bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of a training intervention on nursing care for people with dementia in long-term care: A quasi-experimental study
Authors: Piirainen Paula , Pesonen Hanna-Mari , Siira Heidi , Elo Satu
Published: July 2022

Various dementia training interventions have been developed for nursing staff, but there is inconclusive evidence on their effectiveness and which elements are key to positive outcomes. The aim of this study was to evaluate how nurses assess the prevalence of challenging behavior of people with dementia, nursing staff members’ responses to challenging behavior, and nurses’ competence, before the training and three and 12 months after the training. The main content of the training intervention was advancing person-centered care and its development. Data were collected through a survey of nursing staff ( n = 127) at two Finnish nursing homes across three distinct time points. The TREND statement was used to enhance the quality and transparency of the research. The prevalence of challenging behavior in the experimental group significantly decreased one year after training, while no change was observed in the control group. No change in nursing staff members’ responses to challenging behavior was observed in either group over the study period. Nurses in the experimental group demonstrated significant improvements in self-assessed competence both three months and one year after the training intervention. Hence, regular nursing staff training can decrease the prevalence of challenging behavior among older people with dementia and enhance nurses’ competence in nursing. The support of supervisors plays a significant role in these changes.
Sinus rhythm restoration and improved outcomes in patients with acute ischemic stroke and in-hospital paroxysmal atrial fibrillation
Authors: Sagris Dimitrios , Korompoki Eleni , Ntaios George , Tzeis Stylianos , Manios Efstathios , Kanakakis John , Milionis Haralampos , Papanagiotou Panagiotis , Andrikopoulos George , Lip Gregory YH , Vemmos Konstantinos
Published: July 2022

Aims:

It is unclear whether early cardiac rhythm control is beneficial in patients with acute ischemic stroke and paroxysmal atrial fibrillation (PAF). We sought to investigate whether PAF self-termination and in-hospital sinus rhythm (SR) restoration is associated with improved outcome in ischemic stroke patients with PAF, compared to those with sustained atrial fibrillation (AF).

Methods:

Consecutive patients with first-ever acute stroke and confirmed PAF during hospitalization were followed for up to 10 years after the index stroke or until death. We investigated the association of in-hospital self-terminated PAF and PAF conversion to SR compared to sustained AF with 10-year all-cause mortality, stroke recurrence, and major adverse cardiovascular events (MACE). Cox regression analysis was performed to identify independent predictors of each outcome.

Results:

Among 297 ischemic stroke patients with in-hospital PAF detection, PAF was self-terminated in 87 (29.3%) patients, while 143 (48.1%) patients received antiarrhythmic medication in order to achieve PAF conversion to SR. During a median (Interquartile range, IQR) period of 28 (4–68) months, among patients with self-terminated PAF there were 13.5 deaths, 3.6 stroke recurrences, and 5.3 MACE per 100 patient-year while in patients who underwent medical PAF conversion there were 11.7 deaths, 4.6 stroke recurrences, and 5.8 MACE per 100 patient-year. Patients with sustained AF experienced 23.8 deaths, 8.7 stroke recurrences, and 13.9 MACE per 100 patient-years. In multivariable analysis, compared to patients with sustained AF, PAF self-termination was associated with significantly lower 10 years-risk of death (adjusted hazards ratio (adjHR): HR: 0.63, 95% Confidence interval: 0.40–0.96), stroke recurrence (adjHR: HR: 0.41, 95% CI: 0.19–0.91), and MACE (adjHR: 0.43, 95% CI: 0.23–0.81), while PAF medical conversion to SR was associated with lower 10 years-risk of death (adjHR: 0.65, 95% CI: 0.44–0.97) and MACE (adjHR: 0.56, 95% CI: 0.33–0.95).

Discussion:

This study showed that in-hospital PAF self-termination was associated with lower risk of 10-year mortality, stroke recurrence, and MACE, potentially attributed to the lower burden of AF, whereas in-hospital PAF conversion to SR was associated with lower risk of 10-year mortality and MACE.

Conclusion:

Early restoration of sinus rhythm is associated with improved survival and MACE in patients with acute ischemic stroke and PAF.
Neighborhood disadvantage, health status, and health care utilization after blood or marrow transplant: BMTSS report
Authors: Wolfson Julie A. , Bhatia Smita , Hageman Lindsey , Ross E. S. , Balas Nora , Bosworth Alysia , Te Hok Sreng , Francisco Liton , Funk Erin , Hicks Jessica , Landier Wendy , Wu Jessica , Siler Arianna , Lim Shawn , Wong F. Lennie , Armenian Saro H. , Arora Mukta , Aswani Monica S.
Published: July 2022

