bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational diffusion model to study antibody transport within reconstructed tumor microenvironments
Authors: Cartaxo Ana Luísa , Almeida Jaime , Gualda Emilio J. , Marsal Maria , Loza-Alvarez Pablo , Brito Catarina , Isidro Inês A. 
Published: November 2020

Abstract
Background
Antibodies revolutionized cancer treatment over the past decades. Despite their successfully application, there are still challenges to overcome to improve efficacy, such as the heterogeneous distribution of antibodies within tumors. Tumor microenvironment features, such as the distribution of tumor and other cell types and the composition of the extracellular matrix may work together to hinder antibodies from reaching the target tumor cells. To understand these interactions, we propose a framework combining in vitro and in silico models. We took advantage of in vitro cancer models previously developed by our group, consisting of tumor cells and fibroblasts co-cultured in 3D within alginate capsules, for reconstruction of tumor microenvironment features.

Results
In this work, an experimental-computational framework of antibody transport within alginate capsules was established, assuming a purely diffusive transport, combined with an exponential saturation effect that mimics the saturation of binding sites on the cell surface. Our tumor microenvironment in vitro models were challenged with a fluorescent antibody and its transport recorded using light sheet fluorescence microscopy. Diffusion and saturation parameters of the computational model were adjusted to reproduce the experimental antibody distribution, with root mean square error under 5%. This computational framework is flexible and can simulate different random distributions of tumor microenvironment elements (fibroblasts, cancer cells and collagen fibers) within the capsule. The random distribution algorithm can be tuned to follow the general patterns observed in the experimental models.

Conclusions
We present a computational and microscopy framework to track and simulate antibody transport within the tumor microenvironment that complements the previously established in vitro models platform. This framework paves the way to the development of a valuable tool to study the influence of different components of the tumor microenvironment on antibody transport.
Utilization of different MurNAc sources by the oral pathogen Tannerella forsythia and role of the inner membrane transporter AmpG
Authors: Mayer Valentina M. T. , Tomek Markus B. , Figl Rudolf , Borisova Marina , Hottmann Isabel , Blaukopf Markus , Altmann Friedrich , Mayer Christoph , Schäffer Christina 
Published: November 2020

Abstract
Background
The Gram-negative oral pathogen Tannerella forsythia strictly depends on the external supply of the essential bacterial cell wall sugar N-acetylmuramic acid (MurNAc) for survival because of the lack of the common MurNAc biosynthesis enzymes MurA/MurB. The bacterium thrives in a polymicrobial biofilm consortium and, thus, it is plausible that it procures MurNAc from MurNAc-containing peptidoglycan (PGN) fragments (muropeptides) released from cohabiting bacteria during natural PGN turnover or cell death. There is indirect evidence that in T. forsythia, an AmpG-like permease (Tanf_08365) is involved in cytoplasmic muropeptide uptake. In E. coli, AmpG is specific for the import of N-acetylglucosamine (GlcNAc)-anhydroMurNAc(−peptides) which are common PGN turnover products, with the disaccharide portion as a minimal requirement. Currently, it is unclear which natural, complex MurNAc sources T. forsythia can utilize and which role AmpG plays therein.

Results
We performed a screen of various putative MurNAc sources for T. forsythia mimicking the situation in the natural habitat and compared bacterial growth and cell morphology of the wild-type and a mutant lacking AmpG (T. forsythia ΔampG). We showed that supernatants of the oral biofilm bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, and of E. coli ΔampG, as well as isolated PGN and defined PGN fragments obtained after enzymatic digestion, namely GlcNAc-anhydroMurNAc(−peptides) and GlcNAc-MurNAc(−peptides), could sustain growth of T. forsythia wild-type, while T. forsythia ΔampG suffered from growth inhibition. In supernatants of T. forsythia ΔampG, the presence of GlcNAc-anhMurNAc and, unexpectedly, also GlcNAc-MurNAc was revealed by tandem mass spectrometry analysis, indicating that both disaccharides are substrates of AmpG. The importance of AmpG in the utilization of PGN fragments as MurNAc source was substantiated by a significant ampG upregulation in T. forsythia cells cultivated with PGN, as determined by quantitative real-time PCR. Further, our results indicate that PGN-degrading amidase, lytic transglycosylase and muramidase activities in a T. forsythia cell extract are involved in PGN scavenging.

