bluuebunny/crossref_metadata_2025_split huggingface dataset:
Larval habitat stability and productivity in two sites in Southern Ghana
Authors: Forson Akua O. , Hinne Isaac A. , Sraku Isaac Kwame , Afrane Yaw A. 
Published: March 2023

Abstract
Background
Mosquito larval source management (LSM) is a valuable additional tool for malaria vector control. Understanding the characteristics of mosquito larval habitats and its ecology in different land use types can give valuable insight for an effective larval control strategy. This study determined the stability and productivity of potential anopheline larval habitats in two different ecological sites: Anyakpor and Dodowa in southern Ghana.

Methods
A total of 59 aquatic habitats positive for anopheline larvae were identified, and sampled every two weeks for a period of 30 weeks using a standard dipping method. Larvae were collected using standard dippers and were raised in the insectary for identification. Sibling species of the Anopheles gambiae sensu lato (s.l.) were further identified by polymerase chain reaction. The presence of larval habitats, their stability and larvae positive habitats were compared between the two sites using Mann–Whitney U and the Kruskal–Wallis test. Factors affecting the presence of An. gambiae larvae and physicochemical properties at the sites were determined using multiple logistic regression analysis and Spearman’s correlation.

Results
Out of a total of 13,681 mosquito immatures collected, 22.6% (3095) were anophelines and 77.38% (10,586) were culicines. Out of the 3095 anophelines collected, An. gambiae s.l. was predominant (99.48%, n = 3079), followed by Anopheles rufipes (0.45%, n = 14), and Anopheles pharoensis (0.064%, n = 2). Sibling species of the An. gambiae consisted of Anopheles coluzzii (71%), followed by An. gambiae s.s. (23%), and Anopheles melas (6%). Anopheles mean larval density was highest in wells [6.44 (95% CI 5.0–8.31) larvae/dip], lowest in furrows [4.18 (95% CI 2.75–6.36) larvae/dip] and man-made ponds [1.20 (95% CI 0.671–2.131) larvae/dip].The results also revealed habitat stability was highly dependent on rainfall intensity, and Anopheles larval densities were also dependent on elevated levels of pH, conductivity and TDS.

Conclusion
The presence of larvae in the habitats was dependent on rainfall intensity and proximity to human settlements. To optimize the vector control measures of malaria interventions in southern Ghana, larval control should be focused on larval habitats that are fed by underground water, as these are more productive habitats.

Graphical Abstract
CD39/CD73/A2AR pathway and cancer immunotherapy
Authors: Xia Chenglai , Yin Shuanghong , To Kenneth K. W. , Fu Liwu 
Published: March 2023

AbstractCancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated.
New frontiers in immune checkpoint B7-H3 (CD276) research and drug development
Authors: Getu Ayechew Adera , Tigabu Abiye , Zhou Ming , Lu Jianrong , Fodstad Øystein , Tan Ming 
Published: March 2023

AbstractB7-H3 (CD276), a member of the B7 family of proteins, is a key player in cancer progression. This immune checkpoint molecule is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. In addition to its immune checkpoint function, B7-H3 has been linked to tumor cell proliferation, metastasis, and therapeutic resistance. Furthermore, its drastic difference in protein expression levels between normal and tumor tissues suggests that targeting B7-H3 with drugs would lead to cancer-specific toxicity, minimizing harm to healthy cells. These properties make B7-H3 a promising target for cancer therapy.Recently, important advances in B7-H3 research and drug development have been reported, and these new findings, including its involvement in cellular metabolic reprograming, cancer stem cell enrichment, senescence and obesity, have expanded our knowledge and understanding of this molecule, which is important in guiding future strategies for targeting B7-H3. In this review, we briefly discuss the biology and function of B7-H3 in cancer development. We emphasize more on the latest findings and their underlying mechanisms to reflect the new advances in B7-H3 research. In addition, we discuss the new improvements of B-H3 inhibitors in cancer drug development.
The associations of dietary folate and serum folate with lipid profiles: findings from the national health and nutrition examination survey 2011–2016
Authors: Feng Yunfu , Chen Xiaohua , Pan Ying , Yang Yanting 
Published: March 2023

Abstract
Background
Folate is considered to be related to lipid metabolism. With the increasing numbers of folic acid fortification nations, the associations of dietary folate and serum folate with lipid profiles deserve more attention and are worth further study.

Methods
US adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) were evaluated. Participants taking folic acid supplements were excluded. The multivariate linear regression model and smooth curve fitting were applied to assess the associations. The segmented regression model was employed to examine the threshold effect of nonlinear relationships.

