bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient experiences of being advised by a healthcare professional to get pregnant to manage or treat endometriosis: a cross-sectional study
Authors: Sirohi Diksha , Freedman Sylvia , Freedman Lesley , Carrigan Gretchen , Hey-Cunningham Alison J. , Hull M. Louise , O’Hara Rebecca
Published: November 2023

Background

There is a lack of evidence that pregnancy reduces endometriotic lesions or symptoms, however studies indicate that people with endometriosis are commonly advised to get pregnant to manage or treat endometriosis. This study sought to examine the impact of this advice on patients with endometriosis when the advice was provided by healthcare professionals.

Methods

The Endometriosis Patient Experience Survey was a self-reported, community-based, cross-sectional online survey of people who had been medically diagnosed with endometriosis. Descriptive statistics were used to analyse the quantitative survey data and thematic analysis was undertaken for the qualitative survey data.

Results

1892 participants had received the advice to get pregnant or have a baby to manage or treat their endometriosis, with 89.4% of participants receiving this advice from healthcare professionals. In exploring the qualitative data, seven themes were contextualised relating to the impact of this advice in terms of health literacy, accepting the advice, rejecting the advice, major life decisions, healthcare interactions, mental health and relationships.

Conclusions

This study demonstrates profound and often negative patient impacts of the advice from healthcare professionals to get pregnant to manage or treat endometriosis. Impacts ranged from planning for pregnancy, hastening the making of major life decisions, eroding trust with healthcare professionals, worsening mental health and straining relationships. Providing evidence-based information on the treatment and management of endometriosis is essential. Pregnancy or having a baby should not be suggested as a treatment for endometriosis and the provision of this advice by healthcare professionals can have negative impacts on those who receive it.
A systematic review of faculty development programs based on the Harden teacher’s role framework model
Authors: Kohan Mahmoud , Changiz Tahereh , Yamani Nikoo
Published: November 2023

Background

Despite the changing roles of faculty in the health professions over the past two decades, none of the reviews has been paid enough attention to the impact of the faculty development programs on these roles. The objective of this review is to synthesize the existing evidence that addresses the questions: “What are the types and outcomes of faculty development programs based on the Harden teachers’ role framework and which of the areas described by Harden and Crosby are the authors referring to?”

Methods

This review was conducted according to the guidance for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. In 2020, a literature search was conducted in MEDLINE/PubMed, Scopus, ERIC, ScienceDirect, Google Scholar, Magiran and SID databases. The review included 119 studies (between 1990 and 2020) that met the review criteria. Data were extracted using a modified coding sheet. We used the modified Kirkpatrick model to assess the educational outcomes of faculty development programs.

Results

The majority of faculty development programs were workshops (33.61%) with various durations. Most programs focused on the domain of information provider and coach (76.47%), followed by the facilitator of learning and mentor (53.78%) and assessor and diagnostician (37.81%). Only five faculty development programs focused on the domain of role model. The majority (83.19%) of outcomes reported were at level 2B, level 1 (73.95%) and level 2A (71.42%). Gains in knowledge and skills related to teaching methods and student assessment were frequently noted. Behavior changes included enhanced teaching performance, development of new educational curricula and programs, improved feedback and evaluation processes, new leadership positions, increased academic output and career development. The impact on the organizational practice continued to be underexplored.

Conclusion

Based on the review findings, broadening the scope of faculty development programs beyond the traditional roles of the faculty members by utilizing a competency-based framework for developing a comprehensive faculty development program is recommended. Attention to individualized form of faculty development programs and incorporating more informal approaches into the design and delivery of faculty development programs is also needed.
A socio-political history of South Africa’s National Health Insurance
Authors: Whyle Eleanor Beth , Olivier Jill
Published: November 2023

Background

Spurred by the WHO’s endorsement of universal health coverage as a goal of all health systems, many countries are undertaking health financing reforms. The nature of these reforms, and the policy processes by which they are achieved, will depend on context-specific factors, including the history of reform efforts and the political imperatives driving reforms. South Africa’s pursuit of universal health coverage through a National Health Insurance is the latest in a nearly 100-year history of health system reform efforts shaped by social and political realities.

Methods

We conducted an interdisciplinary, retrospective literature review to explore how these reform efforts have unfolded, and been shaped by the contextual realities of the moment. We began the review by identifying peer-reviewed literature on health system reform in South Africa, and iteratively expanded the search through author tracking, citation tracking and purposeful searches for material on particular events or processes referenced in the initial body of evidence. Data was extracted and organised chronologically into nine periods.

Results

The analysis suggests that in South Africa politics; the power of the private sector; competing policy priorities and budgetary constraints; and ideas, values and ideologies have been particularly important in constraining, and sometimes spurring, health system reform efforts. Political transitions and pressures - including the introduction of apartheid in 1948, anti-apartheid opposition, the transition to democracy, and corruption and governance failures - have alternately created political imperatives for reform, and constrained reform efforts. In addition, the country’s political history has given rise to dominant ideas, values and ideologies that imbue health system reform with a particular social meaning. While these ideas and values increase opposition and complicate reform efforts, they also help to expose the inequities of the current system as problematic and re-emphasise the need for reform.

Conclusion

Ultimately, this analysis demonstrates the context-specific nature of health system reform processes and the influence of history on what sorts of reforms are politically feasible and socially acceptable, even in the context of a global push for universal health coverage.
Immunosignatures associated with TP53 status and co-mutations classify prognostically head and neck cancer patients
Authors: Sacconi Andrea , Muti Paola , Pulito Claudio , Urbani Giulia , Allegretti Matteo , Pellini Raul , Mehterov Nikolay , Ben-David Uri , Strano Sabrina , Bossi Paolo , Blandino Giovanni
Published: November 2023

Background

Immune checkpoint inhibitors (ICIs) are a therapeutic strategy for various cancers although only a subset of patients respond to the therapy. Identifying patients more prone to respond to ICIs may increase the therapeutic benefit and allow studying new approaches for resistant patients.

Methods

We analyzed the TCGA cohort of HNSCC patients in relation to their activation of 26 immune gene expression signatures, as well as their cell type composition, in order to define signaling pathways associated with resistance to ICIs. Results were validated on two cohorts of 102 HNSCC patients and 139 HNSCC patients under treatment with PD-L1 inhibitors, respectively, and a cohort of 108 HNSCC HPV negative patients and by in vitro experiments in HNSCC cell lines.

Results

We observed a significant association between the gene set and TP53 gene status and OS and PFS of HNSCC patients. Surprisingly, the presence of a TP53 mutation together with another co-driver mutation was associated with significantly higher levels of the immune gene expression, in comparison to tumors in which the TP53 gene was mutated alone. In addition, the higher level of TP53 mutated-dependent MYC signature was associated with lower levels of the immune gene expression signature. In vitro and three different patient cohorts validation analyses corroborated these findings.

Conclusions

Immune gene signature sets associated with TP53 status and co-mutations classify with more accuracy HNSCC patients. These biomarkers may be easily implemented in clinical setting.
Associations of serum carotenoids with visceral adiposity index and lipid accumulation product: a cross-sectional study based on NHANES 2001–2006
Authors: Yan Shaohua , Chen Siyu , Liu Yumiao , Liang Hongbin , Zhang Xinlu , Zhang Qiuxia , Xiu Jiancheng
Published: November 2023

Background

Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP.

Methods

The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors.

Results

In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (β) and 95% CI was − 0.98 (− 1.34, − 0.62) for α-carotene, − 1.39 (− 1.77, − 1.00) for β-carotene, − 0.79 (− 1.18, − 0.41) for β-cryptoxanthin, − 0.68 (− 0.96, − 0.39) for lutein/zeaxanthin, and − 0.88 (− 1.50, − 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between β­carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, β-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments.

Conclusion

This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding.
Application of narrow band imaging and Lugol's iodine staining in screening for nasopharyngeal carcinoma
Authors: Yang Fan , Huang Ning , Chen Xianming , Wang Maoxin
Published: November 2023

Background

To investigate the diagnostic value of conventional white light endoscopy (WLE), narrow band imaging (NBI) endoscopy, and Lugol's iodine staining under WLE (endoscopic iodine staining) in the screening and early diagnosis of nasopharyngeal carcinoma.

Methods

Patients with nasopharyngeal lesions requiring biopsy attending the Department of Otolaryngology Head and Neck Surgery in our hospital between January 2021 and April 2023 were included in this study. Before biopsy, all subjects underwent conventional WLE, NBI endoscopy, and endoscopic iodine staining. On WLE, according to nasopharyngeal lesion morphology and color, patients were diagnosed with nasopharyngeal carcinoma ( +) or chronic hyperplastic nasopharyngitis (-). On NBI endoscopy, according to nasopharyngeal lesion vascular morphology, patients with type V manifestations (nasopharyngeal carcinoma) were categorized as NBI ( +) and patients with type I-IV manifestations (chronic hyperplastic nasopharyngitis) were categorized as NBI (-). Endoscopic iodine staining (1.6% Lugol's iodine solution) was positive ( +) if the mucosal surface was brown with no white patches, or negative (-) if there was no or light brown staining of the mucosal surface. Patients were divided into 2 groups based on histopathological diagnosis: nasopharyngeal carcinoma or chronic hyperplastic nasopharyngitis. Endoscopic diagnoses were compared with histopathological findings. The diagnostic performance of WLE, NBI endoscopy and endoscopic iodine staining for nasopharyngeal carcinoma were determined.

