bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing the work stress of inpatient nurses during the COVID-19 pandemic: a systematic review of organizational interventions
Authors: Zink Maria , Pischke Frederike , Wendsche Johannes , Melzer Marlen 
Published: September 2024

Abstract
Background
During the coronavirus disease 2019 (COVID-19) pandemic, inpatient nurses faced various work stressors. Little is known about organizational interventions that can mitigate the negative consequences of pandemic-related stressors.

Objective
The aim was to provide a synopsis of the literature concerning the types and outcomes of organizational interventions performed during the COVID-19 pandemic that directly (re)organized the work structures of inpatient nurses to address pandemic-related work stressors or to increase nurses’ ability to cope.

Methods
Within this preregistered systematic literature review, we searched four databases (PubMed, PsycINFO, PsycARTICLES, CINAHL) and two preprint databases (MedRxiv, PsyArXiv) for interventional studies of organizational interventions published between 01/2020 and 03/2023 (k = 990 records). We included 12 primary studies after title-abstract and full-text screening. A synthesis of results without meta-analysis was conducted. Risk of bias was assessed with the Cochrane risk-of-bias tool for randomized trials – version 2 (RoB-2) and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool.

Results
All interventions were implemented in hospitals. The reasons given for implementation included pandemic-related work stressors such as a high workload, understaffing, and a lack of medical resources. To respond to the various work stressors, half of the studies took a multilevel approach combining organizational and person-oriented interventions (k = 6). Most studies (k = 8) took a secondary prevention approach, focusing on the organization of rest breaks (k = 5). With respect to outcomes, the studies examined nurse-related stress and resilience, turnover intention, job satisfaction, and other factors. Risk-of-bias analyses revealed that conclusions about the effectiveness of the interventions are limited due to confounding factors and self-selection.

Conclusions
The identified interventions provide a basis for future research to draw conclusions on the effectiveness of organizational interventions during pandemics. The promotion of adequate work breaks could be useful if the work stressors associated with strain and negative consequences cannot be changed directly. However, the same stressors (e.g., high workload) can hinder nurses from participating in offered interventions. This emphasizes the importance of directly addressing inpatient nurses’ work stressors.

Registration
Prospero-ID CRD42023364807 (March 2023).
Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers
Authors: Lee Ji Yoon , Lee Ji Won , Chung Min Sung , Choi Jong Gwon , Sim Sung Hoon , Kim Hyo Jeong , Kim Jeong Eun , Lee Kyoung Eun , Park Yeon Hee , Kang Myoung Joo , Ahn Mi Sun , Chae Yee Soo , Park Ji Hyun , Kim Jee Hyun , Kim Gun Min , Byun Jae Ho , Park Keon Uk , Kim Ju Won , Jung Seung Pil , Lee Jung Hyun , An Jung Seok , Jang Byunghyun , Yoon Dayoung , Kim Jiwon , Hong Jisoo , Koo Harim , Cho Kyu Ran , Kim Cheol Yong , Sa Jason K. , Park Kyong Hwa 
Published: September 2024

Abstract
Background
Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive.

Methods
In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities.

Results
We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy.

Conclusions
Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.
An oncolytic HSV-1 vector induces a therapeutic adaptive immune response against glioblastoma
Authors: Reale Alberto , Gatta Andrea , Shaik Amruth Kaleem Basha , Shallak Mariam , Chiaravalli Anna Maria , Cerati Michele , Zaccaria Martina , La Rosa Stefano , Calistri Arianna , Accolla Roberto Sergio , Forlani Greta 
Published: September 2024

Abstract
Background
Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults with the lowest survival rates five years post-diagnosis. Oncolytic viruses (OVs) selectively target and damage cancer cells, and for this reason they are being investigated as new therapeutic tools also against GBM.

Methods
An oncolytic herpes simplex virus type 1 (oHSV-1) with deletions in the γ34.5 neurovirulence gene and the US12 gene, expressing enhanced green fluorescent protein (EGFP-oHSV-1) as reporter gene was generated and tested for its capacity to infect and kill the murine GL261 glioblastoma (GBM) cell line. Syngeneic mice were orthotopically injected with GL261cells. Seven days post-implantation, EGFP-oHSV-1 was administered intratumorally. Twenty-one days after parental tumor challenge in the opposite brain hemisphere, mice were sacrified and their brains were analysed by immunohistochemistry to assess tumor presence and cell infiltrate.

Results
oHSV-1 replicates and induces cell death of GL261 cells in vitro. A single intracranial injection of EGFP-oHSV-1 in established GL261 tumors significantly prolongs survival in all treated mice compared to placebo treatment. Notably, 45% of treated mice became long-term survivors, and rejected GL261 cells upon rechallenge in the contralateral brain hemisphere, indicating an anamnestic antitumoral immune response. Post-mortem analysis revealed a profound modification of the tumor microenvironment with increased infiltration of CD4 + and CD8 + T lymphocytes, intertumoral vascular collapse and activation and redistribution of macrophage, microglia, and astroglia in the tumor area, with the formation of intense fibrotic tissue suggestive of complete rejection in long-term survivor mice.

Conclusions
EGFP-oHSV1 demonstrates potent antitumoral activity in an immunocompetent GBM model as a monotherapy, resulting from direct cell killing combined with the stimulation of a protective adaptive immune response. These results open the way to possible application of our strategy in clinical setting.
Modulation of cannabinoid receptor 2 alters neuroinflammation and reduces formation of alpha-synuclein aggregates in a rat model of nigral synucleinopathy
Authors: Joers Valerie , Murray Benjamin C , McLaughlin Caroline , Oliver Danielle , Staley Hannah E. , Coronado Jazmyn , Achat-Mendes Cindy , Golshani Sanam , Kelly Sean D. , Goodson Matthew , Lee Danica , Manfredsson Fredric P. , Moore II Bob M. , Tansey Malú Gámez 
Published: September 2024

AbstractResearch into the disequilibrium of microglial phenotypes has become an area of intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss in Parkinson’s disease (PD). There is growing evidence that neuroinflammation accompanies and may promote progression of alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From a therapeutic perspective, development of immunomodulatory strategies that dampen overproduction of pro-inflammatory cytokines from chronically activated immune cells and induce a pro-phagocytic phenotype is expected to promote Asyn removal and protect vulnerable neurons. Cannabinoid receptor-2 (CB2) is highly expressed on activated microglia and peripheral immune cells, is upregulated in the substantia nigra of individuals with PD and in mouse models of nigral degeneration. Furthermore, modulation of CB2 protects against rotenone-induced nigral degeneration; however, CB2 has not been pharmacologically and selectively targeted in an Asyn model of PD. Here, we report that 7 weeks of peripheral administration of CB2 inverse agonist SMM-189 reduced phosphorylated (pSer129) Asyn in the substantia nigra compared to vehicle treatment. Additionally, SMM-189 delayed Asyn-induced immune cell infiltration into the brain as determined by flow cytometry, increased CD68 protein expression, and elevated wound-healing-immune-mediator gene expression. Additionally, peripheral immune cells increased wound-healing non-classical monocytes and decreased pro-inflammatory classical monocytes. In vitro analysis of RAW264.7 macrophages treated with lipopolysaccharide (LPS) and SMM-189 revealed increased phagocytosis as measured by the uptake of fluorescence of pHrodo E. coli bioparticles. Together, results suggest that targeting CB2 with SMM-189 skews immune cell function toward a phagocytic phenotype and reduces toxic aggregated species of Asyn. Our novel findings demonstrate that CB2 may be a target to modulate inflammatory and immune responses in proteinopathies.
Knockdown of microglial iron import gene, Slc11a2, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer’s disease
Authors: Robertson Katrina Volk , Rodriguez Alec S. , Cartailler Jean-Philippe , Shrestha Shristi , Schleh Michael W. , Schroeder Kyle R. , Valenti Arianna M. , Kramer Alec T. , Harrison Fiona E. , Hasty Alyssa H. 
Published: September 2024

Abstract
Background
Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer’s disease (AD). In vitro, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo. These studies determined the effects of microglial-specific knockdown of Slc11a2 on AD-related cognitive decline and microglial transcriptional phenotype.