Results
Our cross-sectional study included 3706 participants in total. There was a negative relationship between serum folate (log transformed) and triglycerides (β = –0.223, 95% CI: –0.337, –0.110) and low-density lipoprotein cholesterol (LDL-C) (β = –0.152, 95% CI: –0.296, –0.007) and a positive relationship between serum folate (log transformed) and high-density lipoprotein cholesterol (HDL-C) (β = 0.090, 95% CI: 0.033,0.146). There was a negative association between dietary folate (log transformed) and total cholesterol (TC) (β = –0.299, 95% CI: –0.465, –0.134) and LDL-C (β = –0.266, 95% CI: –0.409, –0.123). A nonlinear relationship was found between dietary folate (log transformed) and HDL-C. Threshold effect analysis showed that the inflection point was 377.57 ug. Within the inflection point, the β-coefficient of HDL-C was 0.105 (95% CI: 0.018, 0.192); beyond the inflection point, there was no relationship (β = –0.067, 95% CI: –0.162, 0.028).

Conclusions
Optimal dietary folate and high serum folate were associated with favorable lipid profiles. Dietary folate, in the recommended 300–400 ug/d, had a beneficial effect on improving lipid profiles.
A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice
Authors: Li Duo , Li Weiran , Zheng Peng , Yang Ying , Liu Qingwen , Hu Yongmao , He Jinrong , Long Qiong , Ma Yanbing 
Published: March 2023

AbstractInnate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, β-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1β, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of β-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.
Graphical Abstract
PI3K pathway mutation predicts an activated immune microenvironment and better immunotherapeutic efficacy in head and neck squamous cell carcinoma
Authors: Wang Libo , Chen Kejun , Weng Siyuan , Xu Hui , Ren Yuqing , Cheng Quan , Luo Peng , Zhang Jian , Liu Zaoqu , Han Xinwei 
Published: March 2023

Abstract
Background
PI3K pathway is the most frequently mutated pathway in head and neck squamous cell carcinoma (HNSC), which plays a crucial role in tumorigenesis and progression. In the present study, we aimed to investigate the role of PI3K pathway mutation in clinical prognosis prediction and the relationship with immune microenvironment and response rate to immunotherapy.

Methods
We collected 129 samples with immunotherapy information from MSKCC-2019 cohort as well as 501 and 40 samples from TCGA-HNSC and MD-Anderson non-immunotherapy cohorts, respectively. Somatic mutation data was utilized to characterize the mutational status of the PI3K pathway. Subsequently, we further analyzed the differences in prognosis, immunotherapy response, genomic alterations, functional characteristics, and immune microenvironment between the mutation and wild groups.

Results
The Kaplan-Meier survival curves displayed that PI3K pathway mutation predicted observably prolonged overall survival (OS) in the immunotherapy cohort MSKCC-2019 (p = 0.012) but did not reach statistical significance in the non-immunotherapy cohorts TCGA-HNSC (p = 0.68) and MD-Anderson (p = 0.68). After incorporating several clinicopathologic features such as age, gender, and tumor mutation burden (TMB), the results of multivariate Cox regression analysis also demonstrated that the PI3K pathway mutation could indicate better immunotherapy outcomes in HNSC patients with a hazard ratio (HR) of 0.533 (95% CI: 0.313–0.910; p = 0.021) in the immunotherapy cohort MSKCC-2019, compared with 0.888 (95% CI: 0.636–1.241; p = 0.487) and 1.939 (95% CI: 0.483–7.781; p = 0.351) in the non-immunotherapy cohorts TCGA-HNSC and MD-Anderson. In addition, the results of the subclass mapping (SubMap) and the tumor immune dysfunction and exclusion (TIDE) also consistently suggested that patients in the mutation group are more likely to benefit from immunotherapy. And further studies showed that the mutation group owned significantly higher TMB, activated immune-related pathways, richer abundance of immune cells, and higher expression levels of immunomodulators. To improve the prognosis of the wild group, we identified five relatively sensitive potential drugs for the wild group, including “BMS-536924,” “linsitinib,” “NVP-TAE684,” “PLX-4720,” and “clonazepam.”

Conclusions
The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients.
De novo familial adenomatous polyposis associated thyroid cancer with a c.2929delG frameshift deletion mutation in APC: a case report and literature review
Authors: Xu Miaorong , Zheng Yuyan , Zuo Zhongchao , Zhou Qin , Deng Qun , Wang Jianwei , Wang Da 
Published: March 2023

Abstract
Background
Germline mutations in the APC gene located on chromosome 5q 21–22 can lead to familial adenomatous polyposis (FAP) and the development of colorectal cancer (CRC) if left untreated. As a rare extracolonic manifestation, thyroid cancer is diagnosed in about 2.6% of FAP patients. The genotype–phenotype correlation in FAP patients with thyroid cancer remains unclear.

Case presentation
We present a 20-year-old female of FAP with thyroid cancer as the initial manifestation. The patient was asymptomatic and developed colon cancer liver metastases 2 years after the diagnosis of thyroid cancer. The patient underwent multiple surgical treatments in several organs, and regular colonoscopy with endoscopic polypectomy was performed. Genetic testing demonstrated the c.2929delG (p.Gly977Valfs*3) variant in exon 15 of the APC gene. This represents a previously undescribed APC mutation. This mutation causes loss of multiple structures on the APC gene including the 20-amino acid repeats, the EB1 binding domain, and the HDLG binding site, which may be pathogenic through β-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation.

