bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression–Based Diagnosis of Infections in Critically Ill Patients—Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort
Authors: Thair Simone , Mewes Caspar , Hinz José , Bergmann Ingo , Büttner Benedikt , Sehmisch Stephan , Meissner Konrad , Quintel Michael , Sweeney Timothy E. , Khatri Purvesh , Mansur Ashham
Published: April 2021

OBJECTIVES:

Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression–based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients.

DESIGN:

Prospective observational cohort study.

SETTING:

Surgical ICUs of the University Medical Center Goettingen, Germany.

PATIENTS:

Critically ill patients with severe traumatic injuries.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85–0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42–0.64) early in the course of infection (p = 0.014).

CONCLUSIONS:

We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.
Retroperitoneal sarcoma: the Transatlantic Australasian Retroperitoneal Sarcoma Working Group Program
Authors: Callegaro Dario , Raut Chandrajit P. , Swallow Carol J. , Gronchi Alessandro
Published: April 2021

Purpose of review

The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is a bottom-up clinical network established in 2013 with the goal of improving the care and outcomes of patients with retroperitoneal sarcoma (RPS). Here, we review the knowledge produced by this collaborative effort and examine the future potential of this group.

Recent findings

TARPSWG has produced retrospective studies focused on patients with primary and recurrent RPS allowing a better understanding of patient prognosis, treatment outcomes and tumor biology. The group has played a pivotal role in a phase III randomized STudy of preoperative RAdiotherapy plus Surgery versus surgery alone for patients with Retroperitoneal Sarcoma (STRASS) trial, favoring patient recruitment and trial completion. A prospective registry for patients with primary RPS populated by TARPSWG members is ongoing. TARPSWG has created consensus papers with recommendations regarding the management of patients with primary, recurrent and metastatic RPS that collated the views of representatives of sarcoma centers from Europe, North America, Asia and Australia.

Since its inception, TARPSWG has become a leading network in the field of RPS. It has made a major contribution to the world of RPS research and cares allowing to overcome the limitations related to the rarity of the disease through collaboration.
Effects of prior exposure to a visual airway cognitive aid on decision-making in a simulated airway emergency
Authors: Zasso Fabricio B. , Perelman Vsevolod S. , Ye Xiang Y. , Melvin Martina , Wild Evan , Tavares Walter , You-Ten Kong Eric
Published: April 2021

BACKGROUND

Decision-making deficits in airway emergencies have led to adverse patient outcomes. A cognitive aid would assist clinicians through critical decision-making steps, preventing key action omission.

OBJECTIVE

We aimed to investigate the effects of a visual airway cognitive aid on decision-making in a simulated airway emergency scenario.

DESIGN

Randomised controlled study.

SETTING

Single-institution, tertiary-level hospital in Toronto, Canada from September 2017 to March 2019.

PARTICIPANTS

Teams consisting of a participant anaesthesia resident, nurse and respiratory therapist were randomised to intervention (N = 20 teams) and control groups (N = 20 teams).

INTERVENTION

Participants in both groups received a 15-min didactic session on crisis resource management which included teamwork communication and the concepts of cognitive aids for the management of nonairway and airway critical events. Only participants in the intervention group were familiarised, oriented and instructed on a visual airway cognitive aid that was developed for this study. Within 1 to 4 weeks after the teaching session, teams were video-recorded managing a simulated ‘cannot intubate-cannot oxygenate’ scenario with the aid displayed in the simulation centre.

MAIN OUTCOME MEASURES

Decision-making time to perform a front-of-neck access (FONA), airway checklist actions, teamwork performances and a postscenario questionnaire.

RESULTS

Both groups performed similar key airway actions; however, the intervention group took a shorter decision-making time than the control group to perform a FONA after a last action [mean ± SD, 80.9 ± 54.5 vs. 122.2 ± 55.7 s; difference (95% CI) −41.2 (−76.5 to −6.0) s, P = 0.023]. Furthermore, the intervention group used the aid more than the control group (63.0 vs. 28.1%, P < 0.001). Total time of scenario completion, action checklist and teamwork performances scores were similar between groups.

CONCLUSIONS

Prior exposure and teaching of a visual airway cognitive aid improved decision-making time to perform a FONA during a simulated airway emergency.
Cardiovascular Disease in Patients With Type 2 Diabetes
Authors: Ciemins Elizabeth L. , McKinnon Monette , Hamersky Carol Mahler , Iyer Neeraj N. , Powelson Jill
Published: April 2021

Guidelines for the management of patients with type 2 diabetes mellitus (T2DM) recommend SGLT-2 (sodium-glucose cotransporter 2) inhibitors and GLP-1 RAs (glucagon-like peptide 1 receptor agonists) as second-line agents for patients with, or at risk for, cardiovascular disease. A better understanding of guideline implementation will further the provision of evidence-based health care to patients. Interviews and surveys of clinicians were conducted to understand providers' knowledge, attitudes, and beliefs related to the 2019 American Diabetes Association Standards of Care for T2DM. There was a lack of widespread knowledge of the guidelines and comfort with their use. Clinicians require additional training and education on the efficacy of the new medications and accompanying clinical guidelines.
Angiotensin Receptor-Neprilysin Inhibition Improves Blood Pressure and Heart Failure Control in Left Ventricular Assist Device Patients
Authors: Goldberg Rachel L. , Freed Kristin E. , Klemans Nancy , Fioretti Rebecca , Choi Chun W. , Kilic Ahmet , Adamo Luigi , Florido Roberta , Sharma Kavita , Gilotra Nisha A. , Hsu Steven
Published: April 2021

