bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐Rate Dual‐Domain Mass Transfer Model: Elucidating Temperature Effects
Authors: Binder M. , Hahnewald A. , Händel F. , Prommer H. , Engelmann C. , Burghardt D. , Stock P. , Tritschler F. , Liedl R. , Walther M. 
Published: March 2021

AbstractIn this study, the influence of varying temperatures on the transport behavior of conservative solutes in heterogeneous porous media has been investigated. Column flow experiments employing potassium bromide as tracer were conducted at four temperature levels (3°C, 10°C, 20°C, and 30°C) and the measured electrical conductivity (EC) signal was interpreted through inverse modeling. Additional experiments were performed with deuterium‐enriched water at 10°C and 30°C. For those experiments, deuterium isotope ratios were analyzed alongside anion and cation concentrations. Obtained EC‐based breakthrough curves showed measurable differences in both the observed peak values and tailing intensities that could be clearly attributed to variations in the experimental temperatures. The EC‐based results were further corroborated by the measured isotope ratios and corresponding anion/cation concentrations, although measured differences were less pronounced. The model‐based interpretation of the results employed the standard advection‐dispersion equation as well as three alternative variants that were all based on the single‐rate dual‐domain mass transfer (DDMT) approach, but embracing varying coupling intensities between the experiments. For all variants transport parameters were determined for EC, bromide, and deuterium, respectively. The estimated ranges of the transport parameters all point toward a direct correlation between the effective DDMT rates and the experimental temperature. The observed correlation directly follows the Arrhenius relationship, but is weaker than the one describing the temperature dependence of the molecular diffusion coefficients, therefore pointing to a contribution of non‐diffusive components.
Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells
Authors: Yasuda Tomoharu , Saito Yuichi , Ono Chisato , Kawata Kazuhiko , Baba Akemi , Baba Yoshihiro 
Published: March 2021

AbstractThe Cre/loxP system is a powerful tool for generating conditional gene knockout (KO) mice and elucidate gene function in vivo. CD19-Cre and Mb1-iCre transgenic mice are commonly used for generating B cell-specific KO mice and investigate the development, as well as the physiological and pathophysiological roles of B cells. However, the CD19-Cre line low efficiency and the Mb1-iCre line occasional ectopic recombination represent challenges for their use. Thus, we developed a CD19-codon-improved Cre (CD19-iCre) knock-in mouse with the T2A-iCre sequence inserted into the Cd19 locus, just before the stop codon. The CD19-iCre mice were compared with existing models, crossed with the Rosa26-EYFP reporter mice, and their recombination activity in B cells carrying different Cre alleles was assessed. CD19-iCre mice showed more effective Cre recombination in the early B cell developmental stages compared with the CD19-Cre mice. The efficiencies of the CD19-iCre and Mb1-iCre lines were similar; however, the B lineage-specific recombination was more stringent in the CD19-iCre line. Furthermore, the utility value of the CD19-iCre model was superior than that of the CD19-Cre mice regarding deletion efficiency in IL10-floxed mice. Thus, the CD19-iCre line is a valuable tool for highly efficient gene targeting specific to the B cell compartment.
Incidence rate of congenital scoliosis estimated from a nationwide health insurance database
Authors: Kwon Ji-Won , Chae Hyun Wook , Lee Hye Sun , Kim Sinae , Sung Sahyun , Lee Soo Bin , Moon Seong-Hwan , Lee Hwan-Mo , Lee Byung Ho 
Published: March 2021

AbstractTo investigate the epidemiology of congenital scoliosis (CS) and treatment trends. An age-matched, nationwide, population-based study was conducted using the National Health Insurance and Health Insurance Review and Assessment databases from 2010 to 2015. Data regarding the diagnosis and treatment of scoliosis were extracted using International Classifications of Diseases, 10th revision codes. The age-matched normal population was determined from the Korean Statistical Information Service database. We analyzed the incidence rate of CS according to age and sex, as well as the proportion of surgically treated patients. A total of 1664 patients (aged 0–19 years) were diagnosed with CS. The overall average incidence rate of CS over the 5-year period was 3.08 per 100,000 persons, with the highest and second highest rates at 0 years and 12–16 years of age, respectively. The incidence rate stratified by age ranged from 1.5 to 20.1 per 100,000 persons among the age-matched normal population, with peaks at 0 years of age and the second growth spurt in adolescence (12–16 years for males; 10–14 years for females). Anterior surgery was rarely performed; posterior surgery was performed in 92 patients (5.5% of all patients), with the highest prevalence (56.5%) in patients diagnosed at 10–14 years of age. The overall average incidence rate of CS over a 5-year period was 3.08 per 100,000 persons. Only 5.5% of patients underwent surgery within 5 years after the initial diagnosis.
NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer
Authors: Pappas Kyrie , Martin Tiphaine C. , Wolfe Andrew L. , Nguyen Christie B. , Su Tao , Jin Jian , Hibshoosh Hanina , Parsons Ramon 
Published: March 2021

