bluuebunny/crossref_metadata_2025 huggingface dataset:
Політика зросійщення України та інших європейських територій Російської імперії: порівняльний аналіз
Authors: Mieliekiestsev Kyrylo , Temirova Nadiia
Published: August 2022

Метою статті є дослідження асимілятивних практик Російської імперії щодо українського та інших підкорених імператорській владі народів Європи. Задля цього здійснено пошук мотивів верхівки імперії до зросійщення українців, проаналізовано асиміляційні практики у «нерусских» регіонах – Польщі, Балтії, Бессарабії, показано характерні риси обмежувальної політики в Україні, порівняно методи зросійщення в Україні з іншими підвладними Романовим землями.

Наукова новизна статті полягає у здійсненні компаративного аналізу застосування політики зросійщення в підросійській Україні з подібними процесами у решті загарбаних Росією європейських земель.

Висновки. Здійснений аналіз дозволив дійти кількох висновків. Початок загальнодержавної політики зросійщення з ідеологічним обґрунтуванням і практичною реалізацією доречно віднести до доби Катерини II. Посилення її жорсткості у другій половині XIX ст. стало реакцією імперського керівництва на «Весну народів» в Європі. Через відверто пропагандистський характер ідеологема «триєдиного російського народу» виявила нежиттєздатність. Це розуміли її головні апологети, які ставилися до українців не як до «своїх», а як до «інородців».

Порівняння асимілятивних заходів до європейських народів у Російській імперії виявило схожі методи, результати та загальні проблеми. Зросійщення українців було майже ідентичним асимілятивним практикам поляків і народів Балтії. До винятків варто віднести відсутність необхідності переведення граматики на кирилицю замість латинки та зручна ідеологічна ширма «єдиного російського народу». Вдавання до гасел про «єдину російську народність» чи атаки самої ідеї вірнопідданості «інородців» імперії без вірності російській мові та культурі демонстрували справжню мету зросійщення – посилення самодержавної влади, ліквідація залишків автономії й об’єднання велетенських просторів імперії навколо імператора. Проте, у підсумку політика царату змогла перетворити на «російський елемент» лише частину еліти підкорених народів. Форми її реалізації відділили широкі народні маси від лояльних імператорові аристократичних еліт. Спроби поширити зросійщення на широкі народні маси та заборонити інтелектуальну діяльність місцевими мовами зазнали поразки. Проаналізовані процеси імперської доби мають відгомін у політиці сучасної Російської Федерації.
Видавнича діяльність інтернованих вояків армії УНР у польському таборі Піотрків Трибунальський (1921 р.)
Authors: Holubnycha-Shlenchak Yuliia
Published: August 2022

Мета статті полягає у спробі на основі комплексного аналізу архівних та опублікованих матеріалів дослідити специфіку видавничого процесу в таборі інтернованих вояків Армії УНР Піотркув Трибунальський у 1921 р. Вивчення особливостей життєдіяльності видавців та їх психологічного стану в умовах таборового соціуму, рівня матеріального та фінансового забезпечення тиражування таборових видань, характеристики читацької аудиторії.

Наукова новизна дослідження полягає у тому, що видавнича діяльність інтернованих Армії УНР у таборі Піотрков Трибунальський вперше стала предметом окремого самостійного дослідження. Зокрема, вперше було комплексно проаналізовано процес видання стіннівки «Всім», охарактеризовано її значення у таборовому повсякденні та ставлення читачів до часопису.

Висновки. Впровадження культурно-освітньої діяльності у таборах мало на меті використати час інтернування з користю для вояків. Вона мала підготувати їх до подальшої боротьби за незалежність і дати духовну розраду та моральний відпочинок. У кожному таборі діяло або своє видавництво, або невеличка друкарня. Піотрков Трибунальський належав до числа тих таборів, де умови перебування були дуже важкими. У таборі не було можливості заснувати видавництво. Однак, незважаючи на складнощі, з якими зітнулися інтерновані, їм власними силами вдалося започаткувати видання трьох часописів: стіннівку «Всім», «На хвилях життя» і «Тернистий шлях». Значна заслуга у видавництві часописів «Всім» і «На хвилях життя» належала Є. Маланюку, який був головними редактором «Всім» і «На хвилях життя». Основною метою тиражування часописів було надати можливість воякам знайти віддушину та поділитися наболілим, що допомагало подолати морально-психологічну кризу. Також мало місце бажання декого проявити себе на літературній ниві. Та, перш за все, до видання стіннівки «Всім» було залучено багато таборових художників і карикатуристів, переважна більшість яких творили під різними псевдонімами.
Doppler evaluation of hepatic hemodynamics after living donor liver transplantation in infants
Authors: Chen Xiping , Xiao Huan , Yang Chunjiang , Chen Jingyu , Gao Yang , Tang Yi , Ji Xiaojuan
Published: August 2022

Objective: The aim of this study was to explore the hemodynamic changes of hepatic artery and portal vein detected by Doppler ultrasound (DU) in infants who underwent living donor liver transplantation (LDLT).

Methods: The data of 41 infant patients (22 Males, 19 Females, median age of 5 months) were collected in the Children’s Hospital affiliated to the Chongqing Medical University from May 2018 to December 2019. The patients underwent left lateral segment LDLT (LLS -LDLT) because of biliary atresia (BA). Hemodynamic parameters, including the peak systolic velocity (PSV), resistivity index (RI) of the hepatic artery (HA), portal vein velocity (PVV), and portal vein flow (PVF) were recorded from Doppler ultrasound on the day before the operation, and on the 1st, the 7th, the 14th and the 30th day after LDLT procedures. The changes of PSVHA, RIHA, PVV and PVF before and on the 1st day after transplantation were analyzed by paired t-test. The comparison of the data between different postoperative time points were assessed by ANOVA.

