bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Composition of Essential Oil, Phenolic Compounds Content, and Antioxidant Activity of Cistus monspeliensis from Northern Morocco
Authors: Haida Sara , Bakkouche Kaltoum , Kribii Abdelaziz Ramadane , Kribii Abderahim
Published: December 2021

Currently, oxidative stress is one of the major problems that threatens human health. It is at the root of many diseases such as cancer. Despite the enormous efforts provided to combat this scourge, oxidative stress is still relevant and hence comes the need for research of new remedies especially from natural origin. For this purpose, the study of the antioxidant activity of extracts of Cistus monspeliensis from Morocco is a principal research objective. The phenolic extracts were obtained by maceration of the plant in a water/acetone mixture and then separated by liquid/liquid extraction with solvents of increasing polarity. The first phytochemical tests carried out on these extracts showed the existence of different families of phenolic compounds, such as flavonoids, tannins, and others. Assays for total polyphenols, flavonoids, hydrolysable, and condensed tannins were carried out by known colorimetric methods. The results of these assays have shown that the studied extracts are rich in phenolic compounds present in the plant in the form of flavonoids (69.81 ± 0.22 mg EQ/g DM), hydrolysable tannins (61.86 ± 0.89 mg ETA/g DM), and condensed tannins (70.05 ± 1.61 mg EC/g DM). The evaluation of the antioxidant activity is carried out by two different methods: the DPPH test (2,2-DiPhenyl-1-Picryl-Hydrazyl) and the FRAP test (Ferric Reducing Antioxidant Power). The results obtained show that the extracts of Cistus monspeliensis are active and have interesting antioxidant powers. In particular, the water/acetone (WAE) (IC50 = 0.079 mg/mL) and butanolic (BUE) (IC0.5 = 0.099 mg/mL) extracts are the most active with values comparable to that of ascorbic acid. The interesting results obtained in this study clearly show that Cistus monspeliensis originating from Morocco can be considered as a source of natural antioxidants. Therefore, the extracts of this plant deserve to be tested in the medicinal field, against cancer and cardiovascular diseases, and in food field as an additive and preservative.
Novel Genes Potentially Involved in Fibroblasts of Diabetic Wound
Authors: Zhu Weirong , Fang Qin , Liu Zhao , Chen Qiming
Published: December 2021

Fibroblasts are the essential cell type of skin, highly involved in the wound regeneration process. In this study, we sought to screen out the novel genes which act important roles in diabetic fibroblasts through bioinformatic methods. A total of 811 and 490 differentially expressed genes (DEGs) between diabetic and normal fibroblasts were screened out in GSE49566 and GSE78891, respectively. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in type 2 diabetes were retrieved from miRWalk. Consequently, the integrated bioinformatic analyses revealed the shared KEGG pathways between DEG-identified and diabetes-related pathways were functionally enriched in the MAPK signaling pathway, and the MAPKAPK3, HSPA2, TGFBR1, and p53 signaling pathways were involved. Finally, ETV4 and NPE2 were identified as the targeted transcript factors of MAPKAPK3, HSPA2, and TGFBR1. Our findings may throw novel sight in elucidating the molecular mechanisms of fibroblast pathologies in patients with diabetic wounds and targeting new factors to advance diabetic wound treatment in clinic.
Optimal Skyhook and Groundhook Control for Semiactive Suspension: A Comprehensive Methodology
Authors: Díaz-Choque C. Steven , Félix-Herrán L. C. , Ramírez-Mendoza Ricardo A.
Published: December 2021

This manuscript establishes a methodology that guides the designers to develop an optimal controller for a semiactive suspension system. The methodology’s processes are generally explained and straightforwardly, so a designer can extrapolate the methodology to a specific problem. Furthermore, this research presents an optimal control strategy for a semiactive control applied to a quarter vehicle model as an example of using the methodology. A particular interest is made in the advantages of such a simple synthesis and in the compromises that must be done in skyhook and groundhook control law applications. This manuscript exposes a logical and straightforward approach for choosing the controllers’ design parameters; also, efforts must be made to express precise performance specifications and constraints in the control design. The herein methodology could be relevant in the process design for intelligent suspensions, from one‐quarter toward the entire vehicle.
CD3+T, CD4+T, CD8+T, and CD4+T/CD8+T Ratio and Quantity of γδT Cells in Peripheral Blood of HIV-Infected/AIDS Patients and Its Clinical Significance
Authors: Zhao Nange , Zhang Tingting , Zhao Yujuan , Zhang Jianping , Wang Keqiang
Published: December 2021

Objective. To investigate the quantity of CD4+T, CD4+T, CD8+T, and γδT cells in peripheral blood of HIV-infected/AIDS patients as well as to explore the possible role of CD4/CD8 ratio and γδT cells in the progression of HIV/AIDS, aimed at providing evidence for the diagnosis and treatment of AIDS. Methods. The quantity levels of CD3+T cells, CD4+T cells, CD8+T cells, and γδT cells in peripheral blood of 46 HIV-infected/AIDS patients and 30 healthy controls were detected by using flow cytometry. Results. The count of CD3+T, CD4+T, CD8+T, and γδT cells (

x
¯

±
s

, A/μl) in the peripheral blood was

1183.64
±
132.58

,

278.39
±
122.38

,

863.13
±
82.38

, and

22.53
±
1.74

in the experimental group as well as

1456.46
±
124.37

,

788.74
±
189.67

,

569.61
±
46.49

, and

10.96
±
0.28

in the control group, respectively. The

p

values of the two groups were <0.005 after the

t

-test, revealing a statistically significant difference. The proportion of CD3+T, CD4+T, CD8+T, and γδT cells in total lymphocytes in the two groups (

x
¯

±
s

, %) was

71.83
±
5.37

,

13.39
±
2.23

,

62.93
±
5.81

, and

3.67
±
0.87

in the experimental group, respectively. In the control group, the values were expressed as

66.72
±
5.48

,

42.77
±
3.38

,

31.41
±
3.62

, and

1.73
±
0.36

, respectively. After performing the

t

-test,

p

values in the two groups were <0.005 except CD3+T, with statistically significant differences. Besides, CD4/CD8 was

0.33
±
0.11

in the experimental group and

1.48
±
0.29

in the control group,

t
=
26.528
,
p
<
0.001

, exhibiting a significant statistical difference. Conclusion. HIV infection induces the activation and proliferation of CD8+T and γδT cells, contributing to the decrease of CD4+T cells, while CD8+T and γδT cells are involved in the immune response and tissue damage after HIV infection.
Some Random Fixed-Point Theorems for Weakly Contractive Random Operators in a Separable Banach Space
Authors: Benkirane Kenza , Adraoui Abderrahim EL , Marhrani El Miloudi
Published: December 2021

The aim of this paper is to prove a common random fixed-point and some random fixed-point theorems for random weakly contractive operators in separable Banach spaces. A random Mann iterative process is introduced to approximate the fixed point. Finally, the main result is supported by an example and used to prove the existence and the uniqueness of a solution of a nonlinear stochastic integral equation system.
The Adoption of Bundled Sustainable Farm and Environmental Practices by Coffee Farmers in Southwest Ethiopia
Authors: Kudama Gezahagn , Wana Hika , Dangia Mabiratu
Published: December 2021

Despite numerous efforts to introduce sustainable farm and environmental practices (SFEPs), such as pruning, soil erosion control, and water pollution abatement measures), their adoption by smallholder farmers is awfully low in Ethiopia. As a result, smallholder coffee farmers in the country remain in poverty traps even if there is room to enjoy coffee returns by doubling the yield by implementing sustainable practices. On the other hand, most previous coffee sustainability studies focus on the economic, livelihood, and poverty alleviation impact of private sustainability standard schemes. Despite the holistic advantages of the adoption of bundled SFEPs over individual adoption practices, it has been overlooked by earlier scholars in the country. In southwest Ethiopia, few farmers applied sustainable coffee farm practices (particularly pruning, stumping, the use of fertilizer, and mulching), and the yields gained by the farmers are quite low. Therefore, this study seeks to examine the factors affecting the adoption of bundled SFEPs and their intensity at the farm household level in southwest Ethiopia based on cross-sectional data obtained from 153 sampled coffee farm households for the 2019/2020 cropping season. The study results showed that the farmers’ adoption of different SFEPs depended on farm and management characteristics (total size of coffee holdings, multiple plots, remoteness of coffee farm, hired labor, and farming experience), socioeconomic variables (literacy, household size, and training), and Fairtrade coffee certification. Likewise, the intensity of SFEPs implementation is influenced by literacy and hired labor. Providing training and supplementing coffee farmers with farm equipment used for SFEPs, promoting small-scale mechanization options to address seasonal labor constraints, as well as strengthening Fairtrade organizations will facilitate the adoption of multiple SFEPs by coffee farmers in the country.
LIBRO DE RESÚMENES CONGRESO LATINOAMERICANO DE EDUCACIÓN DE RESIDENTES: LACRE 2021
Authors: MEDICA ARS
Published: December 2021

El Congreso Latinoamericano de educación de residentes (LatinAmerican Conference on Residency Education: LACRE) se realiza cada 2 años, y desde su primera versión el año 2013, ha tenido un importante impacto en la educación médica de postgrado en Chile y Latinoamérica, contribuyendo a ofrecer nuevos conocimientos y herramientas innovadoras en docencia de especialistas en medicina y otras ciencias de la salud.
Truly Man's Best Friend: Canine Cancers Drive Drug Repurposing in Osteosarcoma
Authors: Weiss Mia C. , Eulo Vanessa , Van Tine Brian A.
Published: December 2021

While metastatic osteosarcoma is rare in humans, it is the most common bone tumor found in any breed of dog. Given the genetic similarities between canine and human osteosarcomas, canine clinical trials allow for rapid testing and drug repurposing at a speed that cannot be achieved using patients with osteosarcoma.

See related article by Regan et al., p. 662
Epigenetic Silencing of 15-Hydroxyprostaglandin Dehydrogenase by Histone Methyltransferase EHMT2/G9a in Cholangiocarcinoma
Authors: Zhang Jinqiang , Chen Weina , Ma Wenbo , Song Kyoungsub , Lee Sean , Han Chang , Wu Tong
Published: December 2021

Cholangiocarcinoma (CCA) is a lethal malignancy with few therapeutic options. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) has been shown to inhibit CCA cell growth in vitro and in xenograft models. However, the role of 15-PGDH in CCA development has not been investigated and the mechanism for 15-PGDH gene regulation remains unclear. Here, we evaluated the role of 15-PGDH in CCA development by using a mouse model with hydrodynamic tail vein injection of transposase-based plasmids expressing Notch1 intracellular domain and myr-Akt, with or without co-injection of 15-PGDH expression plasmids. Our results reveal that 15-PGDH overexpression effectively prevents CCA development. Through patient data mining and experimental approaches, we provide novel evidences that 15-PGDH is epigenetically silenced by histone methyltransferase G9a. We observe that 15-PGDH and G9a expressions are inversely correlated in both human and mouse CCAs. By using CCA cells and mouse models, we show that G9a inhibition restores 15-PGDH expression and inhibited CCA in vitro and in vivo. Mechanistically, our data indicate that G9a is recruited to 15-PGDH gene promoter via protein–protein interaction with the E-box binding Myc/Max heterodimer. The recruited G9a then silences 15-PGDH gene through enhanced methylation of H3K9. Our further experiments have led to the identification of STAT4 as a key transcription factor involved in the regulation of 15-PGDH by G9a. Collectively, our findings disclose a novel G9a-15PGDH signaling axis which is importantly implicated in CCA development and progression.

Implications:

The current study describes a novel G9a-15PGDH signaling axis which is importantly implicated in CCA development and progression.
Building Tools for Machine Learning and Artificial Intelligence in Cancer Research: Best Practices and a Case Study with the PathML Toolkit for Computational Pathology
Authors: Rosenthal Jacob , Carelli Ryan , Omar Mohamed , Brundage David , Halbert Ella , Nyman Jackson , Hari Surya N. , Van Allen Eliezer M. , Marchionni Luigi , Umeton Renato , Loda Massimo
Published: December 2021

Imaging datasets in cancer research are growing exponentially in both quantity and information density. These massive datasets may enable derivation of insights for cancer research and clinical care, but only if researchers are equipped with the tools to leverage advanced computational analysis approaches such as machine learning and artificial intelligence. In this work, we highlight three themes to guide development of such computational tools: scalability, standardization, and ease of use. We then apply these principles to develop PathML, a general-purpose research toolkit for computational pathology. We describe the design of the PathML framework and demonstrate applications in diverse use cases. PathML is publicly available at www.pathml.com.
Evaluation of Transbronchial Lung Cryobiopsy Freezing Time, Biopsy Size, Histological Quality, and Incidence of Complication: A Prospective Clinical Trial
Authors: Li Yishi , Wei Jiawei , Jiang Jinyue , Ao Zhi , Yi Xianghua , Li Xian , Zhu Xuyou , Xiao Yang , Herth Felix J.F. , Guo Shuliang
Published: December 2021

Background: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. Objectives: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. Methods: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. Results: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients’ histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. Conclusion: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3–4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.
Covid-19 Impact on Macular Neovascularization and Retinal Vein Occlusion Treatment: Single-Center Experience
Authors: Vilares-Morgado Rodrigo , Madeira Carolina , Cunha Ana Maria , Falcão Manuel , Beato João , Pedrosa Ana Catarina , Penas Susana , Brandão Elisete , Falcão-Reis Fernando , Carneiro Ângela
Published: December 2021

Purpose: The aim of this study was to evaluate whether the coronavirus disease 19 (COVID-19) pandemic resulted in undertreatment and subsequent loss of visual acuity (VA) in patients with macular neovascularization (MNV) or retinal vein occlusion (RVO) regularly treated with intravitreal antivascular endothelial growth factor injections. Methods: Single-center, retrospective study of patients scheduled for treatment between March 19 and June 1, 2020, the national mandatory quarantine period. Patients’ demographics, VA, and scheduled treatment during this period were reviewed via medical records. All patients were analyzed regarding treatment attendance rates. The visual impact of COVID-19 was assessed in patients who had been treated and presented a stable VA for >6 months before the beginning of the quarantine. Results: This study included 927 eyes from 769 patients. The attendance rate increased throughout the study timeframe (p < 0.001) and correlated negatively with higher patient’s age (r = −0.142; p = 0.005). Patients with age-related macular degeneration (67.6%) had lower attendance rates (p = 0.007) and were older (p < 0.001). The visual impact analysis included 400 eyes from 325 patients. The average VA variation throughout this period was −1.7 ± 8.4 ETDRS letters and was similar in different retinal pathologies (p = 0.334). VA variation did not correlate with the number of missed treatments per patient (r = 0.100; p = 0.150). The prevalence of subretinal fluid and intraretinal fluid, as well as central retinal thickness decreased significantly throughout the study period (p values of <0.001, <0.001, and 0.032, respectively). Conclusion: The COVID-19 pandemic had a significant impact on the attendance rate of patients with MNV or RVO to their scheduled treatments, which was higher in the first week of mandatory quarantine. Nevertheless, VA did not decrease significantly during this period, with a limited VA variation regardless of primary retinal disorder and morphological parameters even improved in the eyes included in the visual impact analysis.
Methylation Status of the miR-141-3p Promoter Regulates miR-141-3p Expression, Inflammasome Formation, and the Invasiveness of HTR-8/SVneo Cells
Authors: Wu Dongcai , Shi Li , Chen Fangrong , Lin Qing , Kong Jiao
Published: December 2021

MicroRNA-141 (miR-141-3p) is upregulated in preeclampsia. This study investigated the effect of methylation of the miR-141-3p promoter on cell viability, invasion capability, and inflammasomes in vitro. The expression of miR-141-3p and methylation status of the miR-141-3p promoter were examined by RT-qPCR and pyrosequencing in villus tissues of women with spontaneous delivery (VTsd), villus tissues of women with preeclampsia (VTpe), and also in HTR-8/SVneo cells treated with a miR-141-3p inhibitor and 20 μmol/L 5-aza-2′-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor. Cell viability and invasion were evaluated by CCK-8 and transwell assays. In addition, the levels of CXCL12, CXCR4, CXCR2, MMPs, NLRP3, and ASC expression were assessed by western blotting, and IL-1β and IL-18 concentrations were assayed by ELISA. miR-141-3p expression was upregulated, and the levels of miR-141-3p promoter methylation and CXCL12, CXCR4, and CXCR2 expression were decreased in VTpe relative to VTsd. In HTR-8/SVneo cells, hypomethylation caused by 5-Aza treatment increased miR-141-3p expression, while DNA methyltransferase 3 (DNMT3) transfection decreased miR-141-3p expression. miRNA-141-3p induced NLRP3, IL-1β, and IL-18 production, decreased CXCR4, MMP, and MMP2 production, and suppressed cell growth and invasion. Furthermore, we observed that NLRP3 plays an important mediatory role in the effects of miR-141-3p described above. Decreased methylation of the miR-141-3p promoter increases miR-141-3p expression, which in turn increases NLRP3 expression, resulting in higher IL-1β and IL-18 levels and lower levels of MMP2/9 and CXCR4. We conclude that modification of the miR-141-3p promoter might be a curial mediator in preeclampsia.
Role of Different Doses of Ketamine in Postoperative Neurocognitive Function in Aged Mice Undergoing Partial Hepatectomy by Regulating the Bmal1/NMDA/NF-Κb Axis
Authors: Niu Xiaoli , Zheng Simin , Li Siyuan , Liu Hongtao
Published: December 2021

