bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Annealing on the Structure and Electric Performance of Polypropylene Films
Authors: Dai Xiying , Xing Zhaoliang , Yang Wei , Zhang Chong , Li Fei , Chen Xin , Li Chen , Zhou Jianjun , Li Lin
Published: November 2022

Biaxially oriented polypropylene (BOPP) and uniaxially oriented polypropylene (UOPP) films were annealed. The effect of annealing temperature (Ta) on dielectric strength was studied. The electric breakdown strength (Eb) of BOPP and UOPP films changes in a quite different trend with the annealing process. Eb of BOPP films decreases with the increase in Ta, whereas Eb of UOPP films increases first and then decreases with Ta. The structural changes during annealing were investigated. The crystallinity rises with Ta, while the orientation degree and Eb show a similar trend with Ta. Although the crystallinity and crystal structure can affect Eb of polypropylene films, the orientation of chain segments has a much larger correlation with Eb. Our results indicate that the deterioration of the metallized BOPP film capacitor may originate from the orientation degree decrease of chain segments after experiencing high temperature.
Next-Day Medical Activities Recommendation Model with Double Attention Mechanism Using Generative Adversarial Network
Authors: Li Wei , Yang Jinzhao , Min Xin
Published: November 2022

Medical activities recommendation is a key aspect of an intelligent healthcare system, which can assist doctors with little clinical experience in clinical decision making. Medical activities recommendation can be seen as a kind of temporal set prediction. Previous studies about them are based on Recurrent Neural Network (RNN), which does not incorporate personalized medical history or differentiate between the impact of medical activities. To address the above-given issues, this paper proposes a Next-Day Medical Activities Recommendation (NDMARec) model. Specifically, our model firstly proposes an inpatient day embedding method based on soft-attention which balances the impact of different medical activities to get a joint representation of medical activities that occurred within the same day. Then, a fusion module is designed to combine features of inpatient day and medical history to achieve personalization. These features are learned by the self-attention mechanism that solves the long-term dependency problem of RNNs. Last, adversarial training is introduced to improve the generalization ability of our model. Extensive experiments on a real dataset from a hospital are conducted to show that NDMARec outperformed both classical and state-of-the-art methods.
Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease
Authors: Yang Bing , Yang Xi , Tan Xumei , Lu Liqing , Fan Wei , Barbier-Torres Lucía , Steggerda Justin , Liu Ting , Yang Heping
Published: November 2022

The pathogenesis of NAFLD is complex and diverse, involving multiple signaling pathways and cytokines from various organs. Hepatokines, stellakines, adipokines, and myokines secreted by hepatocytes, hepatic stellate cells, adipose tissue, and myocytes play an important role in the occurrence and development of nonalcoholic fatty liver disease (NAFLD). The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) contributes to the progression of NAFLD by mediating liver inflammation, immune response, hepatocyte death, and later compensatory proliferation. In this review, we first discuss the crosstalk and interaction between hepatokines, stellakines, adipokines, and myokines and NF-κB in NAFLD. The characterization of the crosstalk of NF-κB with these factors will provide a better understanding of the molecular mechanisms involved in the progression of NAFLD. In addition, we examine new expert management opinions for NAFLD and explore the therapeutic potential of silymarin in NAFLD/NASH.
The Effectiveness of Aloe Vera on Relief of Irritation and Nipple Pain in Lactating Women: Systematic Review and Meta-Analysis
Authors: Maleki Azam , Youseflu Samaneh
Published: November 2022

Background. Aloe vera is one of the herbal products with anti-inflammatory, antioxidant, moisturizing, bactericidal, anti-viral, and anti-fungal effects that were used to relieve pain and irritation. The aim of the current systematic review and meta-analysis is to determine the effect of Aloe vera on the relief of irritation and nipple pain in lactating women. Methods. A search was carried out in four English electronic databases including Scopus, Embase, PubMed, and Web of Science until November 2021. All clinical trials that assessed the effect of Aloe vera on the relief of irritation and nipple pain in lactating women were included. The study’s risk of bias was assessed using the Cochrane risk of bias checklist. Study heterogeneity was determined using the I2 statistic and publication bias using Begg’s and Egger’s tests. Results of the random-effects meta-analysis were presented using standard mean difference (SMD) with 95% confidence intervals (CIs). Data were analyzed using STATA software version 16 MP. Results. In total, 7 articles with 1670 subjects were included in the meta-analysis. Overall, we found a positive impact of Aloe vera on reducing breast pain (pooled SMD= −0.45; CI= −0.83, −0.07,Pvalue <0.02) and irritation (pooled SMD= −0.48; CI= −0.64, −0.32,Pvalue<0.001) in lactating women. There is a high heterogeneity among pain studies (I2= 86%) but was low within irritation studies (I2= 26%). Conclusion. Our result showed that Aloe vera can be considered a choice for relieving breast pain or irritation in lactating women compared with routine care or another treatment. Considering the limited number of studies conducted on this topic and the low sample size, future studies with a larger sample will be required to draw better conclusions.
Evaluation of Data Extracted from Floor Plans for Apartment Complex Remodeling
Authors: Shin Dongik , Ryu Hyeongmin , Kim Jeeyeop , Kim Jinyoung
Published: November 2022