Conclusions
We report a de novo FAP case with thyroid cancer presenting atypically aggressive features harboring a novel APC mutation and review APC germline mutations in patients with FAP-associated thyroid cancer.
Achieving universal health coverage and sustainable development goals by 2030: investment estimates to increase production of health professionals in India
Authors: Karan Anup , Negandhi Himanshu , Kabeer Mehnaz , Zapata Tomas , Mairembam Dilip , De Graeve Hilde , Buchan James , Zodpey Sanjay 
Published: March 2023

Abstract
Background
COVID-19 has reinforced the importance of having a sufficient, well-distributed and competent health workforce. In addition to improving health outcomes, increased investment in health has the potential to generate employment, increase labour productivity and foster economic growth. We estimate the required investment for increasing the production of the health workforce in India for achieving the UHC/SDGs.

Methods
We used data from National Health Workforce Account 2018, Periodic Labour Force Survey 2018–19, population projection of Census of India, and government documents and reports. We distinguish between total stock of health professionals and active health workforce. We estimated current shortages in the health workforce using WHO and ILO recommended health worker:population ratio thresholds and extrapolated the supply of health workforce till 2030, using a range of scenarios of production of doctors and nurses/midwives. Using unit costs of opening a new medical college/nursing institute, we estimated the required levels of investment to bridge the potential gap in the health workforce.

Results
To meet the threshold of 34.5 skilled health workers per 10 000 population, there will be a shortfall of 0.16 million doctors and 0.65 million nurses/midwives in the total stock and 0.57 million doctors and 1.98 million nurses/midwives in active health workforce by the year 2030. The shortages are higher when compared with a higher threshold of 44.5 health workers per 10 000 population. The estimated investment for the required increase in the production of health workforce ranges from INR 523 billion to 2 580 billion for doctors and INR 1 096 billion for nurses/midwives. Such investment during 2021–2025 has the potential of an additional employment generation within the health sector to the tune of 5.4 million and to contribute to national income to the extent of INR 3 429 billion annually.

Conclusion
India needs to significantly increase the production of doctors and nurses/midwives through investing in opening up new medical colleges. Nursing sector should be prioritized to encourage talents to join nursing profession and provide quality education. India needs to set up a benchmark for skill-mix ratio and provide attractive employment opportunities in the health sector to increase the demand and absorb the new graduates.
A scoping review of complex systems methods used in population physical activity research: do they align with attributes of a whole system approach?
Authors: Baugh Littlejohns Lori , Near Erin , McKee Geoff , Rasali Drona , Naiman Daniel , Faulkner Guy 
Published: March 2023

Abstract
Background
Complex systems approaches are increasingly used in health promotion and noncommunicable disease prevention research, policy and practice. Questions emerge as to the best ways to take a complex systems approach, specifically with respect to population physical activity (PA). Using an Attributes Model is one way to understand complex systems. We aimed to examine the types of complex systems methods used in current PA research and identify what methods align with a whole system approach as reflected by an Attributes Model.

Methods
A scoping review was conducted and two databases were searched. Twenty-five articles were selected and data analysis was based upon the following: the complex systems research methods used, research aims, if participatory methods were used and evidence of discussion regarding attributes of systems.

Results
There were three groups of methods used: system mapping, simulation modelling and network analysis. System mapping methods appeared to align best with a whole system approach to PA promotion because they largely aimed to understand complex systems, examined interactions and feedback among variables, and used participatory methods. Most of these articles focused on PA (as opposed to integrated studies). Simulation modelling methods were largely focused on examining complex problems and identifying interventions. These methods did not generally focus on PA or use participatory methods. While network analysis articles focused on examining complex systems and identifying interventions, they did not focus on PA nor use participatory methods. All attributes were discussed in some way in the articles. Attributes were explicitly reported on in terms of findings or were part of discussion and conclusion sections. System mapping methods appear to be well aligned with a whole system approach because these methods addressed all attributes in some way. We did not find this pattern with other methods.

Conclusions
Future research using complex systems methods may benefit from applying the Attributes Model in conjunction with system mapping methods. Simulation modelling and network analysis methods are seen as complementary and could be used when system mapping methods identify priorities for further investigation (e.g. what interventions to implement or how densely connected relationships are in systems).
SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis
Authors: Lee A Ram , Woo Jin Seok , Lee Seon-Yeong , Lee Yeon Su , Jung Jooyeon , Lee Chae Rim , Park Sung-Hwan , Cho Mi-La 
Published: March 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood.

Methods
This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS.

Results
The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein.

Conclusions
The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis.