bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 spike antibodies
Authors: Vargas Leonardo , Valdivieso Nicolás , Tempio Fabián , Simon Valeska , Sauma Daniela , Valenzuela Lucía , Beltrán Caroll , Castillo-Delgado Loriana , Contreras-Benavides Ximena , Acevedo Mónica L. , Acevedo Johanna , Gonzalez Rafael I. , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Rosemblatt Mario , Lopez Mercedes , Osorio Fabiola , Bono María Rosa 
Published: June 2022

Abstract
Background
Chile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters.

Methods
We compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and one homologous or heterologous booster through an ELISA assay directed against the ancestral spike protein of SARS-CoV-2. Sera were collected from individuals during the vaccination schedule and throughout the implementation of homologous and heterologous booster programs in Chile.

Results
Our findings demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 spike antibodies than BNT162b2 in a broad age range (median age 42 years; interquartile range (IQR) 27-61). Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher (induction fold BNT162b2: 11.2x; ChAdoX1; 12.4x; CoronaVac: 6.0x) than the responses induced by the homologous scheme. Both homologous and heterologous boosters induced persistent humoral responses (median 122 days, IQR (108-133)), although heterologous boosters remained superior in activating a humoral response after 100 days.

Conclusions
Two doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous and homologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.
Pentraxin-3 as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis
Authors: Wang Guobin , Jiang Chunyan , Fang Junjun , Li Zhitao , Cai Hongliu 
Published: June 2022

Abstract
Background
The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis.

Methods
Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case–control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion.

Results
A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): −1.06 (−1.43, −0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion.

Conclusions
PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.
Resilience is a dirty word: misunderstood, and how we can truly build it
Authors: Tan Mark Z. Y. 
Published: June 2022

AbstractResilience is ubiquitous in everyday speech, academic literature and governmental policies. Yet it seems to have taken a narrow scope in healthcare, confined to individual and psychological resilience. This short essay aims to broaden the understanding of resilience to organisational levels and calls intensivists to take active roles in fostering resilience for their staff. The article explores firstly the background and etymology of resilience. It then challenges current approaches and briefly signposts some current work in the area. Some examples of structural factors which build individual resilience are listed, followed by a call for intensivists to take active roles to build future resilience. The need for interdisciplinary, cross-sectoral and multi-level approaches is vital to build future healthcare resilience, and we intensivists must continue to be advocates for systemic change.
Testicular cancer in mice: interplay between stem cells and endocrine insults
Authors: Kaushik Ankita , Bhartiya Deepa 
Published: June 2022

Abstract
Background
Incidence of type II germ cell tumors (T2GCT) has increased in young men possibly due to fetal/perinatal exposure to estrogenic compounds. Three-fold increased incidence of T2GCT was reported in men exposed in utero to diethylstilbestrol (DES). T2GCT is a development-related disease arising due to blocked differentiation of gonocytes into spermatogonia in fetal testes which survive as germ cell neoplasia in situ (GCNIS) and initiate T2GCT. In our earlier study, T2GCT-like features were observed in 9 out of 10 adult, 100-day-old mice testes upon neonatal exposure to DES (2 μg/pup/day on days 1–5). Neonatal DES exposure affected testicular very small embryonic-like stem cells (VSELs) and spermatogonial stem cells and resulted in infertility, reduced sperm counts and tumor-like changes leading to our postulate that testicular dysgenesis syndrome possibly has a stem cell basis. The present study was undertaken to further characterize testicular tumor in mice testes.

Methods
DES-exposed mice pups (n = 70) were studied on D100 and after 12 months to understand how T2GCT progresses. Besides histological studies, a carefully selected panel of markers were studied by immuno-fluorescence and qRT-PCR.

Results
DES resulted in either atrophied or highly vascularized, big-sized testes and extra-testicular growth was also observed. GCNIS-like cells with big, vacuolated cytoplasm and increased expression of OCT-4, SSEA-1, SCA-1 and CD166 (cancer stem cells marker) along with reduced c-KIT, MVH and PTEN were evident. Global hypomethylation was found associated with altered expression of Dnmts, Igf2-H19 and Dlk-Meg3 imprinted genes along with reduced expression of Ezh2, cell cycle regulator p57KIP2 and Meg3; however, Pten remained unaltered. Increased expression of PCNA and Ki67 was observed in concert with complete lack of SOX-9 suggesting Sertoli cells independent proliferation.

Conclusions
Mouse model for T2GCT is described which will have immense potential to understand cancer initiation, cancer stem cells and also to develop effective therapies in future. T2GCT initiates from tissue-resident, pluripotent VSELs due to their altered epigenome. Neonatal exposure to DES blocks differentiation (spermatogenesis) and VSELs get transformed into CD166 positive cancer stem cells that undergo excessive self-renewal and initiate cancer in adult life challenging existing concept of fetal origin of T2GCT.
Tauroursodeoxycholic acid (TUDCA) improves intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets
Authors: Song Min , Zhang Fenglin , Fu Yiming , Yi Xin , Feng Shengchun , Liu Zhichang , Deng Dun , Yang Qiang , Yu Miao , Zhu Canjun , Zhu Xiaotong , Wang Lina , Gao Ping , Shu Gang , Ma Xianyong , Jiang Qingyan , Wang Songbo 
Published: June 2022

Abstract
Background
Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases. Meanwhile, TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice. However, the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.

Methods
The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms. In vivo, 72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight, and piglets were fed the basal diet with 0 (control, CON) and 200 mg/kg TUDCA for 30 d, respectively. Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected. In vitro, IPEC-J2 cells were subjected to 100 μmol/L TUDCA to explore the possible underlying mechanisms.

Results
Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets, possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity. In addition, TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria, which might contribute to the improved intestinal barrier function. Furthermore, the in-vitro results showed that TUDCA improved the E. coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5 (TGR5) protein expression. However, knockdown of TGR5 and inhibition of myosin light chain kinase (MLCK) pathway abolished the TUDCA-improved epithelial barrier impairment in E. coli-treated IPEC-J2 cells, indicating the involvement of TGR5-MLCK in this process.

Conclusions
These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets, suggesting the potential application of TUDCA in improving gut health in piglet production.
Synergistic interaction of thymol with Piper ribesioides (Piperales: Piperaceae) extracts and isolated active compounds for enhanced insecticidal activity against Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Kumrungsee Nutchaya , Dunkhunthod Benjawan , Manoruang Wasan , Koul Opender , Pluempanupat Wanchai , Kainoh Yooichi , Yooboon Thitaree , Piyasaengthong Narisara , Bullangpoti Vasakorn , Nobsathian Saksit 
Published: June 2022

Abstract
Background
Plant secondary metabolites or mixtures in extracts or essential oils are well known to enhance the activity in binary mixtures. The present study is the first to report that thymol synergistically or additively enhances the activity of P. ribesioides extracts and isolated compounds against S. exigua larvae at sublethal doses.

Results
Thymol was synergistic when are mixed with hexane extract; however, if the hexane extract level was higher (LD30) than the thymol level (LD10), the reaction was antagonistic. CH2Cl2 extract and thymol were more toxic than the extract or thymol alone, and EtOAc extract was synergized by thymol if the components were combined at similar levels (1:1 thymol:EtOAc extract at the LD10 or LD30). MeOH extract individually had moderate insecticidal activity, but all combinations with thymol were synergistic as binary mixtures. Isolated compounds, piperine, phenethyl cinnamamide and cinnamic acid represented synergistic, additive, and antagonistic action after combining with thymol (1:1 at the LD10 or LD30). Detoxification enzymes after exposure of insects to treatments showed isolated compounds + thymol could inhibit CE, GST and AChE reaction of S. exigua exceptional being piperine + thymol, which induced detoxification enzyme activity.

Conclusion
The synergistic activity was extract- and dose-specific. The impact on detoxification enzymes was variable and dependent on the composition of the extract and the doses of extract and thymol used in a binary mixture. In this metabolic model, the major insect compound in an extract may become detoxified, whereas a minor compound will act unimpeded, showing a lower LD50 than acting alone. This model suggests that thymol synergizes with extract components differently, which could depend on the specific metabolites in the extract and the dose applied. Such studies will help design effective insecticides based on natural plant mixtures and a synergistic compound.

Graphical abstract
The effectiveness of adjunctive measures in managing peri-implant mucositis: an umbrella review
Authors: Chuachamsai Sompol , Acharya Aneesha , Fischer Kai , Nibali Luigi , Ho Dominic , Pelekos Georgios 
Published: June 2022

Abstract
Objectives
The purpose of this umbrella review was to gather and summarize the data from published systematic reviews (SRs) that compared non-surgical mechanical debridement (NSMD) with and without the use of adjunctive treatments on the management of peri-implant mucositis (PIM).

Materials and methods
A protocol was developed and registered in PROSPERO (CRD42021254350) before the systematic search for the SRs. Seven electronic databases, including Cochrane Library, Embase (via Ovid), MEDLINE (via Pubmed), Proquest, Prospero, Scopus and Web of Science, were searched for published reviews. The search for unpublished and informally published reviews was further attempted in the last four databases. The methodological quality of the included reviews was assessed using AMSTAR 2.

Results
Twelve included SRs assessed clinical studies published between 2014 and 2020, including a total of seventeen primary clinical trials. All SRs summarized data from individual studies and provided a narrative conclusion regarding the effectiveness of the adjunctive treatments. Only six SRs performed a meta-analysis (MA) of additional benefits of the adjunctive therapy for PIM, with results indicating no significant difference between the different treatment modalities. The overall confidence was adjudged ranging from critically low to low using AMSTAR 2 and significant additional benefits of any adjunctive treatments in comparison with NSMD were not apparent.

Conclusion
Overall, the reviewed evidence did not support the use of adjunctive treatments for improvement of clinical outcomes in PM management as compared to NSMD alone.
Genotoxicity test of eight natural color additives in the Korean market
Authors: Do Byungkyung , Kwon Hoonjeong 
Published: June 2022

Abstract
Background
Various natural color additives are preferred by many consumers over synthetic color additives because they are perceived to be safer. However, most do not have sufficient toxicity data for safety assurance. Color ingredients in particular have some structures suspected of being toxic. Eight natural color additives, gardenia red, blue, and yellow; lac color; cochineal extract; beet red; Curcuma longa Linne extract (Curcuma extract); and Monascus red, currently permitted for use in Korea, were selected and subjected to genotoxicity tests. Acceptable daily intake values have not been allocated to these color additives (except for cochineal extract) due to the lack of toxicity data. We used genotoxicity testing—the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test, and in vivo alkaline comet test—for minimum safety assurance.

Results
Gardenia red and blue, cochineal extract, lac color, and beet red did not induce mutagenicity or chromosomal abnormalities. Gardenia yellow was mutagenic in the Ames test, but was not positive in the in vitro chromosomal aberration test or in vivo alkaline comet assay. Curcuma extract and Monascus red induced cytotoxicity in the Ames test at high concentrations in Salmonella typhimurium TA1537 and TA100, without showing mutagenicity. On cytotoxicity testing, Curcuma extract and Monascus red showed cytotoxicity at concentrations higher than 313 μg/ml in Chinese hamster ovary CHO-K1 cells and showed equivocal results in chromosomal aberration assay of the same cells. Curcuma extract and Monascus red produced significant increases in DNA damage at a dose of 2000 mg/kg b.w./day, and induced dose-dependent increases in % DNA in the tail and tail moment on in vivo comet assay.

Conclusions
Six out of eight food colorants did not cause genotoxicity and cytotoxicity. However, Monascus red and Curcuma extract showed definite cytotoxicity and probable genotoxicity.
Perception of the general population towards migraine in Jeddah, Saudi Arabia
Authors: Algahtani Hussein , Shirah Bader , Bamsallm Mouaz , Nejaim Kenan , Alobaidi Hussain , Alghamdi Meshal 
Published: June 2022

AbstractBackgroundMigraine is a chronic episodic neurological disorder characterized by a myriad of neurological symptoms including multi-phase attacks of headache, photophobia, phonophobia, and dizziness. To the best of our knowledge, there are no studies conducted about the public perception and attitudes towards migraine in Saudi Arabia. This study aims to determine the public perception and attitudes towards migraine in Jeddah, Saudi Arabia. This cross-sectional study was conducted during the period between September 2019 and January 2020 in various public places including malls in Jeddah, Saudi Arabia. The study utilized a 40-item self-administered survey questionnaire divided into two sections: demographic data of the participants and perception of participants towards migraine, which consisted of three parts—knowledge towards migraine, attitudes towards migraine, and the expected behavior of migraine patients.ResultsThe total number of participants was 385. Three hundred and thirty-nine of the participants (88.1%) heard about migraine before. Relatives and friends are the main source of information for 213 participants (55.3%). In gender predominance, 137 (35.6%) believed that migraine affects both genders equally. Complications of migraine headache are not known for 240 participants (62.3%). The existence of medications or methods for treating migraine is not known for 195 (50.6%). The quality of life for patients with migraine is negatively affected according to 275 (70.9%). One hundred sixty-six participants (43.1%) believe that depression and anxiety are more common in migraineurs. Two hundred forty-four (63.4%) considered migraine to cause a huge psychological and social impact. Two hundred fifteen (55.8%) do not have the knowledge to deal with migraineurs.ConclusionThe present study demonstrated a lack of knowledge in certain aspects of migraine in Jeddah, Saudi Arabia. This study will serve as a basis for developing a health educational program aiming to increase public awareness about migraine. It will also improve the understanding of society regarding migraine, which will subsequently improve the way they interact with migraineurs and understand their difficulties. In addition, finding a trusted source for information about different kinds of medical conditions including migraine is crucial in educating the community and providing them with the most recent and correct information.
SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC).
Authors: Rudin Charles M. , Liu Stephen V. , Lu Shun , Soo Ross A. , Hong Min Hee , Lee Jong-Seok , Bryl Maciej , Dumoulin Daphne W , Rittmeyer Achim , Chiu Chao-Hua , Ozyilkan Ozgur , Navarro Alejandro , Novello Silvia , Ozawa Yuichi , Meng Raymond , Hoang Tien , Lee Anthony , Wen Xiaohui , Huang Meilin , Reck Martin 
Published: June 2022

LBA8507 Background: Atezo, in combination with CE, was the first cancer immunotherapy approved for 1L treatment of ES-SCLC. However, most pts eventually experience disease progression. TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells. Tira (anti-TIGIT) may synergise with other immunotherapies, such as PD-L1/PD-1 inhibitors, and further amplify the immune response to improve clinical outcomes. SKYSCRAPER-02 (NCT04256421) evaluates whether the antitumor effect and survival benefits of the combination of atezo + CE could be enhanced by adding tira in pts with ES-SCLC. Methods: Eligible pts with untreated ES-SCLC (asymptomatic treated or untreated brain metastases [BM] permitted) were randomized 1:1 to receive induction tira 600 mg IV or placebo (pbo) combined with atezo 1200 mg IV + CE for 4 x 21-day cycles followed by maintenance tira or placebo combined with atezo every 3 weeks until disease progression or loss of clinical benefit. Stratification factors include ECOG PS (0 vs 1); presence/history of BM (yes vs no); LDH (≤upper limit of normal [ULN] vs >ULN). Co-primary endpoints were investigator-assessed PFS and OS in all randomized pts without the history/presence of BM at baseline (primary analysis set [PAS]). Additional endpoints include PFS and OS in all randomized pts regardless of BM status (full analysis set [FAS]), objective response rate, duration of response, and safety. Results: A total of 490 patients were randomized (tira + atezo + CE, n=243; pbo + atezo + CE, n=247). As of 6 Feb 2022, median duration of follow-up was 13.9 months (mo); data represent final analysis for PFS and interim analysis for OS. In the PAS, no additional benefit was seen for tira + atezo + CE in PFS or OS compared with pbo + atezo + CE (Table). PFS and OS in the FAS were consistent with those observed in the PAS (Table). Grade 3/4 TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) and Grade 5 TRAEs occurred in 0.4% (tira + atezo + CE) and 2.0% (pbo + atezo + CE). TRAEs leading to any treatment discontinuation occurred in 5.0% and 5.3% with tira + atezo + CE and pbo + atezo + CE, respectively. Conclusions: The addition of tira to atezo + CE did not provide benefit over atezo + CE in pts with untreated ES-SCLC with or without BM. The combination was well tolerated, and no new safety signals were identified. The study will continue to planned final OS analysis. Clinical trial information: NCT04256421. [Table: see text]