bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Intra-articular Injection of Glucocorticoids Be an Alternative Intervention to Achieve Remission in Patients With Rheumatoid Arthritis Exhibiting Low Disease Activity? A Single-Center Longitudinal Study
Authors: Kishimoto Yuji , Kato Yoshihiro , Uemura Manami , Kuranobu Koji
Published: February 2021

Background/Objective

This study aimed at investigating whether a single intra-articular (IA) injection of triamcinolone acetonide (TA) could facilitate to achieve clinical remission in patients with rheumatoid arthritis (RA) exhibiting low disease activity (LDA).

Methods

This longitudinal study included 22 patients with RA exhibiting LDA involving wrist arthritis at our institution between April 2016 and March 2019. A single IA injection of 20 mg TA was administered into the symptomatic wrist joint. Efficacy was assessed by the primary end point of proportion of patients reaching clinical remission. Secondary end points included Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index, adverse events, and ultrasonographic assessment of the injected wrist joints.

Results

Remission rates were 40% and 50% at weeks 4 and 12, respectively, and were maintained at approximately 50% until week 24. The secondary outcomes of CDAI, SDAI, and Health Assessment Questionnaire Disability Index were improved significantly at week 4, and the improvements in CDAI and SDAI continued up to week 24. Ultrasonography showed that synovial hypertrophy, power Doppler signals, and the combined score were significantly reduced at weeks 4, 12, and 24 compared with the baseline. No patient developed severe, irreversible adverse events.

Conclusions

Approximately half of the patients with RA exhibiting LDA who received a single IA injection of TA into the wrist joints achieved clinical remission without serious adverse events in the midterm period, suggesting that IA injection of TA might be considered as an alternative intervention to achieve remission in patients with RA exhibiting LDA.
Surgical and Ophthalmologic Outcomes of Reconstruction in Patients Treated With Eye-Sparing Surgery and Radiation Therapy for Tumors of the Lacrimal Drainage Apparatus
Authors: Olenczak J. Bryce , Ford Joshua R. , Mericli Alexander F. , Adelman David M. , Chang Edward I. , Hanasono Matthew M. , Esmaeli Bita , Kapur Sahil K.
Published: February 2021

Introduction

Tumors involving the lacrimal drainage apparatus can be effectively treated with oncologic eye-sparing resection, immediate reconstruction, and adjuvant radiation. The extirpative technique is well described, whereas the reconstructive approach and outcomes are limited and largely anecdotal. The present study describes the largest series in the literature evaluating outcomes after reconstruction after globe-preserving oncologic resection.

Methods

A retrospective review was performed for all patients undergoing reconstruction after resection of lacrimal gland tumors from 2008 to 2019. Reconstruction and ophthalmologic outcomes were assessed.

Results

Of the 17 patients included, 2 underwent complex repair, 6 were reconstructed with a locoregional flap, and 9 underwent free flap reconstruction. All patients were treated with adjuvant radiation therapy. The median follow-up was 19 months (range, 5–126 months). Defects reconstructed with free flaps had lower rates of wound dehiscence and fistula formation compared with those reconstructed with other techniques (11% vs 25%, P = 0.45). Patients undergoing reconstruction with free tissue transfer also tended to have lower rates of ectropion, keratopathy and decreased visual acuity compared with those undergoing nonmicrosurgical reconstruction (33% vs 50%, P = 0.48; 11% vs 38%, P = 0.20; 56% vs 75%, P = 0.40, respectively). These differences were not statistically significant.

Conclusions

This is the first study to compare reconstructive and functional outcomes of nonmicrosurgical reconstruction and microsurgical free tissue transfer in the setting of eye-sparing surgery for tumors of the lacrimal drainage apparatus. Although various reconstructive options are feasible, microsurgical free tissue transfer is often used at our center and is associated with reliable outcomes.
Sarcoidosis Presenting as Late Seroma Mimicking Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Ibarra Gorka , Vallejo Alfonso , Rivera Andres , Fernandez-Ibarburu Borja , Garcia-Ruano Angela
Published: February 2021

Late seroma related to breast silicone implants is a rare complication. Interest for its characterization has grown after its association with the recently described breast implant–associated anaplastic large cell lymphoma. The differential diagnosis includes infectious diseases, mechanical and traumatic causes, tumors, postpartum seroma, and inflammatory, allergic, or idiopathic causes.

Sarcoidosis has been associated with breast silicone implants over the last decades, but it has never been reported as a cause of breast effusion. We describe a rare presentation of sarcoidosis as a late breast implant seroma simulating the clinical features and radiologic findings of breast implant–associated anaplastic large cell lymphoma and highlight that sarcoidosis can be suspected by the presence of nonnecrotizing epithelioid granulomas in the cytology, with a characteristic inverted ratio of CD4/CD8 T cells.