Results

This study included 159 patients. On histopathology, 29 patients were diagnosed with nasopharyngeal carcinoma, and 130 patients were diagnosed with chronic hyperplastic nasopharyngitis. There were no significant differences in the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic (ROC) curve (AUC) of conventional WLE, NBI endoscopy or endoscopic iodine staining for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. The diagnostic performance of the combination of conventional WLE, NBI endoscopy and endoscopic iodine staining was significantly improved compared to any procedure alone.

Conclusions

Conventional WLE, NBI endoscopy or endoscopic iodine staining had good diagnostic performance for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. In particular, NBI endoscopy and endoscopic iodine staining alone or combined had clinical utility for identifying patients with nasopharyngeal lesions that are eligible for a watch-and-wait strategy.
The SMYD3-dependent H3K4me3 status of IGF2 intensifies local Th2 differentiation in CRSwNP via positive feedback
Authors: Yu Lei , Wei Yi , Lu Tong , Li Zhengqi , Lai Shimin , Yan Yan , Chen Changhui , Wen Weiping
Published: November 2023

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous and common upper airway disease divided into various inflammatory endotypes. Recent epidemiological findings showed a T helper 2 (Th2)-skewed dominance in CRSwNP patients. Histone modification alterations can regulate transcriptional and translational expression, resulting in abnormal pathogenic changes and the occurrence of diseases. Trimethylation of histone H3 lysine 4 (H3K4me3) is considered an activator of gene expression through modulation of accessibility for transcription, which is closely related to CRSwNP. H3K4me3 levels in the human nasal epithelium may change under Th2-biased inflammatory conditions, resulting in exaggerated local nasal Th2 responses via the regulation of naïve CD4+ T-cell differentiation. Here, we revealed that the level of SET and MYND domain-containing protein 3 (SMYD3)-mediated H3K4me3 was increased in NPs from Th2 CRSwNP patients compared with those from healthy controls. We demonstrated that SMYD3-mediated H3K4me3 is increased in human nasal epithelial cells under Th2-biased inflammatory conditions via S-adenosyl-L-methionine (SAM) production and further found that the H3K4me3high status of insulin-like growth factor 2 (IGF2) produced in primary human nasal epithelial cells could promote naïve CD4+ T-cell differentiation into Th2 cells. Moreover, we found that SAM production was dependent on the c-Myc/methionine adenosyltransferase 2A (MAT2A) axis in the nasal epithelium. Understanding histone modifications in the nasal epithelium has immense potential utility in the development of novel classes of therapeutics targeting Th2 polarization in Th2 CRSwNP.
Triglyceride to high-density lipoprotein cholesterol ratio is associated with regression to normoglycemia from prediabetes in adults: a 5-year cohort study in China
Authors: Huang Zhiqiang , Han Yong , Hu Haofei , Cao Changchun , Liu Dehong , Wang Zhibin
Published: November 2023

Objective

The current body of evidence on the association between the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-c) and the reversal of prediabetes to normoglycemia remains limited. The aim of this study is to investigate the association between TG/HDL-c and the reversion to normoglycemia in patients with prediabetes.

Methods

This retrospective cohort study included 15,107 individuals with prediabetes from 32 Chinese districts and 11 cities who completed health checks from 2010 to 2016. The Cox proportional-hazards regression model examined baseline TG/HDL-c and reversion to normoglycemia from prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting determined the non-linear connection between TG/HDL-c and reversion to normoglycemia. We also ran sensitivity and subgroup analysis. By characterizing progression to diabetes as a competing risk for the reversal of prediabetes to normoglycemic event, a multivariate Cox proportional hazards regression model with competing risks was created.

Results

Upon adjusting for covariates, the findings indicate a negative association between TG/HDL-c and the likelihood of returning to normoglycemia (HR = 0.869, 95%CI:0.842–0.897). Additionally, a non-linear relationship between TG/HDL-c and the probability of reversion to normoglycemia was observed, with an inflection point of 1.675. The HR on the left side of the inflection point was 0.748 (95%CI:0.699, 0.801). The robustness of our results was confirmed through competing risks multivariate Cox's regression and a series of sensitivity analyses.

