bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells
Authors: Tan Jingwen , Jia Yujie , Zhou Meixia , Fu Chengcheng , Tuhin Israth Jahan , Ye Jing , Monty Masuma Akter , Xu Nan , Kang Liqing , Li Minghao , Shao Jiaqi , Fang Xiaoyan , Zhu Hongjia , Yan Lingzhi , Qu Changju , Xue Shengli , Jin Zhengming , Chen Suning , Huang Haiwen , Xu Yang , Chen Jia , Miao Miao , Tang Xiaowen , Li Caixia , Yan Zhiqiang , Wu Depei , Yu Lei
Published: April 2022

Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment.
Association of waist circumference with blood pressure and familial dietary habits in preschool children: a cross-sectional study in northeastern China
Authors: Tang Xiao , Liu Yang , Hu Jiajin , Zhai Lingling , Jia Lihong , Ding Ning , Ma Yanan , Wen Deliang
Published: April 2022

Background

Childhood obesity increases the risk of elevated blood pressure (BP) in children. Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) are traditional obesity indices, but the extent to which these indices are associated with elevated BP in childhood remains debatable. Moreover, the familial dietary environment plays an important role in obesity, so it is necessary to determine the most relevant dietary factors for childhood obesity to prevent elevated BP. Our study aimed to identify the obesity indices that are most closely associated with elevated BP and then to determine the independent familial dietary factors for those obesity indices.

Method

A total of 605 children aged 2 to 6 years, as well as their parents, were involved in this study. The weight, height, WC and BP of the children were measured. Information on familial environments was obtained by questionnaires completed by the parents. BMI, WC and WHtR were standardized into z scores, and categorical variables of these three obesity indices were defined as BMI Category, WC Category and WHtR Category. Logistic regression was used to analyse the associations between all obesity indices and elevated BP. Multivariate linear regression and logistic regression were used to determine the independent factors for obesity indices.

Results

The obesity indices that were most closely associated with elevated BP were WC and WC Category. Parental BMI, birth weight, eating wheat as a staple food, appetite, eating speed, snacking while watching TV, parental encouragement to eat a diverse assortment of foods and drinking milk were independently associated with WC in both males and females. The risk of abdominal obesity increased 1.375 times in males and 1.631 times in females if appetite increased one level. If eating speed increased one level, the risk of abdominal obesity increased 1.165 times in males and 0.905 times in females. Females who drank milk more than 6 times per week had a 0.546 times lower risk of abdominal obesity.

Conclusion

WC was an anthropometric parameter more closely associated with elevated BP. In addition to genetics, some familial dietary factors involving eating preference, eating habits and parental feeding practice were independently associated with WC and abdominal obesity in preschool children.
Population-based estimates of age-specific cumulative risk of breast cancer for pathogenic variants in ATM
Authors: Renault Anne-Laure , Dowty James G. , Steen Jason A. , Li Shuai , Winship Ingrid M. , Giles Graham G. , Hopper John L. , Southey Melissa C. , Nguyen-Dumont Tú
Published: April 2022

Background

Multigene panel tests for breast cancer predisposition routinely includeATMas it is now a well-established breast cancer predisposition gene.

Methods

We includedATMin a multigene panel test applied to the Australian Breast Cancer Family Registry (ABCFR), a population-based case–control–family study of breast cancer, with the purpose of estimating the prevalence and penetrance of heterozygousATMpathogenic variants from the family data, using segregation analysis.

Results

The estimated breast cancer hazard ratio for carriers of pathogenicATMvariants in the ABCFR was 1.32 (95% confidence interval 0.45–3.87;P = 0.6). The estimated cumulative risk of breast cancer to age 80 years for heterozygous ATMpathogenic variant carriers was estimated to be 13% (95% CI 4.6–30).

Conclusions

AlthoughATMhas been definitively identified as a breast cancer predisposition gene, further evidence, such as variant-specific penetrance estimates, are needed to inform risk management strategies for carriers of pathogenic variants to increase the clinical utility of population testing of this gene.
The One Nutrition in Complex Environments (ONCE) study protocol: a cluster-randomized multi-level multi-sectoral intervention to improve nutrition in Uganda
Authors: Griswold Stacy P. , Marshak Anastasia , Fitzpatrick Merry , Lantagne Daniele , Shoenmakers Kate , Hebie Marlene , Radday Anne , De Groote Hugo , Mehta Saurabh , Gottlieb Greg , Webb Patrick , Ghosh Shibani
Published: April 2022

Objective

To implement and measure the effects of a multi-level multi-sectoral social behavior change (SBC) intervention in Agago District of Northern Uganda and to determine the potential for scale-up.

Intervention

Compare the Nutrition Impact and Positive Practice (NIPP) approach to a NIPP+ approach. The NIPP approach involves nutrition education and SBC, whereas the NIPP+ adds agricultural inputs, training, and tools to support improved farm and water quality practices. The intervention effect will be measured through lower levels of aflatoxin in grain, lower water contamination, and improved knowledge on nutrition and health.

