bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-scale spatial distribution of deltamethrin resistance and population structure of Anopheles funestus and Anopheles arabiensis populations in Southern Mozambique
Authors: Das Smita , Máquina Mara , Phillips Keeley , Cuamba Nelson , Marrenjo Dulcisaria , Saúte Francisco , Paaijmans Krijn P. , Huijben Silvie 
Published: March 2023

Abstract
Background
Insecticide resistance in malaria vectors can be spatially highly heterogeneous, yet population structure analyses frequently find relatively high levels of gene flow among mosquito populations. Few studies have contemporaneously assessed phenotypic, genotypic and population structure analysis on mosquito populations and none at fine geographical scales. In this study, genetic diversity, population structure, and insecticide resistance profiles of Anopheles funestus and Anopheles arabiensis were examined across mosquito populations from and within neighbouring villages.

Methods
Mosquitoes were collected from 11 towns in southern Mozambique, as well as from different neighbourhoods within the town of Palmeira, during the peak malaria transmission season in 2016. CDC bottle bioassay and PCR assays were performed with Anopheles mosquitoes at each site to determine phenotypic and molecular insecticide resistance profiles, respectively. Microsatellite analysis was conducted on a subsample of mosquitoes to estimate genetic diversity and population structure.

Results
Phenotypic insecticide resistance to deltamethrin was observed in An. funestus sensu stricto (s.s.) throughout the area, though a high level of mortality variation was seen. However, 98% of An. funestus s.s. were CYP6P9a homozygous resistant. An. arabiensis was phenotypically susceptible to deltamethrin and 99% were kdr homozygous susceptible. Both Anopheles species exhibited high allelic richness and heterozygosity. Significant deviations from Hardy–Weinberg equilibrium were observed, and high linkage disequilibrium was seen for An. funestus s.s., supporting population subdivision. However, the FST values were low for both anophelines (− 0.00457 to 0.04213), Nm values were high (9.4–71.8 migrants per generation), AMOVA results showed almost 100% genetic variation among and within individuals, and Structure analysis showed no clustering of An. funestus s.s. and An. arabiensis populations. These results suggest high gene flow among mosquito populations.

Conclusion
Despite a relatively high level of phenotypic variation in the An. funestus population, molecular analysis shows the population is admixed. These data indicate that CYP6P9a resistance markers do not capture all phenotypic variation in the area, but also that resistance genes of high impact are likely to easily spread in the area. Conversely, other strategies, such as transgenic mosquito release programmes will likely not face challenges in this locality.
Combination therapy based on dual-target biomimetic nano-delivery system for overcoming cisplatin resistance in hepatocellular carcinoma
Authors: Huang Yufen , Kou Qinjie , Su Yanrong , Lu Lu , Li Xisheng , Jiang Haiye , Gui Rong , Huang Rong , Nie Xinmin , Li Jian 
Published: March 2023

AbstractStrategies to overcome toxicity and drug resistance caused by chemotherapeutic drugs for targeted therapy against hepatocellular carcinoma (HCC) are urgently needed. Previous studies revealed that high oxidored-nitro domain-containing protein 1(NOR1) expression in HCC was associated with cisplatin (DDP) resistance. Herein, a novel dual-targeting nanocarrier system AR-NADR was generated for the treatment of DDP resistance in HCC. The core of the nanocarrier system is the metal–organic frameworks (MOF) modified with nuclear location sequence (NLS), which loading with DDP and NOR1 shRNA (R). The shell is an A54 peptide inserted into the erythrocyte membrane (AR). Our results show that AR-NADR efficiently internalized by tumor cells due to its specific binding to the A54 receptors that are abundantly expressed on the surface of HCC cells and NLS peptide-mediated nuclear entry. Additionally, DDP is more likely to be released due to the degradation of Ag-MOF in the acidic tumor microenvironment. Moreover, by acting as a vector for gene delivery, AR-NADR effectively inhibits tumor drug resistance by suppressing the expression of NOR1, which induces intracellular DDP accumulation and makes cells sensitive to DDP. Finally, the anti-HCC efficacy and mechanisms of AR-NADR were systematically elucidated by a HepG2/DDP cell model as well as a tumor model. Therefore, AR-NADR constitutes a key strategy to achieve excellent gene silencing and antitumor efficacy, which provides effective gene therapy and precise treatment strategies for cisplatin resistance in HCC.
Graphical Abstract
Risk factors for thrombolysis-related intracranial hemorrhage: a systematic review and meta-analysis
Authors: Chen Jiana , Zeng Zhiwei , Fang Zongwei , Ma Fuxin , Lv Meina , Zhang Jinhua 
Published: March 2023

AbstractBackgroundThrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated.AimWe conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage.MethodThe protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods.ResultsOf 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models.ConclusionThis study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.
Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy
Authors: Shi Saixian , Chen Ye , Luo Zhijian , Nie Guojun , Dai Yan 
Published: March 2023

AbstractDoxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, used alone or in combination in a variety of cancers, while it has been found to cause serious cardiac side effects in clinical application. More and more researchers are trying to explore the molecular mechanisms of DOX-induced cardiomyopathy (DIC), in which oxidative stress and inflammation are considered to play a significant role. This review summarizes signaling pathways related to oxidative stress and inflammation in DIC and compounds that exert cardioprotective effects by acting on relevant signaling pathways, including the role of Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α signaling pathways and NOS, NOX, Fe2+signaling in oxidative stress, as well as the role of NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB pathways in DOX-induced inflammation. Hence, we attempt to explain the mechanisms of DIC in terms of oxidative stress and inflammation, and to provide a theoretical basis or new idea for further drug research on reducing DIC.
CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice
Authors: Lin Jie , Xu Ya , Guo Peiwen , Chen Yù-Jié , Zhou Jiru , Xia Min , Tan Binbin , Liu Xin , Feng Hua , Chen Yujie 
Published: March 2023

Abstract
Background
Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear.

Methods
Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids.

Results
Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway.

Conclusions
CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.
Network pharmacology-based mechanism prediction and pharmacological validation of Bushenhuoxue formula attenuating postmenopausal osteoporosis in ovariectomized mice
Authors: Xia Chenjie , Zhu Haowei , Li Jin , Jin Hongting , Fu Danqing 
Published: March 2023

Abstract
Background
Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, is widely used to treat postmenopausal osteoporosis (PMOP) in China. However, the mechanism is not clear yet.

Methods
The underlying biological processes and signaling pathways were predicted by network pharmacology. In vivo experimental study, 24 female C57BL/6 J mice were randomly divided into sham, ovariectomized (OVX) and BSHX formula groups. Mice in the latter two groups were subjected to bilateral ovariectomy, and mice in the BSHX formula group were extra treated by BSHX formula at an oral dosage of 0.2 mL/10 g for 8 weeks. The femur samples were harvested for tissue analyses including μCT assay, histology and immunohistochemical (IHC) staining of VEGF signaling.

Results
A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 targets of PMOP, 64 overlapping genes were obtained. GO and KEGG enrichment analyses on these 64 genes revealed that angiogenesis and VEGF signaling were considered as the potential therapeutic mechanism of BSHX formula against PMOP. Animal experiments showed that mice in the BSHX formula-treated group presented increased bone mass, microstructural parameters, blood vessel numbers and an activation of VEGF signaling (VEGF, COX2, eNOS and CD31) compared to the OVX mice.

Conclusion
This study revealed that BSHX formula exerts anti-PMOP effects possibly through activating VEGF signaling-mediated angiogenesis.
Combinatorial batching of DNA for ultralow-cost detection of pathogenic variants
Authors: Stoltze Ulrik Kristoffer , Hagen Christian Munch , van Overeem Hansen Thomas , Byrjalsen Anna , Gerdes Anne-Marie , Yakimov Victor , Rasmussen Simon , Bækvad-Hansen Marie , Hougaard David Michael , Schmiegelow Kjeld , Hjalgrim Henrik , Wadt Karin , Bybjerg-Grauholm Jonas 
Published: March 2023

Abstract
Background
Next-generation sequencing (NGS) based population screening holds great promise for disease prevention and earlier diagnosis, but the costs associated with screening millions of humans remain prohibitive. New methods for population genetic testing that lower the costs of NGS without compromising diagnostic power are needed.

Methods
We developed double batched sequencing where DNA samples are batch-sequenced twice — directly pinpointing individuals with rare variants. We sequenced batches of at-birth blood spot DNA using a commercial 113-gene panel in an explorative (n = 100) and a validation (n = 100) cohort of children who went on to develop pediatric cancers. All results were benchmarked against individual whole genome sequencing data.

Results
We demonstrated fully replicable detection of cancer-causing germline variants, with positive and negative predictive values of 100% (95% CI, 0.91–1.00 and 95% CI, 0.98–1.00, respectively). Pathogenic and clinically actionable variants were detected in RB1, TP53, BRCA2, APC, and 19 other genes. Analyses of larger batches indicated that our approach is highly scalable, yielding more than 95% cost reduction or less than 3 cents per gene screened for rare disease-causing mutations. We also show that double batched sequencing could cost-effectively prevent childhood cancer deaths through broad genomic testing.