Conclusion
T. forsythia metabolizes intact PGN as well as muropeptides released from various bacteria and the bacterium’s inner membrane transporter AmpG is essential for growth on these MurNAc sources, and, contrary to the situation in E. coli, imports both, GlcNAc-anhMurNAc and GlcNAc-MurNAc fragments.
AChE-activity in critically ill patients with suspected septic encephalopathy: a prospective, single-centre study
Authors: Zujalovic Benedikt , Mayer Benjamin , Hafner Sebastian , Balling Florian , Barth Eberhard 
Published: November 2020

Abstract
Background
Up to 70% of septic patients develop a diffuse brain dysfunction named “septic associated encephalopathy” which is often solely based on clinical impressions. However, the diagnosis of septic associated encephalopathy is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity. Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients.

Methods
In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed.

Results
About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days.

Conclusion
Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms.

Trial registration
Retrospectively registered at German Clinical Trials Register, registration number DRKS00020542, date of registration: January 27, 2020.
“Standing on common ground” - a qualitative study of self-management support for patients with multimorbidity in primary health care
Authors: Freilich Joel , Nilsson Gunnar H. , Ekstedt Mirjam , Flink Maria 
Published: November 2020

Abstract
Background
Multimorbidity, the co-existence of two or more chronic conditions in an individual, is present in most patients over 65 years. Primary health care (PHC) is uniquely positioned to provide the holistic and continual care recommended for this group of patients, including support for self-management. The aim of this study was to explore professionals’, patients’, and family caregivers’ perspectives on how PHC professionals should support self-management in patients with multimorbidity. This study also includes experiences of using telemedicine to support self-management.

Methods
A mixed qualitative method was used to explore regular self-management support and telemedicine as a tool to support self-management. A total of 42 participants (20 physicians, 3 registered nurses, 12 patients, and 7 family caregivers) were interviewed using focus group interviews (PHC professionals), pair interviews (patients and family caregivers), and individual interviews (registered nurses, patients, and family caregivers). The study was performed in urban areas in central Sweden and rural areas in southern Sweden between April 2018 and October 2019. Data were analyzed using content analysis.

Results
The main theme that emerged was “Standing on common ground enables individualized support.” To achieve such support, professionals needed to understand their own views on who bears the primary responsibility for patients’ self-management, as well as patients’ self-management abilities, needs, and perspectives. Personal continuity and trustful relationships facilitated this understanding. The findings also indicated that professionals should be accessible for patients with multimorbidity, function as knowledge translators (help patients understand their symptoms and how the symptoms correlated with diseases), and coordinate between levels of care. Telemedicine supported continual monitoring and facilitated patient access to PHC professionals.

Conclusion
Through personal continuity and patient-centered consultations, professionals could collaborate with patients to individualize self-management support. For some patients, this means that PHC professionals are in control and monitor symptoms. For others, PHC professionals play a less controlling role, empowering patients’ self-management. Development and improvement of eHealth tools for patients with multimorbidity should focus on improving the ability to set mutual goals, strengthening patients’ inner motivation, and including multiple caregivers to enhance information-sharing and care coordination.
Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report
Authors: Yu Mei-Hong , Wu Xiao-Xin , Chen Chun-Lei , Tang Song-Jia , Jin Jian-Di , Zhong Cheng-Li , Fu Jing , Shi Jie-Qin , Li Lan-Juan 
Published: November 2020

Abstract
Background
Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial.