The aims of this article are to review the current evidence about sarcoidosis related to silicone implants and breast cancer, provide a new alternative in the differential diagnosis of late seroma, and advise the scientific community how early implant removal can improve the disease.
Using Radiographic Domain for Evaluating Indications in Abdominal Wall Transplantation
Authors: Hollins Andrew W. , Napier Kyle , Wildman-Tobriner Benjamin , Erdmann Ralph , Sudan Debra L. , Ravindra Kadiyala V. , Erdmann Detlev , Atia Andrew
Published: February 2021

Background

There is currently no description of abdominal domain changes in small bowel transplantation population or consensus of criteria regarding which patients are at high risk for immediate postoperative abdominal wall complications or would benefit from abdominal wall vascularized composite allotransplantation.

Methods

A retrospective chart review was performed on 14 adult patients receiving intestinal or multivisceral transplantation. Preoperative and postoperative computed tomography scans were reviewed, and multiple variables were collected regarding abdominal domain and volume and analyzed comparing postoperative changes and abdominal wall complications.

Results

Patients after intestinal or multivisceral transplantation had a mean reduction in overall intraperitoneal volume in the immediate postoperative period from 9031 cm3 to 7846 cm3 (P = 0.314). This intraperitoneal volume was further reduced to an average of 6261 cm3 upon radiographic evaluation greater than 1 year postoperatively (P = 0.024). Patients with preexisting abdominal wound (P = 0.002), radiation, or presence of ostomy (P = 0.047) were significantly associated with postoperative abdominal wall complications. No preoperative radiographic findings had a significant association with postoperative abdominal wall complications.

Conclusions

Computed tomography imaging demonstrates that intestinal and multivisceral transplant patients have significant reduction in intraperitoneal volume and domain after transplantation in the acute and delayed postoperative setting. Preoperative radiographic abdominal domain was not able to predict patients with postoperative abdominal wall complications. Patients with abdominal wounds, ostomies, and preoperative radiation therapy were associated with acute postoperative abdominal complications and may be considered for need of reconstructive techniques including abdominal wall transplantation.
Gender-Affirming Mastectomy in Transmasculine Patients
Authors: Rothenberg Kara A. , Gologorsky Rebecca C. , Hojilla J. Carlo , Tang Annie , M. Cohan Caitlin , Beattie Genna , Yokoo Karen M.
Published: February 2021

Background

Obesity can often be a barrier to gender-affirming top surgery in transmasculine patients because of concern for increased surgical site complications.

Study Design

All adult patients (N = 948) within an integrated health care system who underwent gender-affirming mastectomy from 2013 to 2018 were retrospectively reviewed to evaluate the relationship between obesity and surgical site complications or revisions.

Results

One third of patients (n = 295) had obese body mass index (BMI), and those patients were further stratified into obesity class I (BMI of 30–34.9 kg/m2, 9.4%), class II (BMI of 35–39.9 kg/m2, 8.9%), and class III (BMI of ≥40 kg/m2, 2.9%). A majority of patients across BMI categories underwent double incision surgery. There were no significant differences in complications or revisions between patients with obesity versus those with normal BMI, when BMI was treated as a categorical or continuous variable and when evaluating only patients who underwent double incision surgery.

Conclusions

Obesity alone should not be considered a contraindication for gender-affirming mastectomy. Attention should be given to several modifiable risk factors identified in this study, including lesser incision surgical techniques, tobacco use, and testosterone use. Further research is needed to understand risks associated with the highest BMI (≥40 kg/m2) patients and to assess patient satisfaction with surgical outcome.
Confirmation bias is adaptive when coupled with efficient metacognition
Authors: Rollwage Max , Fleming Stephen M.
Published: February 2021

Biases in the consideration of evidence can reduce the chances of consensus between people with different viewpoints. While such altered information processing typically leads to detrimental performance in laboratory tasks, the ubiquitous nature of confirmation bias makes it unlikely that selective information processing is universally harmful. Here, we suggest that confirmation bias is adaptive to the extent that agents have good metacognition, allowing them to downweight contradictory information when correct but still able to seek new information when they realize they are wrong. Using simulation-based modelling, we explore how the adaptiveness of holding a confirmation bias depends on such metacognitive insight. We find that the behavioural consequences of selective information processing are systematically affected by agents' introspective abilities. Strikingly, we find that selective information processing can even improve decision-making when compared with unbiased evidence accumulation, as long as it is accompanied by good metacognition. These results further suggest that interventions which boost people's metacognition might be efficient in alleviating the negative effects of selective information processing on issues such as political polarization.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Reframing social categorization as latent structure learning for understanding political behaviour
Authors: Lau Tatiana
Published: February 2021

