bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of long-term treatment with thrombopoietin receptor agonists of resistant primary immune thrombocytopenia
Authors: Vinogradova O. Yu. , Pankrashkina M. M. , Mukha L. A. , Neverova A. L. , Chernikov M. V. , Ptushkin V. V. 
Published: December 2024

Background. Thrombopoietin receptor agonists (TORAs), which can imitate the biological effect of thrombopoietin, have shown high efficacy in a number of clinical studies and real clinical practice in patients with resistant primary immune thrombocytopenia (IT). It seems extremely relevant to evaluate the success of using various TORAs in a longterm nonrandomized study and their comparative effectiveness.Aim. To evaluate the longterm efficacy of TORAs (romiplostim and eltrombopag) in patients with primary IT who are resistant to standard therapy, and to determine the clinical and hematological factors predicting the efficacy of TORAs therapy.Materials and methods. The study included 456 patients with primary IT (127 (28 %) men and 329 (72 %) women) who were resistant to standard therapy. atients received TORAs therapy at the otkin Hospital. The median age at the start of TORAs therapy was 59 (9–91) years. Romiplostim was received by 339 patients (95 (28 %) men and 244 (72 %) women), eltrombopag – 117 (32 (27 %) men and 85 (73 %) women).Results. The median duration of TORAs therapy was 78 (1–583) weeks for romiplostim and 59 (1–572) weeks for eltrombopag. uring the TORAs therapy the platelet response was obtained in 89 % (n = 405) of cases in total group of IT patients, in the romiplostim group – in 90 % (n = 306), in the eltrombopag group – in 85 % (n = 99). y the time of data analysis in the total cohort of IT patients, 55 % (n = 253) of patients maintained a sustained platelet response, with a median duration of 159 (2–655) weeks. Among patients receiving romiplostim, these parameters were 59 % (n = 200) and 149 (2–655) weeks, for eltrombopag – 45 % (n = 53) and 240 (24–565) weeks, respectively. The 10‑year overall survival rate with TORAs therapy, regardless of the drug chosen, was 86 %. Negative predictors of achieving a platelet response to romiplostim therapy were identified: ≥2 lines of previous therapy (p = 0.03), a history of splenectomy (p = 0.02). No negative predictors of platelet response to eltrombopag therapy were identified.Conclusion. The longterm efficacy of 2 drugs of the same therapeutic class (TORAs), romiplostim and eltrombopag, in patients with resistant IT was demonstrated in a direct comparative analysis in a nonrandomized study. Clinical and hematological factors predicting the longterm effectiveness of romiplostim were identified.
Native and pegylated forms of L-asparaginase: the assessment of effectiveness and toxicity in acute lymphoblastic leukemia treated with Berlin–Frankfurt–Munster (BFM) protocol
Authors: Shervashidze M. A. , Smirnova D. S. , Valiev T. T. , Batmanova N. A. 
Published: December 2024

Background. Lasparaginase is an integral part of chemotherapy regimens in treatment of patients with acute lymphoblastic leukemia (ALL). However, the use of Lasparaginase is limited due to wide range of adverse reactions. Our research demonstrates the toxicity effects and treatment results in patients with ALL who received native and pegylated (EG) Lasparaginase.Materials and methods. From 2013 to 2023 in the study 199 patients with newly diagnosed ALL were enrolled. Patients were treated according to the ALL ICFM 2009 protocol including Lasparaginase. The average age of patients was 4.6 (1–18) years. ALL was diagnosed in 175 (87.9 %) patients, TALL in 24 (12.1 %) patients. Native Lasparaginase was used in the therapy of 51 (25.6 %) patients; if allergic reactions occured, 72 (36.2 %) patients received EG asparaginase. In 76 (38.2 %) patients treatment protocol included only EGasparaginase without native Lasparaginase history.Results. The most common adverse event was a hypersensitivity reaction – 27.6 % (n = 55), which was more common in the cohort of patients receiving native Lasparaginase. The incidence of hypercoagulation for patients treated with native Lasparaginase was 4 % and 0 % – for EGasparaginase group. Hypocoagulation, presented as hypofibrinogenemia registered in 13 % of patients received native Lasparaginase and in 35 % for EGasparaginase group. ancreatitis, complicated ALL treatment were diagnosed in 4 % after native Lasparaginase and 1 % after EGasparaginase. The best 5‑year survival rates were observed in the group of patients who initially received EGasparaginase – overall and eventfree survival were 100 and 87.5 (11.7) %, respectively (р >0.05).Conclusion. espite the absence of convincing survival benefit in patients with newly diagnosed ALL treated with EGasparaginase, the toxicity profile was better in contrast to native Lasparaginase.
El Escorial como “octava Maravilla del mundo”: un estudio léxico-terminológico de “maravilla”/lo “maravilloso” en la Descripción breve del padre Santos (1657)
Authors: Castilla Ortega Marina 
Published: December 2024

