bluuebunny/crossref_metadata_2025 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

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

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

In 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

Supporting 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

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

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

Primary 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

Background

Using 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).

Results

Group 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.

Conclusions

Enamel 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

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

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

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

A 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

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.
A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model
Authors: Trotman-Lucas Melissa , Gibson Claire L.
Published: March 2021

Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers.
Study of Foreign Experience of Learners’ Vocational Self-Determination As an Innovative Potential of Advanced Professional Training
Authors: Lysenko V.
Published: March 2021

The study of Russian as well as foreign experience concerning the effective practices for performing learners’ vocational training and self-determination allows the educators to extrapolate the most adequate ideas, principles, technologies, approaches to the development and implementation of career guidance and vocational training programs intended for specialists. The acquired knowledge can be further used for analysis, comprehension and application of the best practices in the system of advanced vocational training.

The article considers the features of the dual secondary vocational training system of Germany and focuses on the career guidance experience in schools and colleges in the UK. It also presents approaches that are not widespread and less known in Russia than in other countries to apply them to the dual higher education system.

Some elements of effective foreign practices of vocational training, self-determination and career guidance can be used in advanced vocational training centers as well as in institutions involved in general secondary, secondary vocational and additional education.
Understanding dystocia in the field: part 2
Authors: Gormley Rory
Published: March 2021

The approach to resolution of dystocia must be promptly yet carefully planned. Once the cause of dystocia has been diagnosed, the time elapsed since allantochorionic rupture and foetal vitality status should be considered when deciding the next step. Communication with connections is key in enabling one to prioritise the outcome in favour of the foal, mare and/or future fertility. Clinicians should be pragmatic as opposed to dogmatic in their approach and willing to alter their strategy if attempts at resolution fail to achieve progress in a short period of time. Referral for caesarian section or fetotomy are options that should be considered at the start as opposed to once manual corrective efforts have failed.
EquineReview
Authors: McGovern Kate
Published: March 2021

Introduction:

Peritonitis in horses, equine bleeding and the pathogenesis of gamma glutamyl-transferase activity in Thoroughbred horses are discussed in this month's selection of three recent papers for equine practitioners.
Endoparasite control for donkeys in the UK
Authors: Bell Nikki , Thiemann Alex , Sullivan Rebekah
Published: March 2021

The prevalence of endoparasites, their control and clinical relevance in donkeys can often cause confusion and concern to vets and owners alike. While donkeys can be affected by the same parasite species as horses, infection characteristics, presenting signs and symptoms of disease can differ. Donkeys do not always show obvious signs of disease until it is severe so it is important to know what to look out for when clinically assessing a donkey and how best to diagnose potential infection with parasites. There is a limited selection of anthelmintic products available for use in the donkey, so prescribing using the cascade is sometimes warranted. Careful consideration should be given to the choice and frequency of anthelmintic treatments in order to balance controlling disease with preserving anthelmintic efficacy.
¿Son útiles las escuelas de negocios? Una aproximación desde las empresas familiares españolas
Authors: Puig Nuria , Fernandez Moya Maria
Published: March 2021

Este articulo se ocupa del impacto de las escuelas de negocios en la organizacion y el crecimiento de las empresas de su entorno. Aunque se trata de una cuestion crucial para comprender el poder adquirido por esta institucion en la economia global, apenas ha sido abordada desde la historia economica. Nuestra investigacion se centra en la relacion forjada entre el Instituto de Estudios Superiores de la Empresa (IESE) y tres grupos familiares, Salvat, Puig y Lladro, a traves de sus profesores-consultores y alumnos-propietarios-directivos desde la fundacion de la escuela en 1958 hasta finales del siglo xx. El analisis permite, en primer lugar, identificar las fuerzas exogenas y endogenas que participaron en la creacion de IESE, una de las escuelas mas competitivas del mundo en el siglo xxi. En segundo lugar, se comprueba que los primeros programas de formacion de directivos (executive education) del instituto proporcionaron conocimiento especializado, servicios de consultoria y una red de contactos que amplificaron la influencia de IESE en el desarrollo a largo plazo de las empresas vinculadas a sus alumnos. Y en tercer lugar, se explica la participacion activa de la escuela y algunas de las empresas de su entorno en el proceso de legitimacion academica de los estudios de la empresa familiar que tuvo lugar en todo el mundo a partir de los anos ochenta del siglo xx.
Jordi Nadal i Oller (1929-2020): esfuerzo newtoniano, conciencia profética
Authors: Catalan Jordi , Gutiérrez-Poch Miquel , Sánchez Alex , Sudrià Carles
Published: March 2021

Nota biográfica del Dr. Jordi Nadal i Oller, fundador y director emérito de Revista de Historia Industrial, fallecido el pasado 8 de diciembre de 2020.
Cylindrical vector beam revealing multipolar nonlinear scattering for superlocalization of silicon nanostructures
Authors: Wang Bin , Che Ying , Zhong Xiangchao , Yan Wen , Zhang Tianyue , Chen Kai , Xu Yi , Xu Xiaoxuan , Li Xiangping
Published: March 2021

The resonant optical excitation of dielectric nanostructures offers unique opportunities for developing remarkable nanophotonic devices. Light that is structured by tailoring the vectorial characteristics of the light beam provides an additional degree of freedom in achieving flexible control of multipolar resonances at the nanoscale. Here, we investigate the nonlinear scattering of subwavelength silicon (Si) nanostructures with radially and azimuthally polarized cylindrical vector beams to show a strong dependence of the photothermal nonlinearity on the polarization state of the applied light. The resonant magnetic dipole, selectively excited by an azimuthally polarized beam, enables enhanced photothermal nonlinearity, thereby inducing large scattering saturation. In contrast, radially polarized beam illumination shows no observable nonlinearity owing to off-resonance excitation. Numerical analysis reveals a difference of more than 2 orders of magnitude in photothermal nonlinearity under two types of polarization excitations. Nonlinear scattering and the unique doughnut-shaped focal spot generated by the azimuthally polarized beam are demonstrated as enabling far-field high-resolution localization of nanostructured Si with an accuracy approaching 50 nm. Our study extends the horizons of active Si photonics and holds great potential for label-free superresolution imaging of Si nanostructures.
Free-spectral-range-free filters with ultrawide tunability across the S + C + L band
Authors: Sun Chunlei , Zhong Chuyu , Wei Maoliang , Ma Hui , Luo Ye , Chen Zequn , Tang Renjie , Jian Jialing , Lin Hongtao , Li Lan
Published: March 2021

Optical filters are essential parts of advanced optical communication and sensing systems. Among them, the ones with an ultrawide free spectral range (FSR) are especially critical. They are promising to provide access to numerous wavelength channels highly desired for large-capacity optical transmission and multipoint multiparameter sensing. Present schemes for wide-FSR filters either suffer from limited cavity length or poor fabrication tolerance or impose an additional active-tuning control requirement. We theoretically and experimentally demonstrate a filter that features FSR-free operation capability, subnanometer optical bandwidth, and acceptable fabrication tolerance. Only one single deep dip within a record-large waveband (

S
+
C
+
L

band) is observed by appropriately designing a side-coupled Bragg-grating-assisted Fabry–Perot filter, which has been applied as the basic sensing unit for both the refractive index and temperature measurement. Five such basic units are also cascaded in series to demonstrate a multichannel filter. This work provides a new insight to design FSR-free filters and opens up a possibility of flexible large-capacity integration using more wavelength channels, which will greatly advance integrated photonics in optical communication and sensing.
Analysis of spiking synchrony in visual cortex reveals distinct types of top-down modulation signals for spatial and object-based attention
Authors: Wagatsuma Nobuhiko , Hu Brian , von der Heydt Rüdiger , Niebur Ernst
Published: March 2021

The activity of a border ownership selective (BOS) neuron indicates where a foreground object is located relative to its (classical) receptive field (RF). A population of BOS neurons thus provides an important component of perceptual grouping, the organization of the visual scene into objects. In previous theoretical work, it has been suggested that this grouping mechanism is implemented by a population of dedicated grouping (“G”) cells that integrate the activity of the distributed feature cells representing an object and, by feedback, modulate the same cells, thus making them border ownership selective. The feedback modulation by G cells is thought to also provide the mechanism for object-based attention. A recent modeling study showed that modulatory common feedback, implemented by synapses with N-methyl-D-aspartate (NMDA)-type glutamate receptors, accounts for the experimentally observed synchrony in spike trains of BOS neurons and the shape of cross-correlations between them, including its dependence on the attentional state. However, that study was limited to pairs of BOS neurons with consistent border ownership preferences, defined as two neurons tuned to respond to the same visual object, in which attention decreases synchrony. But attention has also been shown to increase synchrony in neurons with inconsistent border ownership selectivity. Here we extend the computational model from the previous study to fully understand these effects of attention. We postulate the existence of a second type of G-cell that represents spatial attention by modulating the activity of all BOS cells in a spatially defined area. Simulations of this model show that a combination of spatial and object-based mechanisms fully accounts for the observed pattern of synchrony between BOS neurons. Our results suggest that modulatory feedback from G-cells may underlie both spatial and object-based attention.
Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis
Authors: Kunkel Amber , White Michael , Piola Patrice
Published: March 2021

Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia. We used a simple compartmental model to predict trends in malaria incidence and resistance in Cambodia from 2020–2025 assuming no changes in transmission since 2018. We assessed three scenarios: a status quo scenario with artesunate-mefloquine (ASMQ) as treatment; a triple ACT scenario with dihydroartemisinin-piperaquine (DP) plus mefloquine (MQ) as treatment; and a chemoprophylaxis scenario with ASMQ as treatment plus DP as chemoprophylaxis. We predicted MQ resistance to increase under the status quo scenario. Triple ACT treatment reversed the spread of MQ resistance, but had no impact on overall malaria incidence. Joint MQ-PPQ resistance declined under the status quo scenario for the baseline parameter set and most sensitivity analyses. Compared to the status quo, triple ACT treatment limited spread of MQ resistance but also slowed declines in PPQ resistance in some sensitivity analyses. The chemoprophylaxis scenario decreased malaria incidence, but increased the spread of strains resistant to both MQ and PPQ; both effects began to reverse after the intervention was removed. We conclude that triple ACTs may limit spread of MQ resistance in the Cambodia, but would have limited impact on malaria incidence and might slow declines in PPQ resistance. Chemoprophylaxis could have greater impact on incidence but also carries higher risks of resistance. Aggressive strategies to limit transmission the GMS are needed to achieve elimination goals, but any intervention should be accompanied by monitoring for drug resistance.
Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature
Authors: Tamarozzi Francesca , Fittipaldo Veronica A. , Orth Hans Martin , Richter Joachim , Buonfrate Dora , Riccardi Niccolò , Gobbi Federico G.
Published: March 2021

Background

Hepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS.

Methodology/principal findings

We reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking.

Conclusions

Most interventions have been developed on the basis of individual groups’ experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.
Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)
Authors: Guo Yan , Mehrabian Zara , Johnson Mary A. , Miller Neil R. , Henderson Amanda D. , Hamlyn John , Bernstein Steven L.
Published: March 2021

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.
Student reactions to traumatic material in literature: Implications for trigger warnings
Authors: Kimble Matthew , Flack William , Koide Jennifer , Bennion Kelly , Brenneman Miranda , Meyersburg Cynthia
Published: March 2021

Introduction

While trigger warnings have garnered significant debate, few studies have investigated how students typically respond to potentially triggering material.

Method

In this study, three hundred and fifty-five undergraduate students from four universities read a passage describing incidences of both physical and sexual assault. Longitudinal measures of subjective distress, PTSD symptoms, and emotional reactivity were taken.

Results

Greater than 96% of participants read the triggering passage even when given a non-triggering alternative to read. Of those who read the triggering passage, those with triggering traumas did not report more distress although those with higher PTSD scores did. Two weeks later, those with trigger traumas and/or PTSD did not report an increase in trauma symptoms as a result of reading the triggering passage.

Conclusions

Students with relevant traumas do not avoid triggering material and the effects appear to be brief. Students with PTSD do not report an exacerbation of symptoms two weeks later as a function of reading the passage.
“When they say weed causes depression, but it’s your fav antidepressant”: Knowledge-aware attention framework for relationship extraction
Authors: Yadav Shweta , Lokala Usha , Daniulaityte Raminta , Thirunarayan Krishnaprasad , Lamy Francois , Sheth Amit
Published: March 2021

With the increasing legalization of medical and recreational use of cannabis, more research is needed to understand the association between depression and consumer behavior related to cannabis consumption. Big social media data has potential to provide deeper insights about these associations to public health analysts. In this interdisciplinary study, we demonstrate the value of incorporating domain-specific knowledge in the learning process to identify the relationships between cannabis use and depression. We develop an end-to-end knowledge infused deep learning framework (Gated-K-BERT) that leverages the pre-trained BERT language representation model and domain-specific declarative knowledge source (Drug Abuse Ontology) to jointly extract entities and their relationship using gated fusion sharing mechanism. Our model is further tailored to provide more focus to the entities mention in the sentence through entity-position aware attention layer, where ontology is used to locate the target entities position. Experimental results show that inclusion of the knowledge-aware attentive representation in association with BERT can extract the cannabis-depression relationship with better coverage in comparison to the state-of-the-art relation extractor.
SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy
Authors: Gili Tommaso , Benelli Giampaolo , Buscarini Elisabetta , Canetta Ciro , La Piana Giuseppe , Merli Guido , Scartabellati Alessandro , Viganò Giovanni , Sfogliarini Roberto , Melilli Giovanni , Assandri Roberto , Cazzato Daniele , Rossi Davide Sebastiano , Usai Susanna , Caldarelli Guido , Tramacere Irene , Pellegata Germano , Lauria Giuseppe
Published: March 2021

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5–99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60–69 years old, 21.1% in 70–79 years old, 38.8% in 80–89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high C-reactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1–98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60–40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment.