bluuebunny/crossref_metadata_2025_split huggingface dataset:
Letting the patients speak: an in-depth, qualitative research-based investigation of factors relevant to health-related quality of life in real-world patients with hereditary angioedema using subcutaneous C1 inhibitor replacement therapy
Authors: Anderson John , Levy Donald S. , Lumry William , Koochaki Patricia , Lanar Sally , Henry Li H. 
Published: June 2021

Abstract
Background
While many studies of effective hereditary angioedema (HAE) therapy have demonstrated improved health-related quality of life (HRQoL) using validated instruments, specific reasons behind the improved scores have never been investigated using qualitative methods. A non-interventional, qualitative research study was designed to investigate the reasons for improvements in HRQoL while using effective prophylaxis, in this case subcutaneous C1INH (C1INH[SC]) replacement therapy.

Methods
Adult patients with HAE-C1INH type 1 or 2 who had been using C1INH(SC) for ≥ 3 consecutive months were recruited through four HAE specialty practices in the US to participate in a 60-min phone interview performed by a trained qualitative research specialist (ICON plc) using a semi-structured interview guide with open-ended questions developed with the Angioedema Quality of Life (AE-QoL) items in mind. Interview transcripts were analyzed using thematic analysis methods to identify concepts (specific symptoms/impacts) and themes (higher-level categories grouping related concepts). A cross-mapping exercise was performed between interview-identified concepts and items included in the AE-QoL.

Results
Fourteen patients were interviewed and included in the analysis (age range, 28–82 years [mean 47.5 years]; 64% female; 93% white). In 10 interviews, patients mentioned having no or nearly no HAE attacks, no longer feeling limited by HAE, less HAE-related anxiety/worry and depression, an improved ability to travel, fewer emergency room/hospital visits, and ease of administration of C1INH(SC), including not requiring assistance from others. Other commonly expressed concepts included: increased feelings of confidence, independence, optimism, and normalcy; less absence from work/school; better productivity; improved sleep and energy; healthier family relationships; and improved cognition. While all AE-QoL items emerged from patient interviews, a number of identified concepts were not addressed by the AE-QoL, including sensitivity to various potential attack-triggers (e.g., stress/anxiety, sports), attack frequency, not having to cancel social plans, improvements in ability to perform day-to-day tasks, and a lower burden from medical visits.

Conclusions
From these interviews, a large number of common themes and concepts emerged: a greater sense of freedom and normalcy, increased productivity, and improved interpersonal relationships while using convenient and effective prophylaxis. These findings provide insights into real-world experiences and the many facets of HRQoL that are important to patients with HAE-C1INH.
A young girl with chronic isolated cervical lymphadenopathy found to have lupus lymphadenopathy, progressing to develop lupus nephritis: a case report
Authors: Jayawickreme K. P. , Subasinghe S. , Weerasinghe S. , Perera L. , Dissanayaka P. 
Published: June 2021

Abstract
Background
Systemic lupus erythematosus is a rare autoimmune disorder, with the prevalence in Asia ranging from 30 to 50/100,000. The diagnosis of systemic lupus erythematosus is made according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria, and it does not contain lymphadenopathy as diagnostic criteria. However, lupus lymphadenopathy has an estimated prevalence of 5–7% at the onset of disease, and 12–15% at any stage of the disease.

