bluuebunny/crossref_metadata_2025_split huggingface dataset:
Massive blood loss protocol ‘Code Red’ at Papworth Hospital: A closed loop audit
Authors: Tennyson M , Redlaff J , Biosse-Duplan G , Lewin M , Jones N , Layard Horsfall H 
Published: September 2020

Aim To investigate if the massive blood loss protocol ‘Code Red’ at a specialist cardiothoracic hospital was activated according to local and national guidelines by a closed loop audit. Methods Electronic and paper patient care systems were searched in 2015 and 2018 to access records for the ‘Code Red’ activations. Activation of the massive blood loss protocol was compared against the national standards set by The British Committee for Standards in Haematology. The percentage of cases meeting each of the ten standards in the specialist cardiac unit’s Protocol for the Management of Massive Blood Loss in Adults (adapted from the national standards) were evaluated. Results ‘Code Red’ protocol was activated on 18 occasions in 2015 and nine occasions in 2018, representing just 0.83 and 0.26% of emergency surgeries, respectively. Between 2015 and 2018, there was a 6% increase of ‘Code Red’ cases being appropriately activated, a 26% increase in the prompt notification of the haematology department upon activation, alongside a 30% increase in the timely delivery of blood products, and a 25% decrease in the average amount of blood transferred prior to ‘Code Red’ activation. Conclusion There has been an improvement in the standards of care and management of massive blood loss this specialist cardiac centre despite the target timeframe being reduced from 30 to 15min between 2015 and 2018. Preparation for and anticipation of massive blood loss has likely decreased the number of incidences requiring ‘Code Red’ activation, permitting delivery of safe patient care.
How I treat anticoagulant-refractory thrombotic antiphospholipid syndrome
Authors: Cohen Hannah , Isenberg David A. 
Published: September 2020

Abstract
The standard treatment of thrombotic antiphospholipid syndrome (APS) is lifelong oral anticoagulation with a vitamin K antagonist (VKA), generally warfarin. A minority of patients with APS rethrombose despite seemingly adequate anticoagulation. These patients are deemed anticoagulant refractory. The management of anticoagulant-refractory APS is largely empirical and extrapolated from other clinically similar situations. Further options include increased VKA anticoagulation intensity or alternative antithrombotic strategies, including low-molecular-weight heparin, fondaparinux, the addition of antiplatelet therapy, and consideration of vascular options. Patients with anticoagulant-refractory thrombotic APS may have APS-associated thrombocytopenia, which necessitates balancing the risk of recurrent thrombosis vs bleeding to achieve adequate anticoagulation. The multiple mechanisms involved in the generation of the thrombotic phenotype in APS suggest that anticoagulation alone may not control thrombosis. Thus, other modalities, including adjunctive treatment (hydroxychloroquine, statins, and vitamin D) for APS-related thrombosis, merit consideration, as do immunomodulatory therapy and complement inhibition. Patients with APS may have coexistent systemic lupus erythematosus, which adds to the complexity of managing their thromboembolic disease. However, with attention to detail and judicious application of the limited data, it is possible to minimize the morbidity resulting from anticoagulant-refractory thrombotic APS. Multicenter studies are required to guide the sequence of interventions and their comparative efficacy in patients with anticoagulant-refractory thrombotic APS.
Chromosome 20 loss is characteristic of breast implant–associated anaplastic large cell lymphoma
Authors: Los-de Vries G. Tjitske , de Boer Mintsje , van Dijk Erik , Stathi Phylicia , Hijmering Nathalie J. , Roemer Margaretha G. M. , Mendeville Matias , Miedema Daniel M. , de Boer Jan Paul , Rakhorst Hinne A. , van Leeuwen Flora E. , van der Hulst René R. W. J. , Ylstra Bauke , de Jong Daphne 
Published: September 2020

Abstract
Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)− nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK+ and ALK− ALCL. Mutational patterns confirm that the interleukin-6–JAK1–STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.
Recipient-specific T-cell repertoire reconstitution in the gut following murine hematopoietic cell transplant
Authors: Zheng Pingping , Tamaresis John , Thangavelu Govindarajan , Xu Liwen , You Xiaoqing , Blazar Bruce R. , Negrin Robert S. , Zehnder James L. , Iliopoulou Bettina P. , Meyer Everett H. 
Published: September 2020

