bluuebunny/crossref_metadata_2025 huggingface dataset:
“Insufficient guidance and a lack of preparation”: Police academy training and the reality of police work
Authors: Miles-Johnson Toby
Published: April 2023

Police academy training is the foundation of police performance. In Australia, police academy programmes are usually delivered internally by police officers and are underpinned by traditional policing practices and acceptable methods of response deemed suitable. There is little research, however, which determines whether Australian police academies adequately prepare recruits to conduct police work or prime recruits for the reality of policing. Analysing data collected from 46 constables working in one of the largest Australian police organisations, this research offers original insight into a previously under-research area regarding the effectiveness of police academy training in preparing recruits for general-duties police work.
Mikenewite, the natural analogue of synthetic α-Mn2+(S4+O3)⋅3H2O, a new sulfite mineral from the Ojuela mine, Mapimí, Mexico
Authors: Yang Hexiong , Jenkins Robert A. , McGlasson James A. , Gibbs Ronald B. , Downs Robert T.
Published: April 2023

A new mineral species, mikenewite (IMA2022-102), ideally Mn2+(S4+O3)⋅3H2O, has been discovered from the San Judas Chimney, Ojuela mine, Mapimí, Durango, Mexico. It occurs as spheres of platy crystals. Associated minerals include goethite, cryptomelane, adamite and lotharmeyerite. Mikenewite is yellowish in transmitted light, transparent with a white streak and vitreous lustre. It is brittle and has a Mohs hardness of 2½–3. Cleavage is perfect on {101}. The measured and calculated densities are 2.48(5) and 2.467 g/cm3, respectively. Optically, mikenewite is biaxial (+), with α = 1.606(5), β = 1.614(5), γ = 1.627(1) (white light), 2V(meas.) = 69(3)° and 2V(calc.) = 77°. An electron microprobe analysis yielded an empirical formula (based on 6 O apfu) of (Mn0.86Zn0.12Fe0.04Ca0.02)Σ1.04(S0.98O3)⋅3H2O, which can be simplified to (Mn,Zn,Fe)(SO3)⋅3H2O.

Mikenewite is the natural analogue of synthetic α-Mn2+(S4+O3)⋅3H2O, as well as the Mn-analogue of albertiniite, Fe2+(S4+O3)⋅3H2O. It is monoclinic, with space group P21/n and unit-cell parameters a = 6.6390(3), b = 8.8895(4), c = 8.7900(4) Å, β = 96.095(2)°, V = 515.83(4) Å3 and Z = 4. The crystal structure of mikenewite is characterised by each Mn atom coordinated octahedrally by six O atoms, three from different sulfite O atoms and three from H2O molecules. Each S4+O3 group is bonded to three Mn atoms, resulting in a sheet parallel to (101) with the sheet composition of Mn2+(S4+O3)⋅3H2O. Such sheets, stacked along [10$\bar{1}$], are joined together by hydrogen bonds, accounting for the perfect cleavage of the mineral. Mikenewite is dimorphous with orthorhombic Pnma gravegliaite, as albertiniite is with fleisstalite. Its discovery from the Ojuela mine, which is particularly rich in Zn, implies the possibility of finding Zn-bearing sulfites there as well.
Evidence of the anthropogenic origin of the ‘Carmel sapphire’ with enigmatic super-reduced minerals
Authors: Galuskin Evgeny , Galuskina Irina
Published: April 2023

Corundum with inclusions of enigmatic super-reduced minerals was found in mineral separates received as a result of alluvial sediment exploration near Mt Carmel, Israel by the Shefa Yamim Company. This corundum, registered as ‘Carmel sapphireTM’, has been an object of numerous publications by W. Griffin's scientific team, in which they propose a questionable hypothesis of sapphire formation at the crust–mantle boundary with the participation of CH4+H2 fluids. Typically the Carmel sapphire is in small fragments of breccia with white cement, which in the opinion of Griffin et al. is a carbonate-cemented volcanic ash. Our investigation of the ‘white breccia’ showed that it consists of unsorted angular fragments of Carmel sapphire from ~1 μm to 7 mm in size cemented by aluminium hydroxides (bauxite) and is a waste product of the fused alumina process, i.e. it has an anthropogenic origin. Phases typical for slags of fused alumina production and metallurgical slags were identified in the ‘white breccia’. Carmel sapphire has numerous microscopic spherical inclusions of Si–Fe alloy indicating that the removal of Si and Fe from the corundum melt occurred at a temperature >2000°С. Osbornite, TiN, from Carmel sapphire has a chemical zonation characteristic of osbornite from fused alumina with enrichment of central zones in carbon. Comparison of the growth heterogeneity of Carmel sapphire and ‘electrocorundum’ indicates that the crystallisation of the corundum melt proceeded in a similar way. Unfortunately, in the case of Carmel sapphire from the Carmel locality, the contamination of geological samples with anthropogenic material has led to popularisation of biased views.
Libbyite, (NH4)2(Na2□)[(UO2)2(SO4)3(H2O)]2⋅7H2O, a new mineral with uranyl–sulfate sheets from the Blue Lizard mine, San Juan County, Utah, USA
Authors: Kampf Anthony R. , Olds Travis A. , Plášil Jakub , Nash Barbara P. , Marty Joe
Published: April 2023

