bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelioid Hemangioendothelioma in a Liver Transplant Recipient: A Case Report of an Extremely Rare Tumor
Authors: Gonçalves Margarida , Pessegueiro Helena , Gandara Judit , Vizcaíno José Ramón , Lopes Vitor , Ferreira Sofia
Published: December 2023

Epithelioid hemangioendothelioma is a very rare vascular neoplasm, which is often multifocal or metastatic at diagnosis. Most frequently arises in the liver, followed by the lung and bones. The authors present a case of a liver transplant recipient who developed a pattern of hepatic cholestasis associated with the appearance of a proliferative hepatic lesion with infiltrative growth. Histological examination and immunohistochemical study were compatible with the diagnosis of epithelioid hemangioendothelioma. Pulmonary micronodules were detected and lung metastases were hypothesized. Therefore, bronchoscopy was performed, which turned out to be normal, and cytology was negative for neoplastic cells. After a multidisciplinary discussion, liver re-transplantation was decided. After 8 years of follow-up, the patient is clinically stable, with no graft dysfunction, no neoplastic recurrence, and dimensional stability of the pulmonary micronodules. Patients with organ transplant have higher risk of developing carcinoma compared to the general population. The development of cancer is a multifactorial process and little is known about the etiology of epithelioid hemangioendothelioma. No standard treatment strategy has been defined yet, and the natural course of the disease is heterogenous and the individual prognosis unpredictable. Complete surgical resection is offered to patients with unifocal disease, and those with unresectable disease should be evaluated for orthotopic liver transplantation.
Impact of Age and Clinico-Biochemical Parameters on Clinical Severity of SARS-CoV-2 Infection
Authors: Wani Shariq Ahmad , Gulzar Babar , Khan Mosin Saleem , Majid Sabhiya , Bhat Irfan Ahmad
Published: December 2023

Introduction: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. Methods: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. Results: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. Conclusion: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.
Risk Factors Associated with Major Adverse Cardiovascular Events after Ischemic Stroke: A Linked Registry Study
Authors: Dharan Ajay S. , Dalli Lachlan L. , Olaiya Muideen T. , Cadilhac Dominique A. , Nedkoff Lee , Kim Joosup , Andrew Nadine E. , Sundararajan Vijaya , Thrift Amanda G. , Faux Steven G. , Grimley Rohan , Kilkenny Monique F. , Kuhn Lisa ,   On behalf of the Stroke123 investigators
Published: December 2023

Introduction: Survivors of stroke are at risk of experiencing subsequent major adverse cardiovascular events (MACE). We aimed to determine the incidence of, and risk factors for, MACE after first-ever ischemic stroke, by age group (18–64 years vs. ≥65 years). Methods: Observational cohort study using patient-level data from the Australian Stroke Clinical Registry (2009–2013), linked with hospital administrative data. We included adults with first-ever ischemic stroke who had no previous acute cardiovascular admissions and followed these patients for 2 years post-discharge, or until the first post-stroke MACE event. A Fine-Gray sub-distribution hazard model, accounting for the competing risk of non-cardiovascular death, was used to determine factors for incident post-stroke MACE. Results: Among 5,994 patients with a first-ever ischemic stroke (median age 73 years, 45% female), 17% were admitted for MACE within 2 years (129 events per 1,000 person-years). The median time to first post-stroke MACE was 117 days (89 days if aged <65 years vs. 126 days if aged ≥65 years; p = 0.025). Among patients aged 18–64 years, receiving intravenous thrombolysis (sub-distribution hazard ratio [SHR] 0.51 [95% CI, 0.28–0.92]) or being discharged to inpatient rehabilitation (SHR 0.65 [95% CI, 0.46–0.92]) were associated with a reduced incidence of post-stroke MACE. In those aged ≥65 years, being unable to walk on admission (SHR 1.33 [95% CI 1.15–1.54]), and history of smoking (SHR 1.40 [95% CI 1.14–1.71]) or atrial fibrillation (SHR 1.31 [95% CI 1.14–1.51]) were associated with an increased incidence of post-stroke MACE. Acute management in a large hospital (>300 beds) for the initial stroke event was associated with reduced incidence of post-stroke MACE, irrespective of age group. Conclusions: MACE is common within 2 years of stroke, with most events occurring within the first year. We have identified important factors to consider when designing interventions to prevent MACE after stroke, particularly among those aged <65 years.
Knowledge and opinions of nursing undergraduate students about basic life support measures
Authors: Matić Anita , Cvijanović Nemanja , Volarić Nikola , Igrec Dunja , Ćosić Mateja , Jakab Jelena
Published: December 2023

Uvod: Osnovne mjere održavanja na životu (BLS, engl. Basic life support) odnose se na hitnu medicinsku skrb pruženu osobi koja se nalazi u hitnom stanju opasnom po život. Provode se u svrhu održavanja vitalnih funkcija i sprečavanja daljnjeg pogoršanja stanja pacijenta dok se ne osigura napredna medicinska skrb. Zbog učestalosti i važnosti navedenog postupka, nužno je da svi zdravstveni djelatnici poznaju osnovne mjere za održavanje na životu.Cilj istraživanja: Cilj je ispitati znanja i mišljenja studenata prijediplomskog studija sestrinstva o BLS postupcima i postupcima kardiopulmonalne reanimacije (KPR), potrebi dodatne edukacije svih budućih zdravstvenih djelatnika, te uvidjeti razlike u razini znanja ovisno o godini obrazovanja.Ispitanici i metode: U istraživanju provedenom u periodu od siječnja do travnja 2023. godine sudjelovalo je 290 redovitih i izvanrednih studenata prijediplomskog studija sestrinstva u dobi 18 – 50 godina. Svi su studenti popunjavali anketni upitnik koji se sastojao od dva dijela: općenitog sa sociodemografskim podacima i specifičnog dijela koji je uključivao pitanja specifična za temu istraživanja. Anketiranje je bilo u potpunosti anonimno i dobrovoljno.Rezultati: Ukupno 85 % ispitanika prethodno je pohađalo srednju školu zdravstvenog usmjerenja te je od tada u najvećem postotku i upoznato s pojmovima BLS i KPR. Na teorijska pitanja o navedenoj temi studenti su u visokom postotku (85 % i više) točno odgovarali na postavljenja pitanja. Promatrano po godinama studija, studenti 3. godine prijediplomskog studija sestrinstva pokazali su najviše znanja. Spremnost studenata za pristupanje i provođenje postupaka BLS-a i KPR-a povećava se s duljinom studiranja i višom razinom stečenih znanja. Svi studenti smatraju važnim poznavanje navedenih postupaka te smatraju da bi se tečajevi i radionice o navedenoj temi trebale periodično ponavljati u svrhu obnavljanja znanja i vještina.Zaključak: Znanja, spremnost i vještine vezane za postupke BLS-a i KPR-a povećavaju se s duljinom i većim obujmom stečenog obrazovanja. Studenti prepoznaju svoju moralnu odgovornost kao zdravstveni djelatnici i važnost opetovanih tečajeva u svrhu što bolje spremnosti u hitnim situacijama.
Bacterial contamination of used surgical masks among high-risk ward staff
Authors: Magaš Morana , Švegar Davorka , Škrobonja Ivana , Janaš Nina , Kranjčević-Ščurić Mihaela , Abram Maja
Published: December 2023

Uvod: Zaštitne maske kontaminiraju se uporabom, mikrobiotom nosne i usne šupljine te kože lica. Izvješća o kontaminaciji i potencijalu za prijenos uzročnika bolničkih infekcija nedostaju ili su rijetka. Istraženo je može li maska postati izvor mikroorganizama i predstavljati rizik za prijenos infekcija povezanih sa zdravstvenom skrbi. Cilj rada bio je usporediti mikrobno opterećenje maski, vestibuluma nosa i ruku djelatnika kako bismo identificirali potencijalne rizike.Metode: Provedena je studija prevalencije u jednom danu u studenom 2022. godine na hematološkom odjelu tercijarne bolnice. Kriterij uključivanja bila je činjenica da se djelatnik tog jutra nalazi u neposrednom radu sa stacionarnim bolesnicima. Uzeti su brisevi nosa, ruku i maski. Sudionici su podijeljeni u dvije skupine: oni koji su masku nosili do 30 minuta i oni koji su je nosili više od 1 sata. Brisevi su obrađeni standardnim mikrobiološkim postupcima.Rezultati: Od 10 ispitanika, njih je 5 masku nosilo 30-ak minuta, a preostalih 5 više od 1 sata. U prvoj skupini nije bilo pozitivnih mikrobioloških nalaza. U skupini djelatnika koji su masku nosili dulje od 1 sata izolirani su koagulaza negativni stafilokoki, Staphylococcus hominis i Staphylococcus warneri u tri od pet ispitanika. Iz briseva vestibuluma nosa u jednom slučaju identificiran je meticilin osjetljiv Staphylococcus aureus. U dva slučaja identificirane su iste vrste, S. hominis i S. warneri, kao i na njihovim maskama. Brisevi ruku kod devetero djelatnika ostali su sterilni, dok su u jednom slučaju izolirani antrakoidi iz roda Bacillus.Rasprava sa zaključkom: Unutar jednog sata na zaštitnim maskama mogu se naći bakterije koje se nalaze u nosu ili koži lica djelatnika. Produljenom uporabom može se očekivati povećanje broja, ali i kontaminacija raznolikim vrstama mikroorganizama što može predstavljati značajan rizik biološke sigurnosti. Osnaživanje prakse higijene ruku minimizira rizik od infekcija i povećava sigurnost pacijenata i osoblja.
Patient informed consent – safety for the patient or the physician
Authors: Koščević Matea , Režić Slađana
Published: December 2023