Living in a disadvantaged neighborhood is associated with poor health outcomes. Blood or Marrow Transplant (BMT) survivors remain at risk of chronic health conditions requiring anticipatory management. We hypothesized that among BMT survivors, neighborhood disadvantage was associated with poor self-reported routine health care utilization and health. We leveraged data from BMTSS – a retrospective cohort study examining long-term outcomes among individuals surviving ≥2 y following BMT at three institutions between 1974 and 2014. Participants in this analysis completed the BMTSS survey (sociodemographics; chronic health conditions; time since routine check-up; self-reported health). The Area Deprivation Index (ADI) represented neighborhood disadvantage; this composite indicator of 17 census measures is a percentile rank (0 = least deprived to 100 = most deprived). Multivariable ordered logit regression adjusted for clinical factors and individual-level sociodemographics, modeling associations between ADI, time since routine check-up, and self-reported health. Among 2,857 survivors, median ADI was 24 (interquartile range: 10-46). Adjusting for self-reported individual-level socioeconomic indicators and chronic health conditions, patients in more disadvantaged neighborhoods had higher odds of reporting longer intervals since routine check-up (ORADI_continuous = 1.007, P < .001) and poorer health status (controlling for time since check-up; ORADI_continuous = 1.005, P = .003). Compared with patients living in the least disadvantaged neighborhood (ADI = 1), patients in the most disadvantaged neighborhood (ADI = 100), had twice the odds (ORADI = 1.007^99 = 2.06) of reporting no routine visits and 1.65-times the odds of reporting poor health (ORADI = 1.005^99 = 1.65). In BMT survivors, access to health care and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors.
NK cells CD56bright and CD56dim subset cytokine loss and exhaustion is associated with impaired survival in myeloma
Authors: Seymour Frances , Cavenagh Jamie D. , Mathews Janet , Gribben John G.
Published: July 2022

Natural killer (NK) cells are the key cells of the innate immune system that share many characteristics with T lymphocytes; their activation, however, is based on the integration of a range of activatory and inhibitory signals via receptors recognizing recurrent pathogen-associated molecular patterns. Two important populations of NK cells with differing functions are recognized: CD56bright and CD56dim. NK cells have the potential to recognize and kill malignant plasma cells, which offers therapeutic opportunities. We used mass cytometry to examine the phenotype and function of NK cell subsets from patients with newly diagnosed multiple myeloma (NDMM). We show that NK cells in NDMM are shifted toward a CD56bright but dysfunctional cytotoxic phenotype, which exhibits selective loss of cytokine production. The CD56dim subset has features of exhaustion with impaired proliferation, upregulation of programmed cell death protein 1, and loss of T-cell immunoglobulin and mucin domain 3 expression. Poor expression of NK cell activation markers is seen and is associated with inferior long-term survival. These results suggest that NK cell exhaustion is already present by the time of myeloma diagnosis and likely contributes to the loss of immunologic control of malignant plasma cells. Restoring NK cell function via immune-directed therapies offers a route to restoring immunologic control in multiple myeloma.
Comparative genomics of the plant-growth promoting bacterium Sphingobium sp. strain AEW4 isolated from the rhizosphere of the beachgrass Ammophila breviligulata
Authors: Boss Brianna L. , Wanees Abanoub E. , Zaslow Shari J. , Normile Tyler G. , Izquierdo Javier A.
Published: July 2022

Background

The genus Sphingobium within the class Alpha-proteobacteria contains a small number of plant-growth promoting rhizobacteria (PGPR), although it is mostly comprised of organisms that play an important role in biodegradation and bioremediation in sediments and sandy soils. A Sphingobium sp. isolate was obtained from the rhizosphere of the beachgrass Ammophila breviligulata with a variety of plant growth-promoting properties and designated as Sphingobium sp. strain AEW4.

Results

Analysis of the 16S rRNA gene as well as full genome nucleotide and amino acid identities revealed that this isolate is most similar to Sphingobium xenophagum and Sphingobium hydrophobicum. Comparative genomics analyses indicate that the genome of strain AEW4 contains unique features that explain its relationship with a plant host as a PGPR, including pathways involved in monosaccharide utilization, fermentation pathways, iron sequestration, and resistance to osmotic stress. Many of these unique features are not broadly distributed across the genus. In addition, pathways involved in the metabolism of salicylate and catechol, phenyl acetate degradation, and DNA repair were also identified in this organism but not in most closely related organisms.

Conclusion

The genome of Sphingobium sp. strain AEW4 contains a number of distinctive features that are crucial to explain its role as a plant-growth promoting rhizobacterium, and comparative genomics analyses support its classification as a relevant Sphingobium strain involved in plant growth promotion of beachgrass and other plants.
Plastome comparison and phylogenomics of Fagopyrum (Polygonaceae): insights into sequence differences between Fagopyrum and its related taxa
Authors: Li Qiu-jie , Liu Yu , Wang An-hu , Chen Qing-fu , Wang Jian-mei , Peng Lu , Yang Yi
Published: July 2022

Background

Fagopyrum (Polygonaceae) is a small plant lineage comprised of more than fifteen economically and medicinally important species. However, the phylogenetic relationships of the genus are not well explored, and the characteristics of Fagopyrum chloroplast genomes (plastomes) remain poorly understood so far. It restricts the comprehension of species diversity in Fagopyrum. Therefore, a comparative plastome analysis and comprehensive phylogenomic analyses are required to reveal the taxonomic relationship among species of Fagopyrum.