South Korea has witnessed an increasing social demand for housing supply due to rapid urban population growth from the 1950s through the 1970s. At least two million houses have been in use for 30 years or more since the implementation of policies related to the mass production of apartment houses 20–30 years ago. Methods for improving the aging of domestic apartment houses and their living environment are reconstruction and remodeling, and the government has been encouraging remodeling by easing laws and regulations related to it. During the early stages of a typical remodeling project, many candidate floor plans arise in the process of finalizing the floor plan, resulting in significant time consumption in the iterative process for reviews and revisions. Extracting quantitative indicators by comparing floor plans before and after remodeling at the initial design stage and comparing the indicators of the target complex with the existing case can facilitate a more time‐efficient and economical decision‐making process. In this study, quantitative indicators were extracted from floor plans by applying a structural evaluation program for remodeling of apartment housing at five existing domestic apartment complexes (nine buildings in total), and a detailed comparative analysis was conducted. Evaluated indices included variations of floor area, load‐bearing wall, nonbearing wall, slab, weight, area moment of inertia, torsional resistance, and visualization of removed, remaining, and new bearing walls. The proposed method can continuously accumulate data from domestic apartment house remodeling projects and accelerate the process by shortening the time required for final decision‐making in future remodeling projects.
Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies
Authors: Tantawy Shady I. , Sarkar Aloke , Hubner Stefan , Tan Zhi , Wierda William G. , Eldeib Abdelraouf , Zhang Shuxing , Kornblau Steven , Gandhi Varsha
Published: November 2022

Purpose:

Several MCL-1 inhibitors (MCL-1i), including AMG-176 and AZD5991, have shown promise in preclinical studies and are being tested for the treatment of hematologic malignancies. A unique feature of these agents is induction and stability of Mcl-1 protein; however, the precise mechanism is unknown. We aim to study the mechanism of MCL-1i–induced Mcl-1 protein stability.

Experimental Design:

Using several B-cell leukemia and lymphoma cell lines and primary chronic lymphocytic leukemia (CLL) lymphocytes, we evaluated molecular events associated with Mcl-1 protein stability including protein half-life, reverse-phase protein array, protein–protein interaction, phosphorylation, ubiquitination, and de-ubiquitination, followed by molecular simulation and modeling.

Results:

Using both in vivo and in vitro analysis, we demonstrate that MCL-1i–induced Mcl-1 protein stability is predominantly associated with defective Mcl-1 ubiquitination and concurrent apoptosis induction in both cell lines and primary CLL subjects. These MCL1i also induced ERK-mediated Mcl-1Thr163 phosphorylation, which partially contributed to Mcl-1 stability. Disruption of Mcl-1:Noxa interaction followed by Noxa degradation, enhanced Mcl-1 de-ubiquitination by USP9x, and Mule destabilization are the major effects of these inhibitors. However, unlike other BH3 proteins, Mule:Mcl-1 interaction was unaffected by MCL-1i. WP1130, a global deubiquitinase (DUB) inhibitor, abrogated Mcl-1 induction reaffirming a critical role of DUBs in the observed Mcl-1 protein stability. Further, in vitro ubiquitination studies of Mcl-1 showed distinct difference among these inhibitors.

Conclusions:

We conclude that MCL-1i blocked Mcl-1 ubiquitination via enhanced de-ubiquitination and dissociation of Mcl-1 from Noxa, Bak and Bax, and Mule de-stabilization. These are critical events associated with increased Mcl-1 protein stability with AMG-176 and AZD5991.
Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine
Authors: Asleh Karama , Lluch Ana , Goytain Angela , Barrios Carlos , Wang Xue Q. , Torrecillas Laura , Gao Dongxia , Ruiz-Borrego Manuel , Leung Samuel , Bines José , Guerrero-Zotano Ángel , García-Sáenz Jose Ángel , Cejalvo Juan Miguel , Herranz Jesus , Torres Roberto , Haba-Rodriguez Juan de la , Ayala Francisco , Gómez Henry , Rojo Federico , Nielsen Torsten O. , Martin Miguel
Published: November 2022

Purpose:

Predictive biomarkers for capecitabine benefit in triple-negative breast cancer (TNBC) have been recently proposed using samples from phase III clinical trials, including non-basal phenotype and biomarkers related to angiogenesis, stroma, and capecitabine activation genes. We aimed to validate these findings on the larger phase III GEICAM/CIBOMA clinical trial.

Experimental Design:

Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using a 164-gene NanoString custom nCounter codeset measuring mRNA expression. A prespecified statistical plan sought to verify the predictive capacity of PAM50 non-basal molecular subtype and tested the hypotheses that breast tumors with increased expression of (meta)genes for cytotoxic cells, mast cells, endothelial cells, PDL2, and 38 individual genes benefit from adjuvant capecitabine for distant recurrence-free survival (DRFS; primary endpoint) and overall survival.

Results:

Of the 876 women enrolled in the GEICAM/CIBOMA trial, 658 (75%) were evaluable for analysis (337 with capecitabine and 321 without). Of these cases, 553 (84%) were profiled as PAM50 basal-like whereas 105 (16%) were PAM50 non-basal. Non-basal subtype was the most significant predictor for capecitabine benefit [HRcapecitabine, 0.19; 95% confidence interval (CI), 0.07–0.54; P < 0.001] when compared with PAM50 basal-like (HRcapecitabine, 0.9; 95% CI, 0.63–1.28; P = 0.55; Pinteraction<0.001, adjusted P value = 0.01). Analysis of biological processes related to PAM50 non-basal subtype revealed its enrichment for mast cells, extracellular matrix, angiogenesis, and features of mesenchymal stem-like TNBC subtype.

Conclusions:

In this prespecified correlative analysis of the GEICAM/CIBOMA trial, PAM50 non-basal status identified patients with early-stage TNBC most likely to benefit from capecitabine.
Drug-Induced Liver Injury from Herbal Liver Detoxification Tea
Authors: Niazi Bilal , Ahmed Kareem , Ahmed Mohamed , Ali Saad , Song Kunchang , Elias Sameh
Published: November 2022

The increasing consumption of unregulated herbal and dietary supplements has presented clinicians with new challenges in assessing and managing acute liver injury. Patients may present in various ways ranging from asymptomatic transaminitis to acute liver failure. Several natural products have been found to mitigate drug-induced liver injury, which has led to the creation of numerous registries to outline all its aspects further. We describe the case of a 36-year-old female who developed a clinically significant acute liver injury with a cholestatic pattern due to an over-the-counter herbal liver detox tea. This is the first case reported of a hepatotoxic effect from any of these compounds or ingredients in the detox tea: burdock root, stinging nettle leaf, cleavers herb, dandelion root, lemon peel, and lemon myrtle leaf (Backhousia citriodora). Idiosyncratic drug-induced liver injury (DILI) remains poorly understood; however, recognizing potential toxins is imperative to understanding toxicogenomics and identifying those at risk.
Supraglottic NUT Carcinoma: A Case Report and Literature Review
Authors: Higashino Masaaki , Kinoshita Ichita , Kurisu Yoshitaka , Kawata Ryo
Published: November 2022

Nuclear protein of the testis (NUT) carcinoma is a very rare cancer that occurs in relatively young patients. In this study, we experienced a case of laryngeal NUT carcinoma that followed a rapid course. A 22-year-old woman was diagnosed with supraglottic squamous cell carcinoma, cT3N2bM0. She underwent chemoradiotherapy (CRT) (total dose, 70 Gy; 2 Gy × 35 Fr; 80 mg/m2 every 3 weeks with CDDP) as a curative treatment and achieved a complete response. However, 3 weeks after the completion of CRT, she presented to the outpatient clinic complaining of abdominal pain. Magnetic resonance imaging revealed a huge neoplastic lesion in the right ovary. Abdominal right adnexal resection plus partial retreatment was performed. The pathology of ovarian tumor was poorly differentiated squamous cell carcinoma, and NUT protein was positive. The laryngeal carcinoma was also positive for NUT protein; therefore, we diagnosed ovarian tumor is metastasis from supraglottic carcinoma. Peritoneal dissemination was observed in the early postoperative period. She was refractory to subsequent chemotherapy and had a rapid progression. Subsequently, CT showed further thickening of the peritoneum, increased ascites, and increased metastases. She died 32 weeks after initial diagnosis and 14 weeks after abdominal surgery. NUT carcinoma is difficult to diagnose without suspicion. Therefore, the possibility of NUT carcinoma should be considered in young patients with laryngeal carcinoma.
Collagen IV and Podocyte-Related Gene Variants in Patients with Concurrent IgA Nephropathy and Thin Basement Membrane Nephropathy
Authors: Xu Hua , Yu XueWen , Li Yun , Huang ZhongHua , Zhang Lu , Min QinQin , Bi JiaXin , Li ZhenGuo , Liu LingYun , Liang YingYing , Xu ZhouWen , Sun HuiLi , Yang ShuDong , Shao MuMin
Published: November 2022

Introduction: IgA nephropathy is the most common primary glomerulonephritis among adults in clinic. Thin basement membrane nephropathy is often underestimated or even omitted if it coincides with IgA nephropathy. Therefore, it is necessary to study the epidemiological, clinical, and molecular characteristics of the concurrence of this entity. Methods: Eight patients with concurrent IgA nephropathy and thin basement membrane nephropathy (IgA-T) were retrospectively analyzed based on their clinicopathological characteristics. Genetic analysis was performed using whole-exome sequencing and Sanger’s sequencing. Data of the patients with IgA nephropathy and normal basement membrane (IgA-N) and variants in the local in-house database were used as controls. All candidate variants were assessed in silico. Results: The clinical manifestations of patients with IgA-T were hematuria, proteinuria, and renal insufficiency. Histopathological analysis showed mild mesangial hyperplasia, focal segmental glomerulosclerosis, podocyte activation, and foot process fusion. Crescent was rarely seen. COL4A and/or podocyte cytoskeleton and mitochondria-related gene variants were detected in seven IgA-T patients. Three patients exhibited pathogenic variants of COL4A, including a new variant. All IgA-T and one IgA-N patient possessed ITGB4 and/or PLEC variants, but there was no corresponding genotype-phenotype relationship. Six patients possessed other podocyte cytoskeleton and mitochondria-related gene variants such as NPHS2, SRGAP1, MYO1E, MYO1C, WT1, and COQ9, which were first reported in patients with IgA-T and were not in controls. Altogether, there were no significant differences in the degrees of proteinuria, serum creatinine, and eGFR during the follow-up period of 5–10 years, but there was a significant difference in the degree of proteinuria between IgA-T patients with podocyte-related gene variants and IgA-N patients. In the IgA-T group, patients with podocyte-related gene variants seemed predisposed to progress than patients without those variants, with higher proteinuria and serum creatinine and reduced eGFR. Conclusion: Concurrent thin basement membrane nephropathy and/or heterozygous COL4A gene pathogenic variants do not necessarily predict the short-term progress of sporadic IgA nephropathy in adults. Predisposition factors for this disease progression should be considered for detecting the variants of COL4A and podocyte cytoskeleton and mitochondria-related genes simultaneously, which also manifests the complexity and heterogeneity of IgA nephropathy with concurrent thin basement membrane nephropathy.
Urinary Immunoglobulin G Is Associated with Deep and Infratentorial Cerebral Microbleeds in Stroke Patients
Authors: Komatsu Teppei , Kida Hiroyuki , Ozawa Masakazu , Mimori Masahiro , Kokubu Tatsushi , Takahashi Junichiro , Kurihara Sumire , Maku Takahiro , Motegi Haruhiko , Takahashi Maki , Shiraishi Tomotaka , Nakada Ryoji , Kitagawa Tomomichi , Sato Takeo , Takatsu Hiroki , Sakai Kenichiro , Umehara Tadashi , Omoto Shusaku , Murakami Hidetomo , Mitsumura Hidetaka , Yokoo Takashi , Iguchi Yasuyuki
Published: November 2022

Background: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. Methods: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. Results: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776–6.818, p < 0.001; OR 3.415, 95% CI: 1.863–6.258, p < 0.001). Conclusions: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.
Deliberation on Deferred Cytoreductive Nephrectomy and Postoperative Treatment for Advanced Renal Cell Carcinoma: A Case Report
Authors: Nakagawa Takuya , Kawasaki Yoshihide , Sato Satoko , Katayama Hiromichi , Satake Yohei , Shimada Shuichi , Sato Takuma , Kawamorita Naoki , Yamashita Shinichi , Mitsuzuka Koji , Kohyama Atsushi , Ishida Masaharu , Ohtsuka Hideo , Unno Michiaki , Ito Akihiro
Published: November 2022

In a rare case, free from systemic therapy, deferred cytoreductive nephrectomy was implemented in treating an advanced renal cell carcinoma with liver, lung, and splenic colon metastases. A 59-year-old man diagnosed with advanced renal cell carcinoma underwent deferred cytoreductive nephrectomy due to a partial response to systemic treatment after a period of 1 year. After the surgery, no additional treatment was implemented. Furthermore, after 10 months, the patient had no recurrence of renal cell carcinoma. Through a review of this case and deferred cases in the current literature, we could emphasize the importance of image evaluation and pathological findings as an indication for surgery and subsequent treatment options. However, there is room for debate with regards to the indications for deferred cytoreductive nephrectomy as well as a therapeutic strategy after the surgery. This report discusses the significance of deferred cytoreductive nephrectomy in terms of prognosis and quality-of-life improvement in advanced renal cancer.
Long-Term Outcomes of Living-Related Kidney Donation for Alport Syndrome Spectrum: A Propensity Score-Matched Analysis
Authors: Oto Ozgur Akin , Safak Seda , Mirioglu Safak , Yelken Berna , Velioglu Arzu , Dirim Ahmet Burak , Guller Nurana , Yildiz Abdulmecit , Ersoy Alparslan , Turkmen Aydin , Yazici Halil , Lentine Krista L. , Caliskan Yasar
Published: November 2022

Introduction: Data to guide the evaluation of living-related donor candidates for kidney transplant recipients with Alport syndrome (AS) spectrum are limited. We aimed to examine a cohort of living-related donors to recipients with AS and compare their outcomes with a control group to improve understanding of the clinical course and outcomes of living donation in this context. Methods: Living donors (LDs) of AS recipients and propensity score-matched control LDs without any family history of AS (control group) were followed for major cardiac events, death, post-donation estimated glomerular filtration rate (eGFR), and proteinuria. Results: There were 31 LDs (48.4% male), in whom relationship to AS recipient included mother (45.2%), father (32.3%), sibling (16.1%), grandparent (3.2%), and uncle (3.2%). Long-term outcomes over 10.0 (IQR, 3.0–15.0) years were evaluated in 25 and 25 LDs from study and control groups, respectively. During follow-up, 5 LDs (20.0%) in study group developed major cardiac event (acute coronary ischemia [n = 4] and severe congestive heart failure [n = 1]) after 5.5 (IQR, 4.5–10.3) years, whereas only 2 (8.0%) LDs in control group developed major cardiac events (p = 0.221). New-onset hypertension was higher in study group (56.0%) compared to the control group (16.0%) (p = 0.003). Three donors in study and 2 donors in control group who developed new-onset hypertension died during follow-up (p = 0.297). Major cardiac event rate was significantly higher in donors who developed hypertension after donation (0 vs. 28.0%, p < 0.001). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.558 and p = 0.120, respectively). Discussion/Conclusion: Although the risk of kidney disease can be minimized by careful donor evaluation, our findings suggest that hypertension risk after the donation is higher than expected in related donors of recipients with AS.
EASO and EFAD Position Statement on Medical Nutrition Therapy for the Management of Overweight and Obesity in Children and Adolescents
Authors: Hassapidou Maria , Duncanson Kerith , Shrewsbury Vanessa , Ells Louisa , Mulrooney Hilda , Androutsos Odysseas , Vlassopoulos Antonis , Rito Ana , Farpourt Nathalie , Brown Tamara , Douglas Pauline , Ramos Sallas Ximena , Woodward Euan , Collins Clare
Published: November 2022

Introduction: This position statement on medical nutrition therapy in the management of overweight or obesity in children and adolescents was prepared by an expert committee convened by the European Association for the Study of Obesity (EASO) and developed in collaboration with the European Federation of the Associations of Dietitians (EFAD). Methods: It is based on the best evidence available from systematic reviews of randomized controlled trials on child and adolescent overweight and obesity treatment and other relevant peer-reviewed literature. Results: Multicomponent behavioural interventions are generally considered to be the gold standard treatment for children and adolescents living with obesity. The evidence presented in this position statement confirms that dietary interventions can effectively improve adiposity-related outcomes. Dietary strategies should focus on the reduction of total energy intake through promotion of food-based guidelines that target modification of usual eating patterns and behaviours. These should target increasing intakes of nutrient-rich foods with a lower energy density, specifically vegetables and fruits, and a reduction in intakes of energy-dense nutrient-poor foods and beverages. In addition, higher intensity, longer duration treatments, delivered by interventionists with specialized dietetic-related skills and co-designed with families, are associated with greater treatment effects. Discussion: Such interventions should be resourced adequately so that they can be implemented in a range of settings and in different formats, including digital or online delivery, to enhance accessibility.
Ten-Year Experience of a Global and Freely Accessible e-Learning Website for Pediatric Endocrinology and Diabetes
Authors: Ng Sze May , Kalaitzoglou Evangelia , Utari Agustini , van Wijngaard-de Vugt Conny , Donaldson Malcolm , Wolfsdorf Joseph I. , Boot Annemieke M. , Drop Stenvert
Published: November 2022

The European Society for Paediatric Endocrinology (ESPE) interactive website, https://www.espe-elearning.org, was first published online in 2012. We describe the various applications of the content of the e-learning website that has been greatly expanded over the last 10 years. A large module on pediatric diabetes was added with the support of the International Society for Paediatric and Adolescent Diabetes (ISPAD). A separate multilingual module was created that focuses on frontline health care providers in limited resource settings. This module has been well received, particularly in targeted parts of the world. e-Learning may also be an opportunity to expand or tailor educational activities for learners according to their differing learning needs. The e-learning website provides guidelines for those interested in general pediatrics, neonatology, clinical genetics, and pediatric gynecology. We also describe various new applications such as master classes in the format of interactive video lectures and joint and complementary e-learning/e-consultation webinars. Finally, international certification was recently realized as e-learning courses were recognized by the European Accreditation Council for Continuing Medical Education (EACCME). As a result of the social distancing measures introduced to control the COVID-19 pandemic, digital education, whether individual or in a virtual classroom setting, has become even more important since e-learning can connect and engage individuals across geographic boundaries as well as those who live in remote areas. The future of education delivery may include hybrid learning strategies, which include in-person and e-learning platforms. Combined e-learning and e-consultation webinars illustrate how international academic institutions, learned medical specialty societies and networks are uniquely placed to deliver balanced, disease-oriented, and patient-centered e-learning education and at the same time provide expert consultation. Moreover, they are well equipped to maintain professional standards and to offer appropriate accreditation.
Вплив міогенних стовбурових клітин на перебіг ферментної та неферментної систем антиоксидантного захисту в щурів із гострим пародонтитом
Authors: Бігуляк Г. Т. , Кліщ І. М.
Published: November 2022

Резюме. Захворювання тканин пародонта разом із каріозними ураженнями є за поширеннням найбільш складною та значною патологію щелепно-лицевої системи. За даними ВООЗ, вони призводять до швидкої втрати зубів, що в 5 разів перевищує ускладнення каріозного процесу.
Мета дослідження – вивчити вплив стовбурових клітин на перебіг ферментної та неферментної систем антиоксидантного захисту за умов експериментального пародонтиту.
Матеріали і методи. Дослідження проводили на білих безпородних щурах-самцях масою тіла 180–200 г. Пародонтит викликали уведенням ліпополісахариду (ЛПС) у тканини ясен по 40 мкл (г/мл) через день протягом 14-ти діб. Через 1-шу, 7-му, 14-ту і 21-шу доби після останнього уведення ЛПС щурів декапітували під тіопенталовим наркозом (50 мг/кг). Контролем слугував матеріал від інтактних тварин. Отримані цифрові дані обробляли за допомогою методу варіаційної статистики. Визначення достовірності відмінностей порівнюваних параметрів між різними вибірками проводили з використанням t-критерію Стьюдента (при нормальному розподілі результатів) чи Манна – Уїтні (у випадку розподілу, що не був нормальним). Достовірним вважали відмінності при р<0,05.
Результати досліджень та їх обговорення. Отримували міогенні стовбурові клітини (МСК) від вагітних самок орієнтовно на 21–24-ту доби вагітності. Для отримання життєздатних МСК використовували ферментний метод. Культивування здійснювали в СО2-інкубаторі за температури 37 оС та концентрації СО2 – 5 %. Стовбурові клітини вводили щурам у ділянку ясен разовою ін’єкцією з розрахунку 1 млн клітин на 1 кг маси тіла. Для максимального збереження життєздатності клітин введення МСК здійснювали протягом 30 хв після отримання суспензії. Вміст супероксиддисмутази (СОД) визначали за методом R. Fried, каталази (КТ) – за методом R. Holmes, церулоплазмін (ЦП) – за методом В. Г. Колб, В. С. Камишнікова. Загальну антиоксидантну активність – за методом J. Stock та співавт.
Висновки. Встановлено, що моделювання гострого пародонтиту спричинило зростання факторів антиксидного захисту на ранньому етапі патологічного процесу з подальшим виснаженням антиоксидантних резервів, що може призвести до надмірного збільшення активності вільнорадикальних процесів та ушкодження тканин пародонта. Корекція із застосуванням МСК мала позитивний ефект, згладжуючи зміни, що виникали.
СУЧАСНІ ПІДХОДИ ДО ФАРМАКОТЕРАПІЇ БОЛЮ У ДІТЕЙ
Authors: Луценко Р. В. , Князькова І. І.
Published: November 2022

Мета дослідження – узагальнення новітніх наявних даних з клінічної фармакології анальгетиків і фармакокорекції болю у дітей.

Матеріали та методи. Проведено бібліографічний пошук результатів дослідження використання анальгетиків для тамування болю у дітей з використанням баз даних PubMed EMBASE як основних пошукових систем.

Результати дослідження та їх обговорення. Представлені основні шкали оцінки болю у дітей, що адаптовані до розроблених у США і Великій Британії. Опіоїдні анальгетики досить часто використовуються при гострому болю, зокрема, морфін у дозі 50–200 мкг/кг; метадон внутрішньо у дозі 50–200 мкг/кг; внутрішньовенно фентаніл 0,5–4 мкг/кг; альфентаніл (10–20 мкг/кг); суфентаніл (10–15 мкг/кг) і реміфентаніл (5 мкг/кг). Опіоїдні анальгетики фентаніл, альфентаніл, суфентаніл і реміфентаніл препарати короткої дії застосовуються при дуже сильному і нестерпному болю. Неопіоїдні анальгетики можна використовувати при помірному болю. Може використовуватись парацетамол (ацетамінофен у дозі 12–15 мг/кг),  мідазолам (50–150 мкг/кг), який не рекомендується новонародженим і пропафол (2,5 мг/кг).

Висновки. Останніми роками для тамування не гострого болю у педіатричних пацієнтів перевагу віддають неопіоїдним анальгетикам.
Morphological criteria of gallbladder destruction in patients with acute cholecystitis, which occurred against the background of COVID-2019
Authors: Orel Yu. M. , Dziubanovskyi I. Ya. , Onyskiv M. O.
Published: November 2022

The aim of the work: to study the morphological features of the gallbladder of acute cholecystitis, which occurred against the background of COVID-2019.

Materials and Methods . Material for histological studies was collected from the proximal and middle third of the gallbladder, as well as from the fundus. The obtained fragments of the gallbladder wall after fixation in a 10 % solution of neutral buffered formalin were processed in the LogosOne histoprocessor and embedded in paraffin blocks. Tissue sections with a thickness of 5 μm obtained on an AMR400 rotary microtome were stained with hematoxylin and eosin. The obtained histological preparations were examined using a Nikon Eclipse Ci-E light microscope. A Sigeta M3CMOS14000 digital video camera with Toup View software was used for photo documentation. With the help of this program, morphometry of tissue structures was also carried out. All histological preparations were divided into 2 groups – patients with acute cholecystitis and those with acute cholecystitis against the background of COVID-19.

Results and Discussion. During the morphological examination of the gallbladder of patients in the cholecystitis + COVID-19 group, it was established that the thickness of the mucous membrane exceeded the similar indicator of the first group by 19.4 %, the differences regarding the muscular and serous membranes were insignificant – an increase of 2.2 % and 1.7 %. The height of covering epitheliocytes regressed by 21.8 %, and the relative volume of affected cells also increased significantly – by 26.0 %. The share of blood vessels increased by 14.4 % in the mucosa and by 9.8 % in the muscle. The described dynamics of morphometric parameters are relevant to the changes detected by microscopy. Thus, the thickening of the mucous membrane under the conditions of a combination of cholecystitis and COVID-2019 can be explained by more pronounced phenomena of edema and hyperemia of the mucous membrane. A decrease in the height of epitheliocytes and an increase in the proportion of damaged cells indicate more intense destructive changes in the epithelium. An increase in the proportion of blood vessels in different parts of the gallbladder wall does not indicate an improvement in its vascularization, but is instead a morphometric marker of the severity of hemodynamic disorders (dilatation and engorgement of vessels, thrombosis). In older people, there was a thinning of the muscle membrane by 11.6 %. Such a structural rearrangement, one should think, has a negative effect on the contractile function of the gallbladder, reduces the force of its tension and contraction. Based on the study of histological preparations, it can be stated that hemodynamic disorders and, in particular, thrombosis play an important role in the pathogenesis of acute cholecystitis, which occurs against the background of COVID-2019.
Мікроскопічні зміни судин підшлункової та надниркових залоз за умов іммобілізаційного стресу на тлі гіпотиреозу
Authors: Кліщ І. М. , Довбуш А. В. , Тупол Л. Д. , Андріїшин О. П. , Гаврилюк-Скиба Г. О.
Published: November 2022