Case presentation
A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital.

Conclusions
This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.
Epidemiological and clinical based study on four passages of COVID-19 patients: intervention at asymptomatic period contributes to early recovery
Authors: Zhang Xiaohong , Wang Hailian , Wang Youwei , Lei Yu , Xu Kaiju , Zhang Jie , Han Ying , Zeng Jun , Deng Shaoping , Wang Yi 
Published: November 2020

Abstract
Background
With the worldwide spread of the 2019 novel coronavirus, scarce knowledge is available on the clinical features of more than two passages of patients. Further, in China, early intervention policy has been enacted since February. Whether early intervention contributes to swift recovery is still unknown. Hence, in this study, we focused on the patients from an isolated area, investigated the epidemiological and clinical characteristics of four serial passages of the virus.

Methods
From January 25 to February 29, 2020, all patient data on the SARS-CoV-2 passages in this isolated area were traced, and the patients were grouped according to the passaging of SARS-CoV-2. Clinical characteristics of patients, including laboratory, radiology, treatment and outcomes, were collected and analyzed.

Results
A total of 78 patients with four passages of virus transmission were included in this study. One patient transmitted SARS-CoV-2 to 8 patients (passage 2, P2), who next infected 23 patients (passage 3, P3), and then 46 patients (passage 4, P4). P2 received antiviral treatment when they had symptom, whereas P4 received antiviral treatment during their asymptomatic period. The incubation periods for P2, P3 and P4 patients were 7 days (IQR:2–12), 8 days (IQR:4–13) and 10 days (IQR:7–15), respectively. P2 patients showed lymphocytopenia (0.79 × 109/L), decreased lymphocyte percentages (12.15%), increased white blood cell count (6.51 × 109/L), increased total bilirubin levels (25% of P2 patients), increased C-reactive protein levels (100% of P2 patients) and abnormal liver function. By chest CT scans, all P2 patients (100%), 15 of P3 patients (65.22%) and 16 of P4 patients (34.78%) showed abnormality with typical feature of ground glass opacity. All of P2 patients (100%) received oxygen therapy, and in contrast, 19 of P4 patients (41.3%) received oxygen therapy. Further, significant decreased nucleic acid positive periods was found in P4 group (16 days, IQR: 10–23), compared with that of P2 group (22 days, IQR: 16–27). Moreover, the severity ratios were sharply decreased from 50% (P2 patients) to 4.35% (P4 patients), and the case fatality rate is zero.

Conclusions
Judged from four passages of patients, early intervention contributes to the early recovery of COVID-19 patients.
A life-threatening case of pregnancy-related atypical Haemolytic uremic syndrome and successful treatment with Eculizumab
Authors: Puri Prianka , Hanxhiu Anida , O’Hara Daniel V. , Hsu Danny , Vucak-Dzumhur Mirna 
Published: November 2020

Abstract
Background
Pregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy.

Case presentation
A 27-year-old female of Lebanese descent presented at 36 weeks’ gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent.

Conclusion
This case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy.
Rhabdomyosarcoma in a child with nephrotic syndrome treated with cyclosporine: a case report with literature review
Authors: Wu Huai-Chueh Gem , Cheng Chao-Neng , Chen Jiann-Shiuh , Chiou Yuan-Yow 
Published: November 2020

Abstract
Background
In patients with frequently relapsing nephrotic syndrome, immunosuppressive therapy such as cyclosporine are often required to maintain remission. Cyclosporine has been noted to have tumorgenesis effects. In this case report, we present a child with relapsing nephrotic syndrom developed a rhabdomyosarcoma on her tongue after adout 4 years of continual immunosuppressive therapy.