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients.
Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Protocol Associated with a Decrease in Complications
Authors: Jenks Christopher L. , Landry Lily M. , Garrison Carrie F. , Campbell Joshua G. , Weeks Mary F. , Tramel Sarah W. , Knudson Jarrod D.
Published: April 2021

Extracorporeal membrane oxygenation (ECMO) in pediatrics has rapidly progressed in recent years; however, there continues to be considerable variation in anticoagulation practices. In 2016, we implemented a standardized anticoagulation protocol in effort to reduce clotting and bleeding complications. A single-center retrospective analysis of pediatric patients requiring ECMO between 2014 and 2018 was performed. One hundred one ECMO cases in 94 pediatric patients met eligibility criteria (preprotocol = 64 cases; postprotocol = 37 cases). Demographics, ECMO parameters, complications, laboratories, and blood product requirements were analyzed for differences between the two groups. There was a significant decrease in the incidence of hematologic (p < 0.022), neurologic (p < 0.001), and renal complications (p < 0.001) in the postprotocol era. Incidence of bleeding, cardiac/pulmonary complications, and circuit changes were similar between the groups. The postprotocol group required fewer transfusions of red blood cells and cryoprecipitate. Additionally, platelet counts and fibrinogen levels were maintained higher in the postprotocol era. In conclusion, implementation of a standardized anticoagulation protocol was associated with improved anticoagulation parameters and a decrease in hematologic and neurologic complications, coagulopathy, renal injury, and blood product administration. We attribute these findings to transitioning to anti-Xa as a measure of heparinization and maintaining higher platelet counts.
Miniaturized Fontan Circulation Assist Device: Chronic In Vivo Evaluation
Authors: Cysyk Joshua P. , Lukic Branka , Joseph Brian Clark , Newswanger Ray , Jhun Choon-Sik , Izer Jenelle , Flory Heidi , Reibson John , Doxtater Bradley , Weiss William , Rosenberg Gerson
Published: April 2021

We have miniaturized and optimized our implantable rotary blood pump developed to provide long-term mechanical right heart support for patients who have failing Fontan circulation. The objective of this study was to evaluate the miniaturized Fontan circulation assist device (mini-FCAD) during 30-day sheep studies (n = 5). A complete right heart bypass was performed and all return flow was supported by the pump. Postoperatively, unfractionated heparin was given to maintain thromboelastography R times of 2× normal. The first two studies were terminated on day 0 and day 4 due to complications. In the final three studies, the animals remained healthy and were electively terminated at 30 ± 2 days. Pump flow was between 5 and 7 lpm, left atrial pressure remained normal, and inlet pressures were between 3 and 18 mm Hg with no incidents of suction. There was no evidence of hemolysis, end organ or pulmonary dysfunction, thromboembolic events, nor thermal damage to the surrounding tissue. Explanted devices from two studies were free of thrombi and in the third study there were unattached thrombi on the SVC inlet of the rotor. The mini-FCAD was successfully tested in vivo as a right heart replacement device demonstrating adequate circulatory support and normal physiologic pulmonary and venous pressures.
Improved Drainage Cannula Design to Reduce Thrombosis in Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Vatani Ashkan , Liao Sam , Burrell Aidan J.C. , Carberry Josie , Azimi Marjan , Steinseifer Ulrich , Arens Jutta , Soria Julio , Pellegrino Vincent , Kaye David , Gregory Shaun D.
Published: April 2021

Thrombosis is a potentially life-threatening complication in veno-arterial extracorporeal membrane oxygenation (ECMO) circuits, which may originate from the drainage cannula due to unfavorable blood flow dynamics. This study aims to numerically investigate the effect of cannula design parameters on local fluid dynamics, and thus thrombosis potential, within ECMO drainage cannulas. A control cannula based on the geometry of a 17 Fr Medtronic drainage cannula concentrically placed in an idealized, rigid-walled geometry of the right atrium and superior and inferior vena cava was numerically modeled. Simulated flow dynamics in the control cannula were systematically compared with 10 unique cannula designs which incorporated changes to side hole diameter, the spacing between side holes, and side hole angles. Local blood velocities, maximum wall shear stress (WSS), and blood residence time were used to predict the risk of thrombosis. Numerical results were experimentally validated using particle image velocimetry. The control cannula exhibited low blood velocities (59 mm/s) at the cannula tip, which may promote thrombosis. Through a reduction in the side hole diameter (2 mm), the spacing between the side holes (3 mm) and alteration in the side hole angle (30° relative to the flow direction), WSS was reduced by 52%, and cannula tip blood velocity was increased by 560% compared to the control cannula. This study suggests that simple geometrical changes can significantly alter the risk of thrombosis in ECMO drainage cannulas.
Understanding the GERD Barrier
Authors: Dunn Colin P. , Wu Jessica , Gallagher Shea P. , Putnam Luke R. , Bildzukewicz Nikolai A. , Lipham John C.
Published: April 2021

Gastroesophageal reflux disease (GERD) is steadily increasing in incidence and now affects 18% to 28% of the population in the United States. A thorough understanding of the pathophysiology underlying this disease is necessary to improve the current standard of care. Most GERD pathophysiology models focus on the lower esophageal sphincter (LES) as the key element which prevents esophageal reflux. More recent research has highlighted the crural diaphragm (CD) as an additional critical component of the GERD barrier. We now know that the CD actively relaxes when the distal esophagus is distended and contracts when the stomach is distended. Crural myotomy in animal models increases esophageal acid exposure, highlighting the CD’s vital role. There are also multiple physiological studies in patients with symptomatic hiatal hernia that demonstrate CD dysfunction is associated with GERD. Finally, computer models integrating physiological data predict that the CD and the LES each contribute roughly 50% to the GERD barrier. This more robust understanding has implications for future procedural management of GERD. Specifically, effective GERD management mandates repair of the CD and reinforcement of the LES. Given the high rate of hiatal hernia recurrences, it seems that novel antireflux procedures should target this essential component of the GERD barrier. Future research should focus on methods to maintain crural integrity, decrease hiatal hernia recurrence, and improve long-term competency of the GERD barrier.
Differential Effectiveness of Tenofovir and Entecavir for Prophylaxis of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Depending on Coexisting Cirrhosis and Prior Exposure to Antiviral Therapy
Authors: Jeong Seogsong , Cho Yuri , Park Sang Min , Kim Won
Published: April 2021

Goals:

This meta-analysis evaluated the comparative effectiveness of tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC).

Background:

It is unclear whether TDF or ETV is more effective in reducing the risk of HCC in chronic hepatitis B (CHB) patients with or without underlying cirrhosis.

Methods:

We searched the MEDLINE database through April 13, 2020, for studies involving CHB treated with TDF and/or ETV. Primary and secondary outcomes were the incidence of HCC and overall survival, respectively, calculated as risk ratios (RRs). Adjusted results were further evaluated by pooling propensity score matched cohorts.

Results:

Of the 229 records identified, 17 studies were included in the quantitative analysis. TDF treatment was associated with a significantly lower risk of HCC development [RR, 0.63; 95% confidence interval (CI), 0.43-0.93; P=0.024] and mortality (RR, 0.69; 95% CI, 0.57-0.84; P=0.003) than ETV treatment. Moreover, TDF significantly lowered HCC risk in patients with cirrhosis (RR, 0.69; 95% CI, 0.56-0.84) and antiviral treatment-naive patients (RR, 0.59; 95% CI, 0.35-0.98) compared with ETV. Among treatment-naive patients, TDF significantly prolonged survival compared with ETV (RR, 0.69; 95% CI, 0.52-0.91).

Conclusions:

TDF likely confers a lower risk of HCC development and longer survival in patients with CHB, especially among treatment-naive patients and those with underlying cirrhosis, than ETV.
Radiologic Predictors of Increased Number of Necrosectomies During Endoscopic Management of Walled-off Pancreatic Necrosis
Authors: Cosgrove Natalie , Shetty Anup , Mclean Richard , Vitta Swaroop , Faisal Mir F. , Mahmood Sultan , Early Dayna , Mullady Dan , Das Koushik , Lang Gabriel , Thai Theresa , Syed Taseen , Maple John , Jonnalagadda Sreeni , Andresen Kelli , Hollander Thomas , Kushnir Vladimir
Published: April 2021

Goals:

No established methods exist to predict who will require a higher number of endoscopic necrosectomy sessions for walled-off necrosis (WON). We aim to identify radiologic predictors for requiring a greater number of necrosectomy sessions. This may help to identify patients who benefit from aggressive endoscopic management.

Materials and Methods:

This is a multicenter retrospective study of patients with WON at 3 tertiary care centers. WON characteristics on preintervention computed tomography imaging were evaluated to determine if they were predictive of requiring more endoscopic necrosectomy.

Results:

A total of 104 patients were included. Seventy patients (67.3%) underwent endoscopic necrosectomy, with median of 2 necrosectomies. WON largest transverse diameters (P=0.02), largest coronal diameters (P=0.01), necrosis pattern [likelihood ratio (LR)=17.85, P<0.001], spread (LR=11.02, P=0.01), hemorrhage (LR=8.64, P=0.003), and presence of disconnected pancreatic duct (LR=6.80, P=0.01) were associated with undergoing ≥2 necrosectomies. Patients with septations/loculations were significantly less likely to undergo ≥2 necrosectomies (LR=4.86, P=0.03).

