bluuebunny/crossref_metadata_2025 huggingface dataset:
Standards for evaluating the quality of undergraduate nursing e-learning programme in low- and middle-income countries: a modified Delphi study
Authors: Mulu Moses Mutua , Nyoni Champion N.
Published: March 2023

Background

The lack of standards for evaluating the quality of undergraduate nursing programmes hampers the evaluation of e-learning programmes in low- and middle-income countries. Fragmented approaches to evaluation coupled with a lack of uniform criteria have been a major deterrent to the growth of e-learning. Adopting standards from high-income countries has contextual challenges in low- and middle-income countries (LMICs). Holistic approaches coupled with uniform standards provide information to stakeholders hence the quality of the programmes is measurable. The e-learning situation in low-and middle-income countries provided an impetus to develop and validate these standards.

Design

A modified Delphi technique.

Review methods

Fourteen experts with experience and expertise in e-learning and regulation of undergraduate nursing from fourteen countries from LMICs participated in three rounds of the modified Delphi process. A pre-described set of standards was shared electronically for independent and blinded ratings. An 80% threshold was set for consensus decisions. The standards were modified based on experts’ comments, and two subsequent rounds were used to refine the standards and criteria.

Results

At the end of round one, the expert consensus was to keep 67, modify 39 and remove three criteria. At the end of the second round, the consensus was to modify 38 and remove one criteria. In the third round, experts agreed that the standards were feasible, usable, and practical in LMICs. A total of six broad standards with 104 criteria were developed.

Conclusion

The Technological bloom permeating all spheres of society, including education is an essential component in the development of e-learning programmes. E-learning in nursing education requires critical evaluation to ensure quality in undergraduate nursing programmes. The intricacies of the Low and middle-income context were taken into consideration in developing the standards to offer sustainable evaluation of the quality of e-learning in LMICs, and local solutions to local problems.
The diversity of Plasmodium falciparum isolates from asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo
Authors: Simpson Shirley V. , Nundu Sabin S. , Arima Hiroaki , Kaneko Osamu , Mita Toshihiro , Culleton Richard , Yamamoto Taro
Published: March 2023

Background

Understanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC).

Methods

A total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3.

Results

Nine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001).

Conclusion

This survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC.
Retraction Note: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p
Authors: Li Jianfa , Huang Chenchen , Zou Yifan , Ye Jing , Yu Jing , Gui Yaoting
Published: March 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-020-01225-2.
Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature
Authors: Li Qiang , Feng Tienan , Zhu Tengteng , Zhang Weituo , Qian Ying , Zhang Huan , Zheng Xiangqian , Li Dapeng , Yun Xinwei , Zhao Jingzhu , Li Yangyang , Yu Herbert , Gao Ming , Qian Biyun
Published: March 2023

Background

Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent.

Methods

We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment.

Results

In addition to the presence ofBRAFmutations andRETfusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched withAFPmutations,IGH@-extfusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor.

Conclusions

Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.
How can corporate taxes contribute to sub-Saharan Africa’s Sustainable Development Goals (SDGs)? A case study of Vodafone
Authors: Hannah Eilish , O’Hare Bernadette , Lopez Marisol , Murray Stuart , Etter-Phoya Rachel , Hall Stephen , Masiya Michael
Published: March 2023

Background

The COVID-19 pandemic and the climate emergency threaten progress in reaching many of the Sustainable Development Goal (SDG) targets by 2030. The under-5 mortality and maternal mortality rates are well below the targets, and if we progress at the current pace, there is a high risk of not meeting the 2030 goals. Furthermore, the initial progress in the decline in child and maternal mortality since 1990 is likely to be eroded. Much of this progress has resulted from increased sanitation, drinking water, education, and health service coverage. The adequate provision of public services is possible if there is sufficient government funding. When governments have more income, they spend more on public services, which increases access to fundamental economic and social rights and, thus, contributes to the SDGs. One of the key drivers of government financing, taxation, constitutes 70% of government revenue in low- and lower-middle-income countries. Corporate income tax constitutes 18.8% of tax revenue in African countries compared to 10% of tax revenue in OECD countries. Therefore, it plays a critical role in SDG progress.

This paper aims to quantify the contribution of one large taxpayer, that publishes their tax payments, (Vodafone Group Plc) on progress towards SDGs in six African countries. We use econometric modelling to estimate the impact of an increase in government revenue equivalent to Vodafone's average tax paid between 2007–2017.

Results

We find that government revenue equivalent to Vodafone’s taxes made a significant contribution to progress in attaining selected SDGs. We found that the revenue equivalent to Vodafone’s taxes allowed 966,188 people to access clean water and 1,371,972 people to access basic sanitation each year. Over the time period studied, 858,054 children spent an extra year in school and 54,275 children under five years and 3,655 mothers survived. In just one of these countries, Tanzania, the revenue equivalent to Vodafone's tax contribution allowed 174,121 people to access clean water and 223,586 to access sanitation each year. Over the time studied 187,023 children spent an additional year at school, 6,569 additional children under five and 625 additional mothers survived.

