bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is inpatient rehabilitation a predictor of a lower incidence of persistent knee pain 3-months following total knee replacement? A retrospective, observational study
Authors: Johns Nathan , Naylor Justine , McKenzie Dean , Brady Bernadette , Olver John 
Published: September 2022

Abstract
Background
Moderate to severe levels of persistent knee pain have been estimated to affect up to 25% of people 3-months or more after a total knee replacement. It is unknown whether the type of rehabilitation pathway is associated with persistent high pain after surgery. Using a prospectively followed Australian cohort who underwent total knee replacement for knee osteoarthritis, this study aimed to i) report the incidence of high-intensity knee pain (defined as a score ≤ 15 on the Oxford Knee Score pain subscale) across time and ii) identify whether referral to inpatient rehabilitation was one of the predictors of persistent pain at 3-months post-surgery.

Methods
A retrospective analysis of a large prospective study was conducted using the Oxford Knee Score pain subscale to determine if participants had high pain at 3-months, 12-months and 36-months post-surgery. Relative risks for high pain at 3-, 12- and 36-months between the type of rehabilitation pathway were determined using Poisson multivariable regression with robust standard errors. The same technique was also employed to determine potential predictors, including rehabilitation pathway, of high pain at 3 months.

Results
The incidence of high pain in all participants was 73% pre-surgery and 10, 5 and 6% at 3-, 12- and 36-months respectively following knee replacement. There was a significant interaction between time and rehabilitation pathway, suggesting that the effect of the rehabilitation pathway varied across time. The incidence of high pain at 3-months did not significantly differ between those who attended inpatient rehabilitation (11.6%) and those discharged directly home (9.5%). Multivariable Poisson regression analysis identified the pre-surgical presence of high pain, co-morbid low back pain or other lower limb problem, younger age and having a major complication within 3-months following surgery as significant predictors of persistent pain whilst discharge to inpatient rehabilitation was not.

Conclusion
A small but clinically significant minority of people continued to have high pain levels at 3-, 12- and 36-months following a primary total knee replacement for osteoarthritis. Participation in an inpatient rehabilitation program does not appear to be an important predictor of ongoing knee pain.

Trial registration
The data were collected in the Evidence-based Processes and Outcomes of Care (EPOC) study, ClinicalTrials.gov Identifier: NCT01899443
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in an Australian institution: lessons from 20 years’ experience
Authors: Farrell R. , Liauw W. S. , Morris D. L. 
Published: September 2022

Abstract
Objectives
We report the 20-year experience of the largest Australian unit performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer and reflect on learning opportunities.

Methods
A retrospective review of all cases of CRS for ovarian cancer at St George Peritonectomy Unit from Jan 1998 to Jan 2018 was performed. Prospectively collected data include age, stage, histology, disease extent (PCI), completeness of cytoreduction (CC score), HIPEC regime, 30-day surgical morbidity, disease recurrence, and death. Survival was computed using Kaplan–Meier method and analysed using log-rank tests and Cox-proportional hazards models.

Results
Forty-one women with advanced ovarian cancer (11 primary stage III/IV, 30 recurrent) underwent CRS, 29 (71%) with HIPEC. Most (68%) had high-volume disease (PCI > 15). In 98%, CC0/CC1 (residual < 2.5 mm) was achieved. Fourteen (34%) had grade 3/4 complications, 1 patient (2%) died within 30 days and 2 patients (5%) died within 90 days. Progression-free and median overall survival was 30.0 and 67.0 months for primary cancer, and 6.7 and 18.1 months for recurrent cancer. Survival was associated with platinum-sensitivity, PCI ≤ 15, and CC score 0, but not HIPEC.

Conclusion
This study reports outcomes for patients with advanced ovarian cancer patients treated in an Australian centre offering CRS and HIPEC. Whilst survival and morbidity outcomes were good for primary disease, they were poorer than predicted from the literature for cases of recurrent disease. The incorporation of evidence-based predictors of survival and multidisciplinary input are essential to achieve the best survival outcomes.
Impact of low health literacy on patients’ health outcomes: a multicenter cohort study
Authors: Shahid Rabia , Shoker Muhammad , Chu Luan Manh , Frehlick Ryan , Ward Heather , Pahwa Punam 
Published: September 2022

AbstractBackgroundThis study aims to assess the health literacy of medical patients admitted to hospitals and examine its correlation with patients’ emergency department visits, hospital readmissions, and durations of hospital stay.MethodsThis prospective cohort study recruited patients admitted to the general internal medicine units at the two urban tertiary care hospitals. Health literacy was measured using the full-length Test of Functional Health Literacy in Adults. Logistic regression analyses were performed to examine the correlation between health literacy and the desired outcomes. The primary outcome of interest of this study was to determine the correlation between health literacy and emergency department revisit within 90 days of discharge. The secondary outcomes of interest were to assess the correlation between health literacy and length of stay and hospital readmission within 90 days of discharge.ResultsWe found that 50% had adequate health literacy, 32% had inadequate, and 18% of patients had marginal health literacy. Patients with inadequate health literacy were more likely to revisit the emergency department as compared to patients with adequate health literacy (odds ratio: 3.0; 95% Confidence Interval: 1.3–6.9,p = 0.01). In patients with inadequate health literacy, the mean predicted probability of emergency department revisits was 0.22 ± 0.11 if their education level was some high school or less and 0.57 ± 0.18 if they had completed college. No significant correlation was noted between health literacy and duration of hospital stay or readmission.ConclusionsOnly half of the patients admitted to the general internal medicine unit had adequate health literacy. Patients with low health literacy, but high education, had a higher probability of emergency department revisits.
Lung function and radiological findings 1 year after COVID-19: a prospective follow-up
Authors: Tarraso Julia , Safont Belen , Carbonell-Asins Juan A. , Fernandez-Fabrellas Estrella , Sancho-Chust José N. , Naval Elsa , Amat Beatriz , Herrera Susana , Ros José A. , Soler-Cataluña Juan J. , Rodriguez-Portal Jose A. , Andreu Ada L. , Marín Margarita , Rodriguez-Hermosa Juan L. , Gonzalez-Villaescusa Cruz , Soriano Joan B. , Signes-Costa Jaime ,   COVID-FIBROTIC study team, García Yolanda , Blasco Natividad , Herrera Antonio , Mulet Alba , Ballester Andrea , Fernandez Lucia , Quezada Antonio , Meneses Elsie Daviana , Carrión Noelia , Celis Carly , Cabanes Luis , Molina Virginia , Valentin Veronica , López Irene , Solana-Martínez Elena , Aparicio-Vicente Mario , López Celia , Cuenca Selene , Vargas Gianna 
Published: September 2022

Abstract
Background
The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge.

Methods
COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months.

Results
Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06–2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98–0.99; p = 0.046).

Conclusion
Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process.
Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020)
Myeloid liver kinase B1 contributes to lung inflammation induced by lipoteichoic acid but not by viable Streptococcus pneumoniae
Authors: Pereverzeva Liza , Otto Natasja A. , Roelofs Joris J. T. H. , de Vos Alex F. , van der Poll Tom 
Published: September 2022

Abstract
Background
Liver kinase B1 (Lkb1, gene name Stk11) functions as a tumor suppressor in cancer. Myeloid cell Lkb1 potentiates lung inflammation induced by the Gram-negative bacterial cell wall component lipopolysaccharide and in host defense during Gram-negative pneumonia. Here, we sought to investigate the role of myeloid Lkb1 in lung inflammation elicited by the Gram-positive bacterial cell wall component lipoteichoic acid (LTA) and during pneumonia caused by the Gram-positive respiratory pathogen Streptococcus pneumoniae (Spneu).

