bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tachycardia and hypertension enhance tracer efflux from the spinal cord
Authors: Liu Shinuo , Bilston Lynne E. , Stoodley Marcus A. , Hemley Sarah J. 
Published: October 2021

Abstract
Background
Disruption of cerebrospinal fluid (CSF)/interstitial fluid (ISF) exchange in the spinal cord is likely to contribute to central nervous system (CNS) diseases that involve abnormal fluid accumulation, including spinal cord oedema and syringomyelia. However, the physiological factors that govern fluid transport in the spinal cord are poorly understood. The aims of this study were to determine the effects of cardiac pulsations and respiration on tracer signal increase, indicative of molecular movement following infusion into the spinal cord grey or white matter.

Methods
In Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachycardia (heart atrial pacing), as well as hypertension (pharmacologically induced) were separately studied. Since fluid outflow from the spinal cord cannot be directly measured, we assessed the molecular movement of fluorescent ovalbumin (AFO-647), visualised by an increase in tracer signal, following injection into the cervicothoracic spinal grey or white matter.

Results
Tachycardia and hypertension increased AFO-647 tracer efflux, while the concomitant negative and positive intrathoracic pressures generated during spontaneous breathing did not when compared to the positive-pressure ventilated controls. Following AFO-647 tracer injection into the spinal grey matter, increasing blood pressure and heart rate resulted in increased tracer movement away from the injection site compared to the hypotensive, bradycardic animals (hypertension: p = 0.05, tachycardia: p < 0.0001). Similarly, hypertension and tachycardia produced greater movement of AFO-647 tracer longitudinally along the spinal cord following injection into the spinal white matter (p < 0.0001 and p = 0.002, respectively). Tracer efflux was strongly associated with all blood vessel types.

Conclusions
Arterial pulsations have profound effects on spinal cord interstitial fluid homeostasis, generating greater tracer efflux than intrathoracic pressure changes that occur over the respiratory cycle, demonstrated by increased craniocaudal CSF tracer movement in the spinal cord parenchyma.
Influence of traumatic brain injury on extracellular tau elimination at the blood–brain barrier
Authors: Eisenbaum Maxwell , Pearson Andrew , Gratkowski Arissa , Mouzon Benoit , Mullan Michael , Crawford Fiona , Ojo Joseph , Bachmeier Corbin 
Published: October 2021

AbstractRepetitive head trauma has been associated with the accumulation of tau species in the brain. Our prior work showed brain vascular mural cells contribute to tau processing in the brain, and that these cells progressively degenerate following repetitive mild traumatic brain injury (r-mTBI). The current studies investigated the role of the cerebrovasculature in the elimination of extracellular tau from the brain, and the influence of r-mTBI on these processes. Following intracranial injection of biotin-labeled tau, the levels of exogenous labeled tau residing in the brain were elevated in a mouse model of r-mTBI at 12 months post-injury compared to r-sham mice, indicating reduced tau elimination from the brain following head trauma. This may be the result of decreased caveolin-1 mediated tau efflux at the blood–brain barrier (BBB), as the caveolin inhibitor, methyl-β-cyclodextrin, significantly reduced tau uptake in isolated cerebrovessels and significantly decreased the basolateral-to-apical transit of tau across an in vitro model of the BBB. Moreover, we found that the upstream regulator of endothelial caveolin-1, Mfsd2a, was elevated in r-mTBI cerebrovessels compared to r-sham, which coincided with a decreased expression of cerebrovascular caveolin-1 in the chronic phase following r-mTBI (> 3 months post-injury). Lastly, angiopoietin-1, a mural cell-derived protein governing endothelial Mfsd2a expression, was secreted from r-mTBI cerebrovessels to a greater extent than r-sham animals. Altogether, in the chronic phase post-injury, release of angiopoietin-1 from degenerating mural cells downregulates caveolin-1 expression in brain endothelia, resulting in decreased tau elimination across the BBB, which may describe the accumulation of tau species in the brain following head trauma.
The role of patient-derived ovarian cancer organoids in the study of PARP inhibitors sensitivity and resistance: from genomic analysis to functional testing
Authors: Tao Mengyu , Wu Xia 
Published: October 2021

AbstractEpithelial ovarian cancer (EOC) harbors distinct genetic features such as homologous recombination repair (HRR) deficiency, and therefore may respond to poly ADP-ribose polymerase inhibitors (PARPi). Over the past few years, PARPi have been added to the standard of care for EOC patients in both front-line and recurrent settings. Next-generation sequencing (NGS) genomic analysis provides key information, allowing for the prediction of PARPi response in patients who are PARPi naïve. However, there are indeed some limitations in NGS analyses. A subset of patients can benefit from PARPi, despite the failed detection of the predictive biomarkers such as BRCA1/2 mutations or HRR deficiency. Moreover, in the recurrent setting, the sequencing of initial tumor does not allow for the detection of reversions or secondary mutations restoring proficient HRR and thus leading to PARPi resistance. Therefore, it becomes crucial to better screen patients who will likely benefit from PARPi treatment, especially those with prior receipt of maintenance PARPi therapy. Recently, patient-derived organoids (PDOs) have been regarded as a reliable preclinical platform with clonal heterogeneity and genetic features of original tumors. PDOs are found feasible for functional testing and interrogation of biomarkers for predicting response to PARPi in EOC. Hence, we review the strengths and limitations of various predictive biomarkers and highlight the role of patient-derived ovarian cancer organoids as functional assays in the study of PARPi response. It was found that a combination of NGS and functional assays using PDOs could enhance the efficient screening of EOC patients suitable for PARPi, thus prolonging their survival time.
Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis
Authors: Lechtenboehmer C. A. , Burkard T. , Reichenbach S. , Walker U. A. , Burden A. M. , Hügle T. 
Published: October 2021

Abstract
Objectives
A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA.

Methods
Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1.

Results
Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings.

Conclusions
These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.
Chemorefractory extranodal nasal-type natural-killer/T-cell lymphoma with great response to pembrolizumab in a young patient: a case report
Authors: Adabifirouzjaei Fatemeh , Khazai Bharam , Azami Ghazaleh , Shoja-e-Razavi Ghazaleh 
Published: October 2021

Abstract
Introduction
Extranodal, natural-killer/T-cell lymphoma of nasal type is a rare but aggressive disease usually presenting as progressive necrotic lesions in the nasal cavity that responds poorly to chemotherapy. In this paper, we report a relapsing, chemorefractory case of extranodal natural-killer/T-cell lymphoma responding to checkpoint inhibitor immunotherapy with pembrolizumab.

Case presentation
A 32-year-old Hispanic woman with a history of recurrent sinusitis and preseptal abscess presented with a hoarse voice, swelling around the right eye, and diplopia. Laryngoscopy showed infiltrating tissue extending to bilateral laryngeal ventricles and false vocal cords. On immunohistochemical examination of laryngeal biopsy, the neoplastic cells showed positivity for CD3 (cytoplasmic), CD7, CD56, granzyme B, CD30, and Epstein–Barr virus-encoded ribonucleic acid (RNA). Extranodal natural-killer/T-cell lymphoma, nasal type, was confirmed. In the absence of distant organ involvement, the decision was to perform chemotherapy with etoposide, ifosfamide, mesna, cisplatin, and dexamethasone (VIPD protocol) followed by concurrent chemoradiation with weekly doses of cisplatin and two cycles of VIPD as adjuvant treatment. However, 1 month after completion of the treatment; disease recurrence was demonstrated. The patient was scheduled to receive salvage chemotherapy with steroid, methotrexate, ifosfamide, L- asparaginase, and etoposide (SMILE) protocol and CD30-targeting monoclonal antibodies. However, the mass was chemorefractory without response to either l-asparaginase-based salvage chemotherapy in combination with high-dose methotrexate or brentuximab vedotin. However, this case of chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, responded well to the novel drug pembrolizumab, which was able to control the disease.

Conclusion
Checkpoint inhibitors are potential treatment option in selected chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, cases.
Impact of ICU transfers on the mortality rate of patients with COVID-19: insights from comprehensive national database in France
Authors: Sanchez Marc-Antoine , Vuagnat Albert , Grimaud Olivier , Leray Emmanuelle , Philippe Jean-Marc , Lescure François-Xavier , Boutonnet Mathieu , Coignard Hélène , Hibon Agnès Ricard , Sanchez Stephane , Pottecher Julien 
Published: October 2021

Abstract
Background
The first wave of the COVID-19 pandemic confronted healthcare systems around the world with unprecedented organizational challenges, particularly regarding the availability of intensive care unit (ICU) beds. One strategy implemented in France to alleviate healthcare pressure during the first COVID-19 wave was inter-hospital transfers of selected ICU patients from overwhelmed areas towards less saturated ones. At the time, the impact of this transfer strategy on patient mortality was unknown. We aimed to compare in-hospital mortality rates among ICU patients with COVID-19 who were transferred to another healthcare facility and those who remained in the hospital where they were initially admitted to.

Method
A prospective observational study was performed from 1 March to 21 June 2020. Data regarding hospitalized patients with COVID-19 were collected from the Ministry of Health-affiliated national SI-VIC registry. The primary endpoint was in-hospital mortality.

Results
In total, 93,351 hospital admissions of COVID-19 patients were registered, of which 18,348 (19.6%) were ICU admissions. Transferred patients (n = 2228) had a lower mortality rate than their non-transferred counterparts (n = 15,303), and the risk decreased with increasing transfer distance (odds ratio (OR) 0.7, 95% CI: 0.6–0.9, p = 0.001 for transfers between 10 and 50 km, and OR 0.3, 95% CI: 0.2–0.4, p < 0.0001 for transfer distance > 200 km). Mortality decreased overall over the 3-month study period.

Conclusions
Our study shows that the mortality rates were lower for patients with severe COVID-19 who were transferred between ICUs across regions, or internationally, during the first pandemic wave in France. However, the global mortality rate declined overall during the study. Transferring selected patients with COVID-19 from overwhelmed regions to areas with greater capacity may have improved patient access to ICU care, without compounding the short-term mortality risk of transferred patients.
Mapping multicenter randomized controlled trials in anesthesiology: a scoping review
Authors: Boet Sylvain , Burns Joseph K. , Cheng-Boivin Olivia , Khan Hira , Derry Kendra , Diep Deric , Djokhdem Abdul Hadi , Um Sung Wook , Huang Johnny W. , Paré Danica , Deng Mimi , Begunova Liza , Fei Linda Yi Ning , Bezzahou Maryam , Andrahennadi Pium Sonali , Grose Elysia , Abebe Ruth G , Mansour Fadi , Talbot Zoé , Dion Pierre-Marc , Kaur Manvinder , Choueiry Justen , Etherington Cole 
Published: October 2021

Abstract
Background
Evidence suggests that there are substantial inconsistencies in the practice of anesthesia. There has not yet been a comprehensive summary of the anesthesia literature that can guide future knowledge translation interventions to move evidence into practice. As the first step toward identifying the most promising interventions for systematic implementation in anesthesia practice, this scoping review of multicentre RCTs aimed to explore and map the existing literature investigating perioperative anesthesia-related interventions and clinical patient outcomes.

Methods
Multicenter randomized controlled trials were eligible for inclusion if they involved a tested anesthesia-related intervention administered to adult surgical patients (≥ 16 years old), with a control group receiving either another anesthesia intervention or no intervention at all. The electronic databases Embase (via OVID), MEDLINE, and MEDLINE in Process (via OVID), and Cochrane Central Register of Control Trials (CENTRAL) were searched from inception to February 26, 2021. Studies were screened and data were extracted by pairs of independent reviewers in duplicate with disagreements resolved through consensus or a third reviewer. Data were summarized narratively.

Results
We included 638 multicentre randomized controlled trials (n patients = 615,907) that met the eligibility criteria. The most commonly identified anesthesia-related intervention theme across all studies was pharmacotherapy (n studies = 361 [56.6%]; n patients = 244,610 [39.7%]), followed by anesthetic technique (n studies = 80 [12.5%], n patients = 48,455 [7.9%]). Interventions were most often implemented intraoperatively (n studies = 233 [36.5%]; n patients = 175,974 [28.6%]). Studies typically involved multiple types of surgeries (n studies = 187 [29.2%]; n patients = 206 667 [33.5%]), followed by general surgery only (n studies = 115 [18.1%]; n patients = 201,028 [32.6%]) and orthopedic surgery only (n studies = 94 [14.7%]; n patients = 34,575 [5.6%]). Functional status was the most commonly investigated outcome (n studies = 272), followed by patient experience (n studies = 168), and mortality (n studies = 153).

Conclusions
This scoping review provides a map of multicenter RCTs in anesthesia which can be used to optimize future research endeavors in the field. Specifically, we have identified key knowledge gaps in anesthesia that require further systematic assessment, as well as areas where additional research would likely not add value. These findings provide the foundation for streamlining knowledge translation in anesthesia in order to reduce practice variation and enhance patient outcomes.
Effects of preoperative physiotherapy on signs and symptoms of pulmonary collapse and infection after major abdominal surgery: secondary analysis of the LIPPSMAck-POP multicentre randomised controlled trial
Authors: Boden I. , Reeve J. , Robertson I. K. , Browning L. , Skinner E. H. , Anderson L. , Hill C. , Story D. , Denehy L. 
Published: October 2021

Abstract
Background
Preoperative education and breathing exercise training by a physiotherapist minimises pulmonary complications after abdominal surgery. Effects on specific clinical outcomes such as antibiotic prescriptions, chest imaging, sputum cultures, oxygen requirements, and diagnostic coding are unknown.