Design

This is a three-arm cluster-randomized controlled superiority trial (cRCT). The study arms include the following: group 1: NIPP; group 2: NIPP+, and group 3: control. Groups 1 and 2 will receive a 12-week intervention (NIPP or NIPP+) with active monitoring and longitudinal follow-up at 2, 6, and 12 months post-intervention. Additionally, an in-depth process and performance evaluation of each intervention arm will be undertaken using quantitative and qualitative methods. A total of 60 clusters from 5 subcounties of the Agago district will be randomly selected, and 15 households per cluster will be recruited using specific inclusion/exclusion criteria for a total of 900 households (300/arm). Respondents for the qualitative portion will be purposely selected.

Analysis

We will collect data from all participants at 3 time points: baseline, endline, and 12 months post-intervention. The analysis will utilize intent-to-treat (ITT) using the initial randomization of the treatment arms to determine the overall impact of having the NIPP vs. NIPP+ vs. control. Mixed effects models will be used to determine the role of time-variant and invariant individual household, and community characteristics, as well as measures of exposure and integration on key outcome indicators. A difference-in-difference analysis (baseline/endline, baseline/12 months post-intervention, endline/12 months post-intervention) will also be used to triangulate findings.

Trial registration

NCT04209569. One Nutrition in Complex Environments (ONCE) Registered 24 December 2019
Oral Huzhang granules for the treatment of acute gouty arthritis: protocol for a double-blind, randomized, controlled trial
Authors: Zhou Mi , Hua Liang , Wang Yi-Fei , Chen Si-Ting , Yang Chun-mei , Zhang Ming , Li Xin , Li Bin
Published: April 2022

Background

Acute gouty arthritis (GA) is the main clinical manifestation and the most common initial symptom of gout. The treatment of acute GA involves the use of colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids. Because of the side effects of these drugs, their clinical applications are limited. The use of traditional Chinese medicine for the treatment of acute GA has unique advantages. The aim of this trial is to clarify the treatment efficacy, safety, and recurrence control efficacy ofHuzhanggranules (HZG) in patients with GA showing dampness-heat syndrome.

Methods/design

This double-blind, randomized, controlled trial was planned to be conducted between July 1, 2020, and December 31, 2022. A sample size of 267 participants (89 per group) with GA will be randomly assigned to three treatment groups in the ratio of 1:1:1: HZG, etoricoxib, and placebo groups. The study duration is 13 days, including a 1-day screening period, 5-day intervention period, and 1-week follow-up period. The primary outcome is analgesic effectiveness, assessed as pain in the worst-affected joint, which will be measured using the visual analog scale. Secondary outcomes include the patient’s assessment of pain in the primary study joint, patient’s global assessment of response to therapy, investigator’s global assessment of response to therapy, investigator’s assessment of tenderness and swelling of the study joint, and TCM syndromes. Furthermore, the number, nature, and severity of adverse events will be recorded.

Discussion

This study will provide evidence regarding the clinical efficacy and safety of Chinese medicine treatment for acute gouty arthritis. This study will provide noteworthy findings.

Trial registration

ClinicalTrials.govNCT04462666. Registered on July 05, 2020 (first version).
Worms and bugs of the gut: the search for diagnostic signatures using barcoding, and metagenomics–metabolomics
Authors: Papaiakovou Marina , Littlewood D. Timothy J. , Doyle Stephen R. , Gasser Robin B. , Cantacessi Cinzia
Published: April 2022

Gastrointestinal (GI) helminth infections cause significant morbidity in both humans and animals worldwide. Specific and sensitive diagnosis is central to the surveillance of such infections and to determine the effectiveness of treatment strategies used to control them. In this article, we: (i) assess the strengths and limitations of existing methods applied to the diagnosis of GI helminth infections of humans and livestock; (ii) examine high-throughput sequencing approaches, such as targeted molecular barcoding and shotgun sequencing, as tools to define the taxonomic composition of helminth infections; and (iii) discuss the current understanding of the interactions between helminths and microbiota in the host gut. Stool-based diagnostics are likely to serve as an important tool well into the future; improved diagnostics of helminths and their environment in the gut may assist the identification of biomarkers with the potential to define the health/disease status of individuals and populations, and to identify existing or emerging anthelmintic resistance.

Graphical Abstract
Alemtuzumab for refractory primary systemic vasculitis—a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE)
Authors: Gopaluni Seerapani , Smith Rona , Goymer Donna , Cahill Hugh , Broadhurst Elizabeth , Wallin Elizabeth , McClure Mark , Chaudhry Afzal , Jayne David
Published: April 2022

Background

Primary systemic vasculitis (PSV) is a heterogeneous group of autoimmune conditions. There is an unmet need for alternative therapies that lead to sustained remission in patients with refractory disease. Alemtuzumab, an anti-CD52 antibody, depletes lymphocytes for prolonged periods and, in retrospective studies, has induced sustained, treatment-free remissions in patients with refractory/relapsing vasculitis but has raised safety concerns of infection and secondary autoimmunity. This phase IIb clinical trial aimed to assess the efficacy and safety of alemtuzumab, at two different doses, in inducing remission in refractory vasculitis patients.

