bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scavenging mitochondrial hydrogen peroxide by peroxiredoxin 3 overexpression attenuates contractile dysfunction and muscle atrophy in a murine model of accelerated sarcopenia
Authors: Ahn Bumsoo , Ranjit Rojina , Kneis Parker , Xu Hongyang , Piekarz Katarzyna M. , Freeman Willard M. , Kinter Michael , Richardson Arlan , Ran Qitao , Brooks Susan V. , Van Remmen Holly 
Published: February 2022

AbstractAge‐related muscle atrophy and weakness, or sarcopenia, are significant contributors to compromised health and quality of life in the elderly. While the mechanisms driving this pathology are not fully defined, reactive oxygen species, neuromuscular junction (NMJ) disruption, and loss of innervation are important risk factors. The goal of this study is to determine the impact of mitochondrial hydrogen peroxide on neurogenic atrophy and contractile dysfunction. Mice with muscle‐specific overexpression of the mitochondrial H2O2 scavenger peroxiredoxin3 (mPRDX3) were crossed to Sod1KO mice, an established mouse model of sarcopenia, to determine whether reduced mitochondrial H2O2 can prevent or delay the redox‐dependent sarcopenia. Basal rates of H2O2 generation were elevated in isolated muscle mitochondria from Sod1KO, but normalized by mPRDX3 overexpression. The mPRDX3 overexpression prevented the declines in maximum mitochondrial oxygen consumption rate and calcium retention capacity in Sod1KO. Muscle atrophy in Sod1KO was mitigated by ~20% by mPRDX3 overexpression, which was associated with an increase in myofiber cross‐sectional area. With direct muscle stimulation, maximum isometric specific force was reduced by ~20% in Sod1KO mice, and mPRDX3 overexpression preserved specific force at wild‐type levels. The force deficit with nerve stimulation was exacerbated in Sod1KO compared to direct muscle stimulation, suggesting NMJ disruption in Sod1KO. Notably, this defect was not resolved by overexpression of mPRDX3. Our findings demonstrate that muscle‐specific PRDX3 overexpression reduces mitochondrial H2O2 generation, improves mitochondrial function, and mitigates loss of muscle quantity and quality, despite persisting NMJ impairment in a murine model of redox‐dependent sarcopenia.
50 Years of speaking up in England—Towards an important history
Authors: Walmsley Jan , Davies Ian , Garratt Danielle 
Published: February 2022

AbstractThe history of self‐advocacy in England has not been recorded, other than the stories of individuals and of some individual groups. We, therefore, decided to interview some leaders of the self‐advocacy movement and some people who were allies and supporters. Three researchers, two self‐advocates and one academic, interviewed 11 self‐advocate leaders on Zoom as the COVID lockdowns made it impossible to meet. Four allies and supporters wrote their answers to our questions, and we interviewed three others. We used the information people gave us to start writing the story of self‐advocacy from 1972 to 2002. There is a lot more to do.
Serial circulating tumor DNA monitoring of CDK4/6 inhibitors response in metastatic breast cancer
Authors: Chin Yoon Ming , Shibayama Tomoko , Chan Hiu Ting , Otaki Masumi , Hara Fumikata , Kobayashi Takayuki , Kobayashi Kokoro , Hosonaga Mari , Fukada Ippei , Inagaki Lina , Ono Makiko , Ito Yoshinori , Takahashi Shunji , Ohno Shinji , Ueno Takayuki , Nakamura Yusuke , Low Siew‐Kee 
Published: February 2022

AbstractCyclin‐dependent kinase 4/6 inhibitors (CDK4/6i) significantly improve progression‐free survival and have become the standard therapy for estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer patients. Treatment surveillance by radiological imaging has some limitations in detection and repeated biopsy genomic profiling is not clinically feasible. Serial circulating tumor DNA (ctDNA) analysis may provide insights into treatment response. Here we performed serial ctDNA analysis (n = 178) on 33 patients. Serial ctDNA analysis identified disease progression with sensitivity of 75% and specificity of 92%. In eight of 12 patients (61%) responding to CDK4/6i who eventually developed progressive disease, serial sampling every 3 or 6 months captured the initial rise of ctDNA with an average lead time of 3 months. In three of eight patients that did not respond to CDK4/6i (progressive disease at first radiological assessment, 3 months), biweekly sequencing within the first cycle of CDK4/6i treatment (1 month) detected sustained ctDNA levels (≥0.2% variant allele frequency), with lead time of 2 months. Serial ctDNA analysis tracked RECIST response, including clinically challenging scenarios (bone metastases or small‐sized target lesions), as well as detecting acquired genetic alterations linked to CDK4/6i resistance in the G1 to S transition phase. Circulating tumor DNA analysis was more sensitive than carcinoembryonic antigen or cancer antigen 15‐3 serum tumor markers at monitoring tumor response to CDK4/6i treatment. Our findings indicated the possible clinical utility of serial ctDNA analysis for earlier progressive disease detection and real‐time monitoring of CDK4/6i response.
Kantian Moral Education and Gendered Socialization
Authors: Dineen Katy 
Published: February 2022

ABSTRACTMovements like #metoo, #timesup, and #ibelieveher have succeeded in shedding light on the ongoing societal issue of misogyny. Against this backdrop, Kate Manne's attempt to analyze the concept of misogyny philosophically in her book Down Girl: The Logic of Misogyny has rightfully received much acclaim. In this article, Katy Dineen takes Manne's ameliorative treatment of misogyny as the starting point for interrogating how Manne's theory might relate to the coercion of male identity and agency toward the ideal of hegemonic masculinity. Dineen notes that her motivation in questioning Manne's account on this point is pragmatic: she aims to provide a groundwork for moral education that will address the coercion of boys' and girls' agency and identity formation within patriarchy. Dineen concludes by describing a Kantian framework for moral education based on an idea of the freedom necessary to render oneself efficacious, autonomous, and creative. She also offers Manne's thoughts on empathy as a reason in support of adopting a Kantian framework.
Interaction analysis between strain concentration and strain localization in cracked body
Authors: Li Wanjia , Hamada Shigeru , Noguchi Hiroshi 
Published: February 2022

AbstractThe appearance of strain localization (SL) in front of the crack tip is a factor that promotes transition toward the fatigue crack extension mode. Therefore, to predict fatigue crack extension behavior in case multiple modes occur, it is necessary to evaluate the degree of SL. In this study, the following simulations were performed on a single‐crystal twinning‐induced plasticity (TWIP) steel: (a) SL characterization by crystal plasticity finite element method (CPFEM) analysis of a smooth specimen under tension, (b) strain concentration (SC) characterization by EP‐FEM analysis of a cracked specimen under tension, and (c) characterization of interaction results between SC and SL of a cracked specimen under tension by CPFEM analysis. A comparison of the above results found that the interaction between SC and SL was large for long cracks and a significant strain field, different from the Hutchinson, Rice, Rosengren (HRR) singular field, was formed in front of the crack tip. Therefore, a parameter was proposed to quantify the SL properties in a smooth specimen. Subsequently, a fracture‐mechanics‐like method was proposed in which the results of (b) and the introduced parameters control the results of (c).
Pervasive, Preferential Flow through Mega‐Thick Unsaturated Zones in the Southern Great Basin
Authors: Jackson Tracie R. , Fenelon Joseph M. , Gainey Seth R. 
Published: February 2022

AbstractRecharge from preferential flow through mega‐thick (100–1000 m) unsaturated zones is a pervasive phenomenon, as demonstrated with a case study of volcanic highland recharge areas in the Great Basin province in southern Nevada, USA. Statistically significant rising water‐level trends occur for most study‐area wells and resulted from a relatively wet period (1969–2005) in south‐central Nevada. Wet and dry winters control water‐level trends, with water levels rising within a few months to a year following a wet‐winter recharge event and declining during sustained dry periods. Even though a megadrought has persisted since 2000, this drought condition did not preclude major recharge events. Modern groundwater reaching the water table is consistent with previous geochemical studies of the study area that indicate mixing of modern and late Pleistocene recharge water. First‐order approximations and simple mixing models of modern and late Pleistocene water indicate that 10% to 40% of recharge is preferential flow and that modern recharge may play a larger role in the water budget than previously thought.
Altered neural control of gait and its association with pain and joint impairment in adults with haemophilic arthropathy: Clinical and methodological implications
Authors: Cruz‐Montecinos Carlos , Maas Huub , Cerda Mauricio , Pérez‐Alenda Sofía 
Published: February 2022

AbstractIntroductionIt is unknown whether altered neural control is associated with clinical outcomes in people with haemophilic arthropathy (PWHA). The dynamic motor control index during walking (Walk‐DMC) is a summary metric of neural control.AimsThe primary aim of this study was to apply the Walk‐DMC to assess if people diagnosed with haemophilic arthropathy have impaired neural control of gait and investigate the association of Walk‐DMC with pain and joint impairment.MethodThe Walk‐DMC was assessed using surface electromyography in 11 leg muscles. Twenty‐two PWHA and 15 healthy subjects walked on a 30‐m walkway at 1 m/s. In addition, pain (visual analogue scale), knee flexion contracture (degrees) and joint impairment (Haemophilia Joint Health Score, HJHS) were assessed. The clinical outcomes were correlated with the Walk‐DMC. Multiple regression analysis was performed to predict the Walk‐DMC using the clinical outcomes.ResultsIn 13 PWHA the Walk‐DMC was beyond the normal range (80–120 pts). PWHA with an altered Walk‐DMC showed more years with arthropathy, more pain, higher knee flexion contracture and a higher HJHS score (P < .05, effect size > .8). Significant negative moderate associations between Walk‐DMC and pain, knee flexion contracture and HJHS were found (P < .05). The model that best predicted the Walk‐DMC was the pain with knee flexion contracture (R2 = .44; P = .004).ConclusionsPWHA with abnormal neural control of gait also has more years with arthropathy, more pain, and more impaired joints. Our results indicate an association between the Walk‐DMC index and joint damage, specifically with pain in combination with knee flexion contracture.
“Dangerous liaisons: NAFLD and liver fibrosis increase cardiovascular risk in HIV”
Authors: Cervo Adriana , Sebastiani Giada , Milic Jovana , Krahn Thomas , Mazzola Sergio , Petta Salvatore , Cascio Antonio , Guaraldi Giovanni , Mazzola Giovanni 
Published: February 2022

AbstractObjectivesNon‐alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. We aimed to assess the impact of NAFLD and liver fibrosis on intermediate‐high cardiovascular risk in people living with HIV.MethodsWe included people living with HIV from three cohorts. NAFLD and significant liver fibrosis were defined using transient elastography: controlled attenuation parameter ≥288 dB/m and liver stiffness measurement ≥7.1 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator in patients aged between 40 and 75 years and categorised as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or with the presence of a previous cardiovascular event. Patients with hepatitis B and/or hepatitis C virus co‐infection, alcohol abuse and unreliable transient elastography measurements were excluded. Predictors of intermediate‐high cardiovascular risk were investigated in multivariable analysis by logistic regression and also by stratifying according to body mass index (BMI; cut‐offs of 25 and 30 kg/m2) and age (cut‐off of 60 years).ResultsOf 941 patients with HIV alone included, 423 (45%), 128 (13.6%), 260 (27.6%) and 130 (13.8%) were categorised as at low, borderline, intermediate and high ASCVD risk, respectively. Predictors of intermediate‐high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.11; 95% confidence interval [CI] 1.40–3.18; p < 0.001), liver fibrosis (aOR 1.64; 95% CI 1.03–2.59; p = 0.034), duration of HIV (aOR 1.04; 95% CI 1.02–1.06; p < 0.001), and previous exposure to thymidine analogues and/or didanosine (aOR 1.54; 95% CI 1.09–2.18; p = 0.014). NAFLD was also associated with higher cardiovascular risk in normoweight patients (aOR 2.97; 95% CI 1.43–6.16; p = 0.003), in those with BMI <30 kg/m2 (aOR 2.30; 95% CI 1.46–3.61; p < 0.001) and in those aged <60 years (aOR 2.19; 95% CI 1.36–3.54; p = 0.001).ConclusionAssessment of cardiovascular disease should be targeted in people living with HIV with NAFLD and/or significant liver fibrosis, even if they are normoweight and young.
Historical perspectives on the International Labour Review 1921–2021: A century of research on the world of work1
Authors: HOEHTKER Dorothea 
Published: February 2022

AbstractThis article analyses the history of the International Labour Review (ILR), which was created in 1921, based on the provisions of Article 396 of the Treaty of Versailles of 1919, as a major periodical publication of the International Labour Organization (ILO). The article reviews, from various perspectives, the ILR's transformation from an institutional multipurpose periodical to today's modern academic journal, including its institutional journey, the role of the editors in charge and the professional and academic profiles of the ILR's authors. It studies the ILR's contribution to important academic and policy debates and its role for the ILO by examining from a historical perspective the contents, topics and geographical focus of the almost 3,000 signed articles published to date.
Repeat radiofrequency catheter ablation of atrial tachycardias in patients with congenital heart disease
Authors: Klehs Sophia , Schneider Heike E. , Backhoff David , Müller Matthias J. , Paul Thomas , Krause Ulrich 
Published: February 2022

AbstractIntroductionAtrial tachycardias (AT) in patients with congenital heart disease (CHD) are significantly contributing to morbidity and mortality. Aim of this study was to evaluate the long‐term course of CHD patients requiring repeat ablation procedures (RAP) of AT.Patients and MethodsAll 144 patients with CHD who had undergone ablation of AT at our center between January 2003 and October 2018 were enrolled. Patients were classified according to the complexity of CHD: complex CHD (cCHD), moderate CHD (mCHD), and simple CHD (sCHD).ResultsA total of 101 RAP were performed in 64 patients. One RAP was performed in n = 40, two in n = 13, three in n = 10, and five in n = 1. Acute success rate was 82% (83/101) and was not associated with the complexity of CHD (p = 1.0). Number of procedures was lower in patients with sCHD than in patients with mCHD and cCHD (sCHD 1.3 ± 0.6, mCHD 1.8 ± 1.0, and cCHD 1.8 ± 1.1, p = .04). RAP were most frequent in patients after Fontan palliation or Atrial switch procedure (2.0 ± 1.1 [n = 41] vs. 1.6 ± 0.9 all others, p = .016) and in patients with multiple unstable AT's (2.5 ± 1.1 [n = 11] vs. 1.7 ± 1.0, p = .008). Major complications occurred in 4/101 procedures. Complete follow‐up was available in 125 patients. Since last RAP 73% of the patients were in sinus/atrial rhythm and 34/125 patients (27%) with AT recurrence did not require re‐ablation with mean follow‐up of 52 ± 40 months.ConclusionsRecurrences after ablation of AT in CHD patients were frequent. After RAP promising long‐term results could be achieved. Data encourage repetitive ablation procedures in this patient population.
Responses of cyprinid (Ancherythroculter nigrocauda) to flow with a semi‐circular cylinder patch
Authors: Yang Fan , Zeng Yuhong , Huai Wenxin , Zha Wei , Wan Yunjiao 
Published: February 2022

AbstractFlows in river habitats are characterized by unsteady turbulence due to the existence of woody debris, boulders and vegetation. As a representative aquatic species, fish is important for the riverine ecosystems, with its complex behavioural responses to turbulent flows. Previous studies investigated the fish–vortices interaction with vortex streets by placing objects with simplified geometries centred at the flow. Nonetheless, complex river morphology in natural rivers results in much more spatially heterogeneous flows due to randomly distributed obstructions. Thus, a semi‐circular cylinder patch located on one side of the flume is used to mimic a vegetation patch at the riverbank. The patch varies in diameter (D0 = 16, 20 and 24 cm) and density (φ = 0.04 and 0.1), whereas the flow velocity is fixed at 25 cm s−1. Fish are observed to swim in three typical patterns, which are “swim around” (pattern 1), “spill” (pattern 2) and “swim through” (pattern 3). For flow with a dense patch, all three patterns are recorded, but only patterns 1 and 2 are observed in sparse patches. It is noticed that in patterns 1 and 2, fish prefer to hold place in zones of low velocity and low turbulence. Moreover, variations in patch diameter have little influence on pattern selection. Results showed that tail beat amplitude (TBA*) in each zone displayed more variations compared with tail beat frequency (TBF). In addition, Spearman's rank tests revealed that TBA* is affected by none of the four hydrodynamic variables (), whereas flow velocity imposes the most influence on TBF. Both diameter and density of the patch displayed no significant influence on TBA* and TBF.
The immunophilin CYCLOPHILIN28 affects PSII‐LHCII supercomplex assembly and accumulation in Arabidopsis thaliana
Authors: Zhu Weining , Xu Linqing , Yu Xiaoxia , Zhong Ying 
Published: February 2022

AbstractIn plant chloroplasts, photosystem II (PSII) complexes, together with light‐harvesting complex II (LHCII), form various PSII‐LHCII supercomplexes (SCs). This process likely involves immunophilins, but the underlying regulatory mechanisms are unclear. Here, by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen‐localized immunophilin CYCLOPHILIN28 (CYP28) to wild‐type and transgenic complemented lines, we determined that CYP28 regulates the assembly and accumulation of PSII‐LHCII SCs. Compared to the wild type, cyp28 plants showed accelerated leaf growth, earlier flowering time, and enhanced accumulation of high molecular weight PSII‐LHCII SCs under normal light conditions. The lack of CYP28 also significantly affected the electron transport rate. Blue native‐polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M‐LHCII‐Lhcb4‐Lhcb6 complexes in cyp28 versus wild‐type plants. Peptidyl‐prolyl cis/trans isomerase (PPIase) activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity. Mutant analysis suggested that CYP28 may regulate PSII‐LHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity. Furthermore, the Lhcb6‐P139 residue is critical for PSII‐LHCII SC assembly and accumulation. Therefore, our findings suggest that CYP28 likely regulates PSII‐LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.
MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression
Authors: Yu Jian‐Qiang , Gu Kai‐Di , Zhang Li‐Li , Sun Cui‐Hui , Zhang Quan‐Yan , Wang Jia‐Hui , Wang Chu‐Kun , Wang Wen‐Yan , Du Meng‐Chi , Hu Da‐Gang 
Published: February 2022

AbstractSugars are involved in plant growth, fruit quality, and signaling perception. Therefore, understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development. Here, we report that MdPFPβ, a pyrophosphate‐dependent phosphofructokinase gene, regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar‐metabolizing enzyme activities in apple (Malus domestica Borkh.). Biochemical analysis revealed that a basic helix‐loop‐helix (bHLH) transcription factor, MdbHLH3, binds to the MdPFPβ promoter and activates its expression, thus promoting soluble sugar accumulation in apple fruit. In addition, MdPFPβ overexpression in tomato influenced photosynthesis and carbon metabolism in the plant. Furthermore, we determined that MdbHLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating MdPFPβ expression. Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit: MdbHLH3 regulates soluble sugar accumulation by activating MdPFPβ gene expression and coordinating carbohydrate allocation.
Symplastic communication in the root cap directs auxin distribution to modulate root development
Authors: Li Meng , Wang Mengxue , Lin Qingyun , Wang Mengyao , Niu Xufang , Cheng Jie , Xu Meizhi , Qin Yaxin , Liao Xinyi , Xu Jian , Wu Shuang 
Published: February 2022

AbstractRoot cap not only protects root meristem, but also detects and transduces the signals of environmental changes to affect root development. The symplastic communication is an important way for plants to transduce signals to coordinate the development and physiology in response to the changing enviroments. However, it is unclear how the symplastic communication between root cap cells affects root growth. Here we exploit an inducible system to specifically block the symplastic communication in the root cap. Transient blockage of plasmodesmata (PD) in differentiated collumella cells severely impairs the root development in Arabidopsis, in particular in the stem cell niche and the proximal meristem. The neighboring stem cell niche is the region that is most sensitive to the disrupted symplastic communication and responds rapidly via the alteration of auxin distribution. In the later stage, the cell division in proximal meristem is inhibited, presumably due to the reduced auxin level in the root cap. Our results reveal the essential role of the differentiated collumella cells in the root cap mediated signaling system that directs root development.