bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the impact of hospital-onset SARS-CoV-2 infections on length of stay in English hospitals using causal inference
Authors: Stimson James , Pouwels Koen B. , Hope Russell , Cooper Ben S. , Presanis Anne M. , Robotham Julie V. 
Published: December 2022

Abstract
Background
From March 2020 through August 2021, 97,762 hospital-onset SARS-CoV-2 infections were detected in English hospitals. Resulting excess length of stay (LoS) created a potentially substantial health and economic burden for patients and the NHS, but we are currently unaware of any published studies estimating this excess.

Methods
We implemented appropriate causal inference methods to determine the extent to which observed additional hospital stay is attributable to the infection rather than the characteristics of the patients. Hospital admissions records were linked to SARS-CoV-2 test data to establish the study population (7.5 million) of all non-COVID-19 admissions to English hospitals from 1st March 2020 to 31st August 2021 with a stay of at least two days. The excess LoS due to hospital-onset SARS-CoV-2 infection was estimated as the difference between the mean LoS observed and in the counterfactual where infections do not occur. We used inverse probability weighted Kaplan–Meier curves to estimate the mean survival time if all hospital-onset SARS-CoV-2 infections were to be prevented, the weights being based on the daily probability of acquiring an infection. The analysis was carried out for four time periods, reflecting phases of the pandemic differing with respect to overall case numbers, testing policies, vaccine rollout and prevalence of variants.

Results
The observed mean LoS of hospital-onset cases was higher than for non-COVID-19 hospital patients by 16, 20, 13 and 19 days over the four phases, respectively. However, when the causal inference approach was used to appropriately adjust for time to infection and confounding, the estimated mean excess LoS caused by hospital-onset SARS-CoV-2 was: 2.0 [95% confidence interval 1.8–2.2] days (Mar-Jun 2020), 1.4 [1.2–1.6] days (Sep–Dec 2020); 0.9 [0.7–1.1] days (Jan–Apr 2021); 1.5 [1.1–1.9] days (May–Aug 2021).

Conclusions
Hospital-onset SARS-CoV-2 is associated with a small but notable excess LoS, equivalent to 130,000 bed days. The comparatively high LoS observed for hospital-onset COVID-19 patients is mostly explained by the timing of their infections relative to admission. Failing to account for confounding and time to infection leads to overestimates of additional length of stay and therefore overestimates costs of infections, leading to inaccurate evaluations of control strategies.
Comparing artificial neural network training algorithms to predict length of stay in hospitalized patients with COVID-19
Authors: Orooji Azam , Shanbehzadeh Mostafa , Mirbagheri Esmat , Kazemi-Arpanahi Hadi 
Published: December 2022

Abstract
Background
The exponential spread of coronavirus disease 2019 (COVID-19) causes unexpected economic burdens to worldwide health systems with severe shortages in hospital resources (beds, staff, equipment). Managing patients’ length of stay (LOS) to optimize clinical care and utilization of hospital resources is very challenging. Projecting the future demand requires reliable prediction of patients’ LOS, which can be beneficial for taking appropriate actions. Therefore, the purpose of this research is to develop and validate models using a multilayer perceptron-artificial neural network (MLP-ANN) algorithm based on the best training algorithm for predicting COVID-19 patients' hospital LOS.

Methods
Using a single-center registry, the records of 1225 laboratory-confirmed COVID-19 hospitalized cases from February 9, 2020 to December 20, 2020 were analyzed. In this study, first, the correlation coefficient technique was developed to determine the most significant variables as the input of the ANN models. Only variables with a correlation coefficient at a P-value < 0.2 were used in model construction. Then, the prediction models were developed based on 12 training algorithms according to full and selected feature datasets (90% of the training, with 10% used for model validation). Afterward, the root mean square error (RMSE) was used to assess the models’ performance in order to select the best ANN training algorithm. Finally, a total of 343 patients were used for the external validation of the models.

