bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Frequency Atmospheric Variability Patterns and Synoptic Types Linked to Large Floods in the Lower Ebro River Basin
Authors: Peña J. C. , Balasch J. C. , Pino D. , Schulte L. , Barriendos M. , Ruiz-Bellet J. L. , Prohom M. , Tuset J. , Mazon J. , Castelltort X.
Published: January 2022

This study analyzes the atmospheric variability that caused the largest floods affecting the town of Tortosa, Spain, in the mouth of the Ebro River (northeast Iberian Peninsula). The Tortosa flood database and flood marks in the nearby town of Xerta are used to define the more relevant flooding episodes (discharges >2900 m3 s−1) of the 1600–2005 period. We explore the atmospheric variability based on low-frequency patterns and synoptic types applying a multivariable analysis to grids at sea level pressure and geopotential at 500 hPa provided by the twentieth-century V3 Reanalysis Project for the instrumental period (since 1836). Output from the Last Millennium Ensemble Project was used to analyze the sea level pressure over the pre-instrumental period (before 1836). Our analysis includes 33 flood episodes. Four synoptic types are related to floods in Tortosa since 1836, characterized by low pressure systems that interact with the Mediterranean warm air mass and promote atmospheric destabilization. Flooding in Tortosa is related to relative high values of solar activity, positive Northern Hemisphere temperature anomalies, and NAO in positive phase. This result indicates that the major floods are related to zonal atmospheric circulations (west-to-east cyclone transfer). During winter, the main impact of the floods is located at the western part of the basin, and the Pyrenean subbasins are affected during autumn. The major finding is that similar flood behavior is detected since 1600, improving our understanding of past climates, enhancing the knowledge base for some aspects and impacts of climate change, and reducing uncertainty about future outcomes.

Significance Statement

A total of 33 large floods (>2900 m3 s−1) were registered since 1600 in Tortosa, Spain, located at the mouth of the Ebro River (northeast Iberian Peninsula). They occur associated with low pressure systems that interact with the Mediterranean warm air mass promoting atmospheric destabilization. The floods in Tortosa are also associated with other important processes occurring at significantly longer time scales: high values of solar activity, positive Northern Hemisphere temperature anomalies, and NAO in positive phase, indicating that the major floods are related to zonal atmospheric circulations. The major finding is that we detect similar flood behaviors since 1600, improving our understanding of past climates, enhancing the knowledge base for some aspects and impacts of climate change, and reducing uncertainty about future outcomes.
Understanding the Extratropical Liquid Water Path Feedback in Mixed-Phase Clouds with an Idealized Global Climate Model
Authors: Frazer Michelle E. , Ming Yi
Published: January 2022

A negative shortwave cloud feedback associated with higher extratropical liquid water content in mixed-phase clouds is a common feature of global warming simulations, and multiple mechanisms have been hypothesized. A set of process-level experiments performed with an idealized global climate model (a dynamical core with passive water and cloud tracers and full Rotstayn–Klein single-moment microphysics) show that the common picture of the liquid water path (LWP) feedback in mixed-phase clouds being controlled by the amount of ice susceptible to phase change is not robust. Dynamic condensate processes—rather than static phase partitioning—directly change with warming, with varied impacts on liquid and ice amounts. Here, three principal mechanisms are responsible for the LWP response, namely higher adiabatic cloud water content, weaker liquid-to-ice conversion through the Bergeron–Findeisen process, and faster melting of ice and snow to rain. Only melting is accompanied by a substantial loss of ice, while the adiabatic cloud water content increase gives rise to a net increase in ice water path (IWP) such that total cloud water also increases without an accompanying decrease in precipitation efficiency. Perturbed parameter experiments with a wide range of climatological LWP and IWP demonstrate a strong dependence of the LWP feedback on the climatological LWP and independence from the climatological IWP and supercooled liquid fraction. This idealized setup allows for a clean isolation of mechanisms and paints a more nuanced picture of the extratropical mixed-phase cloud water feedback than simple phase change.
The Life Cycle and Variability of Antarctic Weak Polar Vortex Events
Authors: Shen Xiaocen , Wang Lin , Osprey Scott , Hardiman Steven C. , Scaife Adam A. , Ma Ji
Published: January 2022

