bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol of a prospective multicenter randomized controlled trial of robot-assisted stereotactic lesioning in the treatment of focal drug-resistant epilepsy
Authors: Gong Mingkun , Xu Ke , Shan Yongzhi , Wang Yihe , Zhang Chao , Wang Xiongfei , Zhou Jian , Guan Yuguang , Li Tianfu , Luan Guoming
Published: June 2023

Background

This protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with a robot-assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy.

Methods

This is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs will also be assessed as secondary outcomes.

Trial registration

Chinese Clinical Trials Registry ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting, and the estimated study completion date is December 31, 2024.
Response to treatment in psoriatic arthritis, the effect of age: analysis of patients receiving ustekinumab in the PsABio real-world study
Authors: Gossec Laure , Theander Elke , Chakravarty Soumya D. , Bergmans Paul , Lavie Frederic , Noël Wim , Sharaf Mohamed , Siebert Stefan , Smolen Josef S.
Published: June 2023

Background

This post-hoc analysis of PsABio (NCT02627768) evaluated safety, effectiveness and treatment persistence in patients < 60 and ≥ 60 years of age receiving ustekinumab over 3 years.

Methods

Measures included adverse events (AE), clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA) including remission, Psoriatic Arthritis Impact of Disease-12 (PsAID-12), Minimal Disease Activity, dactylitis, nail/skin involvement and time to treatment stop. Data were analysed descriptively.

Results

Overall, 336 patients < 60 and 103 ≥ 60 years received ustekinumab, with a similar gender balance. A numerically lower proportion of younger patients reported at least one AE: 124/379 (32.7%) vs 47/115 (40.9%) for patients < 60 and ≥ 60 years, respectively. Serious AEs were low (< 10%) in both groups. At 6 months, the proportion of patients with cDAPSA LDA was 138/267 (51.7%) and 35/80 (43.8%) for patients < 60 and ≥ 60 years, respectively, with the effectiveness being maintained through 36 months. PsAID-12 mean scores reduced for both groups from a baseline mean of 5.73 and 5.61 for patients < 60 and ≥ 60 years, respectively, to 3.81 and 3.88, respectively, at 6 months, and 2.02 and 3.24, respectively, at 36 months. Regarding treatment persistence, 173/336 (51.5%) vs 47/103 (45.6%) patients < 60 and ≥ 60 years, respectively, stopped or switched treatment.

Conclusion

Fewer AEs were observed over 3 years for younger versus older patients with PsA. There were no clinically meaningful treatment response differences. Persistence was numerically higher in the older age group.
Amiodarone-induced blue man syndrome: a case report
Authors: Samadi Takaldani Ali Hossein , Negaresh Mohammad , Salimi Maryam , Javanshir Nima
Published: June 2023

Background

Amiodarone is one of the most commonly used and effective antiarrhythmic drugs to treat ventricular and supraventricular arrhythmias. Besides its advantages, this drug has side effects like liver, digestive, pulmonary, thyroid, neural, skin, optical, hematologic, psychiatric, and cardiac complications. Blue-gray cutaneous discoloration, also known as blue man syndrome, is an undesirable and unusual side-effect of chronic amiodarone therapy in less than 3% of patients.

Case presentation

This report presents a 51-year-old Caucasian man treated for the past 3 years with amiodarone and implantable cardioverter defibrillators due to his ventricular arrhythmia and cardiomyopathy, without any follow-up visit to his doctor. He was referred to the medical center for blue-gray discoloration on his nose and cheeks, which had started to appear in the last 3 weeks.

Conclusion

Considering the findings obtained in this report and the numerous side effects of amiodarone, the blue-man syndrome is a rare yet important finding of this drug which may influence the patient’s daily life. It is recommended that all patients under treatment with this drug be notified about its side effects and visit their doctors regularly. Regarding the high therapeutic value of this drug, the lack of any association between blue man syndrome and other complications, and the related aesthetic problems, the role of the caregiver becomes much more critical in the prescription of amiodarone.
Uncovering the factors influencing the vitality of traditional villages using POI (point of interest) data: a study of 148 villages in Lishui, China
Authors: Liu Sheng , Ge Jian , Bai Ming , Yao Min , Zhu Zhenni
Published: June 2023

