bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Teaming: Leveraging Team Science Sense-Making During COVID-19
Authors: Portman Diane G , Thirlwell Sarah , Donovan Kristine A , Ellington Lee
Published: February 2021

Individuals with cancer anorexia cachexia syndrome (CACS) experience multifaceted distress. To address CACS patient concerns regarding their experience of care, our cancer center established a specialized CACS clinic in 2016. We applied the team science principle of the team mental model (TMM) to support development of an effective interprofessional collaborative CACS care team. In 2020, cessation of CACS clinic in-person visits during coronavirus disease 2019 (COVID-19) threatened the viability of the entrenched TMM and once again jeopardized the patient experience of care.

We present a case-based vignette as a representative composite of patient experiences to illustrate the challenges. A 48-year-old female was referred to our CACS clinic for pancreatic cancer-associated appetite and weight loss during COVID-19. To reduce risk of infection, in-person clinic visits were curtailed. When informed about the resulting need to defer the CACS assessment, the patient and her spouse expressed concern that postponement would adversely affect her ability to undergo anticancer treatments or achieve beneficial outcomes.

To minimize delays in CACS treatment and optimize the patient experience of care, we applied the team science principle of sense-making to help the team rapidly reformulate the TMM to provide interprofessional collaborative CACS care via telemedicine. The sense-making initiative highlights opportunities to examine sense-making within health care teams more broadly during and after the pandemic. The application of sense-making within interprofessional cancer care teams has not been described previously.
Slippage: Bones, intentions, and the construction of memorial meaning
Authors: Conley Bridget
Published: February 2021

Scholarly and policy debates concerning the contributions of memory to political transitions often examine whether memorials contribute to democratic practices, reinforce partisan divides, or depend on the distinct processes and aims of any given memorial endeavor. All three positions rest on the assumption that stakeholder intentions govern the social and political meanings asserted through memorial practices. Another story emerges if one begins with material objects, human remains. Following the story of skeletal remains from Ethiopia’s Red Terror, this essay argues that objects demonstrate how intentions slip and fail to adhere. In so doing, objects provide a lesson in the limits of memorial politics.
Penalized partial least squares for pleiotropy
Authors: Broc Camilo , Truong Therese , Liquet Benoit
Published: February 2021

Background

The increasing number of genome-wide association studies (GWAS) has revealed several loci that are associated to multiple distinct phenotypes, suggesting the existence of pleiotropic effects. Highlighting these cross-phenotype genetic associations could help to identify and understand common biological mechanisms underlying some diseases. Common approaches test the association between genetic variants and multiple traits at the SNP level. In this paper, we propose a novel gene- and a pathway-level approach in the case where several independent GWAS on independent traits are available. The method is based on a generalization of the sparse group Partial Least Squares (sgPLS) to take into account groups of variables, and a Lasso penalization that links all independent data sets. This method, called joint-sgPLS, is able to convincingly detect signal at the variable level and at the group level.

Results

Our method has the advantage to propose a global readable model while coping with the architecture of data. It can outperform traditional methods and provides a wider insight in terms of a priori information. We compared the performance of the proposed method to other benchmark methods on simulated data and gave an example of application on real data with the aim to highlight common susceptibility variants to breast and thyroid cancers.

Conclusion

The joint-sgPLS shows interesting properties for detecting a signal. As an extension of the PLS, the method is suited for data with a large number of variables. The choice of Lasso penalization copes with architectures of groups of variables and observations sets. Furthermore, although the method has been applied to a genetic study, its formulation is adapted to any data with high number of variables and an exposed a priori architecture in other application fields.
Lasting consequences of psyllid (Bactericera cockerelli L.) infestation on tomato defense, gene expression, and growth
Authors: Harrison Kyle , Mendoza-Herrera Azucena , Levy Julien Gad , Tamborindeguy Cecilia
Published: February 2021

Background

The tomato psyllid, Bactericera cockerelli Šulc (Hemiptera: Triozidae), is a pest of solanaceous crops such as tomato (Solanum lycopersicum L.) in the U.S. and vectors the disease-causing pathogen ‘Candidatus Liberibacter solanacearum’. Currently, the only effective strategies for controlling the diseases associated with this pathogen involve regular pesticide applications to manage psyllid population density. However, such practices are unsustainable and will eventually lead to widespread pesticide resistance in psyllids. Therefore, new control strategies must be developed to increase host-plant resistance to insect vectors. For example, expression of constitutive and inducible plant defenses can be improved through selection. Currently, it is still unknown whether psyllid infestation has any lasting consequences on tomato plant defense or tomato plant gene expression in general.

