bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework for evaluating health system surveillance sensitivity to support public health decision-making for malaria elimination: a case study from Indonesia
Authors: Ahmad Riris Andono , Nelli Luca , Surendra Henry , Arisanti Risalia Reni , Lesmanawati Dyah Ayu Shinta , Byrne Isabel , Dumont Elin , Drakeley Chris , Stresman Gillian , Wu Lindsey
Published: July 2022

Background

The effectiveness of a surveillance system to detect infections in the population is paramount when confirming elimination. Estimating the sensitivity of a surveillance system requires identifying key steps in the care-seeking cascade, from initial infection to confirmed diagnosis, and quantifying the probability of appropriate action at each stage. Using malaria as an example, a framework was developed to estimate the sensitivity of key components of the malaria surveillance cascade.

Methods

Parameters to quantify the sensitivity of the surveillance system were derived from monthly malaria case data over a period of 36 months and semi-quantitative surveys in 46 health facilities on Java Island, Indonesia. Parameters were informed by the collected empirical data and estimated by modelling the flow of an infected individual through the system using a Bayesian framework. A model-driven health system survey was designed to collect empirical data to inform parameter estimates in the surveillance cascade.

Results

Heterogeneity across health facilities was observed in the estimated probability of care-seeking (range = 0.01–0.21, mean ± sd = 0.09 ± 0.05) and testing for malaria (range = 0.00–1.00, mean ± sd = 0.16 ± 0.29). Care-seeking was higher at facilities regularly providing antimalarial drugs (Odds Ratio [OR] = 2.98, 95% Credible Intervals [CI]: 1.54–3.16). Predictably, the availability of functioning microscopy equipment was associated with increased odds of being tested for malaria (OR = 7.33, 95% CI = 20.61).

Conclusions

The methods for estimating facility-level malaria surveillance sensitivity presented here can help provide a benchmark for what constitutes a strong system. The proposed approach also enables programs to identify components of the health system that can be improved to strengthen surveillance and support public-health decision-making.
Reducing disparities in kidney transplantation for Spanish-speaking patients through creation of a dedicated center
Authors: Pande Madhura , Grafals Monica , Rizzolo Katherine , Pomfret Elizabeth , Kendrick Jessica
Published: July 2022

Introduction

Hispanic Americans receive disproportionately fewer organ transplants than non-Hispanic whites. In 2018, the Hispanic Kidney Transplant Program (HKTP) was established as at the University of Colorado Hospital (UCH). The purpose of this quality improvement study was to examine the effect of this culturally sensitive program in reducing disparities in kidney transplantation.

Methods

We performed a mixed-methods analysis of data from 436 Spanish-speaking patients referred for transplant to UCH between 2015 and 2020. We compared outcomes for patients referred between 2015–2017 (n = 156) to those referred between 2018–2020 (n = 280). Semi-structured phone interviews were conducted with 6 patients per time period and with 6 nephrology providers in the Denver Metro Area. Patients and providers were asked to evaluate communication, transplant education, and overall experience.

Results

When comparing the two time periods, there was a significant increase in the percentage of patients being referred (79.5% increase, p-0.008) and evaluated for transplant (82.4% increase, p = 0.02) during 2018–2020. While the number of committee reviews and number waitlisted increased during 2018–2020, it did not reach statistical significance (82.9% increase, p = 0.37 and 79.5% increase, p = 0.75, respectively. During patient and provider interviews, we identified 4 themes reflecting participation in the HKTP: improved communication, enhanced patient education, improved experience and areas for advancement. Overall, patients and providers reported a positive experience with the HKTP and noted improved patient understanding of the transplantation process.

Conclusions

The establishment of the HKTP is associated with a significant increase in Spanish-speaking Hispanic patients being referred and evaluated for kidney transplantation.
miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells
Authors: Singh Garima , Sharma Sonika Kumari , Singh Samarendra Kumar
Published: July 2022

MicroRNAs have emerged as an important regulator of cell cycle and various other cellular processes. Aberration in microRNAs has been linked with development of several cancers and other diseases but still very little is known about the mechanism by which they regulate these cellular events. High risk human papilloma virus (HR HPV) is the causative agent of 99% of cervical cancer cases which attenuates multiple tumor suppressors and checkpoint factors of the host cell. The viral proteins also stabilize many oncogenic factors, including an essential cell cycle regulator Cdt2/DTL which in turn promotes cell transformation and proliferation. In this study, we report that a micro-RNA, miR-34a by suppressing HPV E6 protein, destabilizes Cdt2/DTL protein level in HPV infected cervical cancer cell lines. Destabilization of Cdt2 stabilizes pro-apoptotic and onco-suppressor proteins like p21 and Set8 and suppresses cell proliferation, invasion and migration capabilities of the HPV positive cervical cancer cells. Overexpression of either HPV E6 or Cdt2 genes along with miR-34a restored back the suppressed proliferation rate. This study is the first-ever report to show that miR-34a regulates cell cycle factor Cdt2 by suppressing viral E6 protein level, thus opening up the possibility of exploring miR-34a as a specific therapy for cervical cancer treatment.
Shigella-associated mild encephalitis with reversible splenial lesion in Hospital Center Delafontaine, Saint-Denis, France: a case report
Authors: Le Soudéer Louise , Truong Jeanne , Le Gal Julie , Escoda Simon
Published: July 2022

Background

Mild encephalitis with reversible splenial lesion of the corpus callosum (MERS) is a clinical/radiological syndrome characterized by hyperintense signal changes in the splenium of the corpus callosum visible on diffusion weighted imaging (DWI) in the brain Magnetic Resonance Imaging (MRI) associated with various neurological symptoms. Progression is usually favorable with disappearance of the MRI brain lesion and regression of clinical symptoms over a few days to a few weeks. The exact pathophysiology remains unclear. MERS can be associated with various pathogens.

Case presentation

We report here a paediatric case of MERS associated with Shigella flexneri infection. A five-year-old boy with no relevant past medical history presented with symptoms such as headache, fever, profuse diarrhea and hallucinations.

A brain Magnetic Resonance Imaging performed on Day 2 of the symptoms revealed hyperintense signal changes of the splenium of the corpus callosum in T2 FLAIR sequence. This infection had a favorable outcome after antibiotic therapy. No further recurrence of symptoms was observed and a follow-up clinical examination eight weeks later was normal. A follow-up brain Magnetic Resonance Imaging three months after discharge was also normal and the hyperintense signal changes of the splenium of the corpus callosum had disappeared completely.

Conclusions

MERS is a clinical/radiological syndrome with a generally good prognosis.

We believe that this is the first description of a case of Shigella-associated MERS.

It is useful to know about this condition to help distinguish it from acute disseminated encephalomyelitis.
Food insecurity during COVID-19 in children with end-stage kidney disease: a pilot study
Authors: Chan Melvin , Mokiao Reya , Wilson Amy C. , Pottanat Neha , Hingorani Sangeeta , Starr Michelle C.
Published: July 2022

Background

Food insecurity, an important social determinant of health among children, has become more common during the COVID-19 pandemic. Children with chronic diseases including end-stage kidney disease (ESKD) are at higher risk of food insecurity due to their complex care needs, medication burden, and dietary restrictions. No data exists describing food insecurity prevalence in pediatric ESKD patients during the COVID-19 pandemic.

Methods

Food insecurity was assessed among families of children (age 0–18 years) with ESKD on chronic dialysis at two pediatric academic medical centers. Families were screened in April 2020 using the Hunger Vital Sign, a validated 2-question screening tool. We assessed impact of COVID-19 on food insecurity. We compared serum phosphorus “pre-COVID” (January/February 2020) to “during COVID” (April/May 2020).

Results

A total of 29 families enrolled in this study. 62% (18/29) of children with ESKD lived in food insecure households, and of those, 72% (13/18) reported that COVID-19 had worsened their food insecurity status. During the COVID-19 pandemic, food insecure patients experienced greater rise in their serum phosphorus levels (1.1 mg/dL vs. 0 mg/dL, p = 0.03) and decreased likelihood of having adequate phosphorus control (50% vs. 11%, p = 0.03).

Conclusion

Food insecurity was common among children with ESKD on chronic dialysis during the COVID-19 pandemic. Children with food insecurity had a greater increase in their phosphorus levels during the pandemic than did food secure children. Further exploration into how food resources such as an onsite food pantry impacts food insecurity and phosphorus control in children with ESKD is essential.
Influencing factors of multiple adverse outcomes among schizophrenia patients using count regression models: a cross-sectional study
Authors: Chen Lichang , Tan Wenyan , Lin Xiao , Lin Haicheng , Xi Junyan , Zhang Yuqin , Jia Fujun , Hao Yuantao
Published: July 2022

Background

Schizophrenia patients have increased risks of adverse outcomes, including violent crime, aggressiveness, and suicide. However, studies of different adverse outcomes in schizophrenia patients are limited and the influencing factors for these outcomes need clarification by appropriate models. This study aimed to identify influencing factors of these adverse outcomes by examining and comparing different count regression models.

Methods

This study included schizophrenia patients who had at least one follow-up record in the Guangdong Mental Health Center Network Medical System during 2020. Three types of adverse outcomes were included: a) aggressiveness with police dispatch or violent crime, b) aggressiveness without police dispatch, and c) self-harm or suicide attempts. The incidence density of these adverse outcomes was investigated using the Poisson, negative binomial (NB), zero-inflated Poisson (ZIP), and zero-inflated negative binomial (ZINB) models, accordingly. The best model was chosen based on goodness-of-fit tests. We further analyzed associations between the number of occurrences of adverse outcomes and sociodemographic, clinical factors with the best model.

Results

A total of 130,474 schizophrenia patients were enrolled. Adverse outcomes rates were reported to be less than 1% for schizophrenia patients in 2020, in Guangdong. The NB model performed the best in terms of goodness-of-fit and interpretation when fitting for the number of occurrences of aggressiveness without police dispatch, whereas the ZINB models performed better for the other two outcomes. Age, sex, and history of adverse outcomes were influencing factors shared across these adverse outcomes. Higher education and employment were protective factors for aggressive and violent behaviors. Disease onset aged ≥ 18 years served as a significant risk factor for aggressiveness without police dispatch, and self-harm or suicide attempts. Family history of mental diseases was a risk factor for self-harm or suicide attempts individually.

Conclusions

NB and ZINB models were selected for fitting the number of occurrences of adverse outcomes among schizophrenia patients in our studies. Influencing factors for the incidence density of adverse outcomes included both those shared across different types and those individual to specific types. Therefore, comprehensive and customized tools in risk assessment and intervention might be necessary.
What are the economic dimensions of occupational health and how should they be measured? A qualitative study
Authors: Lutz Nathanael , Dalle Grave Lena , Richter Dirk , Deliens Tom , Verhaeghe Nick , Taeymans Jan , Clarys Peter
Published: July 2022

Background

Decision makers want to know if there is a financial benefit in investing scarce resources in occupational health management (OHM). Economic evaluations (EEs) of OHM-strategies try to answer this question. However, EEs of OHM-strategies which are strongly marked by quantitative methods may be limited by contextual, qualitative residuals. Therefore, the objectives of this study were to (1) explore important economic dimensions of OHM and (2) to discuss the methods used in current EEs for measuring these dimensions.

Methods

In this explorative qualitative study, OHM-specialists were recruited via the Swiss organisation for health promotion. Thirteen semi-structured interviews were performed from November 2020 until May 2021. Videotapes were transcribed verbatim and organised by using an open coding strategy. Codes were clustered and synthesised as themes (i.e. the dimensions of EEs of OHM) through a mix of inductive and deductive content analysis. Member check with eight participants was accomplished to validate the results.

Results

The interviews had an average duration of 70.5 min and yielded 609 individual codes. These codes were merged into 28 subcategories which were finally categorised into five main themes: Understanding of OHM, costs, benefits, environmental aspects, and evaluation of OHM. Participants stated that the greater part of costs and benefits cannot be quantified or monetised and thus, considered in quantitative EEs. For example, they see a culture of health as key component for a successful OHM-strategy. However, the costs to establish such a culture as well as its benefits are hard to quantify. Participants were highly critical of the use of absenteeism as a linear measure of productivity. Furthermore, they explained that single, rare events, such as a change in leadership, can have significant impact on employee health. However, such external influence factors are difficult to control.

Conclusions

Participants perceived costs and benefits of OHM significantly different than how they are represented in current EEs. According to the OHM-specialists, most benefits cannot be quantified and thus, monetised. These intangible benefits as well as critical influencing factors during the process should be assessed qualitatively and considered in EEs when using them as a legitimation basis vis-à-vis decision makers.
Comparison of region-of-interest delineation methods for diffusion tensor imaging in patients with cervical spondylotic radiculopathy
Authors: Wu Penghuan , Huang Chengyan , Shi Benchao , Jin Anmin
Published: July 2022

Background

Diffusion tensor imaging is a promising technique for determining the responsible lesion of cervical radiculopathy, but the selection and delineation of the region of interest (ROI) affect the results. This study explored the impact of different ROI sketching methods on the repeatability and consistency of DTI measurement values in patients with cervical spondylotic radiculopathy (CSR).

Methods

This retrospective study included CSR patients who underwent DTI imaging. The images were analyzed independently by two radiologists. Four delineation methods were used: freehand method, maximum roundness, quadrilateral method, and multi-point averaging method. They re-examined the images 6 weeks later. The intra-class correlation coefficient (ICC) was used to investigate the consistency between the two measurements and the reproducibility between two radiologists.

Results

Forty-two CSR patients were included in this study. The distribution of the compressed nerve roots was five C4, eight C5, sixteen C6, eleven C7, and two C8. No differences were found among the four methods in fractional anisotropy (FA) or apparent diffusion coefficient (ADC), irrespective of radiologists (all P>0.05). Similar results were observed between the first and second measurements (all P>0.05), but some significant differences were observed for radiologist 2 for the four-small rounds method (P=0.033). The freehand and single largest circle methods were the two methods with the highest ICC between the two measurements and the two radiologists (all ICC >0.90).

Conclusion

The freehand and single largest circle methods were the most consistent methods for delineating DTI ROI in patients with CSR.
Surgically managed symptomatic intraspinal lumbar facet synovial cyst outcome of surgical treatment with resection and instrumented posterolateral fusion, a case series
Authors: Lalanne Lyonel Beaulieu , Carmona Roberto Larrondo , Cirillo Totera Juan I. , Lemos Facundo Alvarez , Wilson José Tomás Muñoz , Beaulieu Montoya Andre M.
Published: July 2022

Background

There is controversy regarding the treatment of symptomatic synovial cysts, specifically, the need for a concomitant fusion when surgical resection of the synovial cysts is required. We present a retrospective review of a series of patients treated for symptomatic synovial cysts of the lumbar region during the last 20 years by a single surgeon, analyzing the current available literature.

Methods

Retrospective review. The same surgical technique was applied to all patients. Demographic, clinical, surgical data and synovial cyst recurrence rate were recorded. Postoperative results reported by patients were documented according to the McNab score.

Results

Sixty nine subjects, with mean follow-up of 7.4 years. 62% (43) were female, with a mean 57.8 years at the time of surgery. In 91.3% (63), the primary management was conservative for a minimum period of 3 months. All subjects underwent surgery due to the failure of conservative treatment. The segment most operated on was L4–L5 (63.77%). 91.3% (63) of the sample reported excellent and good and 6 subjects (8.6%) fair or poor results. There was no evidence of synovial cysts recurrence at the operated level.

Conclusion

In symptomatic synovial cysts, it seems that conservative treatment is only effective in a limited number of patients and in the short term. Thus, the recommendation of a surgical indication should proceed as soon as the conservative management fails to result in significant symptom relief. Based on our results, we recommend, together with the resection of the cyst, the instrumentation of the segment to avoid its recurrence and the management of axial pain.
The socio-economic inequality in body mass index: a PERSIAN cohort-based cross-sectional study on 20,000 Iranian adults
Authors: Pourfarzi Farhad , Rezaei Satar , Zahirian Moghadam Telma , Zandian Hamed , Dibazar Foad
Published: July 2022

Introduction

The aim of the present study was to explore and determine the association between BMI and socio-economic factors in Iran.

Methods

Adults aged 35 to 70 (n = 20,460) were included from Ardabil Non-Communicable Disease (ArNCD) cohort study. BMI was calculated as kg/m2. Principal Component Analysis (PCA) was used to determine the socio-economic quintiles. Multivariate linear regression was performed to analyze the association of BMI as dependent variable with explanatory variables, Additionally, decomposition analyzing conducted to identify factors that explained wealth-related inequality in obesity.

Results

The prevalence of overweight and obese people was 83.7% (41.4% overweight and 42.5% obese) wherein the highest frequency of obese people belonged to the age group of 45 to 49 years old (19.9%) and to the illiterate people (33.1%). The results of multivariate linear regression model showed that age, being female, marriage, lower education level, having chronic disease, alcohol use, and higher socioeconomic level positively associated with obesity. The results of the decomposition model showed that the most important variables affecting socioeconomic inequality in higher BMI level were socioeconomic status (75.8%), being women (5.6%), education level (− 4.1%), and having chronic disease (2.4%).

Conclusion

BMI showed significant association with socio-economic status, where richest people had significantly higher BMI than poorest group. Considering the direct role of high BMI in non-communicable diseases, new policies are needed to be developed and implemented by means of diet intervention and increased physical activity to control the BMI in the population of Iran.
Factors facilitating clinical application of and adherence to evidence-based healthcare among medical professionals attending national competitions in Taiwan: a study based on the decomposed theory of planned behaviour
Authors: Tsai Jung-Mei , Wu Yu-Hung , Yu Shu
Published: July 2022

Background

Implementing evidence-based healthcare (EBHC) to improve the quality of patient care is a key issue for physicians and nurses. One of the most effective activities for achieving this is the annual topic-oriented clinical application national competition in Taiwan. Hundreds of clinical issues have been presented in this competition. By using the decomposed theory of planned behaviour (DTPB), this study explored physicians’ and nurses’ behaviour and adherence to the clinical application of EBHC after participating in the competitions.

Methods

We conducted a 3-month cross-sectional online survey using a structured questionnaire adapted from the original study of the DTPB to collect behavioural and intention-related data. We also used a model of seven action stages (from aware of to adhered to) to assess target behaviours. We targeted contestants of the EBHC competitions between 1999 and 2017 as study participants. Of 631 teams, 321 teams completed the questionnaire, representing a 49.5% response rate. We applied structural equation modelling to test model fit. Moreover, we executed multivariate logistic regression to identify potential predictors.

Results

Of the respondents, 33.3% reportedly reached the final adhered to stage. The DTPB model exhibited a good fit to the observed data. All constructs (usefulness, compatibility, peer influence, superior influence, self-efficacy, resource facilitating conditions, attitude, subjective norms, behavioural control, and intentions) were positively associated with the target behaviours, except for ease of use and technology facilitating conditions. Furthermore, the study model explained the variance in the target behaviours (37.0%). Having managerial duties (odds ratio [OR] =2.03, 95% confidence interval [CI] =1.10–3.77), resource facilitating conditions (OR = 1.06, 95% CI = 1.01–1.11), behavioural control (OR = 2.21, 95% CI = 1.47–3.32), and intentions (OR = 1.96, 95% CI = 1.40–2.73) were significant predictors of the achievement of the adhered to stage.

Conclusions

The study demonstrated the association between determinants of behaviour and clinical applications and factors influencing adherence to EBHC among competition participants. The adherence rate was not high after the competitions, and this may be improved by promoting certain factors associated with the target behaviours.
Secondary use of health care data and left-over biosamples within the ‘Medical Informatics Initiative’ (MII): a quasi-randomized controlled evaluation of patient perceptions and preferences regarding the consent process
Authors: Roschka Sybille , Leddig Torsten , Bullerjahn Mandy , Richter Gesine , Liedtke Wenke , Langanke Martin , Hoffmann Wolfgang
Published: July 2022

Background

Data collected during routine health care and ensuing analytical results bear the potential to provide valuable information to improve the overall health care of patients. However, little is known about how patients prefer to be informed about the possible usage of their routine data and/or biosamples for research purposes before reaching a consent decision. Specifically, we investigated the setting, the timing and the responsible staff for the information and consent process.

Methods

We performed a quasi-randomized controlled trial and compared the method by which patients were informed either in the patient admission area following patient admission by the same staff member (Group A) or in a separate room by another staff member (Group B). The consent decision was hypothetical in nature. Additionally, we evaluated if there was the need for additional time after the information session and before taking the consent decision. Data were collected during a structured interview based on questionnaires where participants reflected on the information and consent process they went through.

Results

Questionnaire data were obtained from 157 participants in Group A and 106 participants in Group B. Overall, participants in both groups were satisfied with their experienced process and with the way information was provided. They reported that their (hypothetical) consent decision was freely made. Approximately half of the interested participants in Group B did not show up in the separate room, while all interested participants in Group A could be informed about the secondary use of their routine data and left-over samples. No participants, except for one in Group B, wanted to take extra time for their consent decision. The hypothetical consent rate for both routine data and left-over samples was very high in both groups.

Conclusions

The willingness to support medical research by allowing the use of routine data and left-over samples seems to be widespread among patients. Information concerning this secondary data use may be given by trained administrative staff immediately following patient admission. Patients mainly prefer making a consent decision directly after information is provided and discussed. Furthermore, less patients are informed when the process is organized in a separate room.
Proton export upregulates aerobic glycolysis
Authors: Russell Shonagh , Xu Liping , Kam Yoonseok , Abrahams Dominique , Ordway Bryce , Lopez Alex S. , Bui Marilyn M. , Johnson Joseph , Epstein Tamir , Ruiz Epifanio , Lloyd Mark C. , Swietach Pawel , Verduzco Daniel , Wojtkowiak Jonathan , Gillies Robert J.
Published: July 2022

Introduction

Aggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the “Warburg Effect.” It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes. Oncogenic drivers can increase the expression of most proteins in the glycolytic pathway, including the terminal step of exporting H+ equivalents from the cytoplasm. Proton exporters maintain an alkaline cytoplasmic pH, which can enhance all glycolytic enzyme activities, even in the absence of oncogene-related expression changes. Based on this observation, we hypothesized that increased uptake and fermentative metabolism of glucose could be driven by the expulsion of H+ equivalents from the cell.

Results

To test this hypothesis, we stably transfected lowly glycolytic MCF-7, U2-OS, and glycolytic HEK293 cells to express proton-exporting systems: either PMA1 (plasma membrane ATPase 1, a yeast H+-ATPase) or CA-IX (carbonic anhydrase 9). The expression of either exporter in vitro enhanced aerobic glycolysis as measured by glucose consumption, lactate production, and extracellular acidification rate. This resulted in an increased intracellular pH, and metabolomic analyses indicated that this was associated with an increased flux of all glycolytic enzymes upstream of pyruvate kinase. These cells also demonstrated increased migratory and invasive phenotypes in vitro, and these were recapitulated in vivo by more aggressive behavior, whereby the acid-producing cells formed higher-grade tumors with higher rates of metastases. Neutralizing tumor acidity with oral buffers reduced the metastatic burden.

Conclusions

Therefore, cancer cells which increase export of H+ equivalents subsequently increase intracellular alkalization, even without oncogenic driver mutations, and this is sufficient to alter cancer metabolism towards an upregulation of aerobic glycolysis, a Warburg phenotype. Overall, we have shown that the traditional understanding of cancer cells favoring glycolysis and the subsequent extracellular acidification is not always linear. Cells which can, independent of metabolism, acidify through proton exporter activity can sufficiently drive their metabolism towards glycolysis providing an important fitness advantage for survival.
The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma
Authors: Li Quan , Zhang Pan , Hu Huixiao , Huang Hang , Pan Dong , Mao Guangyun , Hu Burong
Published: July 2022

Background

As a DNA surveillance mechanism, cell cycle checkpoint has recently been discovered to be closely associated with lung adenocarcinoma (LUAD) prognosis. It is also an essential link in the process of DNA damage repair (DDR) that confers resistance to radiotherapy. Whether genes that have both functions play a more crucial role in LUAD prognosis remains unclear.

Methods

In this study, DDR-related genes with cell cycle checkpoint function (DCGs) were selected to investigate their effects on the prognosis of LUAD. The TCGA-LUAD cohort and two GEO external validation cohorts (GSE31210 and GSE42171) were performed to construct a prognosis model based on the least absolute shrinkage and selection operator (LASSO) regression. Patients were divided into high-risk and low-risk groups based on the model. Subsequently, the multivariate COX regression was used to construct a prognostic nomogram. The ssGSEA, CIBERSORT algorithm, TIMER tool, CMap database, and IC50 of chemotherapeutic agents were used to analyze immune activity and responsiveness to chemoradiotherapy.

Results

4 DCGs were selected as prognostic signatures, and patients in the high-risk group had a lower overall survival (OS). The lower infiltration levels of immune cells and the higher expression levels of immune checkpoints appeared in the high-risk group. The damage repair pathways were upregulated, and chemotherapeutic agent sensitivity was poor in the high-risk group.

Conclusions

The 4-DCGs signature prognosis model we constructed could predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.
Diverse actions of sirtuin-1 on ovulatory genes and cell death pathways in human granulosa cells
Authors: Sapuleni Jackson , Szymanska Magdalena , Meidan Rina
Published: July 2022

Background

Human granulosa-lutein cells (hGLCs) amply express sirtuin-1 (SIRT1), a NAD + -dependent deacetylase that is associated with various cellular functions. SIRT1 was shown to elevate cAMP on its own and additively with human chorionic gonadotropin (hCG), it is therefore interesting to examine if SIRT1 affects other essential hGLC functions.

Methods

Primary hGLCs, obtained from the follicular aspirates of women undergoing IVF and SV40-transfected, immortalized hGLCs (SVOG cells), were used. Primary cells were treated with SIRT1 specific activator SRT2104, as well as hCG or their combination. Additionally, siRNA-targeting SIRT1 construct was used to silence endogenous SIRT1 in SVOG cells. PTGS2, EREG, VEGFA and FGF2 expression was determined using quantitative polymerase chain reaction (qPCR). Apoptotic and necroptotic proteins were determined by specific antibodies in western blotting. Cell viability/apoptosis was determined by the XTT and flow cytometry analyses. Data were analyzed using student t-test or Mann–Whitney U test or one-way ANOVA followed by Tukey HSD post hoc test.

Results

In primary and immortalized hGLCs, SRT2104 significantly upregulated key ovulatory and angiogenic genes: PTGS2, EREG, FGF2 and VEGFA, these effects tended to be further augmented in the presence of hCG. Additionally, SRT2104 dose and time-dependently decreased viable cell numbers. Flow cytometry of Annexin V stained cells confirmed that SIRT1 reduced live cell numbers and increased late apoptotic and necrotic cells. Moreover, we found that SIRT1 markedly reduced anti-apoptotic BCL-XL and MCL1 protein levels and increased cleaved forms of pro-apoptotic proteins caspase-3 and PARP. SIRT1 also significantly induced necroptotic proteins RIPK1 and MLKL. RIPK1 inhibitor, necrostatin-1 mitigated SIRT1 actions on RIPK1 and MLKL but also on cleaved caspase-3 and PARP and in accordance on live and apoptotic cells, implying a role for RIPK1 in SIRT1-induced cell death. SIRT1 silencing produced inverse effects on sorted cell populations, anti-apoptotic, pro-apoptotic and necroptotic proteins, corroborating SIRT1 activation.

Conclusions

These findings reveal that in hGLCs, SIRT1 enhances the expression of ovulatory and angiogenic genes while eventually advancing cell death pathways. Interestingly, these seemingly contradictory events may have occurred in a cAMP-dependent manner.
Improving allocative efficiency from network consolidation: a solution for the health workforce shortage
Authors: Jithitikulchai Theepakorn
Published: July 2022

Background

Public hospitals are facing a critical shortage of health workers. The area-based network consolidations could be the solution to increase the system capacity for human resources by improving local allocative efficiency.

Methods

This study develops counterfactual simulations for area-based network allocations for the health workforce in 10500 public hospitals in Thailand and examines improvements in allocative efficiency from the health workforce redistribution at different administrative levels such as sub-districts, districts, provinces, and health service areas. The workload per worker is calculated from the output measured by numbers of outpatient and inpatient cases and the input measured by numbers of health workers. Both output and input are weighted with their economic values and controlled for heterogeneity through regression analysis. Finally, this study compares the workload per worker and economic valuation of the area-based networks or ex-ante scenarios with the hospital-level or status quo scenario.

Results

Network consolidations of the sub-district primary-level hospitals within the same district could reduce workload per worker by seven percentage points. Another practical policy option is to consolidate similar hospital levels such as primary, first-level secondary, and mid-level secondary hospitals altogether within the same province which could result in the reduction of the workload per worker by 6–7 percentage points. The total economic value gained from consolidating similar hospital levels within the same province is about 15–18 percentage points of total labor cost in the primary hospitals.

Conclusion

This study illustrates the improvement in allocative efficiency of the health workforce in public hospitals from the area-based network consolidations. The results provide an insightful example of economic gains from efficiently reallocating the medical workforce within the same local areas. Major reforms are required such that the health care delivery units can automate their resources in corresponding to the population's health needs through a strengthening gatekeeping system.
Stock-outs of essential medicines among community health workers (CHWs) in low- and middle-income countries (LMICs): a systematic literature review of the extent, reasons, and consequences
Authors: Olaniran Abimbola , Briggs Jane , Pradhan Ami , Bogue Erin , Schreiber Benjamin , Dini Hannah Sarah , Hurkchand Hitesh , Ballard Madeleine
Published: July 2022

Background

This paper explores the extent of community-level stock-out of essential medicines among community health workers (CHWs) in low- and middle-income countries (LMICs) and identifies the reasons for and consequences of essential medicine stock-outs.

Methods

A systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases were searched with a prespecified strategy and the grey literature examined, January 2006–March 2021. Papers containing information on (1) the percentage of CHWs stocked out or (2) reasons for stock-outs along the supply chain and consequences of stock-out were included and appraised for risk of bias. Outcomes were quantitative data on the extent of stock-out, summarized using descriptive statistics, and qualitative data regarding reasons for and consequences of stock-outs, analyzed using thematic content analysis and narrative synthesis.

Results

Two reviewers screened 1083 records; 78 evaluations were included. Over the last 15 years, CHWs experienced stock-outs of essential medicines nearly one third of the time and at a significantly (p < 0.01) higher rate than the health centers to which they are affiliated (28.93% [CI 95%: 28.79–29.07] vs 9.17% [CI 95%: 8.64–9.70], respectively). A comparison of the period 2006–2015 and 2016–2021 showed a significant (p < 0.01) increase in CHW stock-out level from 26.36% [CI 95%: 26.22–26.50] to 48.65% [CI 95%: 48.02–49.28] while that of health centers increased from 7.79% [95% CI 7.16–8.42] to 14.28% [95% CI 11.22–17.34]. Distribution barriers were the most cited reasons for stock-outs. Ultimately, patients were the most affected: stock-outs resulted in out-of-pocket expenses to buy unavailable medicines, poor adherence to medicine regimes, dissatisfaction, and low service utilization.

Conclusions

Community-level stock-out of essential medicines constitutes a serious threat to achieving universal health coverage and equitable improvement of health outcomes. This paper suggests stock-outs are getting worse, and that there are particular barriers at the last mile. There is an urgent need to address the health and non-health system constraints that prevent the essential medicines procured for LMICs by international and national stakeholders from reaching the people who need them the most.
“The emotions were like a roller-coaster”: a qualitative analysis of e-diary data on healthcare worker resilience and adaptation during the COVID-19 outbreak in Singapore
Authors: Chan Alyssa Yenyi , Ting Celene , Chan Lai Gwen , Hildon Zoe Jane-Lara
Published: July 2022

Background

Uncertainties related to COVID-19 have strained the mental health of healthcare workers (HCWs) worldwide. Gaining the ability to adapt and thrive under pressure will be key to addressing this. We explore what characterises risk, vulnerability and resilient responses of HCWs during the early stages of the outbreak in Singapore.

Methods

We undertook qualitative theory-guided thematic analysis of e-diary entries from HCWs who navigated the outbreak from June–August 2020. Data were extracted from a subset of an online survey of n = 3616 participants collected across 9 institutions, including restructured hospitals, hospices and affiliated primary care partners.

Results

N = 663 or 18% submitted qualitative journal entries included for analyses. All professional cadres, local as well as foreign HCWs participated. Themes are reported according to the Loads–Levers–Lifts model of resilience and highlighted in italics. The model assumes that resilience is a dynamic process. Key factors threatening mental health (loading) risk included a notable rise in anxiety, the effects of being separated from loved ones, and experiencing heightened emotions and emotional overload. Bad situations were made worse, prompting vulnerable outcomes when HCWs experienced stigma in the community and effects of “public paranoia”; or under conditions where HCWs ended up feeling like a prisoner with little control or choice when either confined to staff accommodation or placed on quarantine/Stay Home Notices. Those with strife in their place of residence also described already difficult situations at work being aggravated by home life. Protection (lifts) came from being able to muster a sense of optimism about the future or feeling grateful for the pace of life slowing down and having the space to reprioritise. In contrast, when risk factors were present, balancing these in the direction of resilient outcomes was achieved by choosing to re-direct stress into positive narratives, drawing on inner agency, uptake of therapeutic activities, social support as well as faith and prayer and drawing comfort from religious community among other factors.