Case presentation
A 19-year-old Sinhalese girl had neck nodules since the age of 5 years, which increased in size and became tender since 1 year. She had alopecia and joint stiffness for 6 months. She presented with a 5-day history of worsening joint pain, fever, and painful, enlarging cervical nodules. She had tender cervical lymphadenopathy, and a vasculitic rash on both lower limbs. She had pancytopenia, an erythrocyte sedimentation rate of 92, positive antinuclear antibody titer, and high anti-double-stranded deoxyribonucleic acid (DNA), with low C3 and C4 complements. She had a high reticulocyte count of 5%, with direct and indirect antiglobulin tests being positive, indicating autoimmune hemolytic anemia. Lymph node biopsy showed moderate reactive follicular hyperplasia, with scattered plasma cells and immunoblasts, with varying degree of coagulative necrosis, suggestive of lupus lymphadenopathy. On immunohistochemistry of the lymph node biopsy, Bcl2 was negative, excluding lymphoma. Contrast-enhanced computed tomography of abdomen and chest was normal with no hepatosplenomegaly or lymphadenopathy. Skin biopsy showed leukocytoclastic vasculitis. Later, with development of generalized edema, she was found to have impaired renal function, and renal biopsy showed lupus nephritis. She was started on hydroxychloroquine, prednisolone, and mycophenolate mofetil, and her symptoms improved and lymphadenopathy regressed.

Conclusion
In the case of cervical lymphadenopathy in a patient with systemic lupus erythematosus, the possibilities of lupus lymphadenopathy, Kikuchi–Fujimoto disease, and lymphoma should all be considered, after excluding secondary infection due to immunosuppression. Histology confirms the differentiation of these pathologies. It is important to differentiate the cause for lymphadenopathy in systemic lupus erythematosus as the outcome and treatment varies. Lupus lymphadenopathy is usually generalized, but isolated cervical lymphadenopathy could also rarely be the first presentation of systemic lupus erythematosus. Lupus lymphadenopathy can be the only presenting feature, and needs a high index in suspecting systemic lupus erythematosus, though it is not included in the diagnostic criteria.
Involvement of catalase and superoxide dismutase in hydrophobic organic solvent tolerance of Escherichia coli
Authors: Doukyu Noriyuki , Taguchi Katsuya 
Published: June 2021

AbstractEscherichia coli strains are generally sensitive to hydrophobic organic solvents such as n-hexane and cyclohexane. Oxidative stress in E. coli by exposure to these hydrophobic organic solvents has been poorly understood. In the present study, we examined organic solvent tolerance and oxygen radical generation in E. coli mutants deficient in reactive oxygen species (ROS)-scavenging enzymes. The organic solvent tolerances in single gene mutants lacking genes encoding superoxide dismutase (sodA, sodB, and sodC), catalase (katE and katG), and alkyl hydroperoxide reductase (ahpCF) were similar to that of parent strain BW25113. We constructed a BW25113-based katE katG double mutant (BW25113∆katE∆katG) and sodA sodB double mutant (BW25113sodA∆sodB). These double-gene mutants were more sensitive to hydrophobic organic solvents than BW25113. In addition, the intracellular ROS levels in E. coli strains increased by the addition of n-hexane or cyclohexane. The ROS levels in BW25113∆katE∆katG and BW25113∆sodA∆sodB induced by exposure to the solvents were higher than that in BW25113. These results suggested that ROS-scavenging enzymes contribute to the maintenance of organic solvent tolerance in E. coli. In addition, the promoter activities of sodA and sodB were significantly increased by exposure to n-hexane.
ADP-ribosyltransferase PARP11 suppresses Zika virus in synergy with PARP12
Authors: Li Lili , Shi Yueyue , Li Sirui , Liu Junxiao , Zu Shulong , Xu Xin , Gao Meiling , Sun Nina , Pan Chaohu , Peng Linan , Yang Heng , Cheng Genhong 
Published: June 2021

Abstract
Background
Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. Type I interferon response to ZIKV infection in host cells suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs).

Methods
The study aims to demonstrate the anti-ZIKV mechanism of PARP11. PARP11 knock out and overexpressing A549 cell lines were constructed to evaluate the anti-ZIKV function of PARP11. PARP11−/−, PARP12−/− and PARP11−/−PARP12−/− HEK293T cell lines were constructed to explain the synergistic effect of PARP11 and PARP12 on NS1 and NS3 protein degradation. Western blotting, immunofluorescence and immunoprecipitation assay were performed to illustrate the interaction between PARP11 and PARP12.

