bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with a Zika virus envelope domain III protein induces neutralizing antibodies and partial protection against Asian genotype in immunocompetent mice
Authors: Shin Minna , Kim Kiju , Lee Hyo-Ji , Jung Yu-Jin , Park Jeongho , Hahn Tae-Wook 
Published: December 2022

Abstract
Background
Zika virus (ZIKV) is a mosquito-borne flavivirus classified in Flaviviridae family such as dengue (DENV), yellow fever, and West Nile virus. An outbreak of ZIKV infection can pose a major public health risk because the contagion is unpredictable and induces severe pathology such as Guillan-Barre syndrome and neonatal microcephaly. However, an authorized ZIKV vaccine is not yet available, while several vaccine candidates are under development.

Methods
In this study, we constructed a recombinant ZIKV vaccine (Z_EDIII) that includes ZIKV envelope protein domain III using E. coli expression system. Then both humoral and cellular immunity were examined in C57BL/6 (female, 8-weeks-old) mice via Indirect ELISA assay, PRNT, ELISpot and cytokine detection for IFN-γ, TNF-α, and IL-12. In addition, the cross protection against DENV was evaluated in pups from Z_EDIII vaccinated and infected dam.

Results
Mice immunized by Z_EDIII produced a significant amount of ZIKV EDIII-specific and neutralizing antibodies. Together with antibodies, effector cytokines, such as IFN-γ, TNF-α, and IL-12 were induced. Moreover, vaccinated females delivered the adaptive immunity to neonates who are protective against ZIKV and DENV challenge.

Conclusions
This study observed Z-EDIII-induced humoral and cellular immunity that protected hosts from both ZIKV and DENV challenges. The result suggests that our ZIKV EDIII recombinant vaccine has potential to provide a new preventive strategy against ZIKV infection.
Role of the Hippo pathway in liver regeneration and repair: recent advances
Authors: Pibiri Monica , Simbula Gabriella 
Published: December 2022