Background: The current study set out to probe the function of different doses of ketamine in postoperative neurocognitive disorder (PND) in aged mice undergoing partial hepatectomy (PH) with the involvement of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1)/n-methyl-D-aspartate (NMDA)/nuclear factor-kappa B (NF-κB) axis. Methods: First, aged mice were intraperitoneally injected with different doses of ketamine prior to surgery, followed by hepatic lobectomy. Afterward, mice cognitive function was assessed. In addition, Bmal1 mRNA expression patterns were quantified, while NMDA 2B receptor, NF-κB p65, synapsin 1, and postsynaptic density 95 (PSD95) levels were determined; the release of inflammatory factors was detected, and ionized calcium-binding adapter molecule-1 expression was measured to quantify microglia activation. In addition, Bmal1-knockout (Bmal1-KO) mice were intraperitoneally injected with a subanesthetic dose of ketamine to verify the mechanism of Bmal1 in regulating the NMDA 2B subunit (NR2B)/NF-κB axis to affect PH in aged patients. Results: After PH, hippocampal-dependent memory was impaired, and synapsin 1 and PSD95 levels were downregulated. On the other hand, PH diminished Bmal1 expression but elevated NR2B and NF-κB p65 levels and anesthetic doses of ketamine further regulated the Bmal1/NMDA/NF-κB axis. In Bmal1-KO mice, the NMDA/NF-κB axis was activated, the release of inflammatory cytokines was promoted, and hippocampus-dependent memory was impaired, which were reversed by a subanesthetic dose of ketamine. Conclusion: Altogether, findings obtained in our study indicated that a subanesthetic dose of ketamine activated Bmal1, downregulated the NMDA/NF-κB axis, and reduced inflammation and microglia activation to alleviate PND in aged mice undergoing PH.
Bronchopulmonary Dysplasia and Risk of Developmental Delay: An EPIPAGE-2 Cohort Study
Authors: Tréluyer Ludovic , Jarreau Pierre-Henri , Marchand-Martin Laetitia , Benhammou Valerie , Nuytten Alexandra , Berquin Patrick , Marret Stéphane , Pierrat Véronique , Ancel Pierre-Yves , Torchin Héloïse
Published: December 2021

Background: Overall and respiratory management of preterm children are constantly evolving, which might have changed both the pathophysiology and neurodevelopmental consequences of bronchopulmonary dysplasia (BPD). Objectives: The objective of this study is to determine whether the previously shown association between BPD and risk of developmental delay persists. Methods: The study population was children born before 32 weeks’ gestation from the French prospective cohort EPIPAGE-2. The exposure was BPD assessed at 36 weeks’ postmenstrual age. The main outcome was risk of developmental delay defined by an Age & Stages Questionnaires (ASQ) score below threshold at 24 months’ corrected age. Results: The analyzed population included 2,706 children. Among those with available ASQ score, 196/1,587 had BPD and 671/1,587 had an ASQ score below threshold. BPD was associated with an ASQ score below threshold (odds ratio 1.52, 95% confidence interval 1.11–2.08; p = 0.008). Conclusions: BPD was strongly associated with risk of developmental delay.
Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication
Authors: Baylis Simon , Costa-Pinto Rahul , Hodgson Sarah , Bellomo Rinaldo , Baldwin Ian
Published: December 2021

Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.
Deferring Nail Mycological Sampling during the COVID-19 Pandemic: Recommendations from a Multidisciplinary Panel of Nail Specialists
Authors: Lipner Shari R. , Ghannoum Mahmoud , Hinshaw Molly A. , Rich Phoebe , Ruben Beth S. , Vlahovic Tracey C. , Scher Richard K.
Published: December 2021

Onychomycosis is the most common nail condition seen in clinical practice, with significant impact on quality of life. Clinical examination alone is insufficient for accurate diagnosis, but mycological confirmation can be challenging during the COVID-19 pandemic. In this letter, a multidisciplinary panel of dermatologists, a podiatrist, dermatopathologists, and a mycologist, discuss considerations for mycological sampling during the pandemic.
Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis
Authors: Long Millie D. , Cohen Russell D. , Smith Timothy W. , DiBonaventura Marco , Gruben David , Bargo Danielle , Salese Leonardo , Quirk Daniel
Published: December 2021

Background: Biologic therapies are often used in patients with ulcerative colitis (UC) who are nonresponsive to conventional treatments. However, nonresponse or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with UC in the USA. Methods: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with UC initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N = 1,291], infliximab [N = 810], golimumab [N = 127], and vedolizumab [N = 103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred USD 20,106 higher total UC-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration = 112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with UC initiating biologic therapies. Suboptimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.
Efficacy of Individualized Preventive Treatment of Patients with Severe Hemophilia A Guided by Multiple Clinical Parameters and Pharmacokinetics
Authors: Wang Youqun , Yang Qiao , Zheng Liangda , Wang Xianting , Jiang Wenhua , Lu Lijun , Yan Lixia , Zhang Miaomiao , Chen Lili
Published: December 2021