Резюме. Стрес – це стан, що призводить до порушення гомеостазу, і визначається він як реакція мозку та тіла на стимули, які виникають через сигнали як внутрішні, так і з навколишнього середовища.
Мета дослідження – вивчити мікроскопічні зміни судин підшлункової та надниркових залоз за умов впливу іммобілізаційного стресу на тлі гіпотиреозу.
Матеріали і методи. Експеримент проведено на 20 статевозрілих білих щурах-самцях. Гіпотиреоз моделювали щоденним введенням per os за допомогою зонда фармакопейного тиреостатика «Мерказоліл» у дозі 25 мг/кг протягом 21-ї доби. Гострий іммобілізаційний стрес моделювали шляхом привʼязування дослідних щурів у положенні на спині за 4 кінцівки без обмеження рухомості голови тривалістю 3 год. Дослідження проводили через 2 год (стадія тривоги) після завершення дії стресового чинника. Гістологічні дослідження виконано згідно із загальноприйнятими методиками.
Результати. У щурів більшість судин підшлункової залози типової форми, проте деякі підлягали частковій деформації стінки, визначався незначний набряк усіх оболонок стінки, просвіти середніх та великих артерій були помірно розширеними. Просвіти великих та середніх вен були повнокровними, виявлявся незначний набряк периваскулярних просторів. Просвіти деяких гемокапілярів розширені, кровонаповнені з формуванням сладж-феномену. Судини надниркових залоз мали більш виражені деструктивні зміни. Внутрішня еластична мембрана була нечітка, стоншена, переривчаста, медія потовщена із ознаками набряку. Виявлялися мікросудини з ушкодженою стінкою, що призводило до діапедезу еритроцитів, а у клубочковій та пучковій зонах такі локуси зустрічались лише поодиноко. В мозковій речовині органа судини з широкими просвітами та периваскулярним набряком, адвентиція інфільтрована лейкоцитами, найбільш виражені зміни були в стінці синусоїдних гемокапілярів.
Висновки. Встановлено, що за умов змодельованого стресового впливу при гіпотиреозі відбуваються зміни усіх структурних компонентів стінок кровоносних судин як в підшлунковій, так і в надниркових залозах.
Особливості змін деяких параметрів клітинної та гуморальної ланок імунної системи за умов експериментального відтворення алергічного альвеоліту при іммобілізаційному стресі
Authors: Регеда М. С. , Галій-Луцька В. В.
Published: November 2022

Резюме. На сьогодні не до кінця вивченим залишається питання щодо з’ясування особливостей змін імунної системи за умов алергічного альвеоліту й іммобілізаційного стресу, оскільки ці захворювання є досить розповсюдженими.
Мета дослідження – визначити характер порушень рівнів Т- та В-лімфоцитів, циркулюючих імунних комплексів (ЦІК) крові самців морських свинок (МС) при експериментальному алергічному альвеоліті (ЕАА) та іммобілізаційному стресі (ІС).
Матеріали і методи. Використано 100 самців МС масою 180–210 г, яких поділили на 4 дослідні групи (ДГ): перша – інтактні МС; друга – МС з ЕАА; третя – МС з ІС, четверта – МС з ЕАА і ІС. Виводили тварин з експерименту через 1, 14 та 24 доби від початку, відповідно до стадій розвитку ІС – тривоги, резистентності, виснаження.
Результати. При ЕАА через 1 добу достовірних змін досліджуваних показників не спостерігалось. На 14 та 24 доби відносно значень параметрів інтактних МС відзначено зменшення вмісту Т-лімфоцитів на 27,75 % (p<0,01) і 31,78 % (p<0,01), збільшення В-лімфоцитів – на 19,87 % (p<0,01) і 27,15 % (p<0,01) та ЦІК – на 36,98 % (p<0,01) і 40,89 % (p<0,01) відповідно. При ІС через 1, 14 та 24 доби від початку експерименту, порівняно з групою контролю, помічено різке зниження Т-лімфоцитів на 30,72 % (p<0,01), 28,81 % (p<0,01) та 29,87 % (p<0,01), наростання В-лімфоцитів – на 25,17 % (p<0,01), 19,21 % (p<0,01) і 15,23 % (p<0,01) та ЦІК – на 39,58 % (p<0,01), 33,85 % (p<0,01) і 30,47 % (p<0,01) відповідно. При ЕАА та ІС у вищевказані доби виявлено прогресуюче зменшення рівня Т-лімфоцитів на 33,47 % (p<0,01), 36,23 % (p<0,01) і 39,62 % (p<0,01), збільшення В-лімфоцитів – на 27,82 % (p<0,01), 31,13 % (p<0,01) і 44,37 % (p<0,01) та ЦІК – на 41,15 % (p<0,01), 46,62 % (p<0,01) і 50,78 % (p<0,01)відповідно, відносно показників інтактних МС.
Висновоки. Експериментальний алергічний альвеоліт, поєднаний з іммобілізаційним стресом, супроводжується зниженням вмісту Т-лімфоцитів та зростанням рівня ЦІК і В-лімфоцитів у крові, що свідчить про виражене пригнічення клітинної та активацію гуморальної ланки імунної системи при ЕАА та ІС, особливо на 24-ту добу експерименту.
SHORT TERM STUDY ON CLINICAL RELEVANCE AND OUTCOMES OF FOETAL HYDRONEPHROSIS
Authors: Randhawa J. S. , Rajendran N. , Husain J. , Shankaran R. , Nair V. V. , Dorai B. S.
Published: November 2022

