bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of minimally invasive glaucoma surgery on the ocular surface and quality of life in patients with glaucoma
Authors: Jones Lee , Maes Natalia , Qidwai Umair , Ratnarajan Gokulan
Published: February 2023

Background:

Minimally invasive glaucoma procedures are emerging as clinically effective and safe glaucoma management approaches; however, evidence regarding quality-of-life outcomes is limited.

Objectives:

To explore the impact of minimally invasive glaucoma surgery (MIGS) combined with phacoemulsification on patient-reported outcomes and clinical parameters related to ocular surface disease in people with glaucoma.

Design:

Retrospective observational study.

Methods:

Fifty-seven consecutive patients were examined prior to undergoing iStent combined with phacoemulsification with or without adjunctive endocyclophotocoagulation and at 4-month follow-up.

Results:

At follow-up, on average patients returned statistically significantly improved scores on glaucoma-specific (GQL-15, p < 0.001; GSS, p < 0.001), general health (EQ-5D, p = 0.02) and ocular surface PROMs (OSDI, p = 0.001). Patients were using fewer eye drops on average after MIGS compared with before surgery (1.1 ± 0.9 versus 1.8 ± 0.8; p < 0.001). Undergoing MIGS was associated with improved tear film break-up time ( p < 0.001) and reduced corneal fluorescein staining ( p < 0.001).

Conclusion:

This retrospective audit shows quality of life and clinical parameters related to the ocular surface are improved following MIGS combined with phacoemulsification in patients previously treated with anti-glaucoma therapy.
Literacy disrupted: Re/scripting possibilities for critical curriculum change in Australian primary schools
Authors: Vicars Mark , Sesta Jenny
Published: February 2023

As top-down educational policies continue to dominate and shape pedagogic practices, this paper examines the reconceptualization of curriculum for disrupting literacy in Australian primary schools. It speaks to the pedagogic possibilities arising from change making to curriculum in the teaching and learning of literacy to provide an account of the problematic persistent pedagogic inequalities faced by children who have experience(d) issues of social, cultural, and economic disadvantage. Weaving storied vignettes of classroom practice throughout, we articulate how within the world of schooling, standardized pedagogic practices reinforce inequality and constrain opportunities for how some children learn to be literate. We draw on the process of currere to think with theory about how educators enact the enterprise of critical re-negotiation of curriculum. Central to this paper is recognition of the subjectivities of educators who work with children in classrooms who live between, within, and outside of the technicalities of ‘document-based’ curricular work as enacted in hegemonic literacy classroom routines, practice, and behaviours to articulate a pedagogy of possibility and of hope.
Seismic loss and resilience assessment of tall-coupled cross-laminated timber wall building
Authors: You Tian , Teweldebrhan Biniam Tekle , Wang Wei , Tesfamariam Solomon
Published: February 2023

Balloon-type cross-laminated timber coupled-wall (CLT-CW) structure is an emerging and sustainable option for constructing tall timber buildings. The structure features buckling restrained brace (BRB) hold-downs, balloon-type CLT walls, and coupling beams with replaceable shear links. This study investigates the probabilistic seismic performance (including economic loss, downtime, and resilience index) of a 20-story CLT-CW building. A three-dimensional (3D) structural model is developed to perform incremental dynamic analysis using 30 pairs of ground motion records that represent the seismicity of Vancouver, Canada. Intensity- and time-based loss assessments are conducted to estimate probability distributions of seismic losses according to the FEMA P-58 methodology. Post-earthquake recovery trajectories of the housing function are also presented to calculate the seismic resilience indices under different intensities. The results reveal that the coupling beams contribute the most to repair cost among all structural components. In light of the replaceability and energy dissipating role of coupling beams, the efficiency and resiliency of the CLT-CW building are validated.
Diagnosis and management of pulmonary hypertension in infants with bronchopulmonary dysplasia: a guide for paediatric respiratory specialists
Authors: Chan Sarah , Brugha Rossa , Quyam Sadia , Moledina Shahin
Published: February 2023

Pulmonary hypertension (PH) can develop in babies with bronchopulmonary dysplasia (BPD). PH is common in those with severe BPD and is associated with a high mortality rate. However, in babies surviving beyond 6 months, resolution of PH is likely. There is currently no standardised screening protocol for PH in BPD patients. Diagnosis in this group relies heavily on transthoracic echocardiography. Management of BPD-PH should be led by a multidisciplinary team and focus on optimal medical management of the BPD and associated conditions that may contribute to PH. PH-targeted pharmacotherapies have been used in BPD-PH. To date, these have not been investigated in clinical trials and evidence of their efficacy and safety is absent.

Educational aims

To identify those BPD patients most at risk of developing PH.

To be aware of detection, multidisciplinary management, pharmacological treatment and monitoring strategies for BPD-PH patients.

To understand the potential clinical course for patients with BPD-PH and that evidence on efficacy and safety of PH-targeted pharmacotherapy in BPD-PH is limited.
In vitro and in vivo antiplasmodial activities of leaf extracts from Sonchus arvensis L.
Authors: Wahyuni Dwi Kusuma , Wacharasindhu Sumrit , Bankeeree Wichanee , Wahyuningsih Sri Puji Astuti , Ekasari Wiwied , Purnobasuki Hery , Punnapayak Hunsa , Prasongsuk Sehanat
Published: February 2023

Background

Malaria continues to be a global problem due to the limited efficacy of current drugs and the natural products are a potential source for discovering new antimalarial agents. Therefore, the aims of this study were to investigate phytochemical properties, cytotoxic effect, antioxidant, and antiplasmodial activities of Sonchus arvensis L. leaf extracts both in vitro and in vivo.

Methods

The extracts from S. arvensis L. leaf were prepared by successive maceration with n-hexane, ethyl acetate, and ethanol, and then subjected to quantitative phytochemical analysis using standard methods. The antimalarial activities of crude extracts were tested in vitro against Plasmodium falciparum 3D7 strain while the Peter's 4-day suppressive test model with P. berghei-infected mice was used to evaluate the in vivo antiplasmodial, hepatoprotective, nephroprotective, and immunomodulatory activities. The cytotoxic tests were also carried out using human hepatic cell lines in [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay.

Result

The n-hexane, ethyl acetate, and ethanolic extracts of S. arvensis L. leaf exhibited good in vitro antiplasmodial activity with IC50 values 5.119 ± 3.27, 2.916 ± 2.34, and 8.026 ± 1.23 μg/mL, respectively. Each of the extracts also exhibited high antioxidant with low cytotoxic effects. Furthermore, the ethyl acetate extract showed in vivo antiplasmodial activity with ED50 = 46.31 ± 9.36 mg/kg body weight, as well as hepatoprotective, nephroprotective, and immunomodulatory activities in mice infected with P. berghei.

Conclusion

This study highlights the antiplasmodial activities of S. arvensis L. leaf ethyl acetate extract against P. falciparum and P. berghei as well as the antioxidant, nephroprotective, hepatoprotective, and immunomodulatory activities with low toxicity. These results indicate the potential of Sonchus arvensis L. to be developed into a new antimalarial drug candidate. However, the compounds and transmission-blocking strategies for malaria control of S. arvensis L. extracts are essential for further study.
Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis
Authors: Patel Avignat S. , Miller Ezra , Regis Shawn M. , Hunninghake Gary M. , Price Lori Lyn , Gawlik Melissa , McKee Andrea B. , Rieger-Christ Kimberly M. , Pinto-Plata Victor , Liesching Timothy N. , Wald Christoph , Hashim Jeffrey , McKee Brady J. , Gazourian Lee
Published: February 2023

Background

Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis.

Methods

This was a retrospective study of individuals enrolled in a CT lung cancer screening program from 2012 to 2014. Baseline and longitudinal CT scans were scored for ILA per Fleischner Society guidelines. The primary analyses examined the association between baseline ILA and mortality, all-cause hospitalization, and incidence of lung cancer. Kaplan–Meier plots were generated to visualize the associations between ILA and lung cancer and all-cause mortality. Cox regression proportional hazards models were used to test for this association in both univariate and multivariable models.

Results

1699 subjects met inclusion criteria. 41 (2.4%) had ILA and 101 (5.9%) had indeterminate ILA on baseline CTs. ILD was diagnosed in 10 (24.4%) of 41 with ILA on baseline CT with a mean time from baseline CT to diagnosis of 4.47 ± 2.72 years. On multivariable modeling, the presence of ILA remained a significant predictor of death, HR 3.87 (2.07, 7.21; p < 0.001) when adjusted for age, sex, BMI, pack years and active smoking, but not of lung cancer and all-cause hospital admission. Approximately 50% with baseline ILA had progression on the longitudinal scan.

Conclusions

ILA identified on baseline lung cancer screening exams are associated with all-cause mortality. In addition, a significant proportion of patients with ILA are subsequently diagnosed with ILD and have CT progression on longitudinal scans.