Results

In the current study, 12 plastomes were sequenced and assembled from eight species and two varieties of Fagopyrum. In the comparative analysis and phylogenetic analysis, eight previously published plastomes of Fagopyrum were also included. A total of 49 plastomes of other genera in Polygonaceae were retrieved from GenBank and used for comparative analysis with Fagopyrum. The variation of the Fagopyrum plastomes is mainly reflected in the size and boundaries of inverted repeat/single copy (IR/SC) regions. Fagopyrum is a relatively basal taxon in the phylogenomic framework of Polygonaceae comprising a relatively smaller plastome size (158,768–159,985 bp) than another genus of Polygonaceae (158,851–170,232 bp). A few genera of Polygonaceae have nested distribution of the IR/SC boundary variations. Although most species of Fagopyrum show the same IRb/SC boundary with species of Polygonaceae, only a few species show different IRa/SC boundaries. The phylogenomic analyses of Fagopyrum supported the cymosum and urophyllum groups and resolved the systematic position of subclades within the urophyllum group. Moreover, the repeat sequence types and numbers were found different between groups of Fagopyrum. The plastome sequence identity showed significant differences between intra-group and inter-group.

Conclusions

The deletions of intergenic regions cause a short length of Fagopyrum plastomes, which may be the main reason for plastome size diversity in Polygonaceae species. The phylogenomic reconstruction combined with the characteristics comparison of plastomes supports grouping within Fagopyrum. The outcome of these genome resources may facilitate the taxonomy, germplasm resources identification as well as plant breeding of Fagopyrum.
The Sentiworld project: global mapping of sentinel surveillance networks in general practice
Authors: Meci Andrew , Du Breuil Florence , Vilcu Ana , Pitel Thibaud , Guerrisi Caroline , Robard Quentin , Turbelin Clément , Hanslik Thomas , Rossignol Louise , Souty Cécile , Blanchon Thierry
Published: July 2022

Background

Sentinel networks composed of general practitioners (GPs) represent a powerful tool for epidemiologic surveillance and ad-hoc studies. Globalization necesitates greater international cooperation among sentinel networks. The aim of this study was to inventory GP sentinel networks involved in epidemiological surveillance on a global scale.

Methods

GP sentinel surveillance networks were inventoried globally between July 2016 and December 2019. Each identified network was required to fill out an electronic descriptive survey for inclusion.

Results

A total of 148 networks were identified as potential surveillance networks in general practice and were contacted. Among them, 48 were included in the study. Geographically, 33 networks (68.8%) were located in Europe and 38 (79.2%) had national coverage. The number of GPs registered in these networks represented between 0.1 and 100% of the total number of GPs in the network’s country or region, with a median of 2.5%. All networks were involved in continuous epidemiologic surveillance and 47 (97.9%) monitored influenza-like illness. Data collection methods were paper-based forms (n = 26, 55.3%), electronic forms on a dedicated website (n = 18, 38.3%), electronic forms on a dedicated software program (n = 14, 29.8%), and direct extraction from electronic medical records (n = 14, 29.8%). Along with this study, a website has been created to share all data collected.

Conclusions

This study represents the first global geographic mapping of GP sentinel surveillance networks. By sharing this information, collaboration between networks will be easier, which can strengthen the quality of international epidemiologic surveillance. In the face of crises like that of COVID-19, this is more imperative than ever before.
Multimodal image translation via deep learning inference model trained in video domain
Authors: Fan Jiawei , Liu Zhiqiang , Yang Dong , Qiao Jian , Zhao Jun , Wang Jiazhou , Hu Weigang
Published: July 2022

Background

Current medical image translation is implemented in the image domain. Considering the medical image acquisition is essentially a temporally continuous process, we attempt to develop a novel image translation framework via deep learning trained in video domain for generating synthesized computed tomography (CT) images from cone-beam computed tomography (CBCT) images.

Methods

For a proof-of-concept demonstration, CBCT and CT images from 100 patients were collected to demonstrate the feasibility and reliability of the proposed framework. The CBCT and CT images were further registered as paired samples and used as the input data for the supervised model training. A vid2vid framework based on the conditional GAN network, with carefully-designed generators, discriminators and a new spatio-temporal learning objective, was applied to realize the CBCT–CT image translation in the video domain. Four evaluation metrics, including mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC), and structural similarity (SSIM), were calculated on all the real and synthetic CT images from 10 new testing patients to illustrate the model performance.

Results

The average values for four evaluation metrics, including MAE, PSNR, NCC, and SSIM, are 23.27 ± 5.53, 32.67 ± 1.98, 0.99 ± 0.0059, and 0.97 ± 0.028, respectively. Most of the pixel-wise hounsfield units value differences between real and synthetic CT images are within 50. The synthetic CT images have great agreement with the real CT images and the image quality is improved with lower noise and artifacts compared with CBCT images.