Methods
This post hoc analysis of prospectively collected data within a double-blinded, multicentre, randomised controlled trial involving 432 participants having major abdominal surgery explored effects of preoperative education and breathing exercise training with a physiotherapist on postoperative antibiotic prescriptions, hypoxemia, sputum cultures, chest imaging, auscultation, leukocytosis, pyrexia, oxygen therapy, and diagnostic coding, compared to a control group who received a booklet alone. All participants received standardised postoperative early ambulation. Outcomes were assessed daily for 14 postoperative days. Analyses were intention-to-treat using adjusted generalised multivariate linear regression.

Results
Preoperative physiotherapy was associated with fewer antibiotic prescriptions specific for a respiratory infection (RR 0.52; 95% CI 0.31 to 0.85, p = 0.01), less purulent sputum on the third and fourth postoperative days (RR 0.50; 95% CI 0.34 to 0.73, p = 0.01), fewer positive sputum cultures from the third to fifth postoperative day (RR 0.17; 95% CI 0.04 to 0.77, p = 0.01), and less oxygen therapy requirements (RR 0.49; 95% CI 0.31 to 0.78, p = 0.002). Treatment effects were specific to respiratory clinical coding domains.

Conclusions
Preoperative physiotherapy prevents postoperative pulmonary complications and is associated with the minimisation of signs and symptoms of pulmonary collapse/consolidation and airway infection and specifically results in reduced oxygen therapy requirements and antibiotic prescriptions.

Trial registration
ANZCTR 12613000664741; 19/06/2013.
Sulfur-doped carbon dots synthesis under microwave irradiation as turn-off fluorescent sensor for Cr(III)
Authors: Kamali Siti Raudhatul , Chen Chang-Nan , Agrawal Dinesh Chandra , Wei Tai-Huei 
Published: October 2021

AbstractThis study synthesized a facile and high sensitive fluorescent probe based on sulfur-doped carbon dots (S-CDs) using a one-step microwave irradiation method. The probe exhibited a strong blue emission and a high quantum yield (QY) of 36.40%. In the detection, the presence of trivalent chromium (Cr(III)) strongly quenched the PL intensity of S-CDs by the inner filter effect (IFE) quenching mechanism of Cr(III) on the S-CDs. The S-CDs exhibited good sensitivity to turn-off Cr(III) detection with a linear range concentration of 0–45 μM and a detection limit of 0.17 μM. Furthermore, the proposed method has been successfully applied for Cr(III) detection in natural water samples with the 93.68–106.20% recoveries.
The association between culture positivity and long-term mortality in critically ill surgical patients
Authors: Wu Yu-Cheng , Wong Li-Ting , Wu Chieh-Liang , Chao Wen-Cheng 
Published: October 2021

Abstract
Background
The long-term outcome is an essential issue in critically ill patients, and the identification of early determinant is needed for risk stratification of the long-term outcome. In the present study, we investigate the association between culture positivity during admission and long-term outcome in critically ill surgical patients.

Methods
We linked the 2015–2019 critical care database at Taichung Veterans General Hospital with the nationwide death registration files in Taiwan. We described the long-term mortality and proportion of culture positivity among enrolled subjects. We used a log-rank test to estimate survival curves between patients with and without positive cultures and a multivariable Cox proportional hazards regression model to determine hazard ratio (HR) and 95% confidence interval (CI).

Results
A total of 6748 critically ill patients were enrolled, and 32.5% (2196/6749) of them died during the follow-up period, with the overall follow-up duration was 1.8 ± 1.4 years. We found that 31.4% (2122/6748) of critically ill patients had at least one positive culture during the index admission, and the number of patients with positive culture in the blood, respiratory tract, urinary tract, skin and soft tissue and abdomen were 417, 1702, 554, 194 and 139, respectively. We found that a positive culture from any sites was independently associated with high long-term mortality (aHR 1.579, 95% CI 1.422–1.754) after adjusting relevant covariates, including age, sex, body-mass index, comorbidities, severity score, shock, early fluid overload, receiving mechanical ventilation and the need of renal replacement therapy for critical illness.

Conclusions
We linked two databases to identify that a positive culture during admission was independently correlated with increased long-term mortality in critically ill surgical patients. Our findings highlight the need for vigilance among patients with a positive culture during admission, and more studies are warranted to validate our findings and to clarify underlying mechanisms.