The new mineral libbyite (IMA2022-091), (NH4)2(Na2□)[(UO2)2(SO4)3(H2O)]2⋅7H2O, was found in the Blue Lizard mine, San Juan County, Utah, USA, where it occurs as tightly intergrown aggregates of light green–yellow equant crystals in a secondary assemblage with bobcookite, coquimbite, halotrichite, metavoltine, rhomboclase, römerite, tamarugite, voltaite and zincorietveldite. The streak is very pale green yellow and the fluorescence is strong green under 405 nm ultraviolet light. Crystals are transparent with vitreous lustre. The tenacity is brittle, the Mohs hardness is ~2½, the fracture is curved. The mineral is soluble in H2O and has a calculated density of 3.465 g⋅cm–3. The mineral is optically uniaxial (–) with ω = 1.581(2) and ɛ = 1.540(2). Electron microprobe analyses provided (NH4)1.92K0.08Na2.00U4.00S6.00O41H18.00. Libbyite is tetragonal,P41212,a= 10.7037(11),c= 31.824(2) Å,V= 3646.0(8) Å3andZ= 4. The structural unit is a uranyl–sulfate sheet that has the same topology as the sheets in several synthetic uranyl selenates.
Carbon nanoparticles-Fe(II) complex for efficient theranostics of xenografted colonic tumor
Authors: Xie Ping , Huang Yuanfang , Tang Kexin , Wu Xian , Zeng Cheng , Yang Sheng-Tao , Tang Xiaohai
Published: April 2023

Background

Overwhelming Fe accumulation in tumor arouses strong oxidative stress. To benefit the cancer patients, Fe(II) delivered by carbon nanoparticles-Fe(II) complex (CNSI-Fe) should be visualized to ensure the successful intratumoral injection and the antitumor mechanisms should be investigated at molecular level.

Results

Intracellular Fe accumulations associating with the uptakes of CNSI-Fe were observed both in vitro and in vivo. The retention of Fe(II) in tumor over 72 h was visualized by magnetic resonance imaging. CNSI-Fe inhibited the tumor growth and expanded the lifespan of colonic tumor-bearing mice. The antitumor activity of CNSI-Fe was attributed to the increases of OH radicals and the oxidative stress in tumor cells, which resulted in cell apoptosis and ferroptosis. The transcriptome analyses confirmed the changes of ferroptosis and inflammation signaling pathways by CNSI-Fe treatment. The low toxicity of CNSI-Fe was indicated by the serum biochemistry, hematology, and histopathology.

Conclusion

CNSI-Fe induced the efficient apoptosis and ferroptosis of colonic tumor for cancer therapy. Our results would benefit the clinical applications of CNSI-Fe and stimulate great interest in the nanomedicine.
Registered care home managers’ experiences of responding to the national care home visiting guidance in England during the Covid-19 pandemic; a multi-method qualitative study
Authors: Dixon Josie , Lorenz-Dant Klara , Stubbs Edmund , Harrison Dening Karen , Mostaghim Manna , Casson Daniel
Published: April 2023

Background

Visiting restrictions in care homes in England and many comparable countries during the Covid-19 pandemic were extensive and prolonged. We examined how care home managers experienced, understood and responded to the national care home visiting guidance in England in developing their visiting policies.

Methods

A diverse sample of 121 care home managers across England, recruited through varied sources including the NIHR ENRICH network of care homes, completed a 10-item qualitative survey. Follow-up, in-depth qualitative interviews were conducted with a purposive sub-sample of 40 managers. Data were analysed thematically using Framework, a theoretically and methodologically flexible tool for data analysis in multiple researcher teams.

Findings

Some viewed the national guidance positively; as supporting the restrictive measures they felt necessary to protect residents and staff from infection, or as setting a broad policy framework while allowing local discretion. More commonly, however, managers experienced challenges. These included the guidance being issued late; the initial document and frequent, media-led updates not being user-friendly; important gaps, particularly in relation to dementia and the risks and harms associated with restrictions; guidance being unhelpfully open to interpretation while restrictive interpretations by regulators limited apparent scope for discretion; fragmented systems of local governance and poor central-local coordination; inconsistent access and quality of support from local regulators wider sources of information, advice and support that, while often valued, were experienced as uncoordinated, duplicative and sometimes confusing; and insufficient account taken of workforce challenges.

Conclusions

Underlying many of the challenges experienced were structural issues, for which there have been longstanding calls for investment and strategic reform. For increasing sector resilience, these should be urgently addressed. Future guidance would also be significantly strengthened by gathering better data, supporting well-facilitated peer exchange, engaging the sector more fully and dynamically in policy-making and learning from care home managers’ and staff’s experiences, particularly of assessing, managing and mitigating the wider risks and harms associated with visiting restrictions.
Impaired pulmonary function and associated factors in the elderly with tuberculosis on admission: a preliminary report
Authors: He Meiyan , Yang Xiaoming , Zhang Zunjing , Liu Zhongda
Published: April 2023

Background

Pulmonary tuberculosis (TB) can impair pulmonary function (PF), especially in the elderly. The risk factors associated with the severity of PF impairment in the elderly with pulmonary TB remain unclear. Hence, this retrospective study aimed to address this issue to help improve the management of TB in the elderly population.

Methods

From January 2019 to February 2022, the elderly who were admitted to our hospital for pulmonary TB and underwent PF testing were included in this analysis. The forced expiratory volume in one second percent of predicted (FEV1% predicted) and clinical characteristics were collected and analyzed retrospectively. The extent of impaired PF was then categorized based on the FEV1% predicted and classified as grade 1–5. Logistic regression analysis was used to analyze the risk factors for impaired PF.

Results

A total of 249 patients who met the enrollment criteria were included in this analysis. According to the results of FEV1% predicted, all patients were classified as grade 1 (n = 37), grade 2 (n = 46), grade 3 (n = 55), grade 4 (n = 56), or grade 5 (n = 55). Statistical analysis showed that albumin (adjusted odds ratio (aOR) = 0.928, P = 0.013), body mass index (BMI) < 18.5 kg/m2 (aOR = 4.968, P = 0.046), lesion number ≥ 3 (aOR = 4.229, P < 0.001), male (aOR = 2.252, P = 0.009), respiratory disease (aOR = 1.669, P = 0.046), and cardiovascular disease (aOR = 2.489, P = 0.027) were related to the impairment of PF.

Conclusions

PF impairment is common in the elderly with pulmonary TB. The male sex, BMI < 18.5 kg/m2, lesion number ≥ 3, hypoproteinemia, and respiratory and cardiovascular comorbidities were identified as risk factors for significant PF impairment. Our findings highlight the risk factors associated with PF impairment, which may be helpful to improve the current management of pulmonary TB in the elderly to save their lung function.
Cerebral venous thrombosis with hyperhomocysteinemia due to loss of heterozygosity at methylenetetrahydrofolate reductase (MTHFR) locus: a case report
Authors: Zhang Mingjie , Shi Bingxin , Zhao Mangsuo
Published: April 2023

Background

Loss of heterozygosity (LOH) at methylenetetrahydrofolate reductase (MTHFR) locus has been reported in tumor tissue. But the mutation was never reported in cerebral venous thrombosis (CVT) with hyperhomocysteinemia (HHcy) before.

Case presentation

A 14-year-old girl was admitted with an intermittent headache and nausea for 2 months. The plasma homocysteine level was 77.2 µmol/L. Lumbar puncture revealed an intracranial pressure > 330 mmH2O. Cerebral MRI and MRV revealed superior sagittal sinus thrombosis. Whole-exome sequencing revealed LOH at Chr1:11836597–11,867,232 affects exons 10–21 of C1orf167, the entire MTHFR, and exons 1–2 of the CLCN6 gene. The normal allele was the c.665 C > T/677 C > T variant in MTHFR. The patient was treated with nadroparin for 2 weeks, followed by oral rivaroxaban. Supplemental folate and vitamins B12 and B6 were prescribed. One month later, she had no headache and the intracranial pressure had decreased to 215 mmH2O. MRI showed shrinkage of the thrombosis in the superior sagittal sinus, the degree of stenosis had significantly decreased.

Conclusions

Rare LOH at the MTHFR locus should be analyzed in CVT with HHcy. With anticoagulation treatment, the prognosis was good.
The Effect of 2016 Chinese second-child policy and different maternal age on pregnancy outcomes in Hebei Province, China
Authors: Tian Mei-Ling , Ma Guo-Juan , Du Li-Yan , Jin Ying , Zhang Cui , Xiao Yuan-Ge , Tang Zeng-jun
Published: April 2023

Objective

To explore the effect of the 2016 Chinese second child policy and different maternal ages on adverse perinatal outcomes.

Methods

Clinical data were collected from 22 monitoring hospitals in Hebei Province from January 1, 2013, to December 31, 2021. A total of 413,892 parturient were divided into 3 groups based on delivery age: 20–34, 35–39, and 40–55 years old. The clinical data were analyzed to explore the relationship among the 2016 Chinese second-child policy, maternal age, and various pregnancy risks.

Results

Pregnancy complications showed an upward trend from 2013 to 2021.The top 10 incidences of pregnancy complications in Hebei Province were anemia, small for gestational age (SGA), large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM), premature delivery, preeclampsia (PE), postpartum hemorrhage (PPH), placenta previa, and placental abruption. The two-child policy was implemented in 2016. The incidence of pregnancy complications, anemia, GDM, PE, placental abruption, cesarean delivery, premature delivery, SGA, LGA, macrosomia in 2016–2021 was significantly higher than that in 2013–2015 (P<0.05), and the proportion of women of advanced maternal age (AMA, ≥ 35 years old) increased from 2013 to 2021. Advanced maternal age was a risk factor for most assessed adverse pregnancy outcomes, including GDM, PE, placenta previa, placenta abruption, cesarean delivery, PPH, premature delivery, SGA, LGA and macrosomia.

Conclusion

After the adjustment of the “second-child” policy, the incidence of pregnancy complications increased. Moreover, the risk of adverse pregnancy outcomes in AMA has increased. Early prevention and intervention should be implemented to cope with the occurrence of adverse perinatal outcomes.
Variants of BEST1 and CRYBB2 cause a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy: case report
Authors: Shi Jie , Sun Tengyang , Xu Ke , Zhang Xin , Li Yang
Published: April 2023

Background

Best vitelliform macular dystrophy (BVMD), caused by pathogenic variants of the BEST1 gene, has not been reported in association with cataracts and ocular malformations. We reported a case with a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy.

Case presentation

A six-year-old girl manifested photophobia and a poor visual behavior. A thorough ophthalmic examination revealed the patient to have bilateral microphthalmia, microcornea, congenital cataract, and Best vitelliform macular dystrophy (BVMD). Whole exome sequencing (WES) identified one variant in the BEST1 and one variant in CRYBB2 genes: c.218 T > G p.(Ile73Arg) and c.479G > C p.(Arg160Pro). The first variant was inherited from the proband’s father, who was diagnosed with subclinical BVMD, while the second was a de novo variant. A minigene assay showed that c.218 T > G in BEST1 did not affect pre-mRNA splicing.

Conclusions

This case suggests that the complex ocular phenotype comprising BVMD and congenital cataract with microphthalmia cannot be explained by variation in one gene but is caused by variants in BEST1 and CRYBB2. This case highlights the importance of general clinical evaluation and comprehensive genetic testing for diagnosing complex eye diseases.
Effect of physical activity promotion program on adherence to physical exercise among patients with type II diabetes in North Shoa Zone Amhara region: a quasi-experimental study
Authors: Eshete Akine , Mohammed Sadat , Shine Sisay , Eshetie Yosef , Assefa Yibeltal , Tadesse Nigussie
Published: April 2023

Background

Diabetes is a significant global public health issue that necessitates self-management. However, this is difficult to put into practice and requires a new approach. The purpose of this study was to assess the effects of a physical activity promotion program on adherence to recommended physical activity and lessons to improve self-management.

Methods

A quasi-experimental study was conducted from January 2020 to February 2021 at North Shoa Zone Public Hospital. The study enrolled 216 type II diabetic patients from four public hospitals. Data were entered into Epi Data V.3.1 and analyzed using SPSS version 22. Data were presented as means of standard deviations for continuous variables and percentages for categorical variables. Intervention and control groups were compared before and after intervention using independent t-tests. A p-value less than 0.05 was considered significant for all statistical tests.

Results

A total of 216 type II diabetics participated in this study. Physical activity promotion programs increased adherence to the recommended number of days and duration (spending time) of physical activity (p < 0.0001). Participants who engaged in the physical activity promotion program significantly increased the mean scores for exercising moderate-intensity activities and spending time (p < 0.05), walking for at least 10 min continuously and spending time (p < 0.05), exercising moderate-intensity recreational activities and spending time (p < 0.05).There was a significant reduction in mean fasting blood glucose after participating in a physical activity program (p < 0.05).

Conclusion

This study demonstrates that a physical activity promotion program makes a significant difference in patient compliance with recommended physical activity and effectively improves patient glycemic control. Health care providers should integrate physical activity programs into existing systems as a common therapeutic service. Primary care platforms such as health posts and health centers can play a key role in integrating health promotion programs to improve self-management behaviors.
Association between the time-varying arterial carbon dioxide pressure and 28-day mortality in mechanically ventilated patients with acute respiratory distress syndrome
Authors: Zhang Rui , Chen Hui , Teng Ran , Li Zuxian , Yang Yi , Qiu Haibo , Liu Ling
Published: April 2023

Background

Recent studies have shown an association between baseline arterial carbon dioxide pressure (PaCO2) and outcomes in patients with acute respiratory distress syndrome (ARDS). However, PaCO2probably varies throughout the disease, and few studies have assessed the effect of longitudinal PaCO2on prognosis. We thus aimed to investigate the association between time-varying PaCO2and 28-day mortality in mechanically ventilated ARDS patients.

Methods

In this retrospective study, we included all adult (≥ 18 years) patients diagnosed with ARDS who received mechanical ventilation for at least 24 h at a tertiary teaching hospital between January 2014 and March 2021. Patients were excluded if they received extracorporeal membrane oxygenation (ECMO). Demographic data, respiratory variables, and daily PaCO2were extracted. The primary outcome was 28-day mortality. Time-varying Cox models were used to estimate the association between longitudinal PaCO2measurements and 28-day mortality.

Results

A total of 709 patients were eligible for inclusion in the final cohort, with an average age of 65 years, of whom 70.7% were male, and the overall 28-day mortality was 35.5%. After adjustment for baseline confounders, including age and severity of disease, a significant increase in the hazard of death was found to be associated with both time-varying PaCO2(HR 1.07, 95% CI 1.03–1.11, p<0.001) and the time-varying coefficient of variation for PaCO2(HR 1.24 per 10% increase, 95% CI 1.10–1.40, p<0.001) during the first five days of invasive mechanical ventilation. The cumulative proportion of exposure to normal PaCO2(HR 0.72 per 10% increase, 95% CI 0.58–0.89, p = 0.002) was associated with 28-day mortality.

Conclusion

PaCO2should be closely monitored in mechanically ventilated ARDS patients. The association between PaCO2and 28-day mortality persisted over time. Increased cumulative exposure to normal PaCO2was associated with a decreased risk of death.
Refracture after plate removal of midshaft clavicle fractures after bone union—incidence, risk factors, management and outcomes
Authors: Zhu Yurun , Hu Jianping , Zhan Taicheng , Zhu Kunpeng , Zhang Chunlin
Published: April 2023

Introduction

There is a great debate on the routine use of open reduction and internal fixation (ORIF) for midshaft clavicle fractures, and one concern is the adverse events after ORIF, such as implant removal after bone union. In this retrospective study, we assessed the incidence, risk factors, management and outcomes of refracture after plate removal of midshaft clavicle fractures after bone union.

Materials and methods

Three hundred fifty-two patients diagnosed with acute midshaft clavicle fractures who had complete medical records from primary fractures to refracture were recruited. Details of imaging materials and clinical characteristics were carefully reviewed and analysed.

Results

The incidence rate of refracture was 6.5% (23/352), and the average interval from implant removal to refracture was 25.6 days. Multivariate analysis showed that the risk factors were Robinson type-2B2 and fair/poor reduction. Females were 2.4 times more likely to have refracture, although it was not significant in multivariate analysis (p = 0.134). Postmenopausal females with a short interval (≤ 12 months) from primary surgery to implant removal had a significant risk for refracture. Tobacco use and alcohol use during bone healing were potential risk factors for male patients, although they were not significant in multivariate analysis. Ten patients received reoperation with or without bone graft, and they had a higher rate of bone union than 13 patients who refused reoperation.

Conclusion

The incidence of refracture following implant removal after bone union is underestimated, and severe comminute fractures and unsatisfactory reduction during primary surgery are risk factors. Implant removal for postmenopausal female patients is not recommended due to a high rate of refracture.
Low back pain in patients hospitalised with liver cirrhosis- a retrospective study
Authors: Bednár R. , Líška D. , Gurín D. , Vnenčaková J. , Melichová A. , Koller T. , Skladaný Ľ.
Published: April 2023

Background

Lower back pain is a common issue, but little is known about the prevalence of pain in patients with liver cirrhosis during hospitalisation. Therefore, the objective of this study was to determine lower back pain in patients with liver cirrhosis.

Methods

The sample consisted of patients with liver cirrhosis (n = 79; men n = 55; women n = 24; mean age = 55.79 ± 12.52 years). The hospitalised patients were mobile. The presence and intensity of pain were assessed in the lumbar spine during hospitalisation. The presence of pain was assessed using the visual analogue pain scale (0–10). The range of motion of the lower spine was assessed using the Schober and Stibor tests. Frailty was measured by Liver Frailty Index (LFI). The condition of liver disease was evaluated using The Model For the End-Stage Liver Disease (MELD) and Child–Pugh score (CPS) and ascites classification. Student’s t test and Mann–Whitney test were used for analysis of the difference of group. Analysis of variance (ANOVA) with the Tukey post hoc test was used to test differences between categories of liver frailty index. The Kruskal–Wallis test was used to test pain distribution. Statistical significance was determined at the α-0.05 significance level.

Result

The prevalence of pain in patients with liver cirrhosis was 13.92% (n = 11), and the mean intensity of pain according to the visual analogue scale was 3.73 (± 1.90). Lower back pain was present in patients with ascites (15.91%; n = 7) and without ascites (11.43%; n = 4). The prevalence of lower back pain was not statistically significant between patients with and without ascites (p = 0,426). The base of Schober’s assessment mean score was 3.74 cm (± 1.81), and based on Stibor’s assessment mean score was 5.84 cm (± 2.23).

Conclusion

Lower back pain in patients with liver cirrhosis is a problem that requires attention. Restricted spinal mobility has been reported in patients with back pain, according to Stibor, compared to patients without pain. There was no difference in the incidence of pain in patients with and without ascites.
Incorporating ultrasound training into undergraduate medical education in a faculty-limited setting
Authors: Rathbun Kimberly M. , Patel Arjun N. , Jackowski Jacob R. , Parrish Matthew T. , Hatfield Ryan M. , Powell Tyler E.
Published: April 2023

Background

Point of care ultrasound (POCUS) is becoming a major extension of patient care. From diagnostic efficacy to its widespread accessibility, POCUS has expanded beyond emergency departments to be a tool utilized by many specialties. With the expansion of its use, medical education has begun to implement ultrasound education earlier in curricula. However, at institutions without a formal ultrasound fellowship or curriculum, these students lack the fundamental knowledge of ultrasound. At our institution, we set out to incorporate an ultrasound curriculum, into undergraduate medical education utilizing a single faculty member and minimal curricular time.

Methods

Our stepwise implementation began with the development of a 3-hour fourth-year (M4) Emergency Medicine clerkship ultrasound teaching session, which included pre- and post-tests as well as a survey. The success with this session progressed to the development of a designated fourth-year ultrasound elective, which was evaluated with narrative feedback. Finally, we developed six 1-hour ultrasound sessions that correlated with first-year (M1) gross anatomy and physiology. A single faculty member was responsible for this curriculum and other instructors included residents, M4 students, and second-year (M2) near-peer tutors. These sessions also included pre- and post-tests and a survey. Due to curricular time limitations, all but the M4 Emergency Medicine clerkship session were optional.

Results

87 students participated in the emergency medicine clerkship ultrasound session and 166 M1 students participated in the voluntary anatomy and physiology ultrasound sessions. All participants agreed or strongly agreed that they would like more ultrasound training, that ultrasound training should be integrated into all four years of undergraduate medical education. Students were in strong agreement that the ultrasound sessions helped increase understanding of anatomy and anatomical identification with ultrasound.

Conclusion

We describe the stepwise addition of ultrasound into the undergraduate medical education curriculum of an institution with limited faculty and curricular time.
Caution with competitive gamification in medical education: unexpected results of a randomised cross-over study
Authors: Kirsch Jacqueline , Spreckelsen Cord
Published: April 2023

Background

To intrinsically motivate students in the long term, longitudinal e-learning systems combined with repeated testing and competitive gamification seem promising. The effects of this approach have never been closely examined in the field of evidence-based medicine. The authors investigated if a simple, competitive learning application enhances students’ risk competence and intrinsic motivation.

Methods

Participants were 5.-9. semester medical students (n = 48), recruited in an elective evidence-based medicine subject and randomly distributed to two groups (group 1: n = 23; group 2: n = 25). Both accessed a competitive evidence-based medicine quiz game. Following a cross-over design, each group practiced with one of two thematically different questionnaires A or B, before the allocation switched after one month. To analyse whether there was a measurable learning effect in the practiced topics, a paired t-test was performed with quantitative data from 3 e-tests. Students further reported their experience in evaluation surveys.

Results

Students’ improvements in e-test scores after training with the corresponding topics in the learning application can be attributed to chance. Even though the majority enjoyed playing and felt motivated to study, they invested a minimum of time and rejected competition.

Conclusion

The authors found no evidence for benefits of the investigated learning programme on students’ risk competence or on their internal motivation. The majority disapproved the competitive concept, indicating adverse side effects of the applied gamification element. To intrinsically motivate more students, prospective learning programmes should favour complex and collaborative programmes over simple and competitive ones.
Development and validation of a nomogram for blood transfusion during intracranial aneurysm clamping surgery: a retrospective analysis
Authors: Xiao Shugen , Liu Fan , Yu Liyuan , Li Xiaopei , Ye Xihong , Gong Xingrui
Published: April 2023

Purpose

Intraoperative blood transfusion is associated with adverse events. We aimed to establish a machine learning model to predict the probability of intraoperative blood transfusion during intracranial aneurysm surgery.

Methods

Patients, who underwent intracranial aneurysm surgery in our hospital between January 2019 and December 2021 were enrolled. Four machine learning models were benchmarked and the best learning model was used to establish the nomogram, before conducting a discriminative assessment.

Results

A total of 375 patients were included for analysis in this model, among whom 108 received an intraoperative blood transfusion during the intracranial aneurysm surgery. The least absolute shrinkage selection operator identified six preoperative relative factors: hemoglobin, platelet, D-dimer, sex, white blood cell, and aneurysm rupture before surgery. Performance evaluation of the classification error demonstrated the following: K-nearest neighbor, 0.2903; logistic regression, 0.2290; ranger, 0.2518; and extremely gradient boosting model, 0.2632. A nomogram based on a logistic regression algorithm was established using the above six parameters. The AUC values of the nomogram were 0.828 (0.775, 0.881) and 0.796 (0.710, 0.882) in the development and validation groups, respectively.

Conclusions

Machine learning algorithms present a good performance evaluation of intraoperative blood transfusion. The nomogram established using a logistic regression algorithm showed a good discriminative ability to predict intraoperative blood transfusion during aneurysm surgery.
Cardiovascular disease incidence prediction by machine learning and statistical techniques: a 16-year cohort study from eastern Mediterranean region
Authors: Mehrabani-Zeinabad Kamran , Feizi Awat , Sadeghi Masoumeh , Roohafza Hamidreza , Talaei Mohammad , Sarrafzadegan Nizal
Published: April 2023

Background

Cardiovascular diseases (CVD) are the predominant cause of early death worldwide. Identification of people with a high risk of being affected by CVD is consequential in CVD prevention. This study adopts Machine Learning (ML) and statistical techniques to develop classification models for predicting the future occurrence of CVD events in a large sample of Iranians.

Methods

We used multiple prediction models and ML techniques with different abilities to analyze the large dataset of 5432 healthy people at the beginning of entrance into the Isfahan Cohort Study (ICS) (1990–2017). Bayesian additive regression trees enhanced with “missingness incorporated in attributes” (BARTm) was run on the dataset with 515 variables (336 variables without and the remaining with up to 90% missing values). In the other used classification algorithms, variables with more than 10% missing values were excluded, and MissForest imputes the missing values of the remaining 49 variables. We used Recursive Feature Elimination (RFE) to select the most contributing variables. Random oversampling technique, recommended cut-point by precision-recall curve, and relevant evaluation metrics were used for handling unbalancing in the binary response variable.

Results

This study revealed that age, systolic blood pressure, fasting blood sugar, two-hour postprandial glucose, diabetes mellitus, history of heart disease, history of high blood pressure, and history of diabetes are the most contributing factors for predicting CVD incidence in the future. The main differences between the results of classification algorithms are due to the trade-off between sensitivity and specificity. Quadratic Discriminant Analysis (QDA) algorithm presents the highest accuracy (75.50 ± 0.08) but the minimum sensitivity (49.84 ± 0.25); In contrast, decision trees provide the lowest accuracy (51.95 ± 0.69) but the top sensitivity (82.52 ± 1.22). BARTm.90% resulted in 69.48 ± 0.28 accuracy and 54.00 ± 1.66 sensitivity without any preprocessing step.