Motivated by the strong Antarctic sudden stratospheric warming (SSW) in 2019, a survey on the similar Antarctic weak polar vortex events (WPVs) is presented, including their life cycle, dynamics, seasonality, and climatic impacts. The Antarctic WPVs have a frequency of about four events per decade, with the 2002 event being the only major SSW. They show a similar life cycle to the SSWs in the Northern Hemisphere but have a longer duration. They are primarily driven by enhanced upward-propagating wavenumber 1 in the presence of a preconditioned polar stratosphere (i.e., a weaker and more contracted Antarctic stratospheric polar vortex). Antarctic WPVs occur mainly in the austral spring. Their early occurrence is preceded by an easterly anomaly in the middle and upper equatorial stratosphere in addition to the preconditioned polar stratosphere. The Antarctic WPVs increase the ozone concentration in the polar region and are associated with an advanced seasonal transition of the stratospheric polar vortex by about one week. Their frequency doubles after 2000 and is closely related to the advanced Antarctic stratospheric final warming in recent decades. The WPV-resultant negative phase of the southern annular mode descends to the troposphere and persists for about three months, leading to persistent hemispheric-scale temperature and precipitation anomalies.

Significance Statement

The Antarctic weak polar vortex events (WPVs) are similar to the sudden stratospheric warming (SSW), but many of their characteristics remain unclear. Their climatology is presented as a benchmark based on high-quality reanalysis datasets. WPVs have a life cycle that is similar to that of Arctic SSWs but has a longer duration. They occur due to the amplified tropospheric wave forcing in the presence of a preconditioned polar stratosphere. Its seasonality is partly controlled by the equatorial stratospheric easterly in addition to the polar stratosphere. Its occurrence is closely related to the advanced breakdown of the Antarctic polar vortex and can reduce the size of the Antarctic ozone hole. Moreover, it further causes persistent hemispheric-scale climate anomalies in the troposphere, which provides a prediction potential for surface weather and climate.
Defense Budget Growth and Inflation: A Wavelet-Based Study of the U.S. and Britain
Authors: Wang Yu
Published: January 2022

Despite the extensive theoretical connections between defense budget growth and inflation, empirical findings based on traditional time-domain methods have been inconclusive. This study reexamines the issue from a time–frequency perspective. Applying continuous wavelet analysis to the U.S. and Britain, it shows empirical evidence in support of positive bilateral effects in both cases. In the bivariate context, U.S. defense budget growth promoted inflation at 2- to 4-year cycles in the 1840s and at 8- to 24-year cycles between 1825 and 1940. Conversely, inflation accelerated defense spending growth at 5- to 7-year cycles in the 1830s and at 25- to 64-year cycles between 1825 and 1940. Similarly, British defense budget growth spurred inflation at 8- to 48-year cycles between 1890 and 1940 and at 50- to 65-year cycles between 1790 and 1860. Inflation fueled the growth of defense spending at 7- to 20-year cycles between 1840 and 1870, in the 1940s, and in the 1980s. Preliminary results from multivariate analyses are also supportive, though there is a need for further research that is contingent on advancements in the wavelet method in the direction of simulation-based significance tests.
When Learning Is Life Giving: Redesigning Schools With Indigenous Systems of Relationality
Authors: Meixi  , Moreno-Dulcey Fernando , Alcalá Lucia , Keyser Ulrike , Elliott-Groves Emma
Published: January 2022

This article illustrates how designing schools with Indigenous systems of relationality can be life giving for a healthier post-COVID world. Indigenous systems of relationality—the worldviews, beliefs and practices, and moral precepts of being in relation with the rest of the living world—are the cornerstone of Indigenous knowledges, and the cornerstone of Indigenous families and communities. We consider the ways in which Indigenous systems of relationality can offer strategies for educators, families, and communities to redesign approaches to learning in schools in ways that sustain and promote life. Drawing on three case studies of schools in Thailand, México, and Colombia, we show how educators might respond to the specific needs within their communities, repair the fracturing of humans from nature, and orient us to life-giving forms of activity that are beneficial beyond our current crises and into the future.
How I treat relapsed multiple myeloma
Authors: Kastritis Efstathios , Terpos Evangelos , Dimopoulos Meletios A.
Published: January 2022

Despite recent advances, multiple myeloma remains an incurable disease for most patients, and initial remission will be followed by relapses requiring therapy. For many, there will be several remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically, and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first-line remains the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first-line, and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first-line, and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are the standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improve outcomes and overcomes class resistance, but, until now, while biology is important, it can offer only limited guidance for the choice of therapy.
Autologous stem cell transplantation for large B-cell lymphoma with secondary central nervous system involvement
Authors: Akin Serkan , Hosing Chitra , Khouri Issa , Ahmed Sairah , Alousi Amin , Fowler Nathan , Joseph Jacinth , Truxillo Jonathan , Ramdial Jeremy L. , Maadani Farzaneh , Rondon Gabriela , Daher May , Im Jin S. , Steiner Raphael , Westin Jason , Iyer Swaminathan P. , Dabaja Bouthaina , Anderlini Paolo , Popat Uday R. , Qazilbash Muzaffar H. , Flowers Christopher R. , Shpall Elizabeth , Champlin Richard E. , Nieto Yago , Srour Samer A.
Published: January 2022

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.
Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML
Authors: Ramaswamy Kavitha , Steinherz Peter G. , Agrawal Anurag K. , Forlenza Christopher J. , Mauguen Audrey , Roshal Mikhail , Trippett Tanya , Kernan Nancy A. , Sulis Maria Luisa , Shukla Neerav
Published: January 2022

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline–based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate, defined as complete remission or complete remission with partial recovery of platelet count, was 71.4% (95% confidence interval [CI], 41.9-91.6) for those patients in first relapse (n = 14) and 47.4% (95% CI, 24.4-71.1) for patients in second or greater relapse or with refractory disease. Responses were seen across multiple high-risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year overall survival for patients in first relapse was 46.2% (95% CI, 19.1-73.3) and 50.0% (95% CI, 26.9-73.1) for patients who responded to TVTC. For pediatric and young adult patients with relapsed/refractory AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.
The bisphenol F and bisphenol S and cardiovascular disease: results from NHANES 2013–2016
Authors: Wang Ruihua , Fei Qiaoyuan , Liu Shan , Weng Xueqiong , Liang Huanzhu , Wu Yingying , Wen Lin , Hao Guang , Cao Guangwen , Jing Chunxia
Published: January 2022

Background

Bisphenol F (BPF) and bisphenol S (BPS) have replaced bisphenol A (BPA) in the manufacturing of products containing polycarbonates and epoxy resins; however, the effects of these substitutes on the risk of cardiovascular disease (CVD), including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke, have not been assessed.

Objective

To examine the association of urinary BPS and BPF with CVD risk in a U.S. representative U.S. population.

Methods

Cross-sectional data from 1267 participants aged 20–80 years from the 2013–2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Survey-weighted multiple logistic regression was used to assess the association between BPA, BPF, BPS and CVD. The Bayesian kernel machine regression (BKMR) model was applied to assess the mixture effect.

Results

A total of 138 patients with CVD were identified. After adjusting for potential confounding factors, the T3 tertile concentration of BPS increased the risk of total CVD (OR: 1.99, 95% CI 1.16–3.40). When stratified by age, we found that BPS increased the risk of CVD in the 50–80 age group (OR: 1.40, 95% CI 1.05–1.87). BPS was positively associated with the risk of coronary heart disease, and the T3 tertile concentration of BPS increased the coronary heart disease risk by 2.22 times (95% CI 1.04–4.74). No significant association was observed between BPF and CVD. Although the BKMR model did not identify the mixed exposure effect of BPS, the risk of CVD increased with increasing compound concentration.

