bluuebunny/crossref_metadata_2025_split huggingface dataset:
The long noncoding RNA MIR4435-2HG enhances the migration, promotion, and glycolysis of nonsmall cell lung cancer cells by targeting the miR-371a-5p/SOX2/PI3K/Akt axis
Authors: Yang Jin , Su Yu , Wang Yuchen , Gao Kun , Li Chuang , Li Mengmeng 
Published: November 2024

Background: Nonsmall cell lung cancer is a leading cause of cancer-related death worldwide. The long noncoding RNA MIR4435-2HG has been shown to play a carcinogenic role in various cancers. The purpose of this study was to explore the role and regulatory mechanism of MIR4435-2HG in non-small cell lung cancer. Methods: Quantitative real-time polymerase chain reaction was used to detect MIR4435-2HG and SRY-box transcription factor 2 in nonsmall cell lung cancer cells. Gain- or loss-of-function assays of MIR4435-2HG and SRY-box transcription factor 2 were subsequently conducted. Cell proliferation, apoptosis, migration, glycolysis, and invasion were tested. A nude mouse tumor model was constructed to determine the role of MIR4435-2HG and SRY-box transcription factor 2 in the growth of tumor cells in vivo. Furthermore, the interactions between MIR4435-2HG, miR-371a-5p and SRY-box transcription factor 2 were analyzed via a dual-luciferase reporter gene assay. Results: Quantitative real-time polymerase chain reaction revealed that MIR4435-2HG and SRY-box transcription factor 2 were upregulated in nonsmall cell lung cancer cells. Forced MIR4435-2HG overexpression led to increased cell proliferation, migration, invasion, and glycolysis and repressed cell apoptosis. Overexpressing MIR4435-2HG promoted SRY-box transcription factor 2 expression and PI3K/Akt/mTOR pathway activation. Downregulating MIR4435-2HG had antitumor effects both in vitro and in vivo. SRY-box transcription factor 2 overexpression mostly reversed the suppressive effects of MIR4435-2HG downregulation. Mechanistic studies revealed that MIR4435-2HG, a competitive endogenous RNA, directly targeted and inhibited miR-371a-5p. Rescue assays revealed that miR-371a-5p overexpression or SRY-box transcription factor 2 downregulation significantly inhibited MIR4435-2HG-mediated oncogenic effects. Conclusion: MIR4435-2HG promotes nonsmall cell lung cancer cell malignant behaviors and glycolysis by regulating the miR-371a-5p/SOX2 axis.
Factors influencing in-hospital mortality in cancer patients with COVID-19: A retrospective survival analysis
Authors: Amado-Garzón Sandra Brigitte , Molina-Pimienta Luisana , Vásquez-Jiménez Juan Manuel , Álvarez-Raigoza Karen Lizeth , Manrique-Samer Mauricio , Lombo-Moreno Carlos E , Cañas-Arboleda Alejandra 
Published: November 2024

Objective: The aim of this study was to evaluate survival in patients with COVID-19 and cancer, and to find factors associated with early mortality. Methods: Retrospective cohort derived from a registry of a referral center in Bogotá. Survival was analyzed according to the type of neoplasm using Kaplan–Meier method. A cox regression was performed to look for factors associated to higher risk of death. Results: Two hundred fifty-four patients were included with cancer and COVID-19, most of whom were women (median age 68 years; range 19–97). Cardiovascular comorbidities were frequent. Patients with hematologic neoplasms had higher survival than those with solid neoplasms (log-rank test, p = 0.024). C-reactive protein levels (hazard ratio 1.02; 95% confidence interval 1.00–1.03, p = 0.025), Charlson’s comorbidity index (hazard ratio 1.15; 95% confidence interval 1.06–1.26, p = 0.004) and respiratory failure (hazard ratio 4.83; 95% confidence interval 2.47–9.44, p = <0.001) were significantly associated with higher mortality. No interaction between active anticancer therapy and mortality was observed. Conclusion: In contrast to other reports, survival was worse in patients with solid tumors than in those with hematologic neoplasms. Increased C-reactive protein, Charlson’s comorbidity index and respiratory failure were associated with higher in-hospital mortality. This study reveals the complex impact of cancer and its treatment on COVID-19 outcomes, highlighting the persistent risks to cancer patients. It emphasizes monitoring C-reactive protein levels, comorbidities, and respiratory failure as key indicators of poor prognosis. Furthermore, we provide new insights into the differential impact of COVID-19 on cancer patients with solid organ versus hematologic neoplasms.
3D Analysis of Metatarsal Torsion by Computed Tomography in Normal, Hallux Valgus, and Hallux Rigidus Feet
Authors: Kimura Tadashi , Kubota Makoto , Kihara Takumi , Suzuki Naoki , Hattori Asaki , Saito Mitsuru 
Published: November 2024