Conclusions

We developed a deep-learning-based approach to perform the medical image translation problem in the video domain. Although the feasibility and reliability of the proposed framework were demonstrated by CBCT–CT image translation, it can be easily extended to other types of medical images. The current results illustrate that it is a very promising method that may pave a new path for medical image translation research.
Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report
Authors: Santoso Dara Ninggar , Sinuraya Fira Alyssa Gabriella , Ambarsari Cahyani Gita
Published: July 2022

Background

Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children.

Case presentation

An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation.

Conclusions

This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.
Comparing human milk macronutrients measured using analyzers based on mid-infrared spectroscopy and ultrasound and the application of machine learning in data fitting
Authors: Ruan Huijuan , Tang Qingya , Zhang Yajie , Zhao Xuelin , Xiang Yi , Feng Yi , Cai Wei
Published: July 2022

Objective

Fat, carbohydrates (mainly lactose) and protein in breast milk all provide indispensable benefits for the growth of newborns. The only source of nutrition in early infancy is breast milk, so the energy of breast milk is also crucial to the growth of infants. Some macronutrients composition in human breast milk varies greatly, which could affect its nutritional fulfillment to preterm infant needs. Therefore, rapid analysis of macronutrients (including lactose, fat and protein) and milk energy in breast milk is of clinical importance. This study compared the macronutrients results of a mid-infrared (MIR) analyzer and an ultrasound-based breast milk analyzer and unified the results by machine learning.

Methods

This cross-sectional study included breastfeeding mothers aged 22–40 enrolled between November 2019 and February 2021. Breast milk samples (n = 546) were collected from 244 mothers (from Day 1 to Day 1086 postpartum). A MIR milk analyzer (BETTERREN Co., HMIR-05, SH, CHINA) and an ultrasonic milk analyzer (Honɡyanɡ Co,. HMA 3000, Hebei, CHINA) were used to determine the human milk macronutrient composition. A total of 465 samples completed the tests in both analyzers. The results of the ultrasonic method were mathematically converted using machine learning, while the Bland-Altman method was used to determine the limits of agreement (LOA) between the adjusted results of the ultrasonic method and MIR results.

Results

The MIR and ultrasonic milk analyzer results were significantly different. The protein, fat, and energy determined using the MIR method were higher than those determined by the ultrasonic method, while lactose determined by the MIR method were lower (all p < 0.05). The consistency between the measured MIR and the adjusted ultrasound values was evaluated using the Bland-Altman analysis and the scatter diagram was generated to calculate the 95% LOA. After adjustments, 93.96% protein points (436 out of 465), 94.41% fat points (439 out of 465), 95.91% lactose points (446 out of 465) and 94.62% energy points (440 out of 465) were within the LOA range. The 95% LOA of protein, fat, lactose and energy were - 0.6 to 0.6 g/dl, -0.92 to 0.92 g/dl, -0.88 to 0.88 g/dl and - 40.2 to 40.4 kj/dl, respectively and clinically acceptable. The adjusted ultrasonic results were consistent with the MIR results, and LOA results were high (close to 95%).

Conclusions

While the results of the breast milk rapid analyzers using the two methods varied significantly, they could still be considered comparable after data adjustments using linear regression algorithm in machine learning. Machine learning methods can play a role in data fitting using different analyzers.
The application of the spot the difference teaching method in clinical skills training for residents
Authors: Yang Liu , Li Wen , Zou Jian , An Junnan , Zeng Bin , Zheng Yitao , Yang Jiming , Ren Jia
Published: July 2022

Background

Clinical skill training (CST) is indispensable for first-year surgical residents. It can usually be carried out through video-based flipped learning (FL) within a web-based learning environment. However, we found that residents lack the process of reflection, blindly imitating results in losing interest and passion for learning in the traditional teaching pattern. The teaching method of "spot the difference" (SDTM), which is based on the fundamentals of the popular game of "spot the difference," is designed to improve students' participation and reflective learning during skill training. This study aimed to evaluate this novel educational model's short-term and long-term effectiveness for surgical residents in China.

Methods

First-year residents who required a three-month rotation in the head and neck surgery department were recruited to participate in a series of CSTs. They were randomized into SDTM and traditional FL (control) groups. Clinical skill performance was assessed with validated clinical skill scoring criteria. Evaluations were conducted by comparing the scores that contain departmental rotation skill examinations and the first China medical licensing examination (CMLE) performance on practical skills. In addition, two-way subjective evaluations were also implemented as a reference for the training results. Training effects were assessed using t tests, Mann–Whitney–Wilcoxon tests, chi-square tests, and Cohen’ s effect size (d). The Cohen’ s d value was considered to be small (<0.2), medium (0.2-0.8), or large (>0.8).

