bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Portrayals of Public Debt in the Formation of Modern Italy: From the Ancien Régime to Modern Capitalism
Authors: Conte Giampaolo
Published: March 2023

The unification of Italian public debts in 1861 has been analysed until now without any detailed investigation into the changes that occurred in pre-existent public finance models, particularly as regards the contextualisation of public debt within the evolving framework of Italian capitalism. The Kingdom of Sardinia imposed on the other Italian regions not merely a state, bureaucratic and administrative system, but also an economic and financial one: a modern liberal-capitalist model of northern European origin and inspiration. The transition and incorporation of the Neapolitan public debt into the Great Book of the Italian Public Debt bear witness to this change. The aim of the present article is to investigate the transformation of the Italian public debt's structure. I explore specifically the effects of the shift from registered bonds to bearer bonds in Naples, as exemplifying a more radical metamorphosis and the transition from a public finance model typical of the ancien régime to the modern liberal-capitalist one, which is characterised by the Kingdom of Sardinia.
Effects of physical training on change of direction performance: A systematic review with meta-analysis
Authors: Carvajal-Espinoza Rafael , Talpey Scott , Salazar-Rojas Walter
Published: March 2023

Background

One of the most sought-after skills for performance in team sports is change of direction. Training the physical qualities of strength, speed, and power has been used to improve change of direction. These qualities of change of direction have been studied extensively for the last 20 years, and their influence is still questioned. Additionally, it is currently unknown how moderating training variables affect COD performance.

Objective

This study examines the impact of strength, power, and speed training on change of direction performance.

Method

Following the PRISMA guidelines, a meta-analysis was conducted. Electronic databases were searched for studies conducted from 1991 to April 2021. All studies identified for inclusion were peer-reviewed and published in English and Spanish and used an athlete population as participants. For all analyses, a significance level is set at p < 0.05.

Results

Sixty-six articles were included in this meta-analysis. Two hundred fifty-one effect sizes were calculated, representing 2056 participants aged between 12 and 25 years. The global effect size (ES) for each quality is reported and Cochran's Q test: Strength ( N = 48) ES: 0.844 Q = 77.63 (95%CI: 0.65;1.07); Speed (N = 17) ES: 0.70 Q = 5.69 (CI95% = 0.35;1.05); Power (N = 49) ES: 0.85 Q = 47.58 (CI95% = 0.64;1.06); Agility ( N = 57) ES: 1.05 Q = 79.63 (CI95% = 0.86;1.24); Combined training ( N = 13) ES: 0.51 Q = 13.79 (CI95% = 0.14;0.93), and the Control Group ( N = 67) ES: 0.53 Q = 47.40 (IC95% = −0.12;0.23), all ES were statistically significant except control group. The ANOVA-LIKE presented a statistically significant difference between physical qualities and the control group (Sig = 0.000 Q = 69.18).

Conclusion

The training of strength, speed, power, and agility, are effective training methods for improving change of direction ability. Each of these qualities has one or more moderating variables that influencing its development.
Three-dimensional carpal alignment: computer-aided CT analysis of carpal axes and normal ranges
Authors: Höglund Theresa E. K. , Sippo Robert M. J. , Waris Eero
Published: March 2023

Assessment of carpal alignment traditionally uses carpal bone axes measured on lateral radiographs. In this study, three-dimensional axes were defined for carpal bones using segmentation and numerical modelling of CT data of 121 neutrally positioned, asymptomatic wrists. The geometric axis was used for radius, scaphoid and capitate, whereas the axis based on a line perpendicular to the articular surface was used for the other carpal bones. Normal values of radiocarpal angles in the radial coordinate and the reliability of the computer-aided analysis are reported. The mean sagittal radiocarpal angles (positive in palmar direction) were as follows: scaphoid 58° (SD 10°), lunate 0° (SD 11°), triquetrum 12° (SD 8°), trapezium 17° (SD 8°), trapezoid −10° (SD 7°), capitate −17° (SD 9°) and hamate 2° (SD 7°). The mean coronal radiocarpal angles (positive in ulnar direction) were −42° (SD 9°), −20° (SD 4°), −49° (SD 4°), −32° (SD 6°), −16° (SD 5°), 2° (SD 7°) and 8° (SD 6°), respectively. The intra-observer reliability of the measurements was excellent (mean intraclass correlations coefficient 0.98). This study provides guidelines on how to measure and quantify carpal alignment three-dimensionally, and a database for the normal values. Together, these may be useful when analysing various wrist pathologies and kinematics of the wrist.
Long-term outcomes of the Universal 2 total wrist replacement: revision and loosening at 10 years and beyond
Authors: Newton Ashley , Kandemir Göksu , Joyce Thomas , Murali Raj , Hayton Michael , Talwalkar Sumedh , Trail Ian
Published: March 2023

The aim of this study was to ascertain the long-term revision rates of the Universal 2 wrist prosthesis in a previously published cohort of patients with rheumatoid arthritis. The time to, and reasons for revision were determined. Radiographs were analysed to determine whether loosening had occurred in the long-term according to the Wrightington zonal classification of loosening. Seventy-eight wrists from the original cohort of 85 wrists could be identified for analysis. The longest follow-up was 16 years and 29 wrists had follow-up beyond 10 years. Seventeen wrists had been revised or were on the waiting list for revision, an overall revision rate of 22%. The 10-year survivorship was 78%. Long-term revision was commonly for periprosthetic loosening with pain and component subsidence. In those with more than 10-year follow-up, significant lucency was seen in 16 carpal components and 15 radial components. Explant analysis showed significant polyethylene wear and we postulate this is the principal reason for component loosening.