Results
After implementing feature selection, a total of 20 variables were determined as the contributing factors to COVID-19 patients’ LOS in order to build the models. The conducted experiments indicated that the best performance belongs to a neural network with 20 and 10 neurons in the hidden layer of the Bayesian regularization (BR) training algorithm for whole and selected features with an RMSE of 1.6213 and 2.2332, respectively.

Conclusions
MLP-ANN-based models can reliably predict LOS in hospitalized patients with COVID-19 using readily available data at the time of admission. In this regard, the models developed in our study can help health systems to optimally allocate limited hospital resources and make informed evidence-based decisions.
Plasma and cerebrospinal fluid neurofilament light concentrations reflect neuronal damage in systemic lupus Erythematosus
Authors: Zervides Kristoffer A. , Janelidze Shorena , Nystedt Jessika , Gullstrand Birgitta , Nilsson Petra , Sundgren Pia C. , Bengtsson Anders A. , Hansson Oskar , Jönsen Andreas 
Published: December 2022

Abstract
Background
Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE.

Methods
Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged < 55 years, underwent magnetic resonance imaging (MRI) and neurocognitive testing. NfL concentrations in plasma from all individuals and in CSF from 32 patients were measured with single-molecule array technology. Patients were assessed by a rheumatologist and neurologist to define neuropsychiatric involvement (NPSLE) according to three attribution models: SLICC A, SLICC B and ACR.

Results
Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p < 0.001). Both NPSLE and non-NPSLE patients in all attribution models had higher plasma NfL concentrations compared with healthy controls (log-NfL, pg/ml, mean (SD); healthy controls (0.71 (0.17)); SLICC A model: NPSLE (0.87 (0.13), p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p < 0.001), non-NPSLE (0.81 (0.17), p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively).

Conclusions
Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.
JC virus-induced progressive multifocal leukoencephalopathy in a presumably healthy patient
Authors: Wang Xiang , Chen Jinxiu , Gong Jing , Wu Ying , Liu Xiang-hao 
Published: December 2022

Abstract
Background
JC virus (JCV) is common among healthy individuals and remains latent but may be reactivated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML). Here, we present a rare case of PML caused by JC virus infection in a previously healthy and immunocompetent patient.

Case presentation
A 67-year-old female without any disease history was admitted after presenting with rapidly progressive dementia. The preoperative diagnosis was progressive multifocal leukoencephalopathy, and corticosteroid treatment did not improve the symptoms. Brain lesions were surgically sampled, and JCV infection was confirmed by high-throughput DNA gene detection. This patient received a combined treatment of mirtazapine, mefloquine, and traditional Chinese herbs, and had stabilization of the disease on followed-up.

Conclusions
Although it is a rare, this case demonstrates that JC virus infection within the brain occurs in apparently healthy people. This case may increase our understanding of virus infection when facing the coronavirus epidemic in recent years, considering that similar medications were used.

Graphical Abstract
Placental mesenchymal dysplasia complicated with sudden fetal demise and amniotic fluid embolism: a case report
Authors: Wang Shao-Jing , Lin Li-Ling , Chen Wei-Chih 
Published: December 2022

Abstract
Background
Placenta mesenchymal dysplasia (PMD) is a rare placental anomaly associated with various fetal and maternal complications. Whether close ultrasound surveillance can prevent intrauterine fetal demise (IUFD) in patients with PMD is still under investigation. Amniotic fluid embolism (AFE) is a rare, lethal, and unpredictable maternal complication that has never been described in association with PMD. Here, we report a case of PMD, in which the fetus eventually demised in utero despite weekly color Doppler monitoring, and the mother subsequently encountered AFE during delivery.

Case presentation
A 43-year-old woman who had received three frozen embryo transfer, was found to have a singleton pregnancy with an enlarged multi-cystic placenta at 8 weeks’ gestation. Fetal growth restriction (FGR) was noted since the 21stweek. The fetus eventually demised in-utero at 25 weeks despite weekly color Doppler surveillance. Cesarean section was performed under general anesthesia due to placenta previa totalis and antepartum hemorrhage. During surgery, the patient experienced a sudden blood pressure drop and desaturation followed by profound coagulopathy. AFE was suspected. After administration of inotropic agents and massive blood transfusion, the patient eventually survived AFE. PMD was confirmed after pathological examination of the placenta.

Conclusions
While FGR can be monitored by color Doppler, our case echoed previous reports that IUFD may be unpreventable even under intensive surveillance in PMD cases. Although AFE is usually considered unpredictable, PMD can result in cumulative risk factors contributing to AFE. Whether a specific link exists between the pathophysiology of PMD and AFE requires further investigation.
Adverse pregnancy and birth outcomes in sexual minority women from the National Survey of Family Growth
Authors: Barcelona Veronica , Jenkins Virginia , Britton Laura E. , Everett Bethany G. 
Published: December 2022

Abstract
Background
Few studies have examined how multiple marginalized identities are associated with adverse pregnancy and birth outcomes, especially for Black and Hispanic sexual minority women. Sexual minorities are people who identify as lesbian, gay, bisexual or transgender (LGBT). The purpose of this study was to examine differences in adverse pregnancy (i.e., miscarriage) and birth outcomes (i.e., preterm birth, low birthweight, and stillbirth) in a national sample of women by race and ethnicity, and sexual minority status (LGBT identification and same-sex sexual behavior).

Methods
We conducted a cross-sectional analysis of the National Survey of Family Growth (NSFG). The unit of analysis was pregnancy, not participants. In this study, we examined pregnancies to participants who identified as heterosexual, lesbian, and bisexual, by race and Hispanic ethnicity. We also studied sexual behaviors to categorize participants as women who have sex with women (WSW) and women who have sex with men (WSM). Outcomes included preterm birth, low birthweight, miscarriage, and stillbirth. We employed logistic and linear regression analyses for analyses using STATA.

Results
We studied 53,751 pregnancies, and 9% of these occurred in people who identified as heterosexual, but had engaged in sexual activity with a female partner (heterosexual-WSW), 7% in those identifying as bisexual, and 1% to women who identified as lesbian. Pregnancies ended in preterm birth (10.7%) and low birthweight (9.0%), stillbirths (2–4%), and miscarriages (17–21%) in sexual minority women. We observed that pregnancies reported by Hispanic lesbian women had a higher birthweight (β = 10.71, SE = 4.1, p-value = 0.01) compared to infants born to Hispanic heterosexual-WSM. Pregnancies to lesbian women were significantly more likely to end in stillbirth (aRR = 3.58, 95% CI 1.30,9.79) compared to heterosexual-WSM. No significant differences were noted in risk of adverse birth outcomes by sexual orientation for NH Black or Hispanic women.

Conclusion
In this sample, preterm births were less likely to occur among heterosexual-WSW than in heterosexual-WSM. Pregnancies to lesbians and bisexual women were more likely to end in miscarriage or stillbirth than heterosexual WSM. Lesbian Hispanic women reported higher birthweights compared to heterosexual-WSM Hispanic women. More research should be done to further understand these findings.
Does lack of exposure to individual antidepressants at different points during pregnancy associate with reduced risk of adverse newborn outcomes?
Authors: Tharp Margaret A. , Silvola Rebecca M. , Marks Claire , Teal Evgennia , Quinney Sara K. , Haas David M. 
Published: December 2022

Abstract
Background
The objective of this study was to determine if the lack of exposure to individual antidepressants at certain times in pregnancy improved maternal and infant outcomes.

Methods
This was a retrospective cohort study of 2741 pregnant women prescribed antidepressant(s) before or during pregnancy. Data were obtained from electronic medical records. Analysis was limited to women prescribed one of five antidepressants (bupropion, citalopram, escitalopram, fluoxetine, sertraline). Period of exposure was determined using prescription order dates. Primary outcomes were neonatal intensive care unit (NICU) admission and adaptation syndrome in the newborn. Logistic regression, adjusted for maternal age, race, and insurance, compared consistent exposure throughout pregnancy versus (A) no exposure in the third trimester, (B) no exposure early in pregnancy, and (C) exposure in the midtrimester alone.

