bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of digital breast tomosynthesis in female patients with nipple discharge
Authors: Barsic Ostojic Sanja , Grbanovic Lora , Tonklin Ana , Kovacevic Lucija , Marusic Zlatko , Prutki Maja
Published: February 2022

Background

Nipple discharge is one of the most common symptoms related to the breast, but it is a presenting feature of breast cancer in 5%–12% of women.

Aims

The purpose of this study was to determine the diagnostic performance of digital breast tomosynthesis (DBT) in the evaluation of patients with nipple discharge and to compare it with mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI).

Methods and Results

This retrospective study included 53 patients with nipple discharge. All patients underwent DBT, and results were compared to MMG, breast US, and MRI. Radiological findings for each method were categorized according to BI‐RADS classification: categories 1–2 were considered negative and categories 3–5 positive. If a tissue specimen was obtained, the final diagnosis was established based on the results of histopathological analysis; otherwise, a clinical follow‐up was required for at least 2 years to confirm benign radiological findings. Measures of diagnostic accuracy of DBT, MMG, US, and MRI were calculated and compared.

Results

Final histopathological analysis revealed six malignant breast lesions, all of which were detected in patients with pathologic nipple discharge. DBT and MRI exhibited high sensitivity (100%) and high negative predictive value (100%) for the detection of breast cancer in patients with nipple discharge. DBT showed higher specificity compared to MRI (82.9% vs. 61.9%). Sensitivity and specificity of MMG were 83.3% and 76.6%, respectively. Breast US was determined to have a sensitivity of 66.7% and specificity of 57.5%.

Conclusion

DBT exhibited higher specificity than MRI at the same level of sensitivity and negative predictive value. Therefore, the use of DBT should be considered as an alternative to MRI in the assessment of patients with nipple discharge.
Wilms tumour treatment in Sudan: A 10‐year single‐centre experience
Authors: Abdalla Mohammed , Hameed Somaya
Published: February 2022

Background

In Sudan, the survival of Wilms tumour was reported as 11% in a 2008 study. The impact of establishing paediatric oncology service on survival is studied, and the obstacles of treating Wilms tumour patients were identified.

Aim

This study investigates Wilms tumour treatment outcomes over 10 years at Khartoum Oncology Hospital (KOH).

Methods

All Wilms tumour patients from 2005 to 2014 were analysed retrospectively. Patients received treatment based on the NWTS IV protocol. Patients were analysed for overall survival, and event‐free survival and these outcomes were correlated with age, sex, stage at presentation, and histology.

Results

We analysed 143 files of Wilms tumour patients. The male to female ratio is 1.75. The mean age of patients at diagnosis is 3.5 years. The follow‐up period is 5 years. Most patients (83%) had advanced disease stage 3, and 4. There is a very high abandonment rate 61 (42.6%). The event‐free survival among patients who completed treatment is 75.6%, and is 43.4% for all the (143) patients.

Conclusions

“After initiation of the paediatric oncology service, the survival of Wilms tumour in Sudan is 43%. Abandonment of treatment remains high. Opportunity remains to reduce abandonment and establish a surgical paediatric oncology service to improve outcomes further.”
An abdominal wall neuroendocrine tumor of unknown primary origin: A case report and review of the literature
Authors: Jagiella‐Lodise Olivia , Jagiella Valerie , Weitman Evan
Published: February 2022

Background

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine and nervous system. NETs, often found in the gastrointestinal tract, can be found anywhere in the body, and have metastatic potential. NETs occasionally present with metastatic disease without an identifiable primary tumor.

Case

A 79‐year‐old female patient presented with an abdominal wall mass. Percutaneous biopsy was consistent with a NET. Preoperative endoscopy and PillCam were unremarkable. PET Dotatate demonstrated uptake in the abdominal wall as well as vague uptake in the pelvis. Intraoperatively, we identified a suspicious nodule on the sigmoid colon, which was consistent with a drop metastasis on final pathology.

Conclusion

In this case report we present a patient with a NET metastasis to the abdominal wall without a known primary site. This case highlights the limitations of endoscopy and imaging in the workup of metastatic NETs. Additionally, this is a novel case report of a metastatic NET to the abdominal wall without an identifiable primary site.
DFT Calculations for Mössbauer Properties on Dinuclear Center Models of the Resting Oxidized Cytochrome c Oxidase
Authors: Han Du Wen‐Ge , Götz Andreas W. , Noodleman Louis
Published: February 2022

Mössbauer isomer shift and quadrupole splitting properties have been calculated using the OLYP‐D3(BJ) density functional method on previously obtained (W.‐G. Han Du, et al., Inorg Chem. 2020, 59, 8906–8915) geometry optimized Fea33+−H2O−CuB2+ dinuclear center (DNC) clusters of the resting oxidized (O state) “as‐isolated” cytochrome c oxidase (CcO). The calculated results are highly consistent with the available experimental observations. The calculations have also shown that the structural heterogeneities of the O state DNCs implicated by the Mössbauer experiments are likely consequences of various factors, particularly the variable positions of the central H2O molecule between the Fea33+ and CuB2+ sites in different DNCs, whether or not this central H2O molecule has H‐bonding interaction with another H2O molecule, the different spin states having similar energies for the Fea33+ sites, and whether the Fea33+ and CuB2+ sites are ferromagnetically or antiferromagnetically spin‐coupled.
Investigating service users' perspectives of eating disorder services: A meta‐synthesis
Authors: Babb Charli , Jones Catherine R. G. , Fox John R. E.
Published: February 2022

Objective

Despite a number of qualitative studies published from the perspective of eating disorder (ED) service users, there has been no attempt to exclusively synthesize their views to gain a fuller understanding of their ED service experiences. It is important to understand this perspective, since previous research highlights the difficulties ED healthcare professionals report when working with this client group.

Method

A systematic search of the literature was conducted to identify qualitative studies focusing on experiences of ED services from the perspective of service users. Twenty‐two studies met the inclusion criteria and underwent a quality appraisal check using the Critical Appraisal Skills Programme (CASP) tool for qualitative research. These were then synthesized using a meta‐synthesis approach.

Results

Four overarching themes were generated: “Treatment: Focus on physical vs. psychological symptoms”; “Service Environment: The role of control within services”; “Staff: Experiences with staff and the value of rapport”; and “Peer Influence: Camaraderie vs. comparison.” Service users expressed a desire for more psychological input to tackle underlying difficulties relating to their ED. A complex relationship with feelings of control was described, with some feeling over‐controlled by service providers, while others retrospectively recognized the need for control to be taken away. Staff values, knowledge and trust played a significant role in treatment and recovery. Peers with an ED were described to be a valuable source of understanding and empathy, but some found peer influence to perpetuate comparison and competitiveness.

Discussion

The results portray some of the conflicts and complexities that service users encounter in ED services. A running thread throughout is the perceived importance of adopting an individualized approach within these services.
Characterization of mmWave X‐duplex multi‐relay system in 5G mobile network
Authors: Banar Mohsen , Mohammadi Abbas , Kazemi Mohammad
Published: February 2022

In this paper, we propose a millimeter wave (mmWave) X‐duplex (XD) amplify‐and‐forward (AF) multirelay system for 5G and beyond. Each XD AF relay is equipped with a shared antenna for both transmission and reception radio frequency (RF) chains. Also, the performance of mmWave XD AF multirelay system is analyzed, and a relay selection method in this scenario is suggested, where the best relay and the best operation mode are selected based on maximum end‐to‐end signal‐to‐interference‐plus‐noise ratio (SINR). XD relays can switch adaptively between half‐duplex (HD) and full‐duplex (FD) operation modes. As a practical channel model, Rician fading, path loss with line‐of‐sight (LOS) and non‐line‐of‐sight (NLOS) propagation, and blockage effects are considered for mmWave channel model in both source–relay and relay–destination links. We derive closed‐form expressions for end‐to‐end SINR and its distribution, outage probability, energy efficiency (EE), rate, and average symbol error rate (SER) based on the relay selection method. Monte Carlo simulations are performed to validate our analytical derivations, and also, the simulation results depict that XD relays outperform both HD and FD operation modes in terms of outage probability, EE, SER, and rate. Furthermore, the effects of self‐interference (SI) cancellation, blockage, and number of XD AF relays over the performance and also the comparison of XD relay selection to different existing relay selection policies are presented. In addition, it is shown that the XD relay selection method in our proposed system eliminates the performance floor of the FD caused by the residual SI that it is considered as a significant advantage of our proposed system.
Crosswalk study on blood collection‐tube types for Alzheimer's disease biomarkers
Authors: Jonaitis Erin M. , Zetterberg Henrik , Koscik Rebecca Langhough , Betthauser Tobey J. , Van Hulle Carol A. , Hogan Kirk , Hegge Laura , Kollmorgen Gwendlyn , Suridjan Ivonne , Gleason Carey E. , Engelman Corinne D. , Okonkwo Ozioma C. , Asthana Sanjay , Bendlin Barbara B. , Carlsson Cynthia M. , Johnson Sterling C. , Blennow Kaj
Published: February 2022

Introduction

Blood‐based Alzheimer's disease (AD) biomarkers show promise, but pre‐analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [, , , total tau [t‐tau], neurofilament light chain [NfL], and ) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum).

Methods

Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography‐positive and ‐negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention. We modeled AD biomarker values observed in EDTA plasma versus heparin plasma and serum, and assessed correspondence with brain amyloidosis.

Results

Results suggested bias due to tube type, but crosswalks are possible for some analytes, with excellent model fit for NfL (= 0.94), adequate for amyloid (= 0.40‐0.69), and weaker for t‐tau (= 0.04‐0.42) and ( = 0.22‐0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma (= 1.29).

Discussion

AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood.
Self‐reported word‐finding complaints are associated with cerebrospinal fluid amyloid beta and atrophy in cognitively normal older adults
Authors: Montembeault Maxime , Stijelja Stefan , Brambati Simona M. ,   For the Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

Introduction

Self‐reported word‐finding difficulties are among the most frequent complaints in cognitively normal (CN) older adults. However, the clinical significance is still debated.

Methods

We selected 239 CN from the Alzheimer's Disease Neuroimaging Initiative database who had completed the Everyday Cognition (ECog) questionnaire, as well as a lumbar puncture for amyloid beta (Aβ) and magnetic resonance imaging.

Results

Word‐finding complaints, with a few other memory items, were significantly more severe compared to all other cognitive complaints. Ecog‐Lang1 (Forgetting names of objects) severity significantly predicted Aβ levels in CN, even when controlling for general cognitive complaint, demographic, and psychological variables. Individuals with high Ecog‐Lang1 complaints showed atrophy in the left fusiform gyrus and the left rolandic operculum compared to CN with low complaints.

Discussion

Overall, our results support the fact that word‐finding complaints should be taken seriously. They have the potential to identify CN at risk of AD and support the need to include other cognitive domains in the investigation of subjective cognitive decline.
Thicker macula in asymptomatic APOE Ɛ4 middle‐aged adults at high AD risk
Authors: Rotenstreich Ygal , Sharvit‐Ginon Inbal , Sher Ifat , Zloto Ofira , Fabian Ido Didi , Abd‐Elkader Amir , Weller Aron , Heymann Anthony , Beeri Michal Schnaider , Ravona‐Springer Ramit
Published: February 2022

Introduction

We compared retinal layers’ thickness between apolipoprotein E (APOE) Ɛ4 carriers and non‐carriers in a cohort of cognitively normal middle‐aged adults enriched for Alzheimer's disease (AD) risk.

Methods

Participants (N = 245) underwent spectral domain optical coherence tomography. Multivariate analyses of covariance adjusting for age, sex, education, and best corrected vision acuity was used to compare retinal thickness between APOE groups.

Results

Participants’ mean age was 59.60 (standard deviation = 6.42) with 66.4% women and 32.2% APOE Ɛ4 carriers. Greater macular full thickness was observed in APOE Ɛ4 carriers compared to non‐carriers (P = .017), reaching statistical significance for the inner and outer nasal (P = .009 and P = .005, respectively), inner superior (P = .041), and inner and outer inferior (P = .013 and P = .033, respectively) sectors. The differences between APOE groups were mainly driven by the ganglion cell layer (P < .05) and the inner plexiform layer (P < .05).

Discussion

A thicker macula is observed already in midlife asymptomatic APOE Ɛ4 carriers at high AD risk.
Endurance and gait speed relationships with mild cognitive impairment and dementia
Authors: Windham Beverly Gwen , Parker Sara B. , Zhu Xiaoqian , Gabriel Kelley Pettee , Palta Priya , Sullivan Kevin J. , Parker Kirby G. , Knopman David S. , Gottesman Rebecca F. , Griswold Michael E. , Mosley Thomas H.
Published: February 2022

Introduction

Slower mobility is associated with mild cognitive impairment (MCI) and dementia. We examined the interaction of endurance with gait speed on prevalent MCI and dementia.

Methods

Cross‐sectional multinomial regression in the ARIC cohort (n = 2844 participants; 71 to 94 years; 44% men; 18% Black persons) with cognitive status (normal/MCI/dementia), 4 m gait speed, and endurance (2 minute walk [2MW]).

Results

Faster gait speed (up to but not above 1 m/s) and better 2MW were separately associated with lower dementia risk. Good performance in both (2MW = 200 m, gait speed = 1.2 m/s) was associated with 99% lower dementia (Relative Prevalence Ratio [RPR] = 0.01 [95% CI: 0.0 to 0.06]) and 73% lower MCI, RPR = 0.27 (0.15 to 0.48) compared to poor performance in both (2MW = 100 m, gait speed = 0.8 m/s). Models incorporating a gait speed‐by‐2MW interaction term outperformed gait speed‐only models (P < .001).

Discussion

Gait speed relationships with dementia diminish at faster gait speeds. Combining endurance with gait speed may yield more sensitive markers of MCI and dementia than gait speed alone.
Fitness, risk taking, and spatial behavior covary with boldness in experimental vole populations
Authors: Eccard Jana A. , Herde Antje , Schuster Andrea C. , Liesenjohann Thilo , Knopp Tatjana , Heckel Gerald , Dammhahn Melanie
Published: February 2022

Individuals of a population may vary along a pace‐of‐life syndrome from highly fecund, short‐lived, bold, dispersive “fast” types at one end of the spectrum to less fecund, long‐lived, shy, plastic “slow” types at the other end. Risk‐taking behavior might mediate the underlying life history trade‐off, but empirical evidence supporting this hypothesis is still ambiguous. Using experimentally created populations of common voles (Microtus arvalis)—a species with distinct seasonal life history trajectories—we aimed to test whether individual differences in boldness behavior covary with risk taking, space use, and fitness. We quantified risk taking, space use (via automated tracking), survival, and reproductive success (via genetic parentage analysis) in 8 to 14 experimental, mixed‐sex populations of 113 common voles of known boldness type in large grassland enclosures over a significant part of their adult life span and two reproductive events. Populations were assorted to contain extreme boldness types (bold or shy) of both sexes. Bolder individuals took more risks than shyer ones, which did not affect survival. Bolder males but not females produced more offspring than shy conspecifics. Daily home range and core area sizes, based on 95% and 50% Kernel density estimates (20 ± 10 per individual, n = 54 individuals), were highly repeatable over time. Individual space use unfolded differently for sex‐boldness type combinations over the course of the experiment. While day ranges decreased for shy females, they increased for bold females and all males. Space use trajectories may, hence, indicate differences in coping styles when confronted with a novel social and physical environment. Thus, interindividual differences in boldness predict risk taking under near‐natural conditions and have consequences for fitness in males, which have a higher reproductive potential than females. Given extreme inter‐ and intra‐annual fluctuations in population density in the study species and its short life span, density‐dependent fluctuating selection operating differently on the sexes might maintain (co)variation in boldness, risk taking, and pace‐of‐life.
Forecasting soil erosion and sediment yields during flash floods: The disastrous case of Mandra, Greece, 2017
Authors: Kaffas Konstantinos , Papaioannou George , Varlas George , Al Sayah Mario J. , Papadopoulos Anastasios , Dimitriou Elias , Katsafados Petros , Righetti Maurizio
Published: February 2022

Flash floods, among the most destructive natural hazards, are commonly studied as to their catastrophic power in terms of fatalities, infrastructure damages and economic losses. A devastating aftermath of flash floods, which has not received much‐deserved attention in the literature, is the sizeable and permanent soil loss due to soil erosion and sediment yields. This study aims at forecasting soil erosion and sediment yields due to the disastrous storm event that occurred in Mandra town (western Attica, Greece) on 15 November 2017. Gridded hydrometeorological forecasts were conducted at 5‐min and 1‐h time steps by means of the chemical hydrological atmospheric ocean wave system (CHAOS). The forecasts of soil erosion and sediment yields were achieved by a high‐resolution geographic information system (GIS) application of the modified universal soil loss equation (MUSLE) on the basis of the forecasted surface runoff hydrographs. The entire event lasted from the afternoon of 14 November until noon of 15 November, but the bulk of the disastrous storm occurred in the morning of 15 November 2017, flooding two torrent basins. As a result of the extreme flash flood, 2195 tons and 1435 tons of sediment were forecasted to be detached from the body of the soil's surface and transported to the stream networks of the Soures and Agia Aikaterini Torrent basins which cross Mandra. Soil erosion maps were constructed for every hour and the spatial and temporal evolution of soil erosion was shown throughout the event. This study provides concrete insights on the erosion‐prone areas of the study basins, which can inform actions against erosion.
Data‐driven approach to design energy‐efficient joint precoders at source and relay using deep learning in MIMO‐CRNs
Authors: Sahu Deepak , Maurya Shikha , Bansal Matadeen , Kumar Dinesh
Published: February 2022

This article studies the problem of designing energy‐efficient joint precoder at source and relay for multiple‐input multiple‐output cognitive relay networks (MIMO‐CRNs). Existing optimization methods typically suffer from high computational complexity of finding the optimal solution for such nonconvex fractional programming problems. In contrast to prior works, this article considers a data‐driven approach to design the joint precoders using a deep neural network (DNN). The proposed DNN learns the optimal precoder weights on a set of different channel matrices during the offline training phase and allows the computational cost reduction in the online deployment phase. The numerical results demonstrate that this approach provides a comparable performance at significantly lower computational complexity in comparison with the conventional optimization‐based algorithm. Furthermore, it is shown that the proposed approach is quite robust against the variations in the channel statistics, which makes it suitable for real‐time implementation.
Electric Vehicle Adoption and Grid Emergency Preparedness
Authors: Oloriz Margaret , Vangala Shreyas , Sadowicz Audrey
Published: February 2022

Anthropogenic climate change is considered one of the most impactful threats facing the world today. In response, all sectors of the economy are undergoing or planning changes to improve operational efficiencies to reduce greenhouse gas (GHG) emissions—a major contributor to climate change. The transportation sector in the US is responsible for 29 percent of the country's GHG emissions, as shown on Figure 1. Transitioning to zero emission vehicles (ZEVs), including electric vehicles (EVs), is a key strategy for reducing these emissions in the US.
The Surrogation of Surrogacy: The Perils and Pitfalls of Epistemic Authority
Authors: Teti Stowe Locke
Published: February 2022

While philosophers have long noted that having knowledge alone is not sufficient reason to act, in bioethics, we take epistemic authority to be sufficient justification for decisional authority. A bit of disambiguation focuses this concern; surrogation is a psychological phenomenon found in business practices whereby a measure of something of interest evolves to replace the thing itself. In an everyday example of surrogation, a manager tasked with increasing customer satisfaction begins to believe that the customer satisfaction survey score is in fact customer satisfaction. In the clinical setting, an equivalent would involve the belief that a surrogate decision‐maker's wishes for the patient are the patient's own wishes. Recounting a father's unexpected life‐or‐death decision about treatment for an adult son, this essay explores the perils and pitfalls of taking epistemic authority to be sufficient justification for decisional authority.
Advance Directives: The Principle of Determining Authenticity
Authors: Carter Matilda
Published: February 2022

In medical ethics, there is a well‐established debate about the authority of advance directives over people living with dementia, a dispute often cast as a clash between two principles: respecting autonomy and beneficence toward patients. In this article, I argue that there need be only one principle in substitute decision‐making: determining authenticity. This principle favors a substituted judgment standard in all cases and instructs decision‐makers to determine what the patient would authentically prefer to happen—based not merely on the patient’s decisions but also on their present settled dispositions. Adhering to this principle entails that, in a significant range of cases, an advance directive can (and indeed ought to) be overruled.
Brain‐age estimation accuracy is significantly increased using multishell free‐water reconstruction
Authors: Nemmi Federico , Levardon Mathilde , Péran Patrice
Published: February 2022

Although free‐water diffusion reconstruction for diffusion‐weighted imaging (DWI) data can be applied to both single‐shell and multishell data, recent finding in synthetic data suggests that the free‐water indices from single‐shell acquisition should be interpreted with care, as they are heavily influenced by initialization parameters and cannot discriminate between free‐water and mean diffusivity modifications. However, whether using a longer multishell acquisition protocol significantly improve reconstruction for real human MRI data is still an open question. In this study, we compare canonical diffusion tensor imaging (DTI), single‐shell and multishell free‐water imaging (FW) indices derived from a short, clinical compatible diffusion protocol (b = 500 s/mm2, b = 1,000 s/mm2, 32 directions each) on their power to predict brain age. Age was chosen as it is well‐known to be related to widespread modification of the white matter and because brain‐age estimation has recently been found to be relevant to several neurodegenerative diseases. We used a previously developed and validated data‐driven whole‐brain machine learning pipeline to directly compare the precision of brain‐age estimates in a sample of 89 healthy males between 20 and 85 years old. We found that multishell FW outperform DTI indices in estimating brain age and that multishell FW, even when using low (500 ms2) b‐values secondary shell, outperform single‐shell FW. Single‐shell FW led to lower brain‐age estimation accuracy even of canonical DTI indices, suggesting that single‐shell FW indices should be used with caution. For all considered reconstruction algorithms, the most discriminant indices were those measuring free diffusion of water in the white matter.
Chimeric antigen receptor T‐cell therapy combined with autologous stem cell transplantation improved progression‐free survival of relapsed or refractory diffuse large B‐cell lymphoma patients: A single‐center, retrospective, cohort study
Authors: Wang Tao , Xu Lili , Gao Lei , Tang Gusheng , Chen Li , Chen Jie , Wang Yang , Fu Weijia , Yue Wenqin , Ye Mingyu , Yu Jiechen , Yu Xuejun , Feng Dongge , Zhang Aiping , Yang Jianmin
Published: February 2022

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T‐cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL). However, whether the combination therapy of ASCT and CART (ASCT‐CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT‐CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT‐CART and ASCT groups was 4.71 × 108/kg and 5.36 × 108/kg, respectively (p = 0.469). The median number of CD34+ cell numbers that were infused in the ASCT‐CART and ASCT groups was 2.41 × 106/kg and 3.05 × 106/kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 × 106/kg with a median transduction rate of 59.83%. The objective response rates to ASCT‐CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT‐CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT‐CART group demonstrated superior 3 year progression‐free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT‐CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT‐CART therapy can be used as a salvage therapy for R/R DLBCL patients.
Cancer in twin pairs discordant for smoking: The Nordic Twin Study of Cancer
Authors: Korhonen Tellervo , Hjelmborg Jacob , Harris Jennifer R. , Clemmensen Signe , Adami Hans‐Olov , Kaprio Jaakko ,   Nordic Twin Study of Cancer (NorTwinCan) collaboration
Published: February 2022

The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow‐up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow‐up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co‐twin was diagnosed with any of the following tobacco‐related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co‐twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair‐specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco‐related cancer sites, we recorded 7379 cases during median 27 years of follow‐up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17‐1.48) and current (HR 2.14 [1.95‐2.34]) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15‐2.98) among current smokers and 1.69 (1.00‐2.87) among former smokers when compared to their never smoking co‐twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers.
Origin of Life: Chiral Short RNA Chains Capable of Non‐Enzymatic Peptide Bond Formation
Authors: Bose Tanaya , Fridkin Gil , Bashan Anat , Yonath Ada
Published: February 2022

A semi‐symmetric vestige of an RNA apparatus with stereochemically controlled ribozyme capabilities is embedded and functions as the site of peptide bond formation within all contemporary ribosomes, a finding that is in line with Lahav and Leiserowitz earlier discoveries on stereochemically controlled chemical reactions. As the structure of this semi‐symmetrical self‐folded RNA entity is almost fully conserved in all known ribosomes, it seems to be resilient to evolution, thus hinting at its pre‐biotic origin and hence, suggested by us, to be the protoribosome. Recent studies, described shortly below, demonstrated peptide bond formation by the laboratory‐designed protoribosomes, which supports the notion that a pre‐biotic bonding entity is still functioning in all contemporary ribosomes.
Effective restoration measures in river‐floodplain ecosystems: Lessons learned from the ‘Wilde Mulde’ project
Authors: Schulz‐Zunkel Christiane , Seele‐Dilbat Carolin , Anlanger Christine , Baborowski Martina , Bondar‐Kunze Elisabeth , Brauns Mario , Gapinski Cedric M. , Gründling Ralf , Haaren Christina von , Hein Thomas , Henle Klaus , Junge Frank W. , Kasperidus Hans. D. , Koll Katinka , Kretz Lena , Rast Georg , Schnauder Ingo , Scholz Mathias , Schrenner Heiko , Sendek Agnieszka , Sprössig Claudia , Tavares Claudia Nogueira , Vieweg Michael , von Tümpling Wolf , Weitere Markus , Wirth Christian , Wunsch Tobias , Dziock Frank
Published: February 2022

Over the last 40 years, a growing number of restoration projects have been implemented to improve the ecological conditions of highly degraded rivers and their floodplains. Despite considerable investment in these projects, information is still limited about the effectiveness and the success of such river restoration measures, mainly due to a lack of standardised and interdisciplinary assessment approaches. During the project ‘Wilde Mulde—Restoration of a dynamic riverine landscape in Central Germany’, we implemented hydromorphological restoration measures (installation of large wood, removal of rip‐rap, reconnection of a former river side‐arm) along a lowland river in Central Germany. We carried out intensive scientific monitoring of biodiversity, hydromorphology, ecosystem functions and services, as well as socio‐economic aspects. A Before/After‐Control/Impact (BACI) design was used to identify the spatial and temporal effects of the restoration measures and to distinguish them from changes caused by background variation. For this, we used a comprehensive set of indicators, including abiotic (flow velocity, diversity of riverbed topography, and flow resistance), biological (ecosystem respiration, macroinvertebrates, fish, carabids, vegetation, and birds) and socio‐economic (acceptance and public awareness) indicators as well as the ecosystem service indicator aesthetic quality of the landscape. To meet the inherent challenges of such a large‐scale field experiment, like unpredictable environmental conditions, we used an experimental approach that allowed us to demonstrate a measurable success of the implemented restoration measures. The majority of the abiotic and some of the biological and socio‐economic indicators at the restored sites approached values of a natural reference site while already deviating from values of a nonnatural reference site two years after restoration. In addition to the applied interdisciplinary approach, multiple scales of field investigations and data analyses are essential as key components for evaluating successful river and floodplain restoration projects.
COVID‐19 and risk of retraumatization in adults with a past exposure to potentially traumatic events: A cross‐cultural exploration across Egypt, Germany, and Italy
Authors: Fishere Mariam , Bartoli Eleonora
Published: February 2022

Aims

This study aims to: (1) explore the links between past exposure to potentially traumatic events, fear of contracting COVID‐19 and perceived stress; (2) investigate how the exposure to traumagenic experiences affects one's locus of control over their health; and (3) examine fear, stress reactions and differences in health locus of control across three different sociocultural contexts.

Methods

A total of 524 adult participants were recruited from Egypt, Germany, and Italy through online channels. Self‐reporting instruments were used to assess previous exposure to potentially traumatic events, PTSD symptoms, fear of COVID‐19, perceived stress, and health locus of control.

Results

Our findings highlight differences in reaction to COVID‐19 in relation to past exposure to potentially traumatic events and country of residence, both of which may inform tailored community‐based intervention practices.

Conclusion

The impact of COVID‐19 might be particularly disruptive for people who survived potentially traumatic experiences. Nevertheless, the mass mental health impact of the COVID‐19 pandemic varies across different sociocultural contexts.
The aversiveness of timeout from response‐dependent and response‐independent food deliveries as a function of delivery rate
Authors: Toegel Cory , Holtyn August F. , Toegel Forrest , Perone Michael
Published: February 2022

Seven experiments with rats assessed the aversiveness of timeout using punishment and avoidance procedures. Experiments 1 and 2 considered the contributions of stimulus change, suspending the response–reinforcer contingency, response prevention, the general disruption in the reinforcement schedule during time‐in, and overall decreases in reinforcement. Results support the conclusion that response‐contingent timeouts punish behavior because they are signaled periods during which an ongoing schedule of positive reinforcement is suspended. Experiments 3, 4, and 5 assessed effects of the reinforcement rate during time‐in on the punitive efficacy of timeout and, for comparison, electric shock. Evidence for a direct relation between reinforcement rate and punitive efficacy was equivocal. In Experiments 6 and 7, responding avoided timeout from response‐independent food deliveries. Responding was acquired rapidly when it avoided timeouts from free deliveries of pellets or a sucrose solution, but not when it avoided free deliveries of water. At steady‐state, avoidance rates and proficiency were directly related to the rate of pellet or sucrose deliveries. The relation between the nature of the time‐in environment and the aversiveness of timeout was clear in our avoidance experiments, but not in our punishment experiments. We discuss interpretive problems in evaluating the aversiveness of timeout in the punishment paradigm.
Synthesis a group of 5(6)‐substituted benzimidazole Zn(II) and Co(II) complexes and investigation their cytotoxic and antimicrobial activities
Authors: Yılmaz Ülkü , Apohan Elif , Küçükbay Hasan , Yılmaz Özgür , Tatlıcı Eray , Yeşilada Özfer
Published: February 2022

A series of 5(6)‐substituted benzimidazole ligand‐zinc(II) and cobalt(II) complexes were synthesized and characterized by1H,13C NMR, IR, CHN analysis techniques. In vitro, anticancer and antimicrobial activities of ligand and complexes were evaluated. The cytotoxic activities of compounds were investigated against the human lung adenocarcinoma (A549) cell lines and healthy human lung bronchial epithelium (BEAS2B) cells. Compounds1,6, and8were observed to exhibit higher cytotoxic activity than the others at the 72nd hour. Also, the compounds showed varying degrees of antimicrobial activity against the microorganisms used. Compounds1,5, and8were most effective against standard strainsPseudomonas aeruginosaATCC 27853 andStaphylococcus aureusATCC 29213. As for the antifungal activity, compounds1,5,6, and8showed high antifungal activity against the yeast type fungiCandida albicansATCC 90028 andCandida tropicalis.
T cell activation and IFNγ modulate organ dysfunction in LPS-mediated inflammation
Authors: Taylor Matthew D , Fernandes Tiago D , Yaipen Omar , Higgins Cassidy E , Capone Christine A , Leisman Daniel E , Nedeljkovic-Kurepa Ana , Abraham Mabel N , Brewer Mariana R , Deutschman Clifford S
Published: February 2022

LPS challenge is used to model inflammation-induced organ dysfunction. The effects of T cell activation on LPS-mediated organ dysfunction and immune responses are unknown. We studied these interactions through in vivo administration of anti-CD3ε (CD3) T cell activating antibody and LPS. Mortality in response to high-dose LPS (LPSHi; 600 μg) was 60%; similar mortality was observed with a 10-fold reduction in LPS dose (LPSLo; 60 μg) when administered with CD3 (CD3LPSLo). LPSHi and CD3LPSLo cohorts suffered severe organ dysfunction. CD3LPSLo led to increased IFNγ and IL12p70 produced by T cells and dendritic cells (cDCs) respectively. CD3LPSLo caused cDC expression of CD40 and MHCII and prevented PD1 expression in response to CD3. These interactions led to the generation of CD4 and CD8 cytolytic T cells. CD3LPSLo responded to IFNγ or IL12p40 blockade, in contrast to LPSHi. The combination of TCR activation and LPS (CD3LPSLo) dysregulated T cell activation and increased LPS-associated organ dysfunction and mortality through T cell and cDC interactions.
Repeatability and Reproducibility Assessment of the Apparent Diffusion Coefficient in the Prostate: A Trial of the ECOG‐ACRIN Research Group (ACRIN 6701)
Authors: Boss Michael A. , Snyder Bradley S. , Kim Eunhee , Flamini Dena , Englander Sarah , Sundaram Karthik M. , Gumpeni Naveen , Palmer Suzanne L. , Choi Haesun , Froemming Adam T. , Persigehl Thorsten , Davenport Matthew S. , Malyarenko Dariya , Chenevert Thomas L. , Rosen Mark A.
Published: February 2022

Background

Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion‐weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within‐subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.

Purpose

Evaluation of the repeatability (same‐day) and reproducibility (multi‐day) of whole‐prostate and focal‐lesion ADC assessment in a multi‐site setting.

Study Type

Prospective multi‐institutional.

Subjects

Twenty‐nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions.

Field Strength/Sequence

3T, single‐shot spin‐echo diffusion‐weighted echo‐planar sequence with four b‐values.

Assessment

Sites qualified for the study using an ice‐water phantom with known ADC. Readers performed DWI analyses at visit 1 (“V1”) and visit 2 (“V2,” 2–14 days after V1), where V2 comprised scans before (“V2pre”) and after (“V2post”) a “coffee‐break” interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region‐of‐interests for focal lesions.

Statistical Tests

Reproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC).

Results

The ADC biases from b0–b600 and b0–b800 phantom scans averaged 1.32% and 1.44%, respectively; mean b‐value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICCV1 = 0.89; ICCV2pre = 0.76; ICCV2post = 0.94).

Data Conclusion

This study met the QIBA claim for prostate ADC. Test–retest repeatability and multi‐day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points.

Level of Evidence

1

Technical Efficacy

Stage 2

TOC Category

Pelvis
Selecting Candidates for Organ‐Preserving Strategies After Neoadjuvant Chemoradiotherapy for Rectal Cancer: Development and Validation of a Model Integrating MRI Radiomics and Pathomics
Authors: Wan Lijuan , Sun Zhuo , Peng Wenjing , Wang Sicong , Li Jiangtao , Zhao Qing , Wang Shuhao , Ouyang Han , Zhao Xinming , Zou Shuangmei , Zhang Hongmei
Published: February 2022

Background

Histopathologic evaluation after surgery is the gold standard to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). However, it cannot be used to guide organ‐preserving strategies due to poor timeliness.

Purpose

To develop and validate a multiscale model incorporating radiomics and pathomics features for predicting pathological good response (pGR) of down‐staging to stage ypT0‐1N0 after nCRT.

Study Type

Retrospective.

Population

A total of 153 patients (median age, 55 years; 109 men; 107 training group; 46 validation group) with clinicopathologically confirmed LARC.

Field Strength/Sequence

A 3.0‐T; fast spin echo T2‐weighted and single‐shot EPI diffusion‐weighted images.

Assessment

The differences in clinicoradiological variables between pGR and non‐pGR groups were assessed. Pretreatment and posttreatment radiomics signatures, and pathomics signature were constructed. A multiscale pGR prediction model was established. The predictive performance of the model was evaluated and compared to that of the clinicoradiological model.

Statistical Tests

The χ2 test, Fisher's exact test, t‐test, the minimum redundancy maximum relevance algorithm, the least absolute shrinkage and selection operator logistic regression algorithm, regression analysis, receiver operating characteristic curve (ROC) analysis, Delong method. P < 0.05 indicated a significant difference.

Results

Pretreatment radiomics signature (odds ratio [OR] = 2.53; 95% CI: 1.58–4.66), posttreatment radiomics signature (OR = 9.59; 95% CI: 3.04–41.46), and pathomics signature (OR = 3.14; 95% CI: 1.40–8.31) were independent factors for predicting pGR. The multiscale model presented good predictive performance with areas under the curve (AUC) of 0.93 (95% CI: 0.88–0.98) and 0.90 (95% CI: 0.78–1.00) in the training and validation groups, those were significantly higher than that of the clinicoradiological model with AUCs of 0.69 (95% CI: 0.55–0.82) and 0.68 (95% CI: 0.46–0.91) in both groups.

Data Conclusion

A model incorporating radiomics and pathomics features effectively predicted pGR after nCRT in patients with LARC.

Evidence Level

3

Technical Efficacy

Stage 4
The ScHARR LMIC filter: Adapting a low‐ and middle‐income countries geographic search filter to identify studies on preterm birth prevention and management
Authors: Sutton Anthea , Campbell Fiona
Published: February 2022

Search filters are used to find evidence on specific subjects. Performance of filters can be varied and may need adapting to meet the needs of research topics. There are limited geographic search filters available, and only one pertaining to low‐ and middle‐income countries (LMICs). When searching for literature on preterm birth prevention and management in LMICs for a research project at the School of Health and Related Research (ScHARR), we made use of the Cochrane Effective Practice and Organisation of Care (EPOC) LMIC geographic search filter for the databases; Ovid MEDLINE, Ovid Embase, Cochrane Library. During screening following a broad scoping search in Ovid MEDLINE, it was found that the EPOC LMIC filter did not identify a relevant study. Adaptations were made to the LMIC geographic search filter to maximise retrieval and identify the missing study. Institution was included as a search field, and the search terms high burden or countdown countries were added. The filter was translated for the databases; Ovid Embase, Cochrane Library, Ovid PsycINFO, and CINAHL via EBSCO. The adapted ScHARR LMIC filter is a non‐validated 1st generation filter which increases the sensitivity of the EPOC LMIC search filter. Validating the filter would confirm its retrieval performance and benefit information professionals, researchers, and health professionals. We recommend that the ScHARR LMIC filter is used to improve sensitivity of the Cochrane EPOC LMIC filter and reduce the risk of missing relevant studies.