AbstractGraft-versus-host disease (GVHD) is a complication of hematopoietic cell transplantation (HCT) caused by alloreactive T cells. Murine models of HCT are used to understand GVHD and T-cell reconstitution in GVHD target organs, most notably the gastrointestinal (GI) tract where the disease contributes most to patient mortality. T-cell receptor (TCR) repertoire sequencing was used to measure T-cell reconstitution from the same donor graft (C57BL/6 H-2b) in the GI tract of different recipients across a spectrum of matching, from syngeneic (C57BL/6), to minor histocompatibility (MHC) antigen mismatch BALB.B (H-2b), to major MHC mismatched B10.BR (H-2k) and BALB/c (H-2d). Although the donor T-cell pools had highly similar TCR, the TCR repertoire after HCT was very specific to recipients in each experiment independent of geography. A single invariant natural killer T clone was identifiable in every recipient group and was enriched in syngeneic recipients according to clonal count and confirmatory flow cytometry. Using a novel cluster analysis of the TCR repertoire, we could classify recipient groups based only on their CDR3 size distribution or TCR repertoire relatedness. Using a method for evaluating the contribution of common TCR motifs to relatedness, we found that reproducible sets of clones were associated with specific recipient groups within each experiment and that relatedness did not necessarily depend on the most common clones in allogeneic recipients. This finding suggests that TCR reconstitution is highly stochastic and likely does not depend on the evaluation of the most expanded TCR clones in any individual recipient but instead depends on a complex polyclonal architecture.
Pharmacometric modeling to explore 4F-PCC dosing strategies for VKA reversal in patients with INR below 2
Authors: Sarode Ravi , Fukutake Katsuyuki , Yasaka Masahiro , Tortorici Michael A. , Mangione Antoinette , Pfister Marc , Cuker Adam 
Published: September 2020

AbstractThe indicated dose of 4-factor prothrombin complex concentrate (4F-PCC) for urgent vitamin K antagonist (VKA) reversal in patients with an international normalized ratio (INR) of 2 to 4 is 25 IU/kg, but there is no indicated dose for INR &lt;2. We explored 4F-PCC dosing strategies for baseline INR &lt;2. Clinical trial data were used to develop pharmacometric models for Factor X (FX) and FII, accounting for covariates including baseline INR. FX and FII levels over time were simulated for mean baseline INR levels of the clinical trial participants plus baseline INRs 3.1, 1.9, and 1.6. For each INR, 200 virtual male patients were simulated to evaluate 4F-PCC doses of 35, 25, 20, 15, 12.5, and 10 IU/kg. Given an elevated bleeding risk with VKA therapy in Japanese vs Western populations, results were stratified by Japanese and non-Japanese patients. Target levels of FX and FII were ≥50% activity at 30 minutes after dosing in ≥80% of patients. FX- and FII-time models were developed with 1088 FX observations from 193 patients and 1074 FII observations from 192 patients. Model-based simulations indicated that at baseline INR 3.1, ≥80% of patients achieved ≥50% FX and FII activity with 25 IU/kg and 20 IU/kg 4F-PCC, respectively; at baseline INR 1.9, corresponding doses were 20 IU/kg and 15 IU/kg 4F-PCC, and at baseline INR 1.6, corresponding doses were 15 IU/kg, and 10 IU/kg 4F-PCC. Trends in Japanese and non-Japanese patients were similar. In conclusion, low 4F-PCC doses (15-20 IU/kg) may be sufficient to achieve hemostatic levels of FX and FII in Japanese and non-Japanese patients with baseline INR &lt;2.
Charge-altering releasable transporters enable phenotypic manipulation of natural killer cells for cancer immunotherapy
Authors: Wilk Aaron J. , Weidenbacher Nancy Lynn-Benner , Vergara Rosemary , Haabeth Ole A. W. , Levy Ronald , Waymouth Robert M. , Wender Paul A. , Blish Catherine A. 
Published: September 2020

Abstract
Chimeric antigen receptor (CAR) natural killer (NK) cells are an emerging cell therapy with promising results in oncology trials. However, primary human NK cells are difficult to transfect, hampering both mechanistic studies and clinical applications of NK cells. Currently, NK cell CAR modification relies on viral vectors or cell activation. The former raises cost and tolerability issues, while the latter alters NK cell biology. Here, we report that readily synthesized and inexpensive nonviral charge-altering releasable transporters (CARTs) efficiently transfect primary human NK cells with messenger RNA without relying on NK cell activation. Compared with electroporation, CARTs transfect NK cells more efficiently, better preserve cell viability, and cause minimal reconfiguration of NK cell phenotype and function. We use CARTs to generate cytotoxic primary anti-CD19 CAR NK cells, demonstrating this technology can drive clinical applications of NK cells. To our knowledge, CARTs represent the first efficacious transfection technique for resting primary human NK cells that preserves NK cell phenotype and can enable new biological discoveries and therapeutic applications of this understudied lymphocyte subset.
Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein
Authors: Landeck Natalie , Strathearn Katherine E. , Ysselstein Daniel , Buck Kerstin , Dutta Sayan , Banerjee Siddhartha , Lv Zhengjian , Hulleman John D. , Hindupur Jagadish , Lin Li-Kai , Padalkar Sonal , Stanciu Lia A. , Lyubchenko Yuri L. , Kirik Deniz , Rochet Jean-Christophe 
Published: September 2020

Abstract
Background
α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson’s disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology.

Methods
Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intranigrally with aSyn-encoding adeno-associated viruses were analyzed immunohistochemically to determine nigral dopaminergic neuron viability and striatal dopaminergic terminal density. Recombinant aSyn variants were characterized in terms of fibrillization rates by measuring thioflavin T fluorescence, fibril morphologies via electron microscopy and atomic force microscopy, and protein-lipid interactions by monitoring membrane-induced aSyn aggregation and aSyn-mediated vesicle disruption. Statistical tests consisted of ANOVA followed by Tukey’s multiple comparisons post hoc test and the Kruskal-Wallis test followed by a Dunn’s multiple comparisons test or a two-tailed Mann-Whitney test.

Results
Mouse aSyn was less neurotoxic than human aSyn A53T in cell culture and in rat midbrain, and data obtained for the chimeric variants indicated that the human-to-mouse substitutions D121G and N122S were at least partially responsible for this decrease in neurotoxicity. Human aSyn A53T and a chimeric variant with the human residues D and N at positions 121 and 122 (respectively) showed a greater propensity to undergo membrane-induced aggregation and to elicit vesicle disruption. Differences in neurotoxicity among the human, mouse, and chimeric aSyn variants correlated weakly with differences in fibrillization rate or fibril morphology.

Conclusions
Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders.
Arbuscular mycorrhiza improved drought tolerance of maize seedlings by altering photosystem II efficiency and the levels of key metabolites
Authors: Hu Yanbo , Xie Wei , Chen Baodong 
Published: September 2020

Abstract
Background
Water shortage can limit plant growth, which can be ameliorated by arbuscular mycorrhizal (AM) symbiosis through physiological and metabolic regulations. Deciphering which physiological and metabolic processes are central for AM-mediated regulations is essential for applications of mycorrhizal biotechnology in dryland agriculture.

Methodology
In this study, the influence of AM symbiosis on growth performance, photosynthesis, and organ accumulation of key C and N metabolites were assessed by growing maize (Mo17, Lancaster Sure Crop) seedlings inoculated with or without AM fungus (Rhizophagus irregularis Schenck & Smith BGC AH01) under different water regimes in greenhouse.

Results
Drought stress reduced shoot growth, while AM symbiosis significantly improved growth performances, with significant changes of photochemical processes and organ concentration of the key metabolites. AM symbiosis increased root levels of the metabolites in ornithine cycle and unsaturation of fatty acids regardless of water conditions. Root putrescine (Put) concentration was higher in AM than non-inoculated (NM) plants under well-watered conditions; the conversion of Put via diamine oxidase to γ-aminobutyric acid (GABA) occurred in roots of AM plants under drought stress. Leaf concentration of Put, the tricarboxylic acids, and soluble sugars significantly increased in AM plants under drought stress, showing higher values compared to that of NM plants. Moreover, photosystem II efficiency and chlorophyll concentration were higher in AM than NM plants regardless of water status.

Conclusion
Fatty acid- and ornithine cycle-related metabolites along with soluble sugars, Put, and GABA were the key metabolites of AM-mediated regulations in response to drought stress.
From regional society to migrant society: a study on urban transformation in China
Authors: Zhou Daming 
Published: September 2020

AbstractThis paper considers the process of the change in Chinese society—in which its people went from being regional to being migrant in urban communities—and recognizes urban transformation as being based on and an expression of cultural transformation. The transformation of urban communities accompanied the “migration era,” and China’s urban communities, in fact, have been gradually changing from a relatively closed regional society to a diverse and civilized migrant one. The diversification of migrants has caused many problems for cities during their transition, affecting such aspects of social life as the equal enjoyment of public resources, the changes in family and kinship, regional discrimination, the complexity of interpersonal and ethnic relations, etc. The related topics are worthy of further discussion.
Association between vitamin D status and depression in children with chronic liver disease
Authors: Behairy Ola G. , Abo Amer Al Rawhaa A. , Mansour Amira I. , Mohamed Karim I. 
Published: September 2020

AbstractBackgroundDeficiency of vitamin D and depression are commonly occurring in patients with chronic liver diseases. This study aimed to determine the association between 25-OH-vitamin D status and depressive symptoms among children with chronic liver diseases. Eighty children were enrolled and divided into 2 groups: the patients’ group (60 children with chronic hepatitis) and the control group (20 healthy children). All children have been analyzed for their clinical, biochemical features, histological profile, serum 25-OH-vitamin D levels, and assessment of childhood depression using Arabic form based on Kovacs Children’s Depression Inventory.ResultsSerum level of 25(OH) D was significantly lower in the hepatic group than the control group [17 (5–52) ng/ml, 45 (13–95) ng/ml,p= <0001 respectively]. Depression score was significantly higher in the hepatic group as 30% of the control group had mild depression, while 36.7% of the hepatic group had mild depression, 16.7% had moderate depression, and 10% had severe depression. There was a statistically significant difference between children with depressive symptoms and non-depressive symptoms as regards the level of serum vitamin D as it was lower in children with depressive symptoms [median (range) 17 (5–40) ng/ml, 27.5 (8–52) ng/ml,p= 0.04 respectively]. There were statistically significant differences between the serum level of 25(OH) D and depression as it decreases with increasing severity of depression.ConclusionChildren with chronic liver disease who had depressive symptoms showed significantly lower levels of vitamin D when compared with those without depressive symptoms; also, vitamin D had an inverse correlation with depression scores in these children.
Trends in generalised anxiety disorders and symptoms in primary care: UK population-based cohort study
Authors: Slee April , Nazareth Irwin , Freemantle Nick , Horsfall Laura 
Published: September 2020

BackgroundGeneralised anxiety disorder and symptoms are associated with poor physical, emotional and social functioning and frequent primary and acute care visits. We investigated recent temporal trends in anxiety and related mental illness in UK general practice.AimsThe aims of this analysis are to examine temporal changes in recording of generalised anxiety in primary care and initial pharmacologic treatments.MethodAnnual incidence rates of generalised anxiety diagnoses and symptoms were calculated from 795 UK general practices contributing to The Health Improvement Network (THIN) database between 1998 and 2018. Poisson mixed regression was used to account for age, gender and general practitioner practice. Subsequent pharmacologic treatment was examined.ResultsGeneralised anxiety recording rates increased in both genders aged 18–24 between 2014 and 2018. For women, the increase was from 17.06 to 23.33/1000 person years at risk (PYAR); for men, 8.59 to 11.65/1000 PYAR. Increases persisted for a composite of anxiety and depression (49.74 to 57.81/1000 PYAR for women; 25.41 to 31.45/1000 PYAR for men). Smaller increases in anxiety were seen in both genders age 25–34 and 35–44. Anxiety rates among older patients remained stable, although a composite of anxiety and depression decreased for older women. About half of drug-naïve patients were prescribed anxiety drugs within 1 year following diagnosis. The most common choice was a selective serotonin reuptake inhibitor. Benzodiazepine prescription rate has fallen steadily.ConclusionsWe observed a substantial increase in general practitioner consulting for generalised anxiety and depression recently, concentrated within younger people and in particular women.
Individualized Chemotherapy Benefit Prediction by EndoPredict in Patients With Early Breast Cancer in an Indian Cohort
Authors: Somashekhar S. P. , Zaveri Shabber , Vijay Devanhalli Govinda , Dattatreya Palanki Satya , Kumar Rajeev , Islahi Fatma , Bahl Charu 
Published: September 2020

PURPOSE There are new advancements in the modulation of the treatment of patients with early-stage breast cancer, including the use of several molecular profiling tests to identify or select those patients who require additional adjuvant chemotherapy together with hormonal therapy on the basis of a recurrence score. One such tool is EndoPredict (Myriad Genetics; Salt Lake City, UT), which provides support in clinical decision making. The objective of this analysis was to study the landscape of absolute chemotherapy benefit and the likelihood of recurrence within 5 to 15 years in Indian patients with breast cancer who are undergoing EndoPredict testing. PATIENTS AND METHODS This study included 308 patients with hormone-positive, human epidermal growth factor receptor 2–negative early breast cancer. Their postsurgical blocks were analyzed using the EndoPredict test. The MEDCALC statistical tool (Panum Education; Seoul, Republic of Korea) was used to estimate the correlation coefficient and to conduct multiple regression analysis. RESULTS On the basis of the EndoPredict EPclin Risk Score, 52.12% of patients were classified as being in the low-risk category and could safely forgo adjuvant chemotherapy. For every unit increase in the EPclin Risk Score, the percentage increase in absolute chemotherapy benefit was 6.82%. Similarly, the correlation between the likelihood of recurrence within 5 to 15 years and the EPclin Risk Score suggested that there is a 10.34% increase in recurrence for each unit of EPclin Risk Score. CONCLUSION The EPclin Risk Score has good prognostic and predictive power; it also provides the range of chemotherapy benefit for Indian patients.