bluuebunny/crossref_metadata_2025_split huggingface dataset:
How severe would prioritization-induced bottlenecks need to be offset the benefits from prioritizing COVID-19 vaccination to those most at risk in New York City?
Authors: Kim Hae-Young , Bershteyn Anna , McGillen Jessica B. , Braithwaite R. Scott 
Published: January 2023

Abstract
Background
Prioritization of higher-risk people for COVID-19 vaccination could prevent more deaths, but could slow vaccination speed. We used mathematical modeling to examine the trade-off between vaccination speed and prioritization for individuals age 65+ and essential workers.

Methods
We used a stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths). The model was calibrated to COVID-19 hospitalizations, ICU census, and deaths in NYC. We assumed 10,000 vaccinations per day, initially restricted to healthcare workers and nursing home populations, and subsequently expanded to other populations at alternative times (4, 5, or 6 weeks after vaccine launch) and speeds (20,000, 50,000, 100,000, or 150,000 vaccinations per day), as well as prioritization options (+/− prioritization of people age 65+ and essential workers). In sensitivity analyses, we examined the effect of a SARS-COV-2 variant with greater transmissibility.

Results
To be beneficial, prioritization must not create a bottleneck that decreases vaccination speed by > 50% without a more transmissible variant, or by > 33% with the emergence of the more transmissible variant. More specifically, prioritizing people age 65+ and essential workers increased the number of lives saved per vaccine dose delivered: 3000 deaths could be averted by delivering 83,000 vaccinations per day without prioritization or 50,000 vaccinations per day with prioritization. Other tradeoffs involve vaccination speed and timing. Compared to the slowest-examined vaccination speed of 20,000 vaccinations per day, achieving the fastest-examined vaccination speed of 150,000 vaccinations per day would avert additional 313,700 (28.6%) infections and 1693 (24.1%) deaths. Emergence of a more transmissible variant would double COVID-19 infections, hospitalizations, and deaths over the first 6 months of vaccination. The fastest-examined vaccination speed could only offset the harm of the more transmissible variant if achieved within 5 weeks of vaccine launch.

Conclusions
Faster vaccination speed with sooner vaccination expansion would save more lives. Prioritization of COVID-19 vaccines to higher-risk populations would be more beneficial only if it does not create an excessive vaccine delivery bottleneck.
Deaths during the first year of the COVID-19 pandemic: insights from regional patterns in Germany and Poland
Authors: Myck Michał , Oczkowska Monika , Garten Claudius , Król Artur , Brandt Martina 
Published: January 2023

Abstract
Background
Given the nature of the spread of SARS-CoV-2, strong regional patterns in the fatal consequences of the COVID-19 pandemic related to local characteristics such as population and health care infrastructures were to be expected. In this paper we conduct a detailed examination of the spatial correlation of deaths in the first year of the pandemic in two neighbouring countries – Germany and Poland, which, among high income countries, seem particularly different in terms of the death toll associated with the COVID-19 pandemic. The analysis aims to yield evidence that spatial patterns of mortality can provide important clues as to the reasons behind significant differences in the consequences of the COVID-19 pandemic in these two countries.

Methods
Based on official health and population statistics on the level of counties, we explore the spatial nature of mortality in 2020 in the two countries – which, as we show, reflects important contextual differences. We investigate three different measures of deaths: the officially recorded COVID-19 deaths, the total values of excessive deaths and the difference between the two. We link them to important pre-pandemic regional characteristics such as population, health care and economic conditions in multivariate spatial autoregressive models. From the point of view of pandemic related fatalities we stress the distinction between direct and indirect consequences of COVID-19, separating the latter further into two types, the spatial nature of which is likely to differ.

Results
The COVID-19 pandemic led to much more excess deaths in Poland than in Germany. Detailed spatial analysis of deaths at the regional level shows a consistent pattern of deaths officially registered as related to COVID-19. For excess deaths, however, we find strong spatial correlation in Germany but little such evidence in Poland.

Conclusions
In contrast to Germany, for Poland we do not observe the expected spatial pattern of total excess deaths and the excess deaths over and above the official COVID-19 deaths. This difference cannot be explained by pre-pandemic regional factors such as economic and population structures or by healthcare infrastructure. The findings point to the need for alternative explanations related to the Polish policy reaction to the pandemic and failures in the areas of healthcare and public health, which resulted in a massive loss of life.
Illnesses and hardship financing in India: an evaluation of inpatient and outpatient cases, 2014-18
Authors: Thomas Arya Rachel , Dash Umakant , Sahu Santosh Kumar 
Published: January 2023

Abstract

Background
Progress towards universal health coverage requires strengthening the country's health system. In developing countries, the increasing disease burden puts a lot of stress on scarce household finances. However, this burden is not the same for everyone. The economic burden varies across the disease groups and care levels. Government intervention is vital in formulating policies in addressing financial distress at the household level. In India, even when outpatient care forms a significant proportion of out-of-pocket expenditure, government schemes focus on reducing household expenditure on inpatient care alone. Thus, people resort to hardship financing practices like informal borrowing or selling of assets in the event of health shocks. In this context, the present study aims to identify the disease(s) that correlates with maximum hardship financing for outpatients and inpatients and to understand the change in hardship financing over time.

Methods
We used two waves of National Sample Survey Organisation’s data on social consumption on health- the 71st and the 75th rounds. Descriptive statistics are reported, and logistic regression is carried out to explain the adjusted impact of illness on hardship financing. Pooled logistic regression of the two rounds is estimated for inpatients and outpatients. Marginal effects are reported to study the changes in hardship financing over time.

Results
The results suggest that cancer had the maximum likelihood of causing hardship financing in India for both inpatients (Odds ratio 2.41; 95% Confidence Interval (CI): 2.03 - 2.86 (71st round), 2.54; 95% CI: 2.21 - 2.93 (75th round)) and outpatients (Odds ratio 6.11; 95% CI: 2.95 - 12.64 (71st round), 3.07; 95% CI: 2.14 - 4.40 (75th round)). In 2018, for outpatients, the hardship financing for health care needs was higher at public health facilities, compared to private health facilities (Odds ratio 0.72; 95% CI: 0.62 - 0.83 (75th round). The marginal effects model of pooled cross-section analysis reveals that from 2014 to 2018, the hardship financing had decreased for inpatients (Odds ratio 0.747; 95% CI:0.80 - -0.70), whereas it had increased for outpatients (Odds ratio 0.0126; 95% CI: 0.01 - 0.02). Our results also show that the likelihood of resorting to hardship financing for illness among women was lesser than that of men.

Conclusion
Government intervention is quintessential to decrease the hardship financing caused by cancer. The intra-household inequalities play an important role in explaining their hardship financing strategies. We suggest the need for more financial risk protection for outpatient care to address hardship financing.
Impact of extracorporeal membrane oxygenation in immunocompetent children with severe adenovirus pneumonia
Authors: Shi Tingting , Chen Chen , Fan Huifeng , Yu Minghua , Li Ming , Yang Diyuan , Huang Li , Nie Zhiqiang , Lu Gen 
Published: January 2023

Abstract
Background
Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia.

Methods
This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children’s Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled.

Results
Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO2); the ratio of PaO2 to the fraction concentration of oxygen in inspired air (FiO2; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO2, PO2, and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO2, PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05).

Conclusions
In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia.
Femoral neck fractures in non-geriatric patients: femoral neck system versus cannulated cancellous screw
Authors: Kenmegne Guy Romeo , Zou Chang , Fang Yue , He Xuanhong , Lin Yixiang , Yin Yijie 
Published: January 2023

Abstract
Background
The fractures of femoral neck account for 50% among hip fractures with around 3%-10% occurring in younger population of below 65 years. The newly introduced FNS as management approach appears to be a potential alternative to the traditional CCS. The aim of this study was to compare the clinical efficacy and outcome of the femoral neck system (FNS) and the cannulated cancellous screw (CCS) in the treatment of femoral neck fractures in adult below 65 years of age.

Methods
Data of 114 patients between 18–65 years, admitted in our department for femoral neck fracture from January 2019 to March 2021 were retrospectively studied and ranged into two groups based on the surgical methods: FNS group (56 patients) and CCS group (58 patients). The variables of interest including demographic and clinical variables (age, gender, fracture mechanism, injury side and classification), perioperative parameters(operation time, intraoperative bleeding, incision length and hospitalization time), postoperative outcomes and complications (fracture healing time, nonunion rate, femoral neck avascular necrosis, aseptic screw loosening and the Harris Hip Score), were analyzed and compared between the two groups.

Results
All 114 patients presented satisfactory reduction and were followed-up for a period of 12 to 36 months (mean 27 ± 2.07 months); there were no significant differences between both groups in terms of age, gender, fracture classification, side of injury, mechanism of injury, the operative time, intraoperative blood loss and the hospital length of stay. However, the fracture healing time between FNS group and CCS group was statistically significant (p < 0.05), respectively 2.86 ± 0.77 and 5.10 ± 0.81 months. The significant differences were also found in terms of numbers of fluoroscopies 8.34 ± 1.38 Vs 17.72 ± 2.19, the HHS 87.80 ± 1.92 Vs 84.28 ± 2.24, postoperative complications 8 (14.28%) Vs 26 (44.82) respectively in FNS and CCS group.

Conclusion
FNS presented satisfactory outcomes had significantly lower complications rate, therefore, can be one of the alternatives for internal implantation devices in treatment of femoral neck fracture in non-geriatric population.
Implementation of an educational intervention to improve medical student cost awareness: a prospective cohort study
Authors: Tait Sarah D , Oshima Sachiko M , Leeras Harold J , Gunn Alexander , Sarver Melissa , Gunes Funda , Greenup Rachel A. 
Published: January 2023

Abstract
Background
In the context of rising healthcare costs, formal education on treatment-related financial hardship is lacking in many medical schools, leaving future physicians undereducated and unprepared to engage in high-value care.

Method
We performed a prospective cohort study to characterize medical student knowledge regarding treatment-related financial hardship from 2019 to 2020 and 2020–2021, with the latter cohort receiving a targeted educational intervention to increase cost awareness. Using Kirkpatrick’s four-level training evaluation model, survey data was analyzed to characterize the acceptability of the intervention and the impact of the intervention on student knowledge, attitudes, and self-reported preparedness to engage in cost-conscious care.

Results
Overall, N = 142 medical students completed the study survey; 61 (47.3%) in the non-intervention arm and 81 (66.4%) in the intervention arm. Of the 81 who completed the baseline survey in the intervention arm, 65 (80.2%) completed the immediate post-intervention survey and 39 (48.1%) completed the two-month post-intervention survey. Following the educational intervention, students reported a significantly increased understanding of common financial terms, access to cost-related resources, and level of comfort and preparedness in engaging in discussions around cost compared to their pre-intervention responses. The majority of participants (97.4%) reported that they would recommend the intervention to future students. A greater proportion of financially stressed students reported considering patient costs when making treatment decisions compared to their non-financially stressed peers.

Conclusions
Targeted educational interventions to increase cost awareness have the potential to improve both medical student knowledge and preparedness to engage in cost-conscious care. Student financial stress may impact high-value care practices. Robust curricula on high-value care, including treatment-related financial hardship, should be formalized and universal within medical school training.
The influence of professional identity on how the receiver receives and responds to a speaking up message: a cross-sectional study
Authors: Barlow Melanie , Watson Bernadette , Jones Elizabeth , Maccallum Fiona , Morse Kate J. 
Published: January 2023

AbstractBackgroundResearch focused on understanding what enables or hinders health professionals to speak up about a safety concern has been to date predominately atheoretical and speaker focused. However, the role the receiver of the message plays in these often-difficult encounters is highly influential. To date, speaking up programs have created conversational mnemonics that technically should respectfully engage the receiver, yet speaking up remains challenging. This paper utilises Communication Accommodation Theory to explore the impact the communication behaviour and speaker characteristics has on the receiver of a speaking up message, and if these impacts differ between receiver groups (clinical disciplines).MethodClinicians (N = 208) from varying disciplines responded to two hypothetical speaking up vignettes, where participants were the receivers of speaking up messages. Analysis of variance was used to explore any potential differences between receiver groups.ResultsFindings indicated that the level of perceived accommodation and group membership, whether defined by speaker discipline or seniority, collectively influenced how the receiver of a speaking up message evaluated the interaction, which influenced their anticipated response to the speaker.ConclusionsThe receiver’s perceptions and evaluations of the message, their own professional identity and the presence of others, influenced receivers’ anticipated responses. This has direct implications on healthcare speaking up training and provision of care, as the varying clinical disciplines received and responded to the same messages differently.
Identification of ferroptosis related markers by integrated bioinformatics analysis and In vitro model experiments in rheumatoid arthritis
Authors: Xia Jinjun , Zhang Lulu , Gu Tao , Liu Qingyang , Wang Qiubo 
Published: January 2023

Abstract
Background
Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive and symmetrical joint diseases and synovitis. This research attempted to explore the mechanisms involving ferroptosis in RA, and find the biological markers by integrated analysis.

Methods
Gene expression data (GSE55235 and GSE55457) of synovial tissues from healthy and RA individuals were downloaded. By filtering the differentially expressed genes (DEGs) and intersecting them with the 484 ferroptosis-related genes (FRGs), the overlapping genes were identified. After the enrichment analysis, the machine learning-based approaches were introduced to screen the potential biomarkers, which were further validated in other two datasets (GSE77298 and GSE93272) and cell samples. Besides, we also analyze the infiltrating immune cells in RA and their correlation with the biomarkers.

Results
With the criteria, 635 DEGs in RA were included, and 29 of them overlapped in the reported 484 FRGs. The enrichments of the 29 differentially expressed ferroptosis-related genes indicated that they may involve in the FoxO signaling pathway and inherited metabolic disorder. RRM2, validating by the external datasets and western blot, were identified as the biomarker with the high diagnostic value, whose associated immune cells, such as Neutrophils and Macrophages M1, were also further evaluated.

Conclusion
We preliminary explored the mechanisms between ferroptosis and RA. These results may help us better comprehend the pathophysiological changes of RA in basic research, and provide new evidences for the clinical transformation.
Loop pathways are responsible for tuning the accumulation of C19- and C22-sterol intermediates in the mycobacterial phytosterol degradation pathway
Authors: Song Shikui , He Jianxin , Gao Meng , Huang Yongqi , Cheng Xiyao , Su Zhengding 
Published: January 2023