Methods

The ALEVIATE trial was a randomised, prospective, open-label, dose ranging clinical trial. Patients with refractory ANCA-associated vasculitis (AAV) or Behçet’s disease (BD) were randomised to receive either 60 mg or 30 mg alemtuzumab. Treatments were administered at baseline and 6 months or earlier where clinically appropriate. A maximum of three treatments were allowed within the 12-month study period.

Results

Twenty-three patients received at least one dose of alemtuzumab. Twelve had AAV, and 11 a diagnosis of BD. The median age was 40 years (range 28–44), with a prior disease duration of 61 months (42–103). Sixteen (70%) achieved either complete (6/23, 26%) or partial (10/23, 44%) response at 6 months. Eight (35%) maintained remission to the end of the trial without relapse. Ten severe adverse events were observed in 7 (30%) patients; 4 were related to alemtuzumab. There were no differences in clinical endpoints between the 60 and 30 mg alemtuzumab treatment groups.

Conclusion

In a selected group of refractory vasculitis patients, alemtuzumab led to remission in two thirds of patients at 6 months. Remission was maintained to 12 months in a third of the patients, and the safety profile was acceptable.

Trial registration

ClinicalTrials.gov identifier: NCT01405807, EudraCT Number: 2009-017087-17. Registered on April 07, 2011.
A multiepitope vaccine encoding four Eimeria epitopes with PLGA nanospheres: a novel vaccine candidate against coccidiosis in laying chickens
Authors: Yu ZhengQing , Chen SiYing , Huang JianMei , Ding WenXi , Chen YuFeng , Su JunZhi , Yan RuoFeng , Xu LiXin , Song XiaoKai , Li XiangRui
Published: April 2022

With a worldwide distribution, Eimeria spp. could result in serious economic losses to the poultry industry. Due to drug resistance and residues, there are no ideal drugs and vaccines against Eimeria spp. in food animals. In the current study, a bioinformatics approach was employed to design a multiepitope antigen, named NSLC protein, encoding antigenic epitopes of E. necatrix NA4, E. tenella SAG1, E. acervulina LDH, and E. maxima CDPK. Thereafter, the protective immunity of NSLC protein along with five adjuvants and two nanospheres in laying chickens was evaluated. Based on the humoral immunity, cellular immunity, oocyst burden, and the coefficient of growth, the optimum adjuvant was evaluated. Furthermore, the optimum immune route and dosage were also investigated according to the oocyst burden and coefficient of growth. Accompanied by promoted secretion of antibodies and enhanced CD4+ and CD8+ T lymphocyte proportions, NSLC proteins entrapped in PLGA nanospheres were more effective in stimulating protective immunity than other adjuvants or nanospheres, indicating that PLGA nanospheres were the optimum adjuvant for NSLC protein. In addition, a significantly inhibited oocyst burden and growth coefficient promotion were also observed in animals vaccinated with NSLC proteins entrapped in PLGA nanospheres, indicating that the optimum adjuvant for NSLC proteins was PLGA nanospheres. The results also suggested that the intramucosal route with PLGA nanospheres containing 300 μg of NSLC protein was the most efficient approach to induce protective immunity against the four Eimeria species. Collectively, PLGA nanospheres loaded with NSLC antigens are potential vaccine candidates against avian coccidiosis.
A two-stage detection method of copy-move forgery based on parallel feature fusion
Authors: Ye Wujian , Zeng Qingyuan , Peng Yihang , Liu Yijun , Chang Chin-Chen
Published: April 2022

The copy-move forgery refers to the copying and pasting of a region of the original image into the target region of the same image, which represents a typical tampering method with the characteristics of easy tampering and high-quality tampering. The existing single feature-based methods of forgery detection have certain shortcomings, such as high false alarm rate, low robustness, and low detection accuracy. To address these shortcomings, this paper proposes an improved two-stage detection method based on parallel feature fusion and an adaptive threshold generation algorithm. Firstly, the SLIC super-pixels segmentation algorithm is used for image preprocessing, and a similar region extraction algorithm without threshold is employed to obtain the suspected tampering regions with high similarity. Secondly, the parallel fusion feature is obtained based on the SIFT and HU features to express the characteristics of local regions. Then, the corresponding threshold value is generated based on the histogram of oriented gradient (HOG) to describe the texture characteristics of the obtained regions, which acts as a criterion to judge whether a region has been forged or not. The experimental results show that the proposed method outperforms the existing methods, achieving the accuracy of 99.01% and 98.5% on the MICC-F220 and MICC-F2000 datasets respectively. In addition, the proposed method has stronger robustness performance on COMOFOD dataset than the comparison methods.
Deep learning for end-to-end subsurface modeling and interpretation: An example from the Groningen gas field
Authors: Abubakar Aria , Di Haibin , Kaul Anisha , Li Cen , Li Zhun , Simoes Vanessa , Truelove Leigh , Zhao Tao
Published: April 2022

Subsurface interpretation and modeling are crucial to the success of reservoir exploration and production, which often involves integrating multiple types of subsurface data and accomplishing a series of subtasks consecutively and/or in parallel. Those tasks include data processing and conditioning, structural mapping, property modeling, and others. With the emergence of machine learning (ML), each component of the subsurface modeling and interpretation workflow now has elements of ML automation incorporated into individual steps. However, there have been few attempts to generate an integrated end-to-end workflow that incorporates ML at every stage. This paper presents an end-to-end solution for subsurface modeling and interpretation that is powered by multiple convolutional neural networks (CNNs). Its performance is demonstrated on the Groningen gas field. The workflow can be subdivided into four parts, with the initial phase focusing on data preconditioning, particularly log quality control and reconstruction. Phase two focuses on seismic property estimation (i.e., relative geologic time) and structural feature identification and extraction (i.e., fault and salt). Phase three combines seismic feature extraction, log data, derived seismic properties, and interpretations to generate a 3D rock property model containing modeled gamma ray, density, velocity, and porosity properties. The final component is to validate the estimated subsurface properties by CNN-based seismic image simulation. The results demonstrated in the Groningen field show high accuracy, strong lateral consistency, and a good match with the dominant subsurface features documented in this area, including the Zechstein salt, the complex fault system, and the Rotliegend reservoir model. We conclude that this end-to-end workflow can be readily applied to other fields to provide a one-click solution for efficient subsurface modeling and interpretation.
Reviews
Authors: Green William
Published: April 2022

The Art and Science of Seismic Interpretation, by Christopher Liner and Thomas McGilvery, ISBN 978-3-030-03996-7, 2019, Springer, 116 p. Satellite Gravimetry and the Solid Earth — Mathematical Foundations, by Mehdi Eshagh, ISBN 978-0-12-816936-0, 2020, Elsevier, 486 p.
Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial
Authors: Eckstein Olive S. , Allen Carl E. , Williams P. Mickey , Roy-Chowdhuri Sinchita , Patton David R. , Coffey Brent , Reid Joel M. , Piao Jin , Saguilig Lauren , Alonzo Todd A. , Berg Stacey L. , Ramirez Nilsa C. , Jaju Alok , Mhlanga Joyce , Fox Elizabeth , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Janeway Katherine A. , Seibel Nita L. , Parsons D. Williams
Published: April 2022

PURPOSE

The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib.

METHODS

Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib.

RESULTS

Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), inactivating mutations in NF1 (n = 7), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG ( NF1 mutation, six cycles; KRAS mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug.

CONCLUSION

A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.
Long-read Amplicon Sequencing of the CYP21A2 in 48 Thai Patients With Steroid 21-Hydroxylase Deficiency
Authors: Tantirukdham Nithiphut , Sahakitrungruang Taninee , Chaisiwamongkol Ratikorn , Pongpanich Monnat , Srichomthong Chalurmpon , Assawapitaksakul Adjima , Buasong Aayalida , Tongkobpetch Siraprapa , Yeetong Patra , Shotelersuk Vorasuk
Published: April 2022

Context

Congenital adrenal hyperplasia is most commonly caused by 21-hydroxylase deficiency (21-OHD), an autosomal recessive disorder resulting from biallelic pathogenic variants (PVs) in CYP21A2. With a highly homologous pseudogene and various types of single nucleotide and complex structural variants, identification of PVs in CYP21A2 has been challenging.

Objective

To leverage long-read next-generation sequencing combined with locus-specific polymerase chain reaction (PCR) to detect PVs in CYP21A2 and to determine its diagnostic yield in patients with 21-OHD.

Methods

Forty-eight Thai patients with 21-OHD comprising 38 sporadic cases and 5 pairs of siblings were enrolled. Two previously described locus-specific PCR methods were performed. Amplicons were subject to long-read sequencing.

Results

Ninety-six PVs in CYP21A2 in the 48 patients were successfully identified. The combined techniques were able to detect 26 structural chimeric variants (27%; 26/96) in 22 patients with 18 having monoallelic and 4 having biallelic chimeras. The remaining PVs were pseudogene-derived mutations (63%; 60/96), entire gene deletions (2%; 2/96), missense variants (3%; 3/96), a splice-site variant (2%; 2/96), frameshift variants (2%; 2/96), and a nonsense variant (1%; 1/96). Notably, a splice-site variant, IVS7 + 1G > T, which was identified in a pair of siblings, has not previously been reported.

Conclusions

Our approach exploiting locus-specific PCR and long-read DNA sequencing has a 100% diagnostic yield for our cohort of 48 patients with 21-OHD.
TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila
Authors: Deshpande Rujuta , Lee Byoungchun , Qiao Yuemeng , Grewal Savraj S.
Published: April 2022

When infected by enteric pathogenic bacteria, animals need to initiate local and whole-body defence strategies. Although most attention has focused on the role of innate immune anti-bacterial responses, less is known about how changes in host metabolism contribute to host defence. Using Drosophila as a model system, we identify induction of intestinal target-of-rapamycin (TOR) kinase signalling as a key adaptive metabolic response to enteric infection. We find that enteric infection induces both local and systemic induction of TOR independently of the Immune deficiency (IMD) innate immune pathway, and we see that TOR functions together with IMD signalling to promote infection survival. These protective effects of TOR signalling are associated with remodelling of host lipid metabolism. Thus, we see that TOR is required to limit excessive infection-mediated wasting of host lipid stores by promoting an increase in the levels of gut- and fat body-expressed lipid synthesis genes. Our data support a model in which induction of TOR represents a host tolerance response to counteract infection-mediated lipid wasting in order to promote survival.

This article has an associated First Person interview with the first author of the paper.
Annexin A2 and Ahnak control cortical NuMA–dynein localization and mitotic spindle orientation
Authors: Pascal Aude , Gallaud Emmanuel , Giet Regis , Benaud Christelle
Published: April 2022

Proper mitotic spindle orientation depends on the correct anchorage of astral microtubules to the cortex. It relies on the remodeling of the cell cortex, a process not fully understood. Annexin A2 (Anx2; also known as ANXA2) is a protein known to be involved in cortical domain remodeling. Here, we report that in HeLa cell early mitosis, Anx2 recruits the scaffold protein Ahnak at the cell cortex facing spindle poles, and the distribution of both proteins is controlled by cell adhesion. Depletion of either protein or impaired cortical Ahnak localization result in delayed anaphase onset and unstable spindle anchoring, which leads to altered spindle orientation. We find that Ahnak is present in a complex with dynein–dynactin. Furthermore, Ahnak and Anx2 are required for correct dynein and NuMA (also known as NUMA1) cortical localization and dynamics. We propose that the Ahnak–Anx2 complex influences the cortical organization of the astral microtubule-anchoring complex, and thereby mitotic spindle positioning in human cells. This article has an associated First Person interview with the first author of the paper.
Emerin regulation of nuclear stiffness is required for fast amoeboid migration in confined environments
Authors: Lavenus Sandrine B. , Vosatka Karl W. , Caruso Alexa P. , Ullo Maria F. , Khan Ayesha , Logue Jeremy S.
Published: April 2022

When metastasizing, tumor cells must traverse environments with diverse physicochemical properties. Recently, the cell nucleus has emerged as a major regulator of the transition from mesenchymal to fast amoeboid (leader bleb-based) migration. Here, we demonstrate that increasing nuclear stiffness through elevating lamin A, inhibits fast amoeboid migration in melanoma cells. Importantly, nuclei may respond to force through stiffening. A key factor in this process is the inner nuclear membrane (INM) protein emerin. Accordingly, we determined the role of emerin in regulating fast amoeboid migration. Strikingly, we found that both the up- and downregulation of emerin results in an inhibition of fast amoeboid migration. However, when key Src phosphorylation sites were removed, upregulation of emerin no longer inhibited fast amoeboid migration. Interestingly, as measured by using a Src biosensor, activity of Src was low in cells within a confined environment. Thus, the fast amoeboid migration of melanoma cells depends on the precise calibration of emerin activity.
A perspective on insect water balance
Authors: O’Donnell Michael J.
Published: April 2022

Insects have a large ratio of surface area to volume because of their small size; thus, they face the potential for desiccation in the terrestrial environment. Nonetheless, they constitute over half of identified species and their success on land can be attributed, in part, to adaptations that limit water loss and allow for effective gains of water from food, fluids or atmospheric water vapour. Reduction of water loss from the gut involves sophisticated mechanisms of ion recycling and water recovery by epithelia of the Malpighian tubules and hindgut. Water loss across the body surface is greatly reduced by the evolution of very thin but highly impermeable lipid-rich layers in the epicuticle. Respiratory water loss can be reduced through effective spiracular control mechanisms and by mechanisms for convective rather than diffusive gas exchange. In addition to extracting water from food sources, some insects are capable of absorption of atmospheric water vapour through processes that have evolved independently in multiple groups.
High Marginal Tax Rates on the Top 1 Percent? Lessons from a Life-Cycle Model with Idiosyncratic Income Risk
Authors: Kindermann Fabian , Krueger Dirk
Published: April 2022

This paper argues that high marginal labor income tax rates on top earners are an effective tool for social insurance even when households have high labor supply elasticity, households make dynamic savings decisions, and policies have general equilibrium effects. We construct a large-scale overlapping generations model with uninsurable labor productivity risk, show that it has a realistic wealth distribution, and numerically characterize the optimal top marginal rate. We find that marginal tax rates for top 1 percent earners of 79 percent are optimal as long as the model earnings and wealth distributions display a degree of concentration as observed in US data. (JEL D15, D31, H21, H24, H55, J22, J31)
Sectoral Heterogeneity and Monetary Policy
Authors: Kreamer Jonathan
Published: April 2022

Since sectors differ in their sensitivity to interest rates, monetary policy produces inefficient sectoral fluctuations. In a model with sectoral heterogeneity, I show that policymakers should weight sectors proportionally to their interest elasticities, account for dynamic demand effects from durable goods, and systematically utilize forward guidance to reduce sectoral volatility. A calibrated model confirms these recommendations and finds that neglecting sectoral volatility produces substantial welfare losses. The best-performing policy rule stabilizes a sectorally weighted measure of inflation, plus lags of past durable inflation. (JEL E12, E23, E24, E31, E32, E43, E52)
Πειραματική μελέτη βασικών μηχανισμών δράσης της κροκετίνης στην πρόληψη της νεφρικής βλάβης λόγω του συνδρόμου ισχαιμίας - επαναιμάτωσης
Authors: Μιχαήλ Κωνσταντίνος
Published: April 2022

Η παρούσα εργασία παρουσιάζει αποτελέσματα που υποστηρίζουν τον προστατευτικό ρόλο της κροκετίνης στη νεφρική βλάβη που προκαλείται από ισχαιμία / επαναιμάτωση. Επιπλέον, φαίνεται ότι αυτή η δράση περιλαμβάνει την επαγωγή έκφρασης miR-127. Θα ήταν ιδιαίτερα ενδιαφέρον να διερευνηθεί το ενδεχόμενο προληπτικής δράσης αυτής της ουσίας (δηλαδή η χορήγηση κροκετίνης πριν από την πρόκληση σοκ I / E) και η επανειλημμένη χορήγησή της μετά το σοκ για να καθοριστεί σε ποιο βαθμό αυτή η ουσία είναι ικανή να αναστέλλει τις βλάβες που προκαλούνται. Ωστόσο, αυτές οι προτάσεις μπορούν να αποτελέσουν τη βάση για μελλοντικές εργασίες για να αποδειχθεί ότι τα miRNAs έχουν τη δυνατότητα να είναι αποτελεσματικοί βιοδείκτες και θεραπευτικοί στόχοι για μεταγενέστερη θεραπεία. Ως εκ τούτου, τα miRNAs αντιπροσωπεύουν νέους θεραπευτικούς στόχους για μια εξουθενωτική ασθένεια που συνεχίζει να αυξάνεται σε παγκόσμιο επίπεδο και για την οποία λείπουν πλήρως αποτελεσματικές θεραπείες. Από τα αποτελέσματα που προέκυψαν και από πρόσφατες μελέτες που έχουν δημοσιευθεί θα μπορούσε πιθανά η κροκετίνη σε συνδυασμό με επιλεγμένα miRNAs να χορηγείται με την τεχνολογία των νανοσωματιδίων σε περιπτώσεις νεφρικής δυσλειτουργίας/ βλάβης. Με την παρούσα μελέτη προκαλώντας τεχνητή ισχαιμία/επαναιμάτωση (Ι/Ε) σε μύες και έπειτα από χορήγηση της κροκετίνης, είδαμε περιορισμό των στοιχείων φλεγμονής και του βαθμού καταστροφής του επιθηλίου, αλλαγή βιοχημικών παραμέτρων και μοριακού προφίλ. Μελλοντικές μελέτες μένει να διαλευκάνουν τους μηχανισμούς μέσω των οποίων η κροκετίνη δρα ευεργετικά επηρεάζοντας όλα τα επίπεδα (μοριακά, ιστολογικά & βιοχημικά)
Editorial
Authors: Cyranka Katarzyna
Published: April 2022

Here comes the first 2022 issue of the Archives of Psychiatry and Psychotherapy. It is more than a week since we, or at least the most of us, live in two parallel realities. One is the Russian invasion on Ukraine that not only catched our attention so intensively but also made us aware that Europe is not such a safe region as we thought and the geopolitical situation brings many uncertainties. Many of us have mobilized to bring support to our Ukrainian neighbours. The second reality is the continuation of our everydayness, including clinical and research activities, family and social connections. For us, mental health professionals, it seems obvious that these two realities will finally unite as we should be prepared to bring help to the victims of war and their relatives.
Mental resilience and professional burnout among teachers
Authors: Pluskota Małgorzata , Zdziarski Krzysztof
Published: April 2022

W artykule podjęto próbę przedstawienia zależności między prężnością psychologiczną, a wypaleniem zawodowym nauczycieli szkół podstawowych, ponadpodstawowych oraz uczelni wyższych. W pierwszej części zostały przybliżone zagadnienia prężności psychicznej oraz wypalenia zawodowego. Do przeprowadzenia badania wykorzystano Kwestionariusz Oceny Prężności (KOP-26) i Kwestionariusz LBQ, który ocenia poziom wypalenia zawodowego.  Dalsza część artykułu przedstawia wyniki badań w obszarze zależności między prężnością psychiczną i jej składowymi (kompetencjami osobistymi, relacjami rodzinnymi oraz kompetencjami społecznymi) a syndromem wypalenia zawodowego. Nauczyciele  wykazali istotne różnice pod względem poziomu prężności psychicznej i  różnili się stopniem wypalenia zawodowego. Wykazano silną korelację pomiędzy prężnością psychiczną a wypaleniem zawodowym nauczycieli. Nie zauważono wyższego stopnia wypalenia zawodowego wśród nauczycieli niższych etapów nauczania.  Nauczyciele uczelni wyższych charakteryzowali się minimalnie wyższym stopniem wypalenia zawodowego. Ponadto wykazano, że wsparcie rodziny ma znaczący związek w niwelowaniu wypalenia zawodowego. We wnioskach wskazano potrzebę wprowadzenia profilaktyki wypalenia zawodowego wśród nauczycieli poprzez psychoedukację w zakresie umiejętności składających się na poszczególne elementy prężności psychicznej oraz pogłębienie badań wśród konkretnej grupy nauczycieli.
Methods for Eliciting Informative Prior Distributions: A Critical Review
Authors: Falconer Julia R. , Frank Eibe , Polaschek Devon L. L. , Joshi Chaitanya
Published: April 2022

Eliciting informative prior distributions for Bayesian inference can often be complex and challenging. Although popular methods rely on asking experts probability-based questions to quantify uncertainty, these methods are not without their drawbacks, and many alternative elicitation methods exist. This paper explores methods for eliciting informative priors categorized by type and briefly discusses their strengths and limitations. Most of the review literature in this field focuses on a particular type of elicitation approach. The primary aim of this work, however, is to provide a more complete yet macro view of the state of the art by highlighting new (and old) approaches in one clear easy-to-read article. Two representative applications are used throughout to explore the suitability, or lack thereof, of the existing methods, one of which highlights a challenge that has not been addressed in the literature yet. We identify some of the gaps in the present work and discuss directions for future research.
Gradient Sampling Methods with Inexact Subproblem Solutions and Gradient Aggregation
Authors: Curtis Frank E. , Li Minhan
Published: April 2022

Gradient sampling (GS) methods for the minimization of objective functions that may be nonconvex and/or nonsmooth are proposed, analyzed, and tested. One of the most computationally expensive components of contemporary GS methods is the need to solve a convex quadratic subproblem in each iteration. By contrast, the methods proposed in this paper allow the use of inexact solutions of these subproblems, which, as proved in the paper, can be incorporated without the loss of theoretical convergence guarantees. Numerical experiments show that, by exploiting inexact subproblem solutions, one can consistently reduce the computational effort required by a GS method. Additionally, a strategy is proposed for aggregating gradient information after a subproblem is solved (potentially inexactly) as has been exploited in bundle methods for nonsmooth optimization. It is proved that the aggregation scheme can be introduced without the loss of theoretical convergence guarantees. Numerical experiments show that incorporating this gradient aggregation approach can also reduce the computational effort required by a GS method.
Triadic Advocacy Work
Authors: Jackson Summer Rachel , Kellogg Katherine Cissel
Published: April 2022

Scholars of street-level bureaucracy and institutional research focus primarily on the relationships between advocates and their larger bureaucratic and social systems, assuming that advocates have little need to satisfy their beneficiaries. We find otherwise in our two-year ethnographic study of public defenders advocating for disadvantaged clients in interactions with district attorneys. In our analysis of 82 advocacy opportunities, we demonstrate that, when existing bureaucratic and social systems put beneficiaries at a disadvantage, advocates may be concerned about managing fraught relationships with their beneficiaries in addition to navigating barriers within the bureaucratic and social systems. We further show a tension between the two; ironically, engaging in advocacy work on behalf of beneficiaries can lead to beneficiary mistrust. As a result, advocates engage in triadic advocacy work—managing impressions with their beneficiaries while also influencing powerful actors within the system on behalf of these same beneficiaries. Understanding the process by which advocates navigate this tension is critical to understanding beneficiary outcomes. By reconceptualizing advocacy work as a triadic process among advocate, bureaucratic system, and beneficiary rather than as a dyadic process between advocate and bureaucratic system, this paper develops new theory about how advocates can attempt to garner benefits that advance the rights and opportunities of the disadvantaged.
Preventing yellow fever in travellers: an update
Authors: Gawthrop Mary
Published: April 2022

Yellow fever is a viral haemorrhagic disease spread by day-biting mosquitoes. Infection can cause an acute, potentially fatal illness. Yellow fever is found in tropical regions of Africa and Central and South America and one region in the Caribbean. Avoiding mosquito bites is recommended for anyone living in or travelling to risk areas and the World Health Organization advises yellow fever vaccine is the most important way to prevent yellow fever. Risk areas and vaccine recommendations can change rapidly. Nurses advising travellers must ensure they are familiar with appropriate sources of information and stay up to date with current international yellow fever vaccine recommendations. Yellow fever vaccine is only available at designated UK Yellow Fever Vaccination Centres.
The “Time-Makam Analysis Model” as a graphic notation: A playful tool for collaborative improvised music
Authors: Hatipoğlu Zeynep Ayşe
Published: April 2022

This study seeks to explore the creative performing processes that arise from the use of graphic scores. To achieve this, it uses the Time-Makam Analysis Model to demonstrate how this type of notation can produce “playful” creative processes that are open to evaluation from an ethnomusicological perspective. The study presents a practical, experimental, and multidisciplinary approach to graphic notation, it discusses the individual and collective relationships that performers have with a score of this type, and examines the spontaneous decision-making processes involved. The study is also intended to support performers’ collective creative decision-making, their playful thinking, and their improvisational skills. First, the introduction gives an overview of the concept of notation and provides a historical perspective for contemporary graphic scores. This is followed by an examination of the Time-Makam Analysis Model and its association with graphic notation, and a psychological discussion of creative, playful thinking processes. The final section contains field notes from two performances in which the author of this study took part: an online recording by the SAVT improvisation trio (Elif Canfeza Gündüz classical kemenche, Merve Salgar tanbur, and Zeynep Ayşe Hatipoğlu violoncello) and a real time collaboration with Ülkü Çağlayan (body movement and violoncello).
Hydroxyapatite based on Abalone Mussel Shells Coating on Titanium Alloy using Electrophoretic Deposition Dip Coating as a Bone Implant Candidate
Authors:   Department of Physics, Faculty of Mathematics and Natural Science, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia, Kristianto Nicholas Adi , Sari Mona ,   Department of Physics, Faculty of Mathematics and Natural Science, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia, Yusuf Yusril ,   Department of Physics, Faculty of Mathematics and Natural Science, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Published: April 2022

Abstract In this study, hydroxyapatite (HA) from abalone mussel shells (Haliotis asinina) is synthesized using the precipitation method with a stirring time of 30 min and a calcination temperature of 1000°C. HA was used for coating Ti alloy using the electrophoretic deposition dip coating (EP2D) method. The coating applied three variations, including the DC voltages variation of 25 V and 50 V, the withdrawal speeds of 0.1 mm/s, 0.5 mm/s, 1 mm/s, and the calcination temperatures of 750°C and 950°C. Energy dispersive X-Ray spectroscopy (EDS) revealed the Ca/P molar ratio of HA was 1.63, which is close to the stoichiometric ratio of HA at 1.67. The distance between the crystal planes of the HA was 2.81Å. This result also is relative to the crystal plane of the HA at 2.88Å. The EP2D process and the calcination temperature treatment will remove the B-type carbonate apatite phase, so the purity of the HA layer is higher. SEM results show that the HA layer formed was more homogeneous and thicker at the DC voltage of 50 V and the withdrawal velocity of 0.1 mm/s. At this voltage and velocity, minor cracking and agglomeration were produced. The density of the HA layer was higher with increasing calcination temperature and DC voltages. Keywords: Hydroxyapatite, Titanium Alloy, Coating, Electrophoretic Deposition Dip Coating
Transfibular total ankle arthroplasty
Authors: Maccario Camilla , Paoli Tommaso , Romano Fausto , D’Ambrosi Riccardo , Indino Cristian , Usuelli Federico G.
Published: April 2022

Aims

This study reports updates the previously published two-year clinical, functional, and radiological results of a group of patients who underwent transfibular total ankle arthroplasty (TAA), with follow-up extended to a minimum of five years.

Methods

We prospectively evaluated 89 patients who underwent transfibular TAA for end-stage osteoarthritis. Patients’ clinical and radiological examinations were collected pre- and postoperatively at six months and then annually for up to five years of follow-up. Three patients were lost at the final follow-up with a total of 86 patients at the final follow-up.

Results

A total of 86 patients were evaluated at a mean follow-up of 65.4 months (60 to 90). At five-year follow-up, statistically significant improvements (p < 0.001) were found in the mean American Orthopaedic Foot & Ankle Society Ankle Hindfoot Score (from 33.8 (SD 14.3) to 86.1 (SD 8.8)), visual analogue scale for pain (from 8.5 (SD 1.7) to 1.5 (SD 1.2)), Short Form-12 Physical and Mental Component Scores (from 29.9 (SD 6.7) and 43.3 (SD 8.6) to 47.3 (SD 7.5) and 52.2 (SD 8.0), respectively), and mean ankle dorsiflexion and plantarflexion (from 6.2° (SD 5.5°) and 9.6° (SD 5.8°) to 23.9° (SD 7.7°) and 16.9° (SD 7.2°), respectively). Radiologically, the implants maintained neutral alignment without subsidence. Tibial or talar radiolucency was found in eight patients, but none of these patients was symptomatic. At five-year follow up, 97.7% of implants (95% confidence interval 91.2 to 99.4) were free from revision or removal with 84 implants at risk. We recorded two cases (2.3%) of failure for septic loosening.

Conclusion

Transfibular TAA is safe and effective with a high survival rate at mid-term follow-up and satisfactory clinical and radiological results. Further studies are required to determine the long-term performance of these implants. Cite this article: Bone Joint J 2022;104-B(4):472–478.