Improving vitality has been a major bottleneck in the revitalization of traditional village heritage worldwide. The vitality of traditional village (VTV) varies greatly depending on socioeconomic factors and natural conditions. Significant spatial variation exists in VTV, even within the same urban jurisdictions in China; however, the main determinants for this have not yet been quantified owing to the difficulty of obtaining data from large rural samples, making targeted invigoration difficult. Thus, we applied point of interest data, which are easily accessible big data, to bridge the data source gap. To assess the VTV’s influencing factors and analyze the spatial variations among the factors’ impacting intensity, we used the Ordinary Least Squares and Geographically Weighted Regression models and conducted empirical studies involving 148 traditional villages in Lishui, China. Seven factors influenced the vitality of traditional villages in the study area, with the most significant being topographic relief, elevation, scenic spots and commercial industry. Moreover, the factors’ impacting intensity varied by region. Topographic relief and elevation had the greatest impact intensity in the north and south of Lishui, whereas primary education, transportation facility and agricultural bases had the greatest impact in the north, and scenic spots and commercial industry had the greatest impact in the middle of Lishui. Taken together, this method makes a large sample of VTV’s impact factor analysis feasible, has global implications, and can provide a foundation for the scientific and precise regional promotion of VTV, which is beneficial for rural heritage revitalization.
Anaesthetic management of an infant with severe protein C deficiency and septal cardiac defects—a case report
Authors: Gupta Mayuri , Tiwari Avani , Lather Aditi
Published: June 2023

Background

Protein C deficiency is a rare genetic disorder with varying severity of symptoms and disease. The disorder may vary in presentation from a complete symptomless state to a less severe form like venous thromboembolism. The most severe form of disease is a rare condition called neonatal purpura fulminans (NPF) which is characterized with sudden progressive dermal hemorrhage and necrosis due to vascular thrombosis and disseminated intravascular coagulation. In contrast, congenital atrial and ventricular septal defects are the commonest congenital heart diseases found in pediatric population. An infant presenting with systemic vascular thromboembolism secondary to protein C deficiency along with the cardiac septal defects posted for surgery will be a very challenging task to manage in perioperative period. Also, physiological mechanisms during perioperative period and surgery will promote thromboembolism leading to worsening of the situation further. So, perioperative management of such patient pose a great challenge to the anaesthesiologist. Due to rarity of the condition, there is very limited literature available.

Case presentation

We report the perioperative management of a 2-month-old child suffering with neonatal purpura fulminans with atrial and ventricular septal cardiac defect, scheduled for bilateral foot amputation. The patient was a diagnosed with complete occlusion of abdominal aorta leading to foot gangrene. After initiation of anticoagulant therapy, symptoms were relieved and patient was posted for amputation of gangrenous feet.

Conclusions

There could be an increased risk of thromboembolism and bleeding due to protein C abnormality along with the chances of shunt reversal, paradoxical embolism, and other cardiac morbidities secondary to septal defects. Wise selection of anaesthetic agents like limiting the use of nitrous oxide, ketamine as much as possible to be considered. Conditions like tachycardia, hypotension, and hypothermia should also be prevented perioperatively as these could increase the chances of thrombosis.
Giant hydatid cyst of the liver: a case report with literature review
Authors: Şahin Emrah , Dalda Yasin , Dirican Abuzer
Published: June 2023

Hydatid cyst is a parasitic infection most commonly localized in the liver. They may not be diagnosed early because they remain asymptomatic at small sizes and may reach large sizes at the time of diagnosis. In this situation, compression symptoms may occur and they may present with serious complications such as rupture and anaphylactic shock, which are rare. Treatment methods are determined by classification according to the imaging techniques used in the diagnosis. In the present case, echinococcal cysts originating from segments 5, 6, and 7 in the right lobe of the liver, reaching 35 cm in diameter, caused compression symptoms. The diagnosis was made by abdominal tomography showing characteristic daughter vesicles and calcified cystic wall. The patient underwent pericystectomy and had an uneventful postoperative course with no recurrence in the 5-year follow-up.
Compensating attenuation effects in full-waveform inversion with dissipation-dispersion decoupling
Authors: Xing Guangchi , Zhu Tieyuan
Published: June 2023

Seismic attenuation poses challenges to velocity model building from acoustic/elastic full-waveform inversion (FWI). In particular, when constructing the FWI gradient for velocity inversion, recent studies have indicated that the high-attenuation structure could distort the gradient by damping the amplitudes and shifting the kinematic phases, resulting in an imbalanced update and thus unreliable velocity model. These Q effects are particularly significant in the reflection acquisition geometry due to the “double-damping” issue. Here, we develop a Q-compensated FWI algorithm for constructing a Q-free FWI gradient. By using a recently developed viscoacoustic wave propagator, this compensation can be done conveniently by keeping the dispersion term and flipping the dissipation term in the wave equation when we simulate the forward and time-reversed adjoint wavefields. The resultant gradient obtained by interacting these two wavefields has correct kinematics and Q-free amplitudes. This Q-compensated FWI can balance the update between Q- and no- Q-areas, which we determine using synthetic examples. In addition, we illustrate how to take advantage of the dissipation-dispersion decoupling to determine the anomalous Q value in the Q model building workflow via Q-compensated reverse time migration.
Association of Multiple High-Risk Factors on Observed Outcomes in Real-World Patients With Advanced Ovarian Cancer Treated With First-Line Therapy
Authors: Chase Dana , Perhanidis Jessica , Gupta Divya , Kalilani Linda , Golembesky Amanda , González-Martín Antonio
Published: June 2023

PURPOSE

To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer.

