bluuebunny/crossref_metadata_2025 huggingface dataset:
Public health emergency preparedness for infectious disease emergencies: a scoping review of recent evidence
Authors: Lee Jessica M , Jansen Rachel , Sanderson Kate E , Guerra Fiona , Keller-Olaman Sue , Murti Michelle , O’Sullivan Tracey L , Law Madelyn P , Schwartz Brian , Bourns Laura E , Khan Yasmin
Published: March 2023

Background

The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies.

Methods

Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 to 2020 onward, respectively. Records were included if they: (a) described PHEP, (b) focused on an infectious emergency, and (c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were analyzed deductively and summarized thematically.

Results

The included publications largely aligned with the 11 elements of the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Ten emergent themes were identified that expand on the Resilience Framework for PHEP specific to infectious diseases. Planning to mitigate inequities was a key finding of this review, it was the most frequently identified emergent theme. Additional emergent themes were: research and evidence-informed decision making, building vaccination capacity, building laboratory and diagnostic system capacity, building infection prevention and control capacity, financial investment in infrastructure, health system capacity, climate and environmental health, public health legislation and phases of preparedness.

Conclusion

The themes from this review contribute to the evolving understanding of critical public health emergency preparedness actions. The themes expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to pandemics and infectious disease emergencies. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.
The impact of high-risk lifestyle factors on all-cause mortality in the US non-communicable disease population
Authors: Li Ying , Fan Xue , Wei Lifeng , Yang Kai , Jiao Mingli
Published: March 2023

Background

Previous studies have suggested that lifestyle factors are associated with mortality in different population. However, little is known about the impact of lifestyle factors on all-cause mortality in non-communicable disease (NCD) population.

Methods

This study included 10,111 NCD patients from the National Health Interview Survey. The potential high-risk lifestyle factors were defined as smoking, excessive drinking, abnormal body mass index, abnormal sleep duration, insufficient physical activity (PA), overlong sedentary behavior (SB), high dietary inflammatory index (DII) and low diet quality. Cox proportional hazard model was used to evaluate the impact of the lifestyle factors and the combination on all-cause mortality. The interaction effects and all combinations of lifestyle factors were also analyzed.

Results

During 49,972 person-years of follow-up, 1040 deaths (10.3%) were identified. Among eight potential high-risk lifestyle factors, smoking (HR = 1.25, 95% CI 1.09–1.43), insufficient PA (HR = 1.86, 95% CI 1.61–2.14), overlong SB (HR = 1.33, 95% CI 1.17–1.51) and high DII (HR = 1.24, 95% CI 1.07–1.44) were risk factors for all-cause mortality in the multivariable Cox proportional regression. The risk of all-cause mortality was increased linearly as the high-risk lifestyle score increased (P for trend < 0.01). The interaction analysis showed that lifestyle had stronger impact on all-cause mortality among patients with higher education and income level. The combinations of lifestyle factors involving insufficient PA and overlong SB had stronger associations with all-cause mortality than those with same number of factors.

Conclusion

Smoking, PA, SB, DII and their combination had significant impact on all-cause mortality of NCD patients. The synergistic effects of these factors were observed, suggesting some combinations of high-risk lifestyle factor may be more harmful than others.
Insufficient proximal medullary filling of cephalomedullary nails in intertrochanteric femur fractures predicts excessive postoperative sliding: a case–control study
Authors: Li Shi-Jie , Chen Shi-Yi , Chang Shi-Min , Du Shou-Chao , Hu Sun-Jun
Published: March 2023

Objective

Excessive postoperative sliding is a common complication of intramedullary nails in the treatment of intertrochanteric femur fractures. The aim of this study was to identify risk factors for excessive postoperative sliding in the intertrochanteric fractures treated with an intramedullary nail.

Methods

A retrospective analysis of 369 patients with femoral intertrochanteric fractures treated with short intramedullary nails between February 2017 and September 2020 was performed. Patients were classified into an excessive sliding group (ES group) and a control group according to the sliding distance after 6 months of follow-up. The proximal medullary filling degree (MFD), fracture reduction patterns in the anteroposterior (AP) view and lateral view, and tip-apex distance (TAD) were evaluated and compared in each group.

Results

Thirty-three cases were included in the ES group, and 336 cases were included in the control group. No significant differences in age, sex, fracture side, AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification, Dorr classification, Singh Osteoporosis Index (SOI), American Society of Anesthesiologists classification (ASA), TAD or fracture reduction patterns in the AP view were noted between the two groups. The negative reduction pattern can strongly predict excessive postoperative sliding (OR 4.286, 95% CI 1.637–11.216, P = 0.003). The incidence of excessive postoperative sliding increased by 8.713-fold when the MFD decreased by 10% (OR 8.713, 95% CI 1.925–39.437, P = 0.005).

Conclusions

A low medullary filling degree and negative fracture reduction pattern in the lateral view were both independent risk factors for excessive postoperative sliding.
Cross-sectional analysis of potential risk factors of the pineal gland calcification
Authors: Jalali Nazanin , Firouzabadi Mohammadrasoul Dehghani , Mirshekar Ali , Khalili Parvin , Ravangard Amir reza , Ahmadi Jafar , Askari Pooya Saeed , Jalali Zahra
Published: March 2023

The Pineal gland (PG) is the site of production of melatonin as an important central hormone in the body. It is not known yet whether PG calcification (PGC) is an age-associated physiological process or a pathologic condition caused by lifestyle-factors and metabolic-dysregulations.

Here, we performed a cross-sectional analysis on 586 patients referred to have Computed Tomographic (CT) scans (above 15 years old), in the Ali Ebne Abi Taleb hospital radiology center in 2017–2018. Based on the CT-scans of the brain, the presence of PGC was recorded and a score of scale 0 to 6 (PGC_score) was calculated for its intensity based on the volume and the Hounsfield units of the calcified pineal. Logistic and ordered logistic regression tests were employed to determine potential risk factor of PGC and higher PGC_score, respectively, testing the factors age, sex, history of cardiovascular and metabolic diseases, smoking and opioid use. We found male sex (OR: 2.30 (95% CI:1.39–3.82) and smoking cigarettes (OR: 4.47 (95% CI:1.01–19.78)) as the main potential risk factors for the pineal gland calcification. For PGC_score, we found age to be dose-dependently associated with PGC_score only in patients aged below 63 (p-trend < 0.001). Stratifying for age, in patients < 63 years old, we found age, male sex (positive association) and dyslipidemia (negative association) as the main significantly associated factors of PGC_score. On the contrary, in patients aged >  = 63, cigarette smoking was the only significantly associated factor of higher PGC_score.

In conclusion, our results indicate that at ages below 63, age, male sex and blood lipid are the main associated factors of higher PGC, but at ages above that, the lifestyle factor smoking is significantly associated with higher pineal gland calcification.
Influence of poor sleep on cardiovascular disease-free life expectancy: a multi-resource-based population cohort study
Authors: Huang Bo-Huei , del Pozo Cruz Borja , Teixeira-Pinto Armando , Cistulli Peter A. , Stamatakis Emmanuel
Published: March 2023

Background

The complexity of sleep hinders the formulation of sleep guidelines. Recent studies suggest that different unhealthy sleep characteristics jointly increase the risks for cardiovascular disease (CVD). This study aimed to estimate the differences in CVD-free life expectancy between people with different sleep profiles.

Methods

We included 308,683 middle-aged adults from the UK Biobank among whom 140,181 had primary care data linkage. We used an established composite sleep score comprising self-reported chronotype, duration, insomnia complaints, snoring, and daytime sleepiness to derive three sleep categories: poor, intermediate, and healthy. We also identified three clinical sleep disorders captured by primary care and inpatient records within 2 years before enrollment in the cohort: insomnia, sleep-related breathing disorders, and other sleep disorders. We estimated sex-specific CVD-free life expectancy with three-state Markov models conditioning on survival at age 40 across different sleep profiles and clinical disorders.