Background. Hydronephrosis is the most common urinary tract pathology detected on antenatal screening by Ultrasound. The detection of fetal hydronephrosis by ultrasound pres­ents a treatment dilemma to the treating surgeon and parental anxiety.
Objective. This study aims to examine the role of serial ultrasounds in antenatally detected fetal hydronephrosis to know the disease progression, and to assess indications and timing of surgery in these patients to preserve renal function.
Methods. This is an observational study of 30 cases of foetal hydronephrosis conducted at a tertiary care paediatric surgery centre. A foetal renal pelvic Antero-posterior diameter (APD) >7 mm at 32 weeks of gestation is considered to indicate Foetal hydronephrosis. These patients are followed up for a period of two years from 2018 to 2020. Progression of disease and need for surgical intervention is noted.
Results. The study comprised 30 cases of antenatal foetal hydronephrosis (42 renal units). Of 26 renal units with mild hydronephrosis, all are resolved in the post-natal period. Of 10 renal units with moderate hydronephrosis, 3 (30%) resolved and 7 (70%) worsened and required surgical intervention. Of 6 renal units with severe hydronephrosis, all required surgical intervention and underwent surgery between 12 to 18 months of age.
Conclusions. These results suggest a grading system with antero-posterior diameter of renal pelvis distinguishes those cases with moderate and severe degrees of hydronephrosis that are at higher risk of surgery.
Spatiotemporal Control of Vascular Ca
V
1.2 by α1
C
S1928 Phosphorylation
Authors: Martín-Aragón Baudel Miguel , Flores-Tamez Victor A. , Hong Junyoung , Reddy Gopyreddy R. , Maillard Pauline , Burns Abby E. , Man Kwun Nok Mimi , Sasse Kent C. , Ward Sean M. , Catterall William A. , Bers Donald M. , Hell Johannes W. , Nieves-Cintrón Madeline , Navedo Manuel F.
Published: November 2022

Background:

L-type Ca
V
1.2 channels undergo cooperative gating to regulate cell function, although mechanisms are unclear. This study tests the hypothesis that phosphorylation of the Ca
V
1.2 pore-forming subunit α1
C
at S1928 mediates vascular Ca
V
1.2 cooperativity during diabetic hyperglycemia.

Methods:

A multiscale approach including patch-clamp electrophysiology, super-resolution nanoscopy, proximity ligation assay, calcium imaging‚ pressure myography, and Laser Speckle imaging was implemented to examine Ca
V
1.2 cooperativity, α1
C
clustering, myogenic tone, and blood flow in human and mouse arterial myocytes/vessels.

Results:

Ca
V
1.2 activity and cooperative gating increase in arterial myocytes from patients with type 2 diabetes and type 1 diabetic mice, and in wild-type mouse arterial myocytes after elevating extracellular glucose. These changes were prevented in wild-type cells pre-exposed to a PKA inhibitor or cells from knock-in S1928A but not S1700A mice. In addition, α1
C
clustering at the surface membrane of wild-type, but not wild-type cells pre-exposed to PKA or P2Y
11
inhibitors and S1928A arterial myocytes, was elevated upon hyperglycemia and diabetes. Ca
V
1.2 spatial and gating remodeling correlated with enhanced arterial myocyte Ca
2+
influx and contractility and
in vivo
reduction in arterial diameter and blood flow upon hyperglycemia and diabetes in wild-type but not S1928A cells/mice.

Conclusions:

These results suggest that PKA-dependent S1928 phosphorylation promotes the spatial reorganization of vascular α1
C
into “superclusters” upon hyperglycemia and diabetes. This triggers Ca
V
1.2 activity and cooperativity, directly impacting vascular reactivity. The results may lay the foundation for developing therapeutics to correct Ca
V
1.2 and arterial function during diabetic hyperglycemia.
Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis
Authors: Schliep Karen C. , Mclean Hailey , Yan Bin , Qeadan Fares , Theilen Lauren H. , de Havenon Adam , Majersik Jennifer J. , Østbye Truls , Sharma Surendra , Varner Michael W.
Published: November 2022

Background:

Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP’s vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes.

Methods:

Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer’s disease, vascular dementia, or other/unspecified dementias.

Results:

For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18–1.61];
P
<0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32–4.24];
P
<0.01).

Conclusions:

Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP’s effect on all-cause dementia, and specifically vascular dementia, is warranted.
Effect of Weight Loss on Early Left Atrial Myopathy in People With Obesity But No Established Cardiovascular Disease
Authors: Deal Oscar , Rayner Jennifer , Stracquadanio Antonio , Wijesurendra Rohan S. , Neubauer Stefan , Rider Oliver , Spartera Marco
Published: November 2022

Background

Obesity is associated with left atrial (LA) remodeling (ie, dilatation and dysfunction) which is an independent determinant of future cardiovascular events. We aimed to assess whether LA remodeling is present in obesity even in individuals without established cardiovascular disease and whether it can be improved by intentional weight loss.

Methods and Results

Forty‐five individuals with severe obesity without established cardiovascular disease (age, 45±11 years; body mass index; 39.1±6.7 kg/m
2
; excess body weight, 51±18 kg) underwent cardiac magnetic resonance for quantification of LA and left ventricular size and function before and at a median of 373 days following either a low glycemic index diet (n=28) or bariatric surgery (n=17). Results were compared with those obtained in 27 normal‐weight controls with similar age and sex. At baseline, individuals with obesity displayed reduced LA reservoir function (a marker of atrial distensibility), and a higher mass and LA maximum volume (all
P
<0.05 controls) but normal LA emptying fraction. On average, weight loss led to a significant reduction of LA maximum volume and left ventricular mass (both
P
<0.01); however, significant improvement of the LA reservoir function was only observed in those at the upper tertile of weight loss (≥47% excess body weight loss). Following weight loss, we found an average residual increase in left ventricular mass compared with controls but no residual significant differences in LA maximum volume and strain function (all
P
>0.05).

Conclusions

Obesity is linked to subtle LA myopathy in the absence of overt cardiovascular disease. Only larger volumes of weight loss can completely reverse the LA myopathic phenotype.