Methods
In vitro experiments and RT-qPCR were used to assess a role for DMT1 in amyloid-β-associated inflammation. To determine the effects of microglial Slc11a2 knockdown on AD-related phenotypes in vivo, triple-transgenic Cx3cr1Cre−ERT2;Slc11a2flfl;APP/PS1+or – mice were generated and administered corn oil or tamoxifen to induce knockdown at 5–6 months of age. Both sexes underwent behavioral analyses to assess cognition and memory (12–15 months of age). Hippocampal CD11b+ microglia were magnetically isolated from female mice (15–17 months) and bulk RNA-sequencing analysis was conducted.

Results
DMT1 inhibition in vitro robustly decreased Aβ-induced inflammatory gene expression and cellular iron levels in conditions of excess iron. In vivo, Slc11a2KDAPP/PS1 female, but not male, mice displayed a significant worsening of memory function in Morris water maze and a fear conditioning assay, along with significant hyperactivity compared to control WT and APP/PS1 mice. Hippocampal microglia from Slc11a2KDAPP/PS1 females displayed significant increases in Enpp2, Ttr, and the iron-export gene, Slc40a1, compared to control APP/PS1 cells. Slc11a2KD cells from APP/PS1 females also exhibited decreased expression of markers associated with subsets of disease-associated microglia (DAMs), such as Apoe, Ctsb, Ly9, Csf1, and Hif1α.

Conclusions
This work suggests a sex-specific role for microglial iron import gene Slc11a2 in propagating behavioral and cognitive phenotypes in the APP/PS1 model of AD. These data also highlight an association between loss of a DAM-like phenotype in microglia and cognitive deficits in Slc11a2KDAPP/PS1 female mice. Overall, this work illuminates an iron-related pathway in microglia that may serve a protective role during disease and offers insight into mechanisms behind disease-related sex differences.
Enhancing stroke rehabilitation with whole-hand haptic rendering: development and clinical usability evaluation of a novel upper-limb rehabilitation device
Authors: Rätz Raphael , Conti François , Thaler Irène , Müri René M. , Marchal-Crespo Laura 
Published: September 2024

AbstractIntroductionThere is currently a lack of easy-to-use and effective robotic devices for upper-limb rehabilitation after stroke. Importantly, most current systems lack the provision of somatosensory information that is congruent with the virtual training task. This paper introduces a novel haptic robotic system designed for upper-limb rehabilitation, focusing on enhancing sensorimotor rehabilitation through comprehensive haptic rendering.MethodsWe developed a novel haptic rehabilitation device with a unique combination of degrees of freedom that allows the virtual training of functional reach and grasp tasks, where we use a physics engine-based haptic rendering method to render whole-hand interactions between the patients’ hands and virtual tangible objects. To evaluate the feasibility of our system, we performed a clinical mixed-method usability study with seven patients and seven therapists working in neurorehabilitation. We employed standardized questionnaires to gather quantitative data and performed semi-structured interviews with all participants to gain qualitative insights into the perceived usability and usefulness of our technological solution.ResultsThe device demonstrated ease of use and adaptability to various hand sizes without extensive setup. Therapists and patients reported high satisfaction levels, with the system facilitating engaging and meaningful rehabilitation exercises. Participants provided notably positive feedback, particularly emphasizing the system’s available degrees of freedom and its haptic rendering capabilities. Therapists expressed confidence in the transferability of sensorimotor skills learned with our system to activities of daily living, although further investigation is needed to confirm this.ConclusionThe novel haptic robotic system effectively supports upper-limb rehabilitation post-stroke, offering high-fidelity haptic feedback and engaging training tasks. Its clinical usability, combined with positive feedback from both therapists and patients, underscores its potential to enhance robotic neurorehabilitation.
COVID-19 risk factors and outcomes in individuals with stiff person syndrome spectrum disorders before and after omicron
Authors: Afshar Hanyeh , Simpson Alexandra , Taylor Elena , Miles Ashley , Chen Herbert R. , Newsome Scott D. 
Published: September 2024

Abstract
Background
Stiff person syndrome spectrum disorders (SPSD) are rare, disabling disorders of the nervous system that are associated with risk factors for Coronavirus disease 2019 (COVID-19). However, limited data exist on the overall impact of COVID-19 on SPSD.

Methods
Patients with SPSD and COVID-19 who are followed at Johns Hopkins SPS Center were included. Demographics and SPSD characteristics along with COVID-19-specific data were recorded.

Results
Thirty-five cases of SPSD with COVID-19 cases were reported during the study time period. Mean age of the cohort was 56 (SD ± 10) and most were female (66.7%). Eighty percent of the COVID-19 cases were confirmed with testing, and the rest were highly suggestive of COVID-19. COVID-19 comorbidities among patients were hypertension (n = 6), diabetes (n = 6), obesity (n = 5), and cardiovascular disease (n = 4). The majority of participants were on immune therapies and/or benzodiazepines. Out of the cases reported, only 2 required hospitalization, both of whom had diabetes, and one was on immunosuppressive therapy. The majority of cases were post-full-vaccination cases. Fever was the most common COVID-19-associated symptom. Transient neurological symptoms were also reported.

Conclusion
Risk factors for developing severe COVID-19 in SPSD appear to be the same as historical data in the general population. Importantly, COVID-19 did not appear to be associated with worsening SPSD post-COVID-19. Vaccination may have played a role in preventing severe cases of COVID-19.
Postnatal management of preterm infants with spinal muscular atrophy: experience from German newborn screening
Authors: Trollmann Regina , Johannsen Jessika , Vill Katharina , Köhler Cornelia , Hahn Andreas , Illsinger Sabine , Pechmann Astrid , Hagen Maja von der , Müller-Felber Wolfgang 
Published: September 2024

Abstract
Background
The introduction of newborn screening (NBS) for spinal muscular atrophy (SMA) has increased the early diagnosis of 5q-associated SMA in presymptomatic and symptomatic preterm infants. National and international recommendations for treating preterms and newborns < 38 weeks of gestational age are unavailable. Our retrospective multicentre study aimed to evaluate the postnatal clinical course of preterm infants with 5q-associated SMA diagnosed since the implementation of NBS in Germany in 2021 and to summarize the German experience regarding the decision-making process for available treatment regimens for preterm infants with ≤ 3 survival of motor neuron 2 (SMN2) copies.

Results
Twelve preterm infants with 5q-associated SMA and a mean gestational age of 34.0 weeks (range: 26.1–36.8) and birth weight of 2022 g (range: 645–3370) were reported from 8/20 German SMA NBS follow-up centers using a pseudonymized questionnaire. Confirmatory diagnosis, including SMN2 copy number, was completed on average on postnatal day 13. All patients had a biallelic deletion of exon 7 or exons 7 and 8 of the survival of motor neuron 1 (SMN1) gene, with SMN2 copy numbers of two in 10 patients and three in two patients. The neonatal course was complicated by respiratory distress due to prematurity (n = 2), sepsis (n = 2), and jaundice (n = 2). At birth, 11 preterm infants (91.6%) were presymptomatic. However, the neurological status of one patient deteriorated at five weeks of age (postconceptional age of 41.8 weeks) prior to the start of treatment. Disease-modifying treatments were initiated in all patients at a mean postconceptional age of 38.8 weeks, with the majority receiving onasemnogene abeparvovec (83.3%, including 2 patients with prior risdiplam bridge therapy). Notably, consensus among participating experts from German neuromuscular centers resulted in 83.3% of patients receiving disease-modifying treatment at term.