Results

We observed a gradual loss in CVD-free life expectancy toward poor sleep such as, compared with healthy sleepers, poor sleepers lost 1.80 [95% CI 0.96–2.75] and 2.31 [1.46–3.29] CVD-free years in females and males, respectively, while intermediate sleepers lost 0.48 [0.41–0.55] and 0.55 [0.49–0.61] years. Among men, those with clinical insomnia or sleep-related breathing disorders lost CVD-free life by 3.84 [0.61–8.59] or 6.73 [5.31–8.48] years, respectively. Among women, sleep-related breathing disorders or other sleep disorders were associated with 7.32 [5.33–10.34] or 1.43 [0.20–3.29] years lost, respectively.

Conclusions

Both self-reported and doctor-diagnosed poor sleep are negatively associated with CVD-free life, especially pronounced in participants with sleep-related breathing disorders.
Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model
Authors: Veras Flavio P. , Gomes Giovanni F. , Silva Bruna M. S. , Caetité Diego B. , Almeida Cicero J. L. R. , Silva Camila Meirelles S. , Schneider Ayda H. , Corneo Emily S. , Bonilha Caio S. , Batah Sabrina S. , Martins Ronaldo , Arruda Eurico , Fabro Alexandre T. , Alves-Filho José C. , Cunha Thiago M. , Cunha Fernando Q.
Published: March 2023

Background

COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment.

Methods

Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers.

Results

DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I.

Conclusions

Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.
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

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

Cancer 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

B7-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

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

Innate 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

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

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

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

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

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.
Precision information extraction for rare disease epidemiology at scale
Authors: Kariampuzha William Z. , Alyea Gioconda , Qu Sue , Sanjak Jaleal , Mathé Ewy , Sid Eric , Chatelaine Haley , Yadaw Arjun , Xu Yanji , Zhu Qian
Published: March 2023

Background

The United Nations recently made a call to address the challenges of an estimated 300 million persons worldwide living with a rare disease through the collection, analysis, and dissemination of disaggregated data. Epidemiologic Information (EI) regarding prevalence and incidence data of rare diseases is sparse and current paradigms of identifying, extracting, and curating EI rely upon time-intensive, error-prone manual processes. With these limitations, a clear understanding of the variation in epidemiology and outcomes for rare disease patients is hampered. This challenges the public health of rare diseases patients through a lack of information necessary to prioritize research, policy decisions, therapeutic development, and health system allocations.

Methods

In this study, we developed a newly curated epidemiology corpus for Named Entity Recognition (NER), a deep learning framework, and a novel rare disease epidemiologic information pipeline named EpiPipeline4RD consisting of a web interface and Restful API. For the corpus creation, we programmatically gathered a representative sample of rare disease epidemiologic abstracts, utilized weakly-supervised machine learning techniques to label the dataset, and manually validated the labeled dataset. For the deep learning framework development, we fine-tuned our dataset and adapted the BioBERT model for NER. We measured the performance of our BioBERT model for epidemiology entity recognition quantitatively with precision, recall, and F1 and qualitatively through a comparison with Orphanet. We demonstrated the ability for our pipeline to gather, identify, and extract epidemiology information from rare disease abstracts through three case studies.

Results

We developed a deep learning model to extract EI with overall F1 scores of 0.817 and 0.878, evaluated at the entity-level and token-level respectively, and which achieved comparable qualitative results to Orphanet’s collection paradigm. Additionally, case studies of the rare diseases Classic homocystinuria, GRACILE syndrome, Phenylketonuria demonstrated the adequate recall of abstracts with epidemiology information, high precision of epidemiology information extraction through our deep learning model, and the increased efficiency of EpiPipeline4RD compared to a manual curation paradigm.