Conclusion

The present study reveals a negative and non-linear correlation between TG/HDL-c and the reversion to normoglycemia among Chinese individuals with prediabetes. The findings of this study are anticipated to serve as a valuable resource for clinicians in managing dyslipidemia in prediabetic patients. Interventions aimed at reducing the TG/HDL-c ratio through the reduction of TG or elevation of HDL-c levels may substantially enhance the likelihood of achieving normoglycemia in individuals with prediabetes.
TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy
Authors: Huang Xuliang , Ye Changzhou , Zhao Xinyu , Tong Yao , Lin Wen , Huang Qingqing , Zheng Yuhao , Wang Junlu , Zhang Anqi , Mo Yunchang
Published: November 2023

Background

Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism.

Methods

SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined.

Results

Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8.

Conclusion

TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.

Graphical Abstract
Extensive preclinical evaluation of combined mangiferin and glycyrrhizic acid for restricting synovial neovascularization in rheumatoid arthritis
Authors: Mao Xia , Yan Xiangying , Li Congchong , Liu Yudong , Zhang Yanqiong , Lin Na
Published: November 2023

Background

Synovial neovascularization promotes rheumatoid arthritis (RA) progression. Baihu guizhi decoction (BHGZD) has a potential in restricting this pathological change of RA.

Purpose

To identify bioactive compounds (BACs) of BHGZD and to elucidate the underlying mechanisms in restricting synovial neovascularization of RA.

Method

Through transcriptomic profiling, the chemical profiling of BHGZD and its effective transcriptomic profiling against RA were identified. Then, candidate targets and the corresponding BACs against synovial neovascularization were screened by “disease gene-drug target” interaction network analysis and in silico molecular docking. The binding affinities of candidate BAC-target pairs were verified using surface plasmon resonance, and the pharmacokinetic characteristics of BACs in vivo after BHGZD administration at different time points were detected by Ultra Performance Liquid Chromatography-Mass spectrum/Mass spectrum. After that, in vivo experiments based on adjuvant-induced arthritis (AIA-M) rats, and in vitro experiments based on human umbilical vein endothelial cells (HUVEC) and arthritic synovial fibroblasts (MH7A) were carried out to evaluate the pharmacological effects of BHGZD and the two-BACs-combination, and to verify the associated mechanisms.

Result

VEGFA/VEGFR2/SRC/PI3K/AKT signal axis was screened as one of the key network targets of BHGZD against synovial neovascularization in RA. Mangiferin (MG) and glycyrrhizic acid (GA) were identified as the representative BACs of BHGZD for their strong binding affinities with components of the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis, and their high exposed quantity in vivo. Both BHGZD and the two-BAC combination of MG and GA were demonstrated to be effective in restricting disease severity, reducing synovial inflammation and decreasing the formation of vascular opacities in AIA-M rats, and also reducing the migrative and invasive activities of HUVEC and MH7A cells and attenuating the lumen formation ability of HUVEC cells significantly. Mechanically, both BHGZD and the two-BAC combination markedly reduced the expression of VEGFA in synovial tissues, the serum levels of VEGF and NO, and the enzymatic activity of eNOS, increased the content of endostatin, and also reversed the abnormal alterations in the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis in vivo and in vitro.

Conclusion

MG and GA may be the representative BACs of BHGZD for restricting excessive synovial vascularization in RA via regulating VEGFA/VEGFR2/SRC/PI3K/AKT signal axis.
Self-reported functioning among patients with ultra-rare nemaline myopathy or a related disorder in Finland: a pilot study
Authors: Lehtokari Vilma-Lotta , Similä Minna , Tammepuu Marianne , Wallgren-Pettersson Carina , Strang-Karlsson Sonja , Hiekkala Sinikka
Published: November 2023

Background

Nemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories.

Results

In total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19–75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable.

Conclusions

To our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies.
Preoperative dexamethasone administration in hepatectomy of 25-min intermittent Pringle’s maneuver for hepatocellular carcinoma: protocol for a randomized controlled trial
Authors: Huang Yang , Xu Liangliang , Wang Ning , Pu Xingyu , Wang Wentao , Wen Tianfu , Xu Mingqing , Jiang Li
Published: November 2023

Background

Our previous randomized controlled trial (RCT) have demonstrated that intermittent Pringle’s maneuver (IPM) with a 25-min ischemic interval can be applied safely and efficiently in open or laparoscopic hepatectomy in patients with hepatocellular carcinoma (HCC) patients. But prolonging the hepatic inflow blocking time will inevitably aggravate the ischemia-reperfusion injury (IRI) caused by systemic response. This RCT aims to evaluate the effect of administration of dexamethasone versus placebo before clamping the hilar pedicle on postoperative liver function, inflammatory response, and perioperative outcomes among HCC patients undergoing liver resection with 25-min hepatic inflow occlusion.

Methods and analysis

This will be a randomized, dual-arm, parallel-group, double-blinded trial. All eligible and consecutive patients are coming from a regional medical center who are diagnosed with HCC and underwent radical R0/R1 resection. All participates are randomly allocated in dexamethasone group or placebo group. All surgeons, anesthesiologists, and outcome assessors will be blinded to allocation status. Primary endpoints are transaminase-based postoperative hepatic injury on seven consecutive days after surgery and assessed by their peak values as well as area under the curve (AUC) of the postoperative course of aminotransferases. Secondary endpoints are postoperative total bilirubin (TBil), coagulation function, inflammatory cytokines and their respective peaks, intraoperative blood loss, postoperative hospital stay, morbidity, and mortality. The above parameters will be compared using the corresponding statistical approach. Subgroup analysis will be performed according to the liver cirrhosis and major hepatectomy.

Discussion

Based on our previous study, we will explore further the effect of glucocorticoid administration on attenuating the surgical stress response in order to follow securely 25-min hepatic inflow occlusion. Therefore, the trial protocol is reasonable and the results of the trial may be clinically significant.

Trial registration

This trial was registered on 3 December 2022, in the Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2200066381. The protocol version is V1.0 (20221104).
Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis
Authors: Nishiwaki Ryo , Imoto Ichiro , Oka Satoko , Yasuma Taro , Fujimoto Hajime , D’Alessandro-Gabazza Corina N. , Toda Masaaki , Kobayashi Tetsu , Osamu Hataji , Fujibe Kodai , Nishikawa Kenichiro , Hamaguchi Tetsuya , Sugimasa Natsuko , Noji Midori , Ito Yoshiyuki , Takeuchi Kenji , Cann Isaac , Inoue Yasuhiro , Kato Toshio , Gabazza Esteban C.
Published: November 2023

Background

Acute cholangitis is a severe, life-threatening infection of the biliary system that requires early diagnosis and treatment. The Tokyo Guidelines recommend a combination of clinical, laboratory, and imaging findings for diagnosis and severity assessment, but there are still challenges in identifying severe cases that need immediate intervention. The microbiota and its derived products have been implicated in the pathogenesis of acute cholangitis. Corisin is a microbiome-derived peptide that induces cell apoptosis, acute tissue injury, and inflammation. This study aimed to evaluate the potential of plasma and bile corisin as a biomarker of acute cholangitis.

Methods

Forty patients with acute cholangitis associated with choledocholithiasis or malignant disease were enrolled. Nine patients without acute cholangitis were used as controls. Corisin was measured by enzyme immunoassays in plasma and bile samples. Patients were classified into severe and non-severe groups. The associations of plasma and bile corisin with the clinical grade of acute cholangitis and other parameters were analyzed by univariate and multivariate regression analysis.

Results

Plasma and bile corisin levels were significantly higher in patients with acute cholangitis than in controls. Patients with severe acute cholangitis had significantly higher plasma and bile corisin levels than those with non-severe form of the disease. Bile corisin level was significantly correlated with markers of inflammation, coagulation, fibrinolysis, and renal function. Univariate analysis revealed a significant association of bile corisin but a weak association of plasma corisin with the clinical grade of acute cholangitis. In contrast, multivariate analysis showed a significant relationship between plasma corisin level and the disease clinical grade. The receiver operating characteristic curve analysis showed low sensitivity but high specificity for plasma and bile corisin to detect the severity of acute cholangitis. The plasma and bile corisin sensitivity was increased when serum C-reactive protein level was included in the receiver operating characteristic curve analysis.

Conclusions

Overall, these findings suggest that plasma and bile corisin levels may be useful biomarkers for diagnosing and monitoring acute cholangitis and that corisin may play a role in the pathophysiology of the disease by modulating inflammatory, coagulation and renal pathways.
Analytical study of an 1899 Peruvian dinero: unveiling the mystery of a coin that wasn’t officially minted
Authors: Ortega-San-Martín Luis , Bravo-Hualpa Fabiola
Published: November 2023

The present paper presents the analytical study of an unusual Peruvian 1899 dinero coin whose authenticity has been questioned since the 1970’s. This coin, which is present in some numismatic collections although there is no record of having been minted officially, has been characterized using non-destructive techniques such as X-ray fluorescence (XRF), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM–EDS), and X-ray diffraction (XRD). Results are consistent with a cast counterfeit coin made at the turn of the 19th and 20th using a copper base alloy that was silver-platted to pass unnoticed among the public. The alloy used, generally known as german silver, was common for counterfeits in North America and Europe in that period. The historical reasons for the appearance of this unexpected coin in Peru during a time of economic difficulties, where the public experienced a shortage of small-change coins, are briefly outlined.
The use of class imbalanced learning methods on ULSAM data to predict the case–control status in genome-wide association studies
Authors: Öztornaci R. Onur , Syed Hamzah , Morris Andrew P. , Taşdelen Bahar
Published: November 2023

Machine learning (ML) methods for uncovering single nucleotide polymorphisms (SNPs) in genome-wide association study (GWAS) data that can be used to predict disease outcomes are becoming increasingly used in genetic research. Two issues with the use of ML models are finding the correct method for dealing with imbalanced data and data training. This article compares three ML models to identify SNPs that predict type 2 diabetes (T2D) status using the Support vector machine SMOTE (SVM SMOTE), The Adaptive Synthetic Sampling Approach (ADASYN), Random under sampling (RUS) on GWAS data from elderly male participants (165 cases and 951 controls) from the Uppsala Longitudinal Study of Adult Men (ULSAM). It was also applied to SNPs selected by the SMOTE, SVM SMOTE, ADASYN, and RUS clumping method. The analysis was performed using three different ML models: (i) support vector machine (SVM), (ii) multilayer perceptron (MLP) and (iii) random forests (RF). The accuracy of the case–control classification was compared between these three methods. The best classification algorithm was a combination of MLP and SMOTE (97% accuracy). Both RF and SVM achieved good accuracy results of over 90%. Overall, methods used against unbalanced data, all three ML algorithms were found to improve prediction accuracy.
The region of large site amplification in Northern Hokkaido, Japan, extends to the eastern Soya Region
Authors: Nozu Atsushi
Published: November 2023

In the document titled “predominant period of long-period ground motions and the natural period of deep subsoil” by the Central Disaster Management Council, the west part of Northern Hokkaido facing the Sea of Japan is categorized as a region, where long-period (> 6 s) ground motions are predominant. In contrast, the document categorizes the east part of Northern Hokkaido as a region where short-period (< 1 s) ground motions are predominant. The J-SHIS velocity structure model also implies that a deep sedimentary basin is located in the west part of Northern Hokkaido, but not in the east part. However, the result of a past generalized inversion analysis was inconsistent with these general understanding and suggested that the region of large site amplification in the low-frequency range in Northern Hokkaido extends to the eastern Soya Region. It was preferable to check this result with an independent dataset. Therefore, in this study, the records of the May 24, 2013, MW8.3, Sea of Okhotsk earthquake were used to investigate the distributions of site amplification factors in Northern Hokkaido. Because this is a distant earthquake and the epicentral distance was greater than 1300 km even at the closest station in Hokkaido, it was assumed that the difference of ground motions at different stations represents the difference of the site effects. The Fourier spectra for the S wave part of this earthquake at K-NET and KiK-net stations clearly indicated that the region of large site amplification in the low-frequency range in Northern Hokkaido does extend to the eastern Soya Region. It is desirable in a future study to reveal the cause of the discrepancy between this amplification pattern and the existing velocity structure models.

Graphical Abstract
The quizzical failure of a nudge on academic integrity education: a randomized controlled trial
Authors: Allard Aurélien , Armond Anna Catharina Vieira , Goddiksen Mads Paludan , Johansen Mikkel Willum , Loor Hillar , Schöpfer Céline , Varga Orsolya , Clavien Christine
Published: November 2023

Background

Studies on academic integrity reveal high rates of plagiarism and cheating among students. We have developed an online teaching tool,Integrity Games(https://integgame.eu/), that uses serious games to teach academic integrity. In this paper, we test the impact of a soft intervention – a short quiz – that was added to theIntegrity Gameswebsite to increase users’ interest in learning about integrity. Based on general principles of behavioral science, our quiz highlighted the intricacy of integrity issues, generated social comparisons, and produced personalized advice. We expected that these interventions would create a need for knowledge and encourage participants to spend more time on the website.

Methods

In a randomized controlled trial involvingN = 405 students from Switzerland and France, half of the users had to take a short quiz before playing the serious games, while the other half could directly play the games. We measured how much time they spent playing the games, and, in a post-experimental survey, we measured their desire to learn about integrity issues and their understanding of integrity issues.