Trial registration number: ClinicalTrials.gov; No.: NCT04503044.
The reciprocal interactions between microglia and T cells in Parkinson’s disease: a double-edged sword
Authors: Xu Yuxiang , Li Yongjie , Wang Changqing , Han Tingting , Liu Haixuan , Sun Lin , Hong Jun , Hashimoto Makoto , Wei Jianshe
Published: February 2023

In Parkinson's disease (PD), neurotoxic microglia, Th1 cells, and Th17 cells are overactivated. Overactivation of these immune cells exacerbates the disease process and leads to the pathological development of pro-inflammatory cytokines, chemokines, and contact-killing compounds, causing the loss of dopaminergic neurons. So far, we have mainly focused on the role of the specific class of immune cells in PD while neglecting the impact of interactions among immune cells on the disease. Therefore, this review demonstrates the reciprocal interplays between microglia and T cells and the associated subpopulations through cytokine and chemokine production that impair and/or protect the pathological process of PD. Furthermore, potential targets and models of PD neuroinflammation are highlighted to provide the new ideas/directions for future research.
Decreased thymic output predicts progression of chronic kidney disease
Authors: Iio Kenichiro , Kabata Daijiro , Iio Rei , Shibamoto Shinichi , Watanabe Yuuki , Morita Masashi , Imai Yosuke , Hatanaka Masaki , Omori Hiroki , Isaka Yoshitaka
Published: February 2023

Background

Chronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28− T cells, and CKD progression.

Results

A total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA+CD31+CD4+ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm3) and the proportion of RTE among CD4+ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28− cells among CD4+ T cells (CD28−/CD4+) and CD28− cells among CD8+ T cells (CD28−/CD8+). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m2. The median RTEs, RTE%, CD28−/CD4+, and CD28−/CD8+ were 97.5/mm3, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28−/CD4+ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28−/CD8+ T cells.

Conclusions

Decreased thymic output in CKD patients, as well as increased highly differentiated CD4+ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease.
Ultra-low-coverage genome-wide association study—insights into gestational age using 17,844 embryo samples with preimplantation genetic testing
Authors: Li Shumin , Yan Bin , Li Thomas K. T. , Lu Jianliang , Gu Yifan , Tan Yueqiu , Gong Fei , Lam Tak-Wah , Xie Pingyuan , Wang Yuexuan , Lin Ge , Luo Ruibang
Published: February 2023

Background

Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined.

Methods

We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS.

Results

The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP, ICAM1, and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1, and EGR2 with preterm birth, infant disease, and breast cancer.

Conclusions

This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.
Angiogenesis precedes myogenesis during regeneration following biopsy injury of skeletal muscle
Authors: Jacobsen Nicole L. , Morton Aaron B. , Segal Steven S.
Published: February 2023

Background

Acute injury to skeletal muscle damages myofibers and fragment capillaries, impairing contractile function and local perfusion. Myofibers and microvessels regenerate from satellite cells and from surviving microvessel fragments, respectively, to restore intact muscle. Established models of injury have used myotoxins and physical trauma to demonstrate the concurrence of myogenesis and angiogenesis during regeneration. In these models, efferocytosis removes cellular debris while basal laminae persist to provide guidance during myofiber and microvessel regeneration. It is unknown whether the spatiotemporal coupling between myofiber and microvascular regeneration persists when muscle tissue is completely removed and local guidance cues are lost.

Methods

To test whether complete removal of skeletal muscle tissue affects the spatiotemporal relationship between myogenesis and angiogenesis during regeneration, subthreshold volumetric muscle loss was created with a biopsy punch (diameter, 2 mm) through the center of the gluteus maximus (GM) in adult mice. Regeneration into the void was evaluated through 21 days post-injury (dpi). Microvascular perfusion was evaluated in vivo by injecting fluorescent dextran into the circulation during intravital imaging. Confocal imaging and histological analyses of whole-mount GM preparations and tissue cross-sections assessed the growth of microvessels and myofibers into the wound.

Results

A provisional matrix filled with PDGFRα+ and CD45+ cells spanned the wound within 1 dpi. Regenerating microvessels advanced from the edges of the wound into the matrix by 7 dpi. Nascent microvascular networks formed by 10 dpi with blood-perfused networks spanning the wound by 14 dpi. In striking contrast, the wound remained devoid of myofibers at 7 and 10 dpi. Myogenesis into the wound was apparent by 14 dpi and traversed the wound by 21 dpi. Regenerated myofibers and microvessels were disorganized compared to the uninjured muscle.

Conclusions

Following punch biopsy of adult skeletal muscle, regenerating microvessels span the wound and become perfused with blood prior to myofiber regeneration. The loss of residual guidance cues with complete tissue removal disrupts the spatiotemporal correspondence between microvascular and myofiber regeneration. We conclude that angiogenesis precedes myogenesis during regeneration following subthreshold volumetric muscle loss.
Antimicrobial prescription patterns in East Africa: a systematic review
Authors: Acam Joan , Kuodi Paul , Medhin Girmay , Makonnen Eyasu
Published: February 2023

Background

Antimicrobial resistance is currently a recognized global health problem stemming from poor antibiotic stewardship by health workers and inappropriate antimicrobial use by patients. Data showing the extent of poor antimicrobial stewardship in low- and middle-income countries are scanty though high incidences of antimicrobial resistance are increasingly reported in many settings across the globe. The objective of the present study was, therefore, to evaluate prescriptions for antimicrobials in East Africa.