Conclusions:

Several computed tomography radiologic features were significantly associated with undergoing ≥2 necrosectomies. These could help identify patients who will undergo a higher number of endoscopic necrosectomy sessions.
Implementing capnography to help improve patient safety during procedural sedation: quality improvement in a high-volume gastroenterology department
Authors: Bisschops Raf , Saunders Rhodri , Dooms Christophe , Hoffman Ilse , van der Merwe Schalk , Weissbrod Rachel , Torres Rafael Torrejon , Van Assche Gert , Demedts Ingrid
Published: April 2021

Objective

Respiratory compromise is a major cause of adverse events during procedural sedation; continuous monitoring is vital for identifying and halting decompensation. We performed a quality improvement investigation to assess patient safety during procedural sedation in gastroenterology and the impact of implementing capnography monitoring.

Patients and methods

Sedation-related adverse events and interventions were prospectively recorded during the endoscopic procedure and in recovery. Assuming rates in published literature, power analysis determined that at least 1332 patients were required to show a 20% improvement in patient safety. Recorded sedation-related adverse events (mild and severe oxygen desaturations, bradycardia and tachycardia) and interventions were anonymized and aggregated to evaluate the quality improvement. Patient safety under current care was determined before capnography (Medtronic) was implemented in combination with training.

Results

Between February 2018 and April 2018, a baseline (1092 patients) for outcomes under current care was completed, with 11.45 events per 100 procedures recorded. Between May 2018 and July 2018, 1044 procedures including capnography monitoring were performed with 5.08 events per 100 procedures recorded. The distribution of American Society of Anesthesiologists scores and procedure types between baseline and capnography were comparable. The absolute difference between baseline and capnography was −6.4 events per 100 procedures [95% confidence interval (CI), −4.1 to −8.7; P ≤ 0.0001]. The 55% reduction in adverse events surpassed the 20% improvement in patient safety set as the goal of this quality improvement. After multivariate regression, the adjusted odds ratio for events after implementation of capnography was 0.46 (95% CI, 0.32–0.66).

Conclusions

Addition of capnography to current care significantly decreased procedure-related safety events.
Assessment of adrenal response in patients with stable cirrhosis and ascites using different short Synacthen tests and definitions
Authors: Kalambokis Georgios N. , Tsiakas Ilias , Christaki Maria , Despotis Grigorios , Fillipas-Ntekuan Sempastian , Xourgia Xanthi , Fotopoulos Andreas , Bargiota Alexandra , Stilopoulou Sophia , Tigas Stelios , Bairaktari Eleni , Kolios George , Koustousi Christina , Aggelis Nikolaos , Sergianiti Fotini , Milionis Haralampos
Published: April 2021

Background and Aims

The definition of relative adrenal insufficiency (RAI) in patients with cirrhosis remains controversial. We investigated the serum and salivary cortisol (SalC) response after low-dose and standard-dose Synacthen test in patients with stable cirrhosis and ascites.

Methods

Ninety-five cirrhotic patients with ascites were prospectively evaluated from January 2014 to January 2018. Low-dose [adrenocorticotrophic hormone (ACTH): 1 μg] and standard-dose (ACTH: 250 μg) Synacthen test were successively performed. Paired serum total and saliva cortisol were taken at baseline, 30 min (low-dose test) and 60 min (standard-dose test). Salivary and Δserum total cortisol criteria included post-ACTH SalC < 12.7 ng/ml and/or SalC increase <3 ng/ml and serum total cortisol increase <9 μg/dl, respectively.

Results

The prevalence of RAI varied according to the definition used. SalC-defined RAI was significantly more common after low-dose than standard-dose test (54.7% vs. 20%; P < 0.001). Δserum total cortisol-defined RAI was also significantly more frequent after low-dose than standard-dose test (66.3% vs. 24.2%; P < 0.001). Considering low-dose test/SalC criteria as reference diagnostic criteria, standard-dose/salivary and Δserum total cortisol criteria showed low specificity for RAI diagnosis (43.9% and 52.7%, respectively). Survival probability was significantly lower in patients with low-dose test/SalC-defined RAI compared to those without (53.8% vs. 79.1%; P = 0.01). SalC-defined RAI after low-dose test was significantly more common than that defined after standard-dose test (72.7% vs. 30.3%; P < 0.001) among patients who died.

Conclusion

Low-dose test/SalC definition can identify RAI in about half of patients with stable cirrhosis and ascites and is associated with increased mortality.
Inhibition of angiopoietin-like 3 for the management of severe hypercholesterolemia
Authors: Mohamed Farzahna , Botha Theunis C. , Raal Frederick J.
Published: April 2021

Purpose for review

Despite the therapeutic advances for patients with severe hypercholesterolemia, particularly those with homozygous familial hypercholesterolemia (HoFH), most patients are unable to achieve target low-density lipoprotein cholesterol (LDL-C) levels with the current available standard lipid-lowering therapy (LLT). We review the role of angiopoietin-like 3 (ANGPTL3) inhibition as an additional therapeutic option for severe hypercholesterolemia, particularly HoFH.

Recent findings

Evinacumab is a monoclonal antibody against ANGPTL3, and reduces LDL-C independent of LDL-receptor activity. ANGPTL3 inhibitors are effective in lowering LDL-C in patients with FH, with a 50% reduction in LDL-C in those with HoFH. Longer-term efficacy and safety have been demonstrated with reductions in LDL-C maintained following 48 weeks of therapy. Gene silencing strategies directed against ANGPTL3 include antisense oligonucleotide and small-interfering ribonucleic acid (siRNA). ARO-ANG3 is a siRNA directed against ANGPTL3 messenger ribonucleic acid and is associated with up to a 42% reduction in LDL-C.

With the promise of these emerging novel therapeutics directed against ANGPTL3 on the horizon, achieving acceptable target LDL-C levels in HoFH without the need for lipoprotein apheresis may finally be a realistic goal and we can anticipate a decrease in cardiovascular morbidity and mortality in these difficult to treat patients.
Symptom Treatment Preferences of Cancer Survivors
Authors: Krueger Ellen , Secinti Ekin , Mosher Catherine E. , Stutz Patrick V. , Cohee Andrea A. , Johns Shelley A.
Published: April 2021

Background

Cancer-related fatigue (CRF) is among the most prevalent symptoms in cancer survivors and often co-occurs with other symptoms. However, little is known about survivors' preferences for treating CRF and associated symptoms.

Objective

The aim of this study was to examine cancer survivors' interest in learning skills to manage CRF and associated symptoms and their interest in various nonpharmacologic interventions and modalities. These outcomes were compared between survivors with high and normal fatigue.

Methods

Breast, gastrointestinal, lung, and prostate cancer survivors (N = 338) completed a 1-time survey, including a Patient-Reported Outcomes Measurement Information System fatigue measure and a checklist assessing interest in learning skills to manage CRF and associated symptoms as well as interest in nonpharmacologic interventions and modalities.

Results

Many cancer survivors reported interest in learning skills to manage CRF (range, 35%–78%) and associated symptoms (range, 13%–48%). Compared with survivors with normal fatigue (n = 180), highly fatigued survivors (n = 158; Patient-Reported Outcomes Measurement Information System fatigue T score ≥ 55) were more likely to report interest in learning skills to manage various symptoms, self-compassion training, and programs offered individually and in person. Interest in other interventions and modalities did not vary by fatigue level.

Conclusions

Many cancer survivors, especially those with high fatigue, report interest in learning symptom management skills. Given survivors' high level of interest in complementary and integrative health interventions, future research should continue to assess their impact on symptoms and functioning.

Implications for Practice

Nurses can offer a menu of evidence-based options for symptom management, given survivors' diverse preferences. Nurses can also provide psychoeducation regarding their preferred treatments.
Integrating Self-determination Theory and Upper Limb Factors to Predict Physical Activity in Patients With Breast Cancer During Chemotherapy
Authors: Fu Ying , Li Kun , Zhou Zijun , Wei Wenqi , Wang Canfei , Dong Jianyu , Peng Xin
Published: April 2021

Background

Some empirical investigations try to describe the factors that affect the physical activity of breast cancer survivors, but these investigations rarely focus on the basic psychological needs or motivation regulation of breast cancer survivors in physical activity.

Objective

The aim of this study was to construct structural equation modeling of the self-determination theory and upper limb factors to predict the physical activity of breast cancer patients during chemotherapy.

Methods

A total of 236 breast cancer survivors completed measures of basic psychological needs, behavioral regulation in exercise, symptoms and dysfunction of upper limb factors, and physical activity. Path analyses structured the direct and indirect effects (via motivational orientations) of basic psychological needs and upper limb factors on physical activity.

Results

A total of 216 (91.5%) participants met the standard physical activity metabolic equivalent recommended. The final model has a good degree of fit (χ
2 = 809.363, df = 391, χ
2/df ≤ 2.07 [1–3]; root-mean-square error of approximation, 0.067 [<0.008]). The competence (0.309) of basic psychological needs and amotivation (−0.38) of motivation regulations have the greatest effect on physical activity.

Conclusions

Competence is the most important basic psychological need of breast cancer patients during chemotherapy, and amotivation is the most important motivation regulation.

Implications for Practice

Nurses need to pay more attention to the basic psychological needs and the motivation regulation in breast cancer patients during chemotherapy. Randomized controlled trials of breast cancer survivor interventions based on the self-determination theory are needed.
Why Some Nurses Obtain Specialty Certification and Others Do Not
Authors: Dierkes Andrew M. , Schlak Amelia E. , French Rachel , McHugh Matthew D. , Aiken Linda
Published: April 2021

OBJECTIVE

The aim of this study was to determine whether there are modifiable characteristics of nurses and hospitals associated with nurse specialty certification.

BACKGROUND

Hospitals, nurses, and patients benefit from nurse specialty certification, but little actionable evidence guides administrators seeking higher hospital certification rates.

METHODS

This is a cross-sectional, secondary data analysis of 20 454 nurses in 471 hospitals across 4 states.

RESULTS

Rates of certified nurses varied significantly across hospitals. Higher odds of certification were associated with Magnet® recognition and better hospital work environments at the facility level, and with BSN education, unit type (most notably, oncology), older age, more years of experience, and full-time employment at the individual nurse level.

CONCLUSION

Two strategies that hold promise for increasing nurse specialty certification are improving hospital work environments and preferentially hiring BSN nurses.
Performance Evaluation of a Deep Learning System for Differential Diagnosis of Lung Cancer With Conventional CT and FDG PET/CT Using Transfer Learning and Metadata
Authors: Park Yong-Jin , Choi Dongmin , Choi Joon Young , Hyun Seung Hyup
Published: April 2021

Purpose

We aimed to evaluate the performance of a deep learning system for differential diagnosis of lung cancer with conventional CT and FDG PET/CT using transfer learning (TL) and metadata.

Methods

A total of 359 patients with a lung mass or nodule who underwent noncontrast chest CT and FDG PET/CT prior to treatment were enrolled retrospectively. All pulmonary lesions were classified by pathology (257 malignant, 102 benign). Deep learning classification models based on ResNet-18 were developed using the pretrained weights obtained from ImageNet data set. We propose a deep TL model for differential diagnosis of lung cancer using CT imaging data and metadata with SUVmax and lesion size derived from PET/CT. The area under the receiver operating characteristic curve (AUC) of the deep learning model was measured as a performance metric and verified by 5-fold cross-validation.

Results

The performance metrics of the conventional CT model were generally better than those of the CT of PET/CT model. Introducing metadata with SUVmax and lesion size derived from PET/CT into baseline CT models improved the diagnostic performance of the CT of PET/CT model (AUC = 0.837 vs 0.762) and the conventional CT model (AUC = 0.877 vs 0.817).

Conclusions

Deep TL models with CT imaging data provide good diagnostic performance for lung cancer, and the conventional CT model showed overall better performance than the CT of PET/CT model. Metadata information derived from PET/CT can improve the performance of deep learning systems.
Exploratory Assessment of K-means Clustering to Classify 18F-Flutemetamol Brain PET as Positive or Negative
Authors: Zukotynski Katherine , Black Sandra E. , Kuo Phillip H. , Bhan Aparna , Adamo Sabrina , Scott Christopher J.M. , Lam Benjamin , Masellis Mario , Kumar Sanjeev , Fischer Corinne E. , Tartaglia Maria Carmela , Lang Anthony E. , Tang-Wai David F. , Freedman Morris , Vasdev Neil , Gaudet Vincent
Published: April 2021

Rationale

We evaluated K-means clustering to classify amyloid brain PETs as positive or negative.

Patients and Methods

Sixty-six participants (31 men, 35 women; age range, 52–81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 dementia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 Parkinson–Lewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID software (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpretation based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data.

Results

Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal participants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with Parkinson–Lewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%.

Conclusions

K-means clustering may be a powerful algorithm for classifying amyloid brain PET.
TCAIM controls effector T cell generation by preventing Mitochondria-Endoplasmic Reticulum Contact Site-initiated Cholesterol Biosynthesis
Authors: Iwert Christina , Stein Julia , Appelt Christine , Vogt Katrin , Rainer Roman Josef , Tummler Katja , Mühle Kerstin , Stanko Katarina , Schumann Julia , Uebe Doreen , Jürchott Karsten , Lisec Jan , Janek Katharina , Gille Christoph , Textoris-Taube Kathrin , Sai Somesh , Petersen Ansgar , Kühl Anja A. , Klipp Edda , Meisel Christian , Sawitzki Birgit
Published: April 2021

T cells need to adapt their cellular metabolism for effector cell differentiation. This relies on alterations in mitochondrial physiology. Which signals and molecules regulate those alterations remains unclear. We recently reported, that the mitochondrial protein TCAIM inhibits activation-induced changes in mitochondrial morphology and function and thus, CD4+effector T cell formation. Using conditional TCAIM knock-in (KI) and knockout (KO) mice, we now show that it also applies to CD8+T cells and more importantly, delineate the molecular processes in mitochondria by which TCAIM controls effector cell differentiation. TCAIM KI resulted in reduced activation-induced HIF1α protein expression. Metabolomics and transcriptional data in combination with mathematical flux modeling revealed an impaired induction of anabolic pathways, especially of the mevalonate pathway and cholesterol biosynthesis in TCAIM KI CD8+T cells. Addition of cholesterol completely rescued HIF1α protein expression, activation and proliferation of TCAIM KI CD8+T cells. At the molecular level, TCAIM delayed activation-induced mitochondria-ER contact (MERC) formation by binding to MERC promoting proteins such as RMD3 and VDAC2. In summary, we demonstrate that TCAIM suppresses effector cell differentiation by inhibiting MERC formation, which induce HIF1α-mediated increase in cellular metabolism and cholesterol biosynthesis.
SENSV: Detecting Structural Variations with Precise Breakpoints using Low-Depth WGS Data from a Single Oxford Nanopore MinION Flowcell
Authors: Leung Henry CM , Yu Huijing , Zhang Yifan , Leung Wing Sze , Lo Ivan FM , Luk Ho Ming , Law Wai-Chun , Ma Ka Kui , Wong Chak Lim , Wong Yat Sing , Luo Ruibang , Lam Tak-Wah
Published: April 2021

Structural variation (SV) is a major cause of genetic disorders. In this paper, we show that low-depth (specifically, 4x) whole-genome sequencing using a single Oxford Nanopore MinION flow cell suffices to support sensitive detection of SV, in particular, pathogenic SV for supporting clinical diagnosis. Existing SV calling software, when using 4x ONT WGS data, often fails to detect pathogenic SV especially in the form of long deletion, terminal deletion, duplication, and unbalanced translocation. Our new SV calling software SENSV is able to achieve high sensitivity for all types of SV and a breakpoint precision typically ±100 bp, both features are important for clinical concerns. The improvement achieved by SENSV stems from several new algorithms. We evaluated SENSV and other software using both real and simulated data. The former was based on 24 patient samples, each diagnosed with a genetic disorder. SENSV found the pathogenic SV in 22 out of 24 cases (all heterozygous, size from hundreds of Kbp to a few Mbp), reporting breakpoints within 100 bp of the true answers. No existing software can detect the pathogenic SV in more than 10 out of 24 cases, even when the breakpoint requirement is relaxed to ±2,000 bp.
Host EPAC1 modulates rickettsial adhesion to vascular endothelial cells via regulation of ANXA2 Y23 phosphorylation
Authors: Su Zhengchen , Shelite Thomas , Qiu Yuan , Chang Qing , Wakamiya Maki , Bei Jiani , He Xi , Zhou Changcheng , Liu Yakun , Gaitas Angelo , Saito Tais , Gong Bin
Published: April 2021

Recently we have identified that endothelial surface annexin A2 (ANAX2) functions as a receptor for spotted fever group rickettsial adhesin outer membrane protein B (OmpB), which binds to the endothelial cell (EC) surface. Moreover, we reported that intracellular cAMP receptor EPAC1 modulates ANXA2 tyrosine (Y) 23 phosphorylation, and inactivation of EPAC1 suppresses ANXA2 expression on the EC luminal surface by downregulating Y23 phosphorylation. Since we reported that EPAC1 plays a critical role in the initial step to successfully establish rickettsial infection of ECs, this work aims to answer the following: (a) What is the mechanism underlying the regulatory role of EPAC1 in ECs during the initial step of bacterial infection? (b) Is the EPAC1-ANXA2 signaling pathway involved in the regulation of rickettsial adhesion to ECs?

In the present study, an established system that is anatomically-based and quantifies bacterial adhesion to ECsin vivowas combined with novel fluidic force microscopy (FluidFM) to dissect the functional role of the EPAC1-ANXA2 signaling pathway in rickettsiae–EC adhesion. We reveal that the deletion of theEPAC1gene impedes rickettsial binding to endotheliumin vivo. In addition, single living brain microvascular EC study that employs FluidFM and site-directed mutagenesis provides evidence that supports our finding that EPAC1 governs rickettsial adhesion to EC surfaces via regulation of ANXA2 Y23 phosphorylation.
Rapid and Efficient Inactivation of SARS-CoV-2 from Surfaces using UVC Light Emitting Diode Device
Authors: Dwivedi Varun , Park Jun-Gyu , Grenon Stephen , Medendorp Nicholas , Hallam Cory , Torrelles Jordi B. , Martinez-Sobrido Luis , Kulkarni Viraj
Published: April 2021

Efforts are underway to develop countermeasures to prevent the environmental spread of COVID-19 pandemic caused by SARS-CoV-2. Physical decontamination methods like Ultraviolet radiation has shown to be promising. Here, we describe a novel device emitting ultraviolet C radiation (UVC), called NuvaWave, to rapidly and efficiently inactivate SARS-CoV-2. SARS-CoV-2 was dried on a chambered glass slides and introduced in a NuvaWave robotic testing unit. The robot simulated waving NuvaWave over the virus at a pre-determined UVC radiation dose of 1, 2, 4 and 8 seconds. Post-UVC exposure, virus was recovered and titered by plaque assay in Vero E6 cells. We observed that relative control (no UVC exposure), exposure of the virus to UVC for one or two seconds resulted in a >2.9 and 3.8 log10reduction in viral titers, respectively. Exposure of the virus to UVC for four or eight seconds resulted in a reduction of greater than 4.7-log10reduction in viral titers. The NuvaWave device inactivates SARS-CoV-2 on surfaces to below the limit of detection within one to four seconds of UVC irradiation. This device can be deployed to rapidly disinfect surfaces from SARS-CoV-2, and to assist in mitigating its spread in a variety of settings.
Integrative analysis of the hydroxypyruvate reductases revealing their distinct roles in photorespiration of Chlamydomonas
Authors: Shi Menglin , Zhao Lei , Wang Yong
Published: April 2021

Photorespiration plays an important role in maintaining normal physiological metabolism in higher plants and other oxygenic organisms such as algae. The unicellular eukaryotic organismChlamydomonasis reported to have a different photorespiration system from that in higher plants, and only two out of nine genes encoding photorespiratory enzymes have been experimentally characterized. Hydroxypyruvate reductase (HPR), which is responsible for the conversion of hydroxypyruvate into glycerate, is poorly understood and not yet explored in Chlamydomonas. To identify the candidate genes encoding hydroxypyruvate reductase in Chlamydomonas (CrHPR) and uncover their elusive functions, we performed sequence comparison, enzyme activity measurement, subcellular localization, and analysis of knockout/knockdown strains. Together we identify five proteins to be good candidates as CrHPRs, all of which are detected with the activity of hydroxypyruvate reductase. CrHPR1, a NADH-dependent enzyme in mitochondria, may function as the major component of photorespiration, and deletion ofCrHPR1causes severe photorespiratory defects. CrHPR2 takes parts in the cytosolic bypass of photorespiration as the compensatory pathway of CrHPR1 for the reduction of hydroxypyruvate. CrHPR4, with NADH as the cofactor, may participate in photorespiration by acting as the chloroplastidial glyoxylate reductase in glycolate-quinone oxidoreductase system. Therefore, our results reveal that the CrHPRs are far more complex than previously recognized, and provide a greatly expanded knowledge base for studies to understand how CrHPRs perform their functions in photorespiration. These will facilitate the genetic engineering for crop improvement by synthetic biology.

Brief summary

Identification and characterization of genes encoding hydroxypyruvate reductases in Chlamydomonas, demonstrating difference in the enzymatic activity, subcellular location, as well as function in photorespiration.
The Autophagy Receptor TAX1BP1 (T6BP) is a novel player in antigen presentation by MHC-II molecules
Authors: Pereira Mathias , Richetta Clémence , Sarango Gabriela , Kumari Anita , Ghosh Michael , Bertrand Lisa , Pionneau Cédric , Gall Morgane Le , Grégoire Sylvie , Jeger-Madiot Raphaël , Rosoy Elina , Subra Frédéric , Delelis Olivier , Faure Mathias , Esclatine Audrey , Graff-Dubois Stéphanie , Stevanović Stefan , Manoury Bénédicte , Ramirez Bertha Cecilia , Moris Arnaud
Published: April 2021

CD4+T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented on the surface of antigen presenting cells (APCs) by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy-dependent and -independent endogenous presentation of HIV- and HCMV-derived peptides. By studying the immunopeptidome of MHC-II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces the mislocalization of the MHC-II-loading compartments and a rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. We determined the interactome of T6BP, identified calnexin as a T6BP partner and show that CANX cytosolic tail is required for this interaction. Remarkably, calnexin silencing replicates the functional consequences of T6BP silencing: decreased CD4+T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC-II-restricted endogenous presentation pathway and we propose one potential mechanism of action.
Viscous shear is a key force inDrosophilaventral furrow morphogenesis
Authors: Goldner Amanda Nicole , Cheikh Mohamad Ibrahim , Osterfield Miriam , Doubrovinski Konstantin
Published: April 2021

Ventral furrow (VF) formation inDrosophila melanogasteris an important model of epithelial folding. Previous models of VF formation require cell volume conservation to convert apically localized constriction forces into lateral cell elongation and tissue folding. Here, we investigated embryonic morphogenesis in anillin knockdown (scraRNAi) embryos, where basal cell membranes fail to form and therefore cells can lose cytoplasmic volume through their basal side. Surprisingly, the mesoderm elongation and subsequent folding that comprise VF formation occurred essentially normally. We hypothesized that the effects of viscous shear may be sufficient to drive membrane elongation, providing effective volume conservation, and thus driving tissue folding. Since this hypothesis may not be possible to test experimentally, we turned to a computational approach. A minimal model of VF formation accounting for fluid dynamics indicated that shear forces can indeed explain our experimental observation. However, this conclusion depended on specific values of the model parameters. To test whether viscous shear is a dominant force for morphogenesisin vivo, we developed a highly realistic computational model incorporating both accurate cell and tissue geometry and experimentally measured material parameters. Results from this model demonstrate that viscous shear generates sufficient force to drive cell elongation and tissue foldingin vivo.
Genomic diversification of dehydrin gene family in vascular plants: three distinctive orthologue groups and a novel KS-dehydrin conserved protein motif
Authors: Melgar Alejandra E. , Zelada Alicia M.
Published: April 2021

Dehydrins (DHNs) are a family of plant proteins that play important roles on abiotic stress tolerance and seed development. They are classified into five structural subgroups: K-, SK-, YK-, YSK-, and KS-DHNs, according to the presence of conserved motifs named K-, Y- and S-segments.We carried out a comparative structural and phylogenetic analysis of these proteins, focusing on the less-studied KS-type DHNs. A search for conserved motifs in DHNs from 56 plant genomes revealed that KS-DHNs possess a unique and highly conserved N-terminal, 15-residue amino acid motif not previously described. This novel motif, that we named H-segment, is present in DHNs of angiosperms, gymnosperms and lycophytes, suggesting that HKS-DHNs were present in the first vascular plants. Phylogenetic and microsynteny analyses indicate that the five structural subgroups of angiosperm DHNs can be assigned to three groups of orthologue genes, characterized by the presence of the H-, F- or Y-segments. Importantly, the hydrophilin character of DHNs correlate with the phylogenetic origin of the DHNs rather than to the traditional structural subgroups. We propose that angiosperm DHNs can be ultimately subdivided into three orthologous groups, a phylogenetic framework that should help future studies on the evolution and function of this protein family.