bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Complexities of Postpartum Sexual Health
Authors: O’Malley Deirdre , Higgins Agnes , Smith Valerie
Published: October 2021

Purpose of Review

This paper explores the complexities of postpartum sexual health. It answers the question on what should be considered normal sexual health after birth and what should be considered abnormal.

Recent Findings

Many women experience physical sexual health issues in the months after birth, such as dyspareunia, lack of vaginal lubrication and a loss of sexual desire. For some women, these issues can persist 12 and 18 months after birth. Mode of birth is not associated with long-term dyspareunia 6 and 12 months after birth. There is conflict seen in the literature with regard to the association between perineal trauma and short-and long-term sexual health. Breastfeeding and the existence of pre-existing sexual health issues are strongly predictive of sexual health issues at 6 and 12 months after birth. Women have described a discordance in their sexual desire to that of their partner, for some this caused distress but for couples who communicated their feelings of sexual desire, concern over baby’s well-being and adapting to parenthood distress was not experienced. Resuming sexual intercourse after birth was not spontaneous, women considered their mode of birth, the presence of perineal trauma and their physical and emotional recovery from birth. One fifth of women had not resumed sexual intercourse 12 weeks after birth.

A discussion is presented on the challenges associated with viewing postpartum sexual health from a physical perspective only, and why prevalence studies alone do not capture the nuances of postpartum sexual health. Future research needs to take account of the psychosocial and relational dimensions of postpartum sexual health as well as physical dimensions.
Sant’Imbenia (Alghero): further archaeometric evidence for an Iron Age market square
Authors: Clemenza M. , Billeci B. , Carpinelli M. , Ferrante M. , Fiorini E. , Gasperetti G. , Nisi S. , Oliva P. , Sipala V. , Trincherini P. R. , Villa I. M. , Rendeli M.
Published: October 2021

Lead isotope compositions were determined for 18 metal objects from the archaeological site of Sant’Imbenia, NW Sardinia, dating to the end of the ninth century BCE onwards. The provenance of some objects is unambiguously traced to SW Sardinia; other objects could derive either from central Sardinia or the Iberian coastal ranges. The variety of the provenances attests to a wide trade network that spanned the entire island of Sardinia and extended to the Iberian sites.
Hadley Circulation in the Present and Future Climate Simulations of the K-ACE Model
Authors: Hur Ije , Kim Minju , Kwak Kyungmin , Sung Hyun Min , Byun Young-Hwa , Song Hajoon , Yoo Changhyun
Published: October 2021

Hadley circulation (HC) is a planetary-scale overturning circulation in the tropics that transports momentum, heat, and moisture poleward. In this study, we evaluate the strength and extent of the HC in the historical and future climate simulations of the Korean Meteorological Administration (KMA) Advanced Community Earth system model (K-ACE), which was recently developed by the National Institute of Meteorological Sciences of Korea. Compared with a reanalysis product, the overall structure of the HC is reasonably reproduced by the K-ACE. At the same time, it is also found that the Northern Hemisphere HC in the K-ACE is shifted southward by a few degrees, while the strength of the Southern Hemisphere (SH) HC is under-represented by approximately 20%. These biases in the strength and extent of the HC can be explained by biases in the eddy momentum flux and precipitation in the tropics. In the future climate simulations under the Shared Socioeconomic Pathway 5-Representative Concentration Pathway 8.5 scenario, the HCs in the K-ACE show a weakening and widening trend in both hemispheres, which is consistent with the projections of many Coupled Model Intercomparison Project Phase 6 models. A notable feature of the K-ACE is the widening of the SH HC, which takes place at a rate that is about double the multi-model mean. Climate models that share the component models with the K-ACE, such as UKESM, HadGEM3-GC31-LL, and ACCESS-CM2/ESM1, also show enhanced poleward expansion of the HC in the SH. This strong expansion is shown to be dominated by the expansion of the regional HC over the Pacific.
A New Conceptual Framework for Integrating Earth Observation in Large-scale Wetland Management in East Africa
Authors: Steinbach Stefanie , Cornish Natalie , Franke Jonas , Hentze Konrad , Strauch Adrian , Thonfeld Frank , Zwart Sander J. , Nelson Andrew
Published: October 2021

Wetlands are abundant across the African continent and provide a range of ecosystem services on different scales but are threatened by overuse and degradation. It is essential that national governments enable and ensure the sustainable use of wetland resources to maintain these services in the long run. As informed management decisions require reliable, up-to-date, and large coverage spatial data, we propose a modular Earth observation-based framework for the geo-localisation and characterization of wetlands in East Africa. In this study, we identify four major challenges in spatial data supported wetland management and present a framework to address them. We then apply the framework comprising Wetland Delineation, Surface Water Occurrence, Land Use/Land Cover classification and Wetland Use Intensity for the whole of Rwanda and evaluate the ability of these layers to meet the identified challenges. The layers’ spatial and temporal characteristics make them combinable and the information content, of each layer alone as well as in combination, renders them useful for different wetland management contexts.
Multiple infill criterion-assisted hybrid evolutionary optimization for medium-dimensional computationally expensive problems
Authors: Qin Shufen , Li Chan , Sun Chaoli , Zhang Guochen , Li Xiaobo
Published: October 2021

Surrogate-assisted evolutionary algorithms have been paid more and more attention to solve computationally expensive problems. However, model management still plays a significant importance in searching for the optimal solution. In this paper, a new method is proposed to measure the approximation uncertainty, in which the differences between the solution and its neighbour samples in the decision space, and the ruggedness of the objective space in its neighborhood are both considered. The proposed approximation uncertainty will be utilized in the surrogate-assisted global search to find a solution for exact objective evaluation to improve the exploration capability of the global search. On the other hand, the approximated fitness value is adopted as the infill criterion for the surrogate-assisted local search, which is utilized to improve the exploitation capability to find a solution close to the real optimal solution as much as possible. The surrogate-assisted global and local searches are conducted in sequence at each generation to balance the exploration and exploitation capabilities of the method. The performance of the proposed method is evaluated on seven benchmark problems with 10, 20, 30 and 50 dimensions, and one real-world application with 30 and 50 dimensions. The experimental results show that the proposed method is efficient for solving the low- and medium-dimensional expensive optimization problems by compared to the other six state-of-the-art surrogate-assisted evolutionary algorithms.
Time and the embodied other in education: A dimension of teachers’ everyday judgements of student learning
Authors: Edling Silvia
Published: October 2021

The article explores ethical conceptualisations of time that take the existence of the embodied Other in education into consideration. Kristeva’s time/memory paradox is discussed with regard to teachers’ everyday judgements in relation to student learning. In conclusion, learning as an unruptured endeavour is impossible when the time of the embodied Other is taken into account. In this sense, teachers need to be aware of: 1) the time gap between people, 2) the time gap between the conscious and subconscious (time/timelessness), 3) the fact that teachers’ and students’ meaning-making is always tainted by past memory, 4) the ways in which the timelessness of the subconscious crashes into conscious meaning-making in the present and creates ruptures that affect the content of learning and the life conditions of Others, 5) how frozen time (shadow of time) can be used as a way of learning from ruptures, and 6) that processing time(s) is just as important as ‘progressing in it’.
Grain characteristics, electrical conductivity, and hardness of Zn-doped Cu–3Si alloys system
Authors: Nnakwo K. C. , Osakwe F. O. , Ugwuanyi B. C. , Oghenekowho P. A. , Okeke I. U. , Maduka E. A.
Published: October 2021

The grain characteristics, electrical conductivity, hardness, and bulk density of Cu–3Si–(0.1—1 wt%)Zn alloys system fabricated by gravity casting technique were investigated experimentally using optical microscopy (OM), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The study established the optimal alloy composition and the significance of zinc addition on the tested properties using response surface optimal design (RSOD). The cooled alloy samples underwent normalizing heat treatment at 900 °C for 0.5 h. The average grains size and grains distribution were analyzed using the linear intercept method (ImageJ). The microstructure examination revealed a change in grain characteristics (morphology and size) of the parent alloy by addition of 0.1 wt% zinc. The average grains size of the parent alloy decreased from 12 µm to 7.0 µm after 0.1 wt% zinc addition. This change in grain characteristics led to an increase in the hardness of the parent alloy by 42.2%, after adding 0.1 wt% zinc. The electrical conductivity of the parent alloy decreased from 46.3%IACS to 45.3%IACS, while the density was increased by 8.4% after adding 0.1 wt% zinc. The statistical data confirmed the significance of the change in properties. The result of optimization revealed Cu–3Si–0.233Zn as the optimal alloy composition with optimal properties. The Cu–3Si–xZn alloy demonstrated excellent properties suitable for the fabrication of electrical and automobile components.
The ‘code adjudicator’ model: the Pubs Code, statutory arbitration and the tied lease
Authors: Meers Jed , Hind Liz
Published: October 2021

The ‘code adjudicator’ is a new statutory intervention in business-to-business disputes. They are Janus-faced, combining a statutory arbitration function with a regulatory remit. This paper is a detailed critique of the ‘Pubs Code Adjudicator’, which presides over the Pubs Code Regulations 2016 and intervenes in the contractual relationships between the largest pub-owning companies and their tied tenants. Drawing on a sample of interviews with affected tenants, arbitration data, and legal appeals under the Arbitration Act 1996, we argue that – although these ‘new intermediaries’ show promise – there are a series of limitations with both the function of the Pubs Code Regulations and the ‘code adjudicator’ model itself. In particular, our findings demonstrate the use of delaying tactics, the interaction of code adjudication with the parties’ existing contractual relationships, and issues with the application of arbitration ‘burden of proof’ standards to the exercise of duties under the statutory code.
MONOMIAL AND MONOLITHIC CHARACTERS OF FINITE SOLVABLE GROUPS
Authors: ÇINARCI BURCU
Published: October 2021

Let G be a finite solvable group and let p be a prime divisor of
$|G|$
. We prove that if every monomial monolithic character degree of G is divisible by p, then G has a normal p-complement and, if p is relatively prime to every monomial monolithic character degree of G, then G has a normal Sylow p-subgroup. We also classify all finite solvable groups having a unique imprimitive monolithic character.
Tick infestation effects on haemoglobin levels of deer mice (Peromyscus maniculatus)
Authors: Fellin Erica , Schulte-Hostedde Albrecht
Published: October 2021

Deer mice (Peromyscus maniculatus) are hosts to ixodid ticks as well as the associated tick-borne pathogens they can spread. As the ranges of black-legged ticks (Ixodes scapularis) and American dog ticks (Dermacentor variabilis) expand northwards, naïve host populations of deer mice are likely to become infested by ticks and experience the physiological effects that ticks can have on them via blood-feeding. The prevalence of these haematophagous ticks can affect the haemoglobin levels of the mice they infest. Haemoglobin levels were compared and analysed in deer mice populations at three different sites with varying tick exposure. These results suggested that without confounding effects, the abundance of black-legged and American dog ticks on individual mice had a significant negative effect on the hosts' haemoglobin levels, but only in an area with high tick infestation. This was seen across the average haemoglobin levels between populations, where there was a significant difference between the source population with the longest established tick populations and the source population where neither black-legged nor American dog ticks were prevalent. As the ticks' ranges expand and they become more abundant, it is important to understand how their prevalence and intensity can alter host physiology, potentially affecting their own range expansion and the spread of the diseases they may carry.
Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives
Authors: Fairchild Graeme , Sully Kate , Passamonti Luca , Staginnus Marlene , Darekar Angela , Sonuga-Barke Edmund J. S. , Toschi Nicola
Published: October 2021

Background

Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD.

Methods

Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures.

Results

The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes.

Conclusions

These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.
Improved Weather Forecasting Using Neural Network Emulation for Radiation Parameterization
Authors: Song Hwan‐Jin , Roh Soonyoung
Published: October 2021

In this study, a neural network (NN) emulator for radiation parameterization was developed to use in an operational weather forecasting model in the Korea Meteorological Administration. The development of the NN emulator was based on large‐scale training sets and 96 categories (longwave–shortwave, months, land–ocean, and clear–cloud). As the NN emulator replaced the radiation parameterization, a 60‐fold speedup for the radiation process was achieved, with a decrease of 87.26% in the total computation time. The accuracy of the NN emulator was strictly evaluated through comparison with the results obtained from the infrequent use of the original radiation scheme with the same computational cost. The mean errors of the NN emulator for skin temperature and fluxes were significantly reduced by 22%–34% compared with the infrequent method. The combination of using the NN radiation emulator and applying it infrequently provided an additional speedup of up to 36‐fold, corresponding to 2,160 times speedup compared with the control run, without a significant reduction in accuracy. The optimized structure for the radiation emulator designed in this study also showed universal robustness even in the use of limited training sets with incomplete coverage. As a result of the evaluation using surface observations, the use of the NN emulator showed no significant degradation for precipitation and temperature forecasts in comparison with the control run. In conclusion, the NN emulator for radiation parameterization in this study benefits both accuracy and computational cost, making it useful for improving weather forecasting modeling.
Light People: Professor Aydogan Ozcan
Authors: Sun Tingting
Published: October 2021

Editorial

In 2016, the news that Google’s artificial intelligence (AI) robot AlphaGo, based on the principle of deep learning, won the victory over lee Sedol, the former world Go champion and the famous 9th Dan competitor of Korea, caused a sensation in both fields of AI and Go, which brought epoch-making significance to the development of deep learning. Deep learning is a complex machine learning algorithm that uses multiple layers of artificial neural networks to automatically analyze signals or data. At present, deep learning has penetrated into our daily life, such as the applications of face recognition and speech recognition. Scientists have also made many remarkable achievements based on deep learning. Professor Aydogan Ozcan from the University of California, Los Angeles (UCLA) led his team to research deep learning algorithms, which provided new ideas for the exploring of optical computational imaging and sensing technology, and introduced image generation and reconstruction methods which brought major technological innovations to the development of related fields. Optical designs and devices are moving from being physically driven to being data-driven. We are much honored to have Aydogan Ozcan, Fellow of the National Academy of Inventors and Chancellor’s Professor of UCLA, to unscramble his latest scientific research results and foresight for the future development of related fields, and to share his journey of pursuing Optics, his indissoluble relationship with Light: Science & Applications (LSA), and his experience in talent cultivation.
RING-finger protein 6 promotes colorectal tumorigenesis by transcriptionally activating SF3B2
Authors: Xu Hui , Wong Chi Chun , Li Weilin , Zhou Yunfei , Li Yan , Wang Lifu , Liu Lei , Yu Jun
Published: October 2021

RNF6 is a RING finger protein with oncogenic potential. In this study, we established colon-specific RNF6 transgenic (tg) mice, and demonstrated that RNF6 overexpression accelerated colorectal carcinogenesis compared to wild-type littermates in a chemically induced colorectal cancer (CRC) model. To understand whether transcriptional activity of RNF6 underlies its oncogenic effect, we performed integrated chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis to identify splicing factor 3b subunit 2 (SF3B2) as a potential downstream target of RNF6. RNF6 binds to the SF3B2 promoter and the overexpression of RNF6 activates SF3B2 expression in CRC cells, primary CRC organoids, and RNF6 tg mice. SF3B2 knockout abrogated the tumor promoting effect of RNF6 overexpression, whereas the reexpression of SF3B2 recused cell growth and migration/invasion in RNF6 knockout cells, indicating that SF3B2 is a functional downstream target of RNF6 in CRC. Targeting of RNF6-SF3B2 axis with SF3B2 inhibitor with pladienolide B suppressed the growth of CRC cells with RNF6 overexpression in vitro and in vivo. Moreover, the combination of 5-fluorouracil (5-FU) plus pladienolide B exerted synergistic effects in CRC with high RNF6 expression, leading to tumor regression in xenograft models. These findings indicate that tumor promoting effect of RNF6 is achieved mainly via transcriptional upregulation of SF3B2, and that RNF6-SF3B2 axis is a promising target for CRC therapy.
IER2-induced senescence drives melanoma invasion through osteopontin
Authors: Kyjacova Lenka , Saup Rafael , Rönsch Kerstin , Wallbaum Sabine , Dukowic-Schulze Stefanie , Foss Amelia , Scherer Sandra D. , Rothley Melanie , Neeb Antje , Grau Nicole , Thiele Wilko , Thaler Sonja , Cremers Natascha , Sticht Carsten , Gretz Norbert , Garvalov Boyan K. , Utikal Jochen , Sleeman Jonathan P.
Published: October 2021

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence.
Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England
Authors: Hounsome L. , Eyre T. A. , Ireland R. , Hodson A. , Walewska R. , Ardeshna K. , Chaganti S. , McKay P. , Davies A. , Fox C. P. , Kalakonda N. , Fields P. A.
Published: October 2021

Background

We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome.

Methods

Data were extracted from Public Health England’s National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses.

Results

Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65–79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years.

Conclusions

Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.
Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer
Authors: Wang YouZhi , Wu Ning , Jiang Ning
Published: October 2021

Prostate cancer is a common malignant tumor, which can spread to multiple organs in the body. Metastatic disease is the dominant reason of death for patients with prostate cancer. Prostate cancer usually transfers to bone. Bone metastases are related to pathologic fracture, pain, and reduced survival. There are many known targets for prostate cancer treatment, including androgen receptor (AR) axis, but drug resistance and metastasis eventually develop in advanced disease, suggesting the necessity to better understand the resistance mechanisms and consider multi-target medical treatment. Because of the limitations of approved treatments, further research into other potential targets is necessary. Metastasis is an important marker of cancer development, involving numerous factors, such as AKT, EMT, ECM, tumor angiogenesis, the development of inflammatory tumor microenvironment, and defect in programmed cell death. In tumor metastasis, programmed cell death (autophagy, apoptosis, and necroptosis) plays a key role. Malignant cancer cells have to overcome the different forms of cell death to transfer. The article sums up the recent studies on the mechanism of bone metastasis involving key regulatory factors such as macrophages and AKT and further discusses as to how regulating autophagy is crucial in relieving prostate cancer bone metastasis.
Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis
Authors: Zhang Jingjing , Xu Xingxing , Liu Huitao , Jin Lingting , Shen Xiya , Xie Changnan , Xiang Weiwei , Yang Danlu , Feng Wenjin , Wang Jiaojiao , Wang Mianxian , Dong Tianyingying , Qiu Haoyu , Wu Lihao , Wang Ying , Zhang Xu , Huang Zhihui
Published: October 2021

Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAPGFAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP−/− astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAPGFAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERβ-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAPGFAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.
Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis
Authors: Yang Jing , Zhang Xing , Cao Jiacheng , Xu Penghui , Chen Zetian , Wang Sen , Li Bowen , Zhang Lu , Xie Li , Fang Lang , Xu Zekuan
Published: October 2021

Gastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p-STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.
Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity
Authors: Yang Hua , Wang Fei , Guo Xinya , Liu Feng , Liu Zhonghua , Wu Xiangyang , Zhao Mengmeng , Ma Mingtong , Liu Haipeng , Qin Lianhua , Wang Lin , Tang Tianqi , Sha Wei , Wang Yang , Chen Jianxia , Huang Xiaochen , Wang Jie , Peng Cheng , Zheng Ruijuan , Tang Fen , Zhang Lu , Wu Chunyan , Oehlers Stefan H. , Song Zhigang , She Jialei , Feng Hua , Xie Xunwei , Ge Baoxue
Published: October 2021

Pathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection.
Rewetting does not return drained fen peatlands to their old selves
Authors: Kreyling J. , Tanneberger F. , Jansen F. , van der Linden S. , Aggenbach C. , Blüml V. , Couwenberg J. , Emsens W-J , Joosten H. , Klimkowska A. , Kotowski W. , Kozub L. , Lennartz B. , Liczner Y. , Liu H. , Michaelis D. , Oehmke C. , Parakenings K. , Pleyl E. , Poyda A. , Raabe S. , Röhl M. , Rücker K. , Schneider A. , Schrautzer J. , Schröder C. , Schug F. , Seeber E. , Thiel F. , Thiele S. , Tiemeyer B. , Timmermann T. , Urich T. , van Diggelen R. , Vegelin K. , Verbruggen E. , Wilmking M. , Wrage-Mönnig N. , Wołejko L. , Zak D. , Jurasinski G.
Published: October 2021

Peatlands have been drained for land use for a long time and on a large scale, turning them from carbon and nutrient sinks into respective sources, diminishing water regulation capacity, causing surface height loss and destroying biodiversity. Over the last decades, drained peatlands have been rewetted for biodiversity restoration and, as it strongly decreases greenhouse gas emissions, also for climate protection. We quantify restoration success by comparing 320 rewetted fen peatland sites to 243 near-natural peatland sites of similar origin across temperate Europe, all set into perspective by 10k additional European fen vegetation plots. Results imply that rewetting of drained fen peatlands induces the establishment of tall, graminoid wetland plants (helophytisation) and long-lasting differences to pre-drainage biodiversity (vegetation), ecosystem functioning (geochemistry, hydrology), and land cover characteristics (spectral temporal metrics). The Paris Agreement entails the rewetting of 500,000 km2 of drained peatlands worldwide until 2050-2070. A better understanding of the resulting locally novel ecosystems is required to improve planning and implementation of peatland rewetting and subsequent management.
Diverse sediment microbiota shape methane emission temperature sensitivity in Arctic lakes
Authors: Emerson Joanne B. , Varner Ruth K. , Wik Martin , Parks Donovan H. , Neumann Rebecca B. , Johnson Joel E. , Singleton Caitlin M. , Woodcroft Ben J. , Tollerson Rodney , Owusu-Dommey Akosua , Binder Morgan , Freitas Nancy L. , Crill Patrick M. , Saleska Scott R. , Tyson Gene W. , Rich Virginia I.
Published: October 2021

Northern post-glacial lakes are significant, increasing sources of atmospheric carbon through ebullition (bubbling) of microbially-produced methane (CH4) from sediments. Ebullitive CH4 flux correlates strongly with temperature, reflecting that solar radiation drives emissions. However, here we show that the slope of the temperature-CH4 flux relationship differs spatially across two post-glacial lakes in Sweden. We compared these CH4 emission patterns with sediment microbial (metagenomic and amplicon), isotopic, and geochemical data. The temperature-associated increase in CH4 emissions was greater in lake middles—where methanogens were more abundant—than edges, and sediment communities were distinct between edges and middles. Microbial abundances, including those of CH4-cycling microorganisms and syntrophs, were predictive of porewater CH4 concentrations. Results suggest that deeper lake regions, which currently emit less CH4 than shallower edges, could add substantially to CH4 emissions in a warmer Arctic and that CH4 emission predictions may be improved by accounting for spatial variations in sediment microbiota.
Systematic review and meta-analyses of studies analysing instructions to authors from 1987 to 2017
Authors: Malički Mario , Jerončić Ana , Aalbersberg IJsbrand Jan , Bouter Lex , ter Riet Gerben
Published: October 2021

To gain insight into changes of scholarly journals’ recommendations, we conducted a systematic review of studies that analysed journals’ Instructions to Authors (ItAs). We summarised results of 153 studies, and meta-analysed how often ItAs addressed: 1) authorship, 2) conflicts of interest, 3) data sharing, 4) ethics approval, 5) funding disclosure, and 6) International Committee of Medical Journal Editors’ Uniform Requirements for Manuscripts. For each topic we found large between-study heterogeneity. Here, we show six factors that explained most of that heterogeneity: 1) time (addressing of topics generally increased over time), 2) country (large differences found between countries), 3) database indexation (large differences found between databases), 4) impact factor (topics were more often addressed in highest than in lowest impact factor journals), 5) discipline (topics were more often addressed in Health Sciences than in other disciplines), and 6) sub-discipline (topics were more often addressed in general than in sub-disciplinary journals).
Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity
Authors: Shenoy Anukul T. , Lyon De Ana Carolina , Arafa Emad I. , Salwig Isabelle , Barker Kimberly A. , Korkmaz Filiz T. , Ramanujan Aditya , Etesami Neelou S. , Soucy Alicia M. , Martin Ian M. C. , Tilton Brian R. , Hinds Anne , Goltry Wesley N. , Kathuria Hasmeena , Braun Thomas , Jones Matthew R. , Quinton Lee J. , Belkina Anna C. , Mizgerd Joseph P.
Published: October 2021

Barrier tissues are populated by functionally plastic CD4+ resident memory T (TRM) cells. Whether the barrier epithelium regulates CD4+ TRM cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)lowMHChigh epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells. In vivo ablation of lung epithelial MHC-II results in altered localization of CD4+ TRM cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4+ TRM cells to co-express several classically antagonistic lineage-defining transcription factors, changes their cytokine profiles, and results in dysregulated barrier immunity. In addition, lung epithelial MHC-II is needed for surface expression of PD-L1, which engages its ligand PD-1 to constrain lung CD4+ TRM cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4+ TRM cell function and identify epithelial-CD4+ TRM cell immune interactions as core elements of barrier immunity.
Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy
Authors: Krieger Teresa G. , Le Blanc Solange , Jabs Julia , Ten Foo Wei , Ishaque Naveed , Jechow Katharina , Debnath Olivia , Leonhardt Carl-Stephan , Giri Anamika , Eils Roland , Strobel Oliver , Conrad Christian
Published: October 2021

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished ‘classical’ from ‘basal-like’ tumors with more aggressive clinical behavior. We derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that ‘classical’ and ‘basal-like’ cells coexist in individual organoids. By single-cell transcriptome analysis of PDAC organoids and primary PDAC, we identify distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. Cell states are connected by a differentiation hierarchy, with ‘classical’ cells concentrated at the endpoint. In an imaging-based drug screen, expression of ‘classical’ subtype genes correlates with better drug response. Our results thus uncover a functional hierarchy of PDAC cell states linked to transcriptional tumor subtypes, and support the use of PDAC organoids as a clinically relevant model for in vitro studies of tumor heterogeneity.
Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
Authors: Larsen Mads Delbo , Lopez-Perez Mary , Dickson Emmanuel Kakra , Ampomah Paulina , Tuikue Ndam Nicaise , Nouta Jan , Koeleman Carolien A. M. , Ederveen Agnes L. Hipgrave , Mordmüller Benjamin , Salanti Ali , Nielsen Morten Agertoug , Massougbodji Achille , van der Schoot C. Ellen , Ofori Michael F. , Wuhrer Manfred , Hviid Lars , Vidarsson Gestur
Published: October 2021

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibody-dependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.
Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV
Authors: Alrubayyi Aljawharah , Gea-Mallorquí Ester , Touizer Emma , Hameiri-Bowen Dan , Kopycinski Jakub , Charlton Bethany , Fisher-Pearson Natasha , Muir Luke , Rosa Annachiara , Roustan Chloe , Earl Christopher , Cherepanov Peter , Pellegrino Pierre , Waters Laura , Burns Fiona , Kinloch Sabine , Dong Tao , Dorrell Lucy , Rowland-Jones Sarah , McCoy Laura E. , Peppa Dimitra
Published: October 2021

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.
Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
Authors: Yee Douglas , Isaacs Claudine , Wolf Denise M. , Yau Christina , Haluska Paul , Giridhar Karthik V. , Forero-Torres Andres , Jo Chien A. , Wallace Anne M. , Pusztai Lajos , Albain Kathy S. , Ellis Erin D. , Beckwith Heather , Haley Barbara B. , Elias Anthony D. , Boughey Judy C. , Kemmer Kathleen , Yung Rachel L. , Pohlmann Paula R. , Tripathy Debu , Clark Amy S. , Han Hyo S. , Nanda Rita , Khan Qamar J. , Edmiston Kristen K. , Petricoin Emanuel F. , Stringer-Reasor Erica , Falkson Carla I. , Majure Melanie , Mukhtar Rita A. , Helsten Teresa L. , Moulder Stacy L. , Robinson Patricia A. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Buxton Meredith , Clennell Julia L. , Paoloni Melissa , Sanil Ashish , Berry Scott , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Asare Adam L. , Matthews Jeffrey B. , Hylton Nola M. , DeMichele Angela , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Fraser Symmans W. , van‘t Veer Laura J. , Berry Donald A. , Esserman Laura J.
Published: October 2021

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY’s prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.
Evidence for independent domestication of sheep mtDNA lineage A in India and introduction of lineage B through Arabian sea route
Authors: Kamalakkannan Ranganathan , Kumar Satish , Bhavana Karippadakam , Prabhu Vandana R. , Machado Carolina Barros , Singha Hijam Surachandra , Sureshgopi Dhandapani , Vijay Vincy , Nagarajan Muniyandi
Published: October 2021

India ranks the second in the world in terms of its sheep population with approximately 74.26 million represented by 44 well-described breeds in addition to several non-descript populations. Genetic diversity and phylogeography of Indian sheep breeds remain poorly understood, particularly for south Indian breeds. To have a comprehensive view of the domestication history of Indian sheep, we sequenced the mitochondrial DNA (mtDNA) control region (D-loop) and cytochrome b gene (CYTB) of 16 Indian domestic sheep breeds, most of them (13) from the south India. We analysed these sequences along with published data of domestic and wild sheep from different countries, including India. The haplotype diversity was relatively high in Indian sheep, which were classified into the three known mtDNA lineages, namely A, B and C. Lineage A was predominant among Indian sheep whereas lineages B and C were observed at low frequencies but C was restricted to the breeds of north and east India. The median joining network showed five major expanding haplogroups of lineage A (A1–A5). Out of which, A2, A4 and A5 were more frequent in Indian sheep in contrast to breeds from other parts of the world. Among the 27 Indian sheep breeds analysed, Mandya and Sonadi breeds were significantly different from other Indian breeds in the MDS analyses. This was explained by a very high contribution of lineage B into these two breeds. The Approximate Bayesian Computation (ABC) provided evidence for the domestication of lineage A sheep in the Indian subcontinent. Contrary to the current knowledge, we also found strong support for the introduction of lineage B into Indian subcontinent through sea route rather than from the Mongolian Plateau. The neighbour-joining tree of domestic and wild sheep revealed the close genetic relationship of Indian domestic sheep with Pakistani wild sheep O. vignei blanfordi. Based on our analyses and archaeological evidences, we suggest the Indian subcontinent as one of the domestication centres of the lineage A sheep, while lineage B sheep might have arrived into India from elsewhere via Arabian sea route. To the best of our knowledge, this is the first comprehensive study on Indian sheep where we have analysed more than 740 animals belonging to 27 sheep breeds raised in various regions of India. Our study provides insight into the understanding of the origin and migratory history of Indian sheep.