AbstractDownregulation of the PTEN tumor suppressor transcript is frequent in breast cancer and associates with poor prognosis and triple-negative breast cancer (TNBC) when comparing breast cancers to one another. Here we show that in almost all cases, when comparing breast tumors to adjacent normal ducts, PTEN expression is decreased and the PRC2-associated methyltransferase EZH2 is increased. We further find that when comparing breast cancer cases in large cohorts, EZH2 inversely correlates with PTEN expression. Within the highest EZH2 expressing group, NOTCH alterations are frequent, and also associate with decreased PTEN expression. We show that repression of PTEN occurs through the combined action of NOTCH (NOTCH1 or NOTCH2) and EZH2 alterations in a subset of breast cancers. In fact, in cases harboring NOTCH1 mutation or a NOTCH2 fusion gene, NOTCH drives EZH2, HES-1, and HEY-1 expression to repress PTEN transcription at the promoter, which may contribute to poor prognosis in this subgroup. Restoration of PTEN expression can be achieved with an EZH2 inhibitor (UNC1999), a γ-secretase inhibitor (Compound E), or knockdown of EZH2 or NOTCH. These findings elucidate a mechanism of transcriptional repression of PTEN induced by NOTCH1 or NOTCH2 alterations, and identifies actionable signaling pathways responsible for driving a large subset of poor-prognosis breast cancers.
Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A
Authors: Boutary Suzan , Caillaud Marie , El Madani Mévidette , Vallat Jean-Michel , Loisel-Duwattez Julien , Rouyer Alice , Richard Laurence , Gracia Céline , Urbinati Giorgia , Desmaële Didier , Echaniz-Laguna Andoni , Adams David , Couvreur Patrick , Schumacher Michael , Massaad Charbel , Massaad-Massade Liliane 
Published: March 2021

AbstractCharcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA.
Tidal surface states as fingerprints of non-Hermitian nodal knot metals
Authors: Zhang Xiao , Li Guangjie , Liu Yuhan , Tai Tommy , Thomale Ronny , Lee Ching Hua 
Published: March 2021

AbstractNon-Hermitian nodal knot metals (NKMs) contain intricate complex-valued energy bands which give rise to knotted exceptional loops and new topological surface states. We introduce a formalism that connects the algebraic, geometric, and topological aspects of these surface states with their parent knots. We also provide an optimized constructive ansatz for tight-binding models for non-Hermitian NKMs of arbitrary knot complexity and minimal hybridization range. Specifically, various representative non-Hermitian torus knots Hamiltonians are constructed in real-space, and their nodal topologies studied via winding numbers that avoid the explicit construction of generalized Brillouin zones. In particular, we identify the surface state boundaries as “tidal” intersections of the complex band structure in a marine landscape analogy. Beyond topological quantities based on Berry phases, we further find these tidal surface states to be intimately connected to the band vorticity and the layer structure of their dual Seifert surface, and as such provide a fingerprint for non-Hermitian NKMs.
Clinical Analysis of Primary Nephrotic Syndrome Complicated by
Plastic Bronchitis in Children
Authors: Jia Shi-lei , Ni Fen-fen , Ma Yi-jiao , Wu Yu-hui , Ma Wei-ke , gao Xiao-jie 
Published: March 2021