Results

In order to characterize the genes putatively involved in tomato defense against psyllid infestation, RNA was extracted from psyllid-infested and uninfested tomato leaves (Moneymaker) 3 weeks post-infestation. Transcriptome analysis identified 362 differentially expressed genes. These differentially expressed genes were primarily associated with defense responses to abiotic/biotic stress, transcription/translation, cellular signaling/transport, and photosynthesis. These gene expression changes suggested that tomato plants underwent a reduction in plant growth/health in exchange for improved defense against stress that was observable 3 weeks after psyllid infestation. Consistent with these observations, tomato plant growth experiments determined that the plants were shorter 3 weeks after psyllid infestation. Furthermore, psyllid nymphs had lower survival rates on tomato plants that had been previously psyllid infested.

Conclusion

These results suggested that psyllid infestation has lasting consequences for tomato gene expression, defense, and growth.
The spontaneous resolution of a vortex vein varix: case report
Authors: Weidmayer Sara L , Demirci Hakan
Published: February 2021

Background

The natural course of a vortex vein varix, though not well understood, has been known to remain stable. However, here we report a novel case of a vortex vein varix that resolved after an extended period of monitoring.

Case presentation

An asymptomatic 96-year-old Caucasian man was found to have a vortex vein varix. At his previous examination 13 months prior, his fundus was normal. At 13 months of observation, his vortex vein varix become clinically undetectable. Further follow-up confirmed continued absence of the varix.

Conclusion

This case demonstrates the development then clinical resolution of a vortex vein varix with no clear identifiable factors for its evolution. This case is novel and offers new insight into the natural history of some vortex vein varices, implicating venous congestion as an instigator and venous collateralization as its alleviator, suggesting that vortex vein varices are likely more common than previously reported since some may be temporary and under-identified.
Long bone fracture reduction and deformity correction using the hexapod external fixator with a new method: a feasible study and preliminary results
Authors: Liu Yanshi , Li Hong , Liu Jialin , Zhang Xingpeng , Yushan Maimaiaili , Liu Zhenhui , Ma Chuang , Yusufu Aihemaitijiang
Published: February 2021

Background

The hexapod external fixator (HEF), such as the Taylor spatial frame (TSF), offering the ability of multidirectional deformities correction without changing the structure, whereas there are so many parameters for surgeons to measure and subjective errors will occur inevitably. The purpose of this study was to evaluate the effectiveness of a new method based on computer-assisted three-dimensional (3D) reconstruction and hexapod external fixator for long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage.

Methods

This retrospective study consists of 25 patients with high-energy tibial diaphyseal fractures treated by the HEF at our institution from January 2016 to June 2018, including 22 males and 3 females with a mean age of 42 years (range 14–63 years). Hexapod external fixator treatments were conducted to manage the multiplanar posttraumatic deformities with/without poor soft-tissue that were not suitable for internal fixation. Computer-assisted 3D reconstruction and trajectory planning of the reduction by Mimics were applied to perform virtual fracture reduction and deformity correction. The electronic prescription derived from the length changes of the six struts were calculated by SolidWorks. Fracture reduction was conducted by adjusting the lengths of the six struts according to the electronic prescription. Effectiveness was evaluated by the standard anteroposterior (AP) and lateral X-rays after reduction.

Results

All patients acquired excellent functional reduction and achieved bone union in our study. After correction, the mean translation (1.0 ± 1.1 mm) and angulation (0.8 ± 1.2°) on the coronal plane, mean translation (0.8 ± 1.0 mm) and angulation (0.3 ± 0.8°) on the sagittal plane were all less than those (6.1 ± 4.9 mm, 5.2 ± 3.2°, 4.2 ± 3.5 mm, 4.0 ± 2.5°) before correction (P < 0.05).

Conclusions

The computer-assisted three-dimensional reconstruction and hexapod external fixator-based method allows surgeons to conduct long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage. This method is suggested to apply in those unusually complex cases with extensive soft tissue damage and where internal fixation is impossible or inadvisable.
The design and implementation of a longitudinal social medicine curriculum at the University of Vermont’s Larner College of Medicine
Authors: Goyal Raghav K. , Dawson Christina A. , Epstein Samuel B. , Brach Richard J. , Finnie Sheridan M. , Lounsbury Karen M. , Lahey Timothy , Eldakar-Hein Shaden T.
Published: February 2021

Background

Despite an abundant literature advocating that social determinants of health (SDH) be taught during undergraduate medical education, there are few detailed descriptions of how to design and implement longitudinal core curricula that is delivered to all students and accomplishes this goal.

Methods

In this paper, we describe the design and implementation of a social medicine curriculum at the University of Vermont’s Larner College of Medicine (UVM Larner). Using Kern’s principles, we designed a longitudinal curriculum that extends through both preclinical and clinical training for all students and focused on integrating SDH material directly into basic science and clinical training.

Results

We successfully developed and implemented two primary tools, a “Social Medicine Theme of the Week” (SMTW) in preclinical training, and SDH rounds in the clinical setting to deliver SDH content to all learners at UVM Larner.

Conclusions

Extensive student-faculty partnerships, robust needs assessment, and focusing on longitudinal and integrated SDH content delivery to all students were key features that contributed to successful design and implementation.
Participants’ views and experiences from setting up a shared patient portal for primary and specialist health services- a qualitative study
Authors: Nøst Torunn Hatlen , Faxvaag Arild , Steinsbekk Aslak
Published: February 2021

Background

Recently, there has been an increasing focus among healthcare organisations on implementing patient portals. Previous studies have mainly focussed on the experiences of patient portal use. Few have investigated the processes of deciding what content and features to make available, in particular for shared portals across healthcare domains. The aim of the study was to investigate views on content and experiences from the configuration process among participants involved in setting up a shared patient portal for primary and specialist health services.

Methods

A qualitative study including 15 semi-structured interviews with persons participating in patient portal configuration was conducted from October 2019 to June 2020.

Results

Whether a shared patient portal for all the health services in the region should be established was not questioned by any of the informants. It was experienced as a good thing to have numerous participants present in the discussions on configuration, but it also was said to increase the complexity of the work. The informants considered a patient portal to be of great value for patient care, among other things because it would lead to improvements in patient follow-up and increased patient empowerment. Nevertheless, some informants advocated caution as they thought the patient portal possibly could lead to an increase in healthcare providers’ workloads and to anxiety and worries, as well as to inequality in access to health care among patients. The findings were categorized into the themes ‘A tool for increased patient involvement’, ‘Which information should be available for the patient’, ‘Concerns about increased workload’, ‘Too complex to use versus not interesting enough’, ‘Involving all services’ and ‘Patient involvement’.

Conclusions

Establishing a shared patient portal for primary and specialist health services was considered unproblematic. There was, however, variation in opinions on which content and features to include. This variation was related to concerns about increasing the workload for health care providers, causing anxiety and inequality among patients, and ensuring that the solution would be interesting enough to adopt.
Association between biomass fuel use and the risk of cognitive impairment among older populations in China: a population-based cohort study
Authors: Du Min , Tao Liyuan , Zhu Lin , Liu Jue
Published: February 2021

Background

Cohort studies on the impact of biomass fuel use for cooking on cognitive impairment among older population are still lacking in China and elsewhere. The aim of this study was to examine whether biomass fuel use for cooking is associated with cognitive impairment in Chinese adults aged 65 years or older.

Methods

The prospective population-based cohort study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) included participants aged 65 years or older in 2014 who were followed-up until 2018 in 23 provinces in China. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and cognitive impairment was defined as total MMSE scores less than 18. The association between biomass fuel use and cognitive impairment was evaluated using the Cox proportional hazards model.

Results

Of the 4145 participants included at baseline, participants who reported that they used biomass fuel for cooking (40.43%; IR: 3.11 versus 2.77 per 100 person-years; aHR: 1.27, 95% CI: 1.02–1.58) had a higher risk of cognitive impairment compared with participants who used clean fuels (53.75%). A stratified analyses showed greater effect estimates of cognitive impairment in the older people that lived in the rural areas (aHR: 1.444, 95% CI: 1.08–3.90) and never smoked (aHR: 1.33, 95% CI: 1.04–1.71).

Conclusions

These findings demonstrated that biomass fuel used for cooking was associated with cognitive impairment, as defined by MMSE, in a population-based study of elderly in China. To prevent cognitive impairment, the structure of cooking fuels requires improvements.
DDX3X: structure, physiologic functions and cancer
Authors: Mo Jie , Liang Huifang , Su Chen , Li Pengcheng , Chen Jin , Zhang Bixiang
Published: February 2021

The DEAD-box helicase family member DDX3X (DBX, DDX3) functions in nearly all stages of RNA metabolism and participates in the progression of many diseases, including virus infection, inflammation, intellectual disabilities and cancer. Over two decades, many studies have gradually unveiled the role of DDX3X in tumorigenesis and tumour progression. In fact, DDX3X possesses numerous functions in cancer biology and is closely related to many well-known molecules. In this review, we describe the function of DDX3X in RNA metabolism, cellular stress response, innate immune response, metabolic stress response in pancreatic β cells and embryo development. Then, we focused on the role of DDX3X in cancer biology and systematically demonstrated its functions in various aspects of tumorigenesis and development. To provide a more intuitive understanding of the role of DDX3X in cancer, we summarized its functions and specific mechanisms in various types of cancer and presented its involvement in cancer-related signalling pathways.
Measurement properties of the Dutch–Flemish patient-reported outcomes measurement information system (PROMIS) physical function item bank and instruments: a systematic review
Authors: Abma Inger L. , Butje Bas J. D. , ten Klooster Peter M. , van der Wees Philip J.
Published: February 2021

Background

Limitations in physical functioning are a big concern especially for patients with chronic or musculoskeletal diseases. Therefore, physical functioning is often used as a core outcome of treatments. The generic patient-reported outcomes information system (PROMIS) physical function (PF) item bank has shown potential to measure PF with better precision, interpretability and lower respondent burden compared with traditional patient-reported outcome measures. This study provides an overview of the current evidence on the quality of the measurement properties of the translated Dutch–Flemish PROMIS-PF item bank and its subdomains, and their derived short forms and computer adaptive tests (CATs).

Methods

PubMed was searched up to June 17th 2020 for validation studies of Dutch–Flemish PROMIS-PF in Dutch and Flemish adults. Quality assessment of the included studies was conducted using the COSMIN Risk of bias checklist. The COSMIN criteria for good measurement properties were used to judge the results of the studies, which were adjusted and added to where needed for this review, in the context of IRT instruments and item banks. The quality of evidence was summarized for each measurement property based on the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach.

Results

Eleven studies were included, evaluating the PROMIS-PF item bank, the Upper Extremity (UE) subdomain, and/or their derived short forms and CATs in different clinical populations. There is evidence for sufficient structural validity, measurement precision, construct validity, and cross-cultural validity of the Dutch–Flemish PROMIS-PF item bank. The upper extremity subdomain item bank shows high quality evidence for structural validity and measurement precision. Content validity of these item banks has not been thoroughly demonstrated in a Dutch–Flemish population. Furthermore, the derived instruments have far less robust evidence: there are fewer validation studies available and none examined their performance as stand-alone administered instruments.

Conclusions

The first studies into the Dutch–Flemish PROMIS-PF item bank and the UE subdomain show promising results, with especially high quality evidence for sufficient structural validity and measurement precision. However, more studies, and with higher methodological quality, are needed to study the instruments derived from these item banks. These studies should also evaluate content validity, reliability and responsiveness.
Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study
Authors: Son Ga-Hyun , Choi So Yeon , Ju Yeon-Ji , Lee Keun-Young , Lee Jae Jun , Song Ji-Eun , Kim Youngmi , Park Sung Taek
Published: February 2021

Background

The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls.

Methods

RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA.

Results

Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group.

Conclusions

Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.
Abelson kinase’s intrinsically disordered region plays essential roles in protein function and protein stability
Authors: Rogers Edward M. , Allred S. Colby , Peifer Mark
Published: February 2021

Background

The non-receptor tyrosine kinase Abelson (Abl) is a key player in oncogenesis, with kinase inhibitors serving as paradigms of targeted therapy. Abl also is a critical regulator of normal development, playing conserved roles in regulating cell behavior, brain development and morphogenesis. Drosophila offers a superb model for studying Abl’s normal function, because, unlike mammals, there is only a single fly Abl family member. In exploring the mechanism of action of multi-domain scaffolding proteins like Abl, one route is to define the roles of their individual domains. Research into Abl’s diverse roles in embryonic morphogenesis revealed many surprises. For instance, kinase activity, while important, is not crucial for all Abl activities, and the C-terminal F-actin binding domain plays a very modest role. This turned our attention to one of Abl’s least understood features—the long intrinsically-disordered region (IDR) linking Abl’s kinase and F-actin binding domains. The past decade revealed unexpected, important roles for IDRs in diverse cell functions, as sites of posttranslational modifications, mediating multivalent interactions and enabling assembly of biomolecular condensates via phase separation. Previous work deleting conserved regions in Abl’s IDR revealed an important role for a PXXP motif, but did not identify any other essential regions.

Methods

Here we extend this analysis by deleting the entire IDR, and asking whether Abl∆IDR rescues the diverse roles of Abl in viability and embryonic morphogenesis inDrosophila.

Results

This revealed that the IDR is essential for embryonic and adult viability, and for cell shape changes and cytoskeletal regulation during embryonic morphogenesis, and, most surprisingly, revealed a role in modulating protein stability.

Conclusion

Our data provide new insights into the role of the IDR in an important signaling protein, the non-receptor kinase Abl, suggesting that it is essential for all aspects of protein function during embryogenesis, and revealing a role in protein stability. These data will stimulate new explorations of the mechanisms by which the IDR regulates Abl stability and function, both in Drosophila and also in mammals. They also will stimulate further interest in the broader roles IDRs play in diverse signaling proteins.
Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease
Authors: Desale Smita Eknath , Chinnathambi Subashchandrabose
Published: February 2021

Alzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-β contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-β in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-β deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.
Distinguishing active pediatric COVID-19 pneumonia from MIS-C
Authors: Reiff Daniel D. , Mannion Melissa L. , Samuy Nichole , Scalici Paul , Cron Randy Q.
Published: February 2021

Importance

Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols.

Objective

To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values.

Design

Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children’s of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment.

Findings

111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients.

Conclusions and relevance

This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.
Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial
Authors:   the Study 1053 investigators, Kreitman Robert J. , Dearden Claire , Zinzani Pier Luigi , Delgado Julio , Robak Tadeusz , le Coutre Philipp D. , Gjertsen Bjørn T. , Troussard Xavier , Roboz Gail J. , Karlin Lionel , Gladstone Douglas E. , Kuptsova-Clarkson Nataliya , Liu Shiyao , Patel Priti , Rotolo Federico , Mitry Emmanuel , Pastan Ira , Giles Francis
Published: February 2021

Background

Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).

Methods

Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days.

Results

Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported.

Conclusions

Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.

Trial registration

ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711
Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells
Authors: Shen Xiameng , Wang Conghui , Zhu Huihui , Wang Yaping , Wang Xinyu , Cheng Xiaodong , Ge Wanzhong , Lu Weiguo
Published: February 2021

Objective

To investigate the detailed roles and mechanisms of tumor-derived exosomes in progression and metastasis of ovarian cancer in vitro.

Methods

Exosomes were isolated by differential centrifugation method; the morphology, size and biological markers of exosomes were separately defined by transmission electron microscopy, nanoS90 and Western blotting; Trans-well chambers assay was used to assess the ability of migration and invasion of recipient cells uptaking the exosomes from HO8910PM cells. The downstream molecule was screened by mass spectrometry.CD44 was identified by western blotting and the function of CD44 was identified by trans-well chambers assay and CCK8 assay.

Results

Exosomes derived from HO8910PM cells could be transferred to HO8910 cells and promote cell migration and invasion in the recipient cells of ovarian cancer. And CD44 could be transferred to the HO8910 cells through exosomes from HO8910PM cells and influence the migration and invasion ability of HO8910 cells.

Conclusion

The more aggressive subpopulation can transfer a metastatic phenotype to the less one via secreting exosomes within a heterogeneous tumor. CD44 may be a potential therapeutic approach for ovarian cancer.
Whole blood and blood components from vertebrates differentially affect egg formation in three species of anautogenous mosquitoes
Authors: Harrison Ruby E. , Brown Mark R. , Strand Michael R.
Published: February 2021

Background

Most female mosquitoes are anautogenous and must blood feed on a vertebrate host to produce eggs. Prior studies show that the number of eggs females lay per clutch correlates with the volume of blood ingested and that protein is the most important macronutrient for egg formation. In contrast, how whole blood, blood fractions and specific blood proteins from different vertebrates affect egg formation is less clear. Since egg formation is best understood inAedes aegypti,we examined how blood and blood components from different vertebrates affect this species and two others: the malaria vectorAnopheles gambiaeand arbovirus vectorCulex quinquefasciatus.

Methods

Adult female mosquitoes were fed blood, blood fractions and purified major blood proteins from different vertebrate hosts. Markers of reproductive response including ovary ecdysteroidogenesis, yolk deposition into oocytes and number of mature eggs produced were measured.

Results

Ae. aegypti, An. gambiaeandC. quinquefasciatusresponded differently to meals of whole blood, plasma or blood cells from human, rat, chicken and turkey hosts. We observed more similarities between the anthropophilesAe. aegyptiandAn. gambiaethan the ornithophileC. quinquefasciatus.Focusing onAe. aegypti,the major plasma-derived proteins (serum albumin, fibrinogen and globulins) differentially stimulated egg formation as a function of vertebrate host source. The major blood cell protein, hemoglobin, stimulated yolk deposition when from pigs but not humans, cows or sheep. Serum albumins from different vertebrates also variably affected egg formation. Bovine serum albumin (BSA) stimulated ovary ecdysteroidogenesis, but more weakly induced digestive enzyme activities than whole blood. In contrast, BSA-derived peptides and free amino acids had no stimulatory effects on ecdysteroidogenesis or yolk deposition into oocytes.

Conclusions

Whole blood, blood fractions and specific blood proteins supported egg formation in three species of anautogenous mosquitoes but specific responses varied with the vertebrate source of the blood components tested.

Graphical Abstract
Single-cell transcriptomic profiling and characterization of endothelial progenitor cells: new approach for finding novel markers
Authors: Abdelgawad Mohamed Essameldin , Desterke Christophe , Uzan Georges , Naserian Sina
Published: February 2021

Background

Endothelial progenitor cells (EPCs) are promising candidates for the cellular therapy of peripheral arterial and cardiovascular diseases. However, hitherto there is no specific marker(s) defining precisely EPCs. Herein, we are proposing a new in silico approach for finding novel EPC markers.

Methods

We assembled five groups of chosen EPC-related genes/factors using PubMed literature and Gene Ontology databases. This shortened database of EPC factors was fed into publically published transcriptome matrix to compare their expression between endothelial colony-forming cells (ECFCs), HUVECs, and two adult endothelial cell types (ECs) from the skin and adipose tissue. Further, the database was used for functional enrichment on Mouse Phenotype database and protein-protein interaction network analyses. Moreover, we built a digital matrix of healthy donors’ PBMCs (33 thousand single-cell transcriptomes) and analyzed the expression of these EPC factors.

Results

Transcriptome analyses showed that BMP2, 4, and ephrinB2 were exclusively highly expressed in EPCs; the expression of neuropilin-1 and VEGF-C were significantly higher in EPCs and HUVECs compared with other ECs; Notch 1 was highly expressed in EPCs and skin-ECs; MIR21 was highly expressed in skin-ECs; PECAM-1 was significantly higher in EPCs and adipose ECs. Moreover, functional enrichment of EPC-related genes on Mouse Phenotype and STRING protein database has revealed significant relations between chosen EPC factors and endothelial and vascular functions, development, and morphogenesis, where ephrinB2, BMP2, and BMP4 were highly expressed in EPCs and were connected to abnormal vascular functions. Single-cell RNA-sequencing analyses have revealed that among the EPC-regulated markers in transcriptome analyses, (i) ICAM1 and Endoglin were weekly expressed in the monocyte compartment of the peripheral blood; (ii) CD163 and CD36 were highly expressed in the CD14+ monocyte compartment whereas CSF1R was highly expressed in the CD16+ monocyte compartment, (iii) L-selectin and IL6R were globally expressed in the lymphoid/myeloid compartments, and (iv) interestingly, PLAUR/UPAR and NOTCH2 were highly expressed in both CD14+ and CD16+ monocytic compartments.