Conclusions

EpiPipeline4RD demonstrated high performance of EI extraction from rare disease literature to augment manual curation processes. This automated information curation paradigm will not only effectively empower development of the NIH Genetic and Rare Diseases Information Center (GARD), but also support the public health of the rare disease community.
Epigenetics as a versatile regulator of fibrosis
Authors: Liu Yangdan , Wen Dongsheng , Ho Chiakang , Yu Li , Zheng Danning , O’Reilly Steven , Gao Ya , Li Qingfeng , Zhang Yifan
Published: March 2023

Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications.

Graphical Abstract
Risk, lifestyle and non-communicable diseases of poverty
Authors: Manderson Lenore , Jewett Sara
Published: March 2023

Common discourse in public health and preventive medicine frames non-communicable diseases, including cardiovascular and metabolic diseases, as diseases of ‘lifestyle’; the choice of terminology implies that their prevention, control and management are amenable to individual action. In drawing attention to global increases in the incidence and prevalence of non-communicable disease, however, we increasingly observe that these are non-communicable diseases of poverty. In this article, we call for the reframing of discourse to emphasize the underlying social and commercial determinants of health, including poverty and the manipulation of food markets. We demonstrate this by analysing trends in disease, which indicate that diabetes- and cardiovascular-related DALYS and deaths are increasing particularly in countries categorized as low-middle to middle levels of development. In contrast, countries with very low levels of development contribute least to diabetes and document low levels of CVDs. Although this might suggest that NCDs track increased national wealth, the metrics obscure the ways in which the populations most affected by these diseases are among the poorest in many countries, and hence, disease incidence is a marker of poverty not wealth. We also illustrate variations in five countries — Mexico, Brazil, South Africa, India and Nigeria — by gender, and argue that these differences are associated with gender norms that vary by context rather than sex-specific biological pathways.

We tie these trends to shifts in food consumption from whole foods to ultra-processed foods, under colonialism and with continued globalization. Industrialization and the manipulation of global food markets influence food choice in the context of limited household income, time, and household and community resources. Other factors that constitute risk factors for NCDs are likewise constrained by low household income and the poverty of the environment for people with low income, including the capacity of individuals in sedentary occupations to engage in physical activity. These contextual factors highlight extremely limited personal power over diet and exercise. In acknowledging the importance of poverty in shaping diet and activity, we argue the merit in using the term non-communicable diseases of poverty and the acronym NCDP. In doing so, we call for greater attention and interventions to address structural determinants of NCDs.
Antiviral activities of Artemisia vulgaris L. extract against herpes simplex virus
Authors: Xiao Ji , Liu Ping , Hu Yuze , Liu Tao , Guo Yuying , Sun Pinghua , Zheng Junxia , Ren Zhe , Wang Yifei
Published: March 2023

Background

Artemisia vulgaris L. is often used as a traditional Chinese medicine with the same origin of medicine and food. Its active ingredient in leaves have multiple biological functions such as anti-inflammatory, antibacterial and insecticidal, anti-tumor, antioxidant and immune regulation, etc. It is confirmed that folium Artemisiae argyi has obvious anti-HBV activity, however, its antiviral activity and mechanism against herpesvirus or other viruses are not clear. Hence, we aimed to screen the crude extracts (Fr.8.3) isolated and extracted from folium A. argyi to explore the anti-herpesvirus activity and mechanism.

Methods

The antiherpes virus activity of Fr.8.3 was mainly characterized by cytopathic effects, real-time PCR detection of viral gene replication and expression levels, western blotting, viral titer determination and plaque reduction experiments. The main components of Fr.8.3 were identified by using LC–MS, and selected protein targets of these components were investigated through molecular docking.