Objective: The objective of the study was to investigate the effect of multiple clinical parameters (age, weight, blood types, and bleeding types) on FVIII pharmacokinetic parameters (PK parameters) in adult patients with severe hemophilia A (SHA), draw up individualized preventive treatment plans, and observe clinical efficacy. Methods: Forty SHA patients treated in our hospital from January 2018 to May 2019 were enrolled, with their age, weight, blood types, bleeding types, and PK parameters measured to analyze the effects of clinical parameters on PK parameters. Individualized preventive treatment was developed, and patients were followed up for 1 year. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), and annual FVIII dosage were observed and compared before and after treatment. Results: Weight, blood types, and bleeding types could affect the PK parameters of FVIII. A prophylaxis plan was formulated under the guidance of FVIII half-life. After 1 year of follow-up, the mean ABR dropped from 36.54 to 4.06, decreased by 88.9%, the mean AJBR dropped from 28.36 to 2.75, decreased by 90%, and annual FVIII dosage increased by 47%. The dosage of FVIII in 8 patients after was less than that before prophylaxis, and the average half-life time of these 8 patients was 13.32 h. Conclusions: (1) Weight, blood types, and bleeding types of adult SHA patients could affect FVIII half-life. As body mass index increased, FVIII half-life was significantly prolonged. The FVIII half-life of patients with type O blood was significantly shorter than those with other blood types, and the FVIII half-life of knee joint bleeding was conspicuously shorter than those of elbow joint bleeding. (2) Individualized preventive treatment could markedly reduce the number of bleeds. For patients with a long half-life period, the total annual FVIII dosage could be reduced to achieve bleeding prevention.
Low Shear Stress at Baseline Predicts Expansion and Aneurysm-Related Events in Patients With Abdominal Aortic Aneurysm
Authors: Bappoo Nikhilesh , Syed Maaz B.J. , Khinsoe Georgia , Kelsey Lachlan J. , Forsythe Rachael O. , Powell Janet T. , Hoskins Peter R. , McBride Olivia M.B. , Norman Paul E. , Jansen Shirley , Newby David E. , Doyle Barry J.
Published: December 2021

Background:

Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events.

Methods:

Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate.

Results:

We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43–54 mm) and median follow-up of 914 (interquartile range, 670–1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experienced a higher number of aneurysm-related events (44%) compared with medium (0.4–0.6 Pa; 27%) and high (>0.6 Pa; 29%) shear stress groups (
P
=0.010). This association was independent of known risk factors (adjusted hazard ratio, 1.72 [95% CI, 1.08–2.73];
P
=0.023). Low shear stress was also independently associated with AAA expansion rate (β=+0.28 mm/y [95% CI, 0.02–0.53];
P
=0.037).

Conclusions:

We show for the first time that low shear stress (<0.4 Pa) at baseline is associated with both AAA expansion and future aneurysm-related events. Aneurysms within the lowest tertile of shear stress, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.
Abstract 103: Obesity Paradox in Heart failure- Are African Americans Affected?
Authors: Wariboko Minaba A , Taylor Kimberli , Okafor Chimalum , Mustapha Taopheeq , Nwazue Victor , Figueroa Karem , Mai Chin , Odiete Oghenerukevwe , Sawyer Douglas B , Okafor Henry
Published: December 2021

Background
- Obesity is a major risk factor for heart failure. However, many studies have shown that obesity is paradoxically associated with better outcomes in those with chronic heart failure (HF). Initially thought to occur only in those with left ventricular systolic dysfunction (LVSD), recent studies such as CHARM and I-PRESERVE have described the same phenomenon in those with HF with preserved ejection fraction (HFpEF). It is also known that minorities have the highest rates of obesity in the United States, yet no major studies have included a large enough sample (>10% minority representation) to study this relationship. Thus we propose to examine the relationship of different weight categories to HF outcomes in patients with LVSD (45%) utilizing a minority cohort.

Methods
- Outcomes (HF admissions & cardiac admissions, non-cardiac admissions, and emergency room visits) were assessed for162 HF patients with documentation of body mass index (BMI) and ejection fraction from the Meharry Heart Failure Registry (a registry composed of 80% African Americans and Hispanics). The cohort was evenly divided by EF into HFpEF versus LVSD. Utilizing the Center for Disease Control definitions, 5 categories for BMI were defined: 40.0. ANOVA was applied to test for possible differences among BMI groups and outcomes.

Results
- There was a trend towards a paradoxical relationship noted between BMI and outcome in males with HFpEF when looking at all-cause readmissions (p<0.0606). This same relationship was noted between BMI and outcome in women with HFpEF when looking at the all-cause emergency room visits (p<0.0677). However, we failed to find a significant difference across BMI categories and outcome for those with LVSD.

Conclusion
- Our study suggests that irrespective of race, there is a paradoxical relationship noted between BMI and outcome for both men and women with HFpEF. However, contrary to current literature, we failed to find the same relationship in minority patients with LVSD. This may be due to the small sample size hence a larger prospective study of this group is warranted.
Abstract 116: Is There Gender Disparity in the Use of Drug Eluting Stents after Acute Myocardial Infarction?
Authors: Iyanoye Adeyemi , Gandhi Sampada K , Zang Edith , Cabrera Javier , Cosgrove Nora M , Moreyra Abel E , Kostis John B ,   for the Myocardial Infarction Data Acquisition System (MIDAS) study group
Published: December 2021

Background:
Women are less likely than men to have cardiac catheterization and percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). It is unclear whether such gender disparity extends to the implantation of the type of coronary stent (bare metal stent (BMS) versus drug eluting stent (DES)) after AMI.

Methods:
We examined coronary stent implantation by type within 30 days of AMI in 33,748 patients admitted to non-federal hospitals in New Jersey using a statewide database. Data from 2003 through 2009 in the Myocardial Infarction Data Acquisition System (MIDAS) were used to identify patients with first episode of AMI and single type (BMS versus DES) of coronary stent implantation after the AMI. Multivariate logistic regression was used to analyze the differences by gender after adjustment for age, race, insurance, site of MI, pre-or post discharge stent implantation, and co-morbidities.

Results:
Coronary stent implantations after AMI were stratified by placement periods into: at index of AMI admission, n=16,719; within 2 days, n=22,019; within one week, n=31,618; and within 30 days of index AMI, n=33,748. In 2003, the use of BMS in women declined from 76% (386 of 507) to 68% (986 of 1454) from index AMI to 30 days, and in men from 79% (930 of 1181) to 70% (2017 of 2863). The use of DES in women increased from 24% (121 of 507) at index AMI to 32% (468 of 1454) at 30 days, and in men from 21% (251 of 1181) to 30% (846 of 2863). After adjustment for covariates, in 2003, women were more likely to receive DES than men within 2 days of the index AMI [Odds Ratio (OR): 1.37; 95% Confidence Interval (CI): (1.10, 1.70); p = 0.005], within 1 week of index AMI [OR: 1.21; CI (1.03,1.41); p= 0.02], within 30 days of index AMI [OR: 1.20; CI (1.03, 1.39); p = 0.02)]. In 2004 through 2009, both men and women had higher proportion of DES than BMS implantation after AMI. However, there was no significant gender difference in stent type for these years, except in 2006 when DES implants (received within 1 week and 30 days of index AMI) were significantly more frequent in women compared to men.

Conclusion:
Although women are less likely to receive PCI compared to men after AMI, there is generally no gender difference in the proportion of DES versus BMS received in contemporary years.
Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis
Authors: Al Rifai Mahmoud , Blaha Michael J. , Nambi Vijay , Shea Steven J.C. , Michos Erin D. , Blumenthal Roger S. , Ballantyne Christie M. , Szklo Moyses , Greenland Philip , Miedema Michael D. , Nasir Khurram , Rotter Jerome I. , Guo Xiuqing , Yao Jie , Post Wendy S. , Virani Salim S.
Published: December 2021

Background:

The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up.

Methods:

We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes.

Results:

We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32–3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01–2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06–2.33).

Conclusions:

Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.
Uncrowded Hypervolume-Based Multiobjective Optimization with Gene-Pool Optimal Mixing
Authors: Maree S.C. , Alderliesten T. , Bosman P.A.N.
Published: December 2021

Domination-based multiobjective (MO) evolutionary algorithms (EAs) are today arguably the most frequently used type of MOEA. These methods, however, stagnate when the majority of the population becomes nondominated, preventing further convergence to the Pareto set. Hypervolume-based MO optimization has shown promising results to overcome this. Direct use of the hypervolume, however, results in no selection pressure for dominated solutions. The recently introduced Sofomore framework overcomes this by solving multiple interleaved single-objective dynamic problems that iteratively improve a single approximation set, based on the uncrowded hypervolume improvement (UHVI). It thereby however loses many advantages of population-based MO optimization, such as handling multimodality. Here, we reformulate the UHVI as a quality measure for approximation sets, called the uncrowded hypervolume (UHV), which can be used to directly solve MO optimization problems with a single-objective optimizer. We use the state-of-the-art gene-pool optimal mixing evolutionary algorithm (GOMEA) that is capable of efficiently exploiting the intrinsically available grey-box properties of this problem. The resulting algorithm, UHV-GOMEA, is compared with Sofomore equipped with GOMEA, and the domination-based MO-GOMEA. In doing so, we investigate in which scenarios either domination-based or hypervolume-based methods are preferred. Finally, we construct a simple hybrid approach that combines MO-GOMEA with UHV-GOMEA and outperforms both.
Dead-Ends and New Directions
Authors: Gomes Jean Francesco A.L.
Published: December 2021

The aim of this article is to investigate how Abraham Kuyper and some late neo-Calvinists have addressed the doctrine of creation in light of the challenges posed by evolutionary scientific theory. I argue that most neo-Calvinists today, particularly scholars from the Vrije Universiteit Amsterdam (VU), continue Kuyper’s legacy by holding the core principles of a creationist worldview. Yet, they have taken a new direction by explaining the natural history of the earth in evolutionary terms. In my analysis, Kuyper’s heirs at the VU today offer judicious parameters to guide Christians in conversation with evolutionary science, precisely because of their high appreciation of good science and awareness of the nonnegotiable elements that make up the orthodox Christian narrative.
Does Theology Belong in the University? Schleiermacherian Reflections from an Australian Context
Authors: Myers Ben
Published: December 2021

This article argues that theology belongs in the university not because of its relationship to the other disciplines but because of its relationship to the church. It discusses Schleiermacher’s understanding of theology as a practical science oriented towards Christian leadership in society. It argues that Schleiermacher’s account provides an illuminating perspective on the history of academic theology in Australia. Theology belongs in the university not for any internal methodological reasons but because of specific contextual conditions in societies like Australia where Christianity has exerted a large historical influence. The article concludes by arguing that the ecclesial orientation of university theology is compatible with the aims of public theology, given that service to the Christian community is a means by which the common flourishing of society can be promoted.
Datio ob rem and datio ob causam – the purpose of performance in Roman law
Authors: Sobczyk Marek
Published: December 2021

This paper deals with one of the most important unjustified enrichment claims in Roman law, the condictio causa data causa non secuta concentrating on the crucial issue of the purpose of performance. In Roman law the purpose of performance was denoted by the term res as a part of datio ob rem (giving for a purpose) or causa as a part of datio ob causam (giving on a basis); however, in the secondary literature there is a dispute over the exact meaning of those terms and their mutual relationship. Some scholars identify res with the counter-performance which was expected from the recipient. Others consider this interpretation of res as too narrow, because datio ob rem was applied not only where the giver expected counter-performance but also when he tried to achieve other goals, including that not associated with the recipient’s behaviour at all. In order to find a solution to that long-lasting dispute the article analyses typical examples of cases described in the sources as datio ob rem or datio ob causam.
Income and Employment Potential for Youth and Women in Tanzania’s Micro, Small and Medium Tourism Enterprises
Authors: Aikaeli Jehovaness
Published: December 2021

This paper looks into the income and employment potential for youth and women in tourism micro, small and medium enterprises (MSME s). The survey data collected from seven regions of Tanzania during September–October 2018 is used. Analyses are focused on two main issues: estimation of determinants of income in tourism MSME s and implications for youth and women employment; and examination of perceived youth employment potential in the tourism industry of Tanzania. Quantile regression approach is applied in estimation of determinants of income; and the ratios of perceived employment potential and constraints to the youth employment are analysed. The findings demonstrate earning as the leading employment incentive and is determined by education of the owners of MSME s, inter alia. Larger proportion of enterprises owned by youth than those owned by elderly people are informal, which has a negative bearing on incomes of youth. Women and youth owned enterprises are constrained in terms of credit access. Policy implications include the need to address the social problem of gender inequality, enhancing requisite skills and knowledge for tourism sector professions, and formalisation and scaling up of credit access for the youth and women.
Hygrocybe rimosa (Hygrophoraceae, Agaricales), a new poisonous species from southern China
Authors: WANG CHAO-QUN , ZHANG MING , LI HAI-JIAO , HUANG HAO , DENG WANG-QIU , LI TING , LUO DE-JUN , LI TAI-HUI
Published: December 2021

Hygrocybe rimosa, a new poisonous species belonging to subg. Hygrocybe, is described from southern China with both phylogenetic and morphological data. This species can cause nausea, vomiting, and abdominal pain. Morphologically, it is characterized by its orange to red and fibrillose pileus, irregularly split pileus margin, free, broad to ventricose, white lamellae, and subglobose to oblong basidiospores measuring (7)7.5–11 ×5–8(8.5) μm. Phylogenetically, analyses based on the internal transcribed spacer (ITS) region and the nuclear ribosomal RNA large subunit (LSU) indicate that H. rimosa is a member of subg. Hygrocybe. Ecologically, the new taxon usually grows in subtropical grasslands.