Affiliating with political parties, voting and building coalitions all contribute to the functioning of our political systems. One core component of this is social categorization—being able to recognize others as fellow in-group members or members of the out-group. Without this capacity, we would be unable to coordinate with in-group members or avoid out-group members. Past research in social psychology and cognitive neuroscience examining social categorization has suggested that one way to identify in-group members may be to directly compute the similarity between oneself and the target (dyadic similarity). This model, however, does not account for the fact that the group membership brought to bear is context-dependent. This review argues that a more comprehensive understanding of how we build representations of social categories (and the subsequent impact on our behaviours) must first expand our conceptualization of social categorization beyond simple dyadic similarity. Furthermore, a generalizable account of social categorization must also provide domain-general, quantitative predictions for us to test hypotheses about social categorization. Here, we introduce an alternative model—one in which we infer latent groups of people through latent structure learning. We examine experimental evidence for this account and discuss potential implications for understanding the political mind.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
The sociocognitive processes of ideological obsession: review and policy implications
Authors: Bélanger Jocelyn J.
Published: February 2021

Understanding what motivates people to join violent ideological groups and engage in acts of cruelty against others is of great social and societal importance. In this paper, I posit that one necessary element is ‘ideological obsession’—an ideological commitment fuelled by unmet psychological needs and regulated by inhibitory and ego-defensive mechanisms. Drawing from evidence collected across cultures and ideologies, I describe four processes through which ideological obsession puts individuals on a path towards violence. First, ideological obsession deactivates moral self-regulatory processes, allowing unethical behaviours to be carried out without self-recrimination. Second, ideologically obsessed individuals are easily threatened by information that criticises their ideology, which in turn leads to hatred and violent retaliation. Third, ideological obsession changes people's social interactions by making them gravitate towards like-minded individuals who support ideological violence. As these social networks become more interconnected, they amplify one's adherence to violent extremism. Finally, ideologically obsessed individuals are prone to psychological reactance, making them immune to communication strategies intended to dissuade them from using violence. In fact, messages espousing non-violence can have the opposite effect by reinforcing their violence-supporting ideology. I conclude by presenting evidence-based strategies to prevent radicalisation leading to violence for individuals in pre-criminal spaces.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Corrections of political misinformation: no evidence for an effect of partisan worldview in a US convenience sample
Authors: Ecker Ullrich K. H. , Sze Brandon K. N. , Andreotta Matthew
Published: February 2021

Misinformation often has a continuing effect on people's reasoning despite clear correction. One factor assumed to affect post-correction reliance on misinformation is worldview-driven motivated reasoning. For example, a recent study with an Australian undergraduate sample found that when politically situated misinformation was retracted, political partisanship influenced the effectiveness of the retraction. This worldview effect was asymmetrical, that is, particularly pronounced in politically conservative participants. However, the evidence regarding such worldview effects (and their symmetry) has been inconsistent. Thus, the present study aimed to extend previous findings by examining a sample of 429 pre-screened US participants supporting either the Democratic or Republican Party. Participants received misinformation suggesting that politicians of either party were more likely to commit embezzlement; this was or was not subsequently retracted, and participants' inferential reasoning was measured. While political worldview (i.e. partisanship) influenced the extent to which participants relied on the misinformation overall, retractions were equally effective across all conditions. There was no impact of political worldview on retraction effectiveness, let alone evidence of a backfire effect, and thus we did not replicate the asymmetry observed in the Australian-based study. This pattern emerged despite some evidence that Republicans showed a stronger emotional response than Democrats to worldview-incongruent misinformation.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Political ideology, cooperation and national parochialism across 42 nations
Authors: Romano Angelo , Sutter Matthias , Liu James H. , Balliet Daniel
Published: February 2021

Political ideology has been hypothesized to be associated with cooperation and national parochialism (i.e. greater cooperation with members of one's nation), with liberals thought to have more cooperation with strangers and less national parochialism, compared to conservatives. However, previous findings are limited to few—and predominantly western—nations. Here, we present a large-scale cross-societal experiment that can test hypotheses on the relation between political ideology, cooperation and national parochialism around the globe. To do so, we recruited 18 411 participants from 42 nations. Participants made decisions in a prisoner's dilemma game, and we manipulated the nationality of their interaction partner (national ingroup member, national outgroup member or unidentified stranger). We found that liberals, compared to conservatives, displayed slightly greater cooperation, trust in others and greater identification with the world as a whole. Conservatives, however, identified more strongly with their own nation and displayed slightly greater national parochialism in cooperation. Importantly, the association between political ideology and behaviour was significant in nations characterized by higher wealth, stronger rule of law and better government effectiveness. We discuss the implications of these findings for understanding the association between political ideology and cooperation.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Assessment of Motion Bias on the Detection of Dopamine Response to Challenge
Authors: Levine Michael A. , Calabro Finnegan , Izquierdo-Garcia David , Chonde Daniel B. , Chen Kevin T. , Hong Inki , Price Julie C. , Luna Beatriz , Catana Ciprian
Published: February 2021

11C-Raclopride (RAC) positron emission tomography (PET) is used to study dopamine response to pharmacological and behavioral challenges. Behavioral challenges produce smaller responses than pharmacological challenges and are more susceptible to sources of bias, including motion bias. The purpose of this study was to characterize the effect of motion bias within the context of a behavioral task challenge, examining the impact of different motion correction strategies, different task response magnitudes, and intra-versus interframe motion.

