bluuebunny/crossref_metadata_2025_split huggingface dataset:
“There Should Have Been a More Holistic Approach”—A Qualitative Study of Young Adult Cancer Survivors’ Experiences of Follow-up After Cancer Treatment
Authors: Aase Andrea S. , Ingebretsen Thea K. , Hauken May Aa. 
Published: January 2021

Background
Young adult cancer survivors (YACSs) are in a vulnerable period of life with increased risk of severe physical and psychosocial late effects. However, limited research exists on follow-up of YACSs after cancer treatment.

Objective
The aim of this study was to explore how YACSs experience follow-up from the healthcare system after finishing cancer treatment.

Methods
Using a qualitative method with an interpretive descriptive design, 20 YACSs were interviewed 4 times over a period of 6 months. The transcribed interviews were analyzed using Systematic Text Condensation.

Results
Four main themes were identified: “They should have prepared me better,” “The GP (general practitioner) does not understand my challenges,” “My check-ups are all about cancer relapse,” and “I do not know who’s in charge.”

Conclusion
The findings indicate deficiency in the healthcare system’s follow-up of YACSs in terms of preparation for the survival phase, interdisciplinary cooperation, and acknowledgement of late effects, as well as organization of follow-up care within the healthcare system.

Implications for Practice
A more holistic perspective on follow-up care that addresses YACSs’ multidimensional challenges is suggested, including a multidisciplinary approach where cancer nurses should play an active role.
Targeting fibrosis in the Duchenne Muscular Dystrophy mice model: an uphill battle
Authors: Theret Marine , Low Marcela , Rempel Lucas , Li Fang Fang , Tung Lin Wei , Contreras Osvaldo , Chang Chih-Kai , Wu Andrew , Soliman Hesham , Rossi Fabio M.V. 
Published: January 2021

AbstractAimFibrosis is the most common complication from chronic diseases, and yet no therapy capable of mitigating its effects is available. Our goal is to unveil specific signallings regulating the fibrogenic process and to identify potential small molecule candidates that block fibrogenic differentiation of fibro/adipogenic progenitors.MethodWe performed a large-scale drug screen using muscle-resident fibro/adipogenic progenitors from a mouse model expressing EGFP under theCollagen1a1promotor. We first confirmed that the EGFP was expressed in response to TGFβ1 stimulationin vitro. Then we treated cells with TGFβ1 alone or with drugs from two libraries of known compounds. The drugs ability to block the fibrogenic differentiation was quantified by imaging and flow cytometry. From a two-rounds screening, positive hits were testedin vivoin the mice model for the Duchenne muscular dystrophy (mdx mice). The histopathology of the muscles was assessed with picrosirius red (fibrosis) and laminin staining (myofiber size).Key findingsFrom the in vitro drug screening, we identified 21 drugs and tested 3in vivoon the mdx mice. None of the three drugs significantly improved muscle histopathology.SignificanceThein vitrodrug screen identified various efficient compounds, none of them strongly inhibited fibrosis in skeletal muscle of mdx mice. To explain these observations, we hypothesize that in Duchenne Muscular Dystrophy, in which fibrosis is a secondary event due to chronic degeneration and inflammation, the drugs tested could have adverse effect on regeneration or inflammation, balancing off any positive effects and leading to the absence of significant results.
In vitroinfection of human lung tissue with SARS-CoV-2: Heterogeneity in host defense and therapeutic response
Authors: Schaller Matthew A. , Sharma Yamini , Dupee Zadia , Nguyen Duy , Uruena Juan , Smolchek Ryan , Loeb Julia C. , Machuca Tiago N. , Lednicky John A. , Odde David J. , Campbell Robert F. , Sawyer W. Gregory , Mehrad Borna 
Published: January 2021