Informed consent is a form in which the patient gives his consent or refuses a medical procedure based on the information the physician has provided him. The main purpose of informed consent is to secure the protection of patient’s rights, to verify the identity of the patient, and to acquire the consent for the procedure.Informed consent is mostly used in clinical practice and clinical research. The information provided to the patient through informed consent by a physician in an understandable fashion enables the patient to decide on future procedures that concern his health. Historically, the beginnings of informed consent date back to the 14th century, but it was not until the early 20th century that its importance grew. The reason for that was the development of invasive procedures in medical practice.In hospital institutions, informed consent is obligatory for every high-risk procedure carried out in that health care institution. Most often, this includes invasive diagnostic and therapeutic procedures, as well as surgical procedures.
Impact of Mobile Stroke Units on Patients With Large Vessel Occlusion Acute Ischemic Stroke: A Prespecified BEST‐MSU Substudy
Authors: Czap Alexandra L. , Alexandrov Anne W. , Nour May , Yamal Jose‐Miguel , Wang Mengxi , Jacob Asha P. , Parker Stephanie A. , Tariq Muhammad Bilal , Rajan Suja S. , Alexandrov Andrei V. , Jones William J. , Navi Babak B. , Spokoyny Ilana , Mackey Jason , Lerario Mackenzie P. , Gonzalez Michael O. , Singh Noopur , Bowry Ritvij , Grotta James C.
Published: December 2023

Background

The impact of mobile stroke units (MSUs) on outcomes in patients with large vessel occlusions eligible for endovascular thrombectomy (EVT) has yet to be characterized.

Methods

We completed a prespecified substudy of patients with EVT‐eligible stroke with anterior and posterior circulation large vessel occlusions on computed tomography and/or computed tomography angiography who were enrolled in BEST‐MSU (Benefits of Stroke Treatment using a Mobile Stroke Unit). Primary outcome was 90‐day utility‐weighted modified Rankin scale. Groups were compared using chi‐square or Fisher's exact tests for categorical variables, and 2‐samplet‐tests for continuous variables. Multiple logistic regression was used to assess the effect of MSU on binary outcomes after adjusting for other baseline factors.

Results

Of 1515 trial patients, 293 had large vessel occlusions eligible for EVT: 168 in the MSU group and 125 in the emergency medical services group. Baseline characteristics were comparable, with the exception of baseline National Institutes of Health Stroke Scale score (MSU median 19 [interquartile range 13, 23] versus emergency medical services 16 [11, 20],P= 0.002) and study site. The mean (±SD) score on the utility‐weighted modified Rankin scale at 90 days was 0.63±0.39 in MSU group and 0.51±0.41 in emergency medical services group (mean difference 0.13, 95% CI [0.03–0.22]). After adjustment, MSU had significantly higher odds of functional independence (odds ratio 2.60 [95% CI, 1.45–4.77],P= 0.002). Secondary outcomes also favored MSU: early neurologic recovery (30% improvement in National Institutes of Health Stroke Scale score at 24 hours) 68% versus 52%; adjusted odds ratio 1.98 [95% CI, 1.19–3.33]; time of tissue plasminogen activator bolus from symptom onset 65.0 minutes [50.5–92.0] versus 96.0 [79.3–130.0],P≤0.001. The groups had similar onset to arterial puncture (169.0 minutes [133.5, 210.0] versus 162.0 [135.0–207.0],P= 0.83).

Conclusions

In patients with EVT‐eligible large vessel occlusion stroke, MSU management was associated with better clinical outcomes compared with standard emergency medical services management. MSU management sped thrombolysis but did not expedite EVT treatment times. Future MSU processes should include efforts to capitalize on the potential of MSUs to provide earlier EVT.
Bridging the Gap: A Survey on Integrating (Human) Feedback for Natural Language Generation
Authors: Fernandes Patrick , Madaan Aman , Liu Emmy , Farinhas António , Martins Pedro Henrique , Bertsch Amanda , de Souza José G. C. , Zhou Shuyan , Wu Tongshuang , Neubig Graham , Martins André F. T.
Published: December 2023

Natural language generation has witnessed significant advancements due to the training of large language models on vast internet-scale datasets. Despite these advancements, there exists a critical challenge: These models can inadvertently generate content that is toxic, inaccurate, and unhelpful, and existing automatic evaluation metrics often fall short of identifying these shortcomings. As models become more capable, human feedback is an invaluable signal for evaluating and improving models. This survey aims to provide an overview of recent research that has leveraged human feedback to improve natural language generation. First, we introduce a taxonomy distilled from existing research to categorize and organize the varied forms of feedback. Next, we discuss how feedback can be described by its format and objective, and cover the two approaches proposed to use feedback (either for training or decoding): directly using feedback or training feedback models. We also discuss existing datasets for human-feedback data collection, and concerns surrounding feedback collection. Finally, we provide an overview of the nascent field of AI feedback, which uses large language models to make judgments based on a set of principles and minimize the need for human intervention. We also release a website of this survey at feedback-gap-survey.info.
MissModal: Increasing Robustness to Missing Modality in Multimodal
Sentiment Analysis
Authors: Lin Ronghao , Hu Haifeng
Published: December 2023