Methods

Seventy healthy young adults were administered bolus plus constant infusion 11C-Raclopride (RAC) and imaged for 90 min on a 3-Tesla simultaneous PET/magnetic resonance (MR) scanner during which a functional MRI (fMRI) reward task experiment was conducted. Kinetic analysis was performed using an extension of the multilinear reference tissue model (MRTM), which encoded the task response as a unit step function at the start of the task (t = 40 min). The quantitative impacts of different approaches to motion correction (frame-based, reconstruction-based, none) were compared using voxel maps of change in binding potential (ΔBPND). Motion bias was compared to task effect by simulating different levels of ΔBPND (0%, 5%, 10%, 20%) in conjunction with simulating high and no motion. Intraframe motion was simulated using motion estimates derived from the simultaneously acquired MR data. The relative impact of intraframe motion was evaluated by comparing maps of bias in ΔBPND before and after applying frame-based motion correction.

Results

Among the high-motion subjects, failure to perform motion correction resulted in large artifacts. Frame- and reconstruction-based approaches both corrected for motion effectively, with the former showing moderately more intense ΔBPND values (both positive and negative) in and around the striatum. At low task response magnitudes, simulations showed that motion bias can have a greater relative effect. At 5% ΔBPND, motion bias accounted for 60% of the total bias, while at 10% ΔBPND, it accounted for only 34%. Simulating high-temporal resolution motion, frame-based motion correction was shown to counteract the majority of the of the motion bias effect. The remaining bias attributable to intraframe motion accounted for only 8% of the total.

Conclusion

Motion bias can have a corrupting effect on RAC studies of behavioral task challenges, particularly as the magnitude of the response decreases. Applying motion correction mitigates most of the bias, and specifically correcting for interframe motion provides the bulk of the benefit.
Time-restricted feeding near dawn entrains long-term behavioral changes through the suprachiasmatic nucleus
Authors: Zhai Qiaocheng , Zeng Yizhun , Gu Yue , Zhang Tao , Yuan Baoshi , Wang Tao , Yan Jie , Qin Han , Yang Ling , Chen Xiaowei , Vidal-Puig Antonio , Xu Ying
Published: February 2021

The suprachiasmatic nucleus (SCN) is a master circadian pacemaker known to integrate light intensity and seasonal information with peripheral tissues to coordinate daily rhythms of physiology and behavior. However, the contribution of food information to the regulation of the SCN network remains controversial. Here, we identified the effect induced by time-restricted feeding (TRF) at dawn, but not at another time widow, inducing a robust and long-term shift in locomotor behavior and increased wakefulness. Comparing the oscillations of intracellular Ca2+signals in the SCN GABAergic neurons of freely moving mice, before and after TRF, revealed significant activation of these neurons in dawn-TRF mice. Moreover, RNA-seq profiling in the dawn TRF-induced behavioral changes identified altered expressed genes involved in regulating extracellular exosome, ion transporters, and ECM-receptor interaction, but not core clock genes. Furthermore, injection in the SCN of insulin-like growth factor (IGF2) inhibitor Chromeceptin, targeting the most upregulated gene in extracellular exosome, abolished the after effect induced by ZT0-4 TRF. Finally, GABAergic-neuron-specific disruption of the potassium-chloride cotransporterKcc2intensified the dawn TRF-induced after effect, indicating thatKcc2encodes food intake derived signals that control SCN clock entrainment. Thus, our study functionally links SCN GABAergic neuron activity and central clock entrainment regulation to both hunger- and food-response-related behaviors in mice.
Factors influencing self-harm thoughts and self-harm behaviours over the first year of the COVID-19 pandemic in the UK: a longitudinal analysis of 49,324 adults
Authors: Paul Elise , Fancourt Daisy
Published: February 2021

Background

There is concern that the COVID-19 pandemic and its aftermath will result in excess suicides by increasing known risk factors such as self-harm, but evidence on how pandemic-related risk factors contribute to changes in these outcomes is lacking.

Aims

To examine how different COVID-19-related adverse experiences and adversity worries contribute to changes in self-harm thoughts and behaviours.

Method

Data from 49,324 UK adults in the UCL COVID-19 Social Study were analysed (1 April 2020 to 17 May 2021). Fixed effects regressions explored associations between weekly within-person variation in five categories of adversity experiences and adversity worries with changes in self-harm thoughts and behaviours across age groups (18-29, 30-44, 45-59, and 60+ years).