AbstractCell lines are the mainstay in understanding the biology of COVID-19 infection, but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue allows for thein vitrostudy of the inter-individual heterogeneity of host response to SARS-CoV-2 infection, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 16 donors, most of whom had risk factors for severe illness from COVID-19. Cryopreserved tissues preserved 90% of cell viability and contained heterogeneous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infectible with HCoV-OC43 and SARS-CoV-2 coronavirus strains, and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL-6, CXCL8 and IFNβ in response to SARS-CoV-2 infection. Treatment of tissues with dexamethasone and the experimental drug, N-hydroxycytidine, suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted antiviral activity, suppressed viral replication in tissues from a subset of donors. In summary, we developed a novel system for thein vitrostudy of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis.ImportanceThe current biological systems for the study of COVID-19 arein vitrosystems that differ from the human lung in many respects, and animal hosts to which the virus is not adapted. We developed another alternative for studying pathogenesis and drug susceptibility of SARS-CoV-2 in a cryopreserved bank of human lung tissues. We consider the importance of this work to relate to the practical use of this culture system as a repeatable and scalable approach that allows for the study of an important infection in relevant tissues.The tissue bank highlights the heterogeneous response to SARS-CoV-2 infection and treatment, which allows researchers to investigate why treatments work in some donors but not others.
Symptoms of anxiety and depression in relation to work patterns during the first wave of the COVID-19 epidemic in Philadelphia PA: a cross-sectional survey
Authors: Burstyn Igor , Huynh Tran 
Published: January 2021

AbstractObjectiveWe investigated whether patterns of work during COVID-19 pandemic altered by effort to contain the outbreak affected anxiety and depression.MethodsWe conducted a cross-sectional online survey of 911 residents of Philadelphia, inquiring about their working lives during early months of the epidemic, symptoms of anxiety and depression, plus demographics, perceived sources of support, and general health.ResultsOccupational contact with suspected COVID-19 cases was associated with anxiety. Concerns about return to work, childcare, lack of sick leave, and loss/reduction in work correlated with anxiety and depression, even when there was no evidence of occupational contact with infected persons; patterns differed by gender.ConclusionsHeightened anxiety and depression during COVID-19 pandemic can be due to widespread disruption of working lives, especially in “non-essential” low-income industries, on par with experience in healthcare.The significance to clinical practice of the information being presented:Anxiety and depression symptoms that emerged during COVID-19 pandemic may be related to disruption of working lives even among people who are not the “essential” workers with one-one-one contact with infected persons. Clinicians may find this evidence of occupational correlates and articulated specific worries useful in treating such patients.
Age-dependent heterogeneity of lymph node metastases and survival identified by analysis of a national breast cancer registry
Authors: Behring Michael , Bajpai Prachi , Afaq Farrukh , Elkholy Amr , Kim Hyung-Gyoon , Diffalha Sameer Al , Shrestha Sadeep , Manne Upender 
Published: January 2021

AbstractBackgroundFor several cancers, including those of the breast, young age at diagnosis is associated with an adverse prognosis. Although this effect is often attributed to heritable mutations such as BRCA1/2, the relationship between pathologic features, young age of onset, and prognosis for breast cancer remains unclear. In the present study, we highlight links between age of onset and lymph node metastasis (NM) in US women with breast cancer.MethodsCase listings from Surveillance, Epidemiology, and End Result (SEER) 18 registry data for women with breast cancer, which include information on race, were used. NM and its associated outcomes were evaluated for a subset of women with receptor subtype information and then compared against a larger, pre-subtype validation set of data from the same registry. Age of diagnosis was a 5-category variable; under 40 years, 40-49 years, 50-59 years, 60-69 years and 70+ years. Univariate and adjusted multivariate survival models were applied to both sets of data.ResultsAs determined with adjusted logistic regression models, women under 40 years old at diagnosis had 1.55 times the odds of NM as women 60-69 years of age. The odds of NM for (HR = hormone receptor) HR+/HER2+, HR-/HER2+, and triple-negative breast cancer subtypes were significantly lower than those for HR+/HER2-. In subtype-stratified adjusted models, age of diagnosis had a consistent trend of decreasing odds of NM by age category, most noticeable for HR+ subtypes of luminal A and B. Univariate 5-year survival by age was worst for women under 40 years, with NM attributable for 49% of the hazard of death from cancer in adjusted multivariate models.ConclusionsLymph node metastasis is age-dependent, yet not all molecular subtypes are clearly affected by this relationship. For <40-yr-old women, NM is a major cause for shorter survival. When stratified by subtype, the strongest associations were in HR+ groups, suggesting a possible hormonal connection between young age of breast cancer onset and NM.
Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines
Authors: Lewnard Joseph A. , Patel Manish M. , Jewell Nicholas P. , Verani Jennifer R. , Kobayashi Miwako , Tenforde Mark , Dean Natalie E. , Cowling Benjamin J. , Lopman Benjamin A. 
Published: January 2021

ABSTRACTObservational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. These are now in planning amid the ongoing rollout of SARS-CoV-2 vaccines globally. While traditional case-control (TCC) and test-negative design (TND) studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here we review the theoretical basis for estimation of vaccine direct effects under TCC and TND frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, non-specific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The TCC may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The TND reduces but may not eliminate this confounding, for instance if individuals who receive vaccination seek care or testing for less-severe infection. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.
SARS-CoV-2 Can Infect Human Embryos
Authors: Montano Mauricio , Victor Andrea R. , Griffin Darren K. , Duong Tommy , Bolduc Nathalie , Farmer Andrew , Garg Vidur , Hadjantonakis Anna-Katerina , Coates Alison , Barnes Frank L. , Zouves Christo G. , Greene Warner C. , Viotti Manuel 
Published: January 2021

AbstractThe spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. We note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. Using fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, we observe robust infection of trophectoderm cells, and this permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.
Efficacy of bacteriophage therapy against vancomycin-resistantEnterococcus feacalisin induced and non-induced diabetic mice
Authors: Oli Ajay Kumar , Shivshetty Nagveni , Ahmed Likyat , Chavadi Manjunath , Kambar Rahul N , Kelmani Chandrakanth R 
Published: January 2021

AbstractThe antibiotic resistance of an organism has become an endeavor worldwide. The resistance of bacteria is impacting the immunocompromised patient, especially with diabetic. The bacteriophages are more specific in the elimination of the infections caused by the organism. One of the significant bacteria is Vancomycin-resistantEnterococcus faecalis(VREF), emerging as bioburden rendering infectious diseases in developing countries. We attempted to treat infection of VREF in the induced and non-induced diabetic mice model along with antibiotic and phage treatment. The phage has shown more efficiency than vancomycin antibiotic alone and combined therapy with antibiotic phage treated. The considering phage therapy an alternative source for the treatment in the insulin-dependent diabetic with an infection of bacteria.
4D imaging of soft matter in liquid water
Authors: Marchello Gabriele , De Pace Cesare , Acosta-Gutierrez Silvia , Lopez-Vazquez Ciro , Wilkinson Neil , Gervasio Francesco L. , Ruiz-Perez Lorena , Battaglia Giuseppe 
Published: January 2021

Water is a critical component for both function and structure of soft matter and it is what bestows the adjective soft. Imaging samples in liquid state is thus paramount to gathering structural and dynamical information of any soft materials. Herein we propose the use of liquid phase electron microscopy to expand ultrastructural analysis into dynamical investigations. We imaged two soft matter examples: a polymer micelle and a protein in liquid phase using transmission electron microscopy and demonstrate that the inherent Brownian motion associated with the liquid state can be exploited to gather three-dimensional information of the materials in their natural state. We call such an approach brownian tomography (BT). We combine BT with single particle analysis (Brownian particle analysis BPA) to image protein structures with a spatial resolution close that achievable using cryogenic TEM. We show that BPA allows sub-nanometer resolution of soft materials and enables to gather information on conformational changes, hydration dynamics, and the effect of thermal fluctuations.Abstract Figure
Genetic analysis of the septal peptidoglycan synthase FtsWI complex supports a conserved activation mechanism for SEDS-bPBP complexes
Authors: Li Ying , Gong Han , Zhan Rui , Ouyang Shushan , Park Kung-tae , Lutkenhaus Joe , Du Shishen 
Published: January 2021