Conclusions

This study confirmed that building a prediction model for CVD in each region is valuable for screening and primary prevention strategies in that specific region. Also, results showed that using conventional statistical models alongside ML algorithms makes it possible to take advantage of both techniques. Generally, QDA can accurately predict the future occurrence of CVD events with a fast (inference speed) and stable (confidence values) procedure. The combined ML and statistical algorithm of BARTm provide a flexible approach without any need for technical knowledge about assumptions and preprocessing steps of the prediction procedure.
N-terminal region of Drosophila melanogaster Argonaute2 forms amyloid-like aggregates
Authors: Narita Haruka , Shima Tomohiro , Iizuka Ryo , Uemura Sotaro
Published: April 2023

Background

Argonaute proteins play a central role in RNA silencing by forming protein-small RNA complexes responsible for the silencing process. While most Argonaute proteins have a short N-terminal region, Argonaute2 in Drosophila melanogaster (DmAgo2) harbors a long and unique N-terminal region. Previous in vitro biochemical studies have shown that the loss of this region does not impair the RNA silencing activity of the complex. However, an N-terminal mutant of Drosophila melanogaster has demonstrated abnormal RNA silencing activity. To explore the causes of this discrepancy between in vitro and in vivo studies, we investigated the biophysical properties of the region. The N-terminal region is highly rich in glutamine and glycine residues, which is a well-known property for prion-like domains, a subclass of amyloid-forming peptides. Therefore, the possibility of the N-terminal region functioning as an amyloid was tested.

Results

Our in silico and biochemical assays demonstrated that the N-terminal region exhibits amyloid-specific properties. The region indeed formed aggregates that were not dissociated even in the presence of sodium dodecyl sulfate. Also, the aggregates enhanced the fluorescence intensity of thioflavin-T, an amyloid detection reagent. The kinetics of the aggregation followed that of typical amyloid formation exhibiting self-propagating activity. Furthermore, we directly visualized the aggregation process of the N-terminal region under fluorescence microscopy and found that the aggregations took fractal or fibril shapes. Together, the results indicate that the N-terminal region can form amyloid-like aggregates.

Conclusions

Many other amyloid-forming peptides have been reported to modulate the function of proteins through their aggregation. Therefore, our findings raise the possibility that aggregation of the N-terminal region regulates the RNA silencing activity of DmAgo2.
Cytological, transcriptome and miRNome temporal landscapes decode enhancement of rice grain size
Authors: Mahto Arunima , Yadav Antima , P. V. Aswathi , Parida Swarup K. , Tyagi Akhilesh K. , Agarwal Pinky
Published: April 2023

Background

Rice grain size (GS) is an essential agronomic trait. Though several genes and miRNA modules influencing GS are known and seed development transcriptomes analyzed, a comprehensive compendium connecting all possible players is lacking. This study utilizes two contrasting GS indica rice genotypes (small-grained SN and large-grained LGR). Rice seed development involves five stages (S1–S5). Comparative transcriptome and miRNome atlases, substantiated with morphological and cytological studies, from S1–S5 stages and flag leaf have been analyzed to identify GS proponents.

Results

Histology shows prolonged endosperm development and cell enlargement in LGR. Stand-alone and comparative RNAseq analyses manifest S3 (5–10 days after pollination) stage as crucial for GS enhancement, coherently with cell cycle, endoreduplication, and programmed cell death participating genes. Seed storage protein and carbohydrate accumulation, cytologically and by RNAseq, is shown to be delayed in LGR. Fourteen transcription factor families influence GS. Pathway genes for four phytohormones display opposite patterns of higher expression. A total of 186 genes generated from the transcriptome analyses are located within GS trait-related QTLs deciphered by a cross between SN and LGR. Fourteen miRNA families express specifically in SN or LGR seeds. Eight miRNA-target modules display contrasting expressions amongst SN and LGR, while 26 (SN) and 43 (LGR) modules are differentially expressed in all stages.

Conclusions

Integration of all analyses concludes in a “Domino effect” model for GS regulation highlighting chronology and fruition of each event. This study delineates the essence of GS regulation, providing scope for future exploits. The rice grain development database (RGDD) (
www.nipgr.ac.in/RGDD/index.php; https://doi.org/10.5281/zenodo.7762870) has been developed for easy access of data generated in this paper.
Triglyceride-glucose index, symptomatic intracranial artery stenosis and recurrence risk in minor stroke patients with hypertension
Authors: Wang Yongle , Liu Tingting , Li Yanan , Zhang Kaili , Fan Haimei , Ren Jing , Li Juan , Li Yali , Li Xinyi , Wu Xuemei , Wang Junhui , Xue Lixi , Gao Xiaolei , Yan Yuping , Li Gaimei , Liu Qingping , Niu Wenhua , Du Wenxian , Liu Yuting , Niu Xiaoyuan
Published: April 2023

Background

The triglyceride-glucose (TyG) index, a simple measure of insulin resistance, is associated with intracranial atherosclerosis (ICAS) and stroke. In hypertensive populations, this association may be pronounced. The aim was to investigate the relationship between TyG and symptomatic intracranial atherosclerosis (sICAS) and recurrence risk in ischemic stroke patients with hypertension.

Methods

This prospective, multicenter cohort study included patients with acute minor ischemic stroke with a preadmission diagnosis of hypertension from September 2019 to November 2021 with a 3-month follow-up. The presence of sICAS was determined by a combination of clinical manifestations, the location of the infarction, and the corresponding artery with moderate-to-severe stenosis. ICAS burden was determined by the degree and number of ICAS occurrences. Fasting blood glucose (FBG) and triglyceride (TG) were measured to calculate TyG. The main outcome was ischemic stroke recurrence during the 90-day follow-up. Multivariate regression models were used to explore the association of TyG, sICAS, and ICAS burden with stroke recurrence.

