bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis
Authors: Wang Yong , Niu Huicong , Li Luyu , Han Jing , Liu Zhuohang , Chu Min , Sha Xianyi , Zhao Jing
Published: March 2023

Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen–glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC‐Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury.

Graphical abstract
Survival outcomes and the prognostic significance of clinicopathological features in patients with endometrial clear cell carcinoma: a 35-year single-center retrospective study
Authors: Ma Xiao , Cao Dongyan , Zhou Huimei , Wang Tao , Wang Jinhui , Zhang Ying , Yu Mei , Cheng Ninghai , Peng Peng , Yang Jiaxin , Huang Huifang , Shen Keng
Published: March 2023

Background

To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes.

Methods

Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used.

Results

In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS.

Conclusions

ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.
A framework for sustainable capacity-building for collaborative North–South translational health research and training in a resource-constrained setting
Authors: Maponga Charles C. , Mhazo Alison T. , Morse Gene D.
Published: March 2023

Introduction

Success with highly active antiretroviral therapy (ART) for the human immunodeficiency virus (HIV) in developing countries has been attributed to collaborative North–South resource-sharing and capacity-building. Academic research and training programmes have contributed towards policy entrepreneurship in a manner that influenced capacity-building within health systems. However, the documented capacity-building frameworks rarely elucidate how such programmes can be designed and implemented efficiently and sustainably.

Method

We implemented the University of Zimbabwe (UZ)–State University of New York at Buffalo (UB) collaborative HIV clinical pharmacology capacity-building programme in Zimbabwe in 1998. We intuitively operationalized the programme around a mnemonic acronym, “RSTUVW”, which spells out a supportive framework consisting of “room (space), skills, tools (equipment)”, underpinned by a set of core values, “understanding, voice (clout) and will”. Subsequent to our two decades of successful collaborative experience, we tested the general validity and applicability of the framework within a prospective programme aimed at expanding the role of health professionals.

Results and conclusion

Based on this collaborative North–South research and training capacity-building programme which has been positively validated in Zimbabwe, we propose this novel mnemonic acronym-based framework as an extra tool to guide sustainable capacity-building through collaborative North–South implementation research. Its extended use could also include assessment and evaluation of health systems within resource-constrained settings.
Digital behaviour change interventions to increase vegetable intake in adults: a systematic review
Authors: Livingstone Katherine M. , Rawstorn Jonathan C. , Partridge Stephanie R. , Godrich Stephanie L. , McNaughton Sarah A. , Hendrie Gilly A. , Blekkenhorst Lauren C. , Maddison Ralph , Zhang Yuxin , Barnett Scott , Mathers John C. , Packard Maria , Alston Laura
Published: March 2023

Background

Digital interventions may help address low vegetable intake in adults, however there is limited understanding of the features that make them effective. We systematically reviewed digital interventions to increase vegetable intake to 1) describe the effectiveness of the interventions; 2) examine links between effectiveness and use of co-design, personalisation, behavioural theories, and/or a policy framework; and 3) identify other features that contribute to effectiveness.

Methods

A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane Library, INFORMIT, IEEE Xplore and Clinical Trial Registries, published between January 2000 and August 2022. Digital interventions to increase vegetable intake were included, with effective interventions identified based on statistically significant improvement in vegetable intake. To identify policy-action gaps, studies were mapped across the three domains of the NOURISHING framework (i.e., behaviour change communication, food environment, and food system). Risk of bias was assessed using Cochrane tools for randomized, cluster randomized and non-randomized trials.

Results

Of the 1,347 records identified, 30 studies were included. Risk of bias was high or serious in most studies (n = 25/30; 83%). Approximately one quarter of the included interventions (n = 8) were effective at improving vegetable intake. While the features of effective and ineffective interventions were similar, embedding of behaviour change theories (89% vs 61%) and inclusion of stakeholders in the design of the intervention (50% vs 38%) were more common among effective interventions. Only one (ineffective) intervention used true co-design. Although fewer effective interventions included personalisation (67% vs 81%), the degree of personalisation varied considerably between studies. All interventions mapped across the NOURISHING framework behaviour change communication domain, with one ineffective intervention also mapping across the food environment domain.

Conclusion

Few digital interventions identified in this review were effective for increasing vegetable intake. Embedding behaviour change theories and involving stakeholders in intervention design may increase the likelihood of success. The under-utilisation of comprehensive co-design methods presents an opportunity to ensure that personalisation approaches better meet the needs of target populations. Moreover, future digital interventions should address both behaviour change and food environment influences on vegetable intake.
Comprehensive analysis of scRNA-Seq and bulk RNA-Seq reveals dynamic changes in the tumor immune microenvironment of bladder cancer and establishes a prognostic model
Authors: Tan Zhiyong , Chen Xiaorong , Zuo Jieming , Fu Shi , Wang Haifeng , Wang Jiansong
Published: March 2023

Background

The prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as a prognostic marker for many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) data were combined to construct a prognostic model of BLCA.

Methods

BLCA scRNA-seq data were downloaded from Gene Expression Omnibus (GEO) database. Bulk RNA-seq data were obtained from the UCSC Xena. The R package "Seurat" was used for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were utilized for downscaling and cluster identification. The FindAllMarkers function was used to identify marker genes for each cluster. The limma package was used to obtain differentially expressed genes (DEGs) affecting overall survival (OS) in BLCA patients. Weighted gene correlation network analysis (WGCNA) was used to identify BLCA key modules. The intersection of marker genes of core cells and genes of BLCA key modules and DEGs was used to construct a prognostic model by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between the high and low-risk groups were also investigated.

Results

scRNA-seq data were analyzed to identify 19 cell subpopulations and 7 core cell types. The ssGSEA showed that all 7 core cell types were significantly downregulated in tumor samples of BLCA. We identified 474 marker genes from the scRNA-seq dataset, 1556 DEGs from the Bulk RNA-seq dataset, and 2334 genes associated with a key module identified by WGCNA. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of 3 signature genes, namely MAP1B, PCOLCE2, and ELN. The feasibility of the model was validated by an internal training set and two external validation sets. Moreover, patients with high-risk scores are predisposed to experience poor OS, a larger prevalence of stage III-IV, a greater TMB, a higher infiltration of immune cells, and a lesser likelihood of responding favorably to immunotherapy.

Conclusion

By integrating scRNA-seq and bulk RNA-seq data, we constructed a novel prognostic model to predict the survival of BLCA patients. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.
Closed reduction of dorsally displaced distal radius fractures in the elderly provided improved final radiographic results
Authors: Hassellund Sondre Stafsnes , Oftebro Ingrid , Williksen John Haakon , Søreide Endre , Madsen Jan Erik , Frihagen Frede
Published: March 2023

Background

Recent guidelines recommend non-operative treatment as primary treatment in elderly patients with displaced distal radius fractures. Most of these fractures are closely reduced. We aimed to evaluate the radiological results of closed reduction and casting of dorsally displaced distal radius fractures in patients 65 years or older.

Methods

A total of 290 patients treated during the years 2015, 2018 and 2019 in an urban outpatient fracture clinic with complete follow-up at least 5 weeks post-reduction were available for analysis. Closed fracture reduction was performed by manual traction under hematoma block. A circular plaster of Paris cast was used. Radiographs pre- and post-reduction and at final follow-up were analyzed.

Results

Mean age was 77 years (SD 8) and 258 (89%) were women. Dorsal tilt improved from mean 111° (range 83–139) to 89° (71–116) post-reduction and fell back to mean 98° (range 64–131) at final follow-up. Ulnar variance was 2 mm ((-1)-12) pre-reduction, 0 mm ((-3)-5) post-reduction and ended at mean 2 mm (0–8). Radial inclination went from 17° ((-6)-30) to 23° (SD 7–33), and then back to 18° (0–32) at final follow-up. 41 (14%) patients had worse alignment at final follow-up compared to pre-reduction. 48 (17%) obtained a position similar to the starting point, while 201 (69%) improved. Fractures with the volar cortex aligned after reduction retained 0.4 mm (95% Confidence Interval (CI) 0.1 to 0.7; p = 0,022) more radius length during immobilization. In a regression analysis, less ulnar variance in initial radiographs (OR 1.8 (95% CI 1.4 to 2.3) per mm, p < 0.001) and lower age (OR 1.06 (95% CI 1.02 to 1.09) per year, p < 0.003) protected against loss of reduction.

Conclusion

Subsequent loss of reduction after initial closed reduction was seen in most distal radius fractures. Reduction improved overall alignment in 2/3 of the patients at final follow-up. An aligned volar cortex seemed to protect partially against loss of radial length.
LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia
Authors: Wang Dong , Li Xiaohui , Jiao Defeng , Cai Ying , Qian Liting , Shen Yiqing , Lu Yichen , Zhou Yonggang , Fu Binqing , Sun Rui , Tian Zhigang , Zheng Xiaohu , Wei Haiming
Published: March 2023

Background

Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome.

Methods

First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting.

Results

Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice.

Conclusions

Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.
Current sequence-based models capture gene expression determinants in promoters but mostly ignore distal enhancers
Authors: Karollus Alexander , Mauermeier Thomas , Gagneur Julien
Published: March 2023

Background

The largest sequence-based models of transcription control to date are obtained by predicting genome-wide gene regulatory assays across the human genome. This setting is fundamentally correlative, as those models are exposed during training solely to the sequence variation between human genes that arose through evolution, questioning the extent to which those models capture genuine causal signals.

Results

Here we confront predictions of state-of-the-art models of transcription regulation against data from two large-scale observational studies and five deep perturbation assays. The most advanced of these sequence-based models, Enformer, by and large, captures causal determinants of human promoters. However, models fail to capture the causal effects of enhancers on expression, notably in medium to long distances and particularly for highly expressed promoters. More generally, the predicted impact of distal elements on gene expression predictions is small and the ability to correctly integrate long-range information is significantly more limited than the receptive fields of the models suggest. This is likely caused by the escalating class imbalance between actual and candidate regulatory elements as distance increases.

Conclusions

Our results suggest that sequence-based models have advanced to the point that in silico study of promoter regions and promoter variants can provide meaningful insights and we provide practical guidance on how to use them. Moreover, we foresee that it will require significantly more and particularly new kinds of data to train models accurately accounting for distal elements.
Workload and procedures used by European data protection authorities related to personal data protection: a cross-sectional study
Authors: Puljak Livia , Mladinić Anamarija , Koporc Zvonimir
Published: March 2023

Objective

Data protection authorities (DPAs) are independent public authorities supervising the application of the data protection law. There is one DPA in each European Union (EU) Member State. Workload and procedures used by European DPAs were analyzed via a cross-sectional study.

Results

DPAs from 13 countries participated: Austria, Bulgaria, Croatia, Estonia, Finland, Greece, Italy, Latvia, Liechtenstein, Lithuania, Norway, Romania, and Slovakia. Responding to opinion/guidance requests in DPAs was highly heterogeneous. Procedure types used by DPAs varied, from telephone-based advisory service in Norway to a formal legal opinion in Austria. The deadline for responding to the requests varied considerably in DPAs. The number of opinion/guidance requests sent by data controllers and processors, and the number of opinion/guidance requests and complaints sent by data subjects, increased from 2015 to 2018 when the General Data Protection Regulation (GDPR) came into full effect; it decreased in 2019. Few DPAs organized education about data protection for the research community. In conclusion, the procedures and workload of DPAs in the EU were highly variable. It is important to study these aspects further, as they may assist in tailoring future data protection policies and procedures at the EU level.
Induction of antitoxic antibody and preventive effect against porcine edema disease by the pentameric Stx2eB subunit vaccine
Authors: Yoshimura Masaya , Honda Youko , Yonemitsu Emi , Takahashi Ryota , Suenaga Kiyotaka , Waki Takashi
Published: March 2023

Porcine edema disease (ED) is an enterotoxaemia that frequently occurs in 4–12 week-old piglets and results in high mortality. ED is caused by Shiga toxin 2e (Stx2e), produced by host-adapted Shiga toxin-producing Escherichia coli (STEC) strains. We constructed a recombinant protein in which the B subunit of Stx2e (Stx2eB) was linked to Cartilage Oligomeric Matrix Protein (COMP)’s pentameric domain to enhance antigenicity to induce neutralizing antibodies against Stx2e. We evaluated the efficacy of this antigen as a vaccine on the farm where ED had occurred. The suckling piglets were divided into two groups. The pigs in the vaccinated group were intramuscularly immunized with the vaccine containing 30 µg/head of Stx2eB-COMP at 1 and 4 weeks of age. The control pigs were injected with saline instead of the vaccine. The neutralizing antibody titer to Stx2e, mortality, clinical score, and body weight was evaluated up to 11 weeks after the first vaccination. In the vaccinated group, the Stx2e neutralizing antibody was detected 3 weeks after the first vaccination, its titer increased during the following weeks. The antibody was not detected in the control group during the test period. The STEC gene was detected in both groups during the test period, but a typical ED was observed only in control pigs; the mortality and clinical score were significantly lower in the vaccinated group than in the control group. These data indicate that the pentameric B subunit vaccine is effective for preventing ED and offers a promising tool for pig health control.
Rethinking the path from evidence to decision-making
Authors: Rasooly Alon , Ben-Sheleg Eliana , Davidovitch Nadav , Ellen Moriah
Published: March 2023

Evidence-informed decision-making is increasingly recognized as a standard for policymaking in many fields, including public health. However, many challenges exist in identifying the appropriate evidence, disseminating it to different stakeholders, and implementing it in various settings. The Israel Implementation Science and Policy Engagement Centre (IS-PEC) was established at Ben-Gurion University of the Negev to “bridge the gap” between scientific research and policy. As an illustrative case study, IS-PEC is conducting a scoping review on strategies to engage senior citizens in Israel when developing health policy. In May 2022, IS-PEC brought together international experts and Israeli stakeholders to increase knowledge in the field of evidence-informed policy, develop a research agenda, strengthen international collaborations, and create a community for sharing experience, research, and best practices. Panelists presented the importance of communicating clear, accurate bottom-line messages with the media. Also, they highlighted the once-in-a-generation opportunity to promote the uptake of evidence in public health due to the increased public interest in evidence-informed policymaking post-COVID-19 pandemic and the need to build systems and centers to support the systematic use of evidence. Group discussions focused on various aspects of communication, including challenges and strategies when communicating to policymakers, understanding the nuances of communication between scientists, journalists, and the public, and some ethical issues surrounding data visualization and infographics. Panelists participated in a passionate debate regarding whether and how values play a role when conducting, analyzing, and communicating evidence. Takeaway lessons from the workshop included that going forward, Israel must create lasting systems and a sustainable environment for evidence-informed policy. Novel and interdisciplinary academic programs must be developed to train future policymakers in various fields, including public health, public policy, ethics, communication, social marketing, and infographics. Sustainable professional relationships between journalists, scientists, and policymakers must be fostered and strengthened based on mutual respect and a shared commitment to creating, synthesizing, implementing, and communicating high-quality evidence to serve the public and individual wellbeing.
Novel secure data protection scheme using Martino homomorphic encryption
Authors: Rupa Ch. , Greeshmanth  , Shah Mohd Asif
Published: March 2023

Globally, data maintenance and its security are vital tasks due to the rapid development of advanced technologies. Users now utilise Cloud computing technique and security techniques to preserve their data securely from intruders and hackers. Even yet, because of the technology's rapid advancement and inherent insecurity, attackers are conducting assaults on the cloud data. Hence, a homomorphic encryption technique was proposed based on Matrix Transformations with shifts, rotations, and transpositions of Binary converted ASCII values of each character in the plain text. For both encryption and decryption, symmetric cryptography employs the same secret key. The “avalanche effect” is a desirable feature of symmetric encryption in which two distinct keys generate separate cipher texts for the same message. As there are different conditions for the key, it helps to achieve this effect in this technique. The suggested algorithm's cryptanalysis reveals that it is more powerful than the existing encryption methods and resistant to a variety of attacks. So that an attacker cannot easily predict a plaintext through a statistical analysis.
Prevalence and determinants of depression, anxiety, and burnout among Egyptian house officers during the COVID-19 pandemic
Authors: Sayed Asmaa , Ahmed Marwa , El Sayed Inas , Soliman Saeed , Ali Karim , Elsherbiney Saged , Shahib Alaaelrahman , Fares Samar
Published: March 2023

Background

The COVID-19 pandemic is an unprecedented international health crisis, which has invoked massive consequence on healthcare workers’ mental health and wellbeing. This study aimed to detect the prevalence of anxiety, depression, and burnout among house officers amid the COVID-19 pandemic in Egypt to assess the effect of this pandemic on their mental health.

Results

A total of 254 house officers were included in this study, and their responses were analyzed. Anxiety, burnout, and depression were reported among 35%, 32%, and 22% of participants, respectively. Multivariate regression analysis found that higher levels of overall worry were associated with anxiety, but not depression or burnout. Having a good personal protective equipment attitude was a significant predictor of both anxiety and burnout. Participants with depression had a higher likelihood of also having a burnout, but a lower likelihood of having anxiety. Overall worry related to the pandemic, depression, and clinical burnout status were all significantly associated with anxiety.

Conclusions

The study found that anxiety, depression, and burnout are highly prevalent among house officers, who are newly graduated medical professionals. These findings suggest the need for specific programs to address the wellbeing of these individuals during the COVID-19 pandemic.
A systematic review of dissemination and implementation science capacity building programs around the globe
Authors: Viglione Clare , Stadnick Nicole A. , Birenbaum Beth , Fang Olivia , Cakici Julie A. , Aarons Gregory A. , Brookman-Frazee Lauren , Rabin Borsika A.
Published: March 2023

Background

Research centers and programs focused on dissemination and implementation science (DIS) training, mentorship, and capacity building have proliferated in recent years. There has yet to be a comprehensive inventory of DIS capacity building program (CBP) cataloging information about activities, infrastructure, and priorities as well as opportunities for shared resources, collaboration, and growth. The purpose of this systematic review is to provide the first inventory of DIS CBPs and describe their key features and offerings.

Methods

We defined DIS CBPs as organizations or groups with an explicit focus on building practical knowledge and skills to conduct DIS for health promotion. CBPs were included if they had at least one capacity building activity other than educational coursework or training alone. A multi-method strategy was used to identify DIS CBPs. Data about the characteristics of DIS CBPs were abstracted from each program’s website. In addition, a survey instrument was developed and fielded to gather in-depth information about the structure, activities, and resources of each CBP.

Results

In total, 165 DIS CBPs met our inclusion criteria and were included in the final CBP inventory. Of these, 68% are affiliated with a United States (US) institution and 32% are internationally based. There was one CBP identified in a low- and middle-income country (LMIC). Of the US-affiliated CBPs, 55% are embedded within a Clinical and Translational Science Award program. Eighty-seven CBPs (53%) responded to a follow-up survey. Of those who completed a survey, the majority used multiple DIS capacity building activities with the most popular being Training and Education (n=69, 79%) followed by Mentorship (n=58, 67%), provision of DIS Resources and Tools (n=57, 66%), Consultation (n=58, 67%), Professional Networking (n=54, 62%), Technical Assistance (n=46, 52%), and Grant Development Support (n=45, 52%).

Conclusions

To our knowledge, this is the first study to catalog DIS programs and synthesize learnings into a set of priorities and sustainment strategies to support DIS capacity building efforts. There is a need for formal certification, accessible options for learners in LMICs, opportunities for practitioners, and opportunities for mid/later stage researchers. Similarly, harmonized measures of reporting and evaluation would facilitate targeted cross-program comparison and collaboration.
Cumulative advantage is a double-edge sword for cooperation
Authors: Hu Kaipeng , Shi Lei , Tao Yewei , Perc Matjaž
Published: March 2023

The Matthew effect emphasizes the influence of early advantage on shaping long-term development by amplifying it over time, and its implications for public cooperation are yet to be fully understood. In this letter, we propose and study a spatial public goods game driven by cumulative advantage, where players who achieve high payoffs in a given round receive greater allocations in the next. The simulation results show that the Matthew effect leads to an irreversible polarization of individual wealth on the network. Such polarization makes moderate cooperation levels more prevalent, which helps to explain the widespread coexistence of prosocial and antisocial behavior. Meanwhile, heterogeneous networks may restrict the polarization of wealth, but also inhibit the evolution of cooperation, requiring a reconsideration of the commonly held view that heterogeneous networks enhance cooperation.
Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial
Authors: Taylor Peter , Rajendram Rathie , Hanna Stephanie , Wilson Victoria , Pell Julie , Li Chunhei , Cook Anne , Gattamaneni Rao , Plowman Nicholas , Jackson Sue , Hills Robert , French Robert , Uddin Jimmy M , Lee Richard W J , Dayan Colin M
Published: March 2023

Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up.

Methods

Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy.

Results

Data were available at 3 years from 68 of 126 randomized subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a binary clinical composite outcome measure (BCCOM), modified European Group on Graves’ Orbitopathy score, or Ophthalmopathy Index.

Clinical Activity Score (CAS), Ophthalmopathy Index, and Total Eye Score improved over 3 years (P < .001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24 of 64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery [odds ratio (OR) 16.8; 95% CI 2.95, 95.0; P = .001]. Higher baseline levels of CAS, Ophthalmopathy Index, and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery.

Conclusion

In this long-term follow-up from a clinical trial, 3-year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes.
Post-injury born oligodendrocytes incorporate into the glial scar and contribute to the inhibition of axon regeneration
Authors: Xing Jian , Lukomska Agnieszka , Rheaume Bruce A. , Kim Juhwan , Sajid Muhammad S. , Damania Ashiti , Trakhtenberg Ephraim F.
Published: March 2023

Failure of central nervous system projection neurons to spontaneously regenerate long-distance axons underlies irreversibility of white matter pathologies. A barrier to axonal regenerative research is that the axons regenerating in response to experimental treatments stall growth before reaching post-synaptic targets. Here, we test the hypothesis that the interaction of regenerating axons with live oligodendrocytes, which were absent during developmental axon growth, contributes to stalling axonal growth. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistology to investigate whether post-injury born oligodendrocytes incorporate into the glial scar after optic nerve injury. Then, we administered demyelination-inducing cuprizone and stimulated axon regeneration by Pten knockdown (KD) after optic nerve crush. We found that post-injury born oligodendrocyte lineage cells incorporate into the glial scar, where they are susceptible to the demyelination diet, which reduced their presence in the glial scar. We further found that the demyelination diet enhanced Pten KD-stimulated axon regeneration and that localized cuprizone injection promoted axon regeneration. We also present a resource for comparing the gene expression of scRNA-seq-profiled normal and injured optic nerve oligodendrocyte lineage cells.
Kształcenie nauczycieli geografii w Polsce w latach 2000–2022. Przyczyny i skutki kryzysu, propozycje rozwiązań
Authors: Szkurłat Elżbieta , Hibszer Adam , Piotrowska Iwona , Sadoń-Osowiecka Teresa
Published: March 2023

Przedmiotem badań jest kształcenie kandydatów do zawodu nauczyciela geografii w Polsce. Główną przesłanką ich podjęcia były obserwowane zagrożenia jakości edukacji geograficznej w kontekście zmniejszającej się liczby kształconych nauczycieli geografii na uniwersytetach, obserwowanej niskiej jakości przygotowania nauczycieli w formie studiów podyplomowych, organizowanych przez instytucje pozauniwersyteckie, systematycznego zmniejszania liczby etatów dydaktyków geografii oraz likwidacji jednostek zajmujących się prowadzeniem badań i kształceniem przyszłych nauczycieli na uczelniach. Celem badań było nie tylko szczegółowe – ilościowe i jakościowe – zdiagnozowanie wymienionych problemów, ale przede wszystkim rozpoznanie przyczyn i skutków zauważonych tendencji zmian oraz zaproponowanie skutecznych rozwiązań i sposobów naprawy. Do zebrania informacji posłużono się metodą ankietową, wywiadów pogłębionych oraz analizy dokumentów źródłowych. Badaniami objęto 11 ośrodków uniwersyteckich, które w latach 2000–2022 na studiach geograficznych prowadziły przygotowanie kandydatów do pracy w zawodzie nauczyciela. Wyniki pozwalają dostrzec głęboki ilościowy i jakościowy kryzys w kształceniu nauczycieli geografii oraz towarzyszące temu drastyczne zmiany kadry akademickiej przygotowanej do tego kształcenia. W końcowych rekomendacjach autorzy zaproponowali rozwiązania dostrzeżonych problemów.
Postrzeganie edukacji geograficznej i jej społecznej roli w Polsce
Authors: Szkurłat Elżbieta , Adamczewska Maria , Dzięcioł-Kurczoba Barbara
Published: March 2023

Głównym problemem badawczym było rozpoznanie, jak postrzegana jest w polskim społeczeństwie edukacja geograficzna na różnych etapach kształcenia. Nadrzędnym celem tych badań była próba rozpoznania, jaka rola i miejsce przypisywane są edukacji geograficznej w wykształceniu polskiego społeczeństwa, jakie zadania ona spełnia, jak wykorzystywane są walory edukacyjne geografii, jak jest postrzegana i oceniana jakość geograficznego kształcenia w Polsce na etapie szkolnym i akademickim. Ważnym założeniem było zastosowanie metod ilościowych oraz jakościowych. Badania ilościowe zostały przeprowadzone techniką CAWI na grupie 1000 osób, przedstawicieli polskiego społeczeństwa, oraz wśród 102 geografów – pracowników uczelni. Uzupełniono je badaniami jakościowymi techniką zogniskowanego wywiadu grupowego (Focus Group Interview – FGI). Badania wykazały, że geografia postrzegana jest jako przedmiot szkolny interesujący i lubiany. Jednak głównie kojarzona jest z umiejętnościami orientacji w terenie i posługiwaniem się mapą. Wyróżnia się wysoką wybieralnością na egzaminie maturalnym, ale równocześnie małym zainteresowaniem jako kierunek studiów. W ocenie społecznej roli i rangi edukacji geograficznej duże znaczenie mają negatywne opinie i stereotypy kształtowane przez wiele dziesięcioleci: nadal postrzegana jest jako wiedza opisowa, w znacznie mniejszym wymiarze wyjaśniająca i praktyczna. Głęboka specjalizacja w geografii jako nauce ma swoje odzwierciedlenie w programach kształcenia studentów, co przynosi negatywne skutki w strukturze ich wiedzy, znacząco ograniczając pełnienie jej syntetyzującej roli. Nie sprzyja to również szkolnej edukacji geograficznej. Społeczna rola edukacji geograficznej łączy się nierozerwalnie z pozycją geografii jako nauki. Im silniejsza geografia jako nauka, tym większe szanse na istotną rolę edukacyjną geografii szkolnej i odwrotnie. Istnieje wyraźna potrzeba wspólnoty geografów nie tylko na poziomie dyscyplin i subdyscyplin, ale również wspólnej troski o rozwój i wysoką jakość szkolnej i akademickiej edukacji geograficznej.
Partycypacja uczniowska w kształtowaniu przestrzeni miejskiej na przykładzie szkolnych doświadczeń projektowych
Authors: Wites Tomasz
Published: March 2023

Określenie działań możliwych do realizacji w ramach partycypacji uczniowskiej stanowi jedno z wyzwań współczesnej edukacji. Problemem badawczym pracy jest wskazanie działań w przestrzeni miejskiej w ramach partycypacji uczniowskiej, wypracowanych w szkole oraz poza jej murami. Celem opracowania jest określenie znaczenia partycypacji uczniowskiej na przykładzie kształtowania przestrzeni miejskiej poprzez zaangażowanie uczniów w inicjatywy o dużym znaczeniu społecznym, podejmowane w wyniku doświadczeń projektu Zrozumieć znane, dostrzec nieznane. Jak geografia tłumaczy świat? Dodatkowym celem jest podanie przykładów implementacji utylitarnych rozwiązań opracowanych przez młodzież szkolną w ramach partycypacji uczniowskiej, oddziałujących na poziom administracyjny w perspektywie lokalnej i krajowej. W teoretycznej części pracy wykorzystano metodę analizy literatury przedmiotu, a w części empirycznej, prezentującej praktyczne przykłady włączania się szkół w inicjatywy realizujące zasady partycypacji uczniowskiej, zastosowano metody badań terenowych, obserwacji uczestniczącej i prezentacji.
Three-dimensional transvaginal ultrasonography in the evaluation of diminished ovarian reserve and premature ovarian failure
Authors: Chen Qian , Sun Lu , Huang Jian , Huang Fan , Guo Shuang , Chai Yiqing
Published: March 2023

Objective: To explore the applicability of three-dimensional transvaginal ultrasonography (3D-TVS) in the evaluation of diminished ovarian reserve (DOR) and premature ovarian failure (POF).

Methods: One hundred and twenty female patients, who received 3D-TVS in our hospital from January 2020 to March 2022, were included in the study. Based on sex hormone examination, 25 cases were DOR (DOR-group), 32 cases were POF (POF-group) and 63 cases had normal ovarian function (Normal-group). The 3D-TVS quantitative examination results of the three groups of patients were analyzed and compared.

Results: There was no significant difference between the DOR-group and POF-group regarding antral follicles count (AFC), ovarian volume (OV), vascularization index (VI), vascularization flow index (VFI) and flow index (FI) of left and right ovaries (p>0.05). Compared with the Normal-group, the 3D-TVS examination indexes of the DOR-group and POF-group were significantly lower, and the 3D-TVS examination results of the POF-group were significantly lower than those of the DOR-group (p<0.05). Using sex hormone examination as the gold standard, the diagnostic specificity of 3D-TVS for DOR was 80%, and the sensitivity and accuracy were 90% and 88% respectively; The diagnostic specificity of POF was 87.5%, the sensitivity and accuracy were 95.8% and 93.8% respectively.

Conclusion: 3D-TVS can provide scientific guidance for the clinical diagnosis and evaluation of DOR and POF.

doi: https://doi.org/10.12669/pjms.39.3.7372

How to cite this: Chen Q, Sun L, Huang J, Huang F, Guo S, Chai Y. Three-imensional transvaginal ultrasonography in the evaluation of diminished ovarian reserve and premature ovarian failure. Pak J Med Sci. 2023;39(3):747-751. doi: https://doi.org/10.12669/pjms.39.3.7372

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ανατομική μελέτη, χειρουργική προσπέλαση και παραλλαγές του υπερπλάτιου νεύρου στην άρθρωση του ώμου
Authors: Τσικούρης Γεώργιος
Published: March 2023

Το υπερπλάτιο νεύρο είναι ένα μεικτό νεύρο σημαντικότατο για την ωμική ζώνη. Εκφύεται φυσιολογικά από το άνω πρωτεύον στέλεχος του βραχιονίου πλέγματος και δίνει μυικούς κλάδους για τη νεύρωση του υπερακανθίου και του υπακανθίου μυός και αισθητικούς κλάδους κυρίως για την άρθρωση του ώμου. Η ωμοπλατιαία εντομή και η ακανθογληνική εντομή που γεφυρώνονται από τους αντίστοιχους συνδέσμους είναι οι χαρακτηριστικές θέσεις στο οστούν της ωμοπλάτης στις οποίες το υπερπλάτιο νεύρο είναι πιο επιρρεπές σε συμπίεση και τραυματισμό. Το αποτέλεσμα είναι η άλλοτε άλλου βαθμού υπερπλάτια νευροπάθεια. Σε περιπτώσεις υπερπλάτιας νευροπάθειας όπου έχει πλέον αποτύχει η συντηρητική αντιμετώπιση ή δεν ενδείκνυται, η θεραπεία γίνεται με χειρουργική (κλασσική ανοικτή ή αρθροσκοπική) αποσυμπίεση του υπερπλατίου νεύρου στις θέσεις αυτές. Στην παρούσα μελέτη παρασκευάστηκαν 41 μονιμοποιημένοι πτωματικοί ώμοι, προερχόμενοι από τους εθελοντές δωρητές σώματος στο Εργαστήριο Ανατομίας – «Ανατομείο» της Ιατρικής Σχολής ΕΚΠΑ. Μελετήθηκαν τα ανατομικά χαρακτηριστικά του υπερπλατίου νεύρου (έκφυση, πορεία και διανομή των κλάδων) έγιναν μετρήσεις σχετικά με το μήκος του υπερπλατίου νεύρου αλλά και την μορφομετρία της ωμοπλατιαίας και της ακανθογληνικής εντομής και έγινε ιστολογική μελέτη των εγκαρσίων συνδέσμων της ωμοπλάτης και των ακανθογληνικών συνδέσμων με σκοπό την διερεύνηση της σύστασής τους και του βαθμού οστεοποίησής τους. Στους ώμους που παρασκευάστηκαν, όλα τα υπερπλάτια νεύρα εκφύονταν από το άνω πρωτεύον στέλεχος του βραχιονίου πλέγματος σύμφωνα δηλαδή με τα πρότυπα της κείμενης βιβλιογραφίας. Κατόπιν το νεύρο διερχόταν υπό τον εγκάρσιο σύνδεσμο της ωμοπλάτης έδινε 2-3 μυικούς κλάδους στον υπερακάνθιο και μετά διέλαυνε της ακανθογληνικής εντομής προς τον υπακάνθιο βόθρο δίνοντας 4-5 κλάδους για τον ομώνυμο μυ. Οι εγκάρσιοι σύνδεσμοι της ωμοπλάτης ήταν 6/41 (14.63%) πλήρως οστεοποιημένοι, 12/41 (29.27%) μερικώς και 23/41 (56.1%) μη οστεοποιημένοι. Το σχήμα των εγκαρσίων συνδέσμων ήταν ως επί το πλείστον τριγωνικό. Σε 3/41 ώμους που παρασκευάστηκαν (7.32%) βρέθηκε επιπλέον και ένας πρόσθιος κορακο-ωμοπλατιαίος σύνδεσμος. Από τους 9 ακανθογληνικούς συνδέσμους που ταυτοποιήθηκαν οι 5 ήταν μεμβρανώδεις, 3 γραμμικοί και ένας τριγωνικού σχήματος. Επιπροσθέτως βρέθηκε μια αρκετά σπάνια ανατομική παραλλαγή κατά την οποία το υπερπλάτιο νεύρο χορηγούσε ισχνό νευρικό κλάδο πριν την διέλευσή του από την ωμοπλατιαία εντομή. Η βαθιά γνώση της φυσιολογικής έκφυσης, πορείας και διανομής των κλάδων του υπερπλατίου νεύρου όσο και των διαφόρων ανατομικών παραλλαγών αυτού από μεριάς του ορθοπαιδικού χειρουργού είναι υψίστης σημασίας για ασφαλείς και επιτυχημένες προσπελάσεις (είτε πρόσθιες είτε οπίσθιες) του υπερπλατίου νεύρου και για την αποφυγή πρόκλησης ιατρογενούς βλάβης σε κάποιο από τα ευγενή στοιχεία της περιοχής.
Η στοχαστική φαντασία και το επιχειρηματικό υποκείμενο
Authors: Παππάς Ευθύμιος
Published: March 2023

Η στοχαστική φαντασία και η εξέλιξή της ως στοχαστική νοούσα πραγματικότητα: Είναι η νοούσα ενέργεια, εκείνη η οποία εγκλείεται κατά τη στιγμή που συναντώνται το περατό με το άπειρο στοιχείο μέσα στην αλληλοστοχευμένη οντολογία τους.Είναι η δύναμη εκείνη που παρεμβάλλεται και δημιουργείται ακαριαία εκεί που τέμνονται οι δύο πραγματικότητες, οι δύο κατά Πλάτωνα κόσμοι, αυτός του αισθητού και αυτός του κόσμου των ιδεών. Είναι εκεί, όπου τα όντα και τα νοήματα που βρίσκονται έξω αποκτούν ποιότητα κατά τη διαδικασία ένταξης και αγωνιστικής εισδοχής τους στην εσωτερικότητα, εντός μας δηλαδή, και αποκομίζουν νέο σχήμα, νέα μορφή, ανώτερης ποιότητας, που με την σειρά της φωτίζει με άπλετο φως την «V I R T U» την «Α Ρ Ε Τ Η» και μας δίνει τη δυνατότητα να φερθούμε ολωσδιόλου θετικά, γαλήνια και αποφασιστικά Είναι εκείνη η λάμψη, που με την μεγαλειώδη εισδοχή της στο «Είναι» μας, Μ Α Σ επιτρέπει να περάσουμε στο σύμπαν της θετικής απόφασης, διαμέσου του ποταμού της έμπνευσης, ο οποίος εγκλείεται και δημιουργείται με χαρακτηριστικό γνώρισμα την τάση προς ένωση και επαφή με το άλλο «ΟΝ» σε όλες του τις εκφάνσεις Είναι το γαλανό του ουρανού και της θάλασσας, του ποιητή Ελύτη, που αγωνίζεται να ενώσει την ανατολή με τη δύση, ξεχειλίζοντας την ποίησή του με ελληνικότητα και φως, δημιουργώντας τη διαφάνεια του λόγου και της ύπαρξης για να δώσει στους Έλληνες τον «αμφίσημο Νου» τους, που είχε τη δύναμη να λιπάνει με ακτίνες φωτός τη δυτική αντανάκλασή του. Είναι εκεί που ο Αριστοτέλης ανακαλύπτει και προσδιορίζει την έσχατη μορφή της ύλης αποκαλώντας την «πρώτη», ως «εν ενεργεία» πλέον και όχι «εν δυνάμει».
Phytochemical profiling of Piper crocatum and its antifungal mechanism action as Lanosterol 14 alpha demethylase CYP51 inhibitor: a review
Authors: Siswina Tessa , Miranti Rustama Mia , Sumiarsa Dadan , Kurnia Dikdik
Published: March 2023

Mycoses or fungal infections are general health problem that often occurs in healthy and immunocompromised people in the community. The development of resistant strains in Fungi and the incidence of azole antibiotic resistance in the Asia Pacific which reached 83% become a critical problem nowadays. To control fungal infections, substances and extracts isolated from natural resources, especially in the form of plants as the main sources of drug molecules today, are needed. Especially from Piperaceae, which have long been used in India, China, and Korea to treat human ailments in traditional medicine. The purpose of this review is to describe the antifungal mechanism action from Piper crocatum and its phytochemical profiling against lanosterol 14a demethylase CYP51. The methods used to search databases from Google Scholar to find the appropriate databases using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Flow Diagram as a clinical information retrieval method. From 1.150.000 results searched by database, there is 73 final results article to review. The review shows that P. crocatum contains flavonoids, tannins, terpenes, saponins, polyphenols, eugenol, alkaloids, quinones, chavibetol acetate, glycosides, triterpenoids or steroids, hydroxychavikol, phenolics, glucosides, isoprenoids, and non-protein amino acids. Its antifungal mechanisms in fungal cells occur due to ergosterol especially lanosterol 14a demethylase (CYP51) inhibition, which is one of the main target sites for antifungal activity because it functions to maintain the integrity and function of cell membranes in Candida. P. crocatum has an antifungal activity through its phytochemical profiling against fungal by inhibiting the lanosterol 14a demethylase, make damaging cell membranes, fungal growth inhibition, and fungal cell lysis.