bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractToday, 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

Abstract
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

AbstractImproving 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

Abstract
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

Abstract
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

Abstract
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.