Level of evidence: IV
Somatovisceral Influences on Emotional Development
Authors: Faig Kelly E. , Smith Karen E. , Dimitroff Stephanie J.
Published: March 2023

Frameworks of emotional development have tended to focus on how environmental factors shape children's emotion understanding. However, individual experiences of emotion represent a complex interplay between both external environmental inputs and internal somatovisceral signaling. Here, we discuss the importance of afferent signals and coordination between central and peripheral mechanisms in affective response processing. We propose that incorporating somatovisceral theories of emotions into frameworks of emotional development can inform how children understand emotions in themselves and others. We highlight promising directions for future research on emotional development incorporating this perspective, namely afferent cardiac processing and interoception, immune activation, physiological synchrony, and social touch.
Post-traumatic stress disorder and associated factors among adults exposed to stress in Ethiopia: A meta-analysis and systematic review
Authors: Melkam Mamaru , Tinsae Techilo , Andualem Fantahun , Nakie Girum
Published: March 2023

Objective:

Post-traumatic stress disorder is a complex psychiatric disorder that develops after exposure to traumatic events, such as violent physical assaults, accidents, rape, natural disasters, and conflicts, stranger than usual human experiences. The typical presentation of intrusive thoughts, the persistence of the trauma, the avoidance of pertinent stimuli, emotional numbness, and physiological hyperarousal are the characteristics of this anxiety symptom. Despite the presence of a study conducted on this problem, the pooled effect, particularly in Ethiopia, is not known; therefore, this study assessed the allover burden of post-traumatic stress disorder.

Method:

The available study was extracted and conducted on post-traumatic stress disorder and its associated factors in Ethiopia by three independent authors. The data were analyzed by using STATA version 11 after extraction was done on a Microsoft Excel spreadsheet. The random-effect model was used to estimate the pooled effect size of post-traumatic stress disorder and its effect in the previous studies with 95% confidence intervals. Funnel plots analysis and Egger regression tests were conducted to detect the presence of publication bias. A subgroup analysis and a sensitivity analysis were done.

Result:

Thirteen (13) studies were included with a total of 5874 study participants in this meta-analysis and systematic reviews. The pooled prevalence of post-traumatic stress disorder in Ethiopia was 39.28% with a 95% confidence interval (26.54, 52.01). Poor social support (adjusted odds ratio = 2.86; 95% confidence interval (1.81, 4.53)), being female (adjusted odds ratio = 1.89; 95% confidence interval (1.53, 2.34)), presence of previous mental illness (adjusted odds ratio = 4.72; 95% confidence interval (2.62, 8.36)), and witness (adjusted odds ratio = 2.01; 95% confidence interval (1.30, 3.11)) were associated with post-traumatic stress disorder.

Conclusion:

The burden of post-traumatic stress disorder in this meta-analysis and systematic review is high; therefore, immediate intervention is needed for those specific traumatized individuals.
Retention and engagement of rural caregivers of adolescents in a short message service intervention to reduce sugar-sweetened beverage intake
Authors: Yuhas Maryam , Brock Donna-Jean P , Ritterband Lee M , Chow Philip I , Porter Kathleen J , Zoellner Jamie M
Published: March 2023

Objective

This study investigates a 6-month short message service (SMS) intervention to reduce adolescent sugar-sweetened beverage (SSB) intake. The objectives are to describe caregiver retention and SMS engagement as well as explore differences by caregiver characteristics.

Methods

Caregivers completed a baseline survey then messages were sent two times per week. Message types included the following: SSB intake assessments, educational information, infographic URLs, and strategies. Engagement was measured through interaction with these messages and included: assessment completion, reminders needed, number of strategies chosen, and URLs clicked.

Results

Caregivers (n = 357) had an average baseline SSB intake of 23.9 (SD = 26.8) oz/day. Of those, 89% were retained. Caregivers with a greater income and education were retained at a higher rate. Average engagement included: 4.1 (SD = 1.3) of 5 assessments completed with few reminders needed [4.1 (SD = 3.7) of 14 possible], 3.2 (SD = 1.1) of 4 strategies selected, and 1.2 (SD = 1.6) of 5 URLs clicked. Overall, average engagement was relatively high, even where disparities were found. Demographic characteristics that were statistically related to lower engagement included younger age, lower income, lower educational attainment, single caregivers, lower health literacy. Furthermore, caregivers with a reduced intention to change SSB behaviors completed fewer assessments and needed more reminders. Higher baseline SSB intake was associated with lower engagement across all indicators except URL clicks.