La idea del Real Monasterio de El Escorial como “octava Maravilla del mundo” (y superior a las siete restantes) constituye uno de los tópicos literarios que más fama ha otorgado al monumento desde sus albores, a finales del siglo XVI.
Debido a su pervivencia hasta nuestros días, se plantea un estudio léxico-terminológico monográfico del vocablo “maravilla”/lo “maravilloso” en uno de los textos descriptores del Monasterio que más uso hizo del mismo (así demostrado tras estudios previos comparativos con otras descripciones): la Descripción breve del jerónimo fray Francisco de los Santos (1657). De este modo, la presente investigación, con una metodología inherente a las Humanidades Digitales, arroja luz sobre el significado del concepto en este testimonio, paradigmático de la esencia de la “maravilla” escurialense.
La gestión del riesgo de desastres en la reglamentación local de Bogotá, Medellín y Cali: análisis de la inclusión del enfoque diferencial de género para la garantía de derechos de mujeres y niñas
Authors: Pabón-Mantilla Ana Patricia , Vásquez-Santamaría Jorge Eduardo 
Published: December 2024

The public function of urban planning involves disaster risk management as one of its determinants of superior hierarchy, an administrative function that is governed by legal provisions based on universal subjects, legal neutrality, and formal equality. Local territorial
entities serve as a platform for reviewing this public function of urban planning, as it is subject to international instruments that promote the incorporation of a gender perspective in disaster risk management. In this dilemma, the administrative autonomy of local territorial entities leads to the issuance of regulations that include the gender perspective, which, without directly referring to disaster risk management, can ultimately integrate it into territorial planning.

Therefore, the aim was to analyze the configurations of the gender perspective in disaster risk management that seek to guarantee the rights of women and girls, based on the regulatory exercise undertaken by local territorial entities regarding planning and territorial organization instruments. The study adopted a comprehensive hermeneutic paradigm and qualitative methodology, focusing on the legal dogma in territorial regulation, with a documentary study that triangulated its regulation in Bogotá, Medellín, and Cali to determine the configuration of the differential gender perspective through regulatory practice. The results show that while provisions referring to the gender perspective are included, acknowledging the discrimination and inequities affecting women and girls, they fail to address the realm of risk management. It is concluded that planning and territorial organization do not provide elements for disaster risk management to break the thesis of universality in addressing the needs of individuals who may be affected by a disaster.
ANALYSIS OF DIRECTLY OBSERVED TREATMENT SHORTCOURSE IMPLEMENTATION AS AN EFFORT TO CONTROL TUBERCULOSIS IN YOGYAKARTA
Authors: Liena Sofiana  , Muthiah Tis’a Salma , Putri Nawwara 
Published: December 2024

Introduction: Globally, tuberculosis (TBC) continues to be a factor causing morbidity and death. During the COVID-19 epidemic, case detection has decreased globally; Indonesia is one of the countries that sees this. For many years, the Directly Observed Treatment Shortcourse (DOTS) approach has been used as a TB control program. Based on case studies, the success rate for tuberculosis treatment in Yogyakarta is 86.4%, which does not meet the national target. Aims: To evaluate the Yogyakarta DOTS strategy in reducing TB. Methods: This research uses a qualitative case study design methodology. Six people participated in this research as respondents; two of them were drug swallowing supervisors, and four of them were TBC program participants. Theme analysis was applied to data analysis. Results: Yogyakarta successfully implemented DOTS which consists of five strategies. There are no gubernatorial regulations derived from presidential regulations regarding TB control; however, there was a decision by the governor to accelerate the eradication of TB, which later became a political commitment. Cases were identified through sputum examination using a rapid molecular test. Healthcare institutions have adequate access to medicines, which are monitored by the drug swallowing supervisors. Tuberculosis information system (SITB) is used in monitoring, recording and reporting systems. Conclusion: Implementing the five of Directly Observed Treatment Shortcourse strategies in controlling TBC in Yogyakarta has been done quite well. However, implementation is still hampered by a lack of human resources, computer infrastructure, and connections, all of which impact timely reporting.
Influence of Humeral Component Cement and Bone Grafting on Greater Tuberosity Healing and Functional Outcomes After Reverse Shoulder Arthroplasty for Proximal Humerus Fractures
Authors: Kaiser Andrew H.A. , Buchanan Timothy R. , Bindi Victoria E. , Holt Kara E. , Reddy Akshay R. , Tishad Abtahi , Hones Keegan M. , Wright Jonathan O. , Wright Thomas W. , Schoch Bradley S. , King Joseph J. , Hao Kevin A. 
Published: December 2024

Background:
Reverse shoulder arthroplasty (RSA) is increasingly used in the treatment of displaced proximal humerus fractures (PHFs) with reliable clinical improvement. However, the preferred techniques for humeral stem fixation are varied and may be influenced by patient and injury characteristics, including bone quality and fracture pattern. This systematic review and meta-analysis sought to determine the effect of humeral component cementing and bone grafting on tuberosity healing rates and functional outcomes after RSA for PHFs.

Methods:
A systematic review was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane were queried for clinical studies on RSA performed for PHFs that reported on the use of cemented humeral stems and autograft bone. The primary outcome was the rate of greater tuberosity healing between the various techniques. Secondarily, the authors compared clinical outcomes including postoperative external rotation, forward elevation, abduction, Constant score, and the incidence of complications and revision surgery. Outcomes were compared based on the use of an uncemented press-fit stem, a fully cemented stem without bone graft, or a partially cemented stem with humeral head autograft (i.e., black and tan technique).

Results:
Forty-eight studies reporting on 1,797 RSAs were included (mean patient age, 75 years; follow-up, 34 months; 81% female). Tuberosity healing was highest in the uncemented cohort, then the black and tan cohort, and lowest in the cemented cohort (80% vs. 70% vs. 61%, p = 0.006). No significant differences in postoperative range of motion, Constant score, complication rates, or revision rates were found.

Conclusion:
Uncemented fixation with a press-fit stem was associated with superior greater tuberosity healing rates; however, functional outcomes and complications did not differ among techniques.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Effects of Flow and Geomechanics Coupling in Faulted Reservoirs for CO2 Storage
Authors: Ferrari Andrea , Nardean Stefano , Monaco Silvia , Garipov Timur , Mantica Stefano , Cominelli Alberto 
Published: December 2024

Summary
Accurately reproducing the coupling of fluid flow in porous media and rock mechanics is crucial for the modeling of CO2 geological storage to properly evaluate and prevent the risk of inducing fault instability during injection operations. As an alternative to using monolithic flow/mechanical suites, the process can be modeled by linking individual codes, that is i, a reservoir simulator for flow and a geomechanical package to account for fluid-induced stress change, which tackle the two problems sequentially. We developed a flexible numerical framework from which different coupling logics can be selected (i.e., one-way coupling, two-way iterative coupling, and two-way explicit coupling), which are characterized by different levels of accuracy and computational costs. A multirate, two-way coupling algorithm, which allows the flow and mechanical simulators to exchange information periodically rather than at every timestep, is also available to reduce the computational cost of two-way coupled simulations. In this work, we use this coupling infrastructure to perform numerical experiments aimed at defining whether sequential iterative coupling is strictly needed or not, and which less expensive logic can be used to attain a similar solution accuracy. First, a synthetic test case is used to illustrate the onset of fault instability during CO2 injection operations for different sets of coupling parameters (type and frequency), rock properties, and fault permeability. It is thus possible to evaluate, for a reasonable range of coupling strength, which depends on fluids and rock properties, the optimal level of coupling. Results are strongly influenced by the coupling strength, and two-way iterative coupling should be selected for tightly coupled systems to accurately reproduce the fault behavior. For a loosely coupled system, instead, the one-way approach should be the preferred choice due to its lower computational cost. Later, we consider CO2 injection into a realistic formation, and we analyze the impact of the coupling frequency on the computational performance. We show that, for complex cases, there is no one-to-one correspondence between the reduction in the number of coupling iterations and the reduction in computational time for increasing coupling period.
The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel
Authors: Wang Zhao , Wu Hongjiang , Sun Liang , Wensel Theodore , Horrigan Frank , Huo Tong 
Published: December 2024

Abstract

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality due to Pi's essential role in numerous biological processes. Proper phosphate levels are managed through Pi import and export, facilitated by specific Pi transport proteins. Although the mechanisms of Pi import have been extensively studied, the processes governing Pi export remain less understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals, playing a key role in facilitating Pi efflux from cells. Malfunctions in XPR1 are associated with human diseases, such as primary familial brain calcification and certain cancers, highlighting its critical role in maintaining Pi homeostasis. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter, with a topology not identified in previous computational predictions. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and Pi-dependent activity and large unitary conductance. Using proteoliposomal uptake assays, we demonstrate that purified and reconstituted hXPR1 catalyzes transport of Pi. Further analysis, including the structure of hXPR1 in presence of Pi, and functional effects of mutating a putative Pi binding site, leads us to propose a plausible ion permeation pathway. Together, our results provide novel perspectives on the Pi transport mechanism of XPR1 and its homologues.
Neuroprotective Role of Tocopherol Derivatives in Alzheimer’s Disease: Behavioral and Biochemical Analysis
Authors: Iqbal Zafar , Yousaf Faha , Chatha Humayun Iftikhar , Shahzad Sana , Anwar Fareeha , Shabbir Muhammad Danial , Waseem Syeda Hira , Manan Maria 
Published: December 2024

Abstract

Alzheimer’s Disease (AD) is a terminal disease that results from progressive loss of neurons in the brain leading to cognitive dysfunction, memory loss, and neuroinflammation. The purpose of this investigation was to establish the neurotrophic profile of a newly synthesized naphthalene tocopherol competitive to Vitamin E acetate in an AD mouse model. The learning and memory were examined by the following behavioral paradigms: Fear Conditioning Test, Barnes Maze Test, Elevated Plus Maze Test and Morris Water Maze Test. Immunohistochemical observations were made to assess markers of oxidative stress using MDA, SOD, and GSH and neuroinflammation using IL-6 and TNF-α. The effectiveness was evidenced through the reduction of oxidation stress, reducing cytokines that cause inflammation, and overall enhancement on cognitive functioning among the groups administered with the tocopherol derivative at the dosages of 20 mg/kg and 40 mg/kg. These findings indicate that tocopherol derivatives could indeed have a more robust neuroprotective activity than the standard Vitamin E with an application in the treatment of AD. Carrying out similar experiments in human would be another approach to confirm these findings as well as determine the molecular basis of their effects.
Predictive Modeling of Biodegradation Pathways Using Transformer Architectures
Authors: Brydon Liam , Zhang Kunyang , Dobbie Gillian , Taškova Katerina , Wicker Jörg Simon 
Published: December 2024

Abstract

In recent years, the integration of machine learning techniques into chemical reaction product prediction has opened new avenues for understanding and predicting the behaviour of chemical substances. The necessity for such predictive methods stems from the growing regulatory and social awareness of the environmental consequences associated with the persistence and accumulation of chemical residues. Traditional biodegradation prediction methods rely on expert knowledge to perform predictions. However, creating this expert knowledge is becoming increasingly prohibitive due to the complexity and diversity of newer datasets, leaving existing methods unable to perform predictions on these datasets. We formulate the product prediction problem as a sequence-to-sequence generation task and take inspiration from natural language processing and other reaction prediction tasks. In doing so, we reduce the need for the expensive manual creation of expert-based rules.

Scientific Contribution We contribute the first study of the transformer's ability to predict biodegradation reactions. Our proposed method can more accurately and efficiently predict biodegradation reactions on more compounds than existing methods. We also contribute a framework for evaluating transformer product prediction methods that can better illustrate the method's performance and is more suitable for comparison to other methods.
BMIgap: a new tool to quantify transdiagnostic brain signatures of current and future weight
Authors: Koutsouleris Nikolaos , Khuntia Adyasha Tejaswi , Popovic David , Sarisik Elif , Buciuman Madalina O. , Pedersen Mads L. , Westlye Lars T. , Andreassen Ole , Meyer-Lindenberg Andreas , Kambeitz Joseph , Salokangas Raimo , Hietala Jarmo , Bertolino Alessandro , Borgwardt Stefan , Brambilla Paolo , Upthegrove Rachel , Wood Stephen , Lencer Rebekka , Meisenzahl Eva , Falkai Peter , Schwarz Emanuel , Wiegand Ariane 
Published: December 2024

Abstract

Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. We used support-vector machines and whole-brain voxel-wise grey matter volume to generate and validate a BMI predictor in healthy individuals (N = 1504) and applied it to individuals with schizophrenia (SCZ,N = 146), clinical high-risk states for psychosis (CHR,N = 213) and recent-onset depression (ROD,N = 200). We computed BMIgap (BMIpredicted-BMImeasured), interrogated its brain-level overlaps with SCZ and explored whether BMIgap predicted weight gain at 1- and 2-year follow-up. SCZ (BMIgap = 1.05kg/m2) and CHR individuals (BMIgap = 0.51 kg/m2) showed increased and ROD individuals (BMIgap=-0.82 kg/m2) decreased BMIgap. Shared brain patterns of BMI and SCZ were linked to illness duration, disease onset, and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger ROD individuals, and at 2-year follow-up. Therefore, we propose BMIgap as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control.
Analysing the future trends of foehn-enabling synoptic patterns over two valleys in the Eastern Alps in CMIP5 EURO-CORDEX models
Authors: Maier Philipp , Klisho Tatiana , Formayer Herbert , Lehner Fabian 
Published: December 2024

Abstract

Foehn has an impact on various climatological variables like temperature and humidity in the highly populated valleys of the Eastern Alps. With increasing global warming, the question arises as to how well climate projections are able to produce conditions for foehn and how their occurrence changes with climate change. This study uses four XGBoost models to classify foehn in EURO-CORDEX climate models of the CMIP5 generation for localised and widespread foehn events in Rhine and Inn valley located in the Eastern Alps, whereas ERA5 reanalysis data in combination with training data derived from semi-automated weather stations are used in the training process. Weights for individual models are derived by analysing the performance of EURO-CORDEX models in their ability to produce foehn-enabling conditions and considering their independence from each other in the historical period. Bias analysis shows a systematic negative bias in annual foehn occurrence for the GCMs ICHEC-EC-EARTH and MOHC-HadGEM2-ES, whereas others show no systematic bias. The training data confirm other studies by showing that the two selected valleys behave differently in their foehn occurrence and in the portion of widespread events. A weighted trend analysis for future behaviour of foehn shows a statistically significant increase in widespread events in Rhine valley and a decrease in total events in Inn valley under increasing warming conditions. Further, a shift in foehn seasonality in both valleys can be observed with a higher frequency in the spring months and a lower frequency from July to October, also depending on the climate change signal.