Methods

A comprehensive literature search strategy that includes text words and medical subject headings was developed and applied to predefined electronic databases. Two authors independently screened the titles and abstracts of the outputs of the literature search. Full texts were then independently reviewed by the first and the second authors. Eligible studies were formally assessed for quality and risk of bias using a scoring tool. Extracted data from included studies were combined in a meta-analysis where appropriate and presented using forest plots and tables or in a narrative text. Where data were available, subgroup analyses were performed.

Results

A total of 4284 articles were retrieved, but only 26 articles were included in the review. The majority of the included studies (30.8%) were retrieved from Ethiopia, followed by Sudan, Kenya, and Tanzania each contributing 19.2% of the included studies. The overall proportion of encounters with antimicrobials reported by the included studies was 57% CI [42–73%]. Ethiopia had an overall patient encounter with antimicrobials of 63% [50–76%] followed by Sudan with an overall encounter with antimicrobials of 62% CI [34–85%]. Included studies from Kenya reported an overall encounter with antimicrobials of 54% CI [15–90%], whereas included studies from Tanzania reported an overall patient encounter with antimicrobials of 40% CI [21–60%].

Conclusion

Prescription patterns demonstrated in this review significantly deviate from WHO recommendations suggesting inappropriate antimicrobial use in the East African countries. Further studies have to be pursued to generate more information on antimicrobial use in this region.
Association between sociodemographic factors and mobility limitation among older adults: a systematic review and meta-analysis protocol
Authors: Onyeso Ogochukwu Kelechi , Odole Adesola C. , Scott David R. , Akinrolie Olayinka , Kalu Michael E. , Awosoga Oluwagbohunmi A.
Published: February 2023

Background

Mobility is an independent predictor of physical functionality, healthy ageing, and quality of life. Various literatures have associated mobility limitation in older adulthood with demographic and socioeconomic factors. Hence, we propose a systematic review and meta-analysis to synthesise the association between sociodemographic factors and mobility limitations in older adults.

Methods and analyses

This protocol was written according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. We will perform a comprehensive search of all observational studies that assessed the relationship between age, gender, race, place, education, income, occupation, social status, and walking distance, time, or speed. Electronic databases (MEDLINE, Web of Science, EMBASE, CINAHL, AgeLine, and SPORTDiscus) will be searched from inception to 28 February 2023. We will supplement the database search by manually searching the reference lists of all identified and relevant full-text articles. Two independent reviewers will be responsible for screening articles, data extraction, and assessment of bias. We will appraise the study quality and risk of bias using the Prediction Model Risk of Bias Assessment Tool (PROBAST). A meta-analysis will be considered if data from the selected studies are homogeneous, otherwise, a narrative synthesis of the extracted data will be presented.

Discussion

Mobility limitation leads to frequent falls, dependency, morbidity, and death among older adults. This review is necessary, to identify and prioritise important sociodemographic factors during older adults’ clinical assessment and policy development. It is the first phase of a multi-methods study seeking to develop a prognostic mobility trajectory for community-dwelling older adults.

Systematic review registration

PROSPERO CRD42022298570
Dataset creation and selection methods with a wire drive flexible manipulator for vision-based reconstruction
Authors: Wang Zhenyu , Endo Gen , Takahashi Hideharu , Kikura Hiroshige
Published: February 2023

In order to improve spatial awareness for future investigations of reactor No. 2 at the Fukushima nuclear power plant, it is necessary first to acquire the environment model through reconstruction. To gather images for this task, we have developed a flexible, compact, and lightweight manipulator called the Bundled Wire Drive robot. However, due to mechanism’ shortcomings, the feasibility of using this robot is limited by potential degradations of image quality, including odometry deviation and motion blur. Based on the motion characteristics of the robot, we have proposed a dataset creation and selection method to mitigate the impact of these degradations. The effectiveness of this method was verified through experiments with a hardware prototype robot, which demonstrates that it is possible to avoid the influence of matched joint movement deviation by using overlapping simple trajectories; and pre-filtering out blurry images, which usually concentrate on the beginning and stopping periods. Additionally, we conducted a robustness study of mainstream reconstruction methods under limited illumination conditions to quantitively study the performance degradation in a more realistic environment.
Effects of β-glucan on Salmonella enterica serovar Typhimurium swine colonization and microbiota alterations
Authors: Bearson Shawn M. D. , Trachsel Julian M. , Bearson Bradley L. , Loving Crystal L. , Kerr Brian J. , Shippy Daniel C. , Kiros Tadele G.
Published: February 2023

Background

The 2017 Veterinary Feed Directive eliminated the use of medically important antibiotics for growth promotion of food animals; thus, alternative growth promoters are highly desirable by food animal producers to enhance animal health and reduce pathogen colonization, including the human foodborne pathogen Salmonella. β(1-3)(1-6)-d-glucan (β-glucan) is a soluble fiber with prebiotic characteristics; it has been shown to modulate immune and intestinal functions that strengthen swine resistance to health challenges such as bacterial infections when supplemented in the diets of growing pigs. The current study evaluated the effects of a β-glucan product on gut microbial community structure as well as Salmonella shedding and intestinal colonization.