METHODS

This retrospective study included adult patients from a nationwide electronic health record–derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [ BRCA] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed.

RESULTS

Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors.

CONCLUSION

These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.
Prevalence and Clinical Characteristics of PDX1 Variant Induced Diabetes in Chinese Early-Onset Type 2 Diabetes
Authors: Lian Hong , Gong Siqian , Li Meng , Wang Xirui , Wang Fang , Cai Xiaoling , Liu Wei , Luo Yingying , Zhang Simin , Zhang Rui , Zhou Lingli , Zhu Yu , Ma Yumin , Ren Qian , Zhang Xiuying , Chen Jing , Chen Ling , Wu Jing , Gao Leili , Zhou Xianghai , Li Yufeng , Zhong Liyong , Han Xueyao , Ji Linong
Published: June 2023

Context

Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known.

Objective

This study aimed to investigate the prevalence and clinical characteristics of MODY4 in Chinese people clinically diagnosed with early-onset type 2 diabetes (EOD), and to evaluate the relationship between the PDX1 genotype and the clinical phenotype.

Method

The study cohort consisted of 679 patients with EOD. PDX1 mutations were screened by DNA sequencing, and their pathogenicity was evaluated by functional experiments and American College of Medical Genetics and Genomics guidelines. MODY4 was diagnosed in individuals with diabetes who carry a pathogenic or likely pathogenic PDX1 variant. All reported cases were reviewed for analyzing the genotype–phenotype relationship.

Result

4 patients with MODY4 were identified, representing 0.59% of this Chinese EOD cohort. All the patients were diagnosed before 35 years old, either obese or not obese. Combined with previously reported cases, the analysis revealed that the carriers of homeodomain variants were diagnosed earlier than those with transactivation domain variants (26.10 ± 11.00 vs 41.85 ± 14.66 years old, P < .001), and the proportions of overweight and obese individuals with missense mutation were higher than those with nonsense or frameshift mutations (27/34 [79.4%] vs 3/8 [37.5%], P = .031).

Conclusion

Our study suggested that MODY4 was prevalent in 0.59% of patients with EOD in a Chinese population. It was more difficult to identify clinically than other MODY subtypes owning to its clinical similarity to EOD. Also, this study revealed that there is some relationship between genotype and phenotype.
NEAT1_2/RRAD/EHF Positive Feedback Loop Facilitates Aerobic Glycolysis in Papillary Thyroid Cancer Cells
Authors: Sun Wei , Wang Zhiyuan , Qin Yuan , Ji Xiaoyu , Huang Jiapeng , Zhang Fan , Wang Zhihong , Dong Wenwu , He Liang , Zhang Hao
Published: June 2023

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine-related malignancy. In spite of the good prognosis, a more aggressive disease can develop in some PTC patients, leading to poor survival. Nuclear paraspeckle assembly transcript 1 (NEAT1) enhances tumorigenesis; however, the relationship between NEAT1_2 and glycolysis in PTC has not been identified. The expressions of NEAT1_2, KDM5B, Ras-related associated with diabetes (RRAD), and EHF were determined by quantitative reverse transcription polymerase chain reaction and immunocytochemistry. The effects of NEAT1_2, KDM5B, RRAD, and EHF on PTC glycolysis were ascertained employing in vitro as well as in vivo experiments. Chromatin immunoprecipitation (ChIP), RNA binding protein immunoprecipitation, luciferase reporter assays, and co-immunoprecipitation were utilized to analyze the binding abilities among NEAT1_2, KDM5B, RRAD, and EHF. Overexpression of NEAT1_2 was associated with glycolysis in PTC. NEAT1_2 could activate glycolysis by regulating the expression of RRAD in PTC. NEAT1_2 mediated H3K4me3 modification at the promoter of RRAD by recruiting KDM5B. RRAD further negatively regulated glycolysis by binding and regulating the subcellular location of the transcription factor EHF. EHF could activate the transcription of NEAT1_2, hexokinase 2, and pyruvate kinase M2, thereby forming the NEAT1_2/RRAD/EHF feedback loop. Our study revealed that the NEAT1_2/RRAD/EHF positive feedback loop facilitated glycolysis in PTC, which might avail meaningful insight for PTC management.
Parabens Promote Protumorigenic Effects in Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry
Authors: Tapia Jazma L , McDonough Jillian C , Cauble Emily L , Gonzalez Cesar G , Teteh Dede K , Treviño Lindsey S
Published: June 2023

Context

One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed to products containing parabens.

