bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of monitor unit through analytical method for dynamic IMRT using control points as an effective parameter
Authors: Athiyaman M. , Hemalatha A. , Chougule Arun , Joan Mary , Kumar HS
Published: March 2021

Introduction:

The control points (CP) play a significant role in the delivery of segmented based Intensity-Modulated Radiation Therapy (IMRT) delivery, particularly in dynamic mode. The number of segments is determined by control points and these segments will transfer from one to the other either during beam ON called dynamic delivery or during beam OFF called static delivery or step and shoot. This study was aimed at indirect estimation of the total monitor units (MU) to be delivered per field by exploiting the control points and also to find the MUs at any nth segment.

Materials and methods:

This study was performed in the Eclipse treatment planning software version 13.8.0. The details of control points, metre set weight per segment, leaf positions for each segment, field size, etc. were taken into consideration.

Results:

TPS calculated MU value and analytically estimated MU value were compared and the percentage of difference was estimated. The overall mean percentage of deviation was 1·03% between the TPS calculated method and the analytical method. The paired sample t-test was performed and, p-value <0·05, no significant difference was found. The analytical relationship determined to estimate the total number of MU delivered for any nth control point was also evaluated.

Conclusion:

The control points are a potential parameter in the conventional IMRT delivery. Through this study, we have addressed the indirect method to estimate the monitor units delivered per segment.
The impact of COVID-19 on palliative care workers across the world: A qualitative analysis of responses to open-ended questions
Authors: Pastrana Tania , De Lima Liliana , Pettus Katherine , Ramsey Alison , Napier Genevieve , Wenk Roberto , Radbruch Lukas
Published: March 2021

Objective

With over two million deaths and almost 100 million confirmed cases, the COVID-19 pandemic has caused a “tsunami of suffering.” Health care workers, including palliative care workers, have been severely impacted. This study explores how the COVID-19 pandemic has impacted palliative care workers around the world and describes the coping strategies they have adopted to face their specific situation.

Method

We conducted a qualitative analysis of written, unstructured comments provided by respondents to a survey of IAHPC members between May and June 2020. Free text was exported to MAX QDA, and a thematic analysis was performed by reading the comments and developing a coding frame.

Results

Seventy-seven palliative care workers from 41 countries submitted at least one written comment, resulting in a data corpus of 10,694 words and a total of 374 coded comments. Eight main themes are emerged from the analysis: palliative care development, workforce impact, work reorganization, palliative care reconceptualization, economic and financial impacts, increased risk, emotional impact, and coping strategies.

Significance of results

The pandemic has had a huge impact on palliative care workers including their ability to work and their financial status. It has generated increased workloads and placed them in vulnerable positions that affect their emotional well-being, resulting in distress and burnout. Counseling and support networks provide important resilience-building buffers. Coping strategies such as team and family support are important factors in workers’ capacity to adapt and respond. The pandemic is changing the concept and praxis of palliative care. Government officials, academia, providers, and affected populations need to work together to develop, and implement steps to ensure palliative care integration into response preparedness plans so as not to leave anyone behind, including health workers.
Not Just Sticks and Stones: Psychological Abuse and Physical Violence among U.S. State Senators
Authors: Herrick Rebekah , Thomas Sue
Published: March 2021

In this study, we report results of a survey of U.S. state senators about their experiences of psychological abuse, physical violence, and sexualized abuse and violence on the job, as well as gender differences among senators. Overall, our results indicate that more than 80% of state senators reported having faced abuse and violence, and women senators reported more physical violence than men. Moreover, we found differences in the factors that contributed to abuse and violence among women and men state senators. Most notably, women with higher levels of power (party or committee leaders) were more likely than other women to experience psychological abuse and sexualized abuse and violence, and Democratic women senators faced more sexualized abuse and violence than Republican women. The implications for continued service by state senators in the face of these experiences, the likelihood of attracting future candidates, and the implications for gender diversity in office are explored.
Computation‐Efficient Parameter Estimation for a High‐Resolution Global Tide and Surge Model
Authors: Wang Xiaohui , Verlaan Martin , Apecechea Maialen Irazoqui , Lin Hai Xiang
Published: March 2021

In this study, a computation‐efficient parameter estimation scheme for high‐resolution global tide models is developed. The method is applied to Global Tide and Surge Model with an unstructured grid with a resolution of about 2.5 km in the coastal area and about 4.9 million cells. The estimation algorithm uses an iterative least squares method, known as DUD. We use time‐series derived from the FES2014 tidal database in deep water as observations to estimate corrections to the bathymetry. Although the model and estimation algorithm run in parallel, directly applying of DUD would not be affordable computationally. To reduce the computational demand, a coarse‐to‐fine strategy is proposed by using output from a coarser model to replace the fine model. There are two approaches; One is completely replacing the fine model with a coarser model during calibration (Coarse Calibration) and the second is Coarse Incremental Calibration, that replaces the output increments between the initial model and model with modified parameters by coarser grid model simulations. To further reduce the computation time, the parameter dimension is reduced from O(106) to O(102) based on sensitivity analysis, which greatly reduces the required number of model simulations and storage. In combination, these methods form an efficient optimization strategy. Experiments show that the accuracy of the tidal representation can be improved significantly at affordable cost. Validation for other time‐periods and using coastal tide‐gauges shows that the accuracy is improved significantly. However, the calibration period of two weeks is short and leads to some over‐fitting of the model.
BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Authors: Fiskus Warren , Mill Christopher P. , Perera Dimuthu , Birdwell Christine , Deng Qing , Yang Haopeng , Lara Bernardo H. , Jain Nitin , Burger Jan , Ferrajoli Alessandra , Davis John A. , Saenz Dyana T. , Jin Wendy , Coarfa Cristian , Crews Craig M. , Green Michael R. , Khoury Joseph D. , Bhalla Kapil N.
Published: March 2021

Richter Transformation (RT) develops in CLL as an aggressive, therapy-resistant, diffuse large B cell lymphoma (RT-DLBCL), commonly clonally-related (CLR) to the concomitant CLL. Lack of available pre-clinical human models has hampered the development of novel therapies for RT-DLBCL. Here, we report the profiles of genetic alterations, chromatin accessibility and active enhancers, gene-expressions and anti-lymphoma drug-sensitivity of three newly established, patient-derived, xenograft (PDX) models of RT-DLBCLs, including CLR and clonally-unrelated (CLUR) to concomitant CLL. The CLR and CLUR RT-DLBCL cells display active enhancers, higher single-cell RNA-Seq-determined mRNA, and protein expressions of IRF4, TCF4, and BCL2, as well as increased sensitivity to BET protein inhibitors. CRISPR knockout of IRF4 attenuated c-Myc levels and increased sensitivity to a BET protein inhibitor. Co-treatment with BET inhibitor or BET-PROTAC and ibrutinib or venetoclax exerted synergistic in vitro lethality in the RT-DLBCL cells. Finally, as compared to each agent alone, combination therapy with BET-PROTAC and venetoclax significantly reduced lymphoma burden and improved survival of immune-depleted mice engrafted with CLR-RT-DLBCL. These findings highlight a novel, potentially effective therapy for RT-DLBCL.
Iron limitation by transferrin promotes simultaneous cheating of pyoverdine and exoprotease in Pseudomonas aeruginosa
Authors: Tostado-Islas Oswaldo , Mendoza-Ortiz Alberto , Ramírez-García Gabriel , Cabrera-Takane Isamu Daniel , Loarca Daniel , Pérez-González Caleb , Jasso-Chávez Ricardo , Jiménez-Cortés J Guillermo , Hoshiko Yuki , Maeda Toshinari , Cazares Adrian , García-Contreras Rodolfo
Published: March 2021

Pseudomonas aeruginosa is a primary bacterial model to study cooperative behaviors because it yields exoproducts such as siderophores and exoproteases that act as public goods and can be exploited by selfish nonproducers behaving as social cheaters. Iron-limited growth medium, mainly casamino acids medium supplemented with transferrin, is typically used to isolate and study nonproducer mutants of the siderophore pyoverdine. However, using a protein as the iron chelator could inadvertently select mutants unable to produce exoproteases, since these enzymes can degrade the transferrin to facilitate iron release. Here we investigated the evolutionary dynamics of pyoverdine and exoprotease production in media in which iron was limited by using either transferrin or a cation chelating resin. We show that concomitant loss of pyoverdine and exoprotease production readily develops in media containing transferrin, whereas only pyoverdine loss emerges in medium treated with the resin. Characterization of exoprotease- and pyoverdine-less mutants revealed loss in motility, different mutations, and large genome deletions (13–33 kb) including Quorum Sensing (lasR, rsal, and lasI) and flagellar genes. Our work shows that using transferrin as an iron chelator imposes simultaneous selective pressure for the loss of pyoverdine and exoprotease production. The unintended effect of transferrin uncovered by our experiments can help to inform the design of similar studies.
Mayo Clinic experience with 1123 adults with acute myeloid leukemia
Authors: Begna Kebede H. , Ali Walid , Naseema Gangat  , Elliott Michelle A. , Al-Kali Aref , Litzow Mark R. , Christopher Hook C. , Wolanskyj-Spinner Alexandra P. , Hogan William J. , Patnaik Mrinal M. , Pardanani Animesh , Zblewski Darci L. , Chen Dong , He Rong , Viswanatha David , Hanson Curtis A. , Ketterling Rhett P. , Tefferi Ayalew
Published: March 2021

Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9–2.6), adverse karyotype (HR 2.9, 1.9–4.9), intermediate-risk karyotype (HR 1.6, 1.02–2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5–2.4), and other secondary AML (HR 1.3 (1.1–1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1− (HR 2.8, 1.4–5.6), FLT3+/NPM+ (HR 2.6 (1.3–5.2), and FLT3−NPM1− (HR 1.8, 1.0–3.0).
In vivo chemical reprogramming of astrocytes into neurons
Authors: Ma Yantao , Xie Handan , Du Xiaomin , Wang Lipeng , Jin Xueqin , Zhang Qianqian , Han Yawen , Sun Shicheng , Wang Longteng , Li Xiang , Zhang Changjiang , Wang Mengdi , Li Cheng , Xu Jun , Huang Zhuo , Wang Xiaoqun , Chai Zhen , Deng Hongkui
Published: March 2021

In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.
Large-scale discovery of protein interactions at residue resolution using co-evolution calculated from genomic sequences
Authors: Green Anna G. , Elhabashy Hadeer , Brock Kelly P. , Maddamsetti Rohan , Kohlbacher Oliver , Marks Debora S.
Published: March 2021

Increasing numbers of protein interactions have been identified in high-throughput experiments, but only a small proportion have solved structures. Recently, sequence coevolution-based approaches have led to a breakthrough in predicting monomer protein structures and protein interaction interfaces. Here, we address the challenges of large-scale interaction prediction at residue resolution with a fast alignment concatenation method and a probabilistic score for the interaction of residues. Importantly, this method (EVcomplex2) is able to assess the likelihood of a protein interaction, as we show here applied to large-scale experimental datasets where the pairwise interactions are unknown. We predict 504 interactions de novo in the E. coli membrane proteome, including 243 that are newly discovered. While EVcomplex2 does not require available structures, coevolving residue pairs can be used to produce structural models of protein interactions, as done here for membrane complexes including the Flagellar Hook-Filament Junction and the Tol/Pal complex.
Role of tubular epithelial arginase-II in renal inflammaging
Authors: Huang Ji , Liang Xiujie , Ladeiras Diogo , Fellay Benoit , Ming Xiu-Fen , Yang Zhihong
Published: March 2021

The aging kidney undergoes complex changes and is vulnerable to injury and development of chronic kidney disease (CKD) with preponderance affecting more women than men. Evidence has been presented that the type-II L-arginine:ureohydrolase, arginase-II (Arg-II) plays a role in the acceleration of aging. Arg-II is highly expressed in the kidney. However, the role of Arg-II in renal aging is not known. This study is to investigate whether Arg-II is involved in the kidney aging process dependently on sex. Arg-II level in the kidney of wild type (WT) mice is significantly elevated with aging, which is accompanied by an increase in expression of the inflammatory cytokines/chemokines, tissue macrophages, factors involved in fibrosis, and tubulointestitial fibrosis in both males and females. This renal aging phenotype is significantly suppressed in arg-II−/− mice, mainly in the females in which Arg-II level is higher than in the males. Importantly, numerous factors such as IL-1β, MCP1, VCAM-1, and TGFβ1 are mainly localized in the proximal tubular S3 segment cells expressing Arg-II in the aging kidney. In human proximal tubular cells (HK-2), TNF-α enhances adhesion molecule expression dependently on Arg-II upregulation. Overexpression of Arg-II in the cells enhances TGFβ1 levels which is prevented by mitochondrial ROS inhibition. In summary, our study reveals that renal proximal tubular Arg-II plays an important role in the kidney aging process in females. Arg-II could be a promising therapeutic target for the treatment and prevention of aging-associated kidney diseases.
Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer
Authors: Draganov Dobrin , Han Zhen , Rana Aamir , Bennett Nitasha , Irvine Darrell J. , Lee Peter P.
Published: March 2021

We show that treatment with the FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis which operates in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio. While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p = 0.03) and promoted complete responses (p < 0.01), also leading to immunity against contralateral re-challenge with demonstrated anti-tumor immune responses. Going beyond primary tumors, this combination achieved significant reduction in relapse after neoadjuvant (p = 0.03) and adjuvant treatment (p < 0.001), and potential cures in metastatic disease (p < 0.001). Statistical modeling confirmed bona fide synergistic activity in both the adjuvant (p = 0.007) and metastatic settings (p < 0.001). Ivermectin has dual immunomodulatory and ICD-inducing effects in breast cancer, converting cold tumors hot, thus represents a rational mechanistic partner with checkpoint blockade.
Noise-robust exploration of many-body quantum states on near-term quantum devices
Authors: Borregaard Johannes , Christandl Matthias , Stilck França Daniel
Published: March 2021

We describe a resource-efficient approach to studying many-body quantum states on noisy, intermediate-scale quantum devices. We employ a sequential generation model that allows us to bound the range of correlations in the resulting many-body quantum states. From this, we characterize situations where the estimation of local observables does not require the preparation of the entire state. Instead smaller patches of the state can be generated from which the observables can be estimated. This can potentially reduce circuit size and number of qubits for the computation of physical properties of the states. Moreover, we show that the effect of noise decreases along the computation. Our results apply to a broad class of widely studied tensor network states and can be directly applied to near-term implementations of variational quantum algorithms.
Leadership and tempo perturbation affect coordination in medium-sized groups
Authors: Tunçgenç Bahar , Travers Eoin , Fairhurst Merle T.
Published: March 2021

In marching bands, sports, dance and virtually all human group behaviour, we coordinate our actions with others. Coordinating actions in time and space can act as a social glue, facilitating bonding among people. However, much of our understanding about coordination dynamics is based on research into dyadic interactions. Little is known about the nature of the sensorimotor underpinnings and social bonding outcomes of coordination in medium-sized groups—the type of groups, in which most everyday teamwork takes place. In this study, we explored how the presence of a leader and an unexpected perturbation influence coordination and cohesion in a naturalistic setting. In groups of seven, participants were instructed to walk in time to an auditory pacing signal. We found that the presence of a reliable leader enhanced coordination with the target tempo, which was disrupted when the leader abruptly changed their movement tempo. This effect was not observed on coordination with the group members. Moreover, participants’ perceptions of being a follower and group cooperativeness increased in the presence of a leader. This study extends our knowledge about coordination beyond previous work on dyads. We discuss our results in light of sensorimotor coupling and social cohesion theories of coordination in groups.
Short-stem total hip arthroplasty is not associated with an earlier return to work compared to a straight-stem design
Authors: Hauer Georg , Smolle Maria , Zaussinger Sabrina , Friesenbichler Joerg , Leithner Andreas , Maurer-Ertl Werner
Published: March 2021

Return to work (RTW) has been specifically identified as a high priority in patients undergoing total hip arthroplasty (THA). This investigation sought to assess the effect of the stem design on patients’ RTW. Secondly, the study aimed to identify risk factors that lead to a delayed RTW. Questionnaires inquiring about RTW, employment history, educational level, type of work, physical demands and joint awareness were administered by post. Further data were collected from patients’ hospital records. 176 patients who underwent THA using a short-stem and 97 patients using a straight-stem design were compared. The median return to work time was 10 weeks [IQR 7–14 weeks], with no significant difference between the two groups (short stems vs. straight stems; 10 [IQR 7–14] vs. 11 [7.5–13.5] weeks; p = 0.693). In the multivariate linear regression analysis, self-employment vs. employee (p = 0.001), dimension of preoperative workload (p = 0.001), preoperative sick leave (p < 0.001), and hospital length of stay (LOS) (p < 0.001) independently affected the period until work was resumed. The Forgotten-Joint-Score-12 showed no significant difference between the two groups. The data show that the majority of THA patients can expect to resume work and stem design has no impact on RTW. Employees with preoperative sick leave, prolonged hospital LOS and low workload are at higher risk for a delayed RTW.
Millimeter-wave multi-mode circular antenna array for uni-cast multi-cast and OAM communication
Authors: Assimonis Stylianos D. , Abbasi Muhammad Ali Babar , Fusco Vincent
Published: March 2021

This paper investigates uni-/multi-cast and orbital angular momentum (OAM) mode data transmission in orthogonal directions by the utilization of a new circular antenna array, operating at 28 GHz. In the horizontal plane the proposed antenna array operates as multimode transmitter (i.e., it provides broad-, uni- and/or multi-cast communication), while in the vertical direction OAM transmission occurs (i.e., it is capable of generating up to 15 spatially orthogonal OAM modes). Antenna array is designed using twelve, low-complexity, electromagnetically coupled microstrip patch antennas with high radiation efficiency. Each of these can transmit power of equivalent order of magnitude in both horizontal (i.e., broadside radiation pattern) and vertical direction (i.e., endfire radiation pattern) over electromagnetic waves of orthogonal electric components. This property leads to the formation of uni-/multi-cast and OAM modes in the horizontal plane and vertical direction, respectively. Antenna was tested through full-wave electromagnetic analysis and measurements in terms of impedance matching, mutual coupling and radiation pattern: good agreement between simulated and measurement results was observed. Specifically, it presents up to 8.65 dBi and 6.48 dBi realized gain under the uni-cast (in the horizontal plane) and OAM mode (in the vertical plane), respectively. The proposed antenna array is perfect candidate for high spectral efficiency data transmission for 5G and beyond wireless applications, where orthogonality in communication links and OAM multiplexing is a requirement.
Identification of genetic loci affecting body mass index through interaction with multiple environmental factors using structured linear mixed model
Authors: Jung Hae-Un , Lee Won Jun , Ha Tae-Woong , Kang Ji-One , Kim Jihye , Kim Mi Kyung , Won Sungho , Park Taesung , Lim Ji Eun , Oh Bermseok
Published: March 2021

Multiple environmental factors could interact with a single genetic factor to affect disease phenotypes. We used Struct-LMM to identify genetic variants that interacted with environmental factors related to body mass index (BMI) using data from the Korea Association Resource. The following factors were investigated: alcohol consumption, education, physical activity metabolic equivalent of task (PAMET), income, total calorie intake, protein intake, carbohydrate intake, and smoking status. Initial analysis identified 7 potential single nucleotide polymorphisms (SNPs) that interacted with the environmental factors (P value < 5.00 × 10−6). Of the 8 environmental factors, PAMET score was excluded for further analysis since it had an average Bayes Factor (BF) value < 1 (BF = 0.88). Interaction analysis using 7 environmental factors identified 11 SNPs (P value < 5.00 × 10−6). Of these, rs2391331 had the most significant interaction (P value = 7.27 × 10−9) and was located within the intron of EFNB2 (Chr 13). In addition, the gene-based genome-wide association study verified EFNB2 gene significantly interacting with 7 environmental factors (P value = 5.03 × 10−10). BF analysis indicated that most environmental factors, except carbohydrate intake, contributed to the interaction of rs2391331 on BMI. Although the replication of the results in other cohorts is warranted, these findings proved the usefulness of Struct-LMM to identify the gene–environment interaction affecting disease.
Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: a systematic review and meta-analysis
Authors: Zizza Antonella , Banchelli Federico , Guido Marcello , Marotta Claudia , Di Gennaro Francesco , Mazzucco Walter , Pistotti Vanna , D’Amico Roberto
Published: March 2021

The prophylactic vaccines available to protect against infections by HPV are well tolerated and highly immunogenic. People with HIV have a higher risk of developing HPV infection and HPV-associated cancers due to a lower immune response, and due to viral interactions. We performed a systematic review of RCTs to assess HPV vaccines efficacy and safety on HIV-infected people compared to placebo or no intervention in terms of seroconversion, infections, neoplasms, adverse events, CD4+ T-cell count and HIV viral load. The vaccine-group showed a seroconversion rate close to 100% for each vaccine and a significantly higher level of antibodies against HPV vaccine types, as compared to the placebo group (MD = 4333.3, 95% CI 2701.4; 5965.1 GMT EL.U./ml for HPV type 16 and MD = 1408.8, 95% CI 414.8; 2394.7 GMT EL.U./ml for HPV type 18). There were also no differences in terms of severe adverse events (RR = 0.6, 95% CI 0.2; 1.6) and no severe adverse events (RR = 0.6, 95% CI 0.9; 1.2) between vaccine and placebo groups. Secondary outcomes, such as CD4 + T-cell count and HIV viral load, did not differ between groups (MD = 14.8, 95% CI − 35.1; 64.6 cells/µl and MD = 0.0, 95% CI − 0.3; 0.3 log10 RNA copies/ml, respectively). Information on the remaining outcomes was scarce and that did not allow us to combine the data. The results support the use of the HPV vaccine in HIV-infected patients and highlight the need of further RCTs assessing the effectiveness of the HPV vaccine on infections and neoplasms.
The expanded endoscopic endonasal approach for treatment of tuberculum sellae meningiomas in a series of 40 consecutive cases
Authors: Yu Peng , Xu Tutu , Wu Xinyu , Liu Zhitong , Wang Yong , Wang Yibao
Published: March 2021

Compared with traditional craniotomy, the expanded endoscopic endonasal approach (EEEA) may have some advantages for tuberculum sellae meningioma (TSM) treatment. We described our experience of the therapeutic effect of endoscopic TSM treatment. From August 2015 to December 2019, 40 patients with a TSM were treated by the EEEA in our institution. EEEA outcome in TSM treatment was analyzed. Among 39 patients with visual impairment, 38 (97.4%) improved their visual function to some extent after the EEEA, and one case had no significant change in visual acuity. Among all patients, 38 (95.0%) achieved gross total resection (GTR) and 2 (5.0%) achieved near-total resection (NTR). Cerebrospinal fluid (CSF) leakage occurred in three patients (7.5%) and meningitis (post-CSF leakage) in two patients (5.0%). Eight patients (20.0%) suffered postoperative hyposmia, three of whom developed long-term hyposmia. One patient (2.5%) suffered from bleeding of the branch of the anterior cerebral artery intraoperatively leading to postoperative acute cerebral infarction. The EEEA is a safe and reliable minimally invasive method for TSM removal. Compared with traditional craniotomy, the EEEA may have better visual outcomes and a higher prevalence of GTR, but carries the risk of CSF leakage.
Influence of spatial structure on protein damage susceptibility: a bioinformatics approach
Authors: Fichtner Maximilian , Schuster Stefan , Stark Heiko
Published: March 2021

Aging research is a very popular field of research in which the deterioration or decline of various physiological features is studied. Here we consider the molecular level, which can also have effects on the macroscopic level. The proteinogenic amino acids differ in their susceptibilities to non-enzymatic modification. Some of these modifications can lead to protein damage and thus can affect the form and function of proteins. For this, it is important to know the distribution of amino acids between the protein shell/surface and the core. This was investigated in this study for all known structures of peptides and proteins available in the PDB. As a result, it is shown that the shell contains less susceptible amino acids than the core with the exception of thermophilic organisms. Furthermore, proteins could be classified according to their susceptibility. This can then be used in applications such as phylogeny, aging research, molecular medicine, and synthetic biology.
Automatic delineation of glacier grounding lines in differential interferometric synthetic-aperture radar data using deep learning
Authors: Mohajerani Yara , Jeong Seongsu , Scheuchl Bernd , Velicogna Isabella , Rignot Eric , Milillo Pietro
Published: March 2021

Delineating the grounding line of marine-terminating glaciers—where ice starts to become afloat in ocean waters—is crucial for measuring and understanding ice sheet mass balance, glacier dynamics, and their contributions to sea level rise. This task has been previously done using time-consuming, mostly-manual digitizations of differential interferometric synthetic-aperture radar interferograms by human experts. This approach is no longer viable with a fast-growing set of satellite observations and the need to establish time series over entire continents with quantified uncertainties. We present a fully-convolutional neural network with parallel atrous convolutional layers and asymmetric encoder/decoder components that automatically delineates grounding lines at a large scale, efficiently, and accompanied by uncertainty estimates. Our procedure detects grounding lines within 232 m in 100-m posting interferograms, which is comparable to the performance achieved by human experts. We also find value in the machine learning approach in situations that even challenge human experts. We use this approach to map the tidal-induced variability in grounding line position around Antarctica in 22,935 interferograms from year 2018. Along the Getz Ice Shelf, in West Antarctica, we demonstrate that grounding zones are one order magnitude (13.3 ± 3.9) wider than expected from hydrostatic equilibrium, which justifies the need to map grounding lines repeatedly and comprehensively to inform numerical models.
Accuracy of new Corvis ST parameters for detecting subclinical and clinical keratoconus eyes in a Chinese population
Authors: Ren Shengwei , Xu Liyan , Fan Qi , Gu Yuwei , Yang Kaili
Published: March 2021

This study aimed to compare the values of new corneal visualization Scheimpflug technology (Corvis ST) parameters in normal, subclinical keratoconus (SKC) and keratoconus (KC) eyes, and evaluate the diagnostic ability to distinguish SKC and KC eyes from normal eyes. One-hundred normal, 100 SKC and 100 KC eyes were included in the study. Corvis ST parameters containing dynamic corneal response parameters were measured by one ophthalmologist. The receiver operating characteristic curve was used to evaluate the diagnostic ability of new Corvis ST parameters. The new Corvis ST parameters in KC eyes were different from those in the control and SKC eyes after adjusting for IOP and CCT, and stiffness parameter at the first applanation (SP-A1) and Corvis biomechanical index (CBI) were significantly different between the control and SKC eyes (all P < 0.05). The parameter with the highest diagnostic efficiency was SP-A1 (Youden index = 0.40, AUC = 0.753), followed by CBI (Youden index = 0.38, AUC = 0.703), and Integrated Radius (Youden index = 0.33, AUC = 0.668) in diagnosing SKC from control eyes. New Corvis ST parameters in SKC eyes were significantly different from normal control and KC eyes, and could be considered to distinguish SKC and KC eyes from normal eyes.
A novel device for detecting anaerobic threshold using sweat lactate during exercise
Authors: Seki Yuta , Nakashima Daisuke , Shiraishi Yasuyuki , Ryuzaki Toshinobu , Ikura Hidehiko , Miura Kotaro , Suzuki Masato , Watanabe Takatomo , Nagura Takeo , Matsumato Morio , Nakamura Masaya , Sato Kazuki , Fukuda Keiichi , Katsumata Yoshinori
Published: March 2021

The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland–Altman plot described no bias between the mean values (mean differences: − 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.
Pre-hospital triage of suspected acute stroke patients in a mobile stroke unit in the rural Alberta
Authors: Kate Mahesh P. , Jeerakathil Thomas , Buck Brian H. , Khan Khurshid , Nomani Ali Zohair , Butt Asif , Thirunavukkarasu Sibi , Nowacki Tomasz , Kalashyan Hayrapet , Lloret-Villas Mar Irida , D’Souza Atlantic , Mishra Sachin , McCombe Jennifer , Butcher Kenneth , Jickling Glen , Saqqur Maher , Shuaib Ashfaq
Published: March 2021

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.
Macro-, meso- and microstructural characterization of metallic lattice structures manufactured by additive manufacturing assisted investment casting
Authors: Carneiro V. H. , Rawson S. D. , Puga H . , Withers P. J.
Published: March 2021

Cellular materials are recognized for their high specific mechanical properties, making them desirable in ultra-lightweight applications. Periodic lattices have tunable properties and may be manufactured by metallic additive manufacturing (AM) techniques. However, AM can lead to issues with un-melted powder, macro/micro porosity, dimensional control and heterogeneous microstructures. This study overcomes these problems through a novel technique, combining additive manufacturing and investment casting to produce detailed investment cast lattice structures. Fused filament fabrication is used to fabricate a pattern used as the mold for the investment casting of aluminium A356 alloy into high-conformity thin-ribbed (~ 0.6 mm thickness) scaffolds. X-ray micro-computed tomography (CT) is used to characterize macro- and meso-scale defects. Optical and scanning electron (SEM) microscopies are used to characterize the microstructure of the cast structures. Slight dimensional (macroscale) variations originate from the 3D printing of the pattern. At the mesoscale, the casting process introduces very fine (~ 3 µm) porosity, along with small numbers of (~ 25 µm) gas entrapment defects in the horizontal struts. At a microstructural level, both the (~ 70 μm) globular/dendritic grains and secondary phases show no significant variations across the lattices. This method is a promising alternative means for producing highly detailed non-stochastic metallic cellular lattices and offers scope for further improvement through refinement of filament fabrication.
Enhanced detection of oral dysplasia by structured illumination fluorescence lifetime imaging microscopy
Authors: Hinsdale Taylor A. , Malik Bilal H. , Cheng Shuna , Benavides Oscar R. , Giger Maryellen L. , Wright John M. , Patel Paras B. , Jo Javier A. , Maitland Kristen C.
Published: March 2021

We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63).
SNP-based analysis reveals unexpected features of genetic diversity, parental contributions and pollen contamination in a white spruce breeding program
Authors: Galeano Esteban , Bousquet Jean , Thomas Barb R.
Published: March 2021

Accurate monitoring of genetic diversity levels of seedlots and mating patterns of parents from seed orchards are crucial to ensure that tree breeding programs are long-lasting and will deliver anticipated genetic gains. We used SNP genotyping to characterize founder trees, five bulk seed orchard seedlots, and trees from progeny trials to assess pollen contamination and the impact of severe roguing on genetic diversity and parental contributions in a first-generation open-pollinated white spruce clonal seed orchard. After severe roguing (eliminating 65% of the seed orchard trees), we found a slight reduction in the Shannon Index and a slightly negative inbreeding coefficient, but a sharp decrease in effective population size (eightfold) concomitant with sharp increase in coancestry (eightfold). Pedigree reconstruction showed unequal parental contributions across years with pollen contamination levels between 12 and 51% (average 27%) among seedlots, and 7–68% (average 30%) among individual genotypes within a seedlot. These contamination levels were not correlated with estimates obtained using pollen flight traps. Levels of pollen contamination also showed a Pearson’s correlation of 0.92 with wind direction, likely from a pollen source 1 km away from the orchard under study. The achievement of 5% genetic gain in height at rotation through eliminating two-thirds of the orchard thus generated a loss in genetic diversity as determined by the reduction in effective population size. The use of genomic profiles revealed the considerable impact of roguing on genetic diversity, and pedigree reconstruction of full-sib families showed the unanticipated impact of pollen contamination from a previously unconsidered source.
SARS2 simplified scores to estimate risk of hospitalization and death among patients with COVID-19
Authors: Dashti Hesam , Roche Elise C. , Bates David William , Mora Samia , Demler Olga
Published: March 2021

Although models have been developed for predicting severity of COVID-19 from the medical history of patients, simplified models with good accuracy could be more practical. In this study, we examined utility of simpler models for estimating risk of hospitalization of patients with COVID-19 and mortality of these patients based on demographic characteristics (sex, age, race, median household income based on zip code) and smoking status of 12,347 patients who tested positive at Mass General Brigham centers. The corresponding electronic records were queried (02/26–07/14/2020) to construct derivation and validation cohorts. The derivation cohort was used to fit generalized linear models for estimating risk of hospitalization within 30 days of COVID-19 diagnosis and mortality within approximately 3 months for the hospitalized patients. In the validation cohort, the model resulted in c-statistics of 0.77 [95% CI 0.73–0.80] for hospitalization, and 0.84 [95% CI 0.74–0.94] for mortality among hospitalized patients. Higher risk was associated with older age, male sex, Black ethnicity, lower socioeconomic status, and current/past smoking status. The models can be applied to predict the absolute risks of hospitalization and mortality, and could aid in individualizing the decision making when detailed medical history of patients is not readily available.
Large-scale spatial patterns of small-mammal communities in the Mediterranean region revealed by Barn owl diet
Authors: Riegert Jan , Šindelář Jiří , Zárybnická Markéta , Horáček Ivan
Published: March 2021

Due to mainly opportunistic hunting behaviour of Barn owl can be its diet composition used for assessing local structure of small-mammal community. We evaluated the structure of small-mammal communities in the Mediterranean region by analysing Barn owl diet using own pellets and literature data (85 localities comprising 182,343 prey individuals). Contrary to widely accepted macroecological theory, we found a latitudinal increase of small-mammal alpha diversity, a less distinct west–east increase and lower diversity on islands. The mean prey weight decreased with increasing latitude, while on islands it decreased with increasing island area. The mean prey weight on islands was further negatively affected by mean land modification by human and positively affected by its range. The diet diversity on islands was not affected either by island area or its distance from the mainland. Its composition largely conformed to the main pattern pronounced over whole the region: an unexpected homogeneity of small-mammal community structure. Despite high beta diversity and large between-sample variation in species composition, Crocidura (+ Suncus etruscus) and murids (Apodemus, Mus, Rattus, in marginal regions partly replaced by gerbillids, Meriones or Microtus) composed more than 90% of owl prey in 92% of samples. Peak abundances of these widespread species are associated with a dynamic mosaic of dense patches of sparse herb vegetation and evergreen sclerophyllous shrublands interspersing areas of human activity, the dominant habitat of the inner Mediterranean and richest food resource for foraging Barn owls. The respective small-mammal species can be looked upon as invasive elements accompanying large scale human colonization of the region since the Neolithic and replacing original island biota. Our study documented that desertification of the Mediterranean played an important role in shaping inverse latitudinal gradient in diversity of small-mammals that contradicts to widely accepted mecroecological theory.
A single-chain antibody generation system yielding CAR-T cells with superior antitumor function
Authors: Ochi Toshiki , Maruta Masaki , Tanimoto Kazushi , Kondo Fumitake , Yamamoto Toshihiro , Kurata Mie , Fujiwara Hiroshi , Masumoto Junya , Takenaka Katsuto , Yasukawa Masaki
Published: March 2021

Cancer immunotherapy using T cells redirected with chimeric antigen receptor (CAR) has shown a lot of promise. We have established a single-chain antibody (scFv) generation system in which scFv library-expressing CAR-T cells can be screened appropriately based on their antitumor functions. A variable region library containing the variable and J regions of the human immunoglobulin light or heavy chain was fused with the variable region of a heavy or light chain encoded by an existing tumor-specific antibody to generate a new scFv library. Then, scFv library-expressing CAR-T cells were generated and stimulated with target cells to concentrate the antigen-specific population. Using this system, target-specific recognition of CAR-T cells appeared to be finely tuned by selecting a new variable region. Importantly, we have demonstrated that the newly optimized scFv-expressing CAR-T cells had better proliferation capacity and durable phenotypes, enabling superior reactivity against advanced tumors in vivo in comparison with the original CAR-T cells. Therefore, the optimization of an scFv is needed to maximize the in vivo antitumor functions of CAR-T cells. This system may allow us to adjust an immunological synapse formed by an scFv expressed by CAR-T cells and a target antigen, representing an ideal form of CAR-T-cell immunotherapy.
Structure, intermolecular interactions, and dynamic properties of NTO crystals with impurity defects: a computational study
Authors: Ji Jincheng , Wang Kun , Zhu Simin , Zhu Weihua
Published: March 2021

Frontier orbitals distribute in the position of impurity molecules, whose adjacent NTO molecules begin to decompose first.
Crystallographic tomography and molecular modelling of structured organic polycrystalline powders
Authors: Gajjar Parmesh , Nguyen Thai T. H. , Sun Jun , Styliari Ioanna D. , Bale Hrishikesh , McDonald Samuel A. , Burnett Timothy L. , Tordoff Benjamin , Lauridsen Erik , Hammond Robert B. , Murnane Darragh , Withers Philip J. , Roberts Kevin J.
Published: March 2021

Novel combination of crystallographic tomography and molecular modelling is used to examine the powder packing behaviour and crystal interactions for an organic polycrystalline powder bed.