Results

Five-week-old pigs were fed a β-glucan amended diet at 500 g/ton (n = 13) or a non-amended control diet (n = 14) for three weeks, followed by inoculation of the 27 pigs with 1 × 109 colony forming units of Salmonella enterica serovar Typhimurium strain UK1. While remaining on the respective diets, fecal samples collected at 2, 4, 7, and 16 days post-inoculation (dpi) were similar for Salmonella shedding counts between the two diets. At 16 dpi, Salmonella counts were significantly lower in the cecal contents of the β-glucan-fed pigs (P = 0.0339) and a trend towards a reduction was observed in the Peyer’s patches region of the ileum (P = 0.0790) compared to the control pigs. Pigs fed β-glucan for three weeks exhibited an increase in members of the Clostridia class in their fecal microbial communities, and after inoculation with Salmonella, several potentially beneficial microorganisms were enriched in the microbiota of β-glucan-fed pigs (Lactobacillus, Ruminococcaceae, Prevotellaceae, Veillonellaceae, Bifidobacterium and Olsenella).

Conclusion

Administration of β-glucan altered the swine gut microbiome and reduced Salmonella colonization in the cecal contents.
Stock profiling using time–frequency-varying systematic risk measure
Authors: Mestre Roman
Published: February 2023

This study proposes a wavelets approach to estimating time–frequency-varying betas in the capital asset pricing model (CAPM) framework. The dynamic of systematic risk across time and frequency is analyzed to investigate stock risk-profile robustness. Furthermore, we emphasize the effect of an investor’s investment horizon on the robustness of portfolio characteristics. We use a daily panel of French stocks from 2012 to 2022. Results show that varying systematic risk varies in time and frequency, and that its short and long-run evolutions differ. We observe differences in short and long dynamics, indicating that a stock’s betas differently fluctuate to early announcements or signs of events. However, short-run and long-run betas exhibit similar dynamics during persistent shocks. Betas are more volatile during times of crisis, resulting in greater or lesser robustness of risk profiles. Significant differences exist in short-run and long-run risk profiles, implying a different asset allocation. We conclude that the standard CAPM assumes short-run investment. Then, investors should consider time–frequency CAPM to perform systematic risk analysis and portfolio allocation.
Plasma manganese and selenium levels in paediatric chronic kidney disease patients measured by high resolution sector field inductively coupled plasma mass spectrometry
Authors: Verma Subhrata , Belostotsky Vladimir , Yang Liju , Filler Guido
Published: February 2023

Background

Manganese (Mn) and Selenium (Se) deficiencies are noted in adult patients with chronic kidney disease (CKD). However, levels of these trace elements have not been well studied in the paediatric CKD population. We determined the Mn and Se levels in a single-institution cohort of paediatric patients with CKD.

Methods

Ancillary cross-sectional study to a prospective longitudinal randomized control trial on zinc supplementation, which included 42 children and adolescents aged 0 to 19 years with CKD stages I to IV not on dialysis, who had 1–6 trace element measurements. Cystatin C estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma Mn and Se levels were measured, and anthropomorphic data/blood parameters were collected from electronic health records. The trial was registered on clinicaltrials.gov, NCT02126293.

Results

There were 96 Mn and Se levels in 42 patients (age 12.5 ± 4.6 years). The median Mn concentration was 12.61 nmol/L [10.08, 16.42] with a trend towards lower values with lower eGFR (p = 0.0367 one-sided). Mn z-scores were significantly lower than the general paediatric reference population. The mean Se level was 1.661 ± 0.3399 µmol/L with a significant positive correlation with eGFR (p = 0.0159, r = 0.366). However, only 4 patients with low eGFR had abnormally low Se levels.

Conclusions

This single-institution study of children with CKD demonstrates a significant decrease in Se levels with decreasing eGFR, but no significant difference between mean Se z-scores of our cohort and the reference population. There was no significant relationship between Mn levels and eGFR however the mean Mn z-score was significantly lower than the theoretical mean.

Trial registration: clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293. Date: April 30, 2014.
Fighting wheat rusts in China: a look back and into the future
Authors: Zhao Jie , Kang Zhensheng
Published: February 2023

Wheat rusts, including stripe, leaf, and stem rusts, are severe wheat diseases and cause huge yield loss in China annually. Benefiting from utilizing the genetic resistance wheat varieties, wheat stem rust has been effectively controlled since the 1970s; however, the wheat stripe and leaf rusts are still threating the wheat production in China due to lack of effective agricultural regulations. This review summarizes the research advances on wheat rust physiology, epidemiology, and fungicide resistance in China. In addition, the corresponding field management strategies for the integrated control of rust diseases are also discussed.
Epigallocatechin gallate restores the reduction of protein phosphatase 2 A subunit B caused by middle cerebral artery occlusion
Authors: Shah Murad-Ali , Kang Ju-Bin , Park Dong-Ju , Koh Phil Ok
Published: February 2023

Background

Epigallocatechin gallate (EGCG) is a flavonoid compound commonly found in green tea. It exhibits antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia. Protein phosphatase 2 A (PP2A) is an important serine/threonine phosphatase enzyme involved in various cellular activities. PP2A subunit B is present abundantly in the brain and plays an important role in the nervous system. We investigated the effect of EGCG on the expression level of PP2A subunit B in cerebral ischemia caused by middle cerebral artery occlusion (MCAO). EGCG (50 mg/kg) or vehicle was injected into the peritoneal cavity prior to MCAO surgery. Neurological behavior tests were performed 24 h after MCAO, and right cerebral cortex tissue was collected. Cerebral ischemia caused serious neurological abnormalities, which were alleviated by EGCG administration. We screened the expression of PP2A subunits containing A, B, and C using reverse-transcription PCR. We confirmed that PP2A subunit B exhibited significant changes in MCAO animals compared to subunits A and C. We continuously examined the expression of PP2A subunit B protein in MCAO animals using Western blot analysis.

Results

EGCG alleviated the reduction of PP2A subunit B protein by MCAO damage. In addition, immunohistochemistry demonstrated a decrease in the number of PP2A subunit B-positive cells in the cerebral cortex, and EGCG attenuated this decrease. Maintenance of PP2A subunit B is important for normal brain function.

Conclusion

Therefore, our findings suggest that EGCG exerts neuroprotective effects against cerebral ischemia through modulation of PP2A subunit B expression.
Predictors of recurrence and disease-free survival for salivary gland tumors among children and young adults in Kampala, Uganda: a retrospective follow-up study
Authors: Vuhahula Edda A. M. , Yahaya James J. , Ngaiza Advera I. , Morgan Emmanuel D. , Abraham Zephania S.
Published: February 2023

Background

Salivary gland tumors are a group of tumors which are highly heterogeneous, and they are uncommon among children and young adults. We aimed to investigate the predictors of recurrence and disease-free survival for salivary gland tumors among children and young adults.

Methods

We retrospectively extracted clinical, pathologic, and follow-up data of patients who were diagnosed histologically with salivary gland tumors from January 2013 to December 2018 at the department of pathology, Makerere University in Kampala, Uganda. Then, we applied Cox regression analysis to determine the predictors of disease-free survival using hazard ratio as the measure of probability of the survival with 95% confidence interval. We also used Kaplan–Meier curves to analyze the disease-free survival. P ˂ 0.05 was considered significant.

Results

A total of 144 patients with salivary gland tumors were included in the present study who were aged not more than 20 years with mean age of 13.9 ± 4.5 years. Over one quarter (26.4%, n = 38) of the salivary gland tumors that were analyzed in the present study were malignant. The prevalence of recurrence was (27.1%, n = 39), and the mean disease-free survival was 58.7 ± 1.9 months. Category of the salivary gland (AHR = 1.36, 95% CI = 0.137–0.942, p = 0.037) and behavior of the tumors (AHR = 1.82, 95% CI = 0.729–0.990, p = 0.023) were the potential predictors of disease-free survival.

Conclusion

Over one quarter of the patients had malignant salivary tumors, and also, one-third of the patients developed recurrence at the end of the follow-up period of 6 years. Involvement of minor salivary glands and having a malignant salivary gland tumor both have shown increased risk of recurrence as well as short disease-free survival. Therefore, patients with minor salivary gland involvement and those with malignant variants require optimal surgical resection of the tumors for possible prevention of early recurrence and increasing the survival of the patients without relapse of such tumors after initial resection of the primary lesions.
Antiseizure medications prescribing for behavioural and psychiatric concerns in adults with an intellectual disability living in England
Authors: Branford David , Sun James J. , Shankar Rohit
Published: February 2023