Conclusions

The current study has identified novel EPC markers that could be used for better characterization of EPC subpopulation in adult peripheral blood and subsequent usage of EPCs for various cell therapy and regenerative medicine applications.
Defining, conceptualizing, and measuring perceived maternal care quality in low- to high-income countries: a scoping review protocol
Authors: Brown Kyrah K. , Boateng Godfred O. , Ossom-Williamson Peace , Haygood Laura
Published: February 2021

Background

Health practitioners and researchers must be able to measure and assess maternal care quality in facilities to monitor, intervene, and reduce global maternal mortality rates. On the global scale, there is a general lack of consensus on how maternal care quality is defined, conceptualized, and measured. Much of the literature addressing this problem has focused primarily on defining, conceptualizing, and measuring clinical indicators of maternal care quality. Less attention has been given in this regard to perceived maternal care quality among women which is known to influence care utilization and adherence. Therefore, there is a need to map the literature focused on defining, conceptualizing, and measuring perceived maternal care quality across low-, middle-, and high-income country contexts.

Methods

This scoping review protocol will follow the Arksey and O’Malley methodological framework. A comprehensive search strategy will be used to search for articles published from inception to 2020 in Ovid MEDLINE, Embase, AMED, and WHO Global Index Medicus. Gray literature will be included. Two independent reviewers will screen articles by title and abstract, then by full-text based on pre-determined inclusion/exclusion criteria. A third reviewer will arbitrate any discrepancies. This protocol outlines a four-step analytic approach that includes numerical, graphical, tabular, and narrative summaries to provide a comprehensive description of the body of literature.

Discussion

The findings from this scoping review will provide a comprehensive overview of the existing evidence on perceived maternal care quality. The findings are expected to inform future work on building consensus around the definition and conceptualization of perceived maternal care quality, and lay the groundwork for future research aimed at developing measures of perceived maternal care quality that can be applied across country contexts. Consequently, this review may aid in facilitating coordinated efforts to measure and improve maternal care quality across diverse country contexts (i.e., low-, middle-, and high-income country contexts).

Review registration

This scoping review has been registered in the Open Science Framework (osf.io/k8nqh).
A robust numerical solution to a time-fractional Black–Scholes equation
Authors: Nuugulu S. M. , Gideon F. , Patidar K. C.
Published: February 2021

Dividend paying European stock options are modeled using a time-fractional Black–Scholes (tfBS) partial differential equation (PDE). The underlying fractional stochastic dynamics explored in this work are appropriate for capturing market fluctuations in which random fractional white noise has the potential to accurately estimate European put option premiums while providing a good numerical convergence. The aim of this paper is two fold: firstly, to construct a time-fractional (tfBS) PDE for pricing European options on continuous dividend paying stocks, and, secondly, to propose an implicit finite difference method for solving the constructed tfBS PDE. Through rigorous mathematical analysis it is established that the implicit finite difference scheme is unconditionally stable. To support these theoretical observations, two numerical examples are presented under the proposed fractional framework. Results indicate that the tfBS and its proposed numerical method are very effective mathematical tools for pricing European options.
Resource pooling in vehicular fog computing
Authors: Tang Chaogang , Xia Shixiong , Li Qing , Chen Wei , Fang Weidong
Published: February 2021

Vehicular fog computing (VFC) provisions computing services at the edge of networks by fully exploiting the idle resources of vehicle loaded computer systems. Task scheduling and resource allocation revolved around VFC have gained tremendous attention recently. Currently, most of these works in VFC have focused on response time optimization or energy reduction. Computing services are provisioned in a pay-as-you-go model and vehicles as resource contributors are stimulated by the benefits obtained by leasing these resources. How to maximize their own benefits is one of big concerns but few of current works have recognized its importance in VFC. We in this paper introduce the notion of resource pooling into VFC where the computing resources of vehicles are pooled together to jointly provision computational services in a community. A genetic algorithm based strategy is proposed to solve the optimization problem for the sake of benefit maximization. Extensive experiments have been carried out to evaluate the approach and the numeric results have demonstrated that our strategy outstands other approaches with regards to the optimization objective.
Adapting inpatient addiction medicine consult services during the COVID-19 pandemic
Authors: Harris Miriam T. H. , Peterkin Alyssa , Bach Paxton , Englander Honora , Lapidus Emily , Rolley Theresa , Weimer Melissa B. , Weinstein Zoe M.
Published: February 2021

Background

We describe addiction consult services (ACS) adaptations implemented during the Novel Coronavirus Disease 2019 (COVID-19) pandemic across four different North American sites: St. Paul’s Hospital in Vancouver, British Columbia; Oregon Health & Sciences University in Portland, Oregon; Boston Medical Center in Boston, Massachusetts; and Yale New Haven Hospital in New Haven, Connecticut.

Experiences

ACS made system, treatment, harm reduction, and discharge planning adaptations. System changes included patient visits shifting to primarily telephone-based consultations and ACS leading regional COVID-19 emergency response efforts such as substance use treatment care coordination for people experiencing homelessness in COVID-19 isolation units and regional substance use treatment initiatives. Treatment adaptations included providing longer buprenorphine bridge prescriptions at discharge with telemedicine follow-up appointments and completing benzodiazepine tapers or benzodiazepine alternatives for people with alcohol use disorder who could safely detoxify in outpatient settings. We believe that regulatory changes to buprenorphine, and in Vancouver other medications for opioid use disorder, helped increase engagement for hospitalized patients, as many of the barriers preventing them from accessing care on an ongoing basis were reduced. COVID-19 specific harm reductions recommendations were adopted and disseminated to inpatients. Discharge planning changes included peer mentors and social workers increasing hospital in-reach and discharge outreach for high-risk patients, in some cases providing prepaid cell phones for patients without phones.

Recommendations for the future

We believe that ACS were essential to hospitals’ readiness to support patients that have been systematically marginilized during the pandemic. We suggest that hospitals invest in telehealth infrastructure within the hospital, and consider cellphone donations for people without cellphones, to help maintain access to care for vulnerable patients. In addition, we recommend hospital systems evaluate the impact of such interventions. As the economic strain on the healthcare system from COVID-19 threatens the very existence of ACS, overdose deaths continue rising across North America, highlighting the essential nature of these services. We believe it is imperative that health care systems continue investing in hospital-based ACS during public health crises.
Cerebellar transcranial direct current stimulation reconfigurates static and dynamic functional connectivity of the resting-state networks
Authors: Grami F. , de Marco G. , Bodranghien F. , Manto M. , Habas C.
Published: February 2021

Background

Transcranial direct current stimulation (tDCS) of the cerebellum dynamically modulates cerebello-thalamo-cortical excitability in a polarity-specific manner during motor, visuo- motor and cognitive tasks. It remains to be established whether tDCS of the cerebellum impact also on resting-state intrinsically connected networks (ICNs). Such impact would open novel research and therapeutical doors for the neuromodulation of ICNs in human.

Method

We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS- induced resting-state intrinsic functional reconfiguration, using a randomized, sham-controlled design. fMRI data were recorded both before and after real anodal stimulation (2 mA, 20 min) or sham tDCS in 12 right-handed healthy volunteers. We resorted to a region-of-interest static correlational analysis and to a sliding window analysis to assess temporal variations in resting state FC between the cerebellar lobule VII and nodes of the main ICNs.

Results

After real tDCS and compared with sham tDCS, functional changes were observed between the cerebellum and ICNs. Static FC showed enhanced or decreased correlation between cerebellum and brain areas belonging to visual, default-mode (DMN), sensorimotor and salience networks (SN) (p-corrected < 0.05). The temporal variability (TV) of BOLD signal was significantly modified after tDCS displaying in particular a lesser TV between the whole lobule VII and DMN and central executive network and a greater TV between crus 2 and SN. Static and dynamic FC was also modified between cerebellar lobuli.

Conclusion

These results demonstrate short- and long-range static and majorly dynamic effects of tDCS stimulation of the cerebellum affecting distinct resting-state ICNs, as well as intracerebellar functional connectivity, so that tDCS of the cerebellum appears as a non-invasive tool reconfigurating the dynamics of ICNs.