bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryo‐kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase
Authors: Adesina Aduragbemi S. , Luk Louis Y. P. , Allemann Rudolf K.
Published: April 2021

Effects of isotopic substitution on the rate constants of human dihydrofolate reductase (HsDHFR), an important target for anti‐cancer drugs, have not previously been characterized due to its complex fast kinetics. Here, we report the results of cryo‐measurements of the kinetics of the HsDHFR catalyzed reaction and the effects of protein motion on catalysis. Isotopic enzyme labeling revealed an enzyme KIE (kHLE/kHHE) close to unity above 0 °C; however, the enzyme KIE was increased to 1.72±0.15 at −20 °C, indicating that the coupling of protein motions to the chemical step is minimized under optimal conditions but enhanced at non‐physiological temperatures. The presented cryogenic approach provides an opportunity to probe the kinetics of mammalian DHFRs, thereby laying the foundation for characterizing their transition state structure.
Modulating the Acidic and Basic Site Concentration of Metal‐Organic Framework Derivatives to Promote the Carbon Dioxide Epoxidation Reaction
Authors: Ji Jinhua , Liu Hao , Chen Zewei , Fu Yajun , Yang Weijun , Yin Shuang‐Feng
Published: April 2021

Metal‐organic framework (MOF) is an ideal precursor/template for porous carbon, and its active components are uniformly doped, which can be used in energy storage and catalytic conversion fields. Metal‐organic framework PCN‐224 with carboxylporphyrin as the ligand was synthesized, and then Zn2+ and Co2+ ions were coordinated in the center of the porphyrin ring by post‐modification. Here, PCN‐224−ZnCo with different ratios of bimetallic Zn2+/Co2+ ions were used as the precursor, and the metal‐nitrogen‐carbon(M−N−C) material of PCN‐224−ZnCo‐950 was obtained by pyrolyzing the precursor at 950 °C in Ar. Because Zn is easy to volatilize at 950 °C, the formed M−N−C materials can reflect different Co contents and different basic site concentrations. The formed material still maintains the original basic framework. With the increase of Zn2+/Co2+ ratio in precursor, the concentration of N‐containing alkaline sites in pyrolysis products gradually increase. Compared with the precursor, PCN‐224−ZnCo1‐950 with Zn2+/Co2+=1 : 1 has greatly improved basicity and suitable acidic/ alkaline site concentration. It can be efficiently used to carbon dioxide absorption and catalyze the cycloaddition of CO2 with epoxide. More importantly, the current method of adjusting the acidic/basic sites in M−N−C materials through volatilization of volatile metals can provide an effective strategy for adjusting the catalysis of MOF derivatives with porphyrin structure.
DNA Functionality with Photoswitchable Hydrazone Cytidine**
Authors: Mao Song , Chang Zhihua , Ying Zheng Ya , Shekhtman Alexander , Sheng Jia
Published: April 2021

A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into oligodeoxynucleotides to construct photoswitchable DNA strands. The E‐Z isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by 1H NMR spectroscopy and HPLC in the contexts of both nucleoside and oligodeoxynucleotide. The light activated Z form isomer of this hydrazone‐cytidine with a six‐member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by using Bst DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting a potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that has potential chemical biology and biomedicinal applications to control DNA synthesis and DNA‐enzyme interactions using the cell friendly blue light irradiation.
Human Mass Balance and Metabolite Profiling of [14C]‐Pamiparib, a Poly (ADP‐Ribose) Polymerase Inhibitor, in Patients With Advanced Cancer
Authors: Mu Song , Palmer Daniel , Fitzgerald Richard , Andreu‐Vieyra Claudia , Zhang Heather , Tang Zhiyu , Su Dan , Sahasranaman Srikumar
Published: April 2021

Pamiparib, a selective poly (ADP‐ribose) polymerase 1/2 inhibitor, demonstrated tolerability and antitumor activity in patients with solid tumors at 60 mg orally twice daily. This phase 1 open‐label study (NCT03991494; BGB‐290‐106) investigated the absorption, metabolism, and excretion (AME) of 60 mg [14C]‐pamiparib in 4 patients with solid tumors. The mass balance in excreta, blood, and plasma radioactivity and plasma pamiparib concentration were determined along with metabolite profiles in plasma, urine, and feces. Unchanged pamiparib accounted for the most plasma radioactivity (67.2% ± 10.2%). Pamiparib was rapidly absorbed with a median time to maximum plasma concentration (Cmax) of 2.00 hours (range, 1.00‐3.05 hours). After reaching Cmax, pamiparib declined in a biphasic manner, with a geometric mean terminal half‐life (t1/2) of 28.7 hours. Mean cumulative [14C]‐pamiparib excretion was 84.7% ± 3.5%. Pamiparib was mainly cleared through metabolism, primarily via N‐oxidation and oxidation of the pyrrolidine ring. A dehydrogenated oxidative product (M3) was the most abundant metabolite in biosamples. A mean of 2.11% and 1.11% of [14C]‐pamiparib was excreted as unchanged pamiparib in feces and urine, respectively, indicating near‐complete absorption and low renal clearance of parent drug. Cytochrome P450 (CYP) phenotyping demonstrated CYP2C8 and CYP3A involvement in pamiparib metabolism. These findings provide an understanding of pamiparib AME mechanisms and potential drug‐drug interaction liability.
Modeling population dynamics for information dissemination through Facebook
Authors: Huynh Hiep Xuan , Lai Be Ut , Duong‐Trung Nghia , Nguyen Hai Thanh , Phan Thuong‐Cang
Published: April 2021

Online social networks such as Facebook and Twitter have become part of our daily lives. Their influence on business, politics, and society is considerable. Sensitive or unreliable information can adversely affect individuals, organizations, and governments. Due to the effects of the Covid‐19 epidemic, online news is more plentiful and accessible, which raises concerns about its reliability, quality, and authenticity. This article proposes the use of population dynamics model to study information dissemination on Facebook and a Susceptible‐Infected‐Recovered (SIR) model to examine information propagation as an outbreak of disease. We investigated 27 datasets with more than 270,000 messages, and the experiments showed that the population dynamics model is suitable for modeling the spread of information. The results revealed that information propagation could occur rapidly; after only 1–2 days. Additionally, we discovered that it is very crucial to find immediate solutions for preventing fake information as soon as it appears. This work enables us to understand the mechanism of information dissemination on social networks. This can help control and prevent the spread of misleading information, avoiding unintended consequences.
Could Legitimation Code Theory offer practical insight for teaching disciplinary knowledge? A case study in geography
Authors: Vernon Esther K. L. F.
Published: April 2021

This article explores the relationship between disciplinary knowledge and subject pedagogy, utilising Maton's Legitimation Code Theory (LCT). It suggests ways that LCT could help facilitate deeper communication both within and between subject communities, providing a conceptual framework that gets beneath empirical manifestations to identify epistemic and semantic principles that generate those modalities. LCT’s potential to represent systematised concepts diagrammatically may also enable wider communication. Following this, a small‐scale case study is presented exploring the nature of the knowledge in the core topic Changing Places in the new geography A‐Level (UK). This argued that what could be understood as a mismatch of expectations and dispositions by teachers and students can be understood more fundamentally as a contradiction (a ‘code clash’) regarding what counts as the ‘rules of the game’ within geography. The article ends by outlining implications for school geography rooted in the logic of the knowledge being pedagogically preinscribed, that is, that different knowledges’ distinct epistemologies have real implications for how that knowledge should be recontextualised, reproduced and evaluated. It concludes that the exam board's recontextualisation of this disciplinary knowledge is not merely a simpler interpretation; it is more significantly a different ideal ‘knower’ that is being nurtured and examined.
Fluorene Derivatives Bearing Two to Seven Phthalimidomethyl Groups: Syntheses, Crystal Structures and Conversion to Amines
Authors: Seidel Pierre , Seichter Wilhelm , Schwarzer Anke , Mazik Monika
Published: April 2021

Fluorene derivatives containing four to seven phthalimidomethyl groups (1,3‐dioxo‐1,3‐dihydro‐2H‐isoindol‐2‐yl‐methyl groups) were prepared from 9H‐fluorene, 9,9‐diethyl‐9H‐fluorene as well as from 2,7‐ and 2,4,7‐functionalized 9,9‐diethyl‐9H‐fluorenes by using the conditions of the Tscherniac‐Einhorn reaction. By reacting the 9,9‐diethyl substituted fluorenes with N‐(hydroxymethyl)phthalimide the 2,4,6,7‐ and 2,3,4,6,7‐substituted derivatives were obtained. In the absence of the ethyl groups, as in the case of 9H‐fluorene, the formation of the sixfold and sevenfold substituted compounds was observed (1,2,3,5,7,8‐ and 1,2,3,4,6,7,8‐substituted fluorenes). It should be noted that one position in the bay region of the fluorene skeleton (position 4 or 5) remains unsubstituted in each of the prepared four‐ to sevenfold substituted 9H‐fluorenes. The conversion of the phthalimidomethyl substituted 9,9‐diethyl‐9H‐fluorenes into the corresponding amines takes place with excellent yields. The solid‐state structures of the compounds bearing phthalimidomethyl groups were determined by single‐crystal X‐ray diffraction analysis. The crystal structures are characterized by the presence of C−H⋅⋅⋅O, C−H⋅⋅⋅π and π⋅⋅⋅π interactions as well as C=O⋅⋅⋅π contacts. In the case of the chloroform and dichloromethane solvates the Cl⋅⋅⋅O=C, Cl⋅⋅⋅Cl, and Cl⋅⋅⋅π halogen bonds as well as the C−H⋅⋅⋅Cl hydrogen bonds influence furthermore the crystal packing. Ten‐membered supramolecular motifs of the graph set
(10), which are created by the C−H⋅⋅⋅O bonds, can be recognized in some crystal structures. The manuscript provides information about the synthetic routes to new fluorene derivatives and their molecular structures as well as the patterns of noncovalent interactions in the crystalline state.
Palladium‐Catalysed Carboborylation for the Synthesis of Borylated Indanes
Authors: Zieba Andrzej , Hooper Joel F.
Published: April 2021

A palladium‐catalysed carboborylation reaction for the synthesis of borylated indanes has been investigated. This reaction proceeds in good yields with an achiral catalyst, and is tolerant of substitution on the aryl ring, although sensitivity to the substitution of the alkene was observed. Initial studies towards an enantioselective version of this reaction were undertaken, identifying phosphoramidites as a promising ligand class. This allowed for the synthesis of chiral indane and indolone products with moderate levels of enantioselectivity.
Pricing and calibration of the futures options market: A unified approximation
Authors: Lian Xiaotong , Song Yingda
Published: April 2021

The constant elasticity of variance (CEV) model is widely used in modeling commodity futures prices, but it may not perform well in calibrating corresponding futures options. We consider two variations of the CEV model, that is, CEV with jumps and CEV with regime switching, and compare their performance in calibrating the Chinese futures options market. In particular, we propose a unified framework for pricing American futures options by combining the continuous‐time Markov chain approximation and the dynamic programming method. Results show that the inverse leverage effect in the soybean meal options market can be better described by the CEV regime‐switching model.
Jump activity analysis of the equity index and the corresponding volatility: Evidence from the Chinese market
Authors: Wu Bin , Chen Pengzhan , Ye Wuyi
Published: April 2021

This paper performs a nonparametric analysis of jump activity for the Chinese equities market. More precisely, we perform formal tests to decide whether the jumps in the 50 exchange‐traded fund (50ETF) and its volatility occur together by using the implied volatility index (iVIX) as a proxy for volatility. Our empirical findings are as follows: (i) joint jumps in the 50ETF and iVIX hardly occur, especially during noncrisis periods; (ii) there is a strong degree of dependence between the jump sizes of the 50ETF and iVIX when disaggregating jumps into their positive and negative parts; (iii) the jump component seems to contribute more to the leverage effect than the diffusive component.
Sulphate supergene minerals: An intuitive indicator for deep deposit in plateau regions
Authors: Zhao Ziou , Zhao Zhidan
Published: April 2021

The world‐class Rongna Cu(Au) deposit, located in the Duolong mining district, is the first epithermal‐porphyry deposit along the Bangong–Nujiang metallogenic belt. The acidic spring developed in the centre of the Rongna Deposit and its basin has a high amount of heavy metals. Therefore, metal elements (Cu, Pb, Zn, Cd, As, Cr and Hg), pH, SO42− of the Rongna River and the composition of its supergene minerals are studied to discuss the environmental influence and provide a theoretical basis for the comprehensive utilization and environmental management of the Rongna Deposit. The result shows that there are eight kinds of supergene minerals: natrojarosite, hexahydrite, tamarugite, anhydrite, pickeringite, bloedite, gypsum and naujakasite, among which, naujakasite is discovered for the first time in China. The material sources of these sulphate minerals and acidic water are from the sulphate in the ores that experience the leaching process and oxidation. The spring is severely acidified, whose pH values are 2.70–3.08, the single pollution index of Cr, Cd, Pb, Hg and As are less than 1, but the index of Cu and Zn exceed the Class III National Water Standard by about twice, showing a mild pollution, its comprehensive pollution index values 0.8 ~ (<2.5), showing good quality. The pH of Rongna River water values are 7.70–7.92, the single pollution index is less than 1, indicating no pollution, and the comprehensive pollution index is less than 0.8, indicating good quality. However, considering the vulnerable ecological environment in Tibet, the acidic spring still needs manual intervention. An open‐air reservoir can be built upstream of the acidic spring, and the pollutants can precipitate by natural evaporation and then be recycled.
Breast cancer screening and overdiagnosis
Authors: Bulliard Jean‐Luc , Beau Anna‐Belle , Njor Sisse , Wu Wendy Yi‐Ying , Procopio Pietro , Nickson Carolyn , Lynge Elsebeth
Published: April 2021

Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow‐up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis.
Moderating effects of sleep difficulties on relations between posttraumatic stress disorder symptoms and positive memory count
Authors: Contractor Ateka A. , Slavish Danica C. , Weiss Nicole H. , Alghraibeh Ahmad M. , Alafnan Ali A. , Taylor Daniel J.
Published: April 2021

Objectives

Posttraumatic stress disorder (PTSD) severity relates to positive memory retrieval difficulties. One variable potentially influencing this relation is sleep difficulties. We examined moderating effects of sleep difficulties (duration and quality) on relations between PTSD severity and count of specific positive memories covarying for age, gender, and depression.

Methods

Participants were an Amazon Mechanical Turk‐recruited trauma‐exposed community sample of 205 respondents (M
age = 35.44; 61.40% women).

Results

Moderated regression analyses indicated significant interaction effects between sleep quality (b = 0.03; p = 0.036) and PTSD severity on specific positive memory count. Among individuals reporting better sleep quality, there were negative associations between PTSD severity and specific positive memory count (b = −0.04, SE = 0.02, p = 0.010). Similar results were obtained for PTSD's intrusion and arousal clusters.

Conclusion

Results support targeting sleep quality and PTSD severity to improve positive memory retrieval in PTSD and memory interventions, and the importance of considering sleep when examining links between PTSD and positive memory retrieval.
Preferences for and acceptability of receiving pharmacogenomic results by mail: A focus group study with a primarily African‐American cohort
Authors: Chan Priscilla A. , Lewis Katie L. , Biesecker Barbara B. , Erby Lori H. , Fasaye Grace‐Ann , Epps Sandra , Biesecker Leslie G. , Turbitt Erin
Published: April 2021

Although genetic counseling is traditionally done through in‐person, one‐on‐one visits, workforce shortages call for efficient result return mechanisms. Studies have shown that telephone and in‐person return of cancer genetic results are equivalent for patient outcomes. Few studies have been conducted with other modes, result types or racially diverse participants. This study explored participants’ perspectives on receiving pharmacogenomic results by mail. Two experienced moderators facilitated six focus groups with 49 individuals who self‐identified primarily as African‐American and consented to participate in a genome sequencing cohort study. Participants were given a hypothetical pharmacogenomic result report (positive for c.521T>C in SLCO1B1). An accompanying letter explained that the result was associated with statin intolerance along with a recommendation to share it with one's doctor and immediate relatives. Participants reacted to the idea of receiving this type of result by mail, discussing whether the letter's information was sufficient and what they predicted they would do with the result. Two researchers coded the focus group transcripts and identified themes. Many participants thought that it was appropriate to receive the result through the mail, but some suggested a phone call alerting the recipient to the letter. Others emphasized that although a letter was acceptable for disclosing pharmacogenomic results, it would be insufficient for what they perceived as life‐threatening results. Most participants found the content sufficient. Some participants suggested resources about statin intolerance and warning signs be added. Most claimed they would share the result with their doctor, yet few participants offered they would share the result with their relatives. This exploratory study advances the evidence that African‐American research participants are receptive to return of certain genetic results by approaches that do not involve direct contact with a genetic counselor and intend to share results with providers.

ClinSeq: A Large‐Scale Medical Sequencing Clinical Research Pilot Study (NCT00410241).
Green and blue pigments in Roman wall paintings: A challenge for Raman spectroscopy
Authors: Jorge‐Villar Susana E. , Edwards Howell G. M.
Published: April 2021

In Roman wall paintings, blue and green colours are less commonly encountered than red and yellow and were more expensive. Despite this, Pliny and Vitruvius describe the more common compounds used for these pigments, translated today as azurite, lazurite, chrysocolla, indigo and Egyptian blue for blues and verdigris, malachite, celadonite, glauconite and chlorite for greens. A confusion in their nomenclature is often found in the most common blue pigment that is the first manufactured compound, Egyptian blue. For greens, celadonite and glauconite were usual and called generically ‘green earths’, but they prove to be difficult to characterize analytically. In this paper, we evaluate the Raman spectroscopic identification of the characteristic Roman blue and green pigments as used in wall paintings using two different laser wavelengths (green and near infrared) and clarify their nomenclature.
Diagnostic Accuracy of Ultrasound for Detecting Gastric or Duodenal Ulcers in Pediatric Patients
Authors: Hosokawa Takahiro , Tanami Yutaka , Sato Yumiko , Hara Tomoko , Iwama Itaru , Ishimaru Tetsuya , Kawashima Hiroshi , Oguma Eiji
Published: April 2021

Objective

Direct ultrasound imaging findings alone have low sensitivity for diagnosing duodenal (65%) and gastric ulcers (40%). This retrospective study evaluated the efficiency of ultrasound in detecting gastric/duodenal ulcers in pediatric patients through direct and indirect findings.

Methods

We evaluated 244 children who underwent ultrasound and subsequent endoscopy within 4 weeks for direct and indirect imaging findings indicative of gastric/duodenal ulcers. Positive direct imaging findings revealed gastric or duodenal wall thickness >8 or 5 mm, respectively, and indirect findings revealed inflammatory changes, hyperechogenicity, and presence of lymph node around ulcers. Correspondingly, we calculated the sensitivity and specificity for diagnosing gastric/duodenal ulcers and used the Fisher's exact and Mann–Whitney U tests to compare the frequency of findings and gastroduodenal wall thicknesses in pediatric patients with gastric/duodenal ulcers.

Results

Overall, 6 and 24 were diagnosed with gastric and duodenal ulcers, respectively. The sensitivities of direct and indirect findings were 60.0% (18/30) and 80.0% (24/30), respectively; the corresponding specificities were 98.1% (210/214) and 97.2% (208/214). The frequency of direct and indirect sonographic findings differed significantly between patients with gastric or duodenal ulcers (18/30 versus 24/30, P = .002). Gastric and duodenal wall thicknesses were greater in patients with gastric (6.6 ± 2.6 mm versus 3.6 ± 1.4 mm; P = .003) or duodenal ulcer (5.0 ± 1.4 mm versus 2.2 ± 1.0 mm; P <.0001), respectively, than in those without.

Conclusions

The frequency of indirect finding was greater than that of direct finding in pediatric patients with gastric/duodenal ulcers. Therefore, sonographers should carefully evaluate indirect findings around the stomach or duodenum.
Recovery of foot drop in chronic inflammatory demyelinating polyneuropathy (CIDP)
Authors: Weerasinghe Dinushi , Veerapandiyan Aravindhan , Stanton Michael , Herrmann David N. , Akmyradov Chary , Logigian Eric
Published: April 2021

Introduction/Aims

Foot drop is common in chronic inflammatory demyelinating polyneuropathy (CIDP), but its prognosis is uncertain.

Methods

CIDP patients with less than anti‐gravity strength (<3/5 power) of ankle dorsiflexion (ADF) on Medical Research Council manual muscle testing on presentation at our center were identified by retrospective review. After initiation of standard treatment, ADF power was serially tabulated, and predictors of recovery were determined.

Results

Of the 27 identified patients, ADF power at presentation was <3/5 in 48/54 legs. At 1 y after treatment, ADF power improved to >/= 3/5 in 17/27 patients in one (N = 6) or both (N = 11) legs. On multi‐variate analysis, predictors of recovery of ADF power were tibialis anterior compound muscle action potential amplitude at presentation, shorter disease duration, and female gender.

Discussion

Foot drop improves to anti‐gravity power in most treated CIDP patients depending in part on the severity of fibular motor axon loss at onset of treatment.
Who eats wild meat? Profiling consumers in Ho Chi Minh City, Vietnam
Authors: Olmedo Alegría , Veríssimo Diogo , Challender Daniel W. S. , Dao Huong Thi Thu , Milner‐Gulland E. J.
Published: April 2021

Overexploitation for consumption of meat from wild animals in urban centres currently threatens numerous species across the globe. Indiscriminate offtake to satisfy demand for wild meat affects a range of wildlife of conservation concern in Vietnam. It is essential to understand the consumption of wild meat in Vietnam in order to ensure it is not detrimental to wild species.

We apply the principles of target audience segmentation to a sample of 384 respondents who had consumed wild meat in the previous year in Ho Chi Minh City, Vietnam. We carried out a cluster analysis to divide wild meat consumers into subgroups considering demographic, behavioural and psychographic variables.

We found three consumer groups: Classic Consumers (older, less educated), Up‐and‐coming Professionals (younger, wealthier, more educated) and Students. Compared to Students, Classic Consumers and Up‐and‐coming Professionals were significantly more likely to have paid for their meal at wild meat restaurants and to have ordered a combination of wild meat and other types of food rather than other types of food only.

Classic Consumers match previous characterisations of wild meat consumers, but the other two groups should also be considered in demand reduction campaigns. As Students appear to have limited influence on restaurant/food choices in certain social contexts and less propensity to eat wild meat, Up‐and‐coming Professionals may be an important target group.

A wide variety of species are consumed in wild meat restaurants. Some, such as pangolins, are of conservation concern and were consumed by 5% of our respondents. This is potentially an unsustainable level of consumption.

Our study showcases an audience segmentation approach to understanding wildlife consumers and provides insights for behavioural interventions and further research to curtail demand for wild meat in Ho Chi Minh City, Vietnam where it is of conservation concern.

A free Plain Language Summary can be found within the Supporting Information of this article.
Veno‐occlusive disease risk in pediatric patients with acute myeloid leukemia treated with gemtuzumab ozogamicin before allogeneic hematopoietic cell transplantation
Authors: Duncan Christine , St. Martin Andrew , Pérez Waleska S. , Steinert Patricia , Zhang Mei‐Jie , Chirnomas Deborah , Hoang Caroline J. , Loberiza Fausto R. , Saber Wael
Published: April 2021

Background

Gemtuzumab ozogamicin (GO) administered before allogeneic hematopoietic cell transplantation (alloHCT) has been linked to an increased risk of hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).

Procedure

This retrospective analysis examined VOD/SOS risk and clinical outcomes in pediatric patients with acute myeloid leukemia who received myeloablative alloHCT in 2008–2011 with (n = 148) and without (n = 348; controls) prior GO exposure and were reported to the Center for International Blood and Marrow Transplant Research.

Results

Cumulative incidences (95% confidence interval [CI]) of VOD/SOS and severe VOD/SOS, respectively, at 100 days were 16% (11–23%) and 8% (4–13%) for GO‐exposed patients and 10% (7–13%) and 3% (2–5%) for controls. With a median follow‐up of approximately 7 years, the 5‐year adjusted overall survival probability (95% CI) after alloHCT was 51% (43–58%) and 55% (50–60%) for GO‐exposed patients and controls, respectively; three (4%) and one (<1%) deaths were attributed to VOD/SOS. In multivariate analyses, GO exposure was observed to be associated with an increased risk of VOD/SOS at 100 days, but was not associated with overall survival, disease‐free survival, relapse, or nonrelapse mortality.

Conclusions

Results suggest that GO treatment prior to alloHCT in pediatric patients may increase the risk of VOD/SOS but not death.
Modeling and Simulation of RDX Powder Thermo‐Mechanical Response to Drop Impact
Authors: Yakaboski Otmar , Kumar Ashok V.
Published: April 2021

A computational framework to predict the deformation, flow, and compaction of an energetic material (EM) powder subjected to drop impact is discussed. Explicit dynamic finite element analysis was performed to simulate drop‐weight impact tests for comparison with experimental results and to gain insight into the ignition sensitivity of RDX powder. The computations simulated the Thermo‐Mechanical behavior of a thin layer of energetic powder subjected to drop impact to study the dependence of ignition sensitivity on the anvil material properties. By modeling high strength steel and a low strength copper anvil, a direct comparison is made on how energy dissipation within the EM is influenced by anvil properties. A hybrid finite element model is introduced that captures the mesoscale discrete particle nature of the powder response in regions of interest while using a continuum model elsewhere to reduce computational cost. To capture the mesoscale behavior, a multi‐particle finite element method (MPFEM) approach was used in selected regions in the hybrid model. Powder temperatures were computed to understand how the striker impact energy is dissipated by plasticity and friction into localized heating of the EM that triggers the ignition. Munition designers can use such a framework to study the low‐level impact sensitivity of munitions in a computationally efficient manner. Results of the simulation using the hybrid model suggest that copper anvil undergoes plastic deformation which absorbs a significant portion of the impact energy reducing the energy dissipated within the EM and suppressing ignition.
Did student experience age discrimination?
Authors: Lyerly Eric
Published: April 2021

A student entered the University of Akron's Integrated Bioscience doctoral program at age 61 to pursue his  Ph.D. in biology. The program required its students to choose a major advisor and a Ph.D. advisory committee of five faculty members.
Loop-tree duality from vertices and edges
Authors: Torres Bobadilla William J.
Published: April 2021

Abstract

The causal representation of multi-loop scattering amplitudes, obtained from the application of the loop-tree duality formalism, comprehensively elucidates, at integrand level, the behaviour of only physical singularities. This representation is found to manifest compact expressions for multi-loop topologies that have the same number of vertices. Interestingly, integrands considered in former studies, with up-to six vertices and L internal lines, display the same structure of up-to four-loop ones. The former is an insight that there should be a correspondence between vertices and the collection of internal lines, edges, that characterise a multi-loop topology. By virtue of this relation, in this paper, we embrace an approach to properly classify multi-loop topologies according to vertices and edges. Differently from former studies, we consider the most general topologies, by connecting vertices and edges in all possible ways. Likewise, we provide a procedure to generate causal representation of multi-loop topologies by considering the structure of causal propagators. Explicit causal representations of loop topologies with up-to nine vertices are provided.
Subcritical polarisations of symplectic manifolds have degree one
Authors: Geiges Hansjörg , Sporbeck Kevin , Zehmisch Kai
Published: April 2021

We show that if the complement of a Donaldson hypersurface in a closed, integral symplectic manifold has the homology of a subcritical Stein manifold, then the hypersurface is of degree one. In particular, this demonstrates a conjecture by Biran and Cieliebak on subcritical polarisations of symplectic manifolds. Our proof is based on a simple homological argument using ideas of Kulkarni–Wood.
Frobenius groups of low rank
Authors: Knapp Wolfgang , Schmid Peter
Published: April 2021

Let G be a finite Frobenius group of degree n. We show, by elementary means, that n is a power of some prime p provided the rank $${\mathrm{rk}}(G)\le 3+\sqrt{n+1}$$

rk

(
G
)

≤
3
+

n
+
1

. Then the Frobenius kernel of G agrees with the (unique) Sylow p-subgroup of G. So our result implies the celebrated theorems of Frobenius and Thompson in a special situation.
Liver-targeting drugs and their effect on blood glucose and hepatic lipids
Authors: Gastaldelli Amalia , Stefan Norbert , Häring Hans-Ulrich
Published: April 2021

The global epidemic of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) and the high prevalence among individuals with type 2 diabetes has attracted the attention of clinicians specialising in liver disorders. Many drugs are in the pipeline for the treatment of NAFLD/NASH, and several glucose-lowering drugs are now being tested specifically for the treatment of liver disease. Among these are nuclear hormone receptor agonists (e.g. peroxisome proliferator-activated receptor agonists, farnesoid X receptor agonists and liver X receptor agonists), fibroblast growth factor-19 and -21, single, dual or triple incretins, sodium–glucose cotransporter inhibitors, drugs that modulate lipid or other metabolic pathways (e.g. inhibitors of fatty acid synthase, diacylglycerol acyltransferase-1, acetyl-CoA carboxylase and 11β-hydroxysteroid dehydrogenase type-1) or drugs that target the mitochondrial pyruvate carrier. We have reviewed the metabolic effects of these drugs in relation to improvement of diabetic hyperglycaemia and fatty liver disease, as well as peripheral metabolism and insulin resistance.

Graphical abstract
Patientenspezifische Instrumentierung und Totalendoprothesen am Knie
Authors: Mathis Dominic T. , Hirschmann Michael T.
Published: April 2021

Hintergrund

Die patientenspezifische Instrumentierung (PSI) ist eine vielversprechende neue Technologie in der orthopädischen Chirurgie, die das Ziel verfolgt, die Implantationstechnik der Knietotalendoprothese (Knie-TEP) im Vergleich zur konventionellen Instrumentierung zu vereinfachen und präziser zu machen. Ziel dieses Artikels ist es, Vorteile und Grenzen der PSI für die primäre Knie-TEP zu beschreiben.

Material und Methoden

Es erfolgte eine umfassende Literaturrecherche zum Thema PSI in der Knieprothetik hinsichtlich Evidenz für Planung, Präzision, klinische Ergebnisse, intraoperative Parameter sowie Kosten und Effizienz.

Ergebnisse

Die dreidimensionale Computertomographie (CT) weist in der präoperativen Planung der Knie-TEP eine höhere Genauigkeit auf als 2‑D-Röntgenaufnahmen. Die meisten Arbeiten postulierten keine signifikanten Effekte zugunsten der Genauigkeit der PSI gegenüber der Standard-Knie-TEP. Aber sie berichteten auch nicht, dass die Genauigkeit mit PSI schlechter sei. Hinsichtlich des klinischen Outcomes gibt es genügend Konsens unter den veröffentlichten Studien, um festzuhalten, dass es kurz- und mittelfristig keinen Unterschied zwischen Patienten gibt, die mit PSI oder konventioneller Technik operiert wurden. Eine große Metaanalyse konnte weder eine kürzere Operationszeit noch eine geringere Komplikationsrate für die PSI-Knie-TEP feststellen. Lediglich der intraoperative Blutverlust erwies sich als niedriger im Vergleich zur Standardtechnik, jedoch mit unveränderter Transfusionsrate. Kosteneffektivitätsanalysen lassen schlussfolgern, dass die PSI aktuell (noch) nicht kosteneffektiv ist.

Diskussion

Obwohl die aktuell vorliegenden Studienergebnisse die PSI-Technologie hinsichtlich vieler messbaren Kriterien nicht eindeutig von der Standardtechnik abheben, zeigt die PSI viele theoretische und praktische Vorteile.
Homophilic and heterophilic cadherin bond rupture forces in homo- or hetero-cellular systems measured by AFM-based single-cell force spectroscopy
Authors: Viji Babu Prem Kumar , Mirastschijski Ursula , Belge Ganzanfer , Radmacher Manfred
Published: April 2021

Cadherins enable intercellular adherens junctions to withstand tensile forces in tissues, e.g. generated by intracellular actomyosin contraction. In-vitro single molecule force spectroscopy experiments can reveal cadherin–cadherin extracellular region binding dynamics such as bond formation and strength. However, characterization of cadherin-presenting cell homophilic and heterophilic binding in the proteins’ native conformational and functional states in living cells has rarely been done. Here, we used atomic force microscopy (AFM) based single-cell force spectroscopy (SCFS) to measure rupture forces of homophilic and heterophilic bond formation of N- (neural), OB- (osteoblast) and E- (epithelial) cadherins in living fibroblast and epithelial cells in homo- and hetero-cellular arrangements, i.e., between cells and cadherins of the same and different types. In addition, we used indirect immunofluorescence labelling to study and correlate the expression of these cadherins in intercellular adherens junctions. We showed that N/N and E/E-cadherin homophilic binding events are stronger than N/OB heterophilic binding events. Disassembly of intracellular actin filaments affects the cadherin bond rupture forces suggesting a contribution of actin filaments in cadherin extracellular binding. Inactivation of myosin did not affect the cadherin rupture force in both homo- and hetero-cellular arrangements, but particularly strengthened the N/OB heterophilic bond and reinforced the other cadherins’ homophilic bonds.
Spatially Quasi-Periodic Water Waves of Infinite Depth
Authors: Wilkening Jon , Zhao Xinyu
Published: April 2021

We formulate the two-dimensional gravity-capillary water wave equations in a spatially quasi-periodic setting and present a numerical study of solutions of the initial value problem. We propose a Fourier pseudo-spectral discretization of the equations of motion in which one-dimensional quasi-periodic functions are represented by two-dimensional periodic functions on a torus. We adopt a conformal mapping formulation and employ a quasi-periodic version of the Hilbert transform to determine the normal velocity of the free surface. Two methods of time-stepping the initial value problem are proposed, an explicit Runge–Kutta (ERK) method and an exponential time-differencing (ETD) scheme. The ETD approach makes use of the small-scale decomposition to eliminate stiffness due to surface tension. We perform a convergence study to compare the accuracy and efficiency of the methods on a traveling wave test problem. We also present an example of a periodic wave profile containing vertical tangent lines that is set in motion with a quasi-periodic velocity potential. As time evolves, each wave peak evolves differently, and only some of them overturn. Beyond water waves, we argue that spatial quasi-periodicity is a natural setting to study the dynamics of linear and nonlinear waves, offering a third option to the usual modeling assumption that solutions either evolve on a periodic domain or decay at infinity.
Pars-plana-Vitrektomie – von Saug-Schneide-Systemen bis hin zur Ultraschalltechnik
Authors: Deuchler Svenja , Knoch Timo , Papour Asael , Kohnen Thomas , Koch Frank
Published: April 2021

Um 1970 herum wurde erstmals ein Schneidegerät, in welches ein Infusions- und ein Aspirationskanal integriert wurden – der „vitreous infusion suction cutter“ (V.I.S.C) –, standardmäßig für die Entfernung des Glaskörpers angewandt. Schneidesysteme haben sich von da an immer weiter entwickelt. Schallenergie blieb lange den Vorderabschnittschirurgien vorbehalten. Ab 2020 kann in Form der Vitesse™ Schall auch für den Hinterabschnitt genutzt werden. Bei diesem Verfahren der Liquifizierungstechnik wird Ultraschallenergie auf ein einzelnes, großes inneres Lumen übertragen, das den Port der Nadel mechanisch in Schwingung versetzt. Diese Hochgeschwindigkeitsvibrationen scheren den Glaskörper an den Portkanten ab, bevor er in die Nadel eintritt. Dieser Mechanismus minimiert die Traktion des Glaskörpers und ermöglicht eine schnellere Aspiration bei niedrigerem Vakuum im Vergleich zu herkömmlichen Schneidesystemen. Diese Vorteile können zu einer sichereren und effizienteren vitreoretinalen Chirurgie führen.
Angehörige von Patienten mit Demenz als Bindeglied und Vermittler im Akutkrankenhaus
Authors: Greskötter Jasmin M.
Published: April 2021

Hintergrund

Den Bedürfnissen von Patienten mit Demenz kann im organisations- und ablauforientierten Akutkrankenhaus kaum Rechnung getragen werden. Um dennoch eine gelingende Interaktion zwischen Patienten und medizinisch-pflegerischem Fachpersonal herzustellen, wird die Bedeutung von Angehörigen als Bindeglied und Vermittler betrachtet.

Ziel

Aus Publikationen zu ähnlichen Themen wird abgeleitet, welche Bedingungen Angehörige benötigen, um als Bindeglied und Vermittler agieren zu können.

Material und Methode

In den Datenbanken Medline (PubMed), Cochrane, CINAHL und GeroLit erfolgte eine systematische Recherche.

Ergebnisse

Aus der vorliegenden Literatur lassen sich Gründe für die Begleitung durch Angehörige skizzieren, ihre Tätigkeiten im Akutkrankenhaus beschreiben sowie hinderliche und förderliche Faktoren darlegen.

Diskussion

Angehörige sind bereits als Bindeglied und Vermittler zwischen den Patienten mit Demenz und dem Krankenhauspersonal tätig. Dabei treten sie für den Patienten als Fürsprecher ein und stehen den Fachkräften als Experten und Berater zur Verfügung. Für das Gelingen dieser Aufgabe gibt es Bedingungen, welche die Vermittlungstätigkeit fördern oder erschweren.
Annual trends in Google searches provides insights related to rhinosinusitis exacerbations
Authors: Liu David T. , Schally Martin , Schneider Sven , Eckl-Dorna Julia , Phillips Katie M. , Mueller Christian A. , Sedaghat Ahmad R. , Besser Gerold
Published: April 2021

Purpose

Temporal trends of disease-specific internet searches may provide novel insights into seasonal dynamics of disease burden and, by extension, disease pathophysiology. The aim of this study was to define the temporal trends in rhinosinusitis-specific internet searches.

Methods

This was a cross sectional analysis of search volume for predefined search terms. Google trends was used to explore the volume of searches for five specific search terms related to rhinosinusitis: nose, mucus, sinus, sinusitis, chronic sinusitis, which were entered into Google web search between 2004 and 2019. Results were analyzed within search “context” which included temporally associated related searches. Relative search volume (RSV) was analyzed for English and non-English speaking countries from the Northern and Southern hemispheres. Analysis of seasonality was performed using the cosinor model.

Results

The five specific search terms were most related to rhinosinusitis-related search contexts, indicating that they were appropriately reflective of internet queries by patients for rhinosinusitis. The RSV for rhinosinusitis-related terms and more general search terms increased with each passing year indicating constant interest in rhinosinusitis. Cosinor time series analysis revealed inquiry peaks in winter months for all five specific rhinosinusitis-related search terms independent from the hemisphere.

Conclusion

Over a 15-year period, Google searches with rhinosinusitis-specific search terms consistently peaked during the winter around the world. These findings indirectly support the model of viral infection or exposure as the predominant cause of acute rhinosinusitis and acute exacerbations of chronic rhinosinusitis.
Respiratory parameters on diagnostic sleep studies predict survival in patients with amyotrophic lateral sclerosis
Authors: Engel Markus , Glatz Christian , Helmle Cornelia , Young Peter , Dräger Bianca , Boentert Matthias
Published: April 2021

Objective

In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement and sleep-disordered breathing relate to worse prognosis. The present study investigated whether respiratory outcomes on first-ever sleep studies predict survival in patients with ALS, specifically taking into account subsequent initiation of non-invasive ventilation (NIV).

Methods

From patients with ALS, baseline sleep study records, transcutaneous capnometry, early morning blood gas analysis, survival data and clinical disease characteristics were retrospectively analyzed. Patients were stratified according to whether enduring NIV was consecutively established (“NIV(+)”) or not (“NIV(–)”).

Results

Among the study cohort (n = 158, 72 female, 51 with bulbar onset ALS, 105 deceased) sleep-disordered breathing was present at baseline evaluation in 97 patients. Early morning base excess (EMBE) > 2 mmol/l predicted nocturnal hypercapnia. Ninety-five patients were NIV(+) and 63 were NIV(–). Survival from baseline sleep studies was significantly reduced in NIV(–) but not in NIV(+) patients with nocturnal CO2 tension ≥ 50 mmHg, apnea hypopnea index ≥ 5/h, and EMBE > 2 mmol/l. Hazard ratio for EMBE > 2 mmol/l was increased in NIV(–) patients only, and EMBE independently predicted survival in both NIV(–) and NIV(+) patients. Furthermore, EMBE on baseline sleep studies was the only predictor for survival from symptom onset, and hazard ratio for shorter survival was markedly higher in the NIV(–) than the NIV(+) group (2.85, p = 0.005, vs. 1.71, p = 0.042).

Interpretation: In patients with ALS, EMBE > 2 mmol/l predicts nocturnal hypercapnia and shorter survival. Negative effects of sleep-disordered breathing on survival are statistically abolished by sustained NIV.
Surgical treatment of liver metastases from non-colorectal non-neuroendocrine carcinomas
Authors: Bauschke Astrid , Altendorf-Hofmann Annelore , Homman Merten , Manger Thomas , Pertschy Jörg , Helfritzsch Herry , Göbel Hubert , Settmacher Utz
Published: April 2021

Introduction

In the literature, results after surgical treatment of non-colorectal non-neuroendocrine liver metastases (NCNNLM) are reported that are often inferior to those from colorectal liver metastases. The selection of patients with favorable tumor biology is currently still a matter of discussion.

Materials/methods

The retrospective data analysis was based on data that were collected for the multicenter study “Role of surgical treatment for non-colorectal liver metastases” in county Thuringia.

Results

For the study, 637 patients were included from 1995 to 2018. 5 and 10-year survival of R0 resected patients were 33% and 19%, respectively. In the multi-variate analysis of the entire group, sex, timing, disease-free interval, number of metastases, R-classification as well as lymph node status of the primary lesion showed an independent statistical influence on the 5-year survival. In the group of R0 resected patients, disease-free interval, number of metastases and lymph node status of the primary lesion influenced the 5-year survival in the multi-variate analysis. In kidney malignancies, R-classification, timing and number of liver metastases were statistically significant in the multi-variate analysis of the 5-year survival, in mamma carcinomas only the R-classification.

Conclusion

The Adam score identifies some risk factors which influence prognosis in most but not in all tumor entities. For kidney cancer and breast cancer it can be simplified.