When applying multimodal machine learning in downstream inference, both joint and coordinated multimodal representations rely on the complete presence of modalities as in training. However, modal-incomplete data, where certain modalities are missing, greatly reduces performance in Multimodal Sentiment Analysis (MSA) due to varying input forms and semantic information deficiencies. This limits the applicability of the predominant MSA methods in the real world, where the completeness of multimodal data is uncertain and variable. The generation-based methods attempt to generate the missing modality, yet they require complex hierarchical architecture with huge computational costs and struggle with the representation gaps across different modalities. Diversely, we propose a novel representation learning approach named MissModal, devoting to increasing robustness to missing modality in a classification approach. Specifically, we adopt constraints with geometric contrastive loss, distribution distance loss, and sentiment semantic loss to align the representations of modal-missing and modal-complete data, without impacting the sentiment inference for the complete modalities. Furthermore, we do not demand any changes in the multimodal fusion stage, highlighting the generality of our method in other multimodal learning systems. Extensive experiments demonstrate that the proposed method achieves superior performance with minimal computational costs in various missing modalities scenarios (flexibility), including severely missing modality (efficiency) on two public MSA datasets.
Serendipita officinale sp. nov. (Serendipitaceae): a new species of orchid mycorrhizal fungus
Authors: WANG XIN-JU , GAO JIANG-YUN , LI NENG-QI
Published: December 2023

Serendipita is a prominent fungal genus associated with orchids. In this study, a new species of orchid mycorrhizal fungus, Serendipita officinale, is described and thoroughly studied using morphological and molecular approaches. The fungus was isolated from naturally occurring protocorms of Dendrobium officinale in Chongqing Province, China. S. officinale has been observed to actively promote the germination of seeds and facilitate the seedling development of D. officinale, forming typical mycorrhizal pelotons within protocorm cells. This species is characterized by its characteristics on PDA medium, including the presence of abundant villiform and felty aerial mycelium, uninucleate hyphal cells, and the highest growth rate in terms of colony diameter (78 mm diam. in 2 weeks). Furthermore, analyses of ITS rDNA and LSU sequences also provide additional support for the novelty of this new plant symbiont.
Genista anglica s.l. (Fabaceae): genetic similarities between Iberian and Italian populations
Authors: SANNA MAURO , MARCENÒ CORRADO , PRIETO JOSÉ ANTONIO FERNÁNDEZ , CIRES EDUARDO
Published: December 2023

Genista anglica L. (Fabaceae) is a Western European plant, widespread from Northern Morocco to Southern Sweden, with two geographically isolated populations in Calabria (Italy). Based on morphological characters, some authors considered the southern Italian populations as two different species: Genista silana and Genista brutia. Recent phylogeographical studies reveal that the G. silana and G. brutia populations share genetic similarities with some populations of the widespread G. anglica from Northwestern of Iberian Peninsula, despite a distance of approximately 2000 km. Previously, other authors suggested anthropogenic introduction of these plants in the South of Italy, but this hypothesis has not been thoroughly investigated. To unravel the uncertain origin of the isolated Italian populations, we conducted a more detailed study about the genetic relationships between southern Italian populations and Northwestern of Iberian Peninsula populations of G. anglica s.l., using plastid DNA sequences. Our results show identical and similar haplotypes in some of the populations of the Northwestern of Iberian Peninsula and the Italian populations, which supports the hypothesis of a recent anthropogenic introduction.
On the sharpshooter genus Yunga Melichar, 1924 (Hemiptera: Cicadellidae: Cicadellinae): descriptions of a new species from Panama and of the internal female terminalia of Y. cartwrighti Young, 1968 and Y. coriacea Stål, 1864
Authors: SAUCEDA-V. JEFFERSON , TAKIYA DANIELA M.
Published: December 2023

Yunga Melichar, 1924, is a little-known genus that currently includes three valid species distributed in North America (Mexico), Central America (Costa Rica, Panama), and northern South America (Colombia). A new species of this genus, Y. andresi sp. nov., is described and illustrated based on a single male specimen collected in Bocas del Toro province, Panama. This species can be distinguished from other species of the genus by the following combination of features: (1) apex of style curved inwards, hook-like; (2) aedeagal shaft with paired basal dorsolateral processes, spine-like and short, not extending beyond gonopore; (3) dorsoapical process robust, hook-shaped in lateral view, ending curved and acute; and 4) paraphyses paired, each robust and trifurcate with rami of unequal sizes and thickness. The female genitalia of Y. cartwrighti Young, 1968 and Y. coriacea Stål, 1864 are described and illustrated for the first time. Finally, a distribution map for the species of Yunga, as well as an updated key to species identification, are provided.
A new species of Oecobius Lucas, 1846 from the Thar Desert, India (Araneae: Oecobiidae)
Authors: TRIPATHI RISHIKESH , SUDHIKUMAR AMBALAPARAMBIL V. , SHERWOOD DANNIELLA
Published: December 2023