Background: One factor contributing to rotational deformity of the first metatarsal in hallux valgus is torsion of the metatarsal itself. Hallux rigidus also involves reduction of the longitudinal arch, but metatarsal torsion has not been discussed. We hypothesized that metatarsal torsion may be a morphologic change unique to hallux valgus. We compared 3-dimensional (3D) torsion of the first to fifth metatarsals between feet with hallux valgus, feet with hallux rigidus, and healthy control feet to investigate differences in the effects on pathologic conditions. Methods: Participants were women of East Asian descent. There were 16, 16, and 14 feet in the control, hallux valgus, and hallux rigidus groups, respectively. One randomly selected control foot was designated as the reference foot. For comparison, nonweightbearing computed tomography images of the metatarsals were reconstructed in 3D, and the proximal and distal areas were superimposed on the reference foot. Torsion angle was defined as the rotational angle of the distal part of the articular axis relative to the proximal area. In the hallux valgus group, correlations of torsion angle with hallux valgus angle and intermetatarsal angle were calculated. Results: The hallux valgus group had greater average pronation torsion in the first metatarsal than the control group and hallux rigidus group (11 and 13 degrees greater, respectively, P < .01). No significant differences were observed for the second to fifth metatarsals ( P > .05). There was no significant correlation with hallux valgus angle or first-second intermetatarsal angle in the hallux valgus group ( P > .05). Conclusion: Hallux valgus feet had pronation deformities in the first metatarsals not observed in control or hallux rigidus feet, meaning that torsion toward pronation (eversion) in the first metatarsal was unique to hallux valgus. Improved surgical correction to diminish pronation may be necessary in patients with hallux valgus patients because of first metatarsal pronation in the first tarsometatarsal to normalize mechanical first-ray alignment. Level of Evidence: Level III, case-control stud.
Palliative care consultation in the last week of life and associated factors: a cross-sectional general population study
Authors: Böling Susanna , Gyllensten Hanna , Engström My , Lundberg Emma , Berlin Johan , Öhlén Joakim 
Published: November 2024

Background: Knowledge of access to palliative care services, such as palliative care consultation teams, is crucial to identify areas of improvement for policy and practice. Research on general populations spanning all disease groups and multiple healthcare contexts is needed. Objective: The objective was to investigate the sociodemographic, disease- and care-related, and care structure-related factors associated with palliative care consultations for adult patients in the last week of life. Design: Cross-sectional, general population-level study based on linked Swedish national public authority registers and a national palliative care quality register. Methods: The study population included all adult patients deceased in Sweden between 2013 and 2019 and registered in the Swedish Register of Palliative Care, with an anticipated death, and not enrolled in specialised palliative care. Multivariable logistic regression analyses to investigate association with palliative care consultations. Results: In total, 8.2% of the 265,129 participants had received a palliative care consultation in the last week of life. The main multivariable analysis (Model 1) showed that those dying from neoplasms were more likely to receive a palliative care consultation (odds ratio (OR) 8.55, 95% CI 8.15–8.98) than those dying from circulatory diseases. Palliative care consultation was more likely with an increasing number of symptoms (OR 1.35, CI 1.32–1.37). Patients of old age and patients deceased in hospitals were less likely to receive a palliative care consultation. Moreover, factors such as educational attainment, healthcare region, living in a single-person household, and year of death were also associated with a palliative care consultation in the last week of life. Conclusion: Our findings show inequities in access to palliative care consultations in the last week of life. Considering changes to policy and clinical practice is motivated.
Reliability of Ultrasonographically Acquired Muscle Morphology Based on a Cohort of Men and Women
Authors: Fröhlich Matias , Rabello Rodrigo , Bueno Ingrassia Aline Felicio , Allein Zago Marcolino Miriam , Vaz Marco Aurélio 
Published: November 2024