Conclusions
Premature infants with SMA require interdisciplinary care in close collaboration with the neuromuscular center. SMA NBS facilitates early initiation of disease-modifying therapy, ideally during the presymptomatic phase, which significantly influences the prognosis of the newborn.
γ-Aminobutyric acid type A receptor β1 subunit gene polymorphisms are associated with the sedative and amnesic effects of midazolam
Authors: Kosaki Yoshihiko , Nishizawa Daisuke , Hasegawa Junko , Yoshida Kaori , Ikeda Kazutaka , Ichinohe Tatsuya 
Published: September 2024

AbstractMidazolam is widely used for intravenous sedation. However, wide interindividual variability is seen in the sensitivity to midazolam. The association between genetic factors and interindividual differences in midazolam sensitivity remains unclear. The present study explored the association between common genetic variants and sedative and amnesic effects of midazolam. This prospective study included patients who were scheduled to undergo dental procedures under intravenous sedation. The sedative effect was evaluated using the Ramsay sedation scale 5 min after midazolam (0.05 mg/kg) administration. We employed two parallel approaches in this study: genome-wide approach and candidate gene approach. The γ-aminobutyric acid type A receptor subunit genes were selected as candidate genes. Multivariate linear regression analyses were performed to investigate the association between the Ramsay sedation scale and genetic variants. We also analyzed the association between the presence of anterograde amnesia and genetic variants using multivariate binominal logistic regression analyses. The analyses were adjusted for potential confounding factors. A total of 191 patients were included in the analyses. In the genome-wide association analyses, no significant association was found between the genetic variants and Ramsay scores. In the candidate gene analyses, the rs73247636 (dominant model: β = 0.72 [95% confidence interval, 0.34 to 1.10], P < 0.001) and rs56278524 (dominant model: β = 0.73 [0.37 to 1.10], P < 0.001) polymorphisms of the GABRB1 gene were significantly associated with Ramsay scores. Additionally, the rs73247636 (dominant model: odds ratio [OR] = 8.39 [2.36 to 29.85], P = 0.001) and rs56278524 (dominant model: OR = 15.26 [3.42 to 68.07], P < 0.001) polymorphisms were also significantly associated with the presence of anterograde amnesia. The rs73247636 and rs56278524 single-nucleotide polymorphisms of GABRB1 were associated with the sedative and amnesic effects of midazolam.
OPTimising MEDicine information handover after Discharge (OPTMED-D): protocol for development of a multifaceted intervention and stepped wedge cluster randomised controlled trial
Authors: Hattingh Laetitia , Baysari Melissa T. , Foot Holly , Sim Tin Fei , Keijzers Gerben , Morgan Mark , Scott Ian , Norman Richard , Yong Faith , Mullan Barbara , Jackson Claire , Oldfield Leslie E. , Manias Elizabeth 
Published: September 2024

Abstract
Background
General practitioners (GP) and community pharmacists need information about hospital discharge patients’ medicines to continue their management in the community. This necessitates effective communication, collaboration, and reliable information-sharing. However, such handover is inconsistent, and whilst digital systems are in place to transfer information at transitions of care, these systems are passive and clinicians are not prompted about patients’ transitions. There are also gaps in communication between community pharmacists and GPs. These issues impact patient safety, leading to hospital readmissions and increased healthcare costs.

Methods
A three-phased, multi-method study design is planned to trial a multifaceted intervention to reduce 30-day hospital readmissions. Phase 1 is the co-design of the intervention with stakeholders and end-users; phase 2 is the development of the intervention; phase 3 is a stepped wedge cluster randomised controlled trial with 20 clusters (community pharmacies). Expected intervention components will be a hospital pharmacist navigator, primary care medication management review services, and a digital solution for information sharing. Phase 3 will recruit 10 patients per pharmacy cluster/month to achieve a sample size of 2200 patients powered to detect a 5% absolute reduction in unplanned readmissions from 10% in the control group to 5% in the intervention at 30 days. The randomisation and intervention will occur at the level of the patient’s nominated community pharmacy. Primary analysis will be a comparison of 30-day medication-related hospital readmissions between intervention and control clusters using a mixed effects Poisson regression model with a random effect for cluster (pharmacy) and a fixed effect for each step to account for secular trends.

Trial registration
This trial is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12624000480583p, registered 19 April 2024.