Case presentation
A 2-year-old female child had nephrotic syndrome (urine protein-creatinine ratio 749.1 mg/mg; blood urea nitrogen 11 mg/dL; serum creatinine 0.3 mg/dL; and serum albumin 1.8 g/dL.) Proteinuria resolved on treatment with daily prednisolone for 4 weeks at the dose of 45 mg (2.5 mg/kg/day) but recurred with taper from 25 mg/day to 10 mg/day. At least five more episodes of relapse occurred within about a 3-year period. After the third relapse, she was treated with prednisolone and cyclosporine (at initial dose of 50 mg/day [1.7 mg/kg/day]) for immunosuppression. About 4 years after the diagnosis of nephrotic syndrome had been made, an embryonal rhabdomyosarcoma developed on her tongue. The cancer was treated with TPOG-RMS-LR protocol, with vincristine, actinomycin, and cyclophosphamide. Magnetic resonance imaging scan, performed about 3 years after the start of TPOG-RMS-LR therapy, revealed complete remission of the cancer.

Conclusions
Although treatment with cyclosporine cannot be conclusively implicated as the cause the rhabdomyosarcoma in this patient, the association should prompt consideration of its use in the treatment of frequently relapsing nephrotic syndrome in children.
Development of two instruments for assessing maternity health needs: protocol of a clinimetric study
Authors:   ema-Q Group, Paz-Pascual Carmen , Artieta-Pinedo Isabel , Espinosa Maite , Bully Paola 
Published: November 2020

Abstract
Background
There is an unquestionable need to adapt health care to the needs of each woman, to foster her self-confidence and provide her with the autonomy to manage her own maternity. This involves empowering her to choose and face her model of childbirth and childcare responsibly. The range of self-management health needs tests offered by the scientific community at this stage of life is practically non-existent. In this project, we intend to develop and evaluate the validity, reliability and ease of use of two self-administered analysis instruments for: 1.- Needs of women preparing for childbirth and 2.- Identification of alarm symptoms in the puerperium.

Methods
This is a descriptive study of the clinimetric characteristics and usability of two developed self-applied digital instruments for measuring needs in childbirth and postpartum based on the recommendations made in the consensus-based standards for the selection of health measurement instruments (COSMIN) and by the International Test Commission (ITC). The study consists of two phases: 1 - Evaluation of the clinimetric properties of the two instruments, which were developed and then altered, based on their comprehensibility and global usability estimated from a pilot study and 2 - Pre-implementation study.

Discussion
The final product will be two valid, reliable, usable instruments for self-assessment of health needs that are highly acceptable to young couples and the professionals who serve them. They will be a valuable resource for meeting the needs of the population more efficiently and guiding decision-making, and they will contribute to the greater sustainability of the health system.
Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study
Authors: Huang Shiau-Shian , Chen Hsi-Han , Wang Jui , Chen Wei J. , Chen Hsi-Chung , Kuo Po-Hsiu 
Published: November 2020

Abstract
Background
To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities.

Methods
In total, 31,422 depressive inpatients were followed-up from diagnostic onset for more than 10-years. Patients were diagnosed with TRD if their antidepressant treatment regimen was altered ≥two times or if they were admitted after at least two different antidepressant treatments. Multiple Cox regression model were used to determine whether physical and psychiatric comorbidities, psychosis, and prescription patterns increased the risk of TRD by controlling for relevant demographic covariates. Survival analyses were performed for important TRD-associated clinical variables.

Results
Females with depression (21.24%) were more likely to suffer from TRD than males (14.02%). Early anxiety disorders were more commonly observed in the TRD group than in the non-TRD group (81.48 vs. 58.96%, p < 0.0001). Lifetime anxiety disorders had the highest population attributable fraction (42.87%). Seventy percent of patients with multiple psychiatric comorbidities developed TRD during follow-up. Cox regression analysis further identified that functional gastrointestinal disorders significantly increased TRD risk (aHR = 1.19). Higher doses of antidepressants and benzodiazepines and Z drugs in the early course of major depressive disorder increased TRD risk (p < 0.0001).

Conclusion
Our findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with depression associated with elevated TRD risk.