Conclusion

The Loads–Levers–Lifts model is used to guide analysis to inform intervention designs. Levers promoting resilience through targeting therapies, workplace policies and awareness campaigns accounting for identified loads are proposed.
Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling
Authors: Ribeiro Luiz W. , Pietri Mathéa , Ardila-Osorio Hector , Baudry Anne , Boudet-Devaud François , Bizingre Chloé , Arellano-Anaya Zaira E. , Haeberlé Anne-Marie , Gadot Nicolas , Boland Sonja , Devineau Stéphanie , Bailly Yannick , Kellermann Odile , Bencsik Anna , Schneider Benoit
Published: July 2022

Background

Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer’s disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown.

Results

Here, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aβ40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aβ rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas.

Conclusion

Our in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aβ peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD.
Organ-at-risk sparing with dynamic trajectory radiotherapy for head and neck cancer: comparison with volumetric arc therapy on a publicly available library of cases
Authors: Bertholet Jenny , Mackeprang Paul-Henry , Mueller Silvan , Guyer Gian , Loebner Hannes A. , Wyss Yanick , Frei Daniel , Volken Werner , Elicin Olgun , Aebersold Daniel M. , Fix Michael K. , Manser Peter
Published: July 2022

Background

Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation during beam-on. The aim of the study is to establish DTRT path-finding strategies, demonstrate deliverability and dosimetric accuracy and compare DTRT to state-of-the-art VMAT for common head and neck (HN) cancer cases.

Methods

A publicly available library of seven HN cases was created on an anthropomorphic phantom with all relevant organs-at-risk (OARs) delineated. DTRT plans were generated with beam incidences minimizing fractional target/OAR volume overlap and compared to VMAT. Deliverability and dosimetric validation was carried out on the phantom.

Results

DTRT and VMAT had similar target coverage. For three locoregionally advanced oropharyngeal carcinomas and one adenoid cystic carcinoma, mean dose to the contralateral salivary glands, pharynx and oral cavity was reduced by 2.5, 1.7 and 3.1 Gy respectively on average with DTRT compared to VMAT. For a locally recurrent nasopharyngeal carcinoma, D0.03 cc to the ipsilateral optic nerve was above tolerance (54.0 Gy) for VMAT (54.8 Gy) but within tolerance for DTRT (53.3 Gy). For a laryngeal carcinoma, DTRT resulted in higher dose than VMAT to the pharynx and brachial plexus but lower dose to the upper oesophagus, thyroid gland and contralateral carotid artery. For a single vocal cord irradiation case, DTRT spared most OARs better than VMAT. All plans were delivered successfully on the phantom and dosimetric validation resulted in gamma passing rates of 93.9% and 95.8% (2%/2 mm criteria, 10% dose threshold).

Conclusions

This study provides a proof of principle of DTRT for common HN cases with plans that were deliverable on a C-arm linac with high accuracy. The comparison with VMAT indicates substantial OAR sparing could be achieved.
Pressurized carbon dioxide lavage reduces the incidence of a radiolucent line around the tibial component two years after total knee arthroplasty
Authors: Sasaki Ryo , Nagashima Masaki , Otani Toshiro , Okada Yoshifumi , Aibara Noriyuki , Takeshima Kenichiro , Ishii Ken
Published: July 2022

Introduction

In cemented total knee arthroplasty (TKA), pressurized carbon dioxide (CO2) lavage prior to cement fixation can eliminate debris at the bone-cement interface and is considered effective for increasing cement penetration and preventing aseptic loosening. Regarding the risk of a preliminary diagnosis of implant loosening, a radiolucent line (RLL) is a valuable sign. The purpose of this study was to compare the incidence of a tibial RLL at 2 years after TKA with and without pressurized CO2 lavage.

Methods

This is a retrospective study. One hundred knees from 98 patients were enrolled in this study. TKA was performed without pressurized CO2 lavage (CO2− group) for the first 47 knees, and with pressurized CO2 lavage (CO2+ group) for the next 53 knees. The depth of cement penetration was measured just after surgery, and the incidence of tibial RLL > 2 mm at 2 years after TKA was determined.

Results

Significant differences between groups were not seen regarding pre- and postoperative clinical factors. The depth of cement penetration in each area was significantly higher in the CO2+ group. The frequency of knees with RLL > 2 mm was significantly lower in the CO2+ group than in the CO2− group (p < 0.001).

Conclusions

Pressurized CO2 lavage improved cement penetration and decreased the incidence of tibial RLL > 2 mm at 2 years after TKA.