Results: Compared with the parameters measured before LDLT, PSVHA, and RIHA decreased, and PVV and PVF increased significantly (p < 0.001) on the 1st day after LLS-LDLT. As for PSV, there was no significant difference between the 7th day and the 1st day after transplantation (POD7 VS POD1, p = 0.167) while there was a substantial difference between the 14th, 30th and 1st day after LT (POD14 vs. POD1, p = 0.003) (POD30 vs. POD1, p ＜0.001). And there was a significant difference between the 14th, 30th, and 7th days after LT (POD14 vs. POD7, p = 0.014) (POD30 vs. POD7, p ＜0.001). There was no significant difference between 30th and 14th after transplantation (POD30 vs. POD14, p = 0.092). As for RIHA and PVV, the decrease was slow within the first month after the operation, and there was no significant difference at different times.

Conclusion: We have identified major hepatic flow changes that occurred in 41 infants who underwent LLS -LDLT due to BA. The data could be used for future studies of LDLT in infants including hemodynamic modeling, liver regeneration and clinical management.
Activated platelet membrane nanovesicles recruit neutrophils to exert the antitumor efficiency
Authors: Shang Yinghui , Sun Juntao , Wu Xin , Wang Qinghai
Published: August 2022

Platelets play a crucial role in the recruitment of neutrophils, mediated by P-selectin, CCL5, and ICAM-2. In this study, we prepared platelet membrane nanovesicles from activated platelets. Whether activated platelet membrane nanovesicles can recruit neutrophils has not been reported, nor has their role in antitumor immunity. The results of SDS-PAGE showed that the platelet membrane nanovesicles retained almost all the proteins of platelets. Western blotting showed that both the activated platelets and the platelet membrane nanovesicles expressed P-selectin, ICAM-2, and CCL5.In vivoresults of a mouse model of breast cancer-transplanted tumor showed that tumor volume reduced significantly, Ki-67-positive tumor cells decreased, and TUNEL-positive tumor cells increased in tumors after treatment with activated platelet membrane nanovesicles (aPNs). After treatment with aPNs, not only the number of neutrophils, CD8+, CD4+T cells, and B cells increased, but also IL-12, TNF-α, and IFN-γ levels elevated significantly in tumor tissues.
Simultaneous quantitation of 17 endogenous adrenal corticosteroid hormones in human plasma by UHPLC-MS/MS and their application in congenital adrenal hyperplasia screening
Authors: Zhang Qiaoxuan , Zhan Min , Wu Huihui , Feng Pinning , Jin Xing , Wan Zemin , Yan Jun , Zhang Pengwei , Ke Peifeng , Zhuang Junhua , Zhou Jiuyao , Han Liqiao , Huang Xianzhang
Published: August 2022

Accurate investigation of adrenal hormone levels plays a vital role in pediatric endocrinology for the detection of steroid-related disorders. This study aims to develop a straightforward, sensitive UHPLC-MS/MS method to quantify 17 endogenous adrenal corticosteroid hormones in human plasma. These hormones are the main ingredients in the synthetic and metabolic pathways of adrenal corticosteroid hormones. Chromatographic separation was achieved on a C18 column before electrospray ionization triple-quadrupole mass spectrometry in multiple reaction monitoring mode with a run time of 7 min. The samples were extracted by liquid-liquid extraction and required no derivatization. Analytical performance was evaluated, including linearity, analytical sensitivity, accuracy, precision, and specificity. Plasma specimens from 32 congenital adrenal hyperplasia (CAH) patients and 30 healthy volunteers were analyzed to further reveal the diagnostic value of multiple steroid hormones in the synthetic and metabolic pathways of adrenal corticosteroid in CAH diagnosis. All hormones were effectively extracted and separated using our method. The method was essentially free from potential interference of isomers or structural analogues. The imprecisions were <10%. The lower limits of quantification varied from 0.05 to 15.0 ng/ml. Good linearity coefficients (r2 > 0.998) were also obtained for most hormones in the required concentration range, except for 21-deoxycortisol (r2 = 0.9967) and androstenediol (r2 = 0.9952). The recoveries for the steroid hormones ranged from 91.7 to 109.8%. We developed the UHPLC-MS/MS method for the simultaneous measurement of steroid hormones. The results showed that measurement of steroid hormones simultaneously could improve the diagnostic efficiency of CAH.
Synthesis of naphthalimide-type chemsensor and its application in quality evaluation for polygonatum sibiricum Red
Authors: Wang Zhen , Sun Qiaoxu , Zhao Yuanyuan , Du Jiao , Wang Bin
Published: August 2022