Results
Both mRNA and protein levels of PARP11 were induced in WT but not IFNAR1−/− cells in response to IFNα or IFNβ stimulation and ZIKV infection. ZIKV replication was suppressed in cells expressed PARP11 but was enhanced in PARP11−/− cells. PARP11 suppressed ZIKV independently on itself PARP enzyme activity. PARP11 interacted with PARP12 and promoted PARP12-mediated ZIKV NS1 and NS3 protein degradation.

Conclusion
We identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that it cooperated with PARP12 to enhance ZIKV NS1 and NS3 protein degradation. Our findings have broadened the understanding of the anti-viral function of ADP-ribosyltransferase family members, and provided potential therapeutic targets against viral ZIKV infection.
Existence of a unique weak solution to a non-autonomous time-fractional diffusion equation with space-dependent variable order
Authors: Van Bockstal Karel 
Published: June 2021

AbstractIn this contribution, we investigate an initial-boundary value problem for a fractional diffusion equation with Caputo fractional derivative of space-dependent variable order where the coefficients are dependent on spatial and time variables. We consider a bounded Lipschitz domain and a homogeneous Dirichlet boundary condition. Variable-order fractional differential operators originate in anomalous diffusion modelling. Using the strongly positive definiteness of the governing kernel, we establish the existence of a unique weak solution in$u\in \operatorname{L}^{\infty } ((0,T),\operatorname{H}^{1}_{0}( \Omega ) )$u∈L∞((0,T),H01(Ω))to the problem if the initial data belongs to$\operatorname{H}^{1}_{0}(\Omega )$H01(Ω). We show that the solution belongs to$\operatorname{C} ([0,T],{\operatorname{H}^{1}_{0}(\Omega )}^{*} )$C([0,T],H01(Ω)∗)in the case of a Caputo fractional derivative of constant order. We generalise a fundamental identity for integro-differential operators of the form$\frac{\mathrm{d}}{\mathrm{d}t} (k\ast v)(t)$ddt(k∗v)(t)to a convolution kernel that is also space-dependent and employ this result when searching for more regular solutions. We also discuss the situation that the domain consists of separated subdomains.
Remodeling of the maternal gut microbiome during pregnancy is shaped by parity
Authors: Berry Alexander S. F. , Pierdon Meghann K. , Misic Ana M. , Sullivan Megan C. , O’Brien Kevin , Chen Ying , Murray Samuel J. , Ramharack Lydia A. , Baldassano Robert N. , Parsons Thomas D. , Beiting Daniel P. 
Published: June 2021

Abstract
Background
The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies—referred to as maternal parity—as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans.

Results
Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring “quadrads”—each consisting of one mother sow and three piglets—linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth.

Conclusions
Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants.
Identification of the high-risk area for schistosomiasis transmission in China based on information value and machine learning: a newly data-driven modeling attempt
Authors: Gong Yan-Feng , Zhu Ling-Qian , Li Yin-Long , Zhang Li-Juan , Xue Jing-Bo , Xia Shang , Lv Shan , Xu Jing , Li Shi-Zhu 
Published: June 2021

Abstract
Background
Schistosomiasis control is striving forward to transmission interruption and even elimination, evidence-lead control is of vital importance to eliminate the hidden dangers of schistosomiasis. This study attempts to identify high risk areas of schistosomiasis in China by using information value and machine learning.

Methods
The local case distribution from schistosomiasis surveillance data in China between 2005 and 2019 was assessed based on 19 variables including climate, geography, and social economy. Seven models were built in three categories including information value (IV), three machine learning models [logistic regression (LR), random forest (RF), generalized boosted model (GBM)], and three coupled models (IV + LR, IV + RF, IV + GBM). Accuracy, area under the curve (AUC), and F1-score were used to evaluate the prediction performance of the models. The optimal model was selected to predict the risk distribution for schistosomiasis.

