mutations occurred in 3 acalabrutinib-treated (6%) and 6 ibrutinib-treated patients (20%). One acalabrutinib-treated patient and 4 ibrutinib-treated patients had emergent BTK/PLCG2 comutations. Although common BTK C481 mutations were observed with both treatments, patterns of mutation and comutation frequency, mutation VAF, and uncommon BTK variants varied with acalabrutinib (T474I and E41V) and ibrutinib (L528W and A428D) in this patient population. The trial was registered at www.clinicaltrials.gov as #NCT02477696.
Epigenomic and transcriptomic persistence of heat stress memory in strawberry (Fragaria vesca)
Authors: López María-Estefanía , Denoyes Béatrice , Bucher Etienne
Published: May 2024

Background

In plants, epigenetic stress memory has so far been found to be largely transient. Here, we wanted to assess the heritability of heat stress-induced epigenetic and transcriptomic changes following woodland strawberry (Fragaria vesca) reproduction. Strawberry is an ideal model to study epigenetic inheritance because it presents two modes of reproduction: sexual (self-pollinated plants) and asexual (clonally propagated plants named daughter plants). Taking advantage of this model, we investigated whether heat stress-induced DNA methylation changes can be transmitted via asexual reproduction.

Results

Our genome-wide study provides evidence for stress memory acquisition and maintenance in F. vesca. We found that specific DNA methylation marks or epimutations are stably transmitted over at least three asexual generations. Some of the epimutations were associated with transcriptional changes after heat stress.

Conclusion

Our findings show that the strawberry methylome and transcriptome respond with a high level of flexibility to heat stress. Notably, independent plants acquired the same epimutations and those were inherited by their asexual progenies. Overall, the asexual progenies can retain some information in the genome of past stresses encountered by their progenitors. This molecular memory, also documented at the transcriptional level, might be involved in functional plasticity and stress adaptation. Finally, these findings may contribute to novel breeding approaches for climate-ready plants.
Meta-analysis of the association between interleukin-17 and ischemic cardiovascular disease
Authors: Miao Yu , Yan Tao , Liu Jia , Zhang Chunfa , Yan Jinli , Xu Lei , Zhang Nan , Zhang Xingguang
Published: May 2024

Background

Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD.

Methods

We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis.

Results

A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53–2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies.

Conclusion

Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.
The value of fetal magnetic resonance imaging in diagnosis of congenital anomalies of the fetal body: a systematic review and meta-analysis
Authors: Wilson Louise , Whitby Elspeth H.
Published: May 2024

Objectives

To undertake a systematic review to assess the accuracy of fetal MRI in diagnosis of non-CNS congenital anomalies of the fetal body in comparison with antenatal ultrasound when correlated to postnatal diagnosis.

Methods

Searches were conducted from electronic databases, key journals and reference lists for eligible papers. Inclusion criteria was original research studies comparing the diagnostic results of antenatal ultrasound, fetal MRI and final postnatal diagnosis via imaging, surgery or post-mortem testing. Studies of CNS anomalies were excluded. Studies were assessed for risk of bias by two reviewers working independently and data was then extracted by a single reviewer.

Results

12 studies were included with a total of 361 eligible patients who underwent USS and MRI and had a postnatal diagnosis. USS alone had a diagnostic accuracy of 60.6% whereas MRI had an improved diagnostic accuracy of 86.4%. The overall odds ratio was 0.86 (CI 0.202–1.519 and p-value < 0.01).

Conclusion

Fetal MRI makes a significant contribution to accurate diagnosis of congenital abnormalities of the fetal body; especially in genito-urinary anomalies. More research is needed to improve the evidence base for the role of fetal MRI in diagnosis of congenital anomalies in other body systems.
Insights for clinical management from the real-life data of the centralized West of Scotland biliary cancer clinic
Authors: Zanuso Valentina , Nash Tamsin , Casolino Raffaella , Armstrong Gregory , Pallise Ona , Milne Jen , Braconi Chiara
Published: May 2024

Background

With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations.

Methods and results

We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28–84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT.

Conclusions

About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.
Analysis of similarities and differences between transient symptomatic zinc deficiency and acrodermatitis enteropathica in children: a case report of a Chinese Yi-ethnic infant
Authors: Gu Li , He Xue-Hui , Zhu Peng
Published: May 2024

Background

Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging.

Case presentation

Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient’s blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence.

Conclusions

The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.
Factors associated with the co-utilization of oral rehydration solution and zinc for treating diarrhea among under-five children in 35 sub-saharan Africa countries: a generalized linear mixed effect modeling with robust error variance
Authors: Seifu Beminate Lemma , Legesse Bruck Tesfaye , Yehuala Tirualem Zeleke , Kase Bizunesh Fantahun , Asmare Zufan Alamrie , Mulaw Getahun Fentaw , Tebeje Tsion Mulat , Mare Kusse Urmale
Published: May 2024

Introduction

Even though childhood diarrhea is treated with a simple treatment solution, it continues to be one of the leading causes of under-five child mortality and malnutrition globally. In resource-limited settings such as Sub-Saharan Africa (SSA), the combination of oral rehydration salts (ORS) and zinc is regarded as an effective treatment for diarrhea; however, its utilization is very low. The purpose of this study was to determine the proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA.

Methods

The proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA were determined using secondary data analysis of recent Demographic and Health Surveys (DHS) of 35 SSA countries. The study included a total of 44,341 under-five children with diarrhea in weighted samples. A generalized linear mixed-effects model with robust error variance was used. For the variables included in the final model, adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were estimated. A model with the lowest deviance value were considered as the best-fitted model.

Result

The pooled proportion of co-utilization of ORS and zinc for the treatment of diarrhea among under five children in SSA countries was 43.58% with a 95% CI (43.15%, 44.01%). Sex of the child, maternal age, residence, maternal educational and employment status, wealth index, media exposure, perceived distance to health facility and insurance coverage were statistically significant determinants of ORS and Zinc co-utilization for treating diarrhea among under five children in SSA.

Conclusion

Only less than half of under-five children with diarrhea in SSA were treated with a combination of ORS and zinc. Thus, strengthening information dissemination through mass media, and community-level health education programs are important to scale up the utilization of the recommended combination treatment. Furthermore, increasing health insurance coverage, and establishing strategies to address the community with difficulty in accessing health facilities is also crucial in improving the use of the treatment.
Experiences of UK clinical scientists (Physical Sciences modality) with their regulator, the Health and Care Professions Council: results of a 2022 survey
Authors: McJury Mark
Published: May 2024

Background

In healthcare, regulation of professions is an important tool to protect the public. With increasing regulation however, professions find themselves under increasing scrutiny. Recently there has also been considerable concern with regulator performance, with high profile reports pointing to cases of inefficiency and bias. Whilst reports have often focused on large staff groups, such as doctors, in the literature there is a dearth of data on the experiences of smaller professional groups such Clinical Scientists with their regulator, the Health and Care Professions Council.

This article reports the findings of a survey from Clinical Scientists (Physical Sciences modality) about their experiences with their regulator, and their perception of the quality and safety of that regulation.

Methods

Between July–October 2022, a survey was conducted via the Medical Physics and Engineering mail-base, open to all medical physicists & engineers. Questions covered typical topics of registration, communication, audit and fitness to practice. The questionnaire consisted of open and closed questions. Likert scoring, and thematic analysis were used to assess the quantitative and qualitative data.

Results

Of 146 responses recorded, analysis was based on 143 respondents. Overall survey sentiment was significantly more negative than positive, in terms of regulator performance (negative responses 159; positive 106; significant at p < 0.001). Continuous Professional Development audit was rated median 4; other topics were rated as neutral (fitness to practice, policies & procedures); and some as poor (value).

Conclusions

The Clinical Scientist (Physical Sciences) professional registrants rated the performance of their regulator more negatively than other reported assessments (by the Professional Standards Authority). Survey respondents suggested a variety of performance aspects, such as communication and fitness to practice, would benefit from improvement. Indications from this small dataset, suggest a larger survey of HCPC registrants would be useful.
Responsible coordination of municipal health and care services for individuals with serious mental illness: a participatory qualitative study with service users and professionals
Authors: Skjærpe Jorunn Nærland , Iakovleva Tatiana Aleksandrovna , Storm Marianne
Published: May 2024

Background

Care coordination is crucial to ensure the health of individuals with serious mental illness. The aim of this study was to describe and analyze an inclusive innovation process for coordinating municipal health and care services for individuals with serious mental illness.

Methods

We conducted café dialogues with professionals and service users with serious mental illness. The café dialogues engaged participants in conversation and knowledge exchange about care coordination, adressing topics of efficiency, challenges, and improvement. We used a responsible innovation framework to analyze the innovation process.

Results

Responsible coordination requires promoting service users’ health and ensuring communication and mutual awareness between professionals. Individual-level factors supporting responsible coordination included service users knowing their assigned professionals, personalized healthcare services, and access to meaningful activities. Provider-level factors included effective coordination routines, communication, information exchange, and professional familiarity. Results reflect professionals’ and service users’ perspectives on efficient care coordination, existing challenges, and measures to improve care coordination.

Conclusion

Café dialogues are an inclusive, participatory method that can produce insights into the responsible coordination of municipal health and care services for individuals with serious mental illness. The responsible innovation framework is helpful in identifying care coordination challenges and measures for responsible coordination.
Drawing up the public national Rational Pharmacotherapy Action Plan as part of social and health services reform in Finland: a bottom-up approach involving stakeholders
Authors: Tahvanainen Heidi , Voipio-Pulkki Liisa-Maria , Hämeen-Anttila Katri , Närhi Ulla , Mäntyranta Taina , Holmström Anna-Riia , Airaksinen Marja
Published: May 2024

Background

Ensuring equal access to medicines and their appropriate and safe use at reasonable costs are core functions of health systems. Despite that, few descriptions of national medicines policies' development processes and implementation strategies have been published. This study aimed to describe the government program-based development of the Rational Pharmacotherapy Action Plan in Finland as a part of the undergoing major health and social service system reform, also covering the implementation of rational pharmacotherapy in the reformed system and processes.

Methods

The data of this qualitative study consisted of public reports and Steering Group meeting memos related to the development of the national Rational Pharmacotherapy Action Plan that the Ministry of Social Affairs and Health coordinated. Qualitative content analysis applying systems theory and the conceptual framework of integrated services as theoretical frameworks was used as an analysis method.

Results

The national Rational Pharmacotherapy Action Plan covering 2018–2022 was created in a bottom-up development process involving a wide range of stakeholders. Rational pharmacotherapy was redefined by adding equality as the fifth pillar to complement the previously defined pillars of being effective, safe, high-quality, and cost-effective. The Action Plan formed a normative framework for long-term development, with a vision and principles focusing on people-centeredness, better coordination and management of the medication use processes, the continuity of treatment paths and the flow of patient and medicines information through partnerships, and evidence-informed policies and practices.

Conclusion

Through intensive stakeholder participation, the bottom-up approach created a national vision and principles of rational pharmacotherapy along with strong commitment to implementing the goals and measures. The concern lies in ensuring the continuity of the Action Plan implementation and achieving a balanced long-term development aligned with the integrated and reformed national social and health services system. The development of the pharmaceutical system has several national and EU-level dependencies requiring political long-term commitment. While the Action Plan differs from the national medicines policy, it forms a good basis for long-term development covering important parts of medicine policy at the micro, meso, and macro levels of the service system.
Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
Authors: Li Huayi , Peng Zikun , Zhu Jianqing , Zhao Weidong , Huang Yi , An Ruifang , Zheng Hong , Qu Pengpeng , Wang Li , Zhou Qi , Wang Danbo , Lou Ge , Wang Jing , Wang Ke , Kong Beihua , Xie Xing , Yin Rutie , Low John , Rozita Abdul Malik , Sen Lim Chun , Meng Yong Chee , Kiong Kho Swee , Liu Jihong , Liang Zhiqing , Lv Weiguo , Zhu Yaping , Hu Weiguo , Sun Wei , Su Jingya , Wang Qiqi , Zang Rongyu , Ma Ding , Gao Qinglei
Published: May 2024

Background

The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy.

Methods

HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS).

Results

This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)].

Conclusions

HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2.

Trial registration

NCT03534453. Registered at May 23, 2018.
Element mobility during basalt-water-CO2 interaction: observations in natural systems vs. laboratory experiments and implication for carbon storage
Authors: Romano Pierangelo , Brusca Lorenzo , Liotta Marcello
Published: May 2024

Today, carbon dioxide removal from the atmosphere is the most ambitious challenge to mitigate climate changes. Basalt rocks are abundant on the Earth’s surface (≈ 10%) and very abundant in the ocean floors and subaerial environments. Glassy matrix and minerals constituting these rocks contain metals (Ca2+, Mg2+, Fe2+) that can react with carbonic acid to form metal carbonates (CaCO3, MgO3 and FeCO3). Here, we present a data compilation of the chemical composition of waters circulating in basalt aquifers worldwide and the results of simple basalt-water-CO2 experiments. Induced or naturally occurring weathering of basalts rocks release elements in waters and elemental concentration is closely dependent on water CO2 concentration (and hence on water pH). We also performed two series of experiments where basaltic rock powder interacts with CO2-charged waters for one month at room temperature. Laboratory experiments evidenced that in the first stages of water-rock interaction, the high content of CO2 dissolved in water accelerates the basalt weathering process, releasing in the water not only elements that can form carbonate minerals but also other elements, which depending on their concentration can be essential or toxic for life. Relative mobility of elements such as Fe and Al, together with rare earth elements, increases at low pH conditions, while it decreases notably at neutral pH conditions. The comparison between experimental findings and natural evidence allowed to better understand the geochemical processes in basaltic aquifers hosted in active and inactive volcanic systems and to discuss these findings in light of the potential environmental impact of CO2 storage in mafic and ultramafic rocks.
Importance of the electrophoresis and pulse energy for siRNA-mediated gene silencing by electroporation in differentiated primary human myotubes
Authors: Pavlin Mojca , Škorja Milić Nives , Kandušer Maša , Pirkmajer Sergej
Published: May 2024

Background

Electrotransfection is based on application of high-voltage pulses that transiently increase membrane permeability, which enables delivery of DNA and RNA in vitro and in vivo. Its advantage in applications such as gene therapy and vaccination is that it does not use viral vectors. Skeletal muscles are among the most commonly used target tissues. While siRNA delivery into undifferentiated myoblasts is very efficient, electrotransfection of siRNA into differentiated myotubes presents a challenge. Our aim was to develop efficient protocol for electroporation-based siRNA delivery in cultured primary human myotubes and to identify crucial mechanisms and parameters that would enable faster optimization of electrotransfection in various cell lines.

Results

We established optimal electroporation parameters for efficient siRNA delivery in cultured myotubes and achieved efficient knock-down of HIF-1α while preserving cells viability. The results show that electropermeabilization is a crucial step for siRNA electrotransfection in myotubes. Decrease in viability was observed for higher electric energy of the pulses, conversely lower pulse energy enabled higher electrotransfection silencing yield. Experimental data together with the theoretical analysis demonstrate that siRNA electrotransfer is a complex process where electropermeabilization, electrophoresis, siRNA translocation, and viability are all functions of pulsing parameters. However, despite this complexity, we demonstrated that pulse parameters for efficient delivery of small molecule such as PI, can be used as a starting point for optimization of electroporation parameters for siRNA delivery into cells in vitro if viability is preserved.

Conclusions

The optimized experimental protocol provides the basis for application of electrotransfer for silencing of various target genes in cultured human myotubes and more broadly for electrotransfection of various primary cell and cell lines. Together with the theoretical analysis our data offer new insights into mechanisms that underlie electroporation-based delivery of short RNA molecules, which can aid to faster optimisation of the pulse parameters in vitro and in vivo.
Therapeutic potentials of FexMoyS-PEG nanoparticles in colorectal cancer: a multimodal approach via ROS-ferroptosis-glycolysis regulation
Authors: Yu Zhilong , Wang Chenyi , Ye Yingjiang , Wang Shan , Jiang Kewei
Published: May 2024

Improving cancer therapy by targeting the adverse tumor microenvironment (TME) rather than the cancer cells presents a novel and potentially effective strategy. In this study, we introduced FexMoyS nanoparticles (NPs), which act as sequential bioreactors to manipulate the TME. FexMoyS NPs were synthesized using thermal decomposition and modified with polyethylene glycol (PEG). Their morphology, chemical composition, and photothermal properties were characterized. The capability to produce ROS and deplete GSH was evaluated. Effects on CRC cells, including cell viability, apoptosis, and glycolysis, were tested through various in vitro assays. In vivo efficacy was determined using CRC-bearing mouse models and patient-derived xenograft (PDX) models. The impact on the MAPK signaling pathway and tumor metabolism was also examined. The FexMoyS NPs showed efficient catalytic activity, leading to increased ROS production and GSH depletion, inducing ferroptosis, and suppressing glycolysis in CRC cells. In vivo, the NPs significantly inhibited tumor growth, particularly when combined with NIR light therapy, indicating a synergistic effect of photothermal therapy and chemodynamic therapy. Biosafety assessments revealed no significant toxicity in treated mice. RNA sequencing suggested that the NPs impact metabolism and potentially immune processes within CRC cells. FexMoyS NPs present a promising multifaceted approach for CRC treatment, effectively targeting tumor cells while maintaining biosafety. The nanoparticles exhibit potential for clinical translation, offering a new avenue for cancer therapy.
A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer
Authors: Wu Yue , Zhu Min , Sun Baihe , Chen Yongting , Huang Yuping , Gai Junwei , Li Guanghui , Li Yanfei , Wan Yakun , Ma Linlin
Published: May 2024

Background

Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among cancer patients, coupled with a suboptimal postoperative survival prognosis. Nectin-4, an overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) to treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically for gastric cancer, and conventional immunoglobulin G (IgG)-based ADCs frequently encounter binding site barriers. Based on the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug conjugates (NDCs) for the treatment of gastric cancer.

Results

An immunized phage display library was established and employed for the selection of Nectin-4-specific Nbs using phage display technology. Subsequently, these Nbs were engineered into homodimers to enhance Nb affinity. To prolong in vivo half-life and reduce immunogenicity, we fused an Nb targeting human serum albumin (HSA), resulting in the development of trivalent humanized Nbs. Further, we site-specifically conjugated a monomethyl auristatin E (MMAE) at the C-terminus of the trivalent Nbs, creating Nectin-4 NDC (huNb26/Nb26-Nbh-MMAE) with a drug-to-antibody ratio (DAR) of 1. Nectin-4 NDC demonstrated excellent in vitro cell-binding activities and cytotoxic efficacy against cells with high Nectin-4 expression. Subsequent administration of Nectin-4 NDC to mice bearing NCI-N87 human gastric cancer xenografts demonstrated rapid tissue penetration and high tumor uptake through in vivo imaging. Moreover, Nectin-4 NDC exhibited noteworthy dose-dependent anti-tumor efficacy in in vivo studies.

Conclusion

We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer.

Graphical abstract
Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance
Authors: Sohn Rebecca , Assar Tina , Kaufhold Isabelle , Brenneis Marco , Braun Sebastian , Junker Marius , Zaucke Frank , Pongratz Georg , Jenei-Lanzl Zsuzsa
Published: May 2024

Background

Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements.

Methods

Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed.

Results

GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level.

Conclusions

This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

Graphical abstract
Magnitude of intestinal parasitic infections and its determinants among HIV/AIDS patients attending at antiretroviral treatment centers in East and West Gojam Zones, Northwest, Ethiopia: institution based cross-sectional study
Authors: Endalamaw Mengistu , Alemneh Abel , Amare Gashaw Azanaw , Fenta Abebe , Belew Habtamu
Published: May 2024

Background

Intestinal parasitic infections (IP) are a major source of morbidity in people living with Human immunodeficiency virus (HIV), particularly in resource-limited settings, mostly as a result of high viral load. Hence, this study aimed to investigate the magnitude of intestinal parasitic infections and its determinants among patients with HIV/AIDS attending public health facilities in East and West Gojam Zones in Ethiopia.

Methods

Institution-based cross-sectional study was conducted on 327 people living with HIV visiting public health facilities from December 2022 to May 2023. A simple random sampling technique was used to recruit participants. Face-to-face interviews were used to collect socio-demographics and determinants. The fresh stool was collected from each patient, transported, and tested in accordance with laboratory standard operating procedures of wet mount, formol-ether concentration technique, and modified acid-fast staining. Data were entered and analyzed in the statistical package for Social Science (SPSS) version 20. A 95% CI with p-value < 0.05 was considered statistically significant.

Results

The overall prevalence of IP in patients with HIV/AIDS was 19.3% (63/327). Hookworm was the most identified parasite 33.3% (21/63) followed by E.histolytica 17% (11/63) and G.lamblia 14.3% (9/63). Parasitic infections were significantly higher among viral load > 1000cps/ml (p = 0.035), WHO stage 4 (p = 0.002), CD4 < 200 cell/mm3 (p = 0.001), and bare foot walking (p = 0.001).

Conclusion

IP infections are moderately high among patients with HIV/AIDS in the study area. The proportion of parasites was greatly affected by high viral load, WHO stage 4, CD4 < 200 cell/mm3, and being barefoot; this gives valuable insight to health professionals, health planners and community health workers. As a result, viral load monitoring, and WHO stage controlling were periodically assessed in patients with HIV/AIDS. Health education, awareness creation, routine stool examination, and environmental hygiene were regularly advocated to increase the life of patients with HIV/AIDS.
Effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery
Authors: Chen Huan , Wang Xin , Zhang Yawen , Liu Wei , Zhou Changhao , Zheng Deli
Published: May 2024

Objective

This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.

Methods

Obese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 μg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6.

Results

The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6.

Conclusion

In obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.
Hybrid Environmentally Friendly Method for RCA Concrete Quality Improvement
Authors: Mardani Alieh , Bui Ngoc Kien , Noguchi Takafumi
Published: May 2024

Research on concrete recycling has led to the discovery of many processes for recycled concrete aggregate (RCA) treatment, each with its pros and cons on quality improvement, resource requirements, or scalability. This study aimed to propose a technique that combines two methods (mechanical grinding and acidic soaking) for mortar removal and improves the quality of RCA so as to realize a zero-waste, highly efficient, few-hours-long single-step process which we call acid milling. A quantitative comparison of aggregate and final concrete quality has been performed between each separate method. The proposed method shows about 57% relative improvement of aggregate quality for water absorption and density, while the concrete experiment shows up to 10% relative improvement for the compressive and flexural strengths compared with the untreated RCA concrete. This study paves the way for an efficient and sustainable concrete recycling process to be applied on a large scale.
Target recognition-initiated allosteric probe-based multiple signal amplification strategy for sensitive and direct Pseudomonas aeruginosa detection
Authors: Xue Kun , Kang Shuhong
Published: May 2024

Pseudomonas aeruginosa (P. aeruginosa), a kind of gram-negative pathogenic bacteria, are causative agents of severe infections, such as lower respiratory tract infections in children and cancers. Detecting low levels of P. aeruginosa in clinical samples in an easy-to-operate manner is highly desired but still poses a problem. Herein, we established a target recognition-initiated allosteric probe-based multiple signal amplification strategy for sensitive detection of P. aeruginosa in a wash-free way. This approach involves the allosteric probe’s accurate recognition and binding to target P. aeruginosa, leading to subsequent multiple-cycle amplification. Afterward, the amplified products were translated to induce the aggregation of gold nanoparticles (AuNPs), resulting in color variations. The utilization of the allosteric probe, which is integrated with the aptamer sequences, enables wash-free detection of P. aeruginosa. Taking the merit of multiple signal amplification process, the suggested method showed a strong linear response to the extracted P. aeruginosa within a concentration range of 10–105 cfu/mL, with a low limit of detection for individual P. aeruginosa detection. The proposed technique has considerable clinical promise for early disease diagnosis because to its high sensitivity and wash-free simplicity.