bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct evidence of cheetah (Acinonyx jubatus) as intermediate host of Toxoplasma gondii through isolation of viable strains
Authors: Zhu Niuping , Ren Hongjie , Yang Liulu , Mao Gaohui , Li Junbao , Su Chunlei , Yang Yurong 
Published: February 2024

AbstractToxoplasma gondii causes lifelong infection in most definitive and intermediate hosts. Clinical cases of toxoplasmosis in captive cheetahs have been reported. However, there are few reports of viable T. gondii strains isolated from cheetahs. Here, T. gondii infection was investigated using molecular and serological assays in cheetahs from China. Modified agglutination test (MAT) (cut-off: 1:25) indicated that all six examined cheetahs (n = 6) showed T. gondii antibodies. Toxoplasma gondii DNA was detected in three out of five cheetahs. Two viable T. gondii strains were isolated from the striated muscles of two cheetahs using mice bioassay. They were designated as TgCheetahCHn1 and TgCheetahCHn2. Genetic characterization of DNA derived from tachyzoites was performed using RFLP-PCR of 10 markers. Toxoplasma gondii TgCheetahCHn1 is ToxoDB PCR-RFLP genotype #319, and the alleles of ROP18/ROP5 types were 3/7. TgCheetahCHn2 is ToxoDB genotype #9, and the alleles of ROP18/ROP5 were 3/6. The average survival time of TgCheetahCHn1-infected Swiss mice was 22 ± 1 days (n = 23), and the mice did not have detectable T. gondii-specific antibodies until 117 ± 30 days post-inoculation (n = 8), therefore, TgCheetahCHn1 had intermediate virulence. TgCheetahCHn2 was avirulent for Swiss mice. Few brain tissue cysts (0–50) were observed in the mice inoculated with TgCheetahCHn1 or TgCheetahCHn2. The results provide direct evidence of cheetah as intermediate host of T. gondii.
Causal effects between circulating immune cells and heart failure: evidence from a bidirectional Mendelian randomization study
Authors: Bian Rutao , Xu Xuegong , Li Zishuang 
Published: February 2024

Abstract
Background
Heart failure (HF) is a prevalent cardiac condition characterized by high mortality and morbidity rates. Immune cells play a pivotal role as crucial biomarkers in assessing the overall immune status of individuals. However, the causal relationship between circulating immune cells and the pathogenesis of HF remains an area requiring further investigation.

Objectives
The aim of this study was to investigate the genetic interactions between circulating immune cells and HF, and to further elucidate the genetic associations between different lymphocyte subsets and HF.

Methods
We obtained genetic variants associated with circulating immune cells as instrumental variables (IVs) from the Blood Cell Consortium and publicly available HF summary data. We conducted additional subsets analyses on lymphocyte counts. Our study utilized two-sample and multivariate Mendelian randomization (MVMR) analysis to investigate the causal effect of immune cells on HF. The primary analysis employed inverse variance weighting (IVW) and was complemented by a series of sensitivity analyses.

Results
The findings of the study showed that the IVW model demonstrated a significant correlation between an elevation in lymphocyte count and a decreased risk of HF (OR = 0.97, 95% CI, 0.94 - 1.00, P = 0.032). However, no such correlation was evident in the MVMR analysis for lymphocytes and HF. Furthermore, the examination of the lymphocyte subsets indicated that an increase in CD39+ CD4+ T-cell counts was notably linked to a reduced risk of HF (OR = 0.96, 95% CI, 0.95 - 0.98, P = 0.0002). The MVMR results confirmed that the association between CD39+ CD4+ T-cell counts and HF remained significant. There was no substantial evidence of reverse causality observed between circulating immune cells and HF.

Conclusion
Our MR research provided evidence for a causal relationship between lymphocyte cell and HF. Subsets analyses revealed a causal relationship between CD39+ CD4+ T lymphocytes and HF. These findings will facilitate a future understanding of the mechanisms underlying HF.
Multienzymatic biotransformation of flavokawain B by entomopathogenic filamentous fungi: structural modifications and pharmacological predictions
Authors: Chlipała Paweł , Tronina Tomasz , Dymarska Monika , Urbaniak Monika , Kozłowska Ewa , Stępień Łukasz , Kostrzewa-Susłow Edyta , Janeczko Tomasz 
Published: February 2024

Abstract
Background
Flavokawain B is one of the naturally occurring chalcones in the kava plant (Piper methysticum). It exhibits anticancer, anti-inflammatory and antimalarial properties. Due to its therapeutic potential, flavokawain B holds promise for the treatment of many diseases. However, due to its poor bioavailability and low aqueous solubility, its application remains limited. The attachment of a sugar unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Biotransformation is an environmentally friendly way to improve the properties of compounds, for example, to increase their hydrophilicity and thus affect their bioavailability. Recent studies proved that entomopathogenic filamentous fungi from the genera Isaria and Beauveria can perform O-methylglycosylation of hydroxyflavonoids or O-demethylation and hydroxylation of selected chalcones and flavones.

Results
In the present study, we examined the ability of entomopathogenic filamentous fungal strains of Beauveria bassiana, Beauveria caledonica, Isaria farinosa, Isaria fumosorosea, and Isaria tenuipes to transform flavokawain B into its glycosylated derivatives. The main process occurring during the reaction is O-demethylation and/or hydroxylation followed by 4-O-methylglycosylation. The substrate used was characterized by low susceptibility to transformations compared to our previously described transformations of flavones and chalcones in the cultures of the tested strains. However, in the culture of the B. bassiana KCh J1.5 and BBT, Metarhizium robertsii MU4, and I. tenuipes MU35, the expected methylglycosides were obtained with high yields. Cheminformatic analyses indicated altered physicochemical and pharmacokinetic properties in the derivatives compared to flavokawain B. Pharmacological predictions suggested potential anticarcinogenic activity, caspase 3 stimulation, and antileishmanial effects.

Conclusions
In summary, the study provided valuable insights into the enzymatic transformations of flavokawain B by entomopathogenic filamentous fungi, elucidating the structural modifications and predicting potential pharmacological activities of the obtained derivatives. The findings contribute to the understanding of the biocatalytic capabilities of these microbial cultures and the potential therapeutic applications of the modified flavokawain B derivatives.
Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia
Authors: Rifat Ali , Ossola Bernardino , Bürli Roland W. , Dawson Lee A. , Brice Nicola L. , Rowland Anna , Lizio Marina , Xu Xiao , Page Keith , Fidzinski Pawel , Onken Julia , Holtkamp Martin , Heppner Frank L. , Geiger Jörg R. P. , Madry Christian 
Published: February 2024

AbstractNeuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K+ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K+ efflux in a concentration-dependent manner only via P2X7 and metabotropic potentiation of THIK-1. We further demonstrated that activation of P2X7 was mandatory for ATP-evoked IL-1β release, which was strongly suppressed by blocking THIK-1. Surprisingly, THIK-1 contributed only marginally to the total K+ conductance in the presence of ATP, which was dominated by P2X7. This suggests a previously unknown, K+-independent mechanism of THIK-1 for NLRP3 activation. Nuclear sequencing revealed almost selective expression of THIK-1 in human brain microglia, while P2X7 had a much broader expression. Thus, inhibition of THIK-1 could be an effective and, in contrast to P2X7, microglia-specific therapeutic strategy to contain neuroinflammation.
Graphical Abstract
Ultrasonic microbubbles promote mesenchymal stem cell homing to the fibrotic liver via upregulation of CXCR4 expression
Authors: Xu Heming , Huang Yize , Zhang Fasu , Shi Wei , Cheng Yan , Yang Kai , Tian Pingping , Zhou Fei , Wang Yuan , Fang Xueqing , Song Youliang , Liu Bo , Liu Liwei 
Published: February 2024

Abstract
Objective
To investigate the mechanism of ultrasound microbubbles (UTMB) promoting stem cells homing to fibrotic liver.

Methods
Bone marrow derived mesenchymal stem cells (BMSCs) were divided into 5 groups with or without ultrasound microbubbles and continuously irradiated with ultrasound conditions of frequency 1 MHZ and output power 0.6 W/cm2 for different times, and then injected into a mouse model of liver fibrosis through the tail vein with or without ultrasound microbubbles, with sound intensity. The effect of ultrasound microbubbles on MSC expression of CXC chemokine receptor 4 (CXCR4) and homing fibrotic liver was evaluated by flow cytometry (FCM), western blot (WB) and immunohistochemistry (IHC) analysis.

Results
The level of CXCR4 expression was significantly higher in the ultrasound microbubble group than in the non-intervention group (P < 0.05), and the number of MSC and the rate of CXCR4 receptor positivity in the ultrasound microbubble-treated liver tissues were significantly higher than in the non-intervention group (P < 0.01).

Conclusion
Ultrasonic microbubbles can promote the expression of CXCR4 on the surface of MSCs, thus improving the homing rate of MSCs in fibrotic liver.
Predictors of COVID-19 vaccine uptake among people who use substances: a case study in Tehran
Authors: Karimi Salah Eddin , Amadi Sina , Rampisheh Zahra , Tayefi Batool , Soleimanvandiazar Neda , Higgs Peter , Tehrani-Banihashemi Arash , Hajebi Ahmad , Nojomi Marzieh , Karimijavan Gelavizh 
Published: February 2024

Abstract
Background
Vaccination is one of the most effective ways to manage infectious disease epidemics such as Covid-19. However, the low rates of vaccination in populations at risk including people using illicit substances, hinders the effectiveness of preventive vaccines in reducing transmission. The aim of this study was to investigate the rate of Covid-19 vaccination and its related factors among people who use substances in Tehran, Iran.

Methods
Between July and December 2022, 386 people who use substances aged ≥ 18 years old were recruited by convenience street-based sampling in Tehran. The outcome variable in this study was self-reported completion of at least two doses of the Covid-19 vaccine. Logistic regression was used to investigate the factors related to Covid-19 vaccination. Data were analyzed using SPSS software version 20 at the 0.05 level of significance. As a measure of risk, 95% Confidence interval (CI) was used. The level of significance was considered at 0.05.

Results
Almost three-quarters (n = 286) of the participants reported receiving at least two doses of the Covid-19 vaccine (95% CI, 70.2–79.3). Those participants with high school diplomas were 1.17 times more likely than less educated participants to report having had 2 vaccinations (OR of 1.17, CI 95%: 1.03–1.81). Participants with a higher mean score of having a positive attitude towards Covid-19 vaccination were more likely to have received a vaccination (OR of 1.12, CI 95%: 1.08–1.17). Ethnicity was also an influential variable, people with non-Fars ethnicity were less likely to be vaccinated than those of Fars ethnicity (OR of 0.33, CI 95%: 0.13–0.81). People with higher-than-average monthly income were more likely to report vaccination than those with low monthly incomes (OR of 1.27, CI 95%: 1.09–1.8). Also, participants reporting less access to vaccination centers had a lower chance of reporting having been vaccinated than those who reported high access to vaccination centers (OR of .17, CI 95%: .08-.36).

Conclusions
Covid-19 vaccine uptake was found to be relatively high among people using illicit substances in this study. Higher levels of education, Fars ethnicity, higher income levels, having a positive attitude towards vaccination and access to vaccination centers were the most important predictors of Covid-19 vaccination in this study.
MSCT study for adult esophageal diverticulum with secondary broncho-esophageal fistula
Authors: Dong Xin , Pan Ruonan , Duan Lijun , Lu Xiaoqian , Cao Dianbo 
Published: February 2024

Abstract
Background
Broncho-esophageal fistula (BEF) secondary to esophageal diverticulum is a rare clinical condition, which is often misdiagnosed for a long time. The aim of our study is to summarize and clarify the advantages of MSCT in diagnosing BEF secondary to esophageal diverticulum.

Methods
We retrospectively analyzed patients clinically diagnosed with BEF from January 2005 to January 2022 at Jilin University First Hospital. Only those patients with BEF secondary to esophageal diverticulum and complete clinical data met our enrolled standard. All patients’ clinicopathologic characteristics and MSCT features were systemically evaluated.

Results
17 patients were eligible for our cohort study, including male 10 and female 7. The patient’s mean age was 42.3 ± 12.5. The chronic cough occurred in all seventeen patients and bucking following oral fluid intake was documented in nine patients. MSCT distinctly suggested the fistulous tract between the bronchi and the esophagus in all patients. The mean diameter of the orifices in the wall of the esophagus was 4.40 ± 1.81 mm. The orifice in the midthoracic esophagus side was 15 cases and 2 cases at the lower thoracic esophagus. The involved bronchus included 13 cases at the right lower lobe bronchus, 1 at the right middle lobe bronchus and 3 at the left lower lobe bronchus. The contrast agent was observed in the pulmonary parenchyma in 10 of 13 patients who underwent esophagogram. No definite fistula was observed in 3 of 11 who underwent gastroscopy, while the intra-operative findings supported the existence of fistula.

Conclusions
BEF secondary to esophageal diverticulum tends to occur between the midthoracic esophagus and the right lower lobe bronchus. Compared with esophagography and gastroscopy, MSCT shows more comprehensive information about the fistulous shape, size, course and lung involvement, which are helpful for establishing diagnosis and guiding subsequent treatment.
Treatment guidelines for rare, early-onset conditions associated with epileptic seizures: a literature review on Rett syndrome and tuberous sclerosis complex
Authors: Amin S. , Ruban-Fell B. , Newell I. , Evans J. , Vyas K. , Nortvedt C. , Chin R. F. 
Published: February 2024

AbstractBackgroundRett syndrome (RTT) and tuberous sclerosis complex (TSC) are two rare disorders presenting with a range of different epileptic seizures. Seizure management requires careful therapy selection, thereby necessitating development of high-quality treatment guidelines. This targeted literature review (TLR) aimed to characterise country-specific and international treatment guidelines available for pharmacological management of seizures in RTT and TSC.MethodsA TLR was performed between 25-Jan and 11-Mar 2021. Manual searches of online rare disease and guideline databases, and websites of national heath technology assessment bodies were conducted for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK, and US as defined by pre-specified eligibility criteria. Search terms were developed for each condition and translated into local languages where appropriate. Eligible publications were defined as guidelines/guidance reporting pharmacological management of seizures in patients with RTT and TSC. Guideline development methodology, geographical focus, author information and treatment recommendations were extracted from guidelines. An author map was generated using R version 3.5.1 to visualise extent of collaboration between authors.Results24 total guidelines were included, of which three and six contained only recommendations for RTT and TSC, respectively (some provided recommendations for ≥ 1 condition). Guideline development processes were poorly described (50% [12 guidelines] had unclear/absent literature review methodologies); reported methodologies were variable, including systematic literature reviews (SLRs)/TLRs and varying levels of expert consultation. Most (83% [20/24]) were country-specific, with guideline authors predominantly publishing in contained national groups; four guidelines were classified as ‘International,’ linking author groups in the US, UK, Italy and France. High levels of heterogeneity were observed in the availability of treatment recommendations across indications, with 13 and 67 recommendations found for RTT and TSC, respectively. For RTT, all treatment recommendations were positive and sodium valproate had the highest number of positive recommendations (Khwaja, Sahin (2011) Curr Opin Pediatr 23(6):633–9). All TSC treatments (21 medications) received either exclusively negative (National Organization for Rare Disorders (2019)) or positive (Chu-Shore et al. (2010) Epilepsia 51(7):1236–41) recommendations; vigabatrin received the highest number of positive recommendations (Kaur, Christodoulou (2019)).ConclusionsThis review highlights the need for the development of international high-quality and comprehensive consensus-based guidance for the management of seizures with pharmacological therapy in RTT and TSC.Trial registrationNot applicable.
The global burden of cervical cancer requiring surgery: database estimates
Authors: Allanson Emma R , Zafar Syed Nabeel , Anakwenze Chidinma P , Schmeler Kathleen M , Trimble Edward L , Grover Surbhi 
Published: February 2024

Abstract
Background
Scaling up surgical services for cervical cancer in low and middle income countries requires quantification of the need for those services. The aim of this study was to estimate the global burden of cervical cancer for which access to surgery is required.

Methods
This was a retrospective analysis of publicly available data. Cervical cancer incidence was extracted for each country from the World Health Organization, International Agency for Research, Global Cancer Observatory. The proportion of cases requiring surgery was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The need for cervical cancer surgery was tested against development indicators.

Results
Data were available for 175 countries, representing 2.9 billion females aged 15 and over. There were approximately 566,911 women diagnosed with cervical cancer (95% CI 565,462–568,360). An estimated 56.9% of these women (322,686) would require surgery for diagnosis, treatment or palliation (95% CI 321,955 − 323,417). Cervical cancers for which surgery is required represent less than 1% of cancers in high income countries, and nearly 10% of cancers in low income countries.

Conclusions
At least 300,000 cervical cancer cases worldwide require access to surgical services annually. Gathering data on available cervical cancer surgery services in LMIC are a critical next step.
World AIDS Day 2023: time to prioritize perilous HIV medicine
Authors: Gesesew Hailay Abrha 
Published: February 2024

Abstract
Background
World AIDS Day has been observed on the first of December every year. Whilst there are specific themes during the commemoration, the role of conflict on HIV seems neglected and needs prioritization given the rise of conflicts globally.

Discussion
The global HIV response brought substantial reduction of new HIV infections and HIV-related deaths, and increment of antiretroviral therapy coverage. Nevertheless, there is substantial inequity on the benefit of the response. Individuals with HIV in conflict zones have suffered immensely and are often neglected. The fact that the level, intensity, and number of conflicts is increasing mean more HIV people in conflict or post-conflict settings such as in Ethiopia, South Sudan, the Democratic Republic of Congo, Myanmar, Yemen Russia and Ukraine are at risk of negative HIV care and treatment outcomes. In particular, some conflicts such as the case of Ethiopia’s Tigray have been marked by severe public and humanitarian crises, including medical siege, intentional damage of healthcare infrastructure, targeted attacks on health workers, displacement, and appalling incidents of conflict-related sexual violence. Yet, people living with HIV in these conflict settings seem often overlooked. It is crucial to address the unique challenges in these areas to achieve the goals of AIDS/HIV care.

Conclusion
There is no ideal forum to remind the intricate relationship between conflict and the HIV epidemic other than the World AIDS Day. Thus, this this year’s World AIDS Day should focus on prioritizing on tackling the direct and indirect effects of conflict on HIV transmission and treatment. This way, we can achieve the ambitious UNAIDS 95-95-95 goals and Ending AIDS by 2030.
TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway
Authors: Tian Yi , Xiao Xiao , Liu Weiliang , Cheng Shanqing , Qian Na , Wang Ling , Liu Yang , Ai Rong , Zhu Xiaoping 
Published: February 2024

Abstract
Background
Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD.

Materials and methods
The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed. On postnatal day (PND) 7 and PND 28, the effects of prenatally exposure to VPA on synaptic development and microglia phenotype of offspring rats were observed. Primary microglia were cultured in vitro. Lentivirus and adenovirus were utilized to interfere with TREM2 and overexpress TREM2.

Results
Prenatally VPA exposure induced offspring rats to show typical ASD core symptoms, which led to abnormal expression of synapse-related proteins in the prefrontal cortex of offspring rats, changed the phenotype of microglia in offspring rats, promoted the polarization of microglia to pro-inflammatory type, and increased inflammatory response. The experimental results in vitro showed that overexpression of TREM2 could increase the expression of Gephyrin, decrease the content of CD86 protein and increase the content of CD206 protein. In addition, after the expression of TREM2 was interfered, the content of p-P38 MAPK protein increased and the content of p-ELK-1 protein decreased.

Conclusion
The protective influence of TREM2 on the VPA-induced ASD model is attributed to its inhibition of the P38 MAPK pathway, this protective effect may be achieved by promoting the polarization of microglia to anti-inflammatory phenotype and improving the neuronal synaptic development.