AbstractAlthough the signaling pathways involved in normal liver regeneration have been well characterized, less has been done for livers affected by chronic tissue damage. These “abnormal livers” have an impaired regenerative response that leads to liver repair and fibrosis. The tumor suppressor Hippo pathway plays a key role in liver regeneration and repair. On this basis, this review discusses recent studies focusing on the involvement of the Hippo signaling pathway during “normal healthy liver regeneration” (i.e., in a normal liver after 2/3 partial hepatectomy) and “abnormal liver regeneration” (i.e., in a liver damaged by chronic disease). This could be an important question to address with respect to new therapies aimed at improving impaired liver regenerative responses. The studies reported here have shown that activation of the Hippo coactivators YAP/TAZ during normal liver regeneration promotes the formation of a new bile duct network through direct BEC proliferation or/and hepatocyte dedifferentiation to HPCs which can trans-differentiate to BECs. Moreover, YAP/TAZ signaling interaction with other signaling pathways mediates the recruitment and activation of Kupffer cells, which release mitogenic cytokines for parenchymal and/or non-parenchymal cells and engage in phagocytosis of cellular debris. In addition, YAP-mediated activation of stellate cells (HSCs) promotes liver regeneration through the synthesis of extracellular matrix. However, in chronically diseased livers, where the predetermined threshold for proper liver regeneration is exceeded, YAP/TAZ activation results in a reparative process characterized by liver fibrosis. In this condition, YAP/TAZ activation in parenchymal and non-parenchymal cells results in (i) differentiation of quiescent HSCs into myofibroblastic HSCs; (ii) recruitment of macrophages releasing inflammatory cytokines; (iii) polarization of macrophages toward the M2 phenotype. Since accumulation of damaged hepatocytes in chronic liver injury represent a significant risk factor for the development of hepatocarcinoma, this review also discussed the involvement of the Hippo pathway in the clearance of damaged cells.
High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network
Authors: Hermine Olivier , Jiang Linmiao , Walewski Jan , Bosly André , Thieblemont Catherine , Szymczyk Michal , Pott Christiane , Salles Gilles , Feugier Pierre , Hübel Kai , Haioun Corinne , Casasnovas René Olivier , Schmidt Christian , Bouabdallah Kamal , Ribrag Vincent , Kanz Lothar , Dürig Jan , Metzner Bernd , Sibon David , Cheminant Morgane , Burroni Barbara , Klapper Wolfram , Hiddemann Wolfgang , Unterhalt Michael , Hoster Eva , Dreyling Martin ,   on behalf of the European Mantle Cell Lymphoma Network
Published: December 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In 2004, the European Mantle Cell Lymphoma (MCL) Network initiated the randomized open-label, phase III MCL Younger trial for first-line treatment of patients with advanced-stage MCL, age < 66 years, comparing an alternating rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone/rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-CHOP/R-DHAP) induction followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation (R-DHAP arm) to R-CHOP with standard myeloablative radiochemotherapy and autologous stem-cell transplantation (R-CHOP arm). After a median follow-up of 10.6 years, the time to treatment failure was still significantly improved in the R-DHAP versus R-CHOP arms (medians 8.4 v 3.9 years, 5-/10-year rates 64%/46% v 41%/25%, P = .038, hazard ratio, 0.59). Median overall survival (OS) was not reached in the R-DHAP arm versus 11.3 years in R-CHOP arm (5-/10-year rates, 76%/60% v 69%/55%, P = .12). The unadjusted OS hazard ratios (0.80 [95% CI, 0.61 to 1.06], P = .12) reached significance when adjusted for Mantle Cell Lymphoma International Prognostic Index (MIPI) and MIPI + Ki-67 (MIPI-c) (0.74; 95% CI, 0.56 to 0.98; P = .038 and .60; 95% CI, 0.41 to 0.87; P = .0066). The incidence of secondary hematologic malignancies tended to be higher in the R-DHAP arm (4.5% v 1.4% at 10 years). With mature long-term data, we confirm the previously observed substantially prolonged time to treatment failure and, for the first time to our knowledge, show an improvement of OS. Some patients with MCL may be cured.
Early Growth Hormone Initiation Leads to Favorable Long-Term Growth Outcomes in Children Born Small for Gestational Age
Authors: Juul Anders , Backeljauw Philippe , Cappa Marco , Pietropoli Alberto , Kelepouris Nicky , Linglart Agnès , Pfäffle Roland , Geffner Mitchell 
Published: December 2022

AbstractContextEarly initiation of growth hormone (GH) therapy is recommended for short children born small for gestational age (SGA); however, real-world data indicate that treatment is often delayed.ObjectiveWe aimed to assess the impact of patient age at GH therapy initiation on long-term growth outcomes and safety in short children born SGA.MethodsAnalysis of pooled data from NordiNet® International Outcome Study (NCT00960128; 469 European clinics) and the ANSWER Program (NCT01009905; 207 US clinics), two large, complementary observational studies. Patients received GH as prescribed by their treating physician. Enrolled patients born SGA were categorized into three groups based on their age at GH treatment initiation: 2 to &lt;4 years, 4 to &lt;6 years, and ≥6 years. Patient characteristics at birth and GH initiation, auxology, and safety data were evaluated.ResultsThe effectiveness analysis (treatment-naïve and prepubertal patients at GH initiation) included 3318 patients: 10.7% aged 2 to &lt;4 years at therapy initiation, 31.6% aged 4 to &lt;6 years, and 57.7% aged ≥6 years. Following 8 years of therapy, the mean improvement in height standard deviation score from baseline was significantly greater in the 2 to &lt;4 years group vs the 4 to &lt;6 years (+2.5 vs +2.2; P = 0.0054) and ≥6 years groups (+2.5 vs +1.7; P &lt; 0.0001). No unexpected safety events were reported.ConclusionEarly initiation of GH therapy in short children born SGA may be an important contributor to height optimization. The data are reassuring regarding the long-term safety of GH therapy in this population.
Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations
Authors: Grigoryan Seda , Nhan Winnie , Zhang Lei , Urban Caitlin , Zhao Lili , Turcu Adina F 
Published: December 2022

Abstract

Context
Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking.

Objective
This study aimed to assess the rates and patterns of PPGL screening among eligible patients.

Methods
We conducted a retrospective review of adults with hypertension seen in outpatient clinics of a large academic center between January 1, 2017, and June 30, 2020. We included patients with treatment-resistant hypertension, hypertension at age &lt; 35 years, and/or adrenal mass(es).

Results
Of 203 535 patients with hypertension identified, 71 088 (35%) met ≥ 1 inclusion criteria, and 2013 (2.83%) were screened for PPGL. Patients screened were younger (56.2 ± 17.4 vs 64.0 ± 17.1 years), more often women (54.1% vs 44.2%), and never-smokers (54.6% vs 47.5%, P &lt; 0.001 for all). The rate of screening was highest in patients with hypertension and adrenal mass(es) (51.7%, vs 3.9% in patients with early-onset hypertension, and 2.4% in those with treatment-resistant hypertension). Multivariable logistic regression showed higher odds ratio (OR) of PPGL screening in women (OR [95% CI]: 1.48 [1.34-1.63]); Black vs White patients (1.35 [1.19-1.53]); patients with adrenal mass(es) (55.1 [44.53-68.15]), stroke (1.34 [1.16-1.54]), dyslipidemia (1.41 [1.26-1.58]), chronic kidney disease (1.40 [1.26-1.56]), and obstructive sleep apnea (1.96 [1.76-2.19]).

Conclusion
PPGL screening is pursued in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with treatment-resistant or early-onset hypertension. Similar to screening for other forms of secondary hypertension, PPGL screening occurs more often after serious complications develop.
Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol
Authors: Newman Connie B , Tobert Jonathan A 
Published: December 2022

AbstractThe discovery of PCSK9 and its role in regulating the low-density lipoprotein (LDL) receptor, and the effect of loss-of-function mutations of its gene, identified it as a therapeutic target in 2006. Fully humanized monoclonal antibodies to PCSK9 (alirocumab and evolocumab) proved effective for lowering LDL cholesterol and subsequently for reducing atherosclerotic events in large outcome trials. Suppressing PCSK9 synthesis via gene silencing using inclisiran, a small interfering RNA, is another approach that effectively reduces LDL cholesterol, and a cardiovascular outcome trial is in progress. These treatments are given subcutaneously on a background of maximally tolerated statin treatment and are long-lasting: dosing is once or twice a month, self-administered, for alirocumab and evolocumab, and every 6 months for inclisiran, in the clinic, with an extra dose at 3 months in the initial year of therapy.These 3 agents produce mean LDL reductions of about 55% with no important adverse effects detectable to date. They are indicated in patients with atherosclerotic vascular disease or familial hypercholesterolemia who cannot achieve LDL cholesterol targets with maximally tolerated statin treatment. Such therapy can produce very low plasma LDL cholesterol and PCSK9, but there is no evidence this is harmful. Introduction into clinical practice has been impeded by economic considerations. The barrier to their use has not been scientific or medical, but rather the impact on healthcare resources. Prices have been reduced, but whether they are now cost-effective varies from country to country.
Association of KATP Variants With CMD and RAP in CAD Patients With Increased Serum Lipoprotein(a) Levels
Authors: Pei Jingxian , Liu Cheng , Yang Zhengxia , Lai Yanxian , Zhang Shenghui , Guan Tianwang , Shen Yan 
Published: December 2022

AbstractContextRefractory angina pectoris (RAP) is a specific subtype of coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] and its induced coronary microvascular dysfunction (CMD) play an important role in pathogenesis of RAP, but its metabolism was mostly genetically determined. The adenosine triphosphate (ATP)-sensitive potassium channel (KATP) is involved in lipid metabolism and microvascular homeostasis and becomes a promising target for the management of Lp(a) and its related RAP.ObjectiveTo investigate associations of KATP variants with hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.Design, Patients, SettingsA total of 1148 newly diagnosed patients with CAD were prospectively selected and divided into control (Lp(a) &lt; 180 mg/dL) and case (Lp(a) ≥ 180 mg/dL, hyperlipoprotein(a)emia) group.Methods9 KATP variants were genotyped by MassARRAY system. The expression profile of exosome-derived microRNAs (exo-miRs) was identified by next-generation sequencing, and the expression levels of differentially expressed exo-miRs were evaluated by quantitative RT-PCR in verification cohort.ResultsThree KATP variants were associated with increased risk of hyperlipoprotein(a)emia in patients with CAD as follows: rs2285676 (AA + GA genotype, adjusted odds ratio [OR] = 1.44; 95% CI, 1.10-1.88; P = 0.008), rs1799858 (CC genotype, adjusted OR = 1.33; 95% CI, 1.03-1.73; P = 0.030), and rs141294036 (CC genotype, adjusted OR = 1.43; 95% CI, 1.10-1.87; P = 0.008). Only rs141294036 was associated with increased risk of CMD (CC genotype, adjusted OR = 1.62; 95% CI, 1.23-2.13; P = 0.001), and further with increased RAP risk (CC genotype, adjusted hazard ratio = 2.05; 95% CI, 1.22-3.43; P = 0.007) after median follow-up of 50.6 months. Between the 2 genotypes of rs141294036, 152 exo-miRs were significantly differentially expressed, but only 10 exo-miRs (miR-7110-3p, miR-548az-5p, miR-214-3p, let-7i-5p, miR-218-5p, miR-128-3p, miR-378i, miR-625-3p, miR-128-1-5p, and miR-3187-3p) were further confirmed in patients with RAP with hyperlipoprotein(a)emia and CMD.ConclusionKATP rs141294036 may serve a potential genetic marker for hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.
Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage
Authors: Roethlisberger Michel , Aghlmandi Soheila , Rychen Jonathan , Chiappini Alessio , Zumofen Daniel W. , Bawarjan Schatlo , Stienen Martin N. , Fung Christian , D'Alonzo Donato , Maldaner Nicolai , Steinsiepe Valentin K. , Corniola Marco V. , Goldberg Johannes , Cianfoni Alessandro , Robert Thomas , Maduri Rodolfo , Saliou Guillaume , Starnoni Daniele , Weber Johannes , Seule Martin A. , Gralla Jan , Bervini David , Kulcsar Zsolt , Burkhardt Jan-Karl , Bozinov Oliver , Remonda Luca , Marbacher Serge , Lövblad Karl-Olof , Psychogios Marios , Bucher Heiner C. , Mariani Luigi , Bijlenga Philippe , Blackham Kristine A. , Guzman Raphael 
Published: December 2022

BACKGROUND:
Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated.

OBJECTIVE:
To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge.

METHODS:
Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm.

RESULTS:
This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke.

CONCLUSION:
Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.
THE ISSUE OF NETWORK INTERACTION IN THE EDUCATIONAL PROCESS
Authors: Isaikina Maria A. , Nedogreeva G. Natalia , Pikulik Olga V. 
Published: December 2022

Purpose. The article discusses the issues related to the organization of network interaction in the educational process. The purpose of the work is to study the concepts of “interaction” and “network interaction” provided by scientists who have studied this topic, as well as to determine authors’ definition.
Methods. The authors conduct a review of the literature sources on the issue under study as well as use methods of comparative analysis.
Results. The network interaction between teachers and students is a social, psychological and pedagogical phenomenon. It improves students’ skills of self-consciousness, self-organization and self-assessment. Being a collaborative educational activity, it is a tool for students’ development and self-development. The use of remote technologies and possibilities of communication resources contributes to the growth of students’ informational culture.
Assessment of stress load and its causes among dental students
Authors: Marchewka Wojciech , Kluczewska Monika , Ciszek Karol , Zygmunt Marianna , Popiołek Lech , Marchewka Jakub , Kopeć Grzegorz 
Published: December 2022

Cel pracyCelem pracy była ocena poziomu stresu wśród studentów kierunku lekarsko-dentystycznego, scharakteryzowanie czynników go wywołujących oraz określenie, którzy studenci są najbardziej podatni na stres.MetodaDo przeprowadzenia badania zostały wykorzystane dwa uznane międzynarodowe, niezależne i zwalidowane na język i warunki polskie kwestionariusze. Były to Perceived Stress Scale (PSS-10) oraz Perceived Medical School Stress Instrument (PMSS). Badanie uzyskało zgodę właściwej komisji bioetycznej przy Uniwersytecie Jagiellońskim (nr: 1072.6120.292.2019).WynikiW badaniu wzięło udział 272 studentów ze wszystkich pięciu lat kierunku lekarsko-dentystycznego w Collegium Medicum Uniwersytetu Jagiellońskiego, w tym 197 kobiet i 75 mężczyzn. Ogólny wskaźnik odpowiedzi wyniósł 85%. Łączny wynik PSS-10 dla wszystkich studentów stomatologii wyniósł 22,14 ± 6,65. Wysoki poziom stresu miało 182 (66,91%) respondentów. Studentki były istotnie bardziej zestresowane niż studenci, odpowiednio 22,9 ± 6,51 i 20,12 ± 6,69. Co więcej studenci pierwszego i piątego roku prezentowali najwyższy poziom stresu. Natomiast całkowity wynik PMSS dla wszystkich studentów stomatologii wyniósł 36,84 ± 8,65.WnioskiOgólny poziom stresu wśród polskich studentów stomatologii jest wysoki. Wyniki te sugerują, że usługi wsparcia powinny być szeroko dostępne dla wszystkich studentów stomatologii. Takie usługi powinny być ukierunkowane na szczególne potrzeby mężczyzn i kobiet, studentów stacjonarnych i niestacjonarnych jak i z uwzględnieniem roku studiów.
Exercise addiction symptoms and mental health during the forced exercises deprivation in greatest COVID-19 pandemic restrictions in Poland
Authors: Wyszomirska Julia , Martyniak Ewa , Bąk-Sosnowska Monika , Piekarska-Bugiel Katarzyna , Chwalba Artur , Krzystanek Marek 
Published: December 2022

Cel pracyW pracy opisano związek między nasileniem objawów uzależnienia od ćwiczeń, strategiami behawioralnymi w sytuacji ograniczonych możliwości trenowania a stanem zdrowia psychicznego osób ćwiczących.MetodaW badaniu wzięło udział 391 uczestników, 286 kobiety (73,1%) i 105 mężczyzn (26,9%), w wieku od 18 do 68 lat. Badani po 17-19 dniach barier w rutynowych treningach spowodowanych największymi ograniczeniami COVID-19 w Polsce jednorazowo wypełniali ankietę online. Respondenci wypełniali polskie wersje Exercise Dependence Scale, Oceny Zdrowia Psychicznego (GHQ-28) oraz kwestionariusze umożliwiające zebranie danych demograficznych, klinicznych i dotyczących zachowań związanych z ćwiczeniami.WynikiZmienne związane z uzależnieniem od ćwiczeń i niektóre odnoszące się do zmian behawioralnych są predyktorami zdrowia psychicznego, zwłaszcza w zakresie lęku, bezsenności i objawów somatycznych. Wszystkie wprowadzone zmienne odpowiadały za 27,4% do 43,7% zróżnicowania stanu zdrowia psychicznego badanych, w zależności od podskal GHQ. Łamanie reguł restrykcji przez trening na świeżym powietrzu chroniło przed objawami zaburzeń psychicznych, zwłaszcza w odniesieniu do objawów somatycznych (Beta=-0,23, p<0,001). Indywidualna ocena stresogenności sytuacji była predyktorem wyników we wszystkich podskalach GHQ, najsilniejszym dla objawów lęku i bezsenności (Beta=0,37, p<0,001).WnioskiOsoby z cechami uzależnienia od ćwiczeń są narażone na pogorszenie samopoczucia podczas przymusowej abstynencji. Ponadto subiektywny poziom indukcji stresu w danej sytuacji jest ważną determinantą warunkującą dobrostan psychiczny, zwłaszcza nasilenie objawów depresyjnych. Osoby, które ignorują ograniczenia i oceniają stres jako niski, doświadczają niższych kosztów psychologicznych.