Results

There were 1281 patients with a mean age of 61.6 ± 11.6 years; 70.1% were male, and 26.4% were diagnosed with sICAS. There were 117 patients who experienced stroke recurrence during follow-up. Patients were categorized according to quartiles of TyG. After adjusting for confounders, the risk of sICAS was greater (OR 1.59, 95% CI 1.04–2.43, p = 0.033) and the risk of stroke recurrence was significantly higher (HR 2.02, 95% CI 1.07–3.84, p = 0.025) in the fourth TyG quartile than in the first quartile. The restricted cubic spline (RCS) plot revealed a linear relationship between TyG and sICAS, and the threshold value for TyG was 8.4. Patients were then dichotomized into low and high TyG groups by the threshold. Patients with high TyG combined with sICAS had a higher risk of recurrence (HR 2.54, 95% CI 1.39–4.65) than patients with low TyG without sICAS. An interaction effect on stroke recurrence between TyG and sICAS was found (p = 0.043).

Conclusion

TyG is a significant risk factor for sICAS in hypertensive patients, and there is a synergistic effect of sICAS and higher TyG on ischemic stroke recurrence.

Trial registration number: The study was registered on 16 August 2019 at https://www.chictr.org.cn/showprojen.aspx?proj=41160 (No. ChiCTR1900025214).
Long non-coding RNA crnde promotes deep vein thrombosis by sequestering miR-181a-5p away from thrombogenic Pcyox1l
Authors: He Xin , Liu Yu , Li Yaozhen , Wu Kemin
Published: April 2023

Background

Deep vein thrombosis (DVT) is an interplay of genetic and acquired risk factors, where functional interactions in lncRNA-miRNA-mRNA ceRNA networks contribute to disease pathogenesis. Based on the high-throughput transcriptome sequencing prediction, we have assessed the contribution of lncRNA Crnde/miR-181a-5p/Pcyox1l axis to thrombus formation.

Methods

DVT was modeled in mice by inferior vena cava stenosis, and inferior vena cava tissues were harvested for high-throughput transcriptome sequencing to screen differentially expressed lncRNAs and mRNAs. The key miRNA binding to Crnde and Pcyox1l was obtained through searching the RNAInter and mirWalk databases. The binding affinity between Crnde, miR-181a-5p, and Pcyox1l was examined by FISH, dual luciferase reporter gene, RNA pull-down, and RIP assays. Functional experiments were conducted in DVT mouse models to assess thrombus formation and inflammatory injury in inferior vena cava.

Results

It was noted that Crnde and Pcyox1l were upregulated in the blood of DVT mice. Crnde competitively bound to miR-181a-5p and inhibited miR-181a-5p expression, and Pcyox1l was the downstream target gene of miR-181a-5p. Silencing of Crnde or restoration of miR-181a-5p reduced inflammatory injury in the inferior vena cava, thus curtailing thrombus formation in mice. Ectopic expression of Pcyox1l counterweighed the inhibitory effect of Crnde silencing.

Conclusions

Therefore, Crnde sequesters miR-181a-5p to release Pcyox1l expression via ceRNA mechanism, thus aggravating thrombus formation in DVT.
Mesenchymal–epithelial transition in lymph node metastases of oral squamous cell carcinoma is accompanied by ZEB1 expression
Authors: Horny Kai , Sproll Christoph , Peiffer Lukas , Furtmann Frauke , Gerhardt Patricia , Gravemeyer Jan , Stoecklein Nikolas H. , Spassova Ivelina , Becker Jürgen C.
Published: April 2023

Background

Oral squamous cell carcinoma (OSCC), an HPV-negative head and neck cancer, frequently metastasizes to the regional lymph nodes but only occasionally beyond. Initial phases of metastasis are associated with an epithelial–mesenchymal transition (EMT), while the consolidation phase is associated with mesenchymal–epithelial transition (MET). This dynamic is referred to as epithelial–mesenchymal plasticity (EMP). While it is known that EMP is essential for cancer cell invasion and metastatic spread, less is known about the heterogeneity of EMP states and even less about the heterogeneity between primary and metastatic lesions.

Methods

To assess both the heterogeneity of EMP states in OSCC cells and their effects on stromal cells, we performed single-cell RNA sequencing (scRNAseq) of 5 primary tumors, 9 matching metastatic and 5 tumor-free lymph nodes and re-analyzed publicly available scRNAseq data of 9 additional primary tumors. For examining the cell type composition, we performed bulk transcriptome sequencing. Protein expression of selected genes were confirmed by immunohistochemistry.

Results

From the 23 OSCC lesions, the single cell transcriptomes of a total of 7263 carcinoma cells were available for in-depth analyses. We initially focused on one lesion to avoid confounding inter-patient heterogeneity and identified OSCC cells expressing genes characteristic of different epithelial and partial EMT stages. RNA velocity and the increase in inferred copy number variations indicated a progressive trajectory towards epithelial differentiation in this metastatic lesion, i.e., cells likely underwent MET. Extension to all samples revealed a less stringent but essentially similar pattern. Interestingly, MET cells show increased activity of the EMT-activator ZEB1. Immunohistochemistry confirmed that ZEB1 was co-expressed with the epithelial marker cornifin B in individual tumor cells. The lack of E-cadherin mRNA expression suggests this is a partial MET. Within the tumor microenvironment we found immunomodulating fibroblasts that were maintained in primary and metastatic OSCC.

Conclusions

This study reveals that EMP enables different partial EMT and epithelial phenotypes of OSCC cells, which are endowed with capabilities essential for the different stages of the metastatic process, including maintenance of cellular integrity. During MET, ZEB1 appears to be functionally active, indicating a more complex role of ZEB1 than mere induction of EMT.