Methods
Alveolar and bone marrow derived macrophages (AMs, BMDMs) harvested from myeloid-specific Lkb1 deficient (Stk11-ΔM) and littermate control mice were stimulated with LTA or Spneu in vitro. Stk11-ΔM and control mice were challenged via the airways with LTA or infected with Spneu in vivo.

Results
Lkb1 deficient AMs and BMDMs produced less tumor necrosis factor (TNF)α upon activation by LTA or Spneu. During LTA-induced lung inflammation, Stk11-ΔM mice had reduced numbers of AMs in the lungs, as well as diminished cytokine release and neutrophil recruitment into the airways. During pneumonia induced by either encapsulated or non-encapsulated Spneu, Stk11-ΔM and control mice had comparable bacterial loads and inflammatory responses in the lung, with the exception of lower TNFα levels in Stk11-ΔM mice after infection with the non-encapsulated strain.

Conclusion
Myeloid Lkb1 contributes to LTA-induced lung inflammation, but is not important for host defense during pneumococcal pneumonia.
Small extracellular vesicles: from promoting pre-metastatic niche formation to therapeutic strategies in breast cancer
Authors: Chen Xiaoxiao , Feng Jiamei , Chen Weili , Shao Shijun , Chen Li , Wan Hua 
Published: September 2022

AbstractBreast cancer is the most common cancer in females, and to date, the mortality rate of breast cancer metastasis cannot be ignored. The metastasis of breast cancer is a complex, staged process, and the pattern of metastatic spread is not random. The pre-metastatic niche, as an organ-specific home for metastasis, is a favourable environment for tumour cell colonization. As detection techniques improve, the role of the pre-metastatic niche in breast cancer metastasis is being uncovered. sEVs (small extracellular vesicles) can deliver cargo, which is vital for the formation of pre-metastatic niches. sEVs participate in multiple aspects of creating a distant microenvironment to promote tumour invasion, including the secretion of inflammatory molecules, immunosuppression, angiogenesis and enhancement of vascular permeability, as well as regulation of the stromal environment. Here, we discuss the multifaceted mechanisms through which breast cancer-derived sEVs contribute to pre-metastatic niches. In addition, sEVs as biomarkers and antimetastatic therapies are also discussed, particularly their use in transporting exosomal microRNAs. The study of sEVs may provide insight into immunotherapy and targeted therapies for breast cancer, and we also provide an overview of their potential role in antitumour metastasis.
Liquid biopsy: current technology and clinical applications
Authors: Nikanjam Mina , Kato Shumei , Kurzrock Razelle 
Published: September 2022

AbstractLiquid biopsies are increasingly used for cancer molecular profiling that enables a precision oncology approach. Circulating extracellular nucleic acids (cell-free DNA; cfDNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) can be isolated from the blood and other body fluids. This review will focus on current technologies and clinical applications for liquid biopsies. ctDNA/cfDNA has been isolated and analyzed using many techniques, e.g., droplet digital polymerase chain reaction, beads, emulsion, amplification, and magnetics (BEAMing), tagged-amplicon deep sequencing (TAm-Seq), cancer personalized profiling by deep sequencing (CAPP-Seq), whole genome bisulfite sequencing (WGBS-Seq), whole exome sequencing (WES), and whole genome sequencing (WGS). CTCs have been isolated using biomarker-based cell capture, and positive or negative enrichment based on biophysical and other properties. ctDNA/cfDNA and CTCs are being exploited in a variety of clinical applications: differentiating unique immune checkpoint blockade response patterns using serial samples; predicting immune checkpoint blockade response based on baseline liquid biopsy characteristics; predicting response and resistance to targeted therapy and chemotherapy as well as immunotherapy, including CAR-T cells, based on serial sampling; assessing shed DNA from multiple metastatic sites; assessing potentially actionable alterations; analyzing prognosis and tumor burden, including after surgery; interrogating difficult-to biopsy tumors; and detecting cancer at early stages. The latter can be limited by the small amounts of tumor-derived components shed into the circulation; furthermore, cfDNA assessment in all cancers can be confounded by clonal hematopoeisis of indeterminate potential, especially in the elderly. CTCs can be technically more difficult to isolate that cfDNA, but permit functional assays, as well as evaluation of CTC-derived DNA, RNA and proteins, including single-cell analysis. Blood biopsies are less invasive than tissue biopsies and hence amenable to serial collection, which can provide critical molecular information in real time. In conclusion, liquid biopsy is a powerful tool, and remarkable advances in this technology have impacted multiple aspects of precision oncology, from early diagnosis to management of refractory metastatic disease. Future research may focus on fluids beyond blood, such as ascites, effusions, urine, and cerebrospinal fluid, as well as methylation patterns and elements such as exosomes.
PEEP-FiO2 table versus EIT to titrate PEEP in mechanically ventilated patients with COVID-19-related ARDS
Authors: Somhorst Peter , van der Zee Philip , Endeman Henrik , Gommers Diederik 
Published: September 2022