Conclusions

These findings demonstrate that the reported contributions from a single multinational corporation drive SDG progress. Furthermore, it highlights the importance of transparent taxes and explores the responsibilities of global institutions, governments, investors, and multinational corporations.
Exhaustive drainage versus fixed-time drainage for chronic subdural hematoma after one-burr hole craniostomy (ECHO): study protocol for a multicenter randomized controlled trial
Authors: Wu Liang , Ou Yunwei , Zhu Bingcheng , Guo Xufei , Yu Xiaofan , Xu Long , Li Jinping , Feng Enshan , Li Huaqing , Wang Xiaodong , Chen Huaqun , Sun Zhaosheng , Liu Zaofu , Yang Dawei , Zhang Hongbing , Liu Zhigang , Tang Jie , Zhao Shangfeng , Zhang Guobin , Yao Jiemin , Ma Dongming , Sun Zelin , Zhou Hui , Liu Baiyun , Liu Weiming ,   ECHO Trial Collaborators
Published: March 2023

Background

Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5–33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes.

Methods

This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18–90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months.

Discussion

This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management.

Trial registration

Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.
Radiographic airway abnormalities in untreated early rheumatoid arthritis are associated with peripheral neutrophil activation
Authors: Selldén Tilia , Mårdh Carina Kärrman , Joelsson Martin , Vikgren Jenny , Johnsson Åse , Larsson Gunilla , Glinatsi Daniel , Stubendorff Kajsa , Svensson Karin , Gjertsson Inger , Rudin Anna , Lundell Anna-Carin , Ekwall Anna-Karin Hultgård
Published: March 2023

Background

The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear. Up to 10% of RA patients develop interstitial lung disease which remains a clinical challenge. Understanding early disease mechanisms is of great importance. The objective of this study was to determine whether there is an association between peripheral neutrophil phenotypes and presence of pulmonary abnormalities (PA) on chest high-resolution computed tomography (HRCT) in untreated early RA (ueRA).

Methods

Clinical data and blood were collected, and HRCT performed at diagnosis on 30 consecutive anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) positive ueRA patients. HRCTs were evaluated for the presence of RA-associated parenchymal, airway and/or pleural abnormalities. Expression of phenotype markers on neutrophils were determined by flow cytometry. Levels of calprotectin, ACPA and RF were measured using immunoassays.

Results

The frequency of having any PA was 60%. Airway abnormalities were present in 50%, parenchymal nodules in 43% and interstitial lung abnormalities (ILA) in 10%. Unsupervised multivariate data analysis showed clustering of any PA with neutrophil activation, parameters of inflammation and RF titres. In univariate analysis, the patients with PA displayed significantly increased CD11b and decreased CD62L expression on neutrophils (1.2-fold,p = 0.014; 0.8-fold,p = 0.012) indicating activation and significantly increased RF IgM titre and CRP (5.7-fold,p = 0.0025; 2.3-fold,p = 0.0035) as compared to no PA. Titres of RF, but not ACPA, correlated with expression of the neutrophil activation marker CD11b. A stratified analysis demonstrated that airway involvement was the PA subtype with the strongest association with neutrophil activation.

Conclusion

We report a strong association between radiographic airway findings and activation of circulating neutrophils in early RA supporting a role of innate immunity and the lung at disease onset. Our results also indicate different contributions of RF and ACPA in the RA pathogenesis.
An animal-free preclinical drug screening platform based on human precision-cut kidney slices
Authors: Mutsaers Henricus A. M. , Jensen Michael Schou , Kresse Jean-Claude , Tingskov Stine Julie , Madsen Mia Gebauer , Nørregaard Rikke
Published: March 2023

Objective

Renal fibrosis is one of the main pathophysiological processes underlying the progression of chronic kidney disease and kidney allograft failure. In the past decades, overwhelming efforts have been undertaken to find druggable targets for the treatment of renal fibrosis, mainly using cell- and animal models. However, the latter often do not adequately reflect human pathogenesis, obtained results differ per strain within a given species, and the models are associated with considerable discomfort for the animals. Therefore, the objective of this study is to implement the 3Rs in renal fibrosis research by establishing an animal-free drug screening platform for renal fibrosis based on human precision-cut kidney slices (PCKS) and by limiting the use of reagents that are associated with significant animal welfare concerns.

Results

Using Western blotting and gene expression arrays, we show that transforming growth factor-β (TGF-β) induced fibrosis in human PCKS. In addition, our results demonstrated that butaprost, SC-19220 and tamoxifen – all putative anti-fibrotic compounds – altered TGF-β-induced pro-fibrotic gene expression in human PCKS. Moreover, we observed that all compounds modulated fairly distinct sets of genes, however they all impacted TGF-β/SMAD signaling. In conclusion, this study revealed that it is feasible to use an animal-free approach to test drug efficacy and elucidate mechanisms of action.
The nerve growth factor-delivered signals in prostate cancer and its associated microenvironment: when the dialogue replaces the monologue
Authors: Di Donato Marzia , Giovannelli Pia , Migliaccio Antimo , Castoria Gabriella
Published: March 2023

Prostate cancer (PC) represents the most diagnosed and the second most lethal cancer in men worldwide. Its development and progression occur in concert with alterations in the surrounding tumor microenvironment (TME), made up of stromal cells and extracellular matrix (ECM) that dynamically interact with epithelial PC cells affecting their growth and invasiveness. PC cells, in turn, can functionally sculpt the TME through the secretion of various factors, including neurotrophins. Among them, the nerve growth factor (NGF) that is released by both epithelial PC cells and carcinoma-associated fibroblasts (CAFs) triggers the activation of various intracellular signaling cascades, thereby promoting the acquisition of a metastatic phenotype. After many years of investigation, it is indeed well established that aberrations and/or derangement of NGF signaling are involved not only in neurological disorders, but also in the pathogenesis of human proliferative diseases, including PC. Another key feature of cancer progression is the nerve outgrowth in TME and the concept of nerve dependence related to perineural invasion is currently emerging. NGF released by cancer cells can be a driver of tumor neurogenesis and nerves infiltrated in TME release neurotransmitters, which might stimulate the growth and sustainment of tumor cells.

In this review, we aim to provide a snapshot of NGF action in the interactions between TME, nerves and PC cells. Understanding the molecular basis of this dialogue might expand the arsenal of therapeutic strategies against this widespread disease.
The role of microfinance institutions on women’s entrepreneurship development
Authors: Abebe Abraham , Kegne Meketaw
Published: March 2023

This study investigates the role of microfinance services on women's entrepreneurship development in Assosa town. The study employed both descriptive and explanatory designs and a quantitative research approach. The study targeted 352 women clients of Assosa Woreda Microfinance Institution, and 165 samples were selected using a simple random sampling technique. The data were collected through a questionnaire and analyzed through the statistical package for social science (SPSS) 26 software. The findings from the descriptive mean analysis indicate that the microfinance institution financial and non-financial services offered were found unable to significantly empower disadvantaged and poor women by improving their livelihood and development of their business. The correlation result also indicated a positive and significant association between saving practice, access to credit, skill development training, and the development of women entrepreneurs. Finally, the regression result saving and the credit or loan services of the microfinance institution service have the most decisive influence on women's entrepreneurship development.
The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity
Authors: Dimic-Janjic Sanja , Hoda Mir Alireza , Milenkovic Branislava , Kotur-Stevuljevic Jelena , Stjepanovic Mihailo , Gompelmann Daniela , Jankovic Jelena , Miljkovic Milica , Milin-Lazovic Jelena , Djurdjevic Natasa , Maric Dragana , Milivojevic Ivan , Popevic Spasoje
Published: March 2023

Background

Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations.

Methods

In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed.

Results

COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found.

Conclusions

COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.
Core species and interactions prominent in fish-associated microbiome dynamics
Authors: Yajima Daii , Fujita Hiroaki , Hayashi Ibuki , Shima Genta , Suzuki Kenta , Toju Hirokazu
Published: March 2023

Background

In aquatic ecosystems, the health and performance of fish depend greatly on the dynamics of microbial community structure in the background environment. Nonetheless, finding microbes with profound impacts on fish’s performance out of thousands of candidate species remains a major challenge.

Methods

We examined whether time-series analyses of microbial population dynamics could illuminate core components and structure of fish-associated microbiomes in the background (environmental) water. By targeting eel-aquaculture-tank microbiomes as model systems, we reconstructed the population dynamics of the 9605 bacterial and 303 archaeal species/strains across 128 days.

Results

Due to the remarkable increase/decrease of constituent microbial population densities, the taxonomic compositions of the microbiome changed drastically through time. We then found that some specific microbial taxa showed a positive relationship with eels’ activity levels even after excluding confounding effects of environmental parameters (pH and dissolved oxygen level) on population dynamics. In particular, a vitamin-B12-producing bacteria,Cetobacterium somerae, consistently showed strong positive associations with eels’ activity levels across the replicate time series of the five aquaculture tanks analyzed. Network theoretical and metabolic modeling analyses further suggested that the highlighted bacterium and some other closely-associated bacteria formed “core microbiomes” with potentially positive impacts on eels.

Conclusions

Overall, these results suggest that the integration of microbiology, ecological theory, and network science allows us to explore core species and interactions embedded within complex dynamics of fish-associated microbiomes.
Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration
Authors: Taheri Shiva , Ghazali Hanieh Sadat , Ghazali Zahra Sadat , Bhattacharyya Amitava , Noh Insup
Published: March 2023

Background

Worldwide, many people suffer from knee injuries and articular cartilage damage every year, which causes pain and reduces productivity, life quality, and daily routines. Medication is currently primarily used to relieve symptoms and not to ameliorate cartilage degeneration. As the natural healing capacity of cartilage damage is limited due to a lack of vascularization, common surgical methods are used to repair cartilage tissue, but they cannot prevent massive damage followed by injury.

Main body

Functional tissue engineering has recently attracted attention for the repair of cartilage damage using a combination of cells, scaffolds (constructs), biochemical factors, and biomechanical stimuli. As cyclic biomechanical loading is the key factor in maintaining the chondrocyte phenotype, many studies have evaluated the effect of biomechanical stimulation on chondrogenesis. The characteristics of hydrogels, such as their mechanical properties, water content, and cell encapsulation, make them ideal for tissue-engineered scaffolds. Induced cell signaling (biochemical and biomechanical factors) and encapsulation of cells in hydrogels as a construct are discussed for biomechanical stimulation-based tissue regeneration, and several notable studies on the effect of biomechanical stimulation on encapsulated cells within hydrogels are discussed for cartilage regeneration.

Conclusion

Induction of biochemical and biomechanical signaling on the encapsulated cells in hydrogels are important factors for biomechanical stimulation-based cartilage regeneration.
Wormian bone types: investigating their appearance, correlation to sex, population affinity, and clinical syndromes
Authors: Ogut Eren , Yildirim Fatos Belgin
Published: March 2023

Background

The types of Wormian bones may play a role in population affinity and differential diagnosis of several clinical syndromes. This study investigates the distribution of types in adult skulls, their correlation to sex, population affinity, and several impairments based on the literature. One hundred ten adult Turkish skulls, 80 (72.7%) males and 30 (27.2%) females, were investigated according to type, frequency, location, and sex. Horizontal and vertical diameters and distances from the mastoid process (MP) were measured with a digital caliper. SPSS 25 was used for all statistical analyses.

Results

A total of 58 (52.72%) Wormian bones were identified from 110 skulls, 38 (65.5%) males and 20 (34.5%) females. The types of Wormian bones revealed significant differences between being on the right, left, or center (p = 0.012). The most frequent type was type 6 (n = 14, 24.1%) in males and type 7 (n = 8, 13.8%) in females. The most frequent type was type 7 in the lambdoid suture and type 8 in the parietomastoid suture.

Conclusions

The present study revealed significant differences regarding the asymmetric distribution of Wormian bones and unilateral asymmetrical types in Turkish skulls. Several factors could contribute to this, including underlying clinical syndrome, deficiencies in embryological development, and population affinity.
An overview on the nutritional and bioactive components of green seaweeds
Authors: Xu Jingxiang , Liao Wei , Liu Yuning , Guo Yuling , Jiang Shiyue , Zhao Chao
Published: March 2023

Green seaweed, as the most abundant species of macroseaweeds, is an important marine biological resource. It is a rich source of several amino acids, fatty acids, and dietary fibers, as well as polysaccharides, polyphenols, pigments, and other active substances, which have crucial roles in various biological processes such as antioxidant activity, immunoregulation, and anti-inflammatory response. In recent years, attention to marine resources has accelerated the exploration and utilization of green seaweeds for greater economic value. This paper elaborates on the main nutrients and active substances present in different green seaweeds and provides a review of their biological activities and their applications for high-value utilization.

Graphical abstract
Germline- and Somatic-Inactivating FLCN Variants in Parathyroid Cancer and Atypical Parathyroid Tumors
Authors: Jha Smita , Welch James , Tora Rana , Lack Justin , Warner Andrew , del Rivero Jaydira , Sadowski Samira M , Nilubol Naris , Schmidt Laura S , Linehan W Marston , Weinstein Lee S , Simonds William F , Agarwal Sunita K
Published: March 2023

Context

Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease.

Objective

To investigate for novel genes causing parathyroid cancer.

Methods

We analyzed the germline DNA of 17 patients with “sporadic” PC and 3 with atypical parathyroid tumors (APTs) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including 2 patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants.