Antiseizure medications (ASMs) are the second most widely prescribed psychotropic for people with intellectual disabilities in England. Multiple psychotropic prescribing is prevalent in almost half of people with intellectual disabilities on ASMs. This analysis identifies limited evidence of ASM benefit in challenging behaviour management and suggests improvements needed to inform clinical practice.
Clearance Profile of Circulating Tumor Human Papillomavirus DNA During Radiotherapy Predicts Clinical Outcomes in Human Papillomavirus–Related Oropharyngeal Cancer
Authors: Tanaka Hidenori , Uno Atsuhiko , Takenaka Yukinori , Suzuki Motoyuki , Seo Yuji , Takemoto Norihiko , Fukusumi Takahito , Eguchi Hirotaka , Kanai Haruka , Horie Masafumi , Isohashi Fumiaki , Ogawa Kazuhiko , Yachida Shinichi , Inohara Hidenori
Published: February 2023

PURPOSE

This study aimed to examine whether circulating tumor human papillomavirus type 16 (HPV16) DNA (ctHPV16DNA) can help identify patients with locally advanced HPV16-related oropharyngeal squamous cell carcinoma who may benefit from deintensified treatment.

MATERIALS AND METHODS

We serially collected blood samples before, during, and after treatment from 22 patients who received 70 Gy radiotherapy alone and longitudinally quantified ctHPV16DNA using droplet digital polymerase chain reaction. We correlated the clearance profile of ctHPV16DNA with clinical outcomes.

RESULTS

The percentage of patients with detectable ctHPV16DNA decreased after every 10 Gy of radiotherapy. By contrast, the percentage of patients who later developed treatment failure among patients with detectable ctHPV16DNA gradually increased as radiotherapy proceeded, reaching 100% after 60 Gy of radiotherapy. We defined patients with and without detectable ctHPV16DNA after receiving 40 Gy as having slow and rapid clearance profiles, respectively. All 12 patients with a rapid clearance profile remained disease-free after radiotherapy. Of the 10 patients with a slow clearance profile, three had persistent or progressive disease at response evaluation after radiotherapy and one developed distant metastasis during follow-up (ie, four patients experienced treatment failure). The median follow-up for surviving patients was 38.6 months, and the 3-year failure-free survival rates of patients with rapid and slow clearance profiles were 100% and 58%, respectively ( P = .02). Neither baseline ctHPV16DNA levels nor metabolic tumor volume was an independent predictor of the pattern of the clearance profile.

CONCLUSION

In patients with HPV16-related oropharyngeal squamous cell carcinoma receiving radiotherapy, a slow ctHPV16DNA clearance profile could prelude unfavorable outcomes. Monitoring ctHPV16DNA is essential for determining the clearance profile, which might help optimize treatment intensity individually.
Understanding the Risk of Drug Interactions Between Ritonavir-Containing COVID-19 Therapies and Small-Molecule Kinase Inhibitors in Patients With Cancer
Authors: Hopkins Ashley M. , Sorich Michael J. , McLachlan Andrew J. , Karapetis Christos S. , Miners John O. , van Dyk Madelé , Rowland Andrew
Published: February 2023

PURPOSE

The introduction of COVID-19 therapies containing ritonavir has markedly expanded the scope of use for this medicine. As a strong cytochrome P450 3A4 inhibitor, the use of ritonavir is associated with a high drug interaction risk. There are currently no data to inform clinician regarding the likely magnitude and duration of interaction between ritonavir-containing COVID-19 therapies and small-molecule kinase inhibitors (KIs) in patients with cancer.

METHODS

Physiologically based pharmacokinetic modeling was used to conduct virtual clinical trials with a parallel group study design in the presence and absence of ritonavir (100 mg twice daily for 5 days). The magnitude and time course of changes in KI exposure when coadministered with ritonavir was evaluated as the primary outcome.

RESULTS

Dosing of ritonavir resulted in a > 2-fold increase in steady-state area under the plasma concentration-time curve and maximal concentration for six of the 10 KIs. When the KI was coadministered with ritonavir, dose reductions to between 10% and 75% of the original dose were required to achieve an area under the plasma concentration-time curve within 1.25-fold of the value in the absence of ritonavir.

CONCLUSION

To our knowledge, this study provides the first data to assist clinicians' understanding of the drug interaction risk associated with administering ritonavir-containing COVID-19 therapies to patients with cancer who are currently being treated with KIs. These data may support clinicians to make more informed dosing decisions for patients with cancer undergoing treatment with KIs who require treatment with ritonavir-containing COVID-19 antiviral therapies.
Effect of Restorative Neurostimulation on Major Drivers of Chronic Low Back Pain Economic Impact
Authors: Shaffrey Christopher , Gilligan Christopher
Published: February 2023

BACKGROUND:

High-impact chronic low back pain (CLBP) correlates with high healthcare resource utilization. Therapies that can alter impact status may provide beneficial long-term economic benefits. An implantable restorative neurostimulation system (ReActiv8, Mainstay Medical) designed to over-ride multifidus inhibition to facilitate motor control restoration, thereby resolving mechanical low back pain symptoms, has shown significant durable clinical effects in moderately and severely impacted patients.