We describe a new species of Oecobius Lucas, 1846 from the Thar Desert ecoregion in India, based on both sexes: Oecobius thar sp. nov.. We also provide photographs of the new species in vivo and the general habitat of its type locality.
A case of emergency reconstructive surgery following facial destructive gunshot wounds: clinical and medico-legal assessments
Authors: Tomassini Luca , Ascani Giuliano , Mancini Paolo , Cacaci Claudio , Scendoni Roberto
Published: December 2023

Background

Facial gunshot wounds present a complex challenge to both medical professionals and victims with significant physical, psychological, and economic implications for those who suffer these types of injuries. Reconstructive surgery offers satisfactory aesthetic and functional outcomes, improving a patient’s quality of life. In these cases, the surgical procedure may encompass additional phases beyond those initially identified based on the type of wound and the extent of tissue destruction. As a result, each case necessitates thorough evaluation to determine an appropriate strategy. Nonetheless, it is worth noting that the outcomes achieved in terms of both aesthetics and functionality in this domain have the potential to be excellent.

Case presentation

A 66-year-old man attempted suicide with a shotgun, causing severe facial injuries and fractures. He had a history of depression and was taken to the emergency department promptly. CT scans revealed brain and facial bone injuries, and he underwent surgery to control bleeding and tracheostomy. Postoperative recovery was successful. The patient’s condition stabilized, and he was discharged after 10 days. Follow-up visits showed gradual healing. Despite an offer for further facial reconstruction, he declined, satisfied with the achieved results.

Conclusions

The present case report is intended to support the argument that effective facial reconstruction should be considered in the medico-legal assessment. It could be beneficial to introduce a new classification system and personalized evaluation methods with careful consideration given to treatment costs (which can be very high) and expected results. Since reconstructive surgery modifies damage and impacts the long-term costs of permanent impairments, its inclusion in the decision-making process would promote improved personalized care.
Nrf2 enhances the therapeutic efficiency of adipose-derived stem cells in the treatment of neurogenic erectile dysfunction in a rat model
Authors: Yang Shangbin , Shi Wancheng , Liu Qianhui , Song Yingqiu , Fang Jiafeng
Published: December 2023

Background

Erectile dysfunction (ED) caused by intraoperative nerve injury is a major complication of pelvic surgery. Adipose-derived stem cells (ADSCs) have presented therapeutic potential in a rat model of bilateral cavernous nerve injury (BCNI), while inadequate in vivo viability has largely limited their application. Nuclear factor-E2-related Factor (Nrf2) is a key transcription factor that regulates cellular anti-oxidative stress. In this work, we investigated the effect of Nrf2 expression regulation on the viability of ADSCs, and explore its repair potential in a BCNI rat model.

Results

The survival time of tert-Butylhydroquinone (tBHQ)-ADSCs in BCNI model increased obviously. In addition, the tBHQ-ADSCs group presented better restoration of major pelvic ganglion (MPG) nerve contents and fibers, better improvement of erectile function, and less penile fibrosis than the other groups. Moreover, the expression of Nrf2 and superoxide dismutase 1 (SOD1) were higher than those of other groups.

Conclusion

Nrf2 could enhance the anti-oxidative stress ability of ADSCs, so as to improve the therapeutic effect of ADSCs on BCNI rat model.
Evaluation of ‘implications for research’ statements in systematic reviews of interventions in advanced cancer patients – a meta-research study
Authors: Siemens W. , Bantle G. , Ebner C. , Blümle A. , Becker G. , Schwarzer G. , Meerpohl J. J.
Published: December 2023

Background

Implications for research (IfR) sections are an important part of systematic reviews (SRs) to inform health care researchers and policy makers. PRISMA 2020 recommends reporting IfR, while Cochrane Reviews require a separate chapter on IfR. However, it is unclear to what extent SRs discuss IfR.

We aimed i) to assess whether SRs include an IfR statement and ii) to evaluate which elements informed IfR statements.

Methods

We conducted a meta-research study based on SRs of interventions in advanced cancer patients from a previous project (CRD42019134904).

As suggested in the Cochrane Handbook, we assessed if the following predefined variables were referred to in IfR statements: patient, intervention, control, outcome (PICO) and study design; concepts underlying Grading of Recommendations, Assessment, Development and Evaluation (GRADE) domains: risk of bias, inconsistency, indirectness, imprecision, publication bias. Data were independently extracted by three reviewers after piloting the data extraction form. Discrepancies were resolved in weekly in-depth discussions.

Results

We included 261 SRs. The majority evaluated a pharmacological intervention (n = 244, 93.5%); twenty-nine were Cochrane Reviews (11.1%).

Four out of five SRs included an IfR statement (n = 210, 80.5%). IfR statements commonly addressed ‘intervention’ (n = 121, 57.6%), ‘patient ‘ (n = 113, 53.8%), and ‘study design’ (n = 107, 51.0%). The most frequent PICO and study design combinations were ‘patient and intervention ‘ (n = 71, 33.8%) and ‘patient, intervention and study design ‘ (n = 34, 16.2%).