Conclusions
Our ultracheap genetic diagnostic method, which uses existing sequencing hardware and standard newborn blood spots, should readily open up opportunities for population-wide risk stratification using genetic screening across many fields of clinical genetics and genomics.
Changes in CSF sPDGFRβ level and their association with blood–brain barrier breakdown in Alzheimer’s disease with or without small cerebrovascular lesions
Authors: Lv Xinyi , Zhang Mengguo , Cheng Zhaozhao , Wang Qiong , Wang Peng , Xie Qiang , Ni Ming , Shen Yong , Tang Qiqiang , Gao Feng ,   China Aging Neurodegenerative Disorder Initiative (CANDI) Consortium
Published: March 2023

Abstract
Background
CSF-soluble platelet-derived growth factor receptor beta (sPDGFRβ) is closely associated with pericyte damage. However, the changes in CSF sPDGFRβ levels and their role in blood–brain barrier (BBB) leakage at different stages of Alzheimer’s disease (AD), with or without cerebral small vessel disease (CSVD) burden, remain unclear.

Methods
A total of 158 individuals from the China Aging and Neurodegenerative Disorder Initiative cohort were selected, including 27, 48, and 83 individuals with a clinical dementia rating (CDR) score of 0, 0.5, and 1–2, respectively. CSF total tau, phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured using the Simoa assay. Albumin and CSF sPDGFRβ were measured by commercial assay kits. CSVD burden was assessed by magnetic resonance imaging.

Results
CSF sPDGFRβ was the highest level in the CDR 0.5 group. CSF sPDGFRβ was significantly correlated with the CSF/serum albumin ratio (Q-alb) in the CDR 0–0.5 group (β = 0.314, p = 0.008) but not in the CDR 1–2 group (β = − 0.117, p = 0.317). In the CDR 0–0.5 group, CSF sPDGFRβ exhibited a significant mediating effect between Aβ42/Aβ40 levels and Q-alb (p = 0.038). Q-alb, rather than CSF sPDGFRβ, showed a significant difference between individuals with or without CSVD burden. Furthermore, in the CDR 0.5 group, CSF sPDGFRβ was higher in subjects with progressive mild cognitive impairment than in those with stable mild cognitive impairment subjects (p < 0.001). Meanwhile, CSF sPDGFRβ was significantly associated with yearly changes in MMSE scores in the CDR 0.5 group (β = − 0.400, p = 0.020) and CDR 0.5 (A+) subgroup (β = − 0.542, p = 0.019).

Conclusions
We provide evidence that increased CSF sPDGFRβ is associated with BBB leakage in the early cognitive impairment stage of AD, which may contribute to cognitive impairment in AD progression.
Cluster analysis of COVID-19 recovery center patients at a clinic in Boston, MA 2021–2022: impact on strategies for access and personalized care
Authors: Tukpah Ann-Marcia C. , Patel Jhillika , Amundson Beret , Linares Miguel , Sury Meera , Sullivan Julie , Jocelyn Tajmah , Kissane Brenda , Weinhouse Gerald , Lange-Vaidya Nancy , Lamas Daniela , Ismail Khalid , Pavuluri Chandan , Cho Michael H. , Gay Elizabeth B. , Moll Matthew 
Published: March 2023

Abstract
Background
There are known disparities in COVID-19 resource utilization that may persist during the recovery period for some patients. We sought to define subpopulations of patients seeking COVID-19 recovery care in terms of symptom reporting and care utilization to better personalize their care and to identify ways to improve access to subspecialty care.

Methods
Prospective study of adult patients with prior COVID-19 infection seen in an ambulatory COVID-19 recovery center (CRC) in Boston, Massachusetts from April 2021 to April 2022. Hierarchical clustering with complete linkage to differentiate subpopulations was done with four sociodemographic variables: sex, race, language, and insurance status. Outcomes included ICU admission, utilization of supplementary care, self-report of symptoms.

Results
We included 1285 COVID-19 patients referred to the CRC with a mean age of 47 years, of whom 71% were female and 78% White. We identified 3 unique clusters of patients. Cluster 1 and 3 patients were more likely to have had intensive care unit (ICU) admissions; Cluster 2 were more likely to be White with commercial insurance and a low percentage of ICU admission; Cluster 3 were more likely to be Black/African American or Latino/a and have commercial insurance. Compared to Cluster 2, Cluster 1 patients were more likely to report symptoms (ORs ranging 2.4–3.75) but less likely to use support groups, psychoeducation, or care coordination (all p < 0.05). Cluster 3 patients reported greater symptoms with similar levels of community resource utilization.

Conclusions
Within a COVID-19 recovery center, there are distinct groups of patients with different clinical and socio-demographic profiles, which translates to differential resource utilization. These insights from different subpopulations of patients can inform targeted strategies which are tailored to specific patient needs.
China’s innovation and research contribution to combating neglected diseases: a secondary analysis of China’s public research data
Authors: Ma Jiyan , Zhang Lanchao , Li Xianzhe , Shen Jiashu , Sun Yinuo , Huang Yangmu 
Published: March 2023

Abstract
Background
Many emerging and developing economies, such as China, have played the important roles in combating global neglected diseases (NDs). This study aims to explore China’s public landscape of research projects and funding of NDs and to provide empirical evidence on promoting China’s participation in addressing global health priorities that disproportionately affect developing countries.

Methods
We systematically sourced China’s public funding information from the National Natural Science Foundation of China and provincial science and technology agency websites up to August 16, 2019. Following the G-FINDER R&D scope, we screened projects of NDs for analysis. National-funded projects were reviewed on an annual basis for exploring the trends and distribution of funding flows. Information on provincial-funded projects was compared with national projects by disease, research type, and geographical distribution.

Results
A total of 1266 projects were included for analysis and categorized by year, funding source, recipient, disease, research type, region, and province. China’s national public funding for ND research reached a historical peak of USD 16.22 million in 2018. But the proportion of ND research to all public-funded projects was less than 0.5%, and over half of the ND projects were allocated to “the big three,” i.e., tuberculosis, HIV/AIDS, and malaria. About 58% of national and provincial ND projects focus on basic research. Economically developed regions and municipalities play dominant roles in leading national ND research, such as Beijing, Shanghai, and Guangdong. Provincial ND projects are primarily driven by endemic regions.

Conclusions
As a new emerging high-tech innovator, China has gradually increased public input to ND-related innovation and research. But there is still a large funding gap among NDs that requires China’s increased support and participation. National development plans and cooperative health needs should be taken into account for China’s participation in promoting global research and development (R&D) for combating NDs.
Using EV charging control to provide building load flexibility
Authors: Bhundar Harsimrat Singh , Golab Lukasz , Keshav Srinivasan 
Published: March 2023

AbstractBuildings are responsible for a significant fraction of the overall electrical load. Given the increasing penetration of renewables into the generation mix, it is important to make building loads flexible, to better match the variability in generation. Of course, building loads can be made arbitrarily flexible using sufficient stationary storage, but this comes at considerable cost. In this paper, we investigate how to reduce this cost by exploiting electric vehicle (EV) charging control for unidirectional and bidirectional charging. Specifically, we design a model-predictive control algorithm to reshape building load to match a specified load shape. In realistic settings and for two use cases, we investigate the degree to which the amount of stationary storage is reduced using EV charging control. In both cases, we find that our controller reduces the need for stationary storage compared to existing solutions. Moreover, bidirectional EV charging control substantially reduces the required amount of stationary storage.
Experimental study on transition of dynamic airfoil in pitching oscillation
Authors: Wei Binbin , Gao Yongwei , Hu Shuling 
Published: March 2023

AbstractThe transition characteristics of dynamic airfoil have significant effects on the aerodynamic performance of wind turbines, helicopter rotor blades, jet engine compressor blades, etc. The time domain and time-frequency domain characteristics of transition on a NACA0012 airfoil during its pitching oscillation were experimentally studied using wall pressure measurement technology with high time accuracy in this paper. The variable slip window technology was used to detect the transition position, and the proper orthogonal decomposition (POD) method and wavelet analysis were combined to perform the time-frequency analysis. In the gradual forward movement of the transition, the low-frequency instability is gradually enhanced by the main flow and the inverse pressure gradient, and significantly submerges the high-frequency fluctuated feature. The higher order moments of the wall pressure during dynamic airfoil transition deviate significantly from the Gaussian characteristics, which is caused by the low-frequency instability and high-frequency burst. The POD method is able to distinguish low-frequency instability from the high-frequency feature. The reduced frequency had significant effects on the transition. With the increase of the reduced frequency, the hysteresis effect of the transition became more and more significant, and the frequency component of transition was more concentrated and the energy was stronger.