Results
There is a more prone to schistosomiasis epidemic provided that paddy fields, grasslands, less than 2.5 km from the waterway, annual average temperature of 11.5–19.0 °C, annual average rainfall of 1000–1550 mm. IV + GBM had the highest prediction effect (accuracy = 0.878, AUC = 0.902, F1 = 0.920) compared with the other six models. The results of IV + GBM showed that the risk areas are mainly distributed in the coastal regions of the middle and lower reaches of the Yangtze River, the Poyang Lake region, and the Dongting Lake region. High-risk areas are primarily distributed in eastern Changde, western Yueyang, northeastern Yiyang, middle Changsha of Hunan province; southern Jiujiang, northern Nanchang, northeastern Shangrao, eastern Yichun in Jiangxi province; southern Jingzhou, southern Xiantao, middle Wuhan in Hubei province; southern Anqing, northwestern Guichi, eastern Wuhu in Anhui province; middle Meishan, northern Leshan, and the middle of Liangshan in Sichuan province.

Conclusions
The risk of schistosomiasis transmission in China still exists, with high-risk areas relatively concentrated in the coastal regions of the middle and lower reaches of the Yangtze River. Coupled models of IV and machine learning provide for effective analysis and prediction, forming a scientific basis for evidence-lead surveillance and control.

Graphic Abstract
Adult support during childhood: a retrospective study of trusted adult relationships, sources of personal adult support and their association with childhood resilience resources
Authors: Ashton Kathryn , Davies Alisha R. , Hughes Karen , Ford Kat , Cotter-Roberts Andrew , Bellis Mark A. 
Published: June 2021

Abstract
Background
Adverse childhood experiences (ACEs) can affect health and well-being across the life course. Resilience is an individual characteristic that is known to help negate the effect of adversities and potentially transform toxic stress into tolerable stress. Having access to a trusted adult during childhood is critical to helping children build resiliency. Here, we aim to understand the relationship between always having access to trusted adult support and childhood resilience resources, and examine which sources of personal adult support and the number of sources of adult support, best foster childhood resilience.

Methods
A Welsh national cross-sectional retrospective survey (n = 2497), using a stratified random probability sample. Data were collected via face-to-face interviews at participants’ places of residence by trained interviewers. Analyses use chi-square and binary logistic regression methods. Outcome measures were childhood resilience resources, access to an always-available trusted adult, and sources of personal adult support.

Results
Prevalence of access to an always-available trusted adult decreased with increasing number of ACEs from 86.6% of individuals with no ACEs, to 44.4% of those with four or more ACEs (≥ 4). In addition, for those experiencing ≥ 4 ACEs, individuals with no access to a trusted adult were substantially less likely than those with access, to report childhood resilience resources. For example, for individuals with ≥ 4 ACEs, those with access to an always-available trusted adult were 5.6 times more likely to have had supportive friends and 5.7 times more likely to have been given opportunities to develop skills to succeed in life, compared to those with no access to a trusted adult. When looking at sources of personal adult support, resilience levels increased dramatically for those individuals who had either one parent only or two parents as sources of support, in comparison to those without parental support.

Conclusions
Analyses here suggest strong relationships between elements of childhood resilience, constant access to trusted adults and different sources of personal adult support. While the eradication of ACEs remains unlikely, actions to strengthen childhood access to trusted adults may partially ease immediate harms and protect future generations.
The contribution of single-cell analysis of acute leukemia in the therapeutic strategy
Authors: Madaci Lamia , Colle Julien , Venton Geoffroy , Farnault Laure , Loriod Béatrice , Costello Régis 
Published: June 2021

AbstractAfter decades during which the treatment of acute myeloblastic leukemia was limited to variations around a skeleton of cytarabine/anthracycline, targeted therapies appeared. These therapies, first based on monoclonal antibodies, also rely on specific inhibitors of various molecular abnormalities. A significant but modest prognosis improvement has been observed thanks to these new treatments that are limited by a high rate of relapse, due to the intrinsic chemo and immune-resistance of leukemia stem cell, together with the acquisition of these resistances by clonal evolution. Relapses are also influenced by the equilibrium between the pro or anti-tumor signals from the bone marrow stromal microenvironment and immune effectors. What should be the place of the targeted therapeutic options in light of the tumor heterogeneity inherent to leukemia and the clonal drift of which this type of tumor is capable? Novel approaches by single cell analysis and next generation sequencing precisely define clonal heterogeneity and evolution, leading to a personalized and time variable adapted treatment. Indeed, the evolution of leukemia, either spontaneous or under therapy selection pressure, is a very complex phenomenon. The model of linear evolution is to be forgotten because single cell analysis of samples at diagnosis and at relapse show that tumor escape to therapy occurs from ancestral as well as terminal clones. The determination by the single cell technique of the trajectories of the different tumor sub-populations allows the identification of clones that accumulate factors of resistance to chemo/immunotherapy (“pan-resistant clones”), making possible to choose the combinatorial agents most likely to eradicate these cells. In addition, the single cell technique identifies the nature of each cell and can analyze, on the same sample, both the tumor cells and their environment. It is thus possible to evaluate the populations of immune effectors (T-lymphocytes, natural killer cells) for the leukemia stress-induced alteration of their functions. Finally, the single cells techniques are an invaluable tool for evaluation of the measurable residual disease since not only able to quantify but also to determine the most appropriate treatment according to the sensitivity profile to immuno-chemotherapy of remaining leukemic cells.
Facile distribution of an alkaline microenvironment improves human bone marrow mesenchymal stem cell osteogenesis on a titanium surface through the ITG/FAK/ALP pathway
Authors: Wang Chen-Xi , Ma Ting , Wang Ming-Yue , Guo Hou-Zuo , Ge Xi-Yuan , Zhang Yu , Lin Ye 
Published: June 2021

Abstract
Purpose
Osseointegration at the titanium surface-bone interface is one of the key factors affecting the success rate of dental implants. However, the titanium surface always forms a passive oxide layer and impacts bone marrow–derived mesenchymal stem cell (BMSC) osteogenic differentiation after exposure to the atmosphere, which further leads to poor osseointegration. Given that wet storage helps prevent titanium aging and that weakly alkaline conditions stimulate BMSC osteogenic differentiation, the aim of the present study was to explore whether sodium bicarbonate, a well-known hydrogen ion (pH) buffer, forms an alkaline microenvironment on titanium surfaces to promote BMSC osteogenic differentiation.

Material and methods
In this work, sand-blasted and acid-etched (SLA) titanium discs were soaked in 20 mM, 50 mM, 100 mM, and 200 mM sodium bicarbonate at room temperature for 5 min without rinsing. The influence of this surface modification on BMSC adhesion, proliferation, and osteogenic differentiation was measured. Additionally, cellular osteogenic differentiation–associated signaling pathways were evaluated.

Results
We showed that titanium discs treated with sodium bicarbonate created an extracellular environment with a higher pH for BMSCs than the normal physiological value for 5 days, strongly promoting BMSC osteogenic differentiation via the activation of integrin-focal adhesion kinase-alkaline phosphatase (Itg-FAK-ALP). In addition, the proliferation and adhesion of BMSCs were increased after alkaline treatment. These cellular effects were most significant with 100 mM sodium bicarbonate.

Conclusion
The results indicated that the titanium surface treated with sodium bicarbonate improved BMSC osteogenic differentiation mainly by creating an alkaline microenvironment, which further activated the Itg-FAK-ALP signaling pathway.

Clinical relevance
Surfaces modified with 100 mM sodium bicarbonate had the highest initial pH value and thus showed the greatest potential to improve BMSC performance on titanium surfaces, identifying a novel conservation method for dental implants.