AbstractSEDS family peptidoglycan (PG) glycosyltransferases RodA and FtsW require their cognate transpeptidases PBP2 and FtsI (class B penicillin binding proteins) to synthesize PG along the cell cylinder and at the septum, respectively. The activities of these SEDS-bPBPs complexes are tightly regulated to ensure proper cell elongation and division. InEscherichia coliFtsN switches FtsA and FtsQLB to the active forms that synergize to stimulate FtsWI, but the exact mechanism is not well understood. Previously, we isolated an activation mutation inftsW(M269I) that allows cell division with reduced FtsN function. To try and understand the basis for activation we isolated additional substitutions at this position and found that only the original substitution produced an active mutant whereas drastic changes resulted in an inactive mutant. In another approach we isolated suppressors of an inactive FtsL mutant and obtained FtsWE289Gand FtsIK211Iand found they bypassed FtsN. Epistatic analysis of these mutations and others confirmed that the FtsN-triggered activation signal goes from FtsQLB to FtsI to FtsW. Mapping these mutations and others affecting the activities of FtsWI on the RodA-PBP2 structure revealed they are located at the interaction interface between the extracellular loop 4 (ECL4) of FtsW and the pedestal domain of FtsI (PBP3). This supports a model in which the interaction between the ECL4 of SEDS proteins and the pedestal domain of their cognate bPBPs plays a critical role in the activation mechanism.Author summaryBacterial cell division requires the synthesis of septal peptidoglycan by the widely conserved SEDS-bPBP protein complex FtsWI, but how the complex is activated during cell division is still poorly understood. Previous studies suggest that FtsN initiates a signaling cascade in the periplasm to activate FtsW. Here we isolated and characterized activated FtsW and FtsI mutants and confirmed that the signaling cascade for FtsW activation goes from FtsN to FtsQLB to FtsI and then to FtsW. The residues corresponding to mutations affecting FtsWI activation are clustered to a small region of the interaction interface between the pedestal domain of FtsI and the extracellular loop 4 of FtsW, suggesting that this interaction mediates activation of FtsW. This is strikingly similar to the proposed activation mechanism for the RodA-PBP2 complex, another SEDS-bPBP complex required for cell elongation. Thus, the two homologous SEDS-bPBP complexes are activated similarly by completely unrelated activators that modulate the interaction interface between the SEDS proteins and the bPBPs.
Pannexin 1 influences lineage specification of human iPSCs
Authors: Noort Rebecca J. , Christopher Grace A. , Esseltine Jessica L. 
Published: January 2021

AbstractEvery single cell in the body communicates with nearby cells to locally organize activities with their neighbors and dysfunctional cell-cell communication can be detrimental during cell lineage commitment, tissue patterning and organ development.Pannexin channels (PANX1, PANX2, PANX3)facilitate purinergic paracrine signaling through the passage of messenger molecules out of cells. PANX1 is widely expressed throughout the body and has recently been identified in human oocytes as well as 2 and 4-cell stage human embryos. Given its abundance across multiple adult tissues and its expression at the earliest stages of human development, we sought to understand whether PANX1 impacts human induced pluripotent stem cells (iPSCs) or plays a role in cell fate decisions. Western blot, immunofluorescence and flow cytometry reveal that PANX1 is expressed in iPSCs as well as all three germ lineages derived from these cells: ectoderm, endoderm, and mesoderm. PANX1 demonstrates differential glycosylation patterns and subcellular localization across the germ lineages. Using CRISPR-Cas9 gene ablation, we find that loss of PANX1 has no obvious impact on iPSC morphology, survival, or pluripotency gene expression. However,PANX1knockout iPSCs exhibit apparent lineage specification bias during 2-dimensional and 3-dimensional spontaneous differentiation into the three germ lineages. Indeed, loss of PANX1 significantly decreases the proportion of ectodermal cells within spontaneously differentiated cultures, while endodermal and mesodermal representation is increased in PANX1 knockout cells. Importantly,PANX1knockout iPSCs are fully capable of differentiating toward each specific lineage when exposed to the appropriate external signaling pressures, suggesting that although PANX1 influences germ lineage specification, it is not essential to this process.Graphical abstract
Restoring fertility in yeast hybrids: breeding and quantitative genetics of beneficial traits
Authors: Naseeb S. , Visinoni F. , Hu Y. , Hinks Roberts A. J. , Maslowska A. , Walsh T. , Smart K. A. , Louis E. J. , Delneri D. 
Published: January 2021

AbstractHybrids species can harbour a combination of beneficial traits from each parent and may exhibit hybrid vigour, more readily adapting to new harsher environments. Inter-species hybrids are also sterile and therefore an evolutionary dead-end unless fertility is restored, usually via auto-polyploidisation events. In theSaccharomycesgenus, hybrids are readily found in nature and in industrial settings, where they have adapted to severe fermentative conditions. Due to their hybrid sterility, the development of new commercial yeast strains has so far been primarily conducted via selection methods rather than breeding. In this study, we overcame infertility by creating tetraploid intermediates ofSaccharomycesinter-species hybrids, to allow continuous multigenerational breeding. We incorporated nuclear and mitochondrial genetic diversity within each parental species, allowing for quantitative genetic analysis of traits exhibited by the hybrids, and for nuclear-mitochondrial interactions to be assessed. Using pooled F12 generation segregants of different hybrids with extreme phenotype distributions, we identified QTLs for tolerance to high and low temperatures, high sugar concentration, high ethanol concentration, and acetic acid levels. We identified QTLs that are species specific, that are shared between species, as well as hybrid specific, where the variants do not exhibit phenotypic differences in the original parental species. Moreover, we could distinguish between mitochondria-type dependent and independent traits. This study tackles the complexity of the genetic interactions and traits in hybrid species, bringing hybrids into the realm of full genetic analysis of diploid species, and paves the road for the biotechnological exploitation of yeast biodiversity.
T cell circuits that sense antigen density with an ultrasensitive threshold
Authors: Hernandez-Lopez Rogelio A. , Yu Wei , Cabral Katie , Creasey Olivia , del Pilar Lopez Pazmino Maria , Tonai Yurie , De Guzman Arsenia , Mäkelä Anna , Saksela Kalle , Gartner Zev J. , Lim Wendell A. 
Published: January 2021

AbstractOverexpressed tumor associated antigens (e.g. HER2 and EGFR) are attractive targets for therapeutic T cells, but toxic cross-reaction with normal tissues expressing low antigen levels has been observed with Chimeric Antigen Receptor (CAR) T cells targeting such antigens. Inspired by natural ultrasensitive response circuits, we engineer a two-step positive feedback circuit that allows T cells to discriminate targets based on a sigmoidal antigen density threshold. In this circuit, a low affinity SynNotch receptor for HER2 controls the expression of a high affinity CAR for HER2. Increasing HER2 density thus has cooperative effects on T cells ╌ it both increases CAR expression and activation ╌ leading to a sigmoidal response. T Cells with this circuit show sharp discrimination between target cells expressing normal and disease levels of HER2, bothin vitroandin vivo.One Sentence SummaryA two-step positive feedback circuit generates engineered T cells capable of killing target cells with an ultrasensitive antigen density threshold.