The premise and key of ensuring the safety and effectiveness of traditional Chinese medicine (TCM) is to construct appropriate quality evaluation system of TCM. This study aimed to establish a pre-column derivatization HPLC method for achieving the quality control of Polygonatum sibiricum by reacting synthesized 4-hydrazino-1,8-naphthalimide (HAN) with diverse monosaccharides from the hydrolytic product of P. sibiricum polysaccharides (PSPs), followed by HPLC separation. The HAN was synthesized based on a CuI-catalyzed cross-coupling reaction in water, and then employed as a novel chemosensor that reacts with reducing sugars. Good separation was achieved at a detection wavelength of 448 nm using an ZORBAX SB-C8 column under a gradient elution at a flow rate of 0.5 ml/min within 12 min. The monosaccharide compositions of PSP mainly include two hexoses [glucose (Glc), galactose (Gal)] and two hexuronic acids [glucuronic acid (GlcA) and galacturonic acid (GalA)], and the molar ratio of Glc, Gal, GlcA and GalA is 16.67:52.94:10.58:19.81. The verified HPLC method, possessing excellent precision and good accuracy, successfully achieved rapid qualitative and quantitative determination for PSP. Additionally, the HAN displayed fluorescence enhancement through “push–pull” mode, and fluorescence decreased through “pull–pull” mode after binding to monosaccharides, which is a potential for fluorescence determination of different monosaccharides.
Facile synthesis of nanosized Mn3O4 powder anodes for high capacity Lithium-Ion battery via flame spray pyrolysis
Authors: Wang Hao , Zhao Jiachang , Xie Dongmei , Huang Haiji , Rao Pinhua , Mao Jianfeng
Published: August 2022

Mn3O4 powders with nanometer size are successfully synthesized by a simple one-step method via flame spray pyrolysis. The precursor droplet is generated by heating under high temperature flame with fixed flow rate, and the exothermic reaction is induced to form nanosized Mn3O4 powders. When used as anode material for lithium-ion battery, the Mn3O4 exhibits good cycling capacity and rate performance. It delivers a specific capacity of 1,182 mA h g−1 over 110 cycles at a current density of 200 mA g−1, and has a high capacity of 140 mA h g−1 at 5,000 mA g−1.
Z-score model of foetal ascending aorta diameter distensibility
Authors: Chen Fuli , Zeng Shi , Yi Aijiao , Chen Lihua , Zhou Dan , Liu Yushan , Yao Longmei
Published: August 2022

Objective

The purpose of this study is to establish Z-scores models of normal fetal ascending aorta diameter and diameter distensibility.

Methods

The maximum systolic diameter (Dmax), minimum diastolic diameter (Dmin), and diameter distensibility of the sinotubular junction were measured and taken as dependent variables in 490 normal fetuses at 18–40 gestational weeks, and gestational age (GA), biparietal diameter (BPD), and femoral length (FL) were taken as independent variables. The data were subjected to regression analysis, and the best-fitting equations for the dependent variables based on the independent variables were determined. The fitting equations were then applied to construct the Z-scores models.

Results

The Dmax, Dmin and Diameter Distensibility in normal fetuses between 18 and 40 weeks of GA could be evaluated by utilizing the Z-scores models. Dmax and Dmin increased significantly with increasing GA, BPD, and FL. Diameter distensibility, assessed as (Dmax–Dmin)/Dmin, decreased significantly with increasing GA, BPD, and FL.

Conclusion

The Z-scores are valuable, and can be utilized as a potent supplement to the conventional approach as they can indirectly reflect the development of fetal ascending aortic elastic property.
Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients
Authors: Cheng Ching-Lan , Yen Chi-Tai , Su Chien-Chou , Lee Cheng-Han , Huang Chien-Huei , Yang Yea-Huei Kao
Published: August 2022

Background

Gout or rapid reduction in serum uric acid level may increase the incidence of heart failure (HF). To compare the risk of HF between febuxostat and allopurinol in gout patients with coexisting cardiovascular (CV) diseases, the varying severity would be likely to confound the risk estimation. Gout and HF are both sex-related diseases, and the risk difference from the urate-lowering agents between women and men remains unknown.

Aims

To evaluate the HF hospitalisations risk of febuxostat and allopurinol in gout patients in real-world settings.

Methods

A population-based cohort enrolled patients with allopurinol or febuxostat initiation from 2011 to 2018. Participants were grouped into, without (low CV risk group) or with (high CV risk group) a history of recent major CV admission. The primary outcome was HF hospitalization. The secondary outcomes were composite CV events, all-cause mortality, and the cause of CV mortality. We used the ‘as-treated' analysis and Cox proportional hazards model after propensity score (PS) matching. Patients were further stratified into men and women to evaluate the gender differences.

Results

Febuxostat users had a significantly higher risk of HF hospitalization than allopurinol users in gout patients either with low CV risk [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.25–1.55] or high CV risk [HR 1.36; 95% CI 1.22–1.52]. Particularly, women with gout had a higher risk of HF hospitalization than men.

Conclusion

The HF hospitalization risk was highest in gout women with high CV risk and febuxostat use. Monitoring of HF is warranted in these patients.
The obstacles hierarchy of school disaster preparedness implementation in Mount Sinabung area, Indonesia
Authors: Muzani Muzani , Fatimah Anggun Nadia , Imsa Mentari Anugrah , Casmana Asep Rudi
Published: August 2022

The incidence of natural disasters has an impact on various sectors of life, including the education sector. Schools as educational facilities are considered vulnerable areas that need handling steps to reduce disaster risk. As one of the most vulnerable countries to natural disasters, Indonesia already has several policies and programs from the government to address these problems. However, several studies have shown that the implementation did not go according to plan. These studies also reveal that this implementation lies in the local context in which the program or policy is implemented. That is why the study aims to examine the school disaster preparedness implementation in the Mount Sinabung area as one of the disaster-prone areas in Indonesia. This research utilizes the Interpretative Structural Modeling approach to build a hierarchy and classification of obstacles in implementing school disaster preparedness around that area. Data are collected through a combination of observation, interview, and survey techniques in 2017 and 2018 that involved a total of 35 participants. The result showed 14 sub-elements identified as limiting factors of school preparedness implementation in the Mount Sinabung area. Three elements serve as the first level (or the basis/key element) of the obstacles hierarchy: Integration of subject, school policy, and school curriculum. Intervention at the base level will trigger changes and give impact the other upper-four levels of elements. This hierarchy and classification are relevant to the context of the Mount Sinabung eruption and cannot be applied in other areas. This research did not measure the numeric data per sub-element in disaster preparedness. Therefore, the limitations of this study can be directions for future research to examine the implementation in another area by using numeric data. The results of this study also provide major recommendations to several stakeholders. The existing policies regarding school disaster preparedness and their implementation need to be reviewed to improve the result.
System design for using multimodal trace data in modeling self-regulated learning
Authors: Cloude Elizabeth Brooke , Azevedo Roger , Winne Philip H. , Biswas Gautam , Jang Eunice E.
Published: August 2022

Self-regulated learning (SRL) integrates monitoring and controlling of cognitive, affective, metacognitive, and motivational processes during learning in pursuit of goals. Researchers have begun using multimodal data (e.g., concurrent verbalizations, eye movements, on-line behavioral traces, facial expressions, screen recordings of learner-system interactions, and physiological sensors) to investigate triggers and temporal dynamics of SRL and how such data relate to learning and performance. Analyzing and interpreting multimodal data about learners' SRL processes as they work in real-time is conceptually and computationally challenging for researchers. In this paper, we discuss recommendations for building a multimodal learning analytics architecture for advancing research on how researchers or instructors can standardize, process, analyze, recognize and conceptualize (SPARC) multimodal data in the service of understanding learners' real-time SRL and productively intervening learning activities with significant implications for artificial intelligence capabilities. Our overall goals are to (a) advance the science of learning by creating links between multimodal trace data and theoretical models of SRL, and (b) aid researchers or instructors in developing effective instructional interventions to assist learners in developing more productive SRL processes. As initial steps toward these goals, this paper (1) discusses theoretical, conceptual, methodological, and analytical issues researchers or instructors face when using learners' multimodal data generated from emerging technologies; (2) provide an elaboration of theoretical and empirical psychological, cognitive science, and SRL aspects related to the sketch of the visionary system called SPARC that supports analyzing and improving a learner-instructor or learner-researcher setting using multimodal data; and (3) discuss implications for building valid artificial intelligence algorithms constructed from insights gained from researchers and SRL experts, instructors, and learners SRL via multimodal trace data.
Intraoperative EMG recovery patterns and outcomes after RLN traction-related amplitude decrease during monitored thyroidectomy
Authors: Chiu Kuan-Lin , Lien Ching-Feng , Wang Chih-Chun , Wang Chien-Chung , Hwang Tzer-Zen , Shih Yu-Chen , Yu Wing-Hei Viola , Wu Che-Wei , Dionigi Gianlorenzo , Huang Tzu-Yen , Chiang Feng-Yu
Published: August 2022

Objectives

Traction injury is the most common type of recurrent laryngeal nerve (RLN) injury in thyroid surgery. Intraoperative neuromonitoring (IONM) facilitates early detection of adverse electromyography (EMG) effect, and this corrective maneuver can reduce severe and repeated nerve injury. This study aimed to evaluate intraoperative patterns and outcomes of EMG decrease and recovery by traction injury.

Methods

644 patients received nerve monitored thyroidectomy with 1142 RLNs at risk were enrolled. Intermittent IONM with stimulating dissecting instrument (real-time during surgical procedure) and trans-thyroid cartilage EMG recording method (without electrode malpositioning issue) were used for nerve stimulation and signal recording. When an EMG amplitude showed a decrease of >50% during RLN dissection, the surgical maneuver was paused immediately. Nerve dissection was restarted when the EMG amplitude was stable.

Results

44/1142 (3.9%) RLNs exhibited a >50% EMG amplitude decrease during RLN dissection and all (100%) showed gradual progressive amplitude recovery within a few minutes after releasing thyroid traction (10 recovered from LOS; 34 recovered from a 51-90% amplitude decrease). Three EMG recovery patterns were noted, A-complete EMG recovery (n=14, 32%); B-incomplete EMG recovery with an injury point (n=16, 36%); C-incomplete EMG recovery without an injury point (n=14, 32%). Patients with postoperative weak or fixed vocal cord mobility in A, B, and C were 0(0%), 7(44%), and 2(14%), respectively. Complete EMG recovery was found in 14 nerves, and incomplete recovery was found in another 30 nerves. Temporary vocal cord palsy was found in 6 nerves due to unavoidable repeated traction.

Conclusion

Early detection of traction-related RLN amplitude decrease allows monitoring of intraoperative EMG signal recovery during thyroid surgery. Different recovery patterns show different vocal cord function outcomes. To elucidate the recovery patterns can assist surgeons in the intraoperative decision making and postoperative management.
Global signalling network analysis of luminal T47D breast cancer cells in response to progesterone
Authors: Wright Roni H. G. , Vastolo Viviana , Oliete Javier Quilez , Carbonell-Caballero José , Beato Miguel
Published: August 2022

Background

Breast cancer cells enter into the cell cycle following progestin exposure by the activation of signalling cascades involving a plethora of enzymes, transcription factors and co-factors that transmit the external signal from the cell membrane to chromatin, ultimately leading to a change of the gene expression program. Although many of the events within the signalling network have been described in isolation, how they globally team up to generate the final cell response is unclear.

Methods

In this study we used antibody microarrays and phosphoproteomics to reveal a dynamic global signalling map that reveals new key regulated proteins and phosphor-sites and links between previously known and novel pathways. T47D breast cancer cells were used, and phospho-sites and pathways highlighted were validated using specific antibodies and phenotypic assays. Bioinformatic analysis revealed an enrichment in novel signalling pathways, a coordinated response between cellular compartments and protein complexes.

Results

Detailed analysis of the data revealed intriguing changes in protein complexes involved in nuclear structure, epithelial to mesenchyme transition (EMT), cell adhesion, as well as transcription factors previously not associated with breast cancer cell proliferation. Pathway analysis confirmed the key role of the MAPK signalling cascade following progesterone and additional hormone regulated phospho-sites were identified. Full network analysis shows the activation of new signalling pathways previously not associated with progesterone signalling in T47D breast cancer cells such as ERBB and TRK. As different post-translational modifications can mediate complex crosstalk mechanisms and massive PARylation is also rapidly induced by progestins, we provide details of important chromatin regulatory complexes containing both phosphorylated and PARylated proteins.

Conclusions

This study contributes an important resource for the scientific community, as it identifies novel players and connections meaningful for breast cancer cell biology and potentially relevant for cancer management.
Genetics: Is LADA just late onset type 1 diabetes?
Authors: Hernández M. , Nóvoa-Medina Y. , Faner R. , Palou E. , Esquerda A. , Castelblanco E. , Wägner A. M. , Mauricio D.
Published: August 2022

Background

There is a controversy regarding Latent Autoimmune Diabetes in Adults (LADA) classification and whether it should be considered a slowly progressing form of type 1 (T1) diabetes (DM) or a distinct type of DM altogether.

Methods

This cross-sectional study assessed major genes associated with T1DM (class II HLA, PTPN22 [rs2476601] and INS [rs689]) in patients with LADA, as compared with participants with T1DM (stratified according to age of diagnosis before or after 30) and T2DM. HLA genotyping of the DRB1, DQA1 and DQB1 loci was performed by reverse PCR sequence-specific oligonucleotides. HLA haplotypes were assigned according to those most frequently described in the European population. INS and PTPN22 SNPs were genotyped by real-time PCR.

Results

A total of 578 participants were included: 248 with T1DM (70 diagnosed after the age of 30), 256 with T2DM and 74 with LADA. High risk HLA alleles were significantly more frequent in LADA than in T2DM, whereas the opposite was true for protective alleles. We found a lower frequency of the high-risk DRB1*04-DQB1*03:02-DQA1*03:01 haplotype in LADA (21.1%) than in the overall T1DM (34.7%) (p<0.05), whereas no differences were found between these groups for DRB1*03-DQB1*02:01-DQA1*05:01 or for protective alleles. Only 12% the overall T1DM group had no risk alleles vs 30% of LADA (p<0.0005). However, HLA allele distribution was similar in LADA and T1DM diagnosed after the age of 30. A total of 506 individuals (195 with T1DM [21 diagnosed after age 30] 253 with T2DM and 58 with LADA) were genotyped for the PTPN22 and INS SNPs. The G/A genotype of the PTPN22 rs2476601 was more frequent and the T/T genotype of the INS SNP rs689 was less frequent in T1DM compared to LADA. We did not find any significant differences in the frequency of the mentioned SNPs between LADA and T2DM, or between LADA and T1DM diagnosed after the age of 30.

Conclusion

In this relatively small cross-sectional study, the genetic profile of subjects with LADA showed a similar T1DM-related risk allele distribution as in participants with T1DM diagnosed after the age of 30, but fewer risk alleles than those diagnosed before 30. Differences were present for HLA, as well as PTPN22 and INS genes.
Case report: Goiter and overt hypothyroidism in an iodine-deficient toddler on soy milk and hypoallergenic diet
Authors: Caprio Angela Maria , Umano Giuseppina Rosaria , Luongo Caterina , Aiello Francesca , Dello Iacono Iride , Palumbo Stefania , Miraglia del Giudice Emanuele , Grandone Anna
Published: August 2022

Soy-based infant formulas (SFs) are often consumed by cow’s milk allergic children. However, some concerns have risen since soy intake may adversely affect thyroid function in iodine-deficient or subclinical hypothyroid individuals. We report the first Italian case of SF induced goiter and hypothyroidism registered in our country since National Iodine program has been instituted. Finally, we review cases previously reported in literature. A 22-month-old toddler with a previous diagnosis of cow’s milk protein allergy came to clinical attention for important goiter and overt hypothyroidism. Detailed dietary anamnesis revealed that he was on a restrictive dietary regimen based on soymilk since 12 months of age. A temporary levothyroxine substitution was instituted to avoid hypothyroidism complications. Adequate iodine supplementation and diet diversification completely reversed SF-induced hypothyroidism and goiter, confirming the diagnostic suspicion of soymilk-induced thyroid dysfunction in a iodine-deficient toddler. This case report demonstrates the importance of careful dietary habits investigation and adequate micronutrients supplementation in children on a restrictive diet due to multiple food allergies in order to prevent nutritional deficits.
Effect of Chinese herbal compounds on ocular fundus signs and vision in conventional treated-persons with non-proliferative diabetic retinopathy: A systematic review and meta-analysis
Authors: Li Xiaodong , Zhang Jiaqi , He Runxi , Su Xiaojuan , Li Zhilin , Xie Xuejun
Published: August 2022

Background

Changes in fundus signs and loss of visual acuity are an important basis for screening and treating diabetic patients with retinopathy, and conventional Western medicine is moderately effective in treating diabetic retinopathy(DR),To systematically evaluate the effectiveness and safety of Chinese herbal compounds(CHCs) in the combined treatment of diabetic retinopathy.