Concepts underlying GRADE domains were rarely used for informing IfR recommendations: ‘risk of bias ‘ (n = 2, 1.0%), and ‘imprecision ‘ (n = 1, 0.5%), ‘inconsistency ‘ (n = 1, 0.5%).

Additional elements informing IfR were considerations on cost effectiveness (n = 9, 4.3%), reporting standards (n = 4, 1.9%), and individual patient data meta-analysis (n = 4, 1.9%).

Conclusion

Although about 80% of SRs included an IfR statement, the reporting of PICO elements varied across SRs. Concepts underlying GRADE domains were rarely used to derive IfR. Further work needs to assess the generalizability beyond SRs in advanced cancer patients. We suggest that more specific guidance on which and how IfR elements to report in SRs of interventions needs to be developed. Utilizing PICO elements and concepts underlying GRADE according to the Cochrane Handbook to state IfR seems to be a reasonable approach in the interim.

Registration

CRD42019134904.
Facilitating access to primary care for people living in socio-economically vulnerable circumstances in Belgium through community health workers: towards a conceptual model
Authors: Masquillier Caroline , Cosaert Theo
Published: December 2023

Introduction

Inspired by examples in low- and middle-income countries, 50 community health workers (CHWs) were introduced in Belgium to improve access to primary care for people living in socio-economically vulnerable circumstances. This article aims to explore the ways in which CHWs support people living in socio-economically vulnerable circumstances in their access to primary care.

Methods

The qualitative research focuses on the first year of implementation of this pioneer nationwide CHW programme in Belgium. To respond to the research aim, thirteen semi-structured in-depth interviews were held with people living in socio-economically vulnerable circumstances. In addition, a photovoice study was conducted with fifteen CHWs comprising four phases: (1) photovoice training; (2) participatory observation with each CHW individually; (3) an individual semi-structured in-depth interview; and (4) three focus group discussions. The transcripts and the observation notes were analysed in accordance with the abductive analysis procedures described by Timmermans and Tavory.

Results

The qualitative results show that the CHWs’ outreaching way of working allows them to reach people living at the crossroads of different vulnerabilities that are intertwined and reinforce each other. They experience complex care needs, while at the same time they face several barriers that interrupt the continuum of access to primary care – as conceptualised in the theoretical access-to-care framework of (Levesque et al. Int J Equity Health. 12:18, 2013). Building on the theoretical access-to-care framework described by (Levesque et al. Int J Equity Health. 12:18, 2013), the conceptual model outlines first the underlying mechanisms of CHW-facilitated access to primary care: (I) outreaching and pro-active way of working; (II) building trust; (III) providing unbiased support and guidance in a culturally sensitive manner; and (IV) tailoring the CHWs’ approach to the unique interplay of barriers at the individual and health system level along the access-to-care continuum as experienced by the individual. Further disentangling how CHWs provide support to the barriers in access to care across the continuum and at each step is outlined further in the process characteristics of this conceptual model. Furthermore, the qualitative results show that the way in which CHWs support people is also impacted by the broader health system, such as long waiting times and unwelcoming healthcare professionals after referral from a CHW.

Discussion

The conceptual model of CHW-facilitated access to primary care developed in this article explores the way in which CHWs support people living in socio-economically vulnerable circumstances in their access to primary care in Belgium. Through their outreaching method, they play a valuable bridging role between the Belgian healthcare system and people living in socio-economically vulnerable circumstances.
Rituximab as possible therapy in TNF inhibitor-induced IgA vasculitis with severe renal involvement
Authors: Przygocka Agnieszka , Berti Gian Marco , Campus Anita , Tondolo Francesco , Vischini Gisella , Fabbrizio Benedetta , La Manna Gaetano , Baraldi Olga
Published: December 2023

Background

We observe the increasing use of tumor necrosis factor (TNF) inhibitors in patients affected by chronic inflammatory diseases. These drugs provide good control of symptoms, contributing to significant improvement in the quality of life in individuals with high disease burden. On the other hand, along with their wider use and longer follow-up periods the number of reports regarding their adverse effects is also increasing. The reported complications include drug-induced vasculitis with possible kidney involvement. In the literature we can distinguish more frequently described ANCA-associated vasculitis and more rarely occurring immunoglobulin A vasculitis. Although uncommon, such complications may present with potentially life-threatening vital organ dysfunction; therefore, adequate monitoring and effective therapy are necessary.

Case presentation

We report two cases of TNF inhibitor-induced vasculitis with severe acute worsening of renal function and significant proteinuria. The first patient was receiving golimumab therapy for ankylosing spondylitis and the second patient was treated with adalimumab for psoriasis and psoriatic arthritis. In the second case dialysis treatment was necessary and the patient presented recurrence of vasculitis after rechallenge with adalimumab. Both patients underwent renal biopsy which showed findings compatible with drug-induced IgA vasculitis and both were treated successfully with corticosteroids and rituximab.

Conclusions

To the best of our knowledge this is the first report of rituximab use in drug-induced IgA vasculitis with renal involvement. Combination of corticosteroids and rituximab can be an effective therapy in case of vasculitis with kidney failure and a preferable option for selected patients with drug-induced IgA vasculitis compared to cyclophosphamide. More studies are necessary to establish suitable short- and long-term treatment. Given the rarity of this disorder, case reports and case series can provide practical guidance until additional studies become available.
Development and validation of the Nurse Team Resilience Scale (NTRS) in the context of public health emergencies
Authors: Su Ya , Wang Lin , Chen Tangyu , Liao Liwen , Hu SanLian , Yang Yan
Published: December 2023

Background

Team resilience can help nurse to respond positively to adversity at work and maintain normal team function in complex and unstable environments. However, much less research attention has been paid to team resilience than to individual resilience, and nurses lack reliable and valid tools to measure team resilience. This study aimed to develop and evaluate the psychometric properties of a scale that measures the nursing team resilience in the context of a public health emergency.

Methods

The study was conducted in three stages that item development, scale development, and scale evaluation. This scale was based on that of Morgan and Sharma et al. proposed four-factor team resilience model, and the draft scale was generated based on the literature review, existing scales, experts’ validations, and cognitive interviews. During July 2022 to August 2022, the construct validity and the internal consistency reliability of the NTRS were evaluated through an online survey of 421 nurses.

Results

The 8-item NTRS scale has good reliability and validity and is suitable for measuring the nurse team resilience. The EFA found a common factor solution and explained 72.33% of the common varianc and the CFA score showed construct validity. Reliability of the internal consistency of the scale with a good Cronbach alpha of 0.94.

Conclusion

This scale can assess team resilience in nurses that nursing education and management resources can be allocated to improve policies and training programs to provide effective positive support to nurses in challenging workplace situations and to enable greater health systems resilience in the future.
Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor
Authors: Giang Le Hien , Wu Kuo-Sheng , Lee Wei-Chung , Chu Shing-Shung , Do Anh Duy , Changou Chun A. , Tran Huy Minh , Hsieh Tsung-Han , Chen Hsin-Hung , Hsieh Chia-Ling , Sung Shian-Ying , Yu Alice L. , Yen Yun , Wong Tai-Tong , Chang Che-Chang
Published: December 2023

Background

Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT.

Methods

Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT.

Results

RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells.

Conclusions

Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.
Using the center of pressure movement analysis in evaluating spontaneous movements in infants: a comparative study with general movements assessment
Authors: Celik Halil Ibrahim , Yildiz Ayse , Yildiz Ramazan , Mutlu Akmer , Soylu Ruhi , Gucuyener Kivilcim , Duyan-Camurdan Aysu , Koc Esin , Onal Eray Esra , Elbasan Bulent
Published: December 2023

Background

Researchers have attempted to automate the spontaneous movement assessment and have sought quantitative and objective methods over the past decade. The purpose of the study was to present a quantitative assessment method of spontaneous movement using center-of-pressure (COP) movement analysis.

Methods

A total of 101 infants were included in the study. The infants were placed in the supine position on the force plate with the cranial-caudal orientation. In this position, the recording of video and COP movement data were made simultaneously for 3 min. Video recordings were used to observe global and detailed general movement assessment (GMA), and COP time series data were used to obtain quantitative movement parameters.

Results

According to the global GMA, 13 infants displayed absent fidgety movements (FMs) and 88 infants displayed normal FMs. The binary logistic regression model indicated significant association between global GMA and COP movement parameters (chi-square = 20.817, p < 0.001). The sensitivity, specificity, and overall accuracy of this model were 85% (95% CI: 55–98), 83% (95% CI: 73–90), and 83% (95% CI: 74–90), respectively. The multiple linear regression model showed a significant association between detailed GMA (motor optimality score-revised/MOS-R) and COP movement parameters (F = 10.349, p < 0.001). The MOS-R total score was predicted with a standard error of approximately 1.8 points (6%).

Conclusions

The present study demonstrated the possible avenues for using COP movement analysis to objectively detect the absent FMs and MOS-R total score in clinical settings. Although the method presented in this study requires further validation, it may complement observational GMA and be clinically useful for infant screening purposes, particularly in clinical settings where access to expertise in observational GMA is not available.
Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells
Authors: Gao Jixiang , Liu Jinyi , Yu Tao , Xu Chenggong , Sun Hao , Lu Chunbo , Dan Wenjia , Dai Jiangkun
Published: December 2023

The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC50 = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico. Colony formation and cell cycle arrest assays revealed that EU-5 suppressed cell proliferation by causing cell cycle arrest at G0/G1 phase. Wound healing and transwell assays suggested that EU-5 could effectively inhibit migration of A375 cells in a dose-dependent manner. Calcein-AM/PI staining, Annexin V-FITC/PI apoptosis detection, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), transcriptomics, quantitative real‑time polymerase chain reaction (qRT‑PCR), spectrometric titration and molecular docking assays indicated that EU-5 could activate p53 signaling pathway and trigger mitochondria-mediated cell apoptosis. Taken together, this study provided a promising lead structure for the design of a new generation of anti-melanoma drugs.
A targeted long-read sequencing approach questions the association of OXTR methylation with high-functioning autism
Authors: Wieting Jelte , Jahn Kirsten , Bleich Stefan , Frieling Helge , Deest Maximilian
Published: December 2023

Background

DNA sequence variation and altered epigenetic regulation of the oxytocin receptor gene (OXTR) have been implicated in autism and autistic-like behaviors. While previous studies have examined subsegments of OXTR, nanopore Cas9-targeted sequencing (nCATS) allows deep characterization of entire genes with simultaneous assessment of epigenetic 5-methylcytosine (5mC) modification and without the need for prior DNA amplification or bisulfite conversion. This pilot study uses an nCATS approach to sequence the entire OXTR gene and its regulatory construct and screen for 5mC modification to compare results between individuals with high-functioning autism (HFA) and neurotypical controls (NC).

Methods

Using DNA extracted from peripheral blood, OXTR (Hg38, chr3: 8750381–8770434, 20,054 base pairs) was analyzed by nCATS. 5mC modification probabilities were calculated and visualized across the gene and differential methylation analysis was performed.

Results

Twenty adults with HFA (10 males, 10 females) and 20 age- and sex-matched NC (± 5 years) were included. There were no apparent group differences in the entire OXTR gene sequence, except for the intron variant rs918316, which was clustered in the HFA group. However, differential methylation analysis did not reveal a single significant group-dependent differentially methylated site among the 412 CpG sites captured.

Limitations

Limitations of this study include the small number of samples due to the pilot nature of the study, which particularly limits the relevance of the sequence variants found. It should also be noted that the use of peripheral blood material limits the ability to draw conclusions about central processes.

Conclusions

Previous findings of autism-associated OXTR epigenetic alterations were not reproducible with our method. In our opinion, this may lead to a reconsideration of the relevance of altered methylation at individual OXTR CpG positions in autism research. However, given the pilot nature of the study, these results need to be replicated in independent cohorts and with larger sample sizes.
Hypertonicity induces mitochondrial extracellular vesicles (MEVs) that activate TNF-α and β-catenin signaling to promote adipocyte dedifferentiation
Authors: Liu Guopan , Wang Ying , Pan Yilin , Tian Li , Choi Ming Ho , Wang Li , Kim Jin Young , Zhang Jian , Cheng Shuk Han , Zhang Liang
Published: December 2023

Background

Recent studies demonstrated that elevated osmolarity could induce adipocyte dedifferentiation, representing an appealing procedure to generate multipotent stem cells. Here we aim to elucidate the molecular mechanisms that underlie osmotic induction of adipocyte reprogramming.

Methods

To induce dedifferentiation, the 3T3-L1 or SVF adipocytes were cultured under the hypertonic pressure in 2% PEG 300 medium. Adipocyte dedifferentiation was monitored by aspect ratio measurement, Oil Red staining and qPCR to examine the morphology, lipid droplets, and specific genes of adipocytes, respectively. The osteogenic and chondrogenic re-differentiation capacities of dedifferentiated adipocytes were also examined. To investigate the mechanisms of the osmotic stress-induced dedifferentiation, extracellular vesicles (EVs) were collected from the reprograming cells, followed by proteomic and functional analyses. In addition, qPCR, ELISA, and TNF-α neutralizing antibody (20 ng/ml) was applied to examine the activation and effects of the TNF-α signaling. Furthermore, we also analyzed the Wnt signaling by assessing the activation of β-catenin and applying BML-284, an agonist of β-catenin.

Results

Hypertonic treatment induced dedifferentiation of both 3T3-L1 and the primary stromal vascular fraction (SVF) adipocytes, characterized by morphological and functional changes. Proteomic profiling revealed that hypertonicity induced extracellular vesicles (EVs) containing mitochondrial molecules including NDUFA9 and VDAC. Functionally, the mitochondrial EVs (MEVs) stimulated TNF-α signaling that activates Wnt-β-catenin signaling and adipocyte dedifferentiation. Neutralizing TNF-α inhibited hypertonic dedifferentiation of adipocytes. In addition, direct activation of Wnt-β-catenin signaling using BML-284 could efficiently induce adipocyte dedifferentiation while circumventing the apoptotic effect of the hypertonic treatment.

Conclusions

Hypertonicity prompts the adipocytes to release MEVs, which in turn enhances the secretion of TNF-α as a pro-inflammatory cytokine during the stress response. Importantly, TNF-α is essential for the activation of the Wnt/β-catenin signaling that drives adipocyte dedifferentiation. A caveat of the hypertonic treatment is apoptosis, which could be circumvented by direct activation of the Wnt/β-catenin signaling using BML-284.