Objective

Studies have shown that parabens impact breast cancer cell proliferation, death, migration/invasion, and metabolism, as well as gene expression in vitro. However, these studies were conducted using cell lines of European ancestry; to date, no studies have utilized breast cancer cell lines of West African ancestry to examine the effects of parabens on breast cancer progression. Like breast cancer cell lines with European ancestry, we hypothesize that parabens promote protumorigenic effects in breast cancer cell lines of West African ancestry.

Methods

Luminal breast cancer cell lines with West African ancestry (HCC1500) and European ancestry (MCF-7) were treated with biologically relevant doses of methylparaben, propylparaben, and butylparaben.

Results

Following treatment, estrogen receptor target gene expression and cell viability were examined. We observed altered estrogen receptor target gene expression and cell viability that was paraben and cell line specific.

Conclusion

This study provides greater insight into the tumorigenic role of parabens in the progression of breast cancer in Black women.
Introduction
Authors: Banerjee Anindita , Safran Gabriella
Published: June 2023

This special issue provokes a radical reconsideration of the pasts and futures of world literature thirty years after the dissolution of the Soviet Union, accompanied by triumphalist declarations of the end of history. Conceived in the wake of racial justice protests in the summer of 2020 and completed amid the invasion of Ukraine in 2022—two events with global reverberations that decisively punctured the illusions of a post-imperial, post-socialist, and post-racial world order homogenized by the unfettered spread of neoliberal capitalism—the articles collected here return to the prehistories and afterlives of a distinct body of transnational, transregional, and transmedian works that emerged from a shared desire to think beyond racial capitalism and socialism conceived within narrow ethnocentric and geopolitical frameworks. Looking backward and forward from the turn of the twentieth century to the present and beyond, they present new theoretical approaches and critical toolkits for what we call the literature of socialist anti-racisms. The connected histories of socialist anti-racist literature, however, were far from unadulterated dreamworlds of solidarity and emancipation; its inherent contradictions, visible on the very surfaces of the texts and contexts examined by our authors, assume particularly nightmarish contours from the vantage point of our shared, violent present.
Civilizational Myth and Class Politics
Authors: Chu Jinyi
Published: June 2023

What is the connection between class and race? Socialist revolutionaries in early twentieth-century Russia engaged with this question in their political essays. The imperial partition of China and the construction of the Trans-Siberian Railway made the China question one of the most topical issues in Russia. This article examines Lenin’s essays on China in which he criticizes racist ideas popular in Russia and Europe. By comparing his essays with other Russian political commentaries on China, this article argues that Lenin views racism as a matter of political economy and global class politics. On the one hand, the myth of racial rivalry and clash of civilizations veils class struggle. On the other, racial and ethnic issues complicate class politics. Lenin’s critique of racism elaborated in the discussion of wars and revolutions in China is not a dogmatic extension of Marx, but directly addresses the transnational migration, geopolitical tension, and intellectual network.
Ethnoracial Utopianism and Speculative Aesthetics after the End of History
Authors: Vint Sherryl
Published: June 2023

Using a reading of Hari Kunzru’s novel Red Pill to frame our contemporary political moment, this article asks what techniques of cultural critique are available to the Left today when the strategies of imaginary worldbuilding have become so central to the ethnonationalist politics of the Right. It argues that the end of the Cold War prompted a reconfiguration of political identities and public discourse in both the West and the former Soviet territories—through distinct but interrelated logics—that highlighted the failures of liberalism in ways that set the stage for the mainstream return of fascist politics of white supremacy. In this context of alternative histories taken as fact, of conspiracy rhetoric seemingly impervious to reason, this article asks how we can respond in intellectually robust ways that will help us to ground an inclusive culture and build a better future, practices the author situates in the broad field of Marxist-informed utopian studies.
Whither Trans Studies?
Authors: Amin Kadji
Published: June 2023

In the face of incisive and important critiques by Andrea Long Chu, Emmett Harsin Drager, Che Gossett, and Eva Hayward, this article proposes that trans studies is a field at a crossroads. It can slide further into irrelevance by continuing to promote trans- as an abstract prefix of crossing, or it can become relevant to trans people by focusing on the material heterogeneity of trans populations, histories, and epistemologies. The article sketches out some of the rich and exciting directions the latter inquiry could take. With reference to particularly generative proposals by graduate students in this issue, it argues that trans and gender-variant life is a more than sufficient basis for the field.
Chapter Eight: Toxic Colonialism, Alienation, and Posthuman Dystopia in Chen Qiufan
Authors: Wang Ban
Published: June 2023

Chen Qiufan's sci-fi novel Waste Tide attests to the dual alienation of nature and humans. Global capitalism, geopolitical conflict, the scramble for natural resources, and rash development have destroyed the rural community, ruined the health of local populations, and eroded the natural environment. Technical advances—artificial intelligence, brain-computer interface, biochemical technologies, and cyborg construction—aggravate metabolic rifts in the human-nature relations, threatening human bodies, regional culture, and local traditions. Driven by profit motives and the desire for power, the advanced technologies are accelerating the alienation of humans from their bodies, from one another, and from nature.
Sex-specific transgenerational plasticity: developmental temperatures of mothers and fathers have different effects on sons and daughters
Authors: Seebacher Frank , Bamford Stephanie M. , Le Roy Amelie
Published: June 2023

Each parent can influence offspring phenotype via provisioning of the zygote or sex-specific DNA methylation. Transgenerational plasticity may therefore depend on the environmental conditions experienced by each parent. We tested this hypothesis by conducting a fully factorial experiment across three generations of guppies (Poecilia reticulata), determining the effects of warm (28°C) and cold (21°C) thermal backgrounds of mothers and fathers on mass and length, and thermal performance (sustained and sprint swimming speeds, citrate synthase and lactate dehydrogenase activities; 18, 24, 28, 32 and 36°C test temperatures) of sons and daughters. Offspring sex was significant for all traits except for sprint speed. Warmer mothers produced sons and daughters with reduced mass and length, and warmer fathers produced shorter sons. Sustained swimming speed (Ucrit) of male offspring was greatest when both parents were raised at 28°C, and warmer fathers produced daughters with greater Ucrit. Similarly, warmer fathers produced sons and daughters with greater metabolic capacity. We show that the thermal variation experienced by parents can modify offspring phenotype, and that predicting the impacts of environmental change on populations would require knowledge of the thermal background of each mother and father, particularly where sexes are spatially segregated.
RNA in situ conformation sequencing reveals novel long-range RNA structures with impact on splicing
Authors: Margasyuk Sergey , Kalinina Marina , Petrova Marina , Skvortsov Dmitry , Cao Changchang , Pervouchine Dmitri D.
Published: June 2023

Over recent years, long-range RNA structure has emerged as a factor that is fundamental to alternative splicing regulation. An increasing number of human disorders are now being associated with splicing defects; hence it is essential to develop methods that assess long-range RNA structure experimentally. RNA in situ conformation sequencing (RIC-seq) is a method that recapitulates RNA structure within physiological RNA–protein complexes. In this work, we juxtapose pairs of conserved complementary regions (PCCRs) that were predicted in silico with the results of RIC-seq experiments conducted in seven human cell lines. We show statistically that RIC-seq support of PCCRs correlates with their properties, such as equilibrium free energy, presence of compensatory substitutions, and occurrence of A-to-I RNA editing sites and forked eCLIP peaks. Exons enclosed in PCCRs that are supported by RIC-seq tend to have weaker splice sites and lower inclusion rates, which is indicative of post-transcriptional splicing regulation mediated by RNA structure. Based on these findings, we prioritize PCCRs according to their RIC-seq support and show, using antisense nucleotides and minigene mutagenesis, that PCCRs in two disease-associated human genes,PHF20L1andCASK, and also PCCRs in their murine orthologs, impact alternative splicing. In sum, we demonstrate how RIC-seq experiments can be used to discover functional long-range RNA structures, and particularly those that regulate alternative splicing.
Bayesian transfer learning for personalised well-being forecasting from scarce, sporadic observations
Authors: Χριστινάκη Ειρήνη
Published: June 2023