Results

We identified germline FLCN variants in 3 unrelated patients with PC. The 2 frameshift variants have been described in patients with Birt-Hogg-Dubé (BHD) syndrome, while the pathogenicity of the missense variant c.124G > C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential effect on posttranslational modification. All 3 patients with germline FLCN variants were noted to have renal cysts and 2 had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (1 APT) of 16 patients with PC/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing; however, loss of heterozygosity at the locus was demonstrated in 2 of 3 patients with the identified germline FLCN variant.

Conclusion

The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.
Specialist Perspectives on Delivering High-Quality Telemedicine for Diabetes: A Mixed Methods Survey Study
Authors: Zupa Margaret F , Alexopoulos Anastasia-Stefania , Esteve Lucy , Rosland Ann-Marie
Published: March 2023

Background

Recent recommendations guiding appropriate use of telemedicine for endocrinology care have largely relied on expert opinion due to limited evidence on factors that increase quality of telemedicine care. In this study, we assessed the perspectives of front-line specialists on factors and strategies perceived to increase quality of diabetes care delivered via telemedicine after more than 2 years of widespread use.

Methods

Adult diabetes specialists in 2 academic health systems who recently used video-based telemedicine to provide diabetes care were invited to participate in an online survey study between March and April 2022. Likert-style questions, followed by related open-ended questions, assessed perspectives on availability of key resources, factors affecting quality, and anticipated benefits from telemedicine for diabetes.

Results

Response rate was 52% (56/111). More than half (54%) of participants reported better overall quality of diabetes care with face-to-face care vs telemedicine. Participants reported clinical data supporting high-quality care, such as home blood glucose readings and vital signs, were often not available with telemedicine. Patient factors, including comorbidities and communication barriers, reduced anticipated benefit from telemedicine, while geographic and mobility barriers increased expected benefit. Providers described multiple health care setting resources that could promote high-quality telemedicine diabetes care, including greater support for sharing patient-generated health data and coordinating multidisciplinary care.

Conclusions

After 2 years of sustained use, diabetes specialists identified telemedicine as an important way to enhance access to care. However, specialists identified additional supports needed to increase appropriate use and delivery of high-quality telemedicine care for patients with complex clinical needs.
Neuraxial Use Among Total Knee and Hip Arthroplasty Patients With Multiple Sclerosis or Myasthenia Gravis
Authors: Illescas Alex , Zhong Haoyan , Liu Jiabin , Cozowicz Crispiana , Poeran Jashvant , Memtsoudis Stavros G.
Published: March 2023

BACKGROUND:

Surgical patients with preexisting neurological diseases create greater challenges to perioperative management, and choice of anesthetic is often complicated. We investigated neuraxial anesthesia use in total knee and hip arthroplasty (TKA/THA) recipients with multiple sclerosis or myasthenia gravis compared to the general population.

METHODS:

We retrospectively analyzed patients undergoing a TKA/THA with a diagnosis of multiple sclerosis or myasthenia gravis (Premier Health Database, 2006–2019). The primary outcome was neuraxial anesthesia use in multiple sclerosis or myasthenia gravis patients compared to the general population. Secondary outcomes were length of stay, intensive care unit admission, and mechanical ventilation. We measured the association between the aforementioned subgroups and neuraxial anesthesia use. Subsequently, subgroup-specific associations between neuraxial anesthesia and secondary outcomes were measured. We report odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS:

Among 2,184,193 TKA/THAs, 7559 and 3176 had a multiple sclerosis or myasthenia gravis diagnosis, respectively. Compared to the general population, neuraxial anesthesia use was lower in multiple sclerosis patients (OR, 0.61; CI, 0.57–0.65; P < .0001) and no different in myasthenia gravis patients (OR, 1.05; CI, 0.96–1.14; P = .304). Multiple sclerosis patients administered neuraxial anesthesia (compared to those without neuraxial anesthesia) had lower odds of prolonged length of stay (OR, 0.63; CI, 0.53–0.76; P < .0001) mirroring neuraxial anesthesia benefits seen in the general population.

CONCLUSIONS:

Neuraxial anesthesia use was lower in surgical patients with multiple sclerosis compared to the general population but no different in those with myasthenia gravis. Neuraxial use was associated with lower odds of prolonged length of stay.
Hoboes, Wheat, and Climate Precarity, 1870–1922
Authors: Suits Robert
Published: March 2023

This article explores the role of early migrant workers (“harvest hands” or “hoboes”) in the American wheat industry. It argues that the constant threat of drought and other climatic disasters created a state of climate precarity for workers. In the variable climate of the Great Plains, these disasters could not be forecast, and employers instead shunted climatic risk onto impoverished migrants, whose contracts were ad hoc, informal, and could be made, completed, or broken in a matter of hours. It compiles data from over ten thousand newspapers in the Great Plains to show not only how harvest hand employment varied with the climate but also how climatic instability often only became apparent as harvest hands arrived in the state. This made it virtually impossible for employers to plan ahead for labor, as the demand for harvest hands could vary dramatically even from year to year. Though government and union action pointed the way to possible alternative systems, they never emerged. Ultimately, the hobo-wheat complex was an emergent property of climate and industrial capitalism, unplanned by any group or authority, made by the choices of each.
Natural Partners
Authors: Frens-String Joshua
Published: March 2023

This article examines how Chilean nitrate fertilizer producers and their international marketing agents persuaded farmers in the US South to use nitrogen-rich mineral fertilizers mined from the Atacama Desert, even as cheaper synthetic fertilizers flooded agricultural markets in the early decades of the twentieth century. At the same time, it explores how agricultural experts working in the United States on behalf of Chile's nitrate industry (and increasingly the Chilean government itself) articulated not just connections between nitrogen and soil vitality but also underscored the importance of other mineral “impurities” to healthy plant development. Working in the US Cotton Belt in particular, many of these agents promoted a vision of pan-American ecological and economic interdependence, and through their racialized depictions of agricultural knowledge, they sought to convince US farmers of the unique “all-natural” attributes of Chilean nitrates. In reconstructing this history, the article reveals the far-reaching impact that Chilean fertilizers had on the modernization of US agriculture and advocates for a transnational approach to understanding that process in the early twentieth century. It also traces how the exchange of agricultural commodities and knowledge between Chile and the United States contributed to the emergence of intensive agriculture and what observers would later call the “green revolution.”
A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans
Authors: Podraza-Farhanieh Agnieszka , Raj Dorota , Kao Gautam , Naredi Peter
Published: March 2023

Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals.
Aversive memory conditioning induces fluoxetine-dependent anxiety-like states in the crabNeohelice granulata
Authors: Maza Francisco Javier , Urbano Francisco José , Delorenzi Alejandro
Published: March 2023

The interactions between memory processes and emotions are complex. Our previous investigations in the crab Neohelice led to an adaptation of the affective extension of sometimes opponent processes (AESOP) model. The model proposes that emotions generate separate emotive memory traces, and that the unfolding of emotional responses is a crucial component of the behavioral expression of reactivated memories. Here, we show that an aversive conditioning, that used changes in an innate escape response to an aversive visual stimulus, induced an emotional behavior that endured beyond the stimuli: the aversive memory training built an anxiety-like state evaluated in a dark/light plus-maze. We found that, after the training session, crabs displayed aversion to maze light areas, and an increased time immobilized in the dark zones of the maze, an anxiety-like behavior induced by stressors or physiological conditions in other crustaceans. The training-dependent anxiety-like behavior was blocked by pretraining administration of fluoxetine, suggesting an underlying serotonin-dependent phenomenon. We hypothesize that this training-induced anxiety-like state generates a separate emotive memory trace that is reinstated and crucial for the modulation of memory expression once the memory is reactivated.
Assessing the suitability of CMMN language for knowledge-intensive processes
Authors: Ρούτης Ιωάννης
Published: March 2023

Καθώς οι οργανισμοί μετατοπίζονται από την παραδοσιακή διαχείριση διαδικασιών σε πιο ευέλικτες εναλλακτικές λύσεις, έχει εμφανιστεί η έννοια των διαδικασιών Knowledge-intensive processes (KiPs). Όσον αφορά τη μοντελοποίηση αυτών των διαδικασιών, οι επί του παρόντος διαθέσιμες μέθοδοι και πρακτικές μοντελοποίησης επιχειρηματικών διαδικασιών δεν παρέχουν τα απαραίτητα χαρακτηριστικά. Για να καλύψει αυτό το κενό, το Object Management Group (OMG) κυκλοφόρησε την Case Management Model and Notation (CMMN) ως κατάλληλη γλώσσα για τη μοντελοποίηση μη δομημένων, ευέλικτων ανθρωποκεντρικών διαδικασιών. Ωστόσο, παρά το γεγονός ότι το CMMN έχει αποκτήσει σημαντικό ερευνητικό ενδιαφέρον μετά την κυκλοφορία του, η δυνατότητα εφαρμογής του στα KiPs εξακολουθεί να είναι ανεξερεύνητη, με τις υπάρχουσες ερευνητικές εργασίες να περιορίζονται σε θεωρητικά ευρήματα.Ο στόχος αυτής της έρευνας είναι να αξιολογήσει την καταλληλότητα της CMMN για KiPs από την οπτική γωνία των μοντελιστών, λαμβάνοντας παράλληλα υπόψη τη φύση των KiPs. Η έρευνα αντλεί έμπνευση από την υπάρχουσα βιβλιογραφία σχετικά με τα χαρακτηριστικά μοντελοποίησης των KiPs και τις απαιτήσεις που επιβάλλουν, καθώς και από τα τρέχοντα θεωρητικά ευρήματα σχετικά με την εφαρμογή του CMMN στα KiPs. Λαμβάνεται μια εμπειρική προσέγγιση για τον προσδιορισμό του τρόπου με τον οποίο η νέα γλώσσα CMMN θα μπορούσε να υποστηρίξει τα KiPs, μέσω μιας εμπειρικής μελέτης στην οποία συμμετείχαν μοντελιστές που χρησιμοποίησαν την CMMN για να μοντελοποιήσουν τα KiPs και μοιράστηκαν τις αντιλήψεις τους. Η αξιολόγηση της CMMN πραγματοποιείται σε τρία στάδια, το καθένα αντιπροσωπεύει έναν ξεχωριστό ερευνητικό στόχο, ο οποίος επιτεύχθηκε μέσω μιας ξεχωριστής εμπειρικής μελέτης αξιολόγησης. Αυτοί οι στόχοι ήταν α) η αξιολόγηση των δυνατοτήτων σχεδίασης και εκτέλεσης της CMMN, β) η αξιολόγηση της χρηστικότητας και της δυνατότητας υιοθέτησης της CMMN και γ) η αξιολόγηση της καταλληλότητας της CMMN για συγκεκριμένα χαρακτηριστικά των KiPs. Οι παράγοντες αξιολόγησης καταλληλότητας εισάγονται με βάση την υπάρχουσα βιβλιογραφία, ενώ διαφορετικοί παράγοντες διερευνώνται σε κάθε μελέτη με βάση τον ερευνητικό στόχο που επιδιώκεται.Τα αποτελέσματα των τριών μελετών εμπειρικής αξιολόγησης αποκάλυψαν ότι οι δυνατότητες σχεδίασης και εκτέλεσης της CMMN επιτρέπουν την υποστήριξη διαφορετικών στυλ μοντελοποίησης, παρέχοντας στους μοντελιστές ευελιξία στο επίπεδο αφαίρεσης που χρησιμοποιείται για την απεικόνιση των KiPs. Ωστόσο, οι μηχανές εκτέλεσης της CMMN δεν υποστηρίζουν επαρκώς τη σημασιολογία των πιο συχνά χρησιμοποιούμενων στοιχείων. Όσον αφορά τη χρηστικότητα και τη δυνατότητα υιοθέτησης της γλώσσας CMMN, οι μοντελιστές την αντιλαμβάνονται ως χρήσιμη γλώσσα και είναι θετικά προσκείμενοι στο να την υιοθετήσουν για τη μοντελοποίηση KiPs. Τα Sentries και τα Discretionary items προσδιορίζονται ως τα πιο χρήσιμα στοιχεία της CMMN, συμβάλλοντας στο να υποστηρίζει πλήρως τα Knowledge-driven και Unpredictable χαρακτηριστικά των KiPs.
Μελέτη νεφρού, πνεύμονα και λεπτού εντέρου σε μοντέλο ισχαιμίας επαναιμάτωσης ήπατος στον επίμυ μετά από χορήγηση σιλιμπινίνης
Authors: Κυριακόπουλος Γεώργιος
Published: March 2023

Σκοπός: Η ηπατική βλάβη ισχαιμίας/επαναιμάτωσης (I/R) είναι ένας τύπος ιστικής βλάβης που προκαλείται από μια συστηματική φλεγμονώδη αντίδραση στην αποκατάσταση της παροχής οξυγόνου μετά από παροδική διακοπή της παροχής αίματος στο ήπαρ. Σκοπός της παρούσας μελέτης είναι η διερεύνηση της δυνητικής νεφροπροστατευτικής και πνευμονοπροστατευτικής δράσης της σιλιμπινίνης (Si) μετά από ηπατική βλάβη ισχαιμίας-επαναιμάτωσης (I/R), βάσει της μέτρησης προφλεγμονωδών παραγόντων. Υλικό-Μέθοδος: Συνολικά 63 επίμυες κατανεμήθηκαν τυχαία σε τρεις ομάδες, με τις ακόλουθες παρεμβάσεις: Μία εικονική ομάδα (n=7 επίμυες) υποβλήθηκε μόνο σε άνοιγμα και κλείσιμο της κοιλιάς. Μία ομάδα ελέγχου (n=28 επίμυες) υποβλήθηκε σε ηπατική ισχαιμία 45 λεπτών, ακολουθούμενη από επαναιμάτωση. Μία ομάδα σιλιμπλίνης (n=28), που υποβλήθηκε σε 45λεπτη ηπατική ισχαιμία ακολουθούμενη από ενδοφλέβια χορήγηση λυοφιλοποιημένου SLB-HP-β-CD πριν από την επαναιμάτωση. Οι ομάδες ελέγχου και σιλιμπινίνης υποδιαιρέθηκαν περαιτέρω σε ομάδες χρονικών σημείων, ανάλογα με τη διάρκεια της επαναιμάτωσης (C60, C120, C180, C240 και Si60, Si120, Si180, Si240 για την ομάδα ελέγχου και τη σιλιμπινίνη, μετά από 60, 120, 180 και 240 λεπτά, αντίστοιχα). Η έκφραση των TNF-α, IL-6 και MCP-1 προσδιορίστηκε ανοσοϊστοχημικά και με qrT-PCR στα ανωτέρω χρονικά σημεία.Αποτελέσματα: Η έκφραση του TNF-α στους νεφρούς ήταν σημαντικά χαμηλότερη στα 180 και 240 λεπτά (p<0,05), σε σύγκριση με την ομάδα ελέγχου.. Η σύγκριση μεταξύ της ομάδας ελέγχου και της ομάδας σιλιμπινίνης στο ίδιο χρονικό σημείο, έδειξε πολύ ισχυρές ενδείξεις διαφοράς στα 240 λεπτά, με τα επίπεδα της IL-6 να μετατοπίζονται προς χαμηλότερες τιμές στην ομάδα σιλιμπινίνης. Στους πνεύμονες, η έκφραση της IL-6 ήταν σημαντικά υψηλότερη σε όλα τα χρονικά σημεία σε σύγκριση με την εικονική ομάδα. Τέλος, διαπιστώσαμε υψηλή έκφραση του MCP-1 μετά από 120 λεπτά. Είναι ενδιαφέρον ότι, όταν συγκρίναμε την ομάδα σιλιμπινίνης με την ομάδα ελέγχου στο ίδιο χρονικό σημείο, δεν υπήρχαν ενδείξεις στατιστικά σημαντικής διαφοράς στα 120 και 180 λεπτά, αλλά υπήρχαν πολύ ισχυρές ενδείξεις μετατόπισης προς χαμηλότερες τιμές στα 240 λεπτά.Συμπέρασμα: Συμπεραίνουμε ότι η ηπατική βλάβη ισχαιμίας επαναιμάτωσης αυξάνει τους προφλεγμονώδεις μεσολαβητές, δηλαδή τον TNF-α, τον Il-6 και τον MCP-1 τόσο στο νεφρό όσο και στον πνεύμονα, ενώ η σιλιμπινίνη έχει χρονοεξαρτώμενη προστατευτική δράση και στους δύο παραπάνω απομακρυσμένους ιστούς.
Moringa oleifera fruit extract as a potential antioxidant against liver injury by 2-Nitropropane induction in obese male mice model: pre-clinical study
Authors: Thadeus Maria Selvester , Susantiningsih Tiwuk , Muktamiroh Hikmah , Fauziah Cut , Citrawati Mila , Irmarahayu Agneta , Wahyuningsih Sri , Harjono Hadiwiardjo Yanti , Yusmaini Hany , Bahar Meiskha , Zulfa Fajriati , Agustini Diana , Chairani Aulia
Published: March 2023

Background: Moringa oleifera fruit extract contains beneficial chemical compounds. This study was conducted to observed the power of antioxidant against liver injury by 2-Nitropropane induction in an obese male mice model.

Methods: This research was in vivo laboratory experimental study with a post-test control design group only. The population was obese male mice models, Swiss strain, aged 6–8 weeks, weighing between 60–80 gr. The research sample was determined by Federer's formula for a complete randomized design experimental test, group N (control), O1 (induced by 2-Nitropropane intraperitoneal (i.p) once), O2 (induced by 2-Nitropropane i.p twice), P1 (induced by 2-Nitropropane i.p. once and gavage with M. oleifera fruit extract 500mg/kg bodyweight (BW) once a day), P2 (induced by 2-Nitropropane i.p. twice and gavage of M. oleifera fruit extract 500mg/kg BW once a day), and P3 (induced by 2-Nitropropane i.p. twice and gavage of vitamin C 500mg/kg BW once a day). Antioxidant potential parameters were measured by levels of malondialdehide (MDA), glutation (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), catalase activity, manganese superoxide dismutase (MnSOD), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT). This research was held at the Biochemistry laboratory of Medicine Faculty, UPN Veteran Jakarta in May–September 2020. Analysis was carried out using SPSS version 20.0. The parameters were tested using ANOVA.

Results: MDA levels decreased, GSH increased, 8-OHdG decreased, catalase activity increased, MnSOD activity increased and SGOT, SGPT levels decreased. M. oleifera fruit extract was statistically proven to be a candidate for potential antioxidant against liver injury of 2-Nitropropane induction in obese male mice model. 

Conclusions: M. oleifera fruit extract was statistically evident as an antioxidant substance that reduces oxidative stress in acute liver injury caused by 2-Nitropropane induction.