bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of virtual reality training to enhance laparoscopic assistance skills
Authors: Chen Xiuwen , Liao Peng , Liu Shiqing , Zhu Jianxi , Abdullah Abdullah Sultan , Xiao Yao 
Published: January 2024

Abstract
Background
While laparoscopic assistance is often entrusted to less experienced individuals, such as residents, medical students, and operating room nurses, it is important to note that they typically receive little to no formal laparoscopic training. This deficiency can lead to poor visibility during minimally invasive surgery, thus increasing the risk of errors. Moreover, operating room nurses and medical students are currently not included as key users in structured laparoscopic training programs.

Objectives
The aim of this study is to evaluate the laparoscopic skills of OR nurses, clinical medical postgraduate students, and residents before and after undergoing virtual reality training. Additionally, it aimed to compare the differences in the laparoscopic skills among different groups (OR nurses/Students/Residents) both before and after virtual reality training.

Methods
Operating room nurses, clinical medical postgraduate students and residents from a tertiary Grade A hospital in China in March 2022 were selected as participants. All participants were required to complete a laparoscopic simulation training course in 6 consecutive weeks. One task from each of the four training modules was selected as an evaluation indicator. A before-and-after self-control study was used to compare the basic laparoscopic skills of participants, and laparoscopic skill competency was compared between the groups of operating room nurses, clinical medical postgraduate students, and residents.

Results
Twenty-seven operating room nurses, 31 clinical medical postgraduate students, and 16 residents were included. The training course scores for the navigation training module, task training module, coordination training module, and surgical skills training module between different groups (operating room nurses/clinical medical postgraduate/residents) before laparoscopic simulation training was statistically significant (p < 0.05). After laparoscopic simulation training, there was no statistically significant difference in the training course scores between the different groups. The surgical level scores before and after the training course were compared between the operating room nurses, clinical medical postgraduate students, and residents and showed significant increases (p < 0.05).

Conclusion
Our findings show a significant improvement in laparoscopic skills following virtual surgery simulation training across all participant groups. The integration of virtual surgery simulation technology in surgical training holds promise for bridging the gap in laparoscopic skill development among health care professionals.
Effects of glucagon-like peptide-1 receptor agonists on liver-related and cardiovascular mortality in patients with type 2 diabetes
Authors: Yen Fu-Shun , Hou Ming-Chih , Wei James Cheng-Chung , Shih Ying-Hsiu , Hwu Chii-Min , Hsu Chih-Cheng 
Published: January 2024

Abstract
Background
Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis.

Methods
From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan’s National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups.

Results
The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use.

Conclusions
This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.
Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry
Authors: Buschulte Katharina , Kabitz Hans-Joachim , Hagmeyer Lars , Hammerl Peter , Esselmann Albert , Wiederhold Conrad , Skowasch Dirk , Stolpe Christoph , Joest Marcus , Veitshans Stefan , Höffgen Marc , Maqhuzu Phillen , Schwarzkopf Larissa , Hellmann Andreas , Pfeifer Michael , Behr Jürgen , Karpavicius Rainer , Günther Andreas , Polke Markus , Höger Philipp , Somogyi Vivien , Lederer Christoph , Markart Philipp , Kreuter Michael 
Published: January 2024

Abstract
Background
Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD.

Methods
The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection.

Results
In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005).

Conclusion
Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted.
Complete microbial synthesis of crocetin and crocins from glycerol in Escherichia coli
Authors: Lee Jun Ho , Lee Seong-Rae , Lee Sang Yup , Lee Pyung Cheon 
Published: January 2024

Abstract
Background
Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains.

Results
Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L).

Conclusions
This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries.
Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer
Authors: Xian Zhen-Yu , Song Yi-Wen , Zhang Zong-Jin , Gan Ying-Guo , Chen Yong-Le , Hu Tuo , Wen Xiao-Feng , Mo Tai-Wei , He Xiao-Wen 
Published: January 2024

Abstract
Background
This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future.

Patients and methods
PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan–Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation.

Results
Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004–7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158–5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953–17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623–13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317–6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858–5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613–2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731–2.033, P < 0.001).

Conclusion
Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.
Learning health systems and evidence ecosystems: a perspective on the future of evidence-based medicine and evidence-based guideline development
Authors: Rajit D. , Johnson A. , Callander E. , Teede H. , Enticott J. 
Published: January 2024

AbstractDespite forming the cornerstone of modern clinical practice for decades, implementation of evidence-based medicine at scale remains a crucial challenge for health systems. As a result, there has been a growing need for conceptual models to better contextualise and pragmatize the use of evidence-based medicine, particularly in tandem with patient-centred care. In this commentary, we highlight the emergence of the learning health system as one such model and analyse its potential role in pragmatizing both evidence-based medicine and patient-centred care. We apply the learning health system lens to contextualise the key activity of evidence-based guideline development and implementation, and highlight how current inefficiencies and bottlenecks in the evidence synthesis phase of evidence-based guideline development threaten downstream adherence. Lastly, we introduce the evidence ecosystem as a complementary model to learning health systems, and propose how innovative developments from the evidence ecosystem may be integrated with learning health systems to better enable health impact at speed and scale.
Investing in midwifery for sustainable development goals in low- and middle-income countries: a cost-benefit analysis
Authors: Boukhalfa Chakib , Ouakhzan Brahim , Masbah Hanane , Acharai Leila , Zbiri Saad 
Published: January 2024

Abstract
Background
Maternal and neonatal mortality in low- and middle-income countries is frequently caused by inadequate management of obstetric and neonatal complications and a shortage of skilled health workers. The availability of these workers is essential for effective and high-quality healthcare. To meet the needs of sexual, reproductive, maternal, new-born, child, and adolescent health by 2030, more than one million health workers, including 900 000 midwives, are required globally. Despite this, uncertainty persists regarding the return on investment in the health workforce.

Methods
The objective of this research was to determine the cost-benefit ratio of increasing investment in midwifery in Morocco from 2021 to 2030. A comparative analysis was conducted between scenarios “with” and “without” the additional investment. The costs and benefits were estimated using relevant data from national and international sources.

Results
Following the International Confederation of Midwives’ recommendations, it is advised that Morocco recruit 760 midwives annually to achieve 95% of universal health coverage. This increase in midwifery could result in saving 120 593 lives by 2030, including reducing maternal deaths by 3 201, stillbirths by 48 399, and neonatal deaths by 68 993. The estimated economic benefit of investing in midwives was US$ 10 152 287 749, while the total cost was US$ 638 288 820. Consequently, the cost-benefit ratio was calculated as 15.91, indicating that investing in midwifery would provide 16 times more benefits than costs.

Conclusion
Increasing investment in midwifery appears to be an efficient strategy for achieving comprehensive maternal and child health coverage in low- and middle-income countries.
Racial differences in length of stay and readmission for asthma in the all of us research program
Authors: Correa-Agudelo Esteban , Gautam Yadu , Mendy Angelico , Mersha Tesfaye B. 
Published: January 2024

Abstract
Background
This study addresses the limited research on racial disparities in asthma hospitalization outcomes, specifically length of stay (LOS) and readmission, across the U.S.

Methods
We analyzed in-patient and emergency department visits from the All of Us Research Program, identifying various risk factors (demographic, comorbid, temporal, and place-based) associated with asthma LOS and 30-day readmission using Bayesian mixed-effects models.

Results
Of 17,233 patients (48.0% White, 30.7% Black, 19.7% Hispanic/Latino, 1.3% Asian, and 0.3% Middle Eastern and North African) with 82,188 asthma visits, Black participants had 20% shorter LOS and 12% higher odds of readmission, compared to White participants in multivariate analyses. Public-insured patients had 14% longer LOS and 39% higher readmission odds than commercially insured patients. Weekend admissions resulted in a 12% shorter LOS but 10% higher readmission odds. Asthmatics with chronic diseases had a longer LOS (range: 6–39%) and higher readmission odds (range: 9–32%) except for those with allergic rhinitis, who had a 23% shorter LOS.