Η έρευνα που παρουσιάζεται σε αυτή τη διατριβή έχει διεξαχθεί στο πλαίσιο του έργου NEVERMIND. Ο σκοπός της διδακτορικής διατριβής ήταν να διερευνήσει και να προτείνει νέες προσεγγίσεις για την αντιμετώπιση των προκλήσεων που σχετίζονται με τη δημιουργία εξατομικευμένων μοντέλων και την πραγματοποίηση προβλέψεων σε εφαρμογές που σχετίζονται με την υγεία όταν η εκπαίδευση εκτελείται σταδιακά σε λίγα σποραδικά βιοϊατρικά δεδομένα. Μια ιδιαίτερη πρόκληση ήταν η δυνατότητα παροχής αξιόπιστων εξατομικευμένων προγνώσεων στο πρώιμο στάδιο της συλλογής δεδομένων δηλαδή όταν δεν υπάρχουν επαρκή δεδομένα για εκπαίδευση. Η λύση που προτείνεται σε αυτή τη διατριβή επικεντρώνεται σε τεχνικές Μπεϋζιανής μάθησης με μεταφορά (Bayesian Transfer Learning) που επέτρεψε να γίνουν έγκυρες προγνώσεις ακόμη και σε τέτοιες δύσκολες συνθήκες αξιοποιώντας πληροφορίες που προέρχονται από άλλους ασθενείς. Αρχικά, προτείνεται μια μη παραμετρική προσέγγιση μεταφοράς μάθησης, η οποία επέτρεψε να γίνουν πιο ακριβείς προγνώσεις για έναν συγκεκριμένο ασθενή συνδυάζοντας μοντέλα που έχουν εκπαιδευτεί σε άλλους ασθενείς «δότες» ανάλογα με το πόσο καλά αυτά τα μοντέλα ταιριάζουν με τις προηγούμενες παρατηρήσεις του συγκεκριμένου ασθενούς. Δεύτερον, αναπτύχθηκε μια παραμετρική προσέγγιση μάθησης μεταφοράς, η οποία ενσωματώνει μια τροποποιημένη πρότερη (prior) πιθανότητα που λαμβάνει υπόψιν της τη διαθέσιμη γνώση από όλους τους άλλους ασθενείς «δότες». Τέλος, προτείνονται τροποποιημένες εκδοχές των δύο προηγούμενων προσεγγίσεων, όπου ελέγχετε πόση πληροφορία δανείζεται για μεταφορά με βάση την ομοιότητα στα συναισθηματικά προφίλ μεταξύ του υπό δοκιμή ασθενούς και κάθε ασθενή «δότη». Τα αποτελέσματα δείχνουν ότι οι προτεινόμενες μέθοδοι μεταφοράς μάθησης όχι μόνο αντιμετώπισαν φυσικά τα ακανόνιστα, σποραδικά δεδομένα στο σετ των δεδομένων, αλλά επίσης απέδωσαν πολύ καλά ακόμα και στα πιο δύσκολα σενάρια πρόγνωσης, όπως στην περίπτωση που έχουμε διαθέσιμα δεδομένα μόνο επτά ημερών και το σύστημα απαιτείται να προγνώσει τις επόμενες επτά ημέρες. Γενικά, αυτές οι προσεγγίσεις παρήγαγαν καλύτερα μοντέλα για συμμετέχοντες με πολύ λίγα σποραδικά δεδομένα εκπαίδευσης και απέδωσαν σημαντικά καλύτερα από ορισμένα ανταγωνιστικά μοντέλα.
Habit forming properties of laxatives for chronic constipation: A review
Authors: Balekuduru Avinash , Sahu Manoj Kumar
Published: June 2023

Constipation is a commonly reported disorder in many patients. Constipation treatment using laxatives on a regular and long term basis can lead to patient dependence, especially among the elderly. However, there is scanty data on the habit-forming potential of laxatives in Indian constipated patients. This review has explored literature evidence and expert opinion on patients’ experience regarding habit-forming attributes of stimulant and osmotic laxatives. Additionally, structured face-to-face discussions were conducted with 2 key opinion leaders to understand their clinical experience on the habit-forming aspects stimulant and osmotic laxatives in patients with constipation. Based on literature evidence, lactulose is not known to lead to any habit-forming behaviors in patients. Furthermore, experts pointed out that dependence on stimulant laxatives is common, but not on osmotic laxatives, and emphasized that milk of magnesia is not habit forming. In conclusion, no habit-forming characteristics or dependence was observed with the use of osmotic laxatives in India. Nevertheless, real-world, studies exploring patient and physician perspectives are warranted to establish the dependence and habit forming attributes of laxatives.
Energy security as a research area of international security
Authors: Misiągiewicz Justyna
Published: June 2023

The research objective of the study is to analyse the essence and specificity of energy security in the light of research on international security. Thus, various theoretical approaches, useful in the analysis of energy security issues, were taken into account. The analysis allows us to conclude that energy security issues take into account long-term development trends as well as unpredictable events related to the functioning of energy market and energy technology. Thus, unexpected, sudden phenomena resulting from the dynamics of the international environment gain in importance. The dilemma related to non-linear thinking often ignores a variety of solutions that, taken together, can cause a radical turn in the energy security concept and its evolution.
DEVELOPMENT OF A SUBSYSTEM FOR THE RECOGNITION OF SIGNALS WITH A COMPLEX SHAPE
Authors: Avetisyan Tatiana V. , Lvovich Jakov E. , Preobrazhenskiy Andrey P.
Published: June 2023