Conclusions

Results can be used to develop targeted retention and engagement strategies (e.g., just-in-time and/or adaptive interventions) in rural SMS interventions for identified demographic subsets.

Trial registration

Clincialtrials.gov: NCT03740113.
A ‘Soft’ Balancing Ménage à Trois? China, Iran and Russia Strategic Triangle vis-à-vis US Hegemony
Authors: Papageorgiou Maria (Mary) , Eslami Mohammad , Duarte Paulo Afonso B.
Published: March 2023

The recent rapprochement among China, Iran and Russia reveals the emergence of a new, unexpected, regional strategic triangle with the potential to balance the United States’ dominant position. By focusing on the evolution of this strategic triangle in the post-Cold War period, this article investigates the driving forces that bring the three states together, namely the US power and unilateralism as materialised in NATO’s eastward expansion, the sanctions on Russia after the annexation of Crimea and the war in Ukraine, the sanctions against Iran, the US trade war with China and the hostile US posture during the coronavirus disease-2019 pandemic. Drawing on soft balancing theory, this article provides an empirical assessment of China–Iran– Russia strategies in countering the US power. Thus, this article aims to fill a gap in the existing literature by investigating this triangular relationship and its balancing potential under the analytic construct of a strategic triangle. Finally, the analysis demonstrates that the three states have employed soft balancing mechanisms, primarily economic strengthening and entangling diplomacy in international institutions. At the same time, territorial denial was sought on various occasions due to the regional importance of this triangular relationship. In conclusion, the article also offers insights into potential hard-balancing behaviour in the long run.
Using Experimental Designs to Study Entrepreneurship Education: A Historical Overview, Critical Evaluation of Current Practices in the Field, and Directions for Future Research
Authors: Englis Basil G. , Frederiks Arjan J.
Published: March 2023

Over the last 20 years, there has been growing interest among scholars in conducting experiments in entrepreneurship education. In this paper, we first discuss how experiments as a research method have moved from the natural sciences into the social sciences and how the social sciences, including the educational sciences, have helped to address the challenges of using experiments in studying human behavior. Through the lens of the methodological advances made by the social sciences regarding conducting experiments, we systematically review the literature on entrepreneurship education research that has used experimental designs. By reviewing this literature, we provide an overview of what has and has not yet been studied using experimental designs and which type of experimental designs have been commonly used. Next, we critically evaluate current practices – both good and bad. Based on our critical assessment of the use of experimental designs in the field of entrepreneurship education research, we not only provide a future research agenda and call for experiments that (1) are more theory-driven; (2) answer more ambitious research questions, and (3) use more robust designs, but we also provide several paths forward for experimentalists with an interest in entrepreneurship education to do so.
Re-investigation of ‘minasgeraisite-(Y)’ from the Jaguaraçu pegmatite, Brazil and high-temperature crystal chemistry of gadolinite-supergroup minerals
Authors: Vereshchagin Oleg S. , Gorelova Liudmila A. , Shagova Anastasia K. , Kasatkin Anatoly V. , Škoda Radek , Bocharov Vladimir N. , Vlasenko Natalia S. , Vašinová Galiová Michaela
Published: March 2023

The chemical composition (including B, Be and Li), the Raman spectrum and the crystal-structure evolution (at the temperature range 27–1000°C) of a Mn-bearing, Bi-rich gadolinite-subgroup mineral from the Jaguaraçu Pegmatite, Brazil (type-locality of minasgeraisite-(Y)) was studied. Elemental mapping revealed that the crystal investigated has complex chemical zonation with various Bi (~8–24 wt.% Bi2O3), Ca (~8–10 wt.% CaO) and Y (~11–17 wt.% Y2O3) content. The sample investigated has all the specific features of the chemical composition of minasgeraisite-(Y), except Ca excess and, thus, should be considered as hingganite-(Y). The Raman spectrum of the sample under study has bands at 140, 179, 243, 350, 446, 519, 559, 625, 902, 973, 3224, 3353, 3532 and 3763 cm–1, and is similar to that of hingganite-(Y) / -(Nd). Crystal-structure refinement confirmed that the crystal in question should be considered as hingganite-(Y) and is in line with the previously obtained data on gadolinite-subgroup minerals from the Jaguaraçu Pegmatite. High-temperature single-crystal X-ray diffraction studies revealed that the mineral starts to decompose above 800°C. We can conclude that beryllosilicates are most stable at high-temperature conditions within the gadolinite supergroup and that species with a higher M-site occupancy have higher stability upon heating.
Individual phosphatidylinositol transfer proteins have distinct functions that do not involve lipid transfer activity
Authors: Zhao Liang , Thorsheim Chelsea L. , Suzuki Aae , Stalker Timothy J. , Min Sang H. , Krishnaswamy Sriram , Cockcroft Shamshad , Anderson Karen E. , Weiderhold Brittany , Abrams Charles S.
Published: March 2023