OBJECTIVE:

To examine changes in high-impact chronic low back pain in patients treated with restorative neurostimulation at 2 years.

METHODS:

ReActiv8-B is a prospective, international, multicenter trial to evaluate the safety and efficacy of restorative neurostimulation in patients with intractable CLBP and no prior surgery. For this longitudinal subanalysis, patients were stratified into low-, moderate-, and high-impact CLBP categories using the US Department of Health and Human Services definition comprising pain intensity, duration, and impact on work, self-care, and daily activities.

RESULTS:

Of 2-year completers (n = 146), 71% had high-impact CLBP at baseline and this proportion reduced to 10%, with 85% reporting no or low impact. This corresponds with measurements of HRQoL returning to near-population norms.

CONCLUSION:

In addition to clinically meaningful improvements in pain and function with long-term durability, the overwhelming majority of patients transitioned from a high- to a no- or low-impact CLBP state. This is typically associated with significantly lower healthcare-utilization levels. The of recovery trajectory is consistent with a restorative mechanism of action and suggests that over the long term, the improvement in these health states will be maintained.
Influence of Patient and Technical Variables on Combined Direct and Indirect Cerebral Revascularization: Case Series
Authors: Rennert Robert C. , Brandel Michael G. , Budohoski Karol P. , Twitchell Spencer , Fredrickson Vance L. , Grandhi Ramesh , Couldwell William T.
Published: February 2023

BACKGROUND:

Cerebral bypass for flow augmentation is an important technique for selected neurosurgical patients, with multiple techniques used (direct, indirect, or combined).

OBJECTIVE:

To assess the impact of patient and technical variables on direct and indirect bypass flow after combined revascularization.

METHODS:

This was a retrospective, single-institution review of patients undergoing direct superficial temporal artery-to-middle cerebral artery bypass with indirect encephaloduro-myosynangiosis for moyamoya disease and steno-occlusive cerebrovascular disease over a 2-year period. We evaluated the effect of baseline patient characteristics, preoperative imaging characteristics, and operative variables on direct and indirect patency grades.

RESULTS:

Twenty-six hemispheres (8 moyamoya disease and 18 steno-occlusive cerebrovascular disease) in 23 patients were treated with combined revascularization. The mean patient age was 53.4 ± 19.1 years. Direct bypass patency was 96%. Over a mean follow-up of 8.3 ± 5.4 months, there were 3 strokes in the treated hemispheres (11.5%). The mean modified Rankin Scale score improved from 1.3 ± 1.1 preoperatively to 0.7 ± 0.8 postoperatively. Preservation of the nondonor superficial temporal artery branch was associated with a lower direct bypass grade (P < .01), whereas greater mean time to maximum perfusion (Tmax)> 4 and >6 seconds and mismatch volumes were associated with higher direct bypass grades (P < .05). Tmax >4-second volume inversely predicted indirect bypass patency.

CONCLUSION:

Patient and technical variables may influence the relative contributions of the direct and indirect components of combined revascularizations.
Analysis on factors affecting tourist involvement in coffee tourism after the COVID-19 pandemic in Thailand
Authors: Madhyamapurush Warach
Published: February 2023

Background: The world economy is affected by the coronavirus disease (COVID-19) pandemic, which affects the coffee industry. Coffee tourism is an emerging new type of tourism in Thailand that is formed in response to the growing demand from visitors with a particular affinity for coffee. Coffee tourism may contribute considerably to the expansion of Thai tourism given proper guidance and assistance.

Methods: This study used a stochastic neuro-fuzzy decision tree (SNF-DT) to analyze coffee tourism in Thailand. This research surveyed 400 international and Thai coffee tourists. According to this study, Thai visitors mostly visit coffee tourism locations in Thailand for enjoyment. They also wanted to visit coffee fields to obtain personal knowledge about coffee production and marketing. Responses from foreign coffee tourists indicated that many of their journeys to coffee tourism destinations were entirely for enjoyment rather than business. They also wanted to meet local tour guides and acquire handmade and locally produced things to better understand coffee tourism.

Results: According to the study results, coffee tourism management in northern Thailand appears to be well received by international tourists. We also compared the suggested model with the traditional model to demonstrate its efficacy. The performance metrics are the prediction rate, prediction error, and accuracy. The estimated results for our proposed technique are prediction rate (95%), prediction error (97%), and accuracy (94%).

Recommendations: Major global businesses such as tourism have been harmed by COVID-19’s unprecedented effects. This study attempts to determine the role of coffee tourism in livelihoods based on real-time data using a machine-learning approach. More research is needed to analyse the factors of the coffee tourism experience using different machine learning approaches.