Results
Compared to women prescribed an antidepressant continually throughout pregnancy, NICU admission was less likely for women lacking exposure in the third trimester if they had been taking bupropion (aOR 0.43, 95% CI 0.21–0.90) or escitalopram (aOR 0.49, 95% CI 0.28–0.85). Women previously taking escitalopram but lacking third trimester exposure also had lower odds of adaptation syndrome (aOR 0.19, 95% CI 0.07–0.48). No differences were found in other outcomes for women taking other antidepressants or for any outcomes for women who lacked early pregnancy drug exposure compared to exposure throughout pregnancy.

Conclusion
For the five antidepressants included in this study, lack of exposure early or late in pregnancy compared to consistent exposure throughout pregnancy generally did not change newborn outcomes. The exceptions were bupropion and escitalopram, where lack of exposure in the third trimester associated with lower rates of adaptation syndrome or NICU admission. These data may help pregnant women with depression in need of drug therapy to have informed discussions with providers about the potential risks and benefits to continuing or stopping drugs at different times during pregnancy.
IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation
Authors: Kato Taigo , Matsubara Nobuaki , Shiota Masaki , Eto Masatoshi , Osawa Takahiro , Abe Takashige , Shinohara Nobuo , Yasumizu Yota , Tanaka Nobuyuki , Oya Mototsugu , Nishimoto Koshiro , Hayashi Takuji , Nakayama Masashi , Kojima Takahiro , Namikawa Kenjiro , Fujisawa Takao , Okano Susumu , Hida Eisuke , Nakamura Yoshiaki , Bando Hideaki , Yoshino Takayuki , Nonomura Norio 
Published: December 2022

Abstract
Background
Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis.

Methods
Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood.

Expected outcome
Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs.

Trial registration
The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.
Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study
Authors: McDowell Bethany , Marr Calum , Holmes Clive , Edwards Christopher J. , Cardwell Christopher , McHenry Michelle , Meenagh Gary , McGuinness Bernadette 
Published: December 2022

Abstract
Objective
To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition.

Methods and analysis
Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment.

Results
The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p = .006), being male (p = .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p = 0.008) and high (DAS28 > 5.1) (p = 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p > 0.05).

Conclusion
This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.
Association of meaning in life with preventive healthcare use among Chinese adults: are there age and gender differences?
Authors: Zhang Dexing , Xu Zijun , Yang Zuyao , Zhou Weiju , Cheung Peter Man-hin , Kam-pui Lee Eric , Zhong Baoliang , Xu Dong , Li Xue , Xie Yaojie , Yang Gao , Xiao Shuiyuan , Wong Samuel Yeung-shan 
Published: December 2022

Abstract
Background
Meaning in life could be of clinical importance in stimulating healthy and preventive behaviors. The study aimed to investigate the association between meaning in life and preventive healthcare use among Chinese adults, and to assess their age and gender differences in the association.

Methods
A cross-sectional online survey was conducted among 1444 adults aged 18–64 years in February 2020 in China. Logistic regression models were employed to examine the association of meaning in life with preventive health checkups and assess their age and gender differences.

Results
The mean score of meaning in life was 5.801 (Standard Deviation = 1.349) out of 7. Each unit increase on the level of meaning in life was associated with 12.2% higher likelihood of using preventive health checkups (any type) (adjusted odds ratio 1.122, 95% confidence interval 1.015–1.241) after adjustment for sociodemographic factors, comorbidity and other psychological health factors. Meaning in life was significantly associated with the uses of X-ray (1.125, 1.010–1.253), B-ultrasound (1.176, 1.058–1.306), and blood testing (1.152, 1.042–1.274). The associations between meaning in life and these types of preventive healthcare increased with age, but there were no gender differences in these associations.

Conclusion
Higher meaning in life was independently related to more preventive health checkups. Strategies to strengthen health education and interventions to improve experience of meaning in life might be an important component to increase preventive healthcare use in China.