Abstract
Rationale
It is unknown how to titrate positive end-expiratory pressure (PEEP) in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Guidelines recommend the one-size-fits-all PEEP-FiO2 table. In this retrospective cohort study, an electrical impedance tomography (EIT)-guided PEEP trial was used to titrate PEEP.

Objectives
To compare baseline PEEP according to the high PEEP-FiO2 table and personalized PEEP following an EIT-guided PEEP trial.

Methods
We performed an EIT-guided decremental PEEP trial in patients with moderate-to-severe COVID-19-related ARDS upon intensive care unit admission. PEEP was set at the lowest PEEP above the intersection of curves representing relative alveolar overdistention and collapse. Baseline PEEP was compared with PEEP set according to EIT. We identified patients in whom the EIT-guided PEEP trial resulted in a decrease or increase in PEEP of ≥ 2 cmH2O.

Measurements and main results
We performed a PEEP trial in 75 patients. In 23 (31%) patients, PEEP was decreased ≥ 2 cmH2O, and in 24 (32%) patients, PEEP was increased ≥ 2 cmH2O. Patients in whom PEEP was decreased had improved respiratory mechanics and more overdistention in the non-dependent lung region at higher PEEP levels. These patients also had a lower BMI, longer time between onset of symptoms and intubation, and higher incidence of pulmonary embolism. Oxygenation improved in patients in whom PEEP was increased.

Conclusions
An EIT-guided PEEP trial resulted in a relevant change in PEEP in 63% of patients. These results support the hypothesis that PEEP should be personalized in patients with ARDS.
Predicting conversion of brain β-amyloid positivity in amyloid-negative individuals
Authors: Park Chae Jung , Seo Younghoon , Choe Yeong Sim , Jang Hyemin , Lee Hyejoo , Kim Jun Pyo ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

Abstract
Background
Cortical deposition of β-amyloid (Aβ) plaque is one of the main hallmarks of Alzheimer’s disease (AD). While Aβ positivity has been the main concern so far, predicting whether Aβ (−) individuals will convert to Aβ (+) has become crucial in clinical and research aspects. In this study, we aimed to develop a classifier that predicts the conversion from Aβ (−) to Aβ (+) using artificial intelligence.

Methods
Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort regarding patients who were initially Aβ (−). We developed an artificial neural network-based classifier with baseline age, gender, APOE ε4 genotype, and global and regional standardized uptake value ratios (SUVRs) from positron emission tomography. Ten times repeated 10-fold cross-validation was performed for model measurement, and the feature importance was assessed. To validate the prediction model, we recruited subjects at the Samsung Medical Center (SMC).

