bluuebunny/crossref_metadata_2025 huggingface dataset:
Residing in communal senior housing: situating the ageing self within debates of the universal welfare state
Authors: Vasara Paula
Published: October 2022

Currently, Nordic welfare societies are at a crossroads. Ongoing demographic changes – such as ageing, accompanied by challenges in financing adequate services for all – have highlighted the need to consider the roles of citizens and the state in a novel way. Balancing rights and responsibilities has always been at the core of universalism, even though, traditionally, trust in the welfare state's ability to fulfil its basic function of providing necessary services for all has been strong. However, of late, subtle signs of change have become more visible, and in practice, older people's housing and care provisions have been marked by the state's withdrawal. By employing narrative analysis, this study explores, through the experiences of residents in age-related intermediate housing, how older people make use of, negotiate and embed the arguments being made in societal debates on the rights and responsibilities of ageing citizens. The accounts showcase the ways in which these narrators are able to accommodate the sometimes contradictory elements in their narration, accept the demand for increased responsibility for their later-life arrangements and construct plausible portraits of themselves as morally responsible citizens. These subtle negotiations and the acceptance of personal responsibility indicate a change in their perceptions of and expectations from the citizens and the state. Whilst the findings comprise stories of good outcomes, they also question the legitimacy of the current welfare system's universalism and its ability to guide the way to achieve equally good outcomes for all in the future.
Cooperative control strategy of wheel-legged robot based on attitude balance
Authors: Shen Yaojie , Chen Guangrong , Li Zhaoyang , Wei Ningze , Lu Huafeng , Meng Qingyu , Guo Sheng
Published: October 2022

To integrate the uneven terrain adaptivity of legged robots and the fast capacity of wheeled robots on even terrains, a four wheel-legged robot is addressed and the cooperative control strategy of wheels and legs based on attitude balance is investigated. Firstly, the kinematics of wheel-legged robot is analyzed, which contains the legged and wheeled motion modal. Secondly, the cooperative control strategy of wheel-legged robot based on attitude balance is proposed. The attitude is calculated by using the quaternion method and complementary filtering, and the attitude stability control of the wheel-legged robot is studied. The trajectory planning of leg motion including walk and trot gait is implemented, and the differential control of wheeled motion is deduced. And then, the cooperative motion control of wheels and legs is achieved by keeping the attitude balance of robot body. Finally, a small prototype is set up to validate the feasibility and effectiveness of proposed method. The experimental results show that the established wheel-legged robot can do walk, trot, and wheel-leg compound motion to overcome many complex terrains and environments.
Mothers of Mid-century Spanish Families: Agents of Social Change in the Context of Dictatorship and Patriarchy
Authors: Chuliá Elisa
Published: October 2022

This article focuses on how middle-class families created during the second half of the Francoist dictatorship in Spain decisively contributed to improving the educational level of the biggest generation in Spanish society, born between the late 1950s and the mid-1970s. Mothers played a particularly important role in this ‘educational shift’. Even though under Francoism legislation and moral habits implied female subordination in virtually all spheres of life, many of those mothers were willing and able to promote their children's education irrespective of their gender. Making use of oral history, the article offers an account of how mothers of the Spanish baby boom generation entered into marriage, organised their daily lives at home and took decisions regarding their children's welfare and education. Today in their old age, these women deserve to be considered important agents of the remarkable social change Spain has experienced during the last decades.
Design of an E-sectoral horn based on PRGW technology for 5G applications
Authors: El-Din M. S. H. Salah , Shams Shoukry I. , Allam A. M. M. A. , Gaafar Abdelhamid , Elhennawy Hadia M. , Sree Mohamed Fathy Abo
Published: October 2022