Platelets use signal transduction pathways facilitated by class I phosphatidylinositol transfer proteins (PITPs). The 2 mammalian class I PITPs, PITPα and PITPβ, are single PITP domain soluble proteins that are encoded by different genes and share 77% sequence identity, although their individual roles in mammalian biology remain uncharacterized. These proteins are believed to shuttle phosphatidylinositol and phosphatidylcholine between separate intracellular membrane compartments, thereby regulating phosphoinositide synthesis and second messenger formation. Previously, we observed that platelet-specific deletion of PITPα, the predominantly expressed murine PITP isoform, had no effect on hemostasis but impaired tumor metastasis formation and disrupted phosphoinositide signaling. Here, we found that mice lacking the less expressed PITPβ in their platelets exhibited a similar phenotype. However, in contrast to PITPα-null platelet lysates, which have impaired lipid transfer activity, PITPβ-null platelet lysates have essentially normal lipid transfer activity, although both isoforms contribute to phosphoinositide synthesis in vitro. Moreover, we found that platelet-specific deletion of both PITPs led to ex vivo platelet aggregation/secretion and spreading defects, impaired tail bleeding, and profound tumor dissemination. Our study also demonstrated that PITP isoforms are required to maintain endogenous phosphoinositide PtdInsP2 levels and agonist-stimulated second messenger formation. The data shown here demonstrate that the 2 isoforms are functionally overlapping and that a single isoform is able to maintain the homeostasis of platelets. However, both class I PITP isoforms contribute to phosphoinositide signaling in platelets through distinct biochemical mechanisms or different subcellular domains.
Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals
Authors: Gagnon Marie-France , Provost Sylvie , Sun Maxine , Ayachi Sami , Buscarlet Manuel , Mollica Luigina , Szuber Natasha , Dubé Marie-Pierre , Busque Lambert
Published: March 2023

Blood cell production is a complex process, partly genetically determined and influenced by acquired factors. However, there is a paucity of data on how these factors interplay in the context of aging, which is associated with a myeloid proliferation bias, clonal hematopoiesis (CH), and an increased incidence of myeloid cancers. We investigated hereditary and acquired factors underlying blood cell trait variability in a cohort of 2996 related and unrelated women from Quebec aged from 55 to 101 years. We performed a genome-wide association study, evaluated the impact of chronic diseases, and performed targeted deep sequencing of CH driver genes and X-chromosome inactivation (XCI)–based clonality analyses. Multivariable analyses were conducted using generalized linear mixed models. We document that aging is associated with increasing neutrophil and monocyte counts and decreasing lymphocyte counts. Neutrophil counts were influenced by the variants in the region of GSDMA and PSMD3-CSF3, but this association decreased with age; in parallel, older individuals with cardiometabolic comorbidities exhibited significantly higher neutrophil counts (4.1 × 109/L vs 3.83 × 109/L; P < .001) than younger individuals. These age-related diseases were also associated with an increase in other myeloid-derived cells. Neither CH nor XCI clonality correlated with neutrophil counts. In conclusion, we show that neutrophil counts are genetically influenced, but as individuals age, this contribution decreases in favor of acquired factors. Aging is associated with a myeloid proliferation bias which is greater in the presence of cardiometabolic comorbidities but not of CH. These findings support that cell-extrinsic factors may contribute to the myeloid shift possibly through low-grade inflammation.
Research Progress in Preparation and Application of Photonic Crystals
Authors: Lv Xiaoren , Zhong Bing , Huang Yanfei , Xing Zhiguo , Wang Haidou , Guo Weiling , Chang Xueting , Zhang Zhinan
Published: March 2023

Photonic crystals are periodic structural materials that have an impact on the propagation properties of photons. Due to their excellent optical, electrical and magnetic properties, their advantages and potential for applications in the above areas are gradually emerging. Therefore, an increasing number of researchers have focused on photonic crystals. In this paper, the characteristics of biological photonic crystal structures, such as those found in butterfly wings, sea mouse bristles, peacock feathers, melon jellyfish epidermal cells, and weevil exoskeletons, are described. The preparation methods of photonic crystals are systematically summarized (including the template method, self-assembly technology, electron beam evaporation coating technology, chemical vapor deposition technology, femtosecond laser two-photon technology, spin coating technology, and a variety of technology mixing), and the characteristics, advantages, and disadvantages of the different methods are compared. Furthermore, the development of photonic crystals in the field of sensors, solar cells, filters, and infrared stealth is discussed, demonstrateing the great development potential of photonic crystals. It is concluded that the realization of photonic crystals with high precision, high sensitivity, angle independence, and large-area uniform preparation is a key problem requiring urgent solution. Moreover, photonic crystals have potential development prospects in the fields of equipment stealth, new concept weapons, production, an daily life.
A novel score to estimate thrombus burden and predict intracranial hypertension in cerebral venous sinus thrombosis
Authors: Wang Zhongao , Dandu Chaitu , Guo Yibing , Gao Meini , Lan Duo , Pan Liqun , Zhou Da , Ding Yuchuan , Ji Xunming , Meng Ran
Published: March 2023

Background

Current methods to evaluate the severity of cerebral venous sinus thrombosis (CVST) lack patient-specific indexes. Herein, a novel scoring method was investigated to estimate the thrombus burden and the intracranial pressure (ICP) of CVST.

Methods

In this retrospective study from January 2019 through December 2021, we consecutively enrolled patients with a first-time confirmed diagnosis of CVST by contrast-enhanced magnetic resonance venography (CE-MRV) or computed tomography venography (CTV). In these patients, a comprehensive CVST-Score was established using magnetic resonance black-blood thrombus imaging (MRBTI) to estimate the thrombus burden semi-quantitatively. The relationship between CVST-Score and ICP was explored to assess the potential of using the CVST-score to evaluate ICP noninvasively and dynamically.

Results

A total of 87 patients were included in the final analysis. The CVST-Scores in different ICP subgroups were as follows: 4.29±2.87 in ICP<250mmH2O subgroup, 11.36±3.86 in ICP =250-330mmH2O subgroup and 14.99±3.15 in ICP>330mmH2O subgroup, respectively (p<0.001). For patients with ICP ≤330mmH2O, the CVST-Score was linearly and positively correlated with ICP (R2=0.53). The receiver operating characteristic (ROC) curves showed the optimal CVST-Score cut-off values to predict ICP ≥250mmH2O and >330mmH2O were 7.15 and 11.62, respectively (P<0.001). Multivariate analysis indicated CVST-Score as an independent predictor of ICP ≥250mmH2O (odds ratio, 2.15; 95% confidence interval, 1.49-3.10; p<0.001).

Conclusions

A simple and noninvasive CVST-Score can rapidly estimate the thrombus burden and predict the severity of intracranial hypertension in patients with CVST. The CVST-Score can aid in evaluating therapeutic responses and avoiding unnecessary invasive procedures at long-term follow-up.

Graphical Abstract
Disentangling the Roles of Plant Water Status and Stem Carbohydrate Remobilization on Rice Harvest Index Under Drought
Authors: Dwivedi Sharad K. , Kumar Santosh , Natividad Mignon A. , Quintana Marinell R. , Chinnusamy Viswanathan , Henry Amelia
Published: March 2023

Background

Harvest index is an important component of grain yield and is typically reduced by reproductive stage drought stress in rice. Multiple drought response mechanisms can affect harvest index including plant water status and the degree of stem carbohydrate mobilization during grain filling. In this study, we aimed to dissect the contributions of plant water status and stem carbohydrate mobilization to harvest index. Pairs of genotypes selected for contrasting harvest index but similar biomass and days to flowering were characterized at ICAR-RCER, Patna, India and at IRRI, Philippines.

Results

Multiple traits were related with harvest index across experiments, including mobilization efficiency at both sites as indicated by groupings in principal component analysis, and plant water status as indicated by direct correlations. Biomass-related traits were positively correlated with harvest index at IRRI but biomass was negatively correlated with harvest index at ICER-RCER, Patna. We observed that some pairs of genotypes showed differences in harvest index across environments, whereas other showed differences in harvest index only under drought. Of all time points measured when all genotypes were considered together, the stem carbohydrate levels at maturity were most consistently (negatively) correlated with harvest index under drought, but not under well-watered conditions. However, in the pairs of genotypes grouped as those whose differences in harvest index were stable across environments, improved plant water status resulted in a greater ability to both accumulate and remobilize stored carbohydrate, i.e. starch.

Conclusion

By distinguishing between genotypes whose harvest index was improved across conditions as opposed to specifically under drought, we can attribute the mechanisms behind the stable high-harvest index genotypes to be more related to stem carbohydrate remobilization than to plant water status. The stable high-harvest index lines in this study (Aus 257 and Wanni Dahanala) may confer mechanisms to improve harvest index that are independent of drought response and therefore may be useful for breeding improved rice varieties.
Study protocol of a telephone problem-solving intervention for Spanish-speaking caregivers of veterans post-stroke: an 8-session investigator-blinded, two-arm parallel (intervention vs usual care), randomized clinical trial
Authors: Freytes I. Magaly , Schmitzberger Magda K. , Rivera-Rivera Naiomi , Lopez Janet , Motta-Valencia Keryl , Wu Samuel S. , Orozco Tatiana , Hale-Gallardo Jennifer , Eliazar-Macke Nathaniel , LeLaurin Jennifer H. , Uphold Constance R.
Published: March 2023

Background

Stroke is one of the leading causes of death and the main cause of long-term disability in the United States. The significant risk factors of stroke among Hispanics are well-documented. The majority of stroke survivors return home following a stroke and are cared for by family caregivers. Due to the abrupt nature of strokes, caregivers experience unexpected changes and demands that oftentimes lead to caregiver burden and depression. Given the significant risk factors for stroke in Hispanics and the influence of culture in family norms and family management, we developed a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers. This study tests the impact of a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers on caregiver outcomes.

Methods

The design is a two-arm parallel randomized clinical trial with repeated measures. We will enroll 290 caregivers from 3 Veterans Affairs (VA) medical centers. Participants randomized into the intervention arm receive a problem-solving intervention that uses telephone and online education and care management tools on the previously developed and nationally available RESCUE en Español Caregiver website. In the usual care group, participants receive the information and/or support caregivers of veterans with stroke normally receive through existing VA resources (e.g., stroke-related information and support). The primary outcome is change in caregiver’s depressive symptoms at 1- and 12-weeks post-intervention. Secondary outcomes include changes in stroke caregivers’ burden, self-efficacy, problem-solving, and health-related quality of life (HRQOL) and veterans’ functional abilities. We will also determine the budgetary impact, the acceptability of the intervention and participation barriers and facilitators for Spanish-speaking stroke caregivers.

Discussion

This is an ongoing study. It is the first known randomized controlled trial testing the effect of a telephone and online problem-solving intervention in Spanish for caregivers of veterans post-stroke. If successful, findings will support an evidence-based model that can be transported into clinical practice to improve the quality of caregiving post-stroke.

Trial registration

ClinicalTrials.gov: NCT03142841— Spanish Intervention for Caregivers of Veterans with Stroke (RESCUE Español). Registered on February 23, 2018. Protocol version 8. 08.11.2022.
CT-based Hounsfield unit values reflect the degree of steatohepatitis in patients with low-grade fatty liver disease
Authors: Kim Ha Neul , Jeon Hong Jae , Choi Hei Gwon , Kwon In Sun , Rou Woo Sun , Lee Jeong Eun , Lee Tae Hee , Kim Seok Hyun , Lee Byung Seok , Shin Kyung Sook , Lee Hyun Jung , Eun Hyuk Soo
Published: March 2023

Background/Aims

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard.

Methods

Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard.

Results

The AUROC for diagnosing mild hepatic steatosis was 0.810 (p < 0.001) for the HSI, 0.732 (p < 0.001) for liver HU value, 0.802 (p < 0.001) for the difference between liver and spleen HU value (L-S HU value) and 0.813 (p < 0.001) for the FLI. Liver HU and L-S HU values were negatively correlated with the percentage of hepatic steatosis and NAFLD activity score (NAS) and significantly different between steatosis grades and between NAS grades. The L–S HU value was demonstrated the good performance for grading the severity of hepatic steatosis and the degree of intrahepatic inflammation.

Conclusions

The HU values on CT are feasible for stratifying hepatic fat content and evaluating the degree of intrahepatic inflammation, and the HSI and the FLI demonstrated good performance with high sensitivity and specificity in diagnosing mild hepatic steatosis.
Therapeutic effects of resveratrol and Omega-3 in mice atherosclerosis: focus on histopathological changes
Authors: Mosavi Shamsi Sadat , Rabizadeh Soghra , Yadegar Amirhossein , Seifouri Sara , Mohammadi Fatemeh , Qahremani Reihane , Salehi Salome Sadat , Rajab Armin , Esteghamati Alireza , Nakhjavani Manouchehr
Published: March 2023

Background

Resveratrol and omega-3 have been shown to prevent atherosclerosis. However, histopathological changes and their comparison have not been studied well. This study investigated the therapeutic effects of resveratrol and omega-3 in experimental atherosclerosis of mice.

Methods

We divided sixty 6-week-old male C57BL/6 mice into six groups and followed for 10 weeks: (1) standard diet, (2) atherogenic diet, (3) atherogenic diet along with resveratrol from the start of the sixth week, (4) atherogenic diet along with omega-3 from the start of the sixth week, (5) standard diet along with resveratrol from the start of the sixth week, (6) standard diet along with omega-3 from the start of the sixth week.

Results

The mice fed on an atherogenic diet had a larger fat area and a thicker aortic wall thickness than mice fed on a standard diet. The use of omega-3 and resveratrol in the mice with an atherogenic diet resulted in a significantly reduced fat area (p-value = 0.003), and resveratrol had a significantly higher effect. Omega-3 or resveratrol induced a significant reduction in aortic wall thickness in mice on an atherogenic diet, and there was no significant difference between them. Among the mice with a standard diet, this study did not observe any significant changes in the fat area or the aortic wall thickness with the consumption of omega-3 or resveratrol.

Conclusions

Resveratrol and omega-3 had a regressive and therapeutic role in atherosclerosis, with a more significant effect in favor of resveratrol.
The influence of excessive stress on medical students in the Czech Republic – national sample
Authors: Palička M. , Rybář M. , Mechúrová B. , Paličková N. , Sobelová T. , Pokorná K. , Cvek J.
Published: March 2023

Purpose

The Czech Republic has been dealing with a long-term shortage of doctors, which, according to demographic forecasts, will continue to worsen due to the retirement of stronger generations of doctors in contrast to the gradual aging of the population, which will require more health care over time. The country´s political set is trying to respond to this shortage and demographic forecasts by gradually increasing financial funding of medical faculties with the aim of increasing the number of graduates of the program in the field of general medicine.

Methods

Anonymous questionnaire survey was conducted among students and graduates of general medicine at all eight Czech medical faculties. A total of 3183 respondents participated in the survey. There were 2843 medical students, which represents approximately 28% of all medical students in the Czech Republic. The distribution of respondents within the study years was approximately even and approximately corresponded to the real distribution of students between individual faculties in country, which makes survey a national sample. The statistical processing was performed in the statistical software R. Apart from the basic comparison using percentage relative frequencies and Pearson´s chi-squared test, in this study we used Odds ratios (OR) with CI 0,95 from logistic regression model for a better interpretation of some outputs.

Results

The results show that the vast majority of Czech medical students experience excessive stress during their studies, which increases the risk of students´ somatic problems (OR = 4.89, CI 0.95 = (4.11;5.83), p < 0.001)., targeted alcohol use (OR = 2.29, CI 0.95 = (1.73;3.04), p < 0,001) and the use of anxiolytic or antidepressant medication to reduce it (OR = 2.99, CI 0.95 = (2.24;4.01), p < 0.001). Students experiencing higher levels of excessive stress are more likely to leave their studies based on their own decision (4.20 (CI 0.95 (3.39;5.19), p < 0.001) and not to enter clinical practice after graduation (OR = 2.62, CI 0.95 = (2.06;3.33), p < 0.001).

Conclusions

The survey shows the need for an open discussion at the highest level about the possibilities of reasonable reduction of unnecessary stress during medical studies. Medical students in the Czech Republic are exposed to excessive stress with all the consequences described above. All that remains is to state the existence of unnecessary components of stress, which represent an opportunity to reduce it, thereby achieving better conditions for studying, improvement in the staff situation in the Czech healthcare system and a reduction in inefficiently spent financial resources for the education of young doctors.

Trial registration

No registration.
Minimally invasive approaches for the early detection of endometrial cancer
Authors: Shen Yufei , Yang Wenqing , Liu Jiachen , Zhang Yu
Published: March 2023

Endometrial cancer (EC) is one of the most common gynecologic cancers and its incidence is rising globally. Although advanced EC has a poor prognosis; diagnosing EC at an earlier stage could improve long-term patient outcomes. However, there is no consensus on the early detection strategies for EC and the current diagnostic practices such as transvaginal ultrasound, hysteroscopy and endometrial biopsy are invasive, costly and low in specificity. Thus, accurate and less invasive screening tests that detect EC in women with early stages of the disease are needed. Current research has revolutionized novel EC early detection methodologies in many aspects. This review aims to comprehensively characterizes minimally invasive screening techniques that can be applied to EC in the future, and fully demonstrate their potential in the early detection of EC.
Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue
Authors: Olesen Hanna Ørnes , Pors Susanne Elisabeth , Adrados Cristina Subiran , Zeuthen Mette Christa , Mamsen Linn Salto , Pedersen Anette Tønnes , Kristensen Stine Gry
Published: March 2023

Background

Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex.

Methods

Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24–36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150–200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks.

Results

A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045).

Conclusions

Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.
METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy
Authors: Sun Yueqin , Shen Weitao , Hu Shulu , Lyu Qiong , Wang Qiongyao , Wei Ting , Zhu Weiliang , Zhang Jian
Published: March 2023

Background

Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Although most patients are initially sensitive to first-line combination chemotherapy with cisplatin and etoposide, chemotherapy drug resistance easily develops and quickly leads to tumour progression. Therefore, understanding the mechanisms of chemotherapy drug resistance and how to reverse it is key to improving the prognosis of patients with SCLC. Moreover, N6-methyladenosine (m6A) is the most abundant mRNA modification and is catalysed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit.

Methods

The effects of METTL3 on chemoresistance in SCLC cells were determined using qRT–PCR, Western blotting, immunohistochemistry, cell counting kit (CCK-8) assays, flow cytometry, and tumorigenicity experiments. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP qPCR, immunofluorescence, and drug inhibitor experiments were performed to confirm the molecular mechanism of Decapping Protein 2 (DCP2), which is involved in the chemoresistance of SCLC.

Results

In the present study, we found that METTL3 is a marker for poor SCLC prognosis, and it is highly expressed in chemoresistant SCLC cells. METTL3 promotes SCLC chemoresistance by positively regulating mitophagy. METTL3 induces m6A methylation of DCP2 and causes the degradation of DCP2, which promotes mitochondrial autophagy through the Pink1-Parkin pathway, leading to chemotherapy resistance. We also found that STM2457, a novel METTL3 inhibitor, can reverse SCLC chemoresistance.

Conclusions

The m6A methyltransferase METTL3 regulates Pink1-Parkin pathway-mediated mitophagy and mitochondrial damage in SCLC cells by targeting DCP2, thereby promoting chemotherapy resistance in patients with SCLC.
Impact of a multifaceted early mobility intervention for critically ill children — the PICU Up! trial: study protocol for a multicenter stepped-wedge cluster randomized controlled trial
Authors: Azamfirei Razvan , Mennie Colleen , Dinglas Victor D. , Fatima Arooj , Colantuoni Elizabeth , Gurses Ayse P. , Balas Michele C. , Needham Dale M. , Kudchadkar Sapna R. ,   on behalf of the PICU Up! ﻿Investigators, Alqahtani Mashael , Azar Justin , Berkenbosch John W. , Bjorklund Ashley R. , Corbett Kelly L. , Dorfman Molly V. , Kiragu Andrew W. , Musick Matthew A. , Porter Melissa B. , Rothschild Charles B. , Scarlett Elizabeth E. , Walker Tracie C. , Wright Melvin L.
Published: March 2023

Background

Over 50% of all critically ill children develop preventable intensive care unit-acquired morbidity. Early and progressive mobility is associated with improved outcomes in critically ill adults including shortened duration of mechanical ventilation and improved muscle strength. However, the clinical effectiveness of early and progressive mobility in the pediatric intensive care unit has never been rigorously studied. The objective of the study is to evaluate if the PICU Up! intervention, delivered in real-world conditions, decreases mechanical ventilation duration (primary outcome) and improves delirium and functional status compared to usual care in critically ill children. Additionally, the study aims to identify factors associated with reliable PICU Up! delivery.

Methods

The PICU Up! trial is a stepped-wedge, cluster-randomized trial of a pragmatic, interprofessional, and multifaceted early mobility intervention (PICU Up!) conducted in 10 pediatric intensive care units (PICUs). The trial’s primary outcome is days alive free of mechanical ventilation (through day 21). Secondary outcomes include days alive and delirium- and coma-free (ADCF), days alive and coma-free (ACF), days alive, as well as functional status at the earlier of PICU discharge or day 21. Over a 2-year period, data will be collected on 1,440 PICU patients. The study includes an embedded process evaluation to identify factors associated with reliable PICU Up! delivery.

Discussion

This study will examine whether a multifaceted strategy to optimize early mobility affects the duration of mechanical ventilation, delirium incidence, and functional outcomes in critically ill children. This study will provide new and important evidence on ways to optimize short and long-term outcomes for pediatric patients.

Trial registration

ClinicalTrials.gov NCT04989790. Registered on August 4, 2021.
A comparison of different physical stimulation combined with platelet-rich plasma for the treatment of knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Liu Yan , Xiang Xiao-Na , Wang Qian , He Hong-Chen
Published: March 2023

Background

Platelet-rich plasma (PRP) contains various growth factors and inflammatory regulators, which can effectively reduce inflammation in joints and promote tissue repair. Multiple studies have proved its effectiveness in the treatment of knee osteoarthritis (KOA). Low-intensity focused ultrasound (LIFU) and transcutaneous electrical nerve stimulation (TENS) are non-invasive and safe physical therapy methods for KOA. This study is the first to propose the treatment of KOA with physical stimulation after PRP treatment, and to observe the clinical efficacy of the treatment method.

Methods

This is a protocol paper that outlines a randomized controlled trial, patients will be assigned randomly to the PRP group, PRP+LIFU group, PRP+TENS group, and PRP+LIFU combined TENS group. The patients will be followed at 12-week and 24-week time points to evaluate the primary and secondary outcomes of the study. The primary outcome is the VAS pain score. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Knee Documentation Committee scores (IKDC). After baseline examination, all patients will sign a written informed consent for study participation after a full explanation of the treatment protocol. We have planned a total of 120 patients (30 patients per group).

Discussion

The objective of this clinical trial is to evaluate the effect of different physical stimulation after PRP treatment for KOA. The data will be published after the completion of the study.

Trial registration

This study has been registered with the Chinese Clinical Trials Registry. Registration number: ChiCTR2200065119 (registered date: 10/28/2022).
spSeudoMap: cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data
Authors: Bae Sungwoo , Choi Hongyoon , Lee Dong Soo
Published: March 2023

Since many single-cell RNA-seq (scRNA-seq) data are obtained after cell sorting, such as when investigating immune cells, tracking cellular landscape by integrating single-cell data with spatial transcriptomic data is limited due to cell type and cell composition mismatch between the two datasets. We developed a method, spSeudoMap, which utilizes sorted scRNA-seq data to create virtual cell mixtures that closely mimic the gene expression of spatial data and trains a domain adaptation model for predicting spatial cell compositions. The method was applied in brain and breast cancer tissues and accurately predicted the topography of cell subpopulations. spSeudoMap may help clarify the roles of a few, but crucial cell types.