Results

Contrary to our expectations, the quiz had a negative impact on time spent playing the serious games. Moreover, the quiz did not increase participants' desire to learn about integrity issues or their overall understanding of the topic.

Conclusions

Our quiz did not have any measurable impact on curiosity or understanding of integrity issues, and may have had a negative impact on time spent on theIntegrity gameswebsite. Our results highlight the difficulty of implementing behavioral insights in a real-world setting.

Trial registration

The study was preregistered athttps://osf.io/73xty.
Clinico-laboratory outcomes of plasma transfusion in the Egyptian’s pediatric intensive care units—a prospective observational study
Authors: Megied Mohamed Abdallah Abd El , Mohamed Laila Hussein , Meligy Basant Salah Saad , Eissawy Yasmin Mohamed Ramadan , Ahmed Hanaa Elsayed Mohammed , Younis Ola Soliman Emam Soliman
Published: November 2023

Background

Despite the paucity of data supporting their indications, plasma transfusions (PT) are regularly administered for critically ill patients (CIP) in pediatric intensive care units (PICU). The aim of this study was to identify the actual indications for PT in the Egyptian’s PICUs and determine to what extent it affects the clinic-laboratory outcomes for CIP.

Methods

A prospective observational study was conducted for 6 months on 180 CIP in PICUs of Cairo University Hospital who received plasma for at least one time during their length of stay (LOS). Full history, examination, and investigations were obtained from the medical records.

Results

Plasma was transfused in 64.4% of the studied population to support moderate and severe critical illness identified by multiple organ dysfunction score (MODS). Meanwhile, subjective-based physician conceptions accounted for 12.8% of all indications for plasma transfusion. PT in CIP was associated with a significant reduction in platelet count, prothrombin time, partial thromboplastin time, and international normalized ratio with p-value < 0.001, while there was a significant increase in hemoglobin level with p-value < 0.001. A statistically positive correlation exists between the time interval between admission and 1st PT and LOS with a p-value < 0.001 being shorter with earlier transfusion. Of the 180 patients enrolled in this study, seventy patients (38.9%) died, while 110 patients (61.1%) survived. A statistically significant increase in mechanical ventilation (MV) (p = 0.004), total number of PT (p < 0.001), and MODS score (p < 0.001) were recorded in dead CIP compared with survivors.

Conclusion

Moderate and severe critical illness identified by MODS was the most frequent cause for PT in the Egyptian’s PICUs. Early, precise, and objectively based PT has a strong role in improving the outcomes in CIP.
Two-dimensional and four-dimensional ultrasound in the diagnosis of non-cardiac fetal congenital anomalies in high risk pregnancies: a comparative study
Authors: Ibrahim Nada Ayman Soliman , Elshorbagy Kholoud Hamdy , Darweish Abdelmonem Nooman , Khadrah Rania Sobhy Abou
Published: November 2023

Background

The high incidence of non-cardiac congenital anomalies in high-risk pregnancies is a major worldwide health problem. Congenital deformities represent 20–25% of perinatal deaths. The best non-invasive screening method for diagnosing congenital abnormalities is ultrasound. Four-dimensional ultrasound added additional diagnostic value to two-dimensional ultrasound in evaluating fetal prenatal conditions. Our study's goal was to compare the roles of two-dimensional and four-dimensional ultrasound in the diagnosis of non-cardiac fetal congenital anomalies in high-risk pregnancies.

Results

Out of the 100 pregnant women who underwent examinations, all had high-risk pregnancies and were expected to give birth to babies with deformities, a total of 25 cases (or 25%) of fetal abnormalities were found. The two-dimensional ultrasound diagnosis's accuracy sensitivity, and specificity were 84%, 76%, and 86.67%, respectively, while they were 87%, 80%, and 89.33%, respectively, for four-dimensional ultrasound. The accuracy, sensitivity, and specificity of two-dimensional ultrasound combined with four-dimensional ultrasound were significantly higher (94%, 88%, and 96%, respectively) than those of two-dimensional ultrasound or four-dimensional ultrasound alone. This study also analyzed the risk factors leading to fetal malformations. The results showed that consanguinity, increased maternal age, past history or family history of congenital anomalies, history of medication during pregnancy, and maternal diabetes were major risk factors statistically significant for congenital anomalies.

