bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2
Authors: Acharya Ananya , Kasaciunaite Kristina , Göse Martin , Kissling Vera , Guérois Raphaël , Seidel Ralf , Cejka Petr 
Published: November 2021

AbstractThe Dna2 helicase-nuclease functions in concert with the replication protein A (RPA) in DNA double-strand break repair. Using ensemble and single-molecule biochemistry, coupled with structure modeling, we demonstrate that the stimulation of S. cerevisiae Dna2 by RPA is not a simple consequence of Dna2 recruitment to single-stranded DNA. The large RPA subunit Rfa1 alone can promote the Dna2 nuclease activity, and we identified mutations in a helix embedded in the N-terminal domain of Rfa1 that specifically disrupt this capacity. The same RPA mutant is instead fully functional to recruit Dna2 and promote its helicase activity. Furthermore, we found residues located on the outside of the central DNA-binding OB-fold domain Rfa1-A, which are required to promote the Dna2 motor activity. Our experiments thus unexpectedly demonstrate that different domains of Rfa1 regulate Dna2 recruitment, and its nuclease and helicase activities. Consequently, the identified separation-of-function RPA variants are compromised to stimulate Dna2 in the processing of DNA breaks. The results explain phenotypes of replication-proficient but radiation-sensitive RPA mutants and illustrate the unprecedented functional interplay of RPA and Dna2.
Discovery of putative tumor suppressors from CRISPR screens reveals rewired lipid metabolism in acute myeloid leukemia cells
Authors: Lenoir W. Frank , Morgado Micaela , DeWeirdt Peter C. , McLaughlin Megan , Griffith Audrey L. , Sangree Annabel K. , Feeley Marissa N. , Esmaeili Anvar Nazanin , Kim Eiru , Bertolet Lori L. , Colic Medina , Dede Merve , Doench John G. , Hart Traver 
Published: November 2021

AbstractCRISPR knockout fitness screens in cancer cell lines reveal many genes whose loss of function causes cell death or loss of fitness or, more rarely, the opposite phenotype of faster proliferation. Here we demonstrate a systematic approach to identify these proliferation suppressors, which are highly enriched for tumor suppressor genes, and define a network of 145 such genes in 22 modules. One module contains several elements of the glycerolipid biosynthesis pathway and operates exclusively in a subset of acute myeloid leukemia cell lines. The proliferation suppressor activity of genes involved in the synthesis of saturated fatty acids, coupled with a more severe loss of fitness phenotype for genes in the desaturation pathway, suggests that these cells operate at the limit of their carrying capacity for saturated fatty acids, which we confirm biochemically. Overexpression of this module is associated with a survival advantage in juvenile leukemias, suggesting a clinically relevant subtype.
Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial
Authors: Nakamura Yoshiaki , Okamoto Wataru , Kato Takeshi , Esaki Taito , Kato Ken , Komatsu Yoshito , Yuki Satoshi , Masuishi Toshiki , Nishina Tomohiro , Ebi Hiromichi , Sawada Kentaro , Taniguchi Hiroya , Fuse Nozomu , Nomura Shogo , Fukui Makoto , Matsuda Seiko , Sakamoto Yasutoshi , Uchigata Hiroshi , Kitajima Kana , Kuramoto Naomi , Asakawa Takashi , Olsen Steve , Odegaard Justin I. , Sato Akihiro , Fujii Satoshi , Ohtsu Atsushi , Yoshino Takayuki 
Published: November 2021

AbstractThe applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis (UMIN000027887). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment.
The MRI-based 3D morphologic changes of knee meniscus under knee weight-bearing and early flexion conditions
Authors: Liu Tong , Shen Xianyue , Ji Qingming , Xiao Jianlin , Zuo Jianlin , Gao Zhongli 
Published: November 2021

AbstractThere are few studies investigate morphologic changes of knee meniscus in vivo mechanical loading and three-dimensions (3D) deformation and displacement of the whole meniscus between in vivo mechanical loading and unloading conditions are still unclear. To investigate the displacements and 3D morphological changes of the menisci under knee weight-bearing and early flexion conditions in healthy adults using a Magnetic Resonance Imaging (MRI)-compatible loading device (a 3.0 T MR imaging system) combined with a newly developed 3D comparison technique. Fifteen healthy volunteers were recruited in this cross-sectional observational study. Each subject underwent MRIs of their dominant right knee in eight different scanning conditions using a 3.0-T MRI scanner with a custom-made MRI-compatible loading device. The knee meniscus images were 3D reconstructed, and dimensional comparisons were made for each meniscal model with baseline (0°-unloaded model). The morphologic changes of the meniscal-anterior horn (AH), body (BD), and posterior horn (PH) regions were expressed as mean positive and negative deviations. The displacements were further investigated, and the meniscal extrusions of different subregions were measured. The morphologic changing patterns of human meniscus under loading and flexions were presented using 3D chromatic maps. The bilateral menisci were generally shifting laterally and posteriorly in most flexion angles and were changing medially and anteriorly under fully extended knee loading conditions. The mean deviations were more significant with loading at 0° of knee flexion, while the PH region in the lateral side changed further posteriorly with loading in 30° flexion. Most of the differences were not significant in other flexion angles between loading conditions. The extrusion of meniscus’s medial body was greater in full extension compared to any other flexing angles. Mechanical loading can significantly deform the menisci in knee extension; however, this effect is limited during knee flexion. Current study can be used as a reference for the evaluations of the integrity in meniscal functions.
Rapid characterization of feline leukemia virus infective stages by a novel nested recombinase polymerase amplification (RPA) and reverse transcriptase-RPA
Authors: Lacharoje Sitthichok , Techangamsuwan Somporn , Chaichanawongsaroj Nuntaree 
Published: November 2021

AbstractFeline leukemia virus (FeLV) is a major viral disease in cats, causing leukemia and lymphoma. The molecular detection of FeLV RNA and the DNA provirus are important for staging of the disease. However, the rapid immunochromatographic assay commonly used for antigen detection can only detect viremia at the progressive stage. In this study, nested recombinase polymerase amplification (nRPA) was developed for exogenous FeLV DNA provirus detection, and reverse transcriptase polymerase amplification (RT-RPA) was developed for the detection of FeLV RNA. The approaches were validated using 108 cats with clinicopathologic abnormalities due to FeLV infection, and from 14 healthy cats in a vaccination plan. The nRPA and RT-RPA assays could rapidly amplify the FeLV template, and produced high sensitivity and specificity. The FeLV detection rate in regression cats by nRPA was increased up to 45.8% compared to the rapid immunochromatographic assay. Hence, FeLV diagnosis using nRPA and RT-RPA are rapid and easily established in low resource settings, benefiting FeLV prognosis, prevention, and control of both horizontal and vertical transmission.
Arsenite exposure inhibits the erythroid differentiation of human hematopoietic progenitor CD34+ cells and causes decreased levels of hemoglobin
Authors: Wan Guanghua , Medina Sebastian , Zhang Haikun , Pan Rong , Zhou Xixi , Bolt Alicia M. , Luo Li , Burchiel Scott W. , Liu Ke Jian 
Published: November 2021

AbstractArsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.
Dynamics of cortical oxygenation during immediate adaptation to extrauterine life
Authors: Leroy Léa , Mahmoudzadeh Mahdi , Gondry Jean , Foulon Arthur , Wallois Fabrice 
Published: November 2021

AbstractThe neonatal transition involves physiological modifications as a consequence of the complexity of the perinatal period. Various strategies can be used to attain the same level of postnatal cerebral oxygenation, depending on the status of the infant at birth. We evaluated such strategies by recording 20 full-term newborns by near-infrared spectroscopy during the first 10 min of life. The acid–base status at birth revealed two clustered profiles of cerebral oxygenation dynamics. Lower pH and base excess and higher lactate levels were associated with more rapid attainment of the 95% maximal tissue oxygenation index value. These results suggest that metabolic mechanisms drive initial cerebral oxygenation dynamics during this critical period. These results confirm the capacity of newborns to develop multiple strategies to protect the brain.
The physiological response of different tobacco varieties to chilling stress during the vigorous growing period
Authors: Gu Kaiyuan , Hou Shuang , Chen Jinfen , Guo Jinge , Wang Fenfen , He Chenggang , Zou Congming , Xie Xiaoyu 
Published: November 2021

AbstractTobacco is be sensitively affected by chilling injury in the vigorous growth period, which can easily lead to tobacco leaf browning during flue-curing and quality loss, however, the physiological response of tobacco in the prosperous period under low temperature stress is unclear. The physiological response parameters of two tobacco varieties to low temperature stress were determined. The main results were as follows: ① For tobacco in the vigorous growing period subjected to low-temperature stress at 4–16 °C, the tissue structure of chloroplast changed and photosynthetic pigments significantly decreased compared with each control with the increase of intensity of low-temperature stress. ② For tobacco in the vigorous growing period at 10–16 °C, antioxidant capacity of the protective enzyme system, osmotic adjustment capacity of the osmotic adjusting system and polyphenol metabolism in plants gradually increased due to induction of low temperature with the increase of intensity of low-temperature stress. ③ Under low-temperature stress at 4 °C, the protective enzyme system, osmotic adjusting system and polyphenol metabolism of the plants played an insignificant role in stress tolerance, which cannot be constantly enhanced based on low-temperature resistance at 10 °C. This study confirmed that under the temperature stress of 10–16 °C, the self-regulation ability of tobacco will be enhanced with the deepening of low temperature stress, but there is a critical temperature between 4 and 10 °C. The self-regulation ability of plants under low temperature stress will be inhibited.
Beyond livestock carrying capacity in the Sahelian and Sudanian zones of West Africa
Authors: Rahimi Jaber , Haas Edwin , Grote Rüdiger , Kraus David , Smerald Andrew , Laux Patrick , Goopy John , Butterbach-Bahl Klaus 
Published: November 2021

AbstractWe applied the process-based model, LandscapeDNDC, to estimate feed availability in the Sahelian and Sudanian agro-ecological zones of West Africa as a basis for calculating the regional Livestock Carrying Capacity (LCC). Comparison of the energy supply (S) from feed resources, including natural pasture, browse, and crop residues, with energy demand (D) of the livestock population for the period 1981–2020 allowed us to assess regional surpluses (S > D) or deficits (S < D) in feed availability. We show that in the last 40 years a large-scale shift from surplus to deficit has occurred. While during 1981–1990 only 27% of the area exceeded the LCC, it was 72% for the period 2011–2020. This was caused by a reduction in the total feed supply of ~ 8% and an increase in feed demand of ~ 37% per-decade, driven by climate change and increased livestock population, respectively. Overall, the S/D decreased from ~ 2.6 (surplus) in 1981 to ~ 0.5 (deficit) in 2019, with a north–south gradient of increasing S/D. As climate change continues and feed availability may likely further shrink, pastoralists either need to source external feed or significantly reduce livestock numbers to avoid overgrazing, land degradation, and any further conflicts for resources.
A Majorana perspective on understanding and identifying axion insulators
Authors: Yan Qing , Li Hailong , Zeng Jiang , Sun Qing-Feng , Xie X. C. 
Published: November 2021

AbstractAn axion insulator is theoretically introduced to harbor unique surface states with half-integer Chern number $${{{{{{{\mathcal{C}}}}}}}}$$
C
. Recently, experimental progress has been made in different candidate systems, while a unique Hall response to directly reflect the half-integer Chern number is still lacking to distinguish an axion state from other possible insulators. Here we show that the $${{{{{{{\mathcal{C}}}}}}}}=\frac{1}{2}$$
C
=

1

2

axion state corresponds to a topological state with Chern number $${{{{{{{\mathcal{N}}}}}}}}=1$$
N
=
1
in the Majorana basis. In proximity to an s − wave superconductor, a topological phase transition to an $${{{{{{{\mathcal{N}}}}}}}}=0$$
N
=
0
phase takes place at critical superconducting pairing strength. Our theoretical analysis shows that a chiral Majorana hinge mode emerges at the boundary of $${{{{{{{\mathcal{N}}}}}}}}=1$$
N
=
1
and $${{{{{{{\mathcal{N}}}}}}}}=0$$
N
=
0
regions on the surface of an axion insulator. Furthermore, we propose a half-integer quantized thermal Hall conductance via a thermal transport measurement, which is a signature of the gapless chiral Majorana mode and thus confirms the $${{{{{{{\mathcal{C}}}}}}}}=\frac{1}{2}$$
C
=

1

2

($${{{{{{{\mathcal{N}}}}}}}}=1$$
N
=
1
) topological nature of an axion state. Our proposals help to theoretically comprehend and experimentally identify the axion insulator and may benefit the research of topological quantum computation.
Lunar-like silicate material forms the Earth quasi-satellite (469219) 2016 HO3 Kamoʻoalewa
Authors: Sharkey Benjamin N. L. , Reddy Vishnu , Malhotra Renu , Thirouin Audrey , Kuhn Olga , Conrad Albert , Rothberg Barry , Sanchez Juan A. , Thompson David , Veillet Christian 
Published: November 2021

AbstractLittle is known about Earth quasi-satellites, a class of near-Earth small solar system bodies that orbit the sun but remain close to the Earth, because they are faint and difficult to observe. Here we use the Large Binocular Telescope (LBT) and the Lowell Discovery Telescope (LDT) to conduct a comprehensive physical characterization of quasi-satellite (469219) Kamoʻoalewa and assess its affinity with other groups of near-Earth objects. We find that (469219) Kamoʻoalewa rotates with a period of 28.3 (+1.8/−1.3) minutes and displays a reddened reflectance spectrum from 0.4–2.2 microns. This spectrum is indicative of a silicate-based composition, but with reddening beyond what is typically seen amongst asteroids in the inner solar system. We compare the spectrum to those of several material analogs and conclude that the best match is with lunar-like silicates. This interpretation implies extensive space weathering and raises the prospect that Kamo’oalewa could comprise lunar material.
Clinical Case Study: Muscle Tension Dysphonia
Authors: Shembel Adrianna C. , Atkinson Cory , Childs Lesley 
Published: November 2021

Purpose:
The purpose of this problem-based learning case study is to review and interact with a clinical case involving a patient diagnosed with muscle tension dysphonia. Included in the case study is a case history, a voice sample, and a laryngeal exam.

Conclusions:
The case study provides an opportunity to practice conducting an auditory-perceptual assessment and acoustic voice assessment on the provided voice sample. The case study also provides the opportunity to rate endoscopic and stroboscopic parameters on the laryngeal exam.

Supplemental Material:

https://doi.org/10.23641/asha.16799641
High precision positioning algorithm based on carrier phase and time of arrival
Authors: Zhang Zhenyu , Kang Shaoli , Zhang Xiang 
Published: November 2021

AbstractCarrier phase positioning technology is widely used in global navigation satellite systems (GNSS) but not applied to wireless orthogonal frequency division multiplex (OFDM) systems. Carrier phase technology has a high resolution, which can improve the positioning accuracy of wireless cellular networks. Applying the carrier phase to a wireless mobile positioning system has some problems, such as continuous phase tracking, accurate integer ambiguity resolution, positioning errors caused by non‐line‐of‐sight (NLOS) and so forth. This paper offers a positioning technique combining the time‐of‐arrival (TOA) and carrier phase to solve the above problems. Based on Bayesian theory, a two‐step position estimator is introduced in our scheme to solve the terminal position. Besides, an NLOS identification and suppression scheme is proposed to enhance the robustness of the algorithm. Experiments show that even in the NLOS environment, the joint positioning algorithm using TOA and carrier phase can effectively improve the positioning accuracy.
Method for quantitative assessment of transformer oil‐paper insulation non‐uniform ageing parameters based on frequency domain dielectric response
Authors: Zhang Mingze , Li Lu , Liu Heqian , Jia Haifeng , Liu Ji , Meng Fanhao 
Published: November 2021

AbstractThe stable operation of transformers is an important guarantee of power system security. The temperature distribution of main insulation is different in long‐term operation. The temperature difference between the local hottest spot temperature and the average oil temperature in the transformer exceeds 30 K. Therefore, the oil‐paper insulation inside the transformer will exhibit non‐uniform ageing after long‐term operation. At present, frequency domain dielectric response (FDS) technology is widely used in transformer ageing assessment. However, the existing assessment methods are only used for overall insulation ageing assessment. The average moisture content and polymerization degree of the overall insulation between each phase winding are obtained. But it still cannot be used to assess the non‐uniform ageing of the transformer's main insulation. The radial, axial, and two directions non‐uniform ageing models have been made in the laboratory in this study. The FDS and physicochemical properties of non‐uniform ageing models were tested. The variation law of FDS for non‐uniform ageing models was analysed. Meanwhile, the dielectric relaxation model of non‐uniform ageing for main insulation was established. The method of frequency division iterative calculation was proposed. Combined with the Fessler moisture balance formula of ageing oil‐paper insulation, the quantitative assessment method for ageing parameters of the non‐uniform ageing model can be realized. Compared the calculated results with the chemical analysis results, the relative error of the polymerization degree calculation is less than 4%, and the error of the moisture content calculation is less than 0.3%. The calculation results can meet the needs of the engineering apply. Therefore, this method can realize the quantitative assessment of transformer main insulation ageing, which is of great significance to assess the transformer insulation state.
Joint Preserving Treatment of Chronic Locked Posterior Shoulder
Dislocation by Means of Combined Humeral Allograft Reconstruction and Posterior
Glenoid Autograft Augmentation
Authors: Rüttershoff Katja , Akgün Doruk , Moroder Philipp 
Published: November 2021

AbstractChronic locked posterior shoulder dislocations are challenging to treat and
often warrant total shoulder arthroplasty. While joint preserving treatment
is preferable in young patients, surgical techniques to treat this pathology
have rarely been described in the literature. This technical note presents
the treatment of a 30-year-old male patient with a chronic locked posterior
shoulder dislocation by means of combined humeral allograft reconstruction
and posterior glenoid autograft augmentation. Restoration of the spheric
humeral head surface was obtained using a fresh-frozen femoral allograft
fixed with two reabsorbable screws. Due to the intraoperatively persistent
posterior instability after humeral reconstruction, the posterior glenoid
was augmented with a tricortical iliac crest autograft, which was fixed with
two metal screws. This treatment strategy resulted in a full range of motion
and a centered stable shoulder joint at one-year follow-up. Therefore, the
procedure of segmental reconstruction of the humeral head with a
fresh-frozen allograft combined with a posterior glenoid augmentation with
an iliac crest bone autograft is a joint-preserving treatment alternative to
shoulder arthroplasty in young patients when humeral head reconstruction
alone does not suffice.