Results
A total of 229 participants (53 converters) from the ADNI dataset and a total of 40 subjects (10 converters) from the SMC dataset were included. The average area under the receiver operating characteristic values of three developed models are as follows: Model 1 (age, gender, APOE ε4) of 0.674, Model 2 (age, gender, APOE ε4, global SUVR) of 0.814, and Model 3 (age, gender, APOE ε4, global and regional SUVR) of 0.841. External validation result showed an AUROC of 0.900.

Conclusion
We developed prediction models regarding Aβ positivity conversion. With the growing recognition of the need for earlier intervention in AD, the results of this study are expected to contribute to the screening of early treatment candidates.
Mouse models of SMA show divergent patterns of neuronal vulnerability and resilience
Authors: Woschitz Victoria , Mei Irene , Hedlund Eva , Murray Lyndsay M. 
Published: September 2022

Abstract
Background
Spinal muscular atrophy (SMA) is a form of motor neuron disease affecting primarily children characterised by the loss of lower motor neurons (MNs). Breakdown of the neuromuscular junctions (NMJs) is an early pathological event in SMA. However, not all motor neurons are equally vulnerable, with some populations being lost early in the disease while others remain intact at the disease end-stage. A thorough understanding of the basis of this selective vulnerability will give critical insight into the factors which prohibit pathology in certain motor neuron populations and consequently help identify novel neuroprotective strategies.

Methods
To retrieve a comprehensive understanding of motor neuron susceptibility in SMA, we mapped NMJ pathology in 20 muscles from the Smn2B/- SMA mouse model and cross-compared these data with published data from three other commonly used mouse models. To gain insight into the molecular mechanisms regulating selective resilience and vulnerability, we analysed published RNA sequencing data acquired from differentially vulnerable motor neurons from two different SMA mouse models.

Results
In the Smn2B/- mouse model of SMA, we identified substantial NMJ loss in the muscles from the core, neck, proximal hind limbs and proximal forelimbs, with a marked reduction in denervation in the distal limbs and head. Motor neuron cell body loss was greater at T5 and T11 compared with L5. We subsequently show that although widespread denervation is observed in each SMA mouse model (with the notable exception of the Taiwanese model), all models have a distinct pattern of selective vulnerability. A comparison of previously published data sets reveals novel transcripts upregulated with a disease in selectively resistant motor neurons, including genes involved in axonal transport, RNA processing and mitochondrial bioenergetics.

Conclusions
Our work demonstrates that the Smn2B/- mouse model shows a pattern of selective vulnerability which bears resemblance to the regional pathology observed in SMA patients. We found drastic differences in patterns of selective vulnerability across the four SMA mouse models, which is critical to consider during experimental design. We also identified transcript groups that potentially contribute to the protection of certain motor neurons in SMA mouse models.
Thermo-mechanical simulations of powder bed fusion processes: accuracy and efficiency
Authors: Burkhardt Christian , Steinmann Paul , Mergheim Julia 
Published: September 2022

AbstractIn this contribution, the accuracy and efficiency of various modeling assumptions and numerical settings in thermo-mechanical simulations of powder bed fusion (PBF) processes are analyzed. Thermo-mechanical simulations are used to develop a better understanding of the process and to determine residual stresses and distortions based on the temperature history. In these numerically very complex simulations, modeling assumptions are often made that reduce computational effort but lead to inaccuracies. These assumptions include the omission of the surrounding powder or the use of geometrically linearized material models. The numerical setting, in particular the temporal and spatial discretizations, can further lead to discretization errors. Here, a highly parallelized and adaptive finite element method based on the open source C++ library deal.II is validated and utilized, to investigate some of these modeling assumptions and to identify the required temporal and spatial discretizations for the simulation of PBF of Ti-6Al-4V. The insights initially gained on a simple wall-like geometry are transferred to a larger open rectangular profile where the results of a detailed simulation are compared with those of a more efficient one. The results for the efficient approach show a maximum deviation of $$\approx 8\%$$

≈
8
%

in the displacements and $$\approx 3.5\%$$

≈
3.5
%

in the residual stresses while significantly reducing the computational time.