Method

Six electronic databases, including PubMed, were searched to screen eligible literature. Randomized controlled trials of non-proliferative diabetic retinopathy(NPDR) were included, in which the control group was treated with conventional Western-based drugs or retinal laser photocoagulation, and the intervention group was treated with CHCs in combination based on the control group.The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the literature, and the RevMan 5.4 software was used for statistical analysis.

Results

Compared with Conventional group alone,CHCs group was superior at improving clinical efficacy [RR=1.29, 95%CI=(1.23, 1.36),P<0.01] and best corrected visual acuity(BCVA) [MD=0.10,95%CI=(0.09,0.12),P<0.01],it was also superior at reducing the number of microangiomas [MD=-2.37, 95%CI=(-3.26, -1.49),P<0.01], microangioma volume [MD=-4.72, 95%CI=(-5.14, -4.29), P<0.01], hemorrhagic spots [MD=-2.05, 95%CI=(-2.51,-1.59), P<0.01], hemorrhagic area [MD=-0.76, 95%CI=(-1.06, -0.47), P<0.01], hard exudates [MD= -1.86, 95%CI=(-2.43, -1.28), P<0.01], cotton lint spots [MD= -0.93, 95%CI= (-1.31, -0.55), P<0.01], central macular thickness(CMT) [SMD=-1.52, 95%CI=(-1.85, -1.19),P<0.01], Chinese medicine evidence score [SMD=-1.33,95%CI=(-1.58, -1.08),P<0.01], fasting blood glucose (FBG) [SMD=-0.47, 95%CI=(-0.61,-0.33),P<0.01], 2h postprandial blood glucose(2hPBG) [SMD=-0.87, 95% CI=(-1.06, -0.67), P<0.01], glycosylated hemoglobin (HbAlc) [SMD=-0.76, 95%CI=(-1.16, -0.3),P<0.01], total cholesterol(TC) [SMD=-0.33,95%CI=(-0.51,-0.16),P<0.01],and CHCs group with less adverse events occurred [RR=0.46, 95%CI=(0.29, 0.74),P<0.01].

Conclusion

CHCs combined with conventional medicine for NPDR has better clinical efficacy and higher safety, but the above findings need further validation in more large sample, multicenter, and low-bias RCTs due to the limitation of the quality and quantity of included literature.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022342137.
Can directors’ and officers’ liability insurance improve corporate ESG performance?
Authors: Xu Hanyou , Zhao Jing
Published: August 2022

Directors’ and Officers’ liability insurance (abbreviated as “D&O insurance”) was born in the United States in the 1930s and has been widely used in Western countries. In contrast, China introduced D&O insurance in 2002, and its development has been relatively slow. With the revision and improvement of Chinese regulatory laws and regulations, such as the new Securities Law in March 2020, which further regulates the obligations and responsibilities of corporate management, and increases the penalties for information disclosure violations of listed companies, the risk to directors and executives performing their duties is promoted. This makes D&O insurance the focus of China’s capital market, with huge potential for future development. Therefore, it is of urgent practical importance to study the impact of director liability insurance on corporate governance in China. At the same time, D&O insurance, as an effective risk management mechanism, has not yet reached a unified conclusion in the academic circles on its corporate governance effectiveness. On the one hand, D&O insurance may encourage directors and senior executives to be proactive to enhance the company’s market value by taking risks, and on the other hand, it may induce opportunistic behavior of managers and reduce the company’s value. Under the new development form, analyzing and researching the governance effect of D&O insurance from different angles will help to provide a theoretical basis for its further development and popularization in China’s capital market. Thus, using a sample of Chinese A-share listed companies from 2011 to 2020, this study investigates the impact of D&O insurance on corporate ESG performance. The results show that D&O insurance significantly improves corporate ESG performance. Additional analysis suggests that the contribution of D&O insurance to ESG performance is achieved by improving independent director function-performing effectiveness and increasing corporate risk-taking. The findings of this paper have policy implications for a better understanding of the governance role of D&O insurance, encouraging companies to improve corporate ESG performance.
Optimization of a flood diversion gate scheme in flood storage and detention areas based on flood numerical simulation
Authors: Yu Ping , Ma Huixin , Qiu Lanqing , Zhang Ting , Li Shaofei
Published: August 2022

Flood storage and detention areas are an important aspect of the river flood control system and an effective measure to ensure flood control safety and mitigate disasters in key areas. Using the flood storage and detention area of DaHuangPuWa as an example, the flood diversion evolution of different positions on the Jinbao highway was simulated numerically. The water level, velocity, and flow rate of each observation point during the 100-year flood were calculated. After comprehensive analysis, it is determined that the location of the diversion gate in the flood storage and detention area is better at the diversion gate of Liuwanzhuang. The results of this paper show that the numerical simulation method can provide more scientific and reasonable theoretical support for the design of flood diversion gates in flood storage and detention areas.
Identification of an autophagy-related 12-lncRNA signature and evaluation of NFYC-AS1 as a pro-cancer factor in lung adenocarcinoma
Authors: Tong Fang , Xu Lifa , Xu Sheng , Zhang Mingming
Published: August 2022

Objective: To develop an autophagy-related lncRNA-based risk signature and corresponding nomogram to predict overall survival (OS) for LUAD patients and investigate the possible meaning of screened factors.

Methods: Differentially expressed lncRNAs and autophagy genes were screened between normal and LUAD tumor samples from the TCGA LUAD dataset. Univariate and multivariate Cox regression analyses were performed to construct the lncRNA-based risk signature and nomogram incorporating clinical information. Then, the accuracy and sensitivity were confirmed by the AUC of ROC curves in both training and validation cohorts. qPCR, immunoblot, shRNA, and ectopic expression were used to verify the positive regulation of NFYC-AS1 on BIRC6. CCK-8, immunofluorescence, and flow cytometry were used to confirm the influence of NFYC-AS1 on cell proliferation, autophagy, and apoptosis via BIRC6.

Results: A 12-lncRNA risk signature and a nomogram combining related clinical information were constructed. Furthermore, the abnormal increase of NFYC-AS1 may promote LUAD progression through the autophagy-related gene BIRC6.

Conclusion: 12-lncRNA signature may function as a predictive marker for LUAD patients, and NFYC-AS1 along with BIRC6 may function as carcinogenic factors in a combinatorial manner.
Analysis of chronic kidney disease patients by targeted next-generation sequencing identifies novel variants in kidney-related genes
Authors: Alaamery Manal , Alghamdi Jahad , Massadeh Salam , Alsawaji Mona , Aljawini Nora , Albesher Nour , Alghamdi Bader , Almutairi Mansour , Hejaili Fayez , Alfadhel Majid , Baz Batoul , Almuzzaini Bader , Almutairi Adel F. , Abdullah Mubarak , Quintana Francisco J. , Sayyari Abdullah
Published: August 2022

Despite the enormous economic and societal burden of chronic kidney disease (CKD), its pathogenesis remains elusive, impeding specific diagnosis and targeted therapy. Herein, we sought to elucidate the genetic causes of end-stage renal disease (ESRD) and identify genetic variants associated with CKD and related traits in Saudi kidney disease patients. We applied a genetic testing approach using a targeted next-generation sequencing gene panel including 102 genes causative or associated with CKD. A total of 1,098 Saudi participants were recruited for the study, including 534 patients with ESRD and 564 healthy controls. The pre-validated NGS panel was utilized to screen for genetic variants, and then, statistical analysis was conducted to test for associations. The NGS panel revealed 7,225 variants in 102 sequenced genes. Cases had a significantly higher number of confirmed pathogenic variants as classified by the ClinVar database than controls (i.e., individuals with at least one allele of a confirmed pathogenic variant that is associated with CKD; 279 (0.52) vs. 258 (0.45); p-value = 0.03). A total of 13 genetic variants were found to be significantly associated with ESRD in PLCE1, CLCN5, ATP6V1B1, LAMB2, INVS, FRAS1, C5orf42, SLC12A3, COL4A6, SLC3A1, RET, WNK1, and BICC1, including four novel variants that were not previously reported in any other population. Furthermore, studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.
Inflammatory aging clock: A cancer clock to characterize the patients’ subtypes and predict the overall survival in glioblastoma
Authors: Zhu Lei , Wang Feng , Huang Jiannan , Wang He , Wang Guangxue , Jiang Jianxin , Li Qinchuan
Published: August 2022

Background: Many biological clocks related to aging have been linked to the development of cancer. A recent study has identified that the inflammatory aging clock was an excellent indicator to track multiple diseases. However, the role of the inflammatory aging clock in glioblastoma (GBM) remains to be explored. This study aimed to investigate the expression patterns and the prognostic values of inflammatory aging (iAge) in GBM, and its relations with stem cells.

Methods: Inflammation-related genes (IRG) and their relations with chronological age in normal samples from the Cancer Genome Atlas (TCGA) were identified by the Spearman correlation analysis. Then, we calculated the iAge and computed their correlations with chronological age in 168 patients with GBM. Next, iAge was applied to classify the patients into high- and low-iAge subtypes. Next, the survival analysis was performed. In addition, the correlations between iAge and stem cell indexes were evaluated. Finally, the results were validated in an external cohort.

Results: Thirty-eight IRG were significantly associated with chronological age (|coefficient| > 0.5), and were used to calculate the iAge. Correlation analysis showed that iAge was positively correlated with chronological age. Enrichment analysis demonstrated that iAge was highly associated with immune cells and inflammatory activities. Survival analysis showed the patients in the low-iAge subtype had significantly better overall survival (OS) than those in the high-iAge subtype (p < 0.001). In addition, iAge outperformed the chronological age in revealing the correlations with stem cell stemness. External validation demonstrated that iAge was an excellent method to classify cancer subtypes and predict survival in patients with GBM.

Conclusions: Inflammatory aging clock may be involved in the GBM via potential influences on immune-related activities. iAge could be used as biomarkers for predicting the OS and monitoring the stem cell.
Case Report: Evidences of myasthenia and cerebellar atrophy in a chinese patient with novel compound heterozygous MSTO1 variants
Authors: Liu Liqun , Su Ruiting , Huang Peng , Li Xingfang , Xiong Jie , Xiao Yangyang , Mao Dingan , Liu Lingjuan
Published: August 2022

Misato Mitochondrial Distribution and Morphology Regulator 1 (MSTO1) is a soluble cytoplasmic protein that regulates mitochondrial dynamics by promoting mitochondrial fusion. Variants in the MSTO1 gene cause a rare disease characterized by early-onset myopathy and cerebellar ataxia, with almost 30 cases reported worldwide. Here we report a case of a 3-year-old boy with novel heterozygous variants of the MSTO1 gene (c.1A>G (p.M1?) and c.727G>C(p.Ala243Pro)). Sequencing data and subsequent validation show that the two variants were inherited from the mother and father of the patient (both were heterozygous). The clinical features are infancy-onset mental and motor retardation, language disorder, dysarthria, scoliosis, cerebellar atrophy, tremor, lower-extremity muscle weakness, elevated muscle enzymes, extensive myopathy with chronic atrophy, hyperventilation lungs, and previously unreported hairy back and enlarged gastrocnemius. Finally, novel heterozygous MSTO1 variants were discovered in this case, which expands the gene spectrum and clinical phenotype of this type of disease, and provides a new direction for future treatment and research. Then we summarize the mutational spectrum, pathological, clinical features and imaging of MSTO1 variants in a cohort of reported 31 patients and discuss the pathogenesis of MSTO1 in humans.
Glycolysis, monocarboxylate transport, and purinergic signaling are key events in Eimeria bovis-induced NETosis
Authors: Conejeros Iván , López-Osorio Sara , Zhou Ershun , Velásquez Zahady D. , Del Río María Cristina , Burgos Rafael Agustín , Alarcón Pablo , Chaparro-Gutiérrez Jenny Jovana , Hermosilla Carlos , Taubert Anja
Published: August 2022

The protozoan parasiteEimeria bovisis the causative agent of bovine coccidiosis, an enteric disease of global importance that significantly affects cattle productivity. Previous studies showed that bovine NETosis—an important early host innate effector mechanism of polymorphonuclear neutrophil (PMN)—is elicited byE. bovisstages. So far, the metabolic requirements ofE. bovis-triggered NET formation are unknown. We here studied early glycolytic and mitochondrial responses of PMN as well as the role of pH, distinct metabolic pathways, P2 receptor-mediated purinergic signaling, and monocarboxylate transporters 1 and 2 (MCT1, MCT2) inE. bovissporozoite-induced NET formation. Seahorse-based experiments revealed a rapid induction of both neutrophil oxygen consumption rate (OCR) and early glycolytic responses, thereby reflecting immediate PMN activation and metabolic changes upon confrontation with sporozoites. The impact of these metabolic changes on NET formation was studiedviachemical inhibition experiments targeting glycolysis and energy generation by the use of 2-fluor-2-deoxy-D-glucose (FDG), 6-diazo-5-oxo-L-norleucin (DON), sodium dichloroacetate (DCA), oxythiamine (OT), sodium oxamate (OXA), and oligomycin A (OmA) to block glycolysis, glutaminolysis, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, lactate dehydrogenase, and mitochondrial ATP-synthase, respectively. Overall, sporozoite-induced NET formation was significantly diminishedviaPMN pretreatments with OmA and OXA, thereby indicating a key role of ATP- and lactate-mediated metabolic pathways. Consequently, we additionally studied the effects of extracellular pH, MCT1, MCT2, and purinergic receptor inhibitors (AR-C141900, AR-C155858, theobromine, and NF449, respectively). Pretreatment with the latter inhibitors led to blockage of sporozoite-triggered DNA release from exposed bovine PMN. This report provides first evidence on the pivotal role of carbohydrate-related metabolic pathways and purinergic receptors being involved inE. bovissporozoite-induced NETosis.
Evasion of NK cell immune surveillance via the vimentin-mediated cytoskeleton remodeling
Authors: Peng Jei-Ming , Chiu Ching-Feng , Cheng Jai-Hong , Liu Hui-Ying , Chang Yin-Lun , Luo Jia-Wun , Weng Yu-Ting , Luo Hao-Lun
Published: August 2022

Cancer immunotherapy uses the immune system to achieve therapeutic effects; however, its effect is still limited. Therefore, in addition to immune checkpoint-based treatment, the development of other strategies that can inhibit cancer cells from resisting immune cytotoxicity is important. There are currently few studies on the mechanism of tumors using cytoskeletal proteins reorganization to participate in immune escape. In this study, we identified cancer cell lines that were sensitive or resistant to natural killer cells in urothelial and lung cancer using the natural killer cell sensitivity assay. We found that immunoresistant cancer cells avoid natural killer cell-mediated cytotoxicity by upregulation of vimentin and remodeling of actin cytoskeleton. Immunofluorescence staining showed that immune cells promoted the formation of actin filaments at the immune synapse, which was not found in immunosensitive cancer cells. Pretreatment of the actin polymerization inhibitors latrunculin B increased the cytotoxicity of natural killer cells, suggesting that cytoskeleton remodeling plays a role in resisting immune cell attack. In addition, silencing of vimentin with shRNA potentiated the cytotoxicity of natural killer cells. Interestingly, the upregulation and extension of vimentin was found in tumor islands of upper tract urothelial carcinoma infiltrated by natural killer cells. Conversely, tumors without natural killer cell invasion showed less vimentin signal. The expression level of vimentin was highly correlated with natural killer cell infiltration. In summary, we found that when immune cells attack cancer cells, the cancer cells resist immune cytotoxicity through upregulated vimentin and actin reorganization. In addition, this immune resistance mechanism was also found in patient tumors, indicating the possibility that they can be applied to evaluate the immune response in clinical diagnosis.