bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular remission after combination therapy with blinatumomab and ponatinib with relapsed/refractory Philadelphia chromosome-positive acute lymphocytic leukemia: two case reports
Authors: Yuda Junichiro , Yamauchi Nobuhiko , Kuzume Ayumi , Guo Yong-Mei , Sato Nobue , Minami Yosuke 
Published: March 2021

Abstract
Background
The outcomes of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) can improve with allogeneic hematopoietic stem cell transplantation (HSCT) during the first complete remission after treatment with a tyrosine kinase inhibitor (TKI) combined with chemotherapy. However, frail patients who are not eligible for allogeneic HSCT or those with TKI-resistant mutations within the BCR–ABL kinase domain have a poor clinical course. Blinatumomab (BLIN) is a bispecific T-cell engager antibody construct that directs cytotoxic T cells to CD19-expressing B-ALL cells. To date, only a few studies have shown the safety and efficacy of Blinatumomab (BLIN) + TKI combination therapy for relapsed/refractory (R/R) Ph+ ALL. Here we report the case of two patients with R/R Ph+ ALL who were treated with BLIN + TKI with durable molecular response.

Case presentation
Patient 1: A 69-year-old Japanese male with R/R Ph+ ALL was treated with conventional chemotherapy and dasatinib in April 2016. In May 2018, he developed molecular relapse due to the acquisition of T315I during dasatinib maintenance therapy. Thereafter, he achieved molecular complete remission (mCR) after switching from dasatinib to ponatinib. However, he developed a second relapse after the emergence of triple compound mutations (G250E/D276G/T315I) in November 2018. He subsequently received a total of nine cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR without any adverse events. Patient 2: A 69-year-old Japanese female with R/R Ph+ ALL was treated with chemotherapy and imatinib in April 2008. She developed molecular relapse due to the emergence of the T315I mutation in October 2017. She achieved mCR after switching from imatinib to ponatinib. However, she developed a second relapse after acquiring ABL exon4 skipping in addition to T315I. She subsequently received a total of seven cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR.

Conclusion
In our two cases, BLIN + ponatinib combination therapy was highly effective for R/R Ph+ ALL without any incidence of severe adverse events. Further studies with larger cohorts are warranted to validate the safety and efficacy of this potent combination therapy.
A retrospective analysis of the diagnostic performance of 11C-choline PET/CT for detection of hyperfunctioning parathyroid glands after prior negative or discordant imaging in primary hyperparathyroidism
Authors: Noltes M. E. , Kruijff S. , Jansen L. , Westerlaan H. E. , Zandee W. T. , Dierckx R. A. J. O. , Brouwers A. H. 
Published: March 2021

Abstract
Background
Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the diagnostic performance of 11C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging.

Methods
This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing 11C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the 11C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard.

Results
In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on 11C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of 11C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions.

Conclusions
In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by 11C-choline PET/CT with high sensitivity and accuracy.
New oscillation criteria for second-order neutral differential equations with distributed deviating arguments
Authors: Moaaz Osama , Park Choonkil , Elabbasy Elmetwally M. , Muhsin Waed 
Published: March 2021

AbstractIn this work, we create new oscillation conditions for solutions of second-order differential equations with continuous delay. The new criteria were created based on Riccati transformation technique and comparison principles. Furthermore, we obtain iterative criteria that can be applied even when the other criteria fail. The results obtained in this paper improve and extend the relevant previous results as illustrated by examples.
Eco-mechanisms within economic evolution: Schumpeterian approach
Authors: Lipieta Agnieszka , Malawski Andrzej 
Published: March 2021

AbstractSupporting ecological innovations and economic activities which lead to environmental protection is one of the important challenges to decision-makers. The above is related to the problem of specification of mechanisms resulting in introducing ecological innovations to the economy. The original vision of the economic evolution determined by innovation was firstly presented by Joseph Schumpeter who identified essential innovative changes as well as indicated different mechanisms governing the economic evolution. The aim of the paper is to suggest a cohesive topological approach maintained in the stream of Schumpeter’s thought, to study changes in the economy, which result in the elimination of at least one harmful commodity or technology from the market, by incorporating Hurwicz apparatus in a suitably modified competitive economy. Qualitative properties of mechanisms which can occur within the economic evolution are also analyzed.
Climate change scenario analysis for Baro-Akobo river basin, Southwestern Ethiopia
Authors: Muleta Teressa Negassa 
Published: March 2021

Abstract
Background
Several water resources projects are under planning and implementation in the Baro-Akobo basin. Currently, the planning and management of these projects is relied on historical data. So far, hardly any study has addressed water resources management and adaptation measures in the face of changing water balances due to climate change in the basin. The main bottleneck to this has been lack of future climate change scenario base data over the basin. The current study is aimed at developing future climate change scenario for the basin. To this end, Regional Climate Model (RCM) downscaled data for A1B emission scenario was employed and bias corrected at basin level using observed data. Future climate change scenario was developed using the bias corrected RCM output data with the basic objective of producing baseline data for sustainable water resources development and management in the basin.

Result
The projected future climate shows an increasing trend for both maximum and minimum temperatures; however, for the case of precipitation it does not manifest a systematic increasing or decreasing trend in the next century. The projected mean annual temperature increases from the baseline period by an amount of 1 °C and 3.5 °C respectively, in 2040s and 2090s. Similarly, evapotranspiration has been found to increase to an extent of 25% over the basin. The precipitation is predicted to experience a mean annual decrease of 1.8% in 2040s and an increase of 1.8% in 2090s over the basin for the A1B emission scenario.

Conclusion
The study resulted in a considerable future change in climatic variables (temperature, precipitation, and evapotranspiration) on the monthly and seasonal basis. These have an implication on hydrologic extremes-drought and flooding, and demands dynamic water resources management. Hence the study gives a valuable base information for water resources planning and managers, particularly for modeling reservoir inflow-climate change relations, to adapt reservoir operation rules to the real-time changing climate.
AI-based detection of lung lesions in [18F]FDG PET-CT from lung cancer patients
Authors: Borrelli Pablo , Ly John , Kaboteh Reza , Ulén Johannes , Enqvist Olof , Trägårdh Elin , Edenbrandt Lars 
Published: March 2021

Abstract
Background
[18F]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is a well-established modality in the work-up of patients with suspected or confirmed diagnosis of lung cancer. Recent research efforts have focused on extracting theragnostic and textural information from manually indicated lung lesions. Both semi-automatic and fully automatic use of artificial intelligence (AI) to localise and classify FDG-avid foci has been demonstrated. To fully harness AI’s usefulness, we have developed a method which both automatically detects abnormal lung lesions and calculates the total lesion glycolysis (TLG) on FDG PET-CT.

Methods
One hundred twelve patients (59 females and 53 males) who underwent FDG PET-CT due to suspected or for the management of known lung cancer were studied retrospectively. These patients were divided into a training group (59%; n = 66), a validation group (20.5%; n = 23) and a test group (20.5%; n = 23). A nuclear medicine physician manually segmented abnormal lung lesions with increased FDG-uptake in all PET-CT studies. The AI-based method was trained to segment the lesions based on the manual segmentations. TLG was then calculated from manual and AI-based measurements, respectively and analysed with Bland-Altman plots.

Results
The AI-tool’s performance in detecting lesions had a sensitivity of 90%. One small lesion was missed in two patients, respectively, where both had a larger lesion which was correctly detected. The positive and negative predictive values were 88% and 100%, respectively. The correlation between manual and AI TLG measurements was strong (R2 = 0.74). Bias was 42 g and 95% limits of agreement ranged from − 736 to 819 g. Agreement was particularly high in smaller lesions.

Conclusions
The AI-based method is suitable for the detection of lung lesions and automatic calculation of TLG in small- to medium-sized tumours. In a clinical setting, it will have an added value due to its capability to sort out negative examinations resulting in prioritised and focused care on patients with potentially malignant lesions.
Inborn errors of immunity—recent advances in research on the pathogenesis
Authors: Yamashita Motoi , Inoue Kento , Okano Tsubasa , Morio Tomohiro 
Published: March 2021

AbstractPrimary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.
Elemental and morphological analysis of enamel following the application of two bleaching systems with amorphous calcium phosphate: effect on enamel erosion susceptibility
Authors: Nagi Shaymaa M. , Nabil Shahinaz H. , Zaazou Mohamed H. 
Published: March 2021

AbstractBackgroundUsing remineralizing agents during and after bleaching procedures could maintain enamel surface, decreasing its erosive susceptibility. This study evaluated the efficacy of an in-office and at-home bleaching materials with amorphous calcium phosphate (ACP) on the susceptibility of the enamel to erosion. Forty-five bovine specimens were separated into three groups. Group A: no bleaching (control). Group B: Zoom 2 bleaching followed by ACP application. Group C: Nite White ACP. All specimens in all groups were subjected to an erosive challenge for five days. Using Energy Dispersive X-ray all specimens were subjected to elemental analysis and were examined for morphological changes under Scanning Electron Microscope (SEM).ResultsGroup B showed the highest mean calcium, phosphorus and sodium weight percent (wt%). Both Groups B and C showed statistically significant difference. While, there was no statistically significant difference between both Groups A and B.The sodium mean wt% showed a statistically significant difference in all groups. The magnesium mean wt% showed no statistically significant difference in all groups. SEM photomicrograph revealed hollowing of prism cores with intact prisms peripheries for group A. Group B showed relativity smooth surface with minor pores, while Group C showed an increase in the depth of surface irregularities and depressions.ConclusionsEnamel susceptibility to erosion after bleaching procedure was material dependent. Zoom 2 bleaching agent followed by ACP application did not increase the susceptibility of the enamel surface to erosion. Adding ACP to Nite White bleaching agent had no benefit on reducing enamel susceptibility to erosion.
Evaluation of cardiomyopathy diagnosis in heart transplant recipients: comparison of echocardiographic and pathologic classification
Authors: Behzadnia Neda , Sharif-Kashani Babak , Ahmadi Zargham Hossein , Naghashzadeh Farah , Dorudinia Atosa , Jahangirifard Alireza , Hamarz Hamoun , Abbasi Payam 
Published: March 2021

Abstract
Background
Definite diagnosis of cardiomyopathy types can be challenging in end-stage disease process. New growing data have suggested that there is inconsistency between echocardiography and pathology in defining type of cardiomyopathy before and after heart transplantation. The aim of the present study was to compare the pre-heart transplant echocardiographic diagnosis of cardiomyopathy with the results of post-transplant pathologic diagnosis.

Results
In this retrospective cross-sectional clinicopathological study, 100 consecutive patients have undergone heart transplantation in Masih-Daneshvari hospital, Tehran, Iran, between 2010 and 2019. The mean age of patients was 40 ± 13 years and 79% of patients were male. The frequency of different types of cardiomyopathy was significantly different between two diagnostic tools (echocardiography versus pathology, P < 0.001). On the other hand, in 24 patients, the results of echocardiography as regard to the type of cardiomyopathy were inconsistent with pathologic findings.

Conclusion
Based on the findings of the present study, it could be concluded that there is a significant difference between echocardiographic and pathologic diagnosis of cardiomyopathy; therefore, it is necessary to use additional tools for definite diagnosis of cardiomyopathy like advanced cardiac imaging or even endomyocardial biopsy before heart transplantation to reach an appropriate treatment strategy.
Percutaneous management of reperfusion arrhythmias during primary percutaneous coronary intervention: a case report
Authors: Taha Hesham Salah El Din , Shaker Mirna Mamdouh 
Published: March 2021

Abstract
Background
Myocardial reperfusion may cause profound electrophysiological alterations and can lead to serious reperfusion arrhythmias (RA). Management of RA and the accompanying electrical storm that may occur remains a problem. To our knowledge, the role of balloon re-inflation of the infarct-related artery (IRA) has never been addressed as a treatment modality for RA presenting as ventricular tachycardia (VT) with pulse or supraventricular tachycardia (SVT).

Case presentation
Six patients presenting with ST elevation myocardial infarction (STEMI) in the first 12 h, who underwent successful primary percutaneous coronary intervention (PCI), developed RA in the cathlab after restoration of flow in the IRA. The RA was in the form of VT with pulse, except in one patient who had SVT. In four patients, the RA was associated with hemodynamic instability. The mean age of the studied patients was 59.16 ± 7.94 years, and four were males. Coronary artery disease risk factors were prevalent, with four patients being hypertensive, two dyslipidemic, one diabetic, and 2 current smokers. One patient had a history of prior myocardial infarction (MI), and none had a history of congestive heart failure. The coronary angiography showed 100% occlusion of IRA in all patients and 2–3-vessel disease was present in 50%. PCI was successful with restoration of thrombolysis in myocardial infarction (TIMI) 2–3 flow in IRA in all cases. The mean time to revascularization from the onset of chest pain was 4.88 ± 2.68 h. In all cases, balloon re-inflation was successful in terminating the arrhythmias. None of the patients needed direct current cardioversion or anti-arrhythmic drugs for management of the acute arrhythmia.

Conclusion
Balloon re-inflation of IRA was successful in terminating RA that develop in the form of VT with pulse or SVT.
Gender Segregation in Education: Evidence From Higher Secondary Stream Choice in India
Authors: Sahoo Soham , Klasen Stephan 
Published: March 2021

Abstract
This paper investigates gender-based segregation across different fields of study at the senior secondary level of schooling in a large developing country. We use a nationally representative longitudinal data set from India to analyze the extent and determinants of gender gap in higher secondary stream choice. Using fixed-effects regressions that control for unobserved heterogeneity at the regional and household levels, we find that girls are about 20 percentage points less likely than boys to study in science (STEM) and commerce streams as compared with humanities. This gender disparity is unlikely to be driven by gender-specific differences in cognitive ability, given that the gap remains large and significant even after we control for individuals' past test scores. We establish the robustness of these estimates through various sensitivity analyses: including sibling fixed effects, considering intrahousehold relationships among individuals, and addressing sample selection issues. Disaggregating the effect on separate streams, we find that girls are most underrepresented in the study of science. Our findings indicate that gender inequality in economic outcomes, such as occupational segregation and gender pay gaps, is determined by gendered trajectories set much earlier in the life course, especially at the school level.
Under Whose Roof? Understanding the Living Arrangements of Children in Doubled-Up Households
Authors: Harvey Hope , Dunifon Rachel , Pilkauskas Natasha 
Published: March 2021

AbstractA growing literature in family demography examines children's residence in doubled-up (shared) households with extended family members and nonkin. This research has largely overlooked the role of doubling up as a housing strategy, with “hosts” (householders) providing housing support for “guests” living in their home. Yet, understanding children's experiences in doubled-up households requires attention to host/guest status. Using the American Community Survey and Survey of Income and Program Participation, we identify the prevalence of children doubling up as hosts and guests in different household compositions (multigenerational, extended family, nonkin), show how this varies by demographic characteristics, and examine children's patterns of residence across these household types. We find large variation by demographic characteristics. More disadvantaged children have higher rates of doubling up as guests than hosts, whereas more advantaged children have higher rates of doubling up as hosts than guests. Additionally, compared with hosts, guests more often use doubling up as a longer-term strategy; a greater share of guests live consistently doubled up over a three-year period, but those who do transition between household types experience more transitions on average than do hosts. Our findings show the importance of attending to both housing status and household composition when studying children living in doubled-up households.
Tsga8 is required for spermatid morphogenesis and male fertility in mice
Authors: Kobayashi Yuki , Tomizawa Shin-ichi , Ono Michio , Kuroha Kazushige , Minamizawa Keisuke , Natsume Koji , Dizdarević Selma , Dočkal Ivana , Tanaka Hiromitsu , Kawagoe Tatsukata , Seki Masahide , Suzuki Yutaka , Ogonuki Narumi , Inoue Kimiko , Matoba Shogo , Anastassiadis Konstantinos , Mizuki Nobuhisa , Ogura Atsuo , Ohbo Kazuyuki 
Published: March 2021

ABSTRACT
During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.