The modern stage of development of radio information systems is characterized by one general tendency. It consists in that object of their processing are various kinds of images, difficult enough on structure and with heterogeneous statistical properties. Television, diagnostic and security systems, observation systems for land and water surfaces, near space can serve as an example. The task of such systems is not only a passive function such as formation of images themselves, but first of all the understanding of images - detection on a complex statistically heterogeneous and multigradational in brightness background of the objects of interest, recognition and evaluation of their parameters. The image form is a concentrator of information contained in the image. It is interpreted as an analytically defined signal. This paper proposes a subsystem for the recognition of signals of complex shape, based on sensor networks. The illustration of the structural scheme of the subsystem is given. The technique of image recognition is shown. The results of the recognition are presented.
Domenico Lovascio. John Fletcher’s Rome: Questioning the Classics. Manchester: Manchester University Press, 2022. Pp 212.
Authors: McMullan Gordon
Published: June 2023

Review of John Fletcher’s Rome: Questioning the Classics by Domenico Lovascio
José A. Pérez Díez, ed. Love’s Cure, or The Martial Maid by John Fletcher and Philip Massinger. Manchester: Manchester University Press, 2022. Pp 250.
Authors: Griffin Eric
Published: June 2023

Review of Love's Cure, or The Martial Maid by José Pérez Díez, ed.
Curtailing Bank Loan and Loan Insurance Under Risk Regulations in Supply Chain Finance
Authors: Wang Wenli , Cai Gangshu (George)
Published: June 2023

Because of many firms’ lack of collateral, banks have imposed loan limits as a form of risk-control regulations of bank financing. In response, loan insurance has emerged as a useful instrument to lift loan limits. To study the joint value of bank loans and loan insurance, this article investigates a supply chain composed of one supplier and one capital-constrained buyer who takes out a bank loan and potentially purchases loan insurance. The analysis reveals that both the supplier and the buyer can benefit from the bank financing with loan insurance in an insurance-cooperation region wherein the supplier is willing to reduce the wholesale price to entice the buyer to purchase insurance. Further still, in the insurance-cooperation region, worse contract terms of the bank loan benefit the supplier, whereas worse policy terms of loan insurance help the buyer. Such benefits can lead to a higher order quantity than the capital-abundant one and partially coordinate the entire supply chain. However, when production cost is low, the supplier and the buyer can encounter a Stackelberg prisoner’s dilemma, in which both firms no longer cooperate with each other, and both are worse off. Nevertheless, a government subsidy for the insurance premium can not only reduce the Stackelberg prisoner’s dilemma, but also improve the social welfare although it is not always optimal for the government to provide that subsidy. The main qualitative results are robust in a variety of extensions.

This paper was accepted by Jayashankar Swaminathan, operations management.

Funding: The first author acknowledges support from the National Natural Science Foundation of China (NSFC) [Grant 72171162] and the Humanity and Social Science Youth Foundation of Ministry of Education of China [Grant 20YJC630148], and the second author acknowledges support from the NSFC [Grant 72232001].

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4827 .
Specifics features of the use of didactic games in the formation of speech competence of pre-school children with special educational needs
Authors:   MI ", Kalinina Tetiana ,   Kharkiv Humanitarian and Pedagogical Academy",   of Kharkiv Regional Council, Yatsynik Alla ,   MI "Kharkiv Humanitarian and Pedagogical Academy" of Kharkiv Regional Council
Published: June 2023

In the article the lighted up questions of forming of speech competence of children of preschool age are with the special educational necessities. A basic accent is done on the features of organization of correction help to the children with violation of speech development, namely by the general escalation of broadcasting. Paid attention to the questions of organization of educationally-correction process taking into account the type of leading activity. Reasonable necessity of the use of playing methods receptions for work with preschool children on the basis of type of leading activity. Importance of taking into account of features of leading activity is certain during planning of educational work with children. Experience of scientists and practical workers is analyzed through this question and it is systematized in accordance with the requirements of present time. Designed basic principles of the use of the didactics playing organization of educationally-correction work with the children of preschool age. In modern pedagogy, two types of didactic games are distinguished: activity games and directly didactic games. Certain conformities to law of the use of didactics games, them modern classification and structure, and also basic principles of construction of educational process of children of preschool age the use of didactics games. There are the given practical recommendations in relation to the features of organization of correction help taking into a count the type of leading activity of child of preschool age certain methodical aspects of the use of the didactics playing modern system of educationally-correction process.
The importance of fitness in the recreational training of future specialists in physical culture
Authors:   National University ", Heta Alla ,   Yuri Kondratyuk Poltava Polytechnic", Ostapov Andrian ,   National University "Yuri Kondratyuk Poltava Polytechnic", Moroz Olena ,   Taras Shevchenko National University of Kyiv
Published: June 2023

Modern globalization processes determine the vital necessity of policy implementation in the field of training of highly qualified personnel of higher education. Studying the experience of training specialists requires a critical analysis of the achievements of existing educational systems. Their adaptation to national needs will make it possible to implement positive trends in the higher education sector of Ukraine. The paradigm of education in the field of fitness and recreation has changed significantly in recent decades, which is explained by the orientation towards a fundamentally new understanding of the essence of recreation and its role in the educational system. At the same time, there is a public need in Ukraine for specialists in physical education and sports who are able to perform recreational and recreational activities, which is extremely important for the promotion of a healthy lifestyle, disease prevention and increasing the level of physical activity of various segments of the population, therefore there is a need to define key aspects and trends in the training of specialists in recreational and recreational activities in higher education, where the personality of a specialist in recreational and recreational activities is one of the most important factors in attracting the population to rational motor activity. The study is dedicated to the development of ways to improve the recreational training of future physical culture specialists, a training mechanism for health aerobics, athletic gymnastics, children’s fitness, “fitness class”, etc. has been created. The content of classes has been developed, taking into account the profile of training (sports training, physical education, etc.), models of fitness programs for future use in preschool, school, secondary special and higher educational institutions, sports sections. The effectiveness of fitness in increasing physical fitness, being able to make an individual program of classes and nutrition, solving situational tasks, conducting fitness classes, knowledge of types of recreational activities for the future professional activity of physical culture specialists is shown.
Features of the structure of long-term training of sprinters on short distances
Authors:   State Institution Luhansk Taras Shevchenko National University, Polulyaschenko Tetiana , Pavlov Roman ,   State Institution Luhansk Taras Shevchenko National University
Published: June 2023

The article deals with topical issues regarding the peculiarities of building a long-term training process for short-distance running, taking into account all stages of long-term preparation. An analysis of the latest research and publications related to the training of athletes specializing in shortdistance running and the specifics of their training at various stages of long-term improvement was made. The article reveals the important essence of the interrelationship of all stages of long-term preparation of athletes. The main goal of the work is to study the structure of the long-term training of young sprinters, and the task is to substantiate the structure of the long-term preparation of beginner sprinters. As a result of the study, a number of questions were clarified that contribute to the effective construction of training for sprinters in the process of long-term preparation. The structure of longterm preparation of sprinters was studied, the analysis of structural elements was made. The longterm system was considered as a set of independent and at the same time interconnected stages of athlete preparation. The regularities on which the formation of sportsmanship in sprint running is based on the process of long-term training have been studied. The factors that will determine the effectiveness of competitive activity, the optimal structure of its preparation, the peculiarities of adaptation to the applied pedagogical tools and methods, their influence on the individual characteristics of athletes, the timing of preparation and the achievement of maximum results according to the age of athletes and the stage of long-term training, etc. have been identified. The importance of observing age parameters and their correspondence to the stages of long-term training, the use of model parameters of sprinters of various sports qualifications at the initial stage of training were studied.
The use of therapeutic exercises for thoracic scoliosis of the second degree for secondary school students in the format of telerehabilitation
Authors:   State Institution Luhansk Taras Shevchenko National University, Radchenko Alina , Berezuieva Tetiana ,   State Institution Luhansk Taras Shevchenko National University, Ochkalov Oleksandr ,   State Institution Luhansk Taras Shevchenko National University
Published: June 2023

The article will reveal the issue of organizing physical therapy for second-degree scoliosis in secondary school students in the format of telerehabilitation, which has its own characteristics and approaches to use. The relevance of this modern direction is that the patient independently (as a rule, at home) performs restorative treatment programs at the outpatient stage under remote control and guidance of a specialist doctor. According to the format of telerehabilitation, the program of physical therapy of the thoracic spine included a consultation on the patient’s orthopedic regimen and safety techniques during therapeutic exercises, as well as special sets of therapeutic exercises. Therapeutic exercise classes were held in such periods as gentle, gentle-training and training, each of them had its own tasks. All periods included exercises for forming the correct posture, symmetrical exercises, static exercises, exercises for relaxation, toning muscle building, exercises for adjusting and stabilizing the spine in the correct position, etc. Scoliometry was used to evaluate the results of telerehabilitation. The effectiveness of the organization of telerehabilitation for thoracic scoliosis of the second degree in middle school students showed a positive dynamic of scoliometry, the angle of curvature changed in each patient to a smaller side, which indicates correctly selected methods of physical therapy and their dosage. It was also concluded that the development of telerehabilitation is a very urgent problem nowadays. This direction of physical therapy should be improved through the development of programs for asynchronous telerehabilitation, where the patient will be able to engage in his recovery at a time convenient for him and interact with the physical therapist through appropriate applications.