Results

The SDTM group was significantly superior to the control group in terms of after-department skill examination (t=2.179, p<0.05, d=0.5), taking medical history (t=2.665, p<0.05, d=0.59), and CMLE performance on practical skill (t=2.103, p<0.05, d=0.47). The SDTM members rated the curriculum more highly than the control on the items relating to interestingness and participation (p < 0.05) with large effect sizes (d >0.8). There were no significant differences between the two groups on clinical competence (t=0.819, p=0.415, d=0.18), the first-time pass rate for CMLE (χ2 =1.663, p=0.197, d=0.29), and short-term operational skills improvement (t=1.747, p=0.084, d=0.39).

Conclusions

SDTM may be an effective method for enhancing residents' clinical skills, and the effect is significant both short- and long-term. The improvement effect seemed to be more significant in the peer-involved SDTM than training alone. However, despite positive objective results, SDTM still risks student learning burnout.

Trial registration

ISRCTN registry, ISRCTN10598469, 02/04/2022，retrospectively registered.
Does coinsurance reduction influence informer-sector workers’ and farmers’ utilization of outpatient care? A quasi-experimental study in China
Authors: Xu Mingming , Pei Xingtong
Published: July 2022

Background

In recent years, the Chinese government has been trying to improve informal-sector workers’ and farmers’ access to healthcare and reduce their financial burdens by introducing a plan of cost-sharing reduction, but the effect on outpatient care utilization remains unknown. Furthermore, scarce evidence has been provided to help understand the impact of cost-sharing reduction on healthcare use in low- and middle-income countries. The policy change of the coinsurance reduction for outpatient care from 75 to 55% for the enrollees of the Urban and Rural Residents Basic Medical Insurance in Taizhou, China in 2015 provides us a good quasi-experimental setting to explore such an impact.

Methods

We do a quasi-experimental study to explore the impact of coinsurance reduction on outpatient care use among the informal-sector workers and farmers aged 45 and above by estimating a fixed-effects negative binomial model with the difference-in-differences approach and the matching method. Heterogeneous effects in primary care clinics and for the older people aged 60 and above are also examined. Our data is from the China Health and Retirement Longitudinal Study 2013 and 2015.

Results

We find neither statistically significant impact of coinsurance reduction on outpatient care utilization in all health facilities for informal-sector workers and farmers aged 45 and above, nor heterogeneous effects in primary care clinics and for older people aged 60 and above.

Conclusions

We conclude that the coinsurance reduction cannot effectively improve the informal-sector workers’ and farmers’ utilization of healthcare if the cost-sharing undertaken by patients remains high even after the reduction. Besides, improving healthcare quality in primary care clinics may play a more important role than merely introducing a cost-sharing reduction plan in enhancing the role of primary care clinics as gatekeepers. We propose that only a substantial coinsurance reduction may help influence the utilization of healthcare for informal-sector workers and farmers, and enhancing the healthcare quality in primary care clinics should be given priority in low- and middle-income countries.
Investigating the role of signal transducer and activator of transcription 3 in feline injection site sarcoma
Authors: Shih Cheng-Hsin , Chang Yen-Chen , Lai Yun-Chiang , Chiou Hue-Ying
Published: July 2022

Background

Feline injection-site sarcomas (FISSs) are malignant mesenchymal tumors of different histotypes. The pathogenesis of FISS has been correlated with chronic inflammation, resulting in neoplastic transformation. Activation of the Janus kinase-signal transducer and activator of transcription 3 (STAT3) have been demonstrated to play a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis, and angiogenesis in human medicine. To characterize the role of STAT3 in FISS, we first detected STAT3 and phosphorylated STAT3 in formalin-fixed and paraffin-embedded (FFPE) FISS tissues using immunohistochemical staining.

Results

STAT3 was detected in 88.9% (40/45) of FISS cases, and phosphorylated STAT3 was detected in 53.3% (24/45) of cases. However, the expression levels of both forms of STAT3 were not correlated with tumor grade. To study the role of STAT3 in tumor survival, two primary cells derived from FISSs of two cats exhibiting consistent immunophenotypes with their parental FFPE tissues were established. A dose-dependent inhibitory effect on cell proliferation was observed in both primary FISS cells treated with the STAT3 inhibitor, 5-hydroxy-9,10-dioxo-9,10-dihydroanthracene-1-sulfonamide.

Conclusions

The STAT 3 may play an important role in the tumorigenesis of FISS and be a potential molecular therapeutic target for FISS.
Angiogenic and angiostatic factors present in the saliva of malaria patients
Authors: Lekpor Cecilia Elorm , Botchway Felix , Kusi Kwadwo Asamoah , Adjei Andrew A. , Wilson Michael D. , Stiles Jonathan K. , Wilson Nana O.
Published: July 2022

Background

Malaria related mortality is associated with significant deregulation of host inflammatory factors such as interferon-inducible protein 10, a member of the CXC or α-subfamily (CXCL10), and host angiogenic factors such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). However, detection of these factors in malaria patients requires the drawing of blood, which is invasive and increases the risk of accidental blood-borne infections. There has been an increased interest in the use of saliva as the body fluid of choice for the diagnosis of many infectious diseases including malaria. Here, saliva levels of CXCL10, Ang-1, and Ang-2 previously shown to be predictive of severe malaria in malaria patients in Ghana were assessed in malaria patients.

Methods

This study was conducted in the Shai-Osudoku District Hospital in Dodowa, Accra, Ghana and the study population comprised 119 malaria patients and 94 non-malaria subjects. The non-malaria subjects are healthy community participants with no malaria infection. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 of the study participants were measured using an enzyme-linked immunoassay. Complete blood counts of each participant were measured with a haematology autoanalyzer. Pearson correlation was used to evaluate the correlation between plasma and saliva levels of each biomarker in malaria patients. A p-value of < 0.05 was considered significant. Box plots of median biomarker concentrations were plotted. SPSS version 14.2 software was used for statistical analysis.

Results

The non-malaria subjects had a median age of 29 years compared to 23 years for malaria patients (p = 0.001). Among the malaria patients, there was a strong significant relationship between CXCL10 (R2 = 0.7, p < 0.0001) and Ang-1 (R2 = 0.7, p < 0.0001). Malaria patients had lower saliva levels of Ang-1 (p = 0.009) and higher saliva levels of CXCL10 (p = 0.004) and Ang-2 (p = 0.001) compared to non-malaria subjects.

Conclusions

This study provides the first evidence of elevated levels of CXCL10 and Ang-2 in the saliva of malaria patients. Detection of CXCL10, Ang-1 and Ang-2 in saliva may have a potential application for non-invasive malaria diagnosis.
Maternal serum concentrations of one-carbon metabolism factors modify the association between biomarkers of arsenic methylation efficiency and birth weight
Authors: Clark Jeliyah , Bommarito Paige , Stýblo Miroslav , Rubio-Andrade Marisela , García-Vargas Gonzalo G. , Gamble Mary V. , Fry Rebecca C.
Published: July 2022

Background

Inorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes.

Methods

Data from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012)  with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10).

Results

Among urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise.

Conclusions

Tissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.
16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study
Authors: Bartoletti Riccardo , Pastore Antonio Luigi , Fabris Filippo Menchini , Di Vico Tommaso , Morganti Riccardo , Mogorovich Andrea , Morelli Girolamo , Peroni Diego , Al Salhi Yazan , Zucchi Alessandro
Published: July 2022

Background

To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987–1997, were evaluated.

Methods

Two hundred fifty-five subjects were enrolled and 192 patients completed the follow-upt. One hundred fifty-six patients and 36 out 192 had monolateral and bilateral cryptorchidism, respectively. Twenty-nine out of 192 were previously treated by surgery alone (Group A), 93/192 by hormone therapy alone (Group B), 51/192 received sequential combined hormone therapy plus surgery (Group C) whilst 19/192 refused any type of treatment (Group D). The other 63 patients were considered lost to follow-up. All the patients underwent medical consultation, scrotal ultrasound scan, sperm analysis and Inhibin B, Follicular Stimulating Hormone (FSH) and Testosterone (T) serum level determination.

Results

Testicular volume was found decreased in the Group D patients whilst hormone serum levels were comparable in all groups. Statistically significant differences for sperm characteristics were found in patients treated with hormonal therapy alone or combined with surgery (Groups B and C). These two groups reported better semen quality than patients who received surgery alone or no treatment. No differences were observed between monolateral and bilateral cryptorchidism patients.

Conclusions

Early prolonged hormonal therapy is advisable in all patients with cryptorchidism independently from the surgical option of promoting testicular descent to the scrotum. Hormonal therapy provides in our study better chance to obtain adequate sperm quality in adult life.
Longitudinal change in physical activity and adiposity in the transition from adolescence to early adulthood: the 1993 Pelotas cohort study
Authors: Kwon Soyang , Menezes Ana M. B. , Ekelund Ulf , Wehrmeister Fernando C. , Gonçalves Helen , da Silva Bruna Gonçalves C. , Janz Kathleen F.
Published: July 2022

Background

In the current Physical Activity Guidelines (PAG) for moderate- and vigorous-intensity physical activity (MVPA), abrupt transition from ≥ 60 min/day [youth PAG] to ≥ 150 min/week (≥ 22 min/day on average) [adult PAG] during emerging adulthood is poorly justified. The aim of this study was to examine body fat mass changes according to whether meeting the youth and adult PAGs in late adolescence (age 18 years) to early adulthood (age 22 years).