Results

26.1% and 7.9% respondents reported self-harm thoughts and behaviours, respectively, at least once over the study period. More adverse experiences were more strongly related to outcomes than worries. The largest specific adversity contributing to increases in both outcomes was having experienced physical or psychological abuse. Financial worries increased the likelihood of both outcomes in most age groups, whilst having had COVID-19 increased the likelihood of both outcomes in young (18-29 years) and middle-aged (45-59 years) adults.

Conclusions

Findings suggest that a significant portion of UK adults may be at increased risk for self-harm thoughts and behaviours during the pandemic. Given the likelihood that the economic and social consequences of the pandemic will accumulate, policy makers can begin adapting evidence-based suicide prevention strategies and other social policies to help mitigate its consequences.
Antiviral effect of a nucleic acid hydrolyzing scFv against oseltamivir resistant influenza A virus
Authors: Lee Yongjun , Kim Dongjun , Kim Taehyun , Oh Yeonsu , Kim Won-Keun , Lee Sukchan
Published: February 2021

Influenza viral genome is frequently mutated due to antigenic shift and drift, and therefore the existing antiviral drugs have been suffered from low efficacy against the viruses. Here we report an innovative strategy for treating influenza Type A (IAV) infection by 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity and the epidermal cell penetration ability. In this study, we first analyzed antiviral activity directed by 3D8 scFv to three different strains, two oseltamivir-sensitive (A/PuertoRico/8/1934, A/X-31) and oseltamivir-resistant (A/Korea/2785/2009pdm) using cell culture models, suggesting that 3D8 scFv reduces viral genomic RNA. Moreover, we further addressed antiviral effect to analyze clinical outcomes inin vivomice model. Intranasal administered 3D8 scFv rescued the mice challenged by oseltamivir resistant H1N1. Consistent results are observed through IHC pathology and molecular virological analysis. Taken together, these results demonstrate that 3D8 scFv has antiviral potential against a wide range of IAV.
Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant
Authors: Edara Venkata Viswanadh , Norwood Carson , Floyd Katharine , Lai Lilin , Davis-Gardner Meredith E. , Hudson William H. , Mantus Grace , Nyhoff Lindsay E. , Adelman Max W. , Fineman Rebecca , Patel Shivan , Byram Rebecca , Gomes Dumingu Nipuni , Michael Garett , Abdullahi Hayatu , Beydoun Nour , Panganiban Bernadine , McNair Nina , Hellmeister Kieffer , Pitts Jamila , Winters Joy , Kleinhenz Jennifer , Usher Jacob , O’Keefe James B. , Piantadosi Anne , Waggoner Jesse J. , Babiker Ahmed , Stephens David S. , Anderson Evan J. , Edupuganti Srilatha , Rouphael Nadine , Ahmed Rafi , Wrammert Jens , Suthar Mehul S.
Published: February 2021

The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.
FAM114A1 Influences Cardiac Fibrosis by Regulating Angiotensin II Signaling in Cardiac Fibroblasts
Authors: Subbaiah Kadiam C Venkata , Wu Jiangbin , Tang Wai Hong Wilson , Yao Peng
Published: February 2021

Cardiac fibrosis, a primary contributor to heart failure (HF) and sudden death, is considered as an important target for HF therapy. However, the signaling pathways that govern cardiac fibroblast (CF) function during cardiac fibrosis have not been fully elucidated. Here, we found that a functionally unannotated human myocardial infarction (MI) associated gene, family with sequence similarity 114 member A1 (FAM114A1), is induced in failing human and mouse hearts compared to non-failing hearts. Homozygous knockout ofFam114a1(Fam114a1−/−) in the mouse genome reduces cardiac hypertrophy and fibrosis while significantly restores cardiac function in angiotensin (Ang) II- and MI-induced HF mouse models.Fam114a1deletion antagonizes Ang II induced inflammation and oxidative stress. Using isolated mouse primary CFs in wild type andFam114a1−/−mice, we found that FAM114A1 is a critical autonomous factor for CF proliferation, activation, and migration. We discovered that FAM114A1 interacts with angiotensin receptor associated protein (AGTRAP) and regulates the expression of angiotensin type 1 receptor (AT1R) and downstream Ang II signaling transduction, and subsequently influences pro-fibrotic response. Using RNA-Seq in mouse primary CFs, we identified differentially expressed genes including extracellular matrix proteins such as Adamts15. RNAi-mediated inactivation of Adamts15 attenuates CF activation and collagen deposition. Our results indicate that FAM114A1 regulates Ang II signaling and downstream pro-fibrotic and pro-inflammatory gene expression, thereby activating cardiac fibroblasts and augmenting pathological cardiac remodeling. These findings provide novel insights into regulation of cardiac fibrosis and identify FAM114A1 as a new therapeutic target for treatment of cardiac disease.

Significance

Cardiac fibrosis is a hallmark of heart failure and angiotensin II signaling promotes pro-fibrotic response in the heart. This study is a pioneering investigation of the role of a functionally unknown protein FAM114A1. We show that FAM114A1 expression is induced in human and mouse failing hearts. Genetic ablation of FAM114A1 can effectively reduce cardiac fibrosis and pathological remodeling. Isolated cardiac fibroblasts fromFam114a1knockout mice show reduced response to Ang II stimulation and compromised myofibroblast activation. Mechanistically, FAM114A1 binds to AGTRAP and influences AT1R protein expression, thereby enhancing angiotensin II signaling and pro-fibrotic response. Thus, FAM114A1 is a novel factor that modulates cardiac fibrosis and pharmacological inhibition of FAM114A1 may be a therapeutic strategy for the treatment of heart disease.
Precise topology of adjacent domain-general and sensory-biased regions in the human brain
Authors: Assem Moataz , Shashidhara Sneha , Glasser Matthew F. , Duncan John
Published: February 2021

Recent functional MRI studies identified sensory-biased regions across much of the association cortices and cerebellum. However, their anatomical relationship to multiple-demand (MD) regions, characterized as domain-general due to their co-activation during multiple cognitive demands, remains unclear. For a better anatomical delineation, we used multimodal MRI techniques of the Human Connectome Project to scan subjects performing visual and auditory versions of a working memory (WM) task. The contrast between hard and easy WM showed strong domain generality, with essentially identical patterns of cortical, subcortical and cerebellar MD activity for visual and auditory materials. In contrast, modality preferences were shown by contrasting easy WM with baseline; most MD regions showed visual preference while immediately adjacent to cortical MD regions, there were interleaved regions of both visual and auditory preference. The results may exemplify a general motif whereby domain-specific regions feed information into and out of an adjacent, integrative MD core.
A Transient Metabolic State In Melanoma Persister Cells Mediated By Chemotherapeutic Treatments
Authors: Karki Prashant , Angardi Vahideh , Mier Juan C. , Orman Mehmet A.
Published: February 2021

Persister cells are defined as the small fraction of quiescent cells in a bulk cancer cell population that can tolerate unusually high levels of drugs. Persistence is a transient state that poses an important health concern in cancer therapy. The mechanisms associated with persister phenotypes are highly diverse and complex, and many aspects of persister cell physiology remain to be explored. We applied a melanoma cell line and panel of chemotherapeutic agents to show that melanoma persister cells are not necessarily preexisting dormant cells or stem cells; in fact, they may be induced by cancer chemotherapeutics. Our metabolomics analysis and phenotype microarray assays further demonstrated that the levels of Krebs cycle molecules are significantly lower in the melanoma persister subpopulation than in the untreated bulk cell population due to increased utilization rates in persisters. Our data indicate that this observed metabolic remodeling is transient, as the consumption rates of Krebs cycle metabolites are significantly reduced in the progenies of persisters. Given that the mitochondrial electron transport chain (ETC) is more active in the persister subpopulation than in the bulk cancer cell population, we also verified that targeting ETC activity can reduce melanoma persistence. The reported metabolic remodeling feature seems to be a conserved characteristic of melanoma persistence, as it has been observed in various melanoma persister subpopulations derived from a diverse range of chemotherapeutics. Elucidating a global metabolic mechanism that contributes to persister survival and reversible switching will ultimately foster the development of novel cancer therapeutic strategies.
A chimeric nuclease substitutes CRISPR-Cas: A phage weaponizes laterally acquired specificity to destroy subviral parasites
Authors: Barth Zachary K. , Nguyen Maria H.T. , Seed Kimberley D.
Published: February 2021

Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their hosts fitness. The PLE is a mobile element that integrates into the chromosome ofVibrio choleraeand parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA binding domain that is highly similar to some PLE replication origin binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.
Genome-wide transcriptional responses of marine nematodeLitoditis marinato hyposaline and hypersaline stresses
Authors: Xie Yusu , Zhang Pengchi , Zhang Liusuo
Published: February 2021

Maintenance of osmotic homeostasis is essential for all organisms, especially for marine animals in the ocean with 30‰ salinity or higher. However, the underlying molecular mechanisms that how marine animals adapt to high salinity environment compared to their terrestrial relatives, remain elusive. Here, we investigated marine animal’s genome-wide transcriptional responses to salinity stresses using an emerging marine nematode modelLitoditis marina. We found that the transthyretin-like family genes were significantly increased in both hyposaline and hypersaline conditions, while multiple neurotransmitter receptor and ion transporter genes were down-regulated in both conditions, suggesting the existence of conserved strategies for response to stressful salinity environments inL. marina. Unsaturated fatty acids biosynthesis related genes, neuronal related tubulins and intraflagellar transport genes were specifically up-regulated in hyposaline treated worms, while exhibited the opposite regulation in hypersaline condition. By contrast, cuticle related collagen genes were enriched and up-regulated for hypersaline response, interestingly, the expression of these collagen genes was significantly decreased in hyposaline condition. Given a wide range of salinity tolerance of the marine nematodes, this study and further genetic analysis of key gene(s) of osmoregulation inL. marinawill likely provide important insights into biological evolution and environmental adaptation mechanisms in nematodes and other invertebrate animals in general.
bMSI-CAST: a systematic method for next generation sequencing-based microsatellite instability detection in plasma cell-free DNA
Authors: Huang Fengchang , Zhao Lili , Xie Hongyu , Huang Jian , Wang Xiaoqing , Yang Jun , Hong Yuanyuan , Shu Jingchao , Yu Jianing , Li Qingyun , Zhang Hongbin , Chen Weizhi , He Ji , Li Wenliang
Published: February 2021

Microsatellite instability (MSI) is a well-established prognostic and predictive biomarker in certain types of cancers. MSI detection using tumour tissue is often limited by the availability of specimens. Next generation sequencing (NGS)-based MSI detection in plasma cell-free DNA (cfDNA) is challenged by a much lower signal-to-noise ratio. We developed a highly accurate cfDNA MSI detection method called bMSI-CAST (blood MSI Caller Adjusted with Sequence duplicaTes), with improvement on three features including a set of locus selection principles ensuring loci with high robustness and compatibility across sequencing platforms, an MSI-specific duplicate removal strategy, and a calling algorithm that dynamically matches baselines with a broad range of duplication levels. Analytical validation via MSI-high (MSI-H) cell gDNA showed an LOD of 0.15%. Furthermore, in an analysis of 95 evaluable cfDNA samples from patients with gastrointestinal cancers, bMSI-CAST exhibited a positive predictive agreement (PPA) of 92.9% (39/42) and negative predictive agreement (NPA) of 100% (53/53) with tissue MSI-PCR. In conclusion, bMSI-CAST provides novel and advanced solutions to key aspects fundamental to cfDNA MSI calling but not sufficiently addressed by existing methods, and it is a validated method ready to be applied to aid clinical decisions for cancer patients.
Dynamic Predictive Coding with Hypernetworks
Authors: Jiang Linxing Preston , Gklezakos Dimitrios C. , Rao Rajesh P. N.
Published: February 2021

The original predictive coding model of Rao & Ballard [1] focused on spatial prediction to explain spatial receptive fields and contextual effects in the visual cortex. Here, we introduce a new dynamic predictive coding model that achieves spatiotemporal prediction of complex natural image sequences using time-varying transition matrices. We overcome the limitations of static linear transition models (as in, e.g., Kalman filters) using a hypernetwork to adjust the transition matrix dynamically for every time step, allowing the model to predict using a time-varying mixture of possible transition dynamics. We developed a single level model with recurrent modulation of transition weights by a hypernetwork and a two-level hierarchical model with top-down modulation based on a hypernetwork. At each time step, the model predicts the next input and estimates a sparse neural code by minimizing prediction error. When exposed to natural movies, the model learned localized, oriented spatial filters as well as both separable and inseparable (direction-selective) space-time receptive fields at the first level, similar to those found in the primary visual cortex (V1). Longer timescale responses and stability at the second level also emerged naturally from minimizing prediction errors for the first level dynamics. Our results suggest that the multiscale temporal response properties of cortical neurons could be the result of the cortex learning a hierarchical generative model of the visual world with higher order areas predicting the transition dynamics of lower order areas.
CCM2 deficient endothelial cells undergo a mechano-dependent reprogramming into senescence associated secretory phenotype used to recruit endothelial and immune cells
Authors: Vannier Daphné Raphaëlle , Shapeti Apeksha , Chuffart Florent , Planus Emmanuelle , Manet Sandra , Rivier Paul , Destaing Olivier , Albiges-Rizo Corinne , Van Oosterwyck Hans , Faurobert Eva
Published: February 2021

Cerebral Cavernous Malformations (CCM) is a cerebrovascular disease in which stacks of dilated haemorrhagic capillaries form focally in the brain. Whether and how defective mechanotransduction, cellular mosaicism and inflammation interplay to sustain the progression of CCM diseases is unknown. Here, we reveal that CCM1- and CCM2-silenced endothelial cells enter into senescence associated with secretory phenotype (SASP) that they use to invade the extracellular matrix and attract surrounding wild-type endothelial and immune cells. Further, we demonstrate that this SASP is driven by the mechanical and molecular disorders provoked by ROCKs dysfunctions. By this, we identify CCM1/2 and ROCKs as parts of a scaffold controlling senescence, bringing new insights into the emerging field of the control of aging by cellular mechanics. This discovery reconciles the dysregulated traits of CCM1/2-deficient endothelial cells into a unique mechano-dependent endothelial fate that links perturbed mechanics to microenvironment remodelling and long-range activation of endothelial and immune cells.
Physically interacting beta-delta pairs in the regenerating pancreas revealed by single-cell sequencing
Authors: Yanowski Eran , Yacovzada Nancy-Sarah , David Eyal , Giladi Amir , Jaitin Diego , Farack Lydia , Egozi Adi , Ben-Zvi Danny , Itzkovitz Shalev , Amit Ido , Hornstein Eran
Published: February 2021

The endocrine pancreas is able to regenerate in response to insult, including by driving beta-cells into the cell division cycle. Until recently, communication between neighboring cells in islets of Langerhans was overlooked by single-cell genomic technologies, which require rigorous tissue dissociation into single cells. Here, we utilize sorting of physically interacting cells (PICs) with single-cell RNA-sequencing to systematically map cellular interactions in the regenerating endocrine pancreas. The cellular landscape of the regenerated pancreas features regeneration-associated endocrine populations.

We explore the unexpected heterogeneity of beta-cells in regeneration, including an interaction-specific program between paired beta and delta-cells. Our analysis suggests that the particular cluster of beta-cells that pair with delta-cells benefits from stress protection, implying that the interaction between beta and delta-cells safeguards against regeneration-associated challenges.
Key performance indicators for turboelectric distributed propulsion
Authors: Alrashed Mosab , Nikolaidis Theoklis , Pilidis Pericles , Jafari Soheil , Alrashed Wael
Published: February 2021

Purpose

Recent advancements in electrified transportation have been necessitated by the need to reduce environmentally harmful emissions. Accordingly, several aviation organisations and governments have introduced stringent emission reduction targets for 2050. One of the most promising technologies proposed for achieving these targets is turboelectric distributed propulsion (TeDP). The objective of this study was to explore and identify key indicators for enhancing the applicability of TeDP in air transportation.

Design/methodology/approach

An enhancement valuation method was proposed to overcome the challenges associated with TeDP in terms of technological, economic and environmental impacts. The result indicators (RIs) were determined; the associated performance indicators (PIs) were analysed and the key RIs and PIs for TeDP were identified. Quantitative measurements were acquired from a simulated TeDP case study model to estimate the established key PIs.

Findings

It was determined that real-world TeDP efficiency could be enhanced by up to 8% by optimising the identified key PIs.

Originality/value

This study is the first to identify the key PIs of TeDP and to include a techno-economic environmental risk analysis (TERA) based on the identified key PIs. The findings could guide developers and researchers towards potential focus areas to realise the adoption of TeDP.
Stakeholder participation in Lopburi Old Town conservation master plan
Authors: Sorat Tritsana , Rawangkarn Nug-Rob , Rawang Wee , Kantamaturapoj Kanang
Published: February 2021

Purpose

This study aims to evaluate the meaningful public participation in activities relating to the master plan development and, at the same time, propose some recommendations for improvement.

Design/methodology/approach

The study was carried out with in-depth interviews of 35 key-informants selected from various stakeholder groups involving in public participation activities. The evaluation frameworks for meaningful participation were developed from various scholars.

Findings

The evaluation showed that the public hearings partially met the criteria of information provision and representativeness. However, there are rooms for improvement on participation in decision-making process, social learning and influence over policy decision-making. Therefore, this study proposes two recommendations. First, more flexible form of public participation is needed to enable discussions among various groups of stakeholders. Second, the organizer should communicate with stakeholders about how their opinions influence the final master plan in order to create sense of belonging among community members.

Originality/value

This research developed the evaluation framework for public participation in old town conservation master plan in developing country.
Does insourcing of processes pay off?
Authors: Grela Grzegorz , Hofman Mariusz
Published: February 2021

Purpose

This study aims to examine whether insourcing of processes pays off and verifies key hypotheses regarding the financial ratios of organisations.

Design/methodology/approach

This paper randomly selects and then surveys 1996 organisations, of which 9.5% (190) stated that they used insourcing, 1.9% (37) made a decision to implement insourcing in the near future and 88.6% did not use insourcing. Then, for available firm data (100 insourcing firms and 100 firms without it), the financial statements of the surveyed companies were obtained to compare the most important financial ratios. The financial situation was compared at four-time points. The mean and median values of individual indicators were compared with the significance of relevant statistical tests.

Findings

A U-shaped curve of financial results in the time of enterprises that implemented insourcing and reverse U-shaped curve for enterprises that did not have insourcing are seen. Thus, the insourcing of processes pays off in the long run.

Research limitations/implications

Limitations exist in the generalisation of the results obtained, due to the limited number of samples qualified for analyses (limited reliable financial data).

Practical implications

The research highlights the importance of effective insourcing projects in the long term.

Originality/value

This study is the first to quantify the financial performance of companies that have used insourcing in comparison with a reference group. This paper defines insourcing and contributes to the growing number of studies on insourcing by bringing attention to the financial outcomes in the long run.