Conclusions
A comprehensive understanding of the factors influencing asthma hospitalization, in conjunction with diverse datasets and clinical-community partnerships, can help physicians and policymakers to systematically address racial disparities, healthcare utilization and equitable outcomes in asthma care.
On the use of receiver operating characteristic curve analysis to determine the most appropriate p value significance threshold
Authors: Habibzadeh Farrokh 
Published: January 2024

Abstract
Background
p value is the most common statistic reported in scientific research articles. Choosing the conventional threshold of 0.05 commonly used for the p value in research articles, is unfounded. Many researchers have tried to provide a reasonable threshold for the p value; some proposed a lower threshold, eg, 0.005. However, none of the proposals has gained universal acceptance. Using the analogy between the diagnostic tests with continuous results and statistical inference tests of hypothesis, I wish to present a method to calculate the most appropriate p value significance threshold using the receiver operating characteristic curve (ROC) analysis.

Results
As with diagnostic tests where the most appropriate cut-off values are different depending on the situation, there is no unique cut-off for the p significance threshold. Unlike the previous proposals, which mostly suggest lowering the threshold to a fixed value (eg, from 0.05 to 0.005), the most appropriate p significance threshold proposed here, in most instances, is much less than the conventional cut-off of 0.05 and varies from study to study and from statistical test to test, even within a single study. The proposed method provides the minimum weighted sum of type I and type II errors.

Conclusions
Given the perplexity involved in using the frequentist statistics in a correct way (dealing with different p significance thresholds, even in a single study), it seems that the p value is no longer a proper statistic to be used in our research; it should be replaced by alternative methods, eg, Bayesian methods.
Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice
Authors: Zhu Ya-Jing , Huang Jing , Chen Ru , Zhang Yu , He Xin , Duan Wen-Xin , Zou Yuan-Lei , Sun Meng-Mei , Sun Hui-Li , Cheng Si-Min , Wang Hao-Chuan , Zhang Hao , Wu Wen-Ning 
Published: January 2024

AbstractBackgroundMajor depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known.MethodsAnimal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy.Nlrp1aknockdown was performed using an adeno-associated virus (AAV) vector containingNlrp1a–shRNA–eGFP infusion.ResultsCSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. HippocampalNlrp1aknockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect.ConclusionsAutophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.
Cholinergic signaling via the α7 nicotinic acetylcholine receptor regulates the migration of monocyte-derived macrophages during acute inflammation
Authors: Keever Kasey R. , Cui Kui , Casteel Jared L. , Singh Sanjay , Hoover Donald B. , Williams David L. , Pavlov Valentin A. , Yakubenko Valentin P. 
Published: January 2024

Abstract
Background
The involvement of the autonomic nervous system in the regulation of inflammation is an emerging concept with significant potential for clinical applications. Recent studies demonstrate that stimulating the vagus nerve activates the cholinergic anti-inflammatory pathway that inhibits pro-inflammatory cytokines and controls inflammation. The α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages plays a key role in mediating cholinergic anti-inflammatory effects through a downstream intracellular mechanism involving inhibition of NF-κB signaling, which results in suppression of pro-inflammatory cytokine production. However, the role of the α7nAChR in the regulation of other aspects of the immune response, including the recruitment of monocytes/macrophages to the site of inflammation remained poorly understood.

Results
We observed an increased mortality in α7nAChR-deficient mice (compared with wild-type controls) in mice with endotoxemia, which was paralleled with a significant reduction in the number of monocyte-derived macrophages in the lungs. Corroborating these results, fluorescently labeled α7nAChR-deficient monocytes adoptively transferred to WT mice showed significantly diminished recruitment to the inflamed tissue. α7nAChR deficiency did not affect monocyte 2D transmigration across an endothelial monolayer, but it significantly decreased the migration of macrophages in a 3D fibrin matrix. In vitro analysis of major adhesive receptors (L-selectin, β1 and β2 integrins) and chemokine receptors (CCR2 and CCR5) revealed reduced expression of integrin αM and αX on α7nAChR-deficient macrophages. Decreased expression of αMβ2 was confirmed on fluorescently labeled, adoptively transferred α7nAChR-deficient macrophages in the lungs of endotoxemic mice, indicating a potential mechanism for α7nAChR-mediated migration.

Conclusions
We demonstrate a novel role for the α7nAChR in mediating macrophage recruitment to inflamed tissue, which indicates an important new aspect of the cholinergic regulation of immune responses and inflammation.