Conclusion

The diagnosis rate of fetal abnormalities can be significantly increased by combining two-dimensional ultrasound with four-dimensional ultrasound. Avoiding risk factors that raise the likelihood of fetal abnormalities should take priority for pregnant women with high risk factors. To lower the incidence of fetal abnormalities, prenatal screening and diagnosis should be standardized.
Inflammatory Tongue Conditions and Risk of Oral Tongue Cancer Among the US Elderly Individuals
Authors: Tota Joseph E. , Engels Eric A. , Lingen Mark W. , Agrawal Nishant , Kerr Alexander R. , Zumsteg Zachary S. , Cheung Li C. , Katki Hormuzd A. , Abnet Christian C. , Chaturvedi Anil K.
Published: November 2023

PURPOSE

The incidence of oral tongue cancers has increased since the 1980s among US men and women for unknown reasons. We investigated associations of inflammatory tongue conditions with risk of cancers of the oral tongue, other oral cavity, and oropharynx among the US elderly individuals (age 65 years or older).

METHODS

We conducted a case-control study (2,534 oral tongue cancers, 6,832 other oral cavity cancers, 9,373 oropharyngeal cancers, and 200,000 controls) within the SEER-Medicare data set (1992-2013). Medicare records were used to identify patients with clinically diagnosed inflammatory tongue conditions (glossitis, benign migratory glossitis, median rhomboid glossitis, atrophic glossitis, glossodynia, other specified conditions [eg, atrophy and hypertrophy], and other unspecified conditions) and oral precancer (leukoplakia/erythroplakia). Only conditions preceding cancer/control selection by >12 months were included.

RESULTS

The prevalence of inflammatory tongue conditions was significantly higher in patients with tongue cancer than controls (6.0% v 0.6%; odds ratios [ORs], adjusted for age, sex, race, Medicare utilization, and precancer, 5.8 [95% CI, 4.7 to 7.2]). This overall association primarily arose from glossitis, 5.6 (95% CI, 4.4 to 7.2); other specified conditions, 9.1 (95% CI, 5.5 to 15.2); and other unspecified conditions, 13.7 (95% CI, 8.0 to 23.7). These associations remained strongly elevated >5 years preceding tongue cancer (arguing against reverse causation), for conditions diagnosed by a specialist (arguing against misclassification), and among patients who received an oral biopsy (arguing against missed cancer). During 2013, an estimated 1 in 11 patients with oral tongue cancer had a preceding diagnosis of inflammatory tongue conditions. Associations of inflammatory tongue conditions were relatively weak for other oral cavity cancers (ORs, 1.8 [95% CI, 1.5 to 2.3]) and oropharyngeal cancer (OR, 1.3 [95% CI, 1.0 to 1.6]) and were observed only closest to cancer diagnosis.

CONCLUSION

Inflammatory tongue conditions were associated with strongly increased risks of oral tongue cancers and preceded cancer diagnosis by several years, underscoring the need for increased clinical surveillance among patients with such apparently benign diagnoses.
Association Between Copayment Assistance, Insurance Type, Prior Authorization, and Time to Receipt of Oral Anticancer Drugs
Authors: Lichtenstein Morgan R.L. , Beauchemin Melissa P. , Raghunathan Rohit , Lee Shing , Doshi Sahil D. , Law Cynthia , Accordino Melissa K. , Elkin Elena B. , Wright Jason D. , Hershman Dawn L.
Published: November 2023

PURPOSE

Oral anticancer drugs (OACDs) have become increasingly prevalent over the past decade. OACD prescriptions require coordination between payers and providers, which can delay drug receipt. We examined the association between insurance type, pursuit of copayment assistance, pursuit of prior authorization (PA), and time to receipt (TTR) for new OACD prescriptions.

METHODS

We prospectively collected data on new OACD prescriptions for adult oncology patients from January 1, 2018, to December 31, 2019, including demographic and clinical characteristics, insurance type, and pursuit of PA and copayment assistance. TTR was defined as the number of days from prescription to OACD receipt. We summarized TTR using cumulative incidence and compared TTR by insurance type, pursuit of copayment assistance, and PA activity using the log-rank test.

RESULTS

Our cohort of 1,024 patients was 53% male, and 40% were younger than 65. Twenty-six percent had commercial insurance only, 16% had Medicaid only, and 59% had Medicare with or without additional insurance. Eighty-six percent of prescriptions were successfully received. Across all prescriptions, 69% involved PA activity, and 21% involved the copayment assistance process. In unadjusted analyses, prescriptions involving the copayment assistance process had longer TTR compared with those not involving assistance (log-rank P value = .005) and OACDs covered by Medicare/commercial insurance had a longer TTR compared with Medicaid (log-rank P value = .006). The PA process was not associated with TTR (log-rank P value = .124).

CONCLUSION

The process for obtaining OACDs is complex. The copayment assistance process and Medicare/commercial insurance are associated with delayed TTR. New policies are needed to reduce time to OACD receipt.