Conclusion

Our results suggest that BPS may increase the risk of total CVD and coronary heart disease in the US population, and prospective studies are needed to confirm the results.
Brucellosis relapse causing thoracic aortic ulcers and aneurysm formation: a case report
Authors: Li Shuai , Wang Qiang
Published: January 2022

Background

Brucellosis is an infectious disease caused by Brucella spp, which can involve the cardiovascular, digestive, and respiratory systems. Cardiovascular involvement is a rare occurrence, it has an extremely high mortality rate.

Case presentation

A 67-year-old Chinese man presented with thoracic aortic multiple ulcers and partial aneurysm formation that caused symptoms of left waist and left buttock pain. The man was admitted to our hospital due to abdominal aorta pseudoaneurysms 5 years ago. The diagnosis was made by thoracic computed tomography angiography (CTA), previous history, and positive culture of Brucella, and the patient was successfully treated by thoracic aortic covered stent-graft implantation and specific medical treatment.

Conclusions

People who have a history of contact with cattle and sheep, should beware of the possibility of Brucella infection. If chest and abdominal pain occur, timely medical treatment is recommended, aortic aneurysm, the disease with a high risk of death, can be identified or excluded by CTA. Early treatment and prevention of disease progression are more beneficial to patients.
Recurrent amnesia caused by early seizures after hippocampal infarction: a case report
Authors: Schlemm Eckhard , Magnus Tim , Rimmele Leander D. , Münsterberg Justine , Bester Maxim , Kessner Simon S. , Gelderblom Mathias , Gerloff Christian
Published: January 2022

Background

We report the case of a patient with recurrent episodes of disturbed memory suggestive of transient epileptic amnesia, and a focal hippocampal lesion typically associated with transient global amnesia. We argue how careful consideration of clinical, electrophysiological and imaging findings can resolve this apparent contradiction and lead to a diagnosis of early symptomatic post-stroke seizures that links brain structure to function in a new, clinically relevant way.

Case presentation

A 70-year-old patient was identified in clinical practice in our tertiary care centre and was evaluated clinically as well as by repeated electroencephalography and magnetic resonance imaging. The presenting complaint were recurrent episodes of short-term memory disturbance which manifested as isolated anterograde amnesia on neurocognitive evaluation. EEG and MRI revealed predominantly right frontotemporal spikes and a punctate diffusion-restricted lesion in the left hippocampus, respectively. Both symptoms and EEG changes subsided under anticonvulsant treatment with levetiracetam.

Conclusions

Our report contributes to the current discussion of clinical challenges in the differential diagnosis of transient memory disturbance. It suggests that focal diffusion-restricted hippocampal lesions, as seen in TGA, might be ischemic and thus highlights the importance of considering post-stroke seizures as a possible cause of transient memory disturbance.
Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study
Authors: Paliogiannis Panagiotis , Colombino Maria , Sini Maria Cristina , Manca Antonella , Casula Milena , Palomba Grazia , Pisano Marina , Doneddu Valentina , Zinellu Angelo , Santeufemia Davide ,   Sardinian Lung Cancer (SLC) Study Group, Pirina Pietro , Fois Alessandro Giuseppe , Putzu Carlo , Astara Giorgio , Scartozzi Mario , Carta Anna Maria , Porcu Giuseppe , Bardino Gianfranco , Sini Claudio , Capelli Francesca , Sarobba Maria Giuseppina , Sotgiu Giovanni , Cossu Antonio , Palmieri Giuseppe
Published: January 2022

Background

Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations.

Methods

A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline).

Results

The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001).

Conclusions

In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.
Clinical and radiographic outcomes after total hip arthroplasty with the NANOS neck preserving hip stem: a 10 to 16-year follow-up study
Authors: De Santis Vincenzo , Bonfiglio Nadia , Basilico Mattia , Tanzi Germani Greta , Matrangolo Maria Rosaria , Carosini Angelo , Malerba Giuseppe , Maccauro Giulio
Published: January 2022

Background

Short-stem Hip Arthroplasty (SHA) are increasingly implanted in recent years thanks to their potential advantage in preserving metaphyseal bone-stock. Among them, the NANOS® short-stem implant demonstrated satisfactory results to short and mid-term. The purpose of this retrospective study was to evaluate the clinical and radiographic outcome of the Nanos® short stem at a minimum follow-up of 10 years.

Methods

Sixty-seven patients aged 53 ± 20 years were enlisted in the study, for a total of 72 hips. Primary outcomes were survivorship of the implant and clinical outcome measured using the Hip disability and Osteoarthritis Outcome scores (HOOS) and the Short Form Survey (SF12) questionnaire. The secondary outcome was a radiological evaluation calculating the inclination and the anteversion angle of the acetabular cup for each implant and investigating osteolysis, heterotopic ossifications and stem position.

Results

We observed a 95.5% stem survivorship. The complication rate was 7.6% and three implants underwent revision because of an aseptic loosening, an infection and a periprosthetic fracture due to trauma.

Among 58 patients (63 hips) evaluated in an outpatient visit 10–16 years after surgery, improvement in clinically relevant scores comparing with baseline was observed: HOOS score increased after surgery in all its subcategories (from 32.25 ± 14.07% up to 91.91 ± 9.13%) as well as SF12 which increased by more than 18 percentage points.

On clinical assessment, the range of motion (ROM) was restored at follow-up, 1 patient (1.7%) showed a squeaking hip and 2 (3.4%) reported leg-length discrepancy. Neutral stem positioning was achieved in 58 hips and heterotopic ossifications occurred in 10 hips (16%).

Conclusions

The current study reports good clinical and radiological outcomes following NANOS® short-stem hip implant at minimum 10 years-follow-up. Since the high rate of stem survivorship, the low complication rate demonstrated and the overall patient satisfaction, our results suggest NANOS® neck-preserving prostheses should be considered as a valid alternative to standard implants.
Overcoming the language barrier: a novel curriculum for training medical students as volunteer medical interpreters
Authors: Carlson Erik S , Barriga Tatiana M , Lobo Dale , Garcia Guadalupe , Sanchez Dayana , Fitz Matthew
Published: January 2022

Background

Over 41 million people in the United States speak Spanish as their primary language, of which 16 million have limited English proficiency (LEP). It is well-established that language barriers contribute to health disparities and that the use of ad-hoc interpretation by untrained family members results in substandard care. We developed a novel interpreter training program for medical students to serve as in-person interpreters at a charitable, resident continuity clinic so as to overcome the language barrier in the delivery of healthcare to LEP patients.

Methods

The Medical Student Interpreter Training Program (MSITP) consists of three steps. First, fluent Spanish-speaking students shadowed a licensed interpreter. Second, students took a standardized phone exam to demonstrate language proficiency. Finally, students completed a three-hour training on the methodology and ethics of interpreting conducted by the Department of Interpreter Services.

Results

Pre- and post-tests were administered to assess students’ familiarity with the Interpreter Code of Ethics and interpreter skills. Familiarity with the Interpreter Code of Ethics increased significantly with all students reporting feeling comfortable (47%) or very comfortable (53%) after training. The pre- and post-tests included free response questions, which were administered to assess competence in the methodology and ethics of interpreting. The cohort’s aggregate score increased by 35% after the training (Wilcoxon signed rank z-score = 2.53;p = .01).

Conclusions

Implementing the MSITP resulted in an increased number of trained, Spanish-speaking interpreters available to provide their services to LEP patients at an affiliated charitable clinic and throughout the university hospital. Unlike other program models which are time and resource-intensive, this program is replicable and easily managed by volunteers. The MSITP is an effective model for training students as medical interpreters to ensure the delivery of quality healthcare for LEP patients.
Development and evaluation of an electronic nursing documentation system
Authors: Shafiee Mohsen , Shanbehzadeh Mostafa , Nassari Zeinab , Kazemi-Arpanahi Hadi
Published: January 2022

Background

Nursing documentation is a critical aspect of the nursing care workflow. There is a varying degree in how detailed nursing reports are described in scientific literature and care practice, and no uniform structured documentation is provided. This study aimed to describe the process of designing and evaluating the content of an electronic clinical nursing documentation system (ECNDS) to provide consistent and unified reporting in this context.

Methods

A four-step sequential methodological approach was utilized. The Minimum Data Set (MDS) development process consisted of two phases, as follows: First, a literature review was performed to attain an exhaustive overview of the relevant elements of nursing and map the available evidence underpinning the development of the MDS. Then, the data included from the literature review were analyzed using a two-round Delphi study with content validation by an expert panel. Afterward, the ECNDS was developed according to the finalized MDS, and eventually, its performance was evaluated by involving the end-users.

Results

The proposed MDS was divided into administrative and clinical sections; including nursing assessment and the nursing diagnosis process. Then, a web-based system with modular and layered architecture was developed based on the derived MDS. Finally, to evaluate the developed system, a survey of 150 registered nurses (RNs) was conducted to identify the positive and negative impacts of the system.

Conclusions

The developed system is suitable for the documentation of patient care in nursing care plans within a legal, ethical, and professional framework. However, nurses need further training in documenting patient care according to the nursing process, and in using the standard reporting templates to increase patient safety and improve documentation.
The interactome of CLUH reveals its association to SPAG5 and its co-translational proximity to mitochondrial proteins
Authors: Hémono Mickaële , Haller Alexandre , Chicher Johana , Duchêne Anne-Marie , Ngondo Richard Patryk
Published: January 2022

Background

Mitochondria require thousands of proteins to fulfill their essential function in energy production and other fundamental biological processes. These proteins are mostly encoded by the nuclear genome, translated in the cytoplasm before being imported into the organelle. RNA binding proteins (RBPs) are central players in the regulation of this process by affecting mRNA translation, stability, or localization. CLUH is an RBP recognizing specifically mRNAs coding for mitochondrial proteins, but its precise molecular function and interacting partners remain undiscovered in mammals.

Results

Here we reveal for the first time CLUH interactome in mammalian cells. Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells. We reveal stable RNA-independent interactions of CLUH with itself and with SPAG5 in cytosolic granular structures. More importantly, we uncover an unexpected proximity of CLUH to mitochondrial proteins and their cognate mRNAs in the cytosol. We show that this interaction occurs during the process of active translation and is dependent on CLUH TPR domain.

Conclusions

Overall, through the analysis of CLUH interactome, our study sheds a new light on CLUH molecular function by revealing new partners and by highlighting its link to the translation and subcellular localization of some mRNAs coding for mitochondrial proteins.
Expression of phenylalanine ammonia lyases in Synechocystis sp. PCC 6803 and subsequent improvements of sustainable production of phenylpropanoids
Authors: Kukil Kateryna , Lindberg Pia
Published: January 2022

Background

Phenylpropanoids represent a diverse class of industrially important secondary metabolites, synthesized in plants from phenylalanine and tyrosine. Cyanobacteria have a great potential for sustainable production of phenylpropanoids directly from CO2, due to their photosynthetic lifestyle with a fast growth compared to plants and the ease of generating genetically engineered strains. This study focuses on photosynthetic production of the starting compounds of the phenylpropanoid pathway, trans-cinnamic acid and p-coumaric acid, in the unicellular cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis).

Results

A selected set of phenylalanine ammonia lyase (PAL) enzymes from different organisms was overexpressed in Synechocystis, and the productivities of the resulting strains compared. To further improve the titer of target compounds, we evaluated the use of stronger expression cassettes for increasing PAL protein levels, as well as knock-out of the laccase gene slr1573, as this was previously reported to prevent degradation of the target compounds in the cell. Finally, to investigate the effect of growth conditions on the production of trans-cinnamic and p-coumaric acids from Synechocystis, cultivation conditions promoting rapid, high density growth were tested. Comparing the different PALs, the highest specific titer was achieved for the strain AtC, expressing PAL from Arabidopsis thaliana. A subsequent increase of protein level did not improve the productivity. Production of target compounds in strains where the slr1573 laccase had been knocked out was found to be lower compared to strains with wild type background, and the Δslr1573 strains exhibited a strong phenotype of slower growth rate and lower pigment content. Application of a high-density cultivation system for the growth of production strains allowed reaching the highest total titers of trans-cinnamic and p-coumaric acids reported so far, at around 0.8 and 0.4 g L−1, respectively, after 4 days.

Conclusions

Production of trans-cinnamic acid, unlike that of p-coumaric acid, is not limited by the protein level of heterologously expressed PAL in Synechocystis. High density cultivation led to higher titres of both products, while knocking out slr1573 did not have a positive effect on production. This work contributes to capability of exploiting the primary metabolism of cyanobacteria for sustainable production of plant phenylpropanoids.
More often than not, we’re in sync: patient and caregiver well-being over time in stem cell transplantation
Authors: Sannes Timothy S. , Ranby Krista W. , Yusufov Miryam , Brewer Benjamin W. , Jacobs Jamie M. , Callan Stephanie , Ulrich Gillian R. , Pensak Nicole A. , Natvig Crystal , Laudenslager Mark L.
Published: January 2022

Background

Hematopoietic stem cell transplantation (HSCT) is an aggressive medical procedure which significantly impacts the shared emotional well-being of patients and family caregivers (FC). Prior work has highlighted the significant overlap in well-being among patients and FCs; however, how this interdependence may change over the course of HSCT has received less attention.

Methods

We conducted secondary analyses of a supportive intervention delivered to 154 FCs of HSCT patients and examined relationships at baseline, 6 weeks, 3 and 6 months post-HSCT. Actor Partner Interdependence Modeling examined patient quality of life (QOL) and FC anxiety/depression.

Results

The data did not fit a multigroup approach limiting our ability to test intervention effects; however, bivariate analyses indicated FC depression significantly correlated to patient QOL at baseline (r = − .32), 6 weeks (r = − .22) and 6 months post-HSCT (r = − .34;p’s < .05); whereas FC anxiety was only correlated with patient QOL at the first two timepoints (p’s < .05). There was an unexpected, partner effect such that worse patient QOL at 6-weeks significantly related tolowerFC depression at 3-months (B = .193;p = .026) and changed direction with patient QOL at 3-months being related to more FC depression at 6-months (B = − .187;p = .001).

Conclusions

These findings highlight the significant, yet nuanced, interdependence of patient QOL and FC well-being during HSCT. Specifically, greater interdependence was observed between patient QOL and FC depression compared to FC anxiety, suggesting potential treatment targets for patients and their families.

Trial was registered at ClinicalTrials.gov Identifier: NCT02037568; first registered: January 16, 2014;https://clinicaltrials.gov/ct2/show/NCT02037568
Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia
Authors: Guisado-Vasco P. , Carralón-González M. M. , Aguareles-Gorines J. , Martí-Ballesteros E. M. , Sánchez-Manzano M. D. , Carnevali-Ruiz D. , García-Coca M. , Barrena-Puertas R. , de Viedma R. García , Luque-Pinilla J. M. , Sotres-Fernandez G. , Fernández-Sousa J. M. , Luepke-Estefan X. E. , López-Martín J. A. , Jimeno J. M.
Published: January 2022

Background

There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies.

Case presentation

Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved.

Conclusions

Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.
METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis
Authors: Pan Jiashu , Liu Feng , Xiao Xiaoli , Xu Ruohui , Dai Liang , Zhu Mingzhe , Xu Hanchen , Xu Yangxian , Zhao Aiguang , Zhou Wenjun , Dang Yanqi , Ji Guang
Published: January 2022

Background

Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification.

Methods

Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression.

Results

M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain–containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown.

Conclusions

M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A–CRB3–Hippo pathway.
A registry-based observational study comparing emergency calls assessed by emergency medical dispatchers with and without support by registered nurses
Authors: Torlén Wennlund Klara , Kurland Lisa , Olanders Knut , Castrén Maaret , Bohm Katarina
Published: January 2022

Background

The requirement concerning formal education for emergency medical dispatcher (EMD) is debated and varies, both nationally and internationally. There are few studies on the outcomes of emergency medical dispatching in relation to professional background. This study aimed to compare calls handled by an EMD with and without support by a registered nurse (RN), with respect to priority level, accuracy, and medical condition.

Methods

A retrospective observational study, performed on registry data from specific regions during 2015. The ambulance personnel’s first assessment of the priority level and medical condition was used as the reference standard. Outcomes were: the proportion of calls dispatched with a priority in concordance with the ambulance personnel’s assessment; over- and undertriage; the proportion of most adverse over- and undertriage; sensitivity, specificity and predictive values for each of the ambulance priorities; proportion of calls dispatched with a medical condition in concordance with the ambulance personnel’s assessment. Proportions were reported with 95% confidence intervals. χ2-test was used for comparisons. P-levels < 0.05 were regarded as significant.

Results

A total of 25,025 calls were included (EMD n = 23,723, EMD + RN n = 1302). Analyses relating to priority and medical condition were performed on 23,503 and 21,881 calls, respectively. A dispatched priority in concordance with the ambulance personnel’s assessment were: EMD n = 11,319 (50.7%) and EMD + RN n = 481 (41.5%) (p < 0.01). The proportion of overtriage was equal for both groups: EMD n = 5904, EMD + RN n = 306, (26.4%) p = 0.25). The proportion of undertriage for each group was: EMD n = 5122 (22.9%) and EMD + RN n = 371 (32.0%) (p < 0.01). Sensitivity for the most urgent priority was 54.6% for EMD, compared to 29.6% for EMD + RN (p < 0.01), and specificity was 67.3% and 84.8% (p < 0.01) respectively. A dispatched medical condition in concordance with the ambulance personnel’s assessment were: EMD n = 13,785 (66.4%) and EMD + RN n = 697 (62.2%) (p = 0.01).

Conclusions

A higher precision of emergency medical dispatching was not observed when the EMD was supported by an RN. How patient safety is affected by the observed divergence in dispatched priorities is an area for future research.
Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality
Authors: Martín-Fernández Marta , Heredia-Rodríguez María , González-Jiménez Irene , Lorenzo-López Mario , Gómez-Pesquera Estefanía , Poves-Álvarez Rodrigo , Álvarez F. Javier , Jorge-Monjas Pablo , Beltrán-DeHeredia Juan , Gutiérrez-Abejón Eduardo , Herrera-Gómez Francisco , Guzzo Gabriella , Gómez-Sánchez Esther , Tamayo-Velasco Álvaro , Aller Rocío , Pelosi Paolo , Villar Jesús , Tamayo Eduardo
Published: January 2022

Background

Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery.

Methods

We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation.

Results

In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39–0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded.

Conclusions

Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.
Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients
Authors: Kaur Navchetan , Oskotsky Boris , Butte Atul J. , Hu Zicheng
Published: January 2022

Background

Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression.

Results

We develop GENEVA (GENe Expression Variance Analysis), a semi-automated framework for exploring massive amounts of RNA-seq datasets. We apply GENEVA to 286,650 publicly available RNA-seq samples to identify any previously studied experimental conditions that could be directly or indirectly associated with ACE2 expression. We identify multiple drugs, genetic perturbations, and diseases that are associated with the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole. Our joint analysis of seven datasets confirms ACE2 upregulation in all cardiomyopathy categories. Using electronic health records data from 3936 COVID-19 patients, we demonstrate that patients with pre-existing cardiomyopathy have an increased mortality risk than age-matched patients with other cardiovascular conditions. GENEVA is applicable to any genes of interest and is freely accessible athttp://genevatool.org.

Conclusions

This study identifies multiple diseases and drugs that are associated with the expression of ACE2. The effect of these conditions should be carefully studied in COVID-19 patients. In particular, our analysis identifies cardiomyopathy patients as a high-risk group, with increased ACE2 expression in the heart and increased mortality after SARS-COV-2 infection.