E-plane sectoral horn antenna based on printed ridge gap waveguide (PRGW) technology is designed for 5G applications. It is implemented on the top plate of the PRGW structure to avoid the losses and dispersion associated with conventional feeding mechanisms. The quasi-transverse electromagneticPRGW-based antenna is excited through a planar microstrip transition. First, the single horn antenna element is introduced with the microstrip feeding section. It shows an impedance bandwidth of fractional bandwidth 26% from 45.7 to 55.4 GHz with the realized gain of 12.7 dBi and radiation efficiency of 90%. In order to maximize the realized gain, a four-element linear horn array is introduced. The same impedance bandwidth is maintained with the array having a gain of 18.6 dBi from 45.7 to 55.4 GHz. The overall antenna array performance in the entire operating frequency range is stable with a radiation efficiency around 85%. Three matching sections are implemented to achieve better impedance matching. One is used to match the horn with the feeding aperture via the PRGW line. Another section is designed to match microstrip transition with PRGW ridge. Finally, two-stage quarter wavelength transformers are required to match the power divider with the array feeding network. A prototype of single-element horn antenna was fabricated to verify the concept of the design. Simulated and measured results show that the proposed antenna can operate in the frequency band of 45–55 GHz with good agreement of radiation performance. Moreover, the proposed designs are implemented and simulated using two microwave simulation tools (CST and HFSS) to verify the radiation performance, which exhibits good agreement. The design of an E-sectoral horn antenna and its array with high gain based on PRGW is demonstrated for the first time which is considered a novel issue. It can be integrated with other passive and active elements in communication systems. Thus, it can be a valuable component in 5G communication due to its high gain, compact size and ultra-wide band.
“You feel a bit unsexy sometimes”: The psychosocial impact of a spinal cord injury on sexual function and sexual satisfaction
Authors: Barrett Olivia E. C. , Mattacola Emily , Finlay Katherine A.
Published: October 2022

Study design

A qualitative, semi-structured interview design.

Objectives

This study aimed to identify, from the perspective of people living with a Spinal Cord Injury (SCI), the primary psychosocial barriers and facilitators that impact on their sexual function and sexual satisfaction post-injury.

Setting

Community-dwelling sample of people with SCI in England, United Kingdom

Methods

Semi-structured interviews with twenty people with SCI (15 males; 5 females) were conducted using an 8-item interview schedule. Inductive thematic analysis was undertaken of verbatim transcripts coded using Braun and Clarke’s (2021) six phases of thematic analysis.

Results

Six inductive themes were generated, collectively describing the psychosocial barriers and facilitators impacting on sexual function and satisfaction post-SCI: (1) Internalising societal views and stigmatisation; (2) Diminished sexual confidence; (3) Navigating communication; (4) Managing relationship dynamics; (5) Lack of sexual support provision; and (6) Intervention development recommendations.

Conclusion

Sexual function and satisfaction are highly challenging areas of rehabilitation for males and females living with SCI. Increased efforts are needed to educate others in society to overcome the negative stereotypical attitudes obstructing acceptance of sex despite disability. Countering sexual stigmatisation for people with SCI would facilitate growth in sexual confidence. Techniques to enhance interpersonal sexual communication and involve the partner/spouse in regaining mutual sexual satisfaction are foundational. The current study highlighted key outpatient-based recommendations for intervention development, clarifying primary targets for future SCI-focused sexual therapeutic work.
Koller and the dawn of cancer cytogenetics
Authors: Norbury Chris J.
Published: October 2022

Shortly before the DNA era began, PC Koller described lagging chromosomes and chromosome numerical abnormalities in human carcinomas. While present-day cancer geneticists would question some of Koller’s conclusions, this study ultimately contributed to the realisation that chromosomal instability is a widespread feature of solid tumours.
Advancing clinical and translational research in germ cell tumours (GCT): recommendations from the Malignant Germ Cell International Consortium
Authors: Fonseca Adriana , Lobo João , Hazard Florette K. , Gell Joanna , Nicholls Peter K. , Weiss Robert S. , Klosterkemper Lindsay , Volchenboum Samuel L. , Nicholson James C. , Frazier A. Lindsay , Amatruda James F. , Bagrodia Aditya , Lockley Michelle , Murray Matthew J.
Published: October 2022

Germ cell tumours (GCTs) are a heterogeneous group of rare neoplasms that present in different anatomical sites and across a wide spectrum of patient ages from birth through to adulthood. Once these strata are applied, cohort numbers become modest, hindering inferences regarding management and therapeutic advances. Moreover, patients with GCTs are treated by different medical professionals including paediatric oncologists, neuro-oncologists, medical oncologists, neurosurgeons, gynaecological oncologists, surgeons, and urologists. Silos of care have thus formed, further hampering knowledge dissemination between specialists. Dedicated biobank specimen collection is therefore critical to foster continuous growth in our understanding of similarities and differences by age, gender, and site, particularly for rare cancers such as GCTs. Here, the Malignant Germ Cell International Consortium provides a framework to create a sustainable, global research infrastructure that facilitates acquisition of tissue and liquid biopsies together with matched clinical data sets that reflect the diversity of GCTs. Such an effort would create an invaluable repository of clinical and biological data which can underpin international collaborations that span professional boundaries, translate into clinical practice, and ultimately impact patient outcomes.
Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer
Authors: Meltzer Sebastian , Negård Anne , Bakke Kine M. , Hamre Hanne M. , Kersten Christian , Hofsli Eva , Guren Marianne G. , Sorbye Halfdan , Flatmark Kjersti , Ree Anne Hansen
Published: October 2022

Background

Immune checkpoint blockade (ICB) results in radiologic tumour response dynamics that differ from chemotherapy efficacy measures and require an early signal of clinical utility.

Methods

Previously untreated, unresectable microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) colorectal cancer (CRC) patients were randomly assigned to the oxaliplatin-based Nordic FLOX regimen (control arm) or repeat sequential two FLOX cycles and two ICB cycles (experimental arm). The radiologic response was assessed every 8 weeks. In this post hoc analysis, we explored early target lesion (TL) dynamics as indicator of ICB responsiveness. Progression-free survival (PFS) was the primary endpoint.

Results

Using a landmark analysis approach, we categorised experimental-arm patients into ≥10% (N = 19) or <10% (N = 16) TL reduction at the first post-baseline response assessment. Median PFS for the groups was 16.0 (95% confidence interval (CI), 12.3–19.7) and 3.9 months (95% CI, 2.3–5.5), respectively, superior and inferior (both P < 0.01) to the median PFS of 9.8 months (95% CI, 4.9–14.7) for control arm patients (N = 31).

Conclusions

Radiologic TL reduction of ≥10% at the first post-baseline response assessment identified patients with ICB-responsive metastatic MSS/pMMR-CRC. This pragmatic measure may be used to monitor patients in investigational ICB schedules, enabling early treatment adaptation for unresponsive cases.

Trial registration

ClinicalTrials.gov number, NCT03388190 (02/01/2018).
Anti-ANGPTL3-FLD monoclonal antibody treatment ameliorates podocyte lesions through attenuating mitochondrial damage
Authors: Lv Qianying , Han Xinli , Ni Jiajia , Ma Qianqian , Dai Rufeng , Liu Jiaojiao , Liu Jialu , Zhai Yihui , Shen Qian , Sun Li , Liu Haimei , Rao Jia , Xu Hong
Published: October 2022

Proteinuria, an indication of kidney disease, is caused by the malfunction of podocytes, which play a key role in maintaining glomerular filtration. Angiopoietin-like 3 (ANGPTL3) has been documented to have a cell-autonomous involvement in podocytes, and deletion of Angptl3 in podocytes reduced proteinuria in adriamycin-induced nephropathy. Here, we developed a monoclonal antibody (mAb) against ANGPTL3 to investigate its effects on podocyte injury in an ADR nephropathy mouse model and puromycin (PAN) induced podocyte damage in vitro. The mAb against the human ANGPTL3-FLD sequence (5E5F6) inhibited the binding of ANGPTL3-FLD to integrin β3. Treatment with the 5E5F6 mAb in ADR nephropathy mice mitigated proteinuria and led to a significant decline in podocyte apoptosis, reactive oxygen species (ROS) generation and mitochondrial fragmentation. In PAN-induced podocyte damage in vitro, the 5E5F6 mAb blocked the ANPGPLT3-mediated activation of integrin αvβ3 and Rac1, which regulated the mitochondrial homeostasis. Altogether, anti-ANGPLT3-FLD mAb attenuates proteinuria and podocyte lesions in ADR mice models, as well as PAN-induced podocyte damage, in part through regulating mitochondrial functions. Our study provides a therapeutic approach for targeting ANGPTL3 in proteinuric kidney disease.
Real-time holographic lensless micro-endoscopy through flexible fibers via fiber bundle distal holography
Authors: Badt Noam , Katz Ori
Published: October 2022

Fiber-based micro-endoscopes are a critically important tool for minimally-invasive deep-tissue imaging. However, current micro-endoscopes cannot perform three-dimensional imaging through dynamically-bent fibers without the use of bulky optical elements such as lenses and scanners at the distal end, increasing the footprint and tissue-damage. Great efforts have been invested in developing approaches that avoid distal bulky optical elements. However, the fundamental barrier of dynamic optical wavefront-distortions in propagation through flexible fibers limits current approaches to nearly-static or non-flexible fibers. Here, we present an approach that allows holographic, bend-insensitive, coherence-gated, micro-endoscopic imaging using commercially available multi-core fibers (MCFs). We achieve this by adding a partially-reflecting mirror to the distal fiber-tip, allowing to perform low-coherence full-field phase-shifting holography. We demonstrate widefield diffraction-limited reflection imaging of amplitude and phase targets through dynamically bent fibers at video-rate. Our approach holds potential for label-free investigations of dynamic samples.
INTS13 variants causing a recessive developmental ciliopathy disrupt assembly of the Integrator complex
Authors: Mascibroda Lauren G. , Shboul Mohammad , Elrod Nathan D. , Colleaux Laurence , Hamamy Hanan , Huang Kai-Lieh , Peart Natoya , Singh Moirangthem Kiran , Lee Hane , Merriman Barry , Jodoin Jeanne N. , Sitaram Poojitha , Lee Laura A. , Fathalla Raja , Al-Rawashdeh Baeth , Ababneh Osama , El-Khateeb Mohammad , Escande-Beillard Nathalie , Nelson Stanley F. , Wu Yixuan , Tong Liang , Kenney Linda J. , Roy Sudipto , Russell William K. , Amiel Jeanne , Reversade Bruno , Wagner Eric J.
Published: October 2022

Oral-facial-digital (OFD) syndromes are a heterogeneous group of congenital disorders characterized by malformations of the face and oral cavity, and digit anomalies. Mutations within 12 cilia-related genes have been identified that cause several types of OFD, suggesting that OFDs constitute a subgroup of developmental ciliopathies. Through homozygosity mapping and exome sequencing of two families with variable OFD type 2, we identified distinct germline variants in INTS13, a subunit of the Integrator complex. This multiprotein complex associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. We determined that INTS13 utilizes its C-terminus to bind the Integrator cleavage module, which is disrupted by the identified germline variants p.S652L and p.K668Nfs*9. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Accordingly, its knockdown in Xenopus embryos leads to motile cilia anomalies. Altogether, we show that mutations in INTS13 cause an autosomal recessive ciliopathy, which reveals key interactions between components of the Integrator complex.
Mechanistic insights into CO2 conversion chemistry of copper bis-(terpyridine) molecular electrocatalyst using accessible operando spectrochemistry
Authors: Zhang Huihui , Xu Chang , Zhan Xiaowen , Yu Yu , Zhang Kaifu , Luo Qiquan , Gao Shan , Yang Jinlong , Xie Yi
Published: October 2022

The implementation of low-cost transition-metal complexes in CO2 reduction reaction (CO2RR) is hampered by poor mechanistic understanding. Herein, a carbon-supported copper bis-(terpyridine) complex enabling facile kilogram-scale production of the catalyst is developed. We directly observe an intriguing baton-relay-like mechanism of active sites transfer by employing a widely accessible operando Raman/Fourier-transform infrared spectroscopy analysis coupled with density functional theory computations. Our analyses reveal that the first protonation step involves Cu-N bond breakage before the *COOH intermediate forms exclusively at the central N site, followed by an N-to-Cu active site transfer. This unique active site transfer features energetically favorable *CO formation on Cu sites, low-barrier CO desorption and reversible catalyst regeneration, endowing the catalyst with a CO selectively of 99.5 %, 80 h stability, and a turn-over efficiency of 9.4 s−1 at −0.6 V vs. the reversible hydrogen electrode in an H-type cell configuration. We expect that the approach and findings presented here may accelerate future mechanistic studies of next-generation CO2RR electrocatalysts.
Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England
Authors: Webster H. H. , Nyberg T. , Sinnathamby M. A. , Aziz N. Abdul , Ferguson N. , Seghezzo G. , Blomquist P. B. , Bridgen J