Methods

The study sample included 2,099 participants (1,113 females) from the 1993 Pelotas (Brazil) Study. At ages 18 and 22 years, MVPA was measured using wrist-worn accelerometry and fat mass was measured using dual-energy X-ray absorptiometry. MVPA at age 18 was categorized into two groups: 0–59 or ≥ 60 min/day (no [N] or yes [Y] for meeting the youth recommendation, respectively). MVPA at age 22 was categorized into three groups: 0–21, 22–59, or ≥ 60 min/day (N, Y22, or Y60 for not meeting the adult recommendation, meeting the adult recommendation, or meeting the youth recommendation, respectively). The combination of these groups created six MVPA groups (N&N, N&Y22, N&Y60, Y&N, Y&Y22, and Y&Y60). Sex-specific multivariable linear regression analyses were conducted to estimate change in fat mass index (FMI) from age 18 to 22 years in the six MVPA groups.

Results

Among males, compared to Y&Y60 (FMI increase = 1.2 kg/m2 [95% CI = 1.0, 1.4]), Y&Y22 and Y&N had larger FMI increases (1.9 [1.6, 2.1] and 1.9 [1.2, 2.5], respectively). Among females, Y&Y60 and Y&Y22 had an equal FMI increase (1.6 [1.4, 1.9] for both groups), while Y&N had a larger FMI increase (2.4 [1.8, 3.0]).

Conclusions

These findings suggest that among those who were active in late adolescence, engaging in ≥ 22 min/day of MVPA in adulthood is associated with lower body fat gain for females, but not for males.
Associations of accelerometer measured school- and non-school based physical activity and sedentary time with body mass index: IPEN Adolescent study
Authors: Van Dyck Delfien , Barnett Anthony , Cerin Ester , Conway Terry L. , Esteban-Cornejo Irene , Hinckson Erica , Rubín Lukáš , Rush Elaine , Baron-Epel Orna , Cain Kelli L. , Christiansen Lars Breum , Islam Mohammed Zakiul , Mitáš Josef , Molina-García Javier , Oyeyemi Adewale , Ranjani Harish , Reis Rodrigo , Santos Maria Paula , Sit Cindy , Timperio Anna , Muda Wan Abdul Manan Wan , Sallis James F.
Published: July 2022

Background

This study examined the strength, shape and direction of associations of accelerometer-assessed overall, school- and non-school-based moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) with BMI among adolescents across the world. Second, we examined whether these associations differed by study site and sex.

Methods

Cross-sectional data from the IPEN Adolescent study, an observational multi-country study, were used. Participants wore an accelerometer for seven days, reported height and weight, and completed a socio-demographic survey. In total, 4852 adolescents (46.6% boys), aged 11–19 years (mean age = 14.6, SD = 1.7 years) were included in the analyses, using generalized additive mixed models.

Results

Adolescents accumulated on average 41.3 (SD = 22.6) min/day of MVPA and 531.8 (SD = 81.1) min/day of ST, and the prevalence of overweight and obesity was 17.2% (IOTF), but these mean values differed by country. Linear negative associations of accelerometer-based MVPA and ST with standardized BMI scores and the likelihood of being overweight/obese were found. School-based ST and non-school-based MVPA were more strongly negatively associated to the outcomes than non-school based ST and school-based MVPA. Study site moderated the associations; adolescent sex did not. No curvilinear associations were found.

Conclusions

This multi-country study confirmed the importance of MVPA as a potential protective factor against overweight/obesity in adolescents. Non-school-based MVPA seemed to be the main driver of these associations. Unexpected results were found for ST, calling for further examination in methodologically sound international studies but using inclinometers or pressure sensors to provide more precise ST measures.
Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells
Authors: Llorián-Salvador María , Byrne Eimear M. , Szczepan Manon , Little Karis , Chen Mei , Xu Heping
Published: July 2022

Background

We previously reported higher plasma levels of complement fragments C3a and C5a in neovascular Age-related Macular Degeneration (nAMD) patients with macular fibrosis. This study aimed to understand whether complement activation contributes to the development of macular fibrosis and the underlying mechanisms involved.

Methods

Complement activation was blocked using a C5 neutralizing antibody (BB5.1) in C57BL/6J mice after induction of subretinal fibrosis using the two-stage laser protocol. Fibrotic lesions were examined 10 days after the 2nd laser through fundus examination and immunohistochemistry. The expression of C5aR in fibrotic lesions and retinal pigment epithelial (RPE) cultures were examined by confocal microscopy. Primary murine RPE cells were treated with C3a or C5a (10–100 ng/mL) or TGF-β2 (10 ng/mL). Epithelial-to-mesenchymal transition (EMT) was assessed through various readouts. The expression of E-cadherin, vimentin, fibronectin, α-SMA, Slug, ERK/AKT and pSMAD2/3 were determined by Western blot and immunocytochemistry. Collagen contraction and wound-healing assays were used as functional readouts of EMT. The production of IL-6, TGF-β1, TGF-β2 and VEGF by RPE cells were determined by ELISA. PMX53 was used to block C5aR in RPE cultures and in vivo in mice with subretinal fibrosis.

Results

Extensive C5b-9 deposition was detected at the site of subretinal fibrosis. BB5.1 treatment completely abrogated complement activation and significantly reduced subretinal fibrosis. C5aR was detected in RPE and infiltrating MHC-II+ cells in subretinal fibrosis. In vitro, RPE cells constitutively express C5/C5a and C5aR, and their expression was increased by TGF-β2 treatment. C5a but not C3a increased fibronectin, α-SMA, vimentin and Slug expression, and decreased E-cadherin expression in RPE cells. C5a treatment also increased the contractility and migration of RPE cells and enhanced the production of VEGF and TGF-β1/2. C5a treatment induced pSmad2/3 and pERK1/2 expression in RPE cells and this was blocked by PMX53. PMX53 treatment significantly reduced sodium fluorescein leakage in the subretinal fibrosis model, while collagen-I+ lesions only mildly reduced.

Conclusions

Complement activation is critically involved in the development of subretinal fibrosis, partially through C5a–C5aR-mediated EMT in RPE cells. Targeting complement activation rather than C5a may be a novel approach for the management of macular fibrosis.
The impact of virtual learning on students’ educational behavior and pervasiveness of depression among university students due to the COVID-19 pandemic
Authors: Azmi Fatima M. , Khan Habib Nawaz , Azmi Aqil M.
Published: July 2022

Background

One of the worst pandemics of recent memory, COVID-19, severely impacted the public. In particular, students were physically and mentally affected by the lockdown and the shift from physical person-to-person classrooms to virtual learning (online classes). This increased the prevalence of psychological stress, anxiety, and depression among university students. In this study, we investigated the depression levels in Saudi Arabian university students who were learning virtually because of the COVID-19 pandemic and examined its impact on their educational proficiency.

Methods

The study focused on two points: first, examining the depression levels among undergraduate students in Saudi Arabia, by adapting the Zung (Self-Rating Depression Scale) questionnaire. Second, whether there is an association between the levels of depression and various distress factors associated with virtual (online) learning resulting from the COVID-19 pandemic and its impact on students’ educational behaviors. The questionnaire was prepared using a monkey survey and shared online, via email, and on WhatsApp groups, with participants in two universities, a public and private university in the largest city of Saudi Arabia. A total of 157 complete responses were received. Data were analyzed using SPSS-24, the chi-square test, descriptive statistics, and multilinear regression.

Results

The results indicated that three-fourths of the university students suffered from different depressive symptoms, half of which had moderate to extreme levels of depression. Our study confirmed that a boring virtual (online) learning method, stress, fear of examinations, and decreased productivity were significantly associated with increased depression. In addition, 75% and 79% of the students suffered from stress and fear of examinations, respectively. About half of the students were associated with increased depression. The outcome also indicated that female students experienced extreme depression, stress, and fear of examinations more than males.

Conclusion

These findings can inform government agencies and representatives of the importance of making swift, effective decisions to address students’ depression levels. It is essential to provide training for students to change their educational experience mindset, which might help decrease "depression and stress-related growth." There is also a need to search for a better virtual teaching delivery method to lessen students' stress and fear of examinations.
Cryoglobulinemia in systemic lupus erythematosus: a retrospective study of 213 patients
Authors: Roubertou Yoann , Mainbourg Sabine , Hot Arnaud , Fouque Denis , Confavreux Cyrille , Chapurlat Roland , Debarbieux Sébastien , Jullien Denis , Sève Pascal , Juillard Laurent , Kolopp-Sarda Marie-Nathalie , Lega Jean-Christophe
Published: July 2022

Objectives

The clinical value of cryoglobulinemia (CG) in systemic lupus erythematosus (SLE) is largely unknown. The aim of this retrospective study was to describe the characteristics of CG in SLE, its impact on SLE phenotype, and the features associated with cryoglobulinemic vasculitis (CryoVas) in SLE patients.

Methods

This retrospective study conducted in a French university hospital reviewed the data from 213 SLE patients having been screened for CG between January 2013 and December 2017. SLE patients positive for CG were compared to SLE patients without CG. Patients were classified as CryoVas using the criteria of De Vita et al.

Results

Of the 213 SLE patients included (mean age 29.2 years, female sex 85%), 142 (66%) had at least one positive CG in their history, 67% of them having a persistent CG at follow-up. CG was type III in 114 (80%) cases and type II in 27 (19%) cases. The mean concentration of the cryoprecipitate was 40mg/L (range 0-228). Patients with CG had significantly more C4 consumption. Among patients with CG, 21 (15%) developed a CryoVas. The clinical manifestations of patients with CryoVas were mainly cutaneous (purpura, ulcers, digital ischemia) and articular, without any death at follow-up. Severe manifestations of CG included glomerulonephritis in 1/21 (5%) patients and central nervous system involvement in 4/21 (19%) patients. A response to first-line treatments was observed in 12/13 (92%) patients, but relapses were observed for 3 of them.

Conclusion

CG is frequent in SLE, but mostly asymptomatic. CryoVas features involve mostly joints, skin, and general symptoms. CryoVas in SLE appears to be a specific condition, with a low prevalence of neuropathy, membranoproliferative glomerulonephritis, and severe manifestations.