Abstract
Objective To summarize the clinical features of primary nephrotic
syndrome (PNS) complicated by plastic bronchitis (PB) in children to provide
guidance for treatment.
Methods We conducted a retrospective review of the clinical data of
25 children hospitalized with NS complicated by PB in our Hospital between
10/2016 and 03/2019, and summarized the clinical
manifestations, imaging and fiberoptic bronchoscopy (FOB) examinations,
treatment course and outcome of them.
Results 1). The 25 children, with a nephrotic syndrome (NS) course of
one to 36 months, were all diagnosed with PB after FOB, among which 8 cases
(32%) had respiratory failure and required ventilatory support. All
of them started with respiratory symptoms such as fever and cough, and then
suffered from dyspnea and progressive aggravation after 1–3 day(s)
of onset, with rapid occurrence of bidirectional dyspnea and even
respiratory failure in severe cases. 2). Laboratory test for pathogens:
influenza A virus H1N1 (11 cases), influenza B virus (9 cases), adenovirus
(3 cases) and mycoplasma pneumoniae (2 cases). There was no statistically
significant difference (P>0.05) between children with common NS
complicated by influenza virus (IV) infection (not accompanied by dyspnea)
and those with kidney disease who developed PB in the white blood cell
count, lymphocyte count, the inflammatory biomarkers C-reactive protein
(CRP), procalcitonin (PCT) and humoral immunity (IgG level), yet the total
IgG level was found significantly higher and the blood albumin level lower
in the latter (P<0.05). 3). The 25 children were all examined with
the FOB and treated with lavage, 15 of which had typical bronchial tree-like
casts and 10 broken and stringy casts. Based on histopathological
classification, all children were of Type I. 4). Twenty children
(80%) with influenza were administered the antiviral drug
Oseltamivir, 20 (80%) were treated with antibiotics, oral hormones
were replaced with the same dosage of intravenous Methylprednisolone for 5
cases (20%), and 20 (80%) were intravenously administered
gamma globulins (400–500 mg/kg x 3 days). These children
showed a remarkable improvement after treatment and there were no
deaths.
Conclusion NS children are at high risk of influenza virus infection.
Children with a severe case of NS are more susceptible to PB. If symptoms
like shortness of breath, wheezing and progressive bidirectional dyspnea
occur, FOB examination and lavage treatment should be performed as early as
possible. Hyper-IgE-emia and hypoproteinemia may be the high risk factors
for PNS complicated by PB in children.
Veränderungen der Hepatitis-C-Virus-Genotyp-1a/1b-Verteilung zwischen 2004 und 2018 in Deutschland – eine Analyse von 17093 Patienten aus verschiedenen Real-World-Registern
Authors: Simon Karl-Georg , Serfert Yvonne , Buggisch Peter , Mauss Stefan , Boeker Klaus H.W. , Klinker Hartwig , Müller Tobias , Merle Uta , Hüppe Dietrich , Manns Michael P. , Wedemeyer Heiner 
Published: March 2021

Zusammenfassung
Einleitung Der Hepatitis C Genotyp 1 ist der häufigste Genotyp in West- und Zentraleuropa. In dieser Arbeit werden die Veränderungen der Baselinecharakteristika von 17 093 HCV-Patienten mit Genotyp 1a/1b, die im Zeitraum 2004–2018 in Deutschland antiviral therapiert wurden, analysiert. Es wurden insgesamt 5 Zeiträume betrachtet: (i) 2004–2007, (ii) 2008–2010, (iii) 2010–2013, (iv) 2014–2016, (v) 2017–2018.
Methoden Die vorliegende Analyse basiert auf 5 deutschlandweit durchgeführten nicht-interventionellen Registern und umfasst Daten von Patienten, die mit dem HCV-GT1a und HCV-GT1b infiziert waren und zwischen 2004 und 2018 dokumentiert wurden [ML17071, ML19464, ML21645, ML25724 (Peginterferon alfa-2a® non-interventional study (PAN)) und dem Deutschen Hepatitis-C-Register (DHC-R)].
Ergebnisse Im Untersuchungszeitraum (2004–2018) hatten 7662 Patienten eine HCV-GT1a- und 9431 Patienten eine HCV-GT-1b-Infektion. GT1a-Patienten waren im Vergleich zu GT1b-Patienten jünger (46,5 Jahre vs. 51,2 Jahre) und häufiger männlich (70 % vs. 52 %). Drogenkonsum in der Vorgeschichte oder derzeit war im Untersuchungszeitraum häufiger bei GT1a-Patienten mit höchster Frequenz im aktuellsten Zeitraum (2017–2018; 44 % GT1a, 10 % GT1b). Metabolische Komorbiditäten wie Übergewicht und Diabetes mellitus waren häufiger bei mit GT1b infizierten Frauen. Der Anteil des Genotyps 1a nahm von 34 % (Zeitraum 2004–2007) auf ca. 50 % (Zeitraum 2017–2018) relevant zu. 2004–2018 zeigte sich ein relevanter Wechsel des GT1a/1b-Quotienten bei Männern (2004–2007: 38 %/63 %; 2017–2018: 59 %/41 %) bei weitgehend konstantem GT1a-Anteil der Frauen von ca. 30 % deutschlandweit über alle 5 untersuchten Zeiträume.Der Anteil der weiblichen Patienten mit GT1a in der Region Ost war im Vergleich zu den anderen 3 Regionen über nahezu alle Zeiträume niedriger, am deutlichsten ausgeprägt 2004–2007: 14 % GT1a vs. 86 % GT1b.
Zusammenfassung Im untersuchten Zeitraum (2004–2018) zeigte sich ein relevanter Anstieg der Genotyp-1a-Infektion bei Männern, nicht bei Frauen, assoziiert mit Drogenkonsum. Die Daten zeigen eine grundlegende Änderung in der HCV-Epidemiologie in Deutschland an, die Konsequenzen für das Therapiemanagement und die allgemeine Versorgung der Hepatitis-C-Patienten haben.
First German Guideline on Diagnostics and Therapy of Clinically Non-Functioning Pituitary Tumors
Authors: Deutschbein Timo , Jaursch-Hancke Cornelia , Knappe Ulrich J. , Saeger Wolfgang , Flitsch Jörg , Bojunga Jörg , Buchfelder Michael , Ditzen Beate , Gerlach Rüdiger , Gertzen Elfriede , Honegger Jürgen , Horstmann Gerhard A. , Koch Arend , Kreitschmann-Andermahr Ilonka , Kunz Mirjam , Lagrèze Wolf A. , Nicolay Nils H. , Paulus Werner , Reincke Martin , Schmidt Manuel A. , Weber Matthias M. , Wilhelm Helmut , Fassnacht Martin 
Published: March 2021

AbstractAlthough non-functioning pituitary tumors are frequent, diagnostic and therapeutic concepts are not well standardized. We here present the first German multidisciplinary guideline on this topic. The single most important message is to manage the patients by a multidisciplinary team (consisting at least of an endocrinologist, a neurosurgeon, and a (neuro-) radiologist). The initial diagnostic work-up comprises a detailed characterization of both biochemical (focusing on hormonal excess or deficiency states) and morphological aspects (with magnetic resonance imaging of the sellar region). An ophthalmological examination is only needed in presence of symptoms or large tumors affecting the visual system. Asymptomatic, hormonally inactive tumors allow for a 'wait and scan' strategy. In contrast, surgical treatment by an experienced pituitary surgeon is standard of care in case of (impending) visual impairment. Therapeutic options for incompletely resected or recurrent tumors include re-operation, radiotherapy, and observation; the individual treatment plan should be developed multidisciplinary. Irrespective of the therapeutic approach applied, patients require long-term follow-up. Patient with larger pituitary tumors or former surgery/radiotherapy should be regularly counseled regarding potential symptoms of hormonal deficiency states.
Thymoquinone with Metformin Decreases Fasting, Post Prandial Glucose, and HbA1c in Type 2 Diabetic Patients
Authors: Ali Shoukath M. , Chen Paul , Sheikh Saifuddin , Ahmad Ateeq , Ahmad Moghis , Paithankar Mahesh , Desai Brijesh , Patel Piyush , Khan Mujtaba , Chaturvedi Alok , Patel Ronak , Panchal Dharmendra T. , Shah Kuntal , Chavda Vipul , Saboo Banshi D. , Patel Alpesh , Ahmad Imran 
Published: March 2021

AbstractObjective Antihyperglycemic activity of Thymoquinone (TQ) was evaluated in diabetic mouse model and patients.Methods TQ (50 mg/kg) was orally administered daily for 21 days in combination with metformin in diabetic mice and a reduction on blood glucose level was monitored. In human, a 90-day randomized study was carried out in 60 Type 2 Diabetes mellitus patients to evaluate safety and efficacy of TQ administration with metformin in a 3-arm study. Patients in arm 1 (T1) received 1 tablet of metformin SR 1000 mg and 1 tablet of TQ 50 mg once daily. The second arm (T2) patients received 1 tablet of metformin SR 1000 mg and 2 tablets of TQ 50 mg once daily. Patients in arm 3 (R) received 1 tablet of metformin SR 1000 mg only.Results The diabetic mice treated with combination of TQ and metformin showed significant decrease in blood sugar compared to those treated with only metformin. In patients who completed the study, the glycated hemoglobin (HbA1c) values in T1, T2 and R decreased after 3 months from 7.2, 7.2 and 7.3 to 6.7, 6.8, and 7.1, respectively. A greater reduction in Fasting Blood Glucose and Post Prandial Blood Glucose was also observed in T1 and T2 arms compared to R.Conclusion At dose levels of 50 and 100 mg of TQ combined with a daily dose of 1000 mg Metformin demonstrated a reduction in the levels of HbA1c and blood glucose compared to the standard treatment of diabetic patients with metformin alone.
Synthesis of Unsymmetrically Substituted Tetraphenylenes through Palladium-Catalyzed C(sp2)–H Activation
Authors: Zhang Yanghui , Wan Bin 
Published: March 2021

AbstractAn efficient protocol for the palladium-catalyzed cross-coupling reaction of 2-iodobiphenyls with biphenylene has been developed through C–H activation. The reaction provides a simple and efficient method for the synthesis of unsymmetrically substituted tetra­phenylenes.
Epidemiological Study of Patients with Spinal Cord Injury Treated in POLEM, a Specialized Clinic in São Paulo State – Brazil
Authors: Lopes José Eduardo de Andrade , Santos Karl Alex Patteis dos , Machado Caroline da Costa , Borges Meire Cristina , Coelho Eder Ferreira , Simões Ìris Lino Kemp , Pereira Ivone Mara , Dalera Mariele Torricelli Brunelli , Bertazini Talita Schneider de Camargo , Lopes José Eduardo de Andrade 
Published: March 2021

Abstract
Objective To analyze the epidemiological profile of patients with spinal cord injury treated at POLEM – Associação de Apoio às Pessoas com Lesão Medular (Association for Supporting People with Spinal Cord Injury).
Method The population studied comprised 113 patients with spinal cord injury, of traumatic or nontraumatic etiology, and the data obtained were compared with those of other institutions.
Results Of the 113 patients, 70.8% were male and 29.2% female. Traumatic lesions were responsible for 54% of the patients, and nontraumatic for 46%. Of the patients with traumatic injury, 90.2% were male, the main cause being traffic accidents. In nontraumatic lesions, women were the most affected, 51.9%; and dysraphism and myelitis were the main causes (31% and 21%, respectively).
Conclusion The results showed an important incidence of spinal cord injury due to trauma, mainly affecting young individuals of productive age and low educational level, representing high economic and social costs. The data found in the present study are similar to those of other studies performed in our country.
Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients
Authors: Sweeney Joseph M. , Barouqa Mohammad , Krause Gregory J. , Gonzalez-Lugo Jesus D. , Rahman Shafia , Gil Morayma Reyes 
Published: March 2021

AbstractThe causes of coagulopathy associated with coronavirus disease 2019 (COVID-19) are poorly understood. We aimed to investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with balanced distribution of survivors and nonsurvivors. Patients who died had significantly lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, significantly elevated lactate dehydrogenase levels, significantly increased shistocyte/RBC fragment counts, and significantly elevated VWF antigen and activity levels compared with patients discharged alive. These biomarkers correlate with markedly elevated D-dimers. Additionally, only 30% of patients who had an ADAMTS13 activity level of less than 43% on admission survived, yet 60% of patients survived who had an ADAMTS13 activity level of greater than 43% on admission. In conclusion, COVID-19 may present with low ADAMTS13 activity in a subset of hospitalized patients. Presence of schistocytes/RBC fragment and elevated D-dimer on admission may warrant a work-up for ADAMTS13 activity and VWF antigen and activity levels. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of treatments aimed at prevention and/or amelioration of microangiopathy in COVID-19.