Abstract4-Androstene-3,17-dione (4-AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (BA) are the most important and representative C19- and C22-steroidal materials. The optimalization of sterol production with mycobacterial phytosterol conversion has been investigated for decades. One of the major challenges is that current industrial mycobacterial strains accumulate unignorable impurities analogous to desired sterol intermediates, significantly hampering product extractions and refinements. Previously, we identified Mycobacterium neoaurum HGMS2 as an efficient 4-AD-producing strain (Wang et al. in Microb Cell Fact. 19:187, 2020). Recently, we have genetically modified the HGMS2 strain to remove its major impurities including ADD and 9OH-AD (Li et al. in Microb Cell Fact. 20:158, 2021). Unexpectedly, the modified mutants started to significantly accumulate BA compared with the HGMS2 strain. In this work, while we attempted to block BA occurrence during 4-AD accumulation in HGMS2 mutants, we identified a few loop pathways that regulated metabolic flux switching between 4-AD and BA accumulations and found that both the 4-AD and BA pathways shared a 9,10-secosteroidial route. One of the key enzymes in the loop pathways was Hsd4A1, which played an important role in determining 4-AD accumulation. The inactivation of the hsd4A1 gene significantly blocked the 4-AD metabolic pathway so that the phytosterol degradation pathway flowed to the BA metabolic pathway, suggesting that the BA metabolic pathway is a complementary pathway to the 4-AD pathway. Thus, knocking out the hsd4A1 gene essentially made the HGMS2 mutant (HGMS2Δhsd4A1) start to efficiently accumulate BA. After further knocking out the endogenous kstd and ksh genes, an HGMS2Δhsd4A1 mutant, HGMS2Δhsd4A1/Δkstd1, enhanced the phytosterol conversion rate to BA in 1.2-fold compared with the HGMS2Δhsd4A1 mutant in pilot-scale fermentation. The final BA yield increased to 38.3 g/L starting with 80 g/L of phytosterols. Furthermore, we knocked in exogenous active kstd or ksh genes to HGMS2Δhsd4A1/Δ kstd1 to construct DBA- and 9OH-BA-producing strains. The resultant DBA- and 9OH-BA-producing strains, HGMS2Δhsd4A1/kstd2 and HGMS2Δkstd1/Δhsd4A1/kshA1B1, efficiently converted phytosterols to DBA- and 9OH-BA with the rates of 42.5% and 40.3%, respectively, and their final yields reached 34.2 and 37.3 g/L, respectively, starting with 80 g/L phytosterols. Overall, our study not only provides efficient strains for the industrial production of BA, DBA and 9OH-BA but also provides insights into the metabolic engineering of the HGMS2 strain to produce other important steroidal compounds.
In silico profiling of nonsynonymous SNPs of fat mass and obesity-associated gene: possible impacts on the treatment of non-alcoholic fatty liver disease
Authors: Patnaik Damini , Jena Atala Bihari , Kerry Rout George , Duttaroy Asim K. 
Published: January 2023

AbstractBackgroundNonalcoholic fatty liver, or NAFLD, is the most common chronic liver ailment. It is characterized by excessive fat deposition in hepatocytes of individuals who consume little or no alcohol and are unaffected by specific liver damaging factors. It is also associated with extrahepatic manifestations such as chronic kidney disease, cardiovascular disease, and sleep apnea. The global burden of NAFLD is increasing at an alarming rate. However, no pharmacologically approved drugs against NAFLD are available owing to their complex pathophysiology. Genome-wide association studies have uncovered SNPs in the fat mass and obesity-associated gene (FTO) that are robustly associated with obesity and higher BMI. The prevalence of NAFLD increases in parallel with the increasing prevalence of obesity. Since FTO might play a crucial role in NAFLD development, the current study identified five potentially deleterious mutations from 383 ns-SNPs in the human FTO gene using various in silico tools.MethodsThis study aims to identify potentially deleterious nonsynonymous SNPs (ns-SNPs) employing various in silico tools. Additionally, molecular modeling approaches further studied the structural changes caused by identified SNPs. Moreover, molecular dynamics studies finally investigated the binding potentials of the phytochemicals resveratrol, rosmarinic acid, and capsaicin with different mutant forms of FTO.ResultsThe current investigation has five potentially deleterious mutations from 383 ns-SNPs in the human FTO gene using various in silico tools. The present study identified five nsSNPs of the human gene FTO, Gly103Asp, Arg96Pro, Tyr295Cys, and Arg322Gln, with an apparent connection to the disease condition. Modulation of demethylation activity by phytomolecule scanning explains the hepatoprotective action of molecules. The current investigation also suggested that predicted mutations did not affect the binding ability of three polyphenols: rosamarinic acid, resveratrol, and capsaicin.ConclusionThis study showed that the predicted mutations in FTO did not affect the binding of three polyphenols. Thus, these three molecules can significantly aid drug development against FTO and NAFLD.