Results

We collected and isolated a variety of A. vulgaris L. samples from Tangyin County, Henan Province and then screened the A. vulgaris L. leaf extracts for anti-HSV-1 activity. The results of the plaque reduction test showed that the crude extract of A. vulgaris L.-Fr.8.3 had anti-HSV-1 activity, and we further verified the anti-HSV-1 activity of Fr.8.3 at the DNA, RNA and protein levels. Moreover, we found that Fr.8.3 also had a broad spectrum of antiviral activity. Finally, we explored its anti-HSV-1 mechanism, and the results showed that Fr.8.3 exerted an anti-HSV-1 effect by acting directly on the virus itself. Then, the extracts were screened on HSV-1 surface glycoproteins and host cell surface receptors for potential binding ability by molecular docking, which further verified the phenotypic results. LC–MS analysis showed that 1 and 2 were the two main components of the extracts. Docking analysis suggested that compounds from extract 1 might similarly cover the binding domain between the virus and the host cells, thus interfering with virus adhesion to cell receptors, which provides new ideas and insights for clinical drug development for herpes simplex virus type 1.

Conclusion

We found that Fr.8.3 has anti-herpesvirus and anti-rotavirus effects. The main 12 components in Fr.8.3 were analyzed by LC–MS, and the protein targets were finally predicted through molecular docking, which showed that alkaloids may play a major role in antiviral activity.
A comprehensive review on traditional uses, phytochemistry and pharmacological properties of Paeonia emodi Wall. ex Royle: current landscape and future perspectives
Authors: Zahra Nida , Iqbal Javed , Arif Muhammad , Abbasi Banzeer Ahsan , Sher Hassan , Nawaz Ayesha Fazal , Yaseen Tabassum , Ydyrys Alibek , Sharifi-Rad Javad , Calina Daniela
Published: March 2023

Paeoniaemodi Wall. ex Royle is commonly known as Himalayan paeony has great importance as a food and medicine. The practice of Paeoniaemodi Wall. ex Royle is very ancient and it is conventionally used for a wide range of illnesses in the folk system of medicine because of its wide beneficial phytochemical profile. The main purpose of the current review was the synthesis of recent data on botany, ethnopharmacology, phytochemistry and potential pharmacological mechanisms of action of Paeoniaemodi Wall. ex Royle, thus offering new prospects for the development of new adjuvant natural therapies. Using scientific databases such as PubMed/MedLine, Scopus, Web of Science, ScienceDirect, Google Scholar, Springer, and Wiley, a comprehensive literature search was performed for Paeoniaemodi Wall. ex Royle. For searching, we used the next MeSH terms: “Biological Product/isolation and purification”, “Biological Products/pharmacology”, “Drug Discovery/methods”, “Ethnopharmacology, Medicine”, “Traditional/methods”, “Paeonia/chemistry”, “Plant Extracts/pharmacology”, “Phytochemicals/chemistry”, “Phytochemicals/pharmacology”, “Plants, Medicinal”. The results of the most recent studies were analyzed and the most important data were summarized in tables and figures. Phytochemical research of Paeoniaemodi Wall. ex Royle has led to the isolation of triterpenes, monoterpenes, phenolic acids, fatty acids, organic compounds, steroids, free radicals and some other classes of primary metabolites. In addition, diverse pharmacological activities like antibacterial, antifungal, anticoagulant, airway relaxant lipoxygenase and beta-glucuronidase inhibiting activity, radical scavenging activity, phytotoxic and insecticidal activities have been reported for Paeoniaemodi Wall. ex Royle. Different bioactive compounds of Paeoniaemodi Wall. ex Royle has proven their therapeutic potential in modern pharmacological and biomedical research to cure numerous gastrointestinal and nervous disorders. In future, further in vitro and in vivo therapeutic studies are required to identify new mechanisms of action, pharmacokinetics studies, and new pharmaceutical formulations for target transport and possible interaction with allopathic drugs. Also, new research regarding quality evaluation, toxicity and safety data in humans is needed.