Objective: The objective was to evaluate intrarater and inter-rater reliability of ultrasonography muscle morphology measurements in men and women, considering morphological differences between the genders. Materials and Methods: Thirty-two healthy subjects (16 male; 16 female; 26.6 ± 4.9 years) participated in two evaluation days. On day 1, subjects were evaluated by a single experienced rater, who repeated the evaluation on the next testing day along with two other raters. Muscle morphology of quadriceps femoris (QMT), rectus femoris (RFMT), vastus intermedius (VIMT), vastus medialis (VMMT), and vastus lateralis (VLMT) muscle thickness, rectus femoris muscle cross-sectional area (RFCSA), vastus lateralis muscle fascicle length (VLFL), and pennation angle (VLPA) were obtained. Reliability was evaluated by intraclass correlation coefficients (ICCs). Results: All intrarater comparisons demonstrated good reliability (ICC >0.90), even after participants’ gender stratification (ICC >0.81). Inter-rater comparisons for RFCSA, and muscle thickness showed good reliability (ICC >0.76). Male’s VLFL and VLPA reliability was considered insufficient (ICC = 0.58 and 0.60, respectively), while female’s was slightly higher (ICC = 0.79 and 0.75, respectively). Conclusion: Ultrasonography has potential to be used to observe changes in muscle size, but pennation angle and fascicle length should be evaluated by the same rater.
USP15 regulates radiation-induced DNA damage and intestinal injury through K48-linked deubiquitination and stabilisation of ATM
Authors: Zhu Ruiqiu , Li Mingyue , Wang Difan , Liu Chengzhi , Xie Liwei , Yang Yinyin , Gu Xuhao , Zhao Kui , Tian Ye , Cai Shang 
Published: November 2024

Abstract
Background
Radiation-induced intestinal injury (RIII) interrupts the scheduled processes of abdominal and pelvic radiotherapy (RT) and compromises the quality of life of cancer survivors. However, the specific regulators and mechanisms underlying the effects of RIII remain unknown. The biological effects of RT are caused primarily by DNA damage, and ataxia telangiectasia mutated (ATM) is a core protein of the DNA damage response (DDR). However, whether ATM is regulated by deubiquitination signaling remains unclear.

Methods
We established animal and cellular models of RIII. The effects of ubiquitin-specific protease 15 (USP15) on DNA damage and radion-induced intestinal injury were evaluated. Mass spectrometry analysis, truncation tests, and immunoprecipitation were used to identify USP15 as a binding partner of ATM and to investigate the ubiquitination of ATM. Finally, the relationship between the USP15/ATM axes was further determined via subsequent experiments.

Results
In this study, we identified the deubiquitylating enzyme USP15 as a regulator of DNA damage and the pathological progression of RIII. Irradiation upregulates the expression of USP15, whereas pharmacological inhibition of USP15 exacerbates radiation-induced DNA damage and RIII both in vivo and in vitro. Mechanistically, USP15 interacts with, deubiquitinates, and stabilises ATM via K48-linked deubiquitination. Notably, ATM overexpression blocks the effect of USP15 genetic inhibition on DNA damage and RIII progression.

Conclusions
These findings describe ATM as a novel deubiquitination target of USP15 upon radiation-induced DNA damage and intestinal injury, and provides experimental support for USP15/ATM axis as a potential target for developing strategies that mitigate RIII.
The optimal approach for retrieving systematic reviews was achieved when searching MEDLINE and Epistemonikos in addition to reference checking: a methodological validation study
Authors: Heinen Lena , Goossen Käthe , Lunny Carole , Hirt Julian , Puljak Livia , Pieper Dawid 
Published: November 2024

Abstract
Background
Systematic reviews (SRs) are used to inform clinical practice guidelines and healthcare decision making by synthesising the results of primary studies. Efficiently retrieving as many relevant SRs as possible is challenging with a minimum number of databases, as there is currently no guidance on how to do this optimally. In a previous study, we determined which individual databases contain the most SRs, and which combination of databases retrieved the most SRs. In this study, we aimed to validate those previous results by using a different, larger, and more recent set of SRs.

Methods
We obtained a set of 100 Overviews of Reviews that included a total of 2276 SRs. SR inclusion was assessed in MEDLINE, Embase, and Epistemonikos. The mean inclusion rates (% of included SRs) and corresponding 95% confidence intervals were calculated for each database individually, as well as for combinations of MEDLINE with each other database and reference checking. Features of SRs not identified by the best database combination were reviewed qualitatively.

Results
Inclusion rates of SRs were similar in all three databases (mean inclusion rates in % with 95% confidence intervals: 94.3 [93.9–94.8] for MEDLINE, 94.4 [94.0-94.9] for Embase, and 94.4 [93.9–94.9] for Epistemonikos). Adding reference checking to MEDLINE increased the inclusion rate to 95.5 [95.1–96.0]. The best combination of two databases plus reference checking consisted of MEDLINE and Epistemonikos (98.1 [97.7–98.5]). Among the 44/2276 SRs not identified by this combination, 34 were published in journals from China, four were other journal publications, three were health agency reports, two were dissertations, and one was a preprint. When discounting the journal publications from China, the SR inclusion rate in the recommended combination (MEDLINE, Epistemonikos and reference checking) was even higher than in the previous study (99.6 vs. 99.2%).

Conclusions
A combination of databases and reference checking was the best approach to searching for biomedical SRs. MEDLINE and Epistemonikos, complemented by checking the references of the included studies, was the most efficient and produced the highest recall. However, our results point to the presence of geographical bias, because some publications in journals from China were not identified.

Study registration
https://doi.org/10.17605/OSF.IO/R5EAS (Open Science Framework).
The hazard of using the Poisson model to cope with immortal time bias in the case of time-varying hazard
Authors: Rea Federico , Morabito Gabriella , Corrao Giovanni , Cantarutti Anna 
Published: November 2024

Abstract
Background
A time-dependent analysis, usually by means of Poisson and Cox regression models, can be applied to prevent immortal time bias. However, the use of the Poisson model requires the assumption that the event rate is constant over time. This study aims to assess the potential consequences of using the Poisson model to cope with immortal time bias on estimating the exposure-outcome relationship in the case of time-varying risks.

Methods
A simulation study was carried out. Survival times were assumed to follow a Weibull distribution, and the Weibull parameters were chosen to identify three different scenarios: the hazard of the event is constant, decreases, or increases over time. A dichotomous time-varying exposure in which patients can change at most once from unexposed to exposed was considered. The Poisson model was fitted to estimate the exposure-outcome association.

Results
Small changes in the outcome risk over time (as denoted by the shape parameter of the Weibull distribution) strongly affected the exposure-outcome association estimate. The estimated effect of exposure was always lower and greater than the true exposure effect when the event risk decreases or increases over time, and this was the case irrespective of the true exposure effect. The bias magnitude was positively associated with the prevalence of and time to exposure.

Conclusions
Biased estimates were obtained from the Poisson model to cope with immortal time. In settings with a time-varying outcome risk, the model should adjust for the trend in outcome risk. Otherwise, other models should be considered.
The impact of COVID-19 on private healthcare service utilisation: time series analysis in the capital region of Finland during 2020–2022
Authors: Niemenoja Oskar , Ämmälä Antti-Jussi , Riihijärvi Sari , Lillrank Paul , Bono Petri , Taimela Simo 
Published: November 2024

Abstract
Background
Most current studies on COVID-19 have focused on the first weeks or months of the pandemic or have addressed specific diseases. The long-term effects of the COVID-19 pandemic on healthcare services are insufficiently understood. We analysed the long-term effects of the COVID-19 pandemic on outpatient healthcare utilisation in the full spectrum of diseases in Uusimaa, the capital region of Finland.

Methods
Our data included 632 466 individual patients between the ages of 18 and 65 and 6 521 394 visits to healthcare personnel from electronic health records. We fitted an autoregressive integrated moving average (ARIMA) model to pre-2020 data to predict the expected quantity of diagnoses for the period between 1 January 2020 and 16 June 2022. Expected and observed quantities of diagnoses were compared.

Results
The overall quantity of diagnoses declined by one-fourth immediately following the onset of the pandemic and remained around 15% below predicted values for most of the pandemic. After the pandemic-related restrictions were lifted, the total diagnostic activity started to recover to pre-pandemic projection levels. However, this recovery has been mainly driven by upper respiratory system-related activity. The number of diagnoses for many diagnosis groups has remained below the predicted levels, even after the concurrent removal of mobility restrictions and increased coverage of vaccinations in this population.

Conclusions
The pandemic resulted in an overall reduction in outpatient healthcare utilisation which persisted for 30 months. While the overall diagnostic activity has eventually recovered to predicted levels, many classes of diagnoses display reduced levels in the study population over the follow-up period. Some diseases that may have long-lasting effects when left untreated seem to remain underdiagnosed, potentially increasing pressure on the healthcare system in the future.
Ethical considerations related to virtual visiting for families and critically ill patients in intensive care: a qualitative descriptive study
Authors: Clarke Kirsty , Borges Karen , Hatab Sultan , Richardson Lauren , Taylor Jessica , Evans Robyn , Chung Bethany , Cleverdon Harriet , Xyrichis Andreas , Cook Amelia , Meyer Joel , Rose Louise 
Published: November 2024

Abstract
Background
During the COVID-19 pandemic, virtual visiting technologies were rapidly integrated into the care offered by intensive care units (ICUs) in the UK and across the globe. Today, these technologies offer a necessary adjunct to in-person visits for those with ICU access limited by geography, work/caregiving commitments, or frailty. However, few empirical studies explore the ethical issues associated with virtual visiting. This study aimed to explore the anticipated or unanticipated ethical issues raised by using virtual visiting in the ICU, such that healthcare professionals can be informed about how to carry out virtual visits ethically, safely and productively.

Methods
We used a descriptive exploratory qualitative research approach recruiting a convenience sample of newly-graduated junior doctors facilitating ICU virtual visits in a tertiary academic centre. Eight newly graduated junior doctors, seven female and one male, aged 23–27, participated in semi-structured interviews. We analysed transcripts using an inductive coding approach.

Results
Five overarching themes emerged. Two of the themes namely, ‘fulfilling a moral instinct to connect families’ and ‘promoting autonomy’, arose from participants’ descriptions of how virtual visits aligned with healthcare standards and practices they considered ethical. Three further themes, ‘preserving dignity and privacy’, ‘managing emotional distress’, and ‘providing equitable access’ to virtual visiting technologies, highlight how virtual visits might exacerbate ethical issues related to family communications.

Conclusion
Virtual visiting may potentially both ameliorate and exacerbate aspects of ethical healthcare delivery for ICU patients and family members. ICU team members should consider unique ethical considerations related to using virtual visiting. We recommend virtual communications skills training for staff and advocate for the use of easily accessible educational resources for families who wish to visit critically unwell patients remotely.
Rehabilitation coordinator – managers’ experiences of a new function in health care
Authors: Strid Catharina , Benner Rosie , Stefansdotter Ronja , Stigmar Kjerstin 
Published: November 2024

Abstract
Background
Several actions have been taken to improve the sick listing process, patient safety and return to work. One of them is the implementation of the rehabilitation coordinator function, of which the benefits have not yet been fully explored. Neither has the role of the manager, who has significant impact on the implementation and support of a new function. This study aimed to explore how first line managers’, who employed a rehabilitation coordinator that had completed a one-year specialized study program, perceived, and experience the function rehabilitation coordinator.

Methods
This is an interview study using a semi structured interview guide for data collection and thematic analysis was applied to the data. Ten first line managers in health care were interviewed.

Results
Four themes were identified: The Saviour, A personalized function, Change takes time and Strengthen status and legitimacy. The managers experienced the rehabilitation coordinator as a valuable function who facilitates collaboration in the team and with external stakeholders and perceived them as a much-needed resources, supporting physicians with sick leave issues. The assignment was ambiguous and dependent on the rehabilitation coordinators individual characteristics, which may result in a risk of overload. The managers were engaged in the implementation process, but this required time. They considered it important to strengthen legitimacy for the function which required support and encouragement to take part in specialized education and training.

Conclusions
The managers experienced the rehabilitation coordinators as playing a crucial role in the return-to-work process. They were willing to support how this new function will improve and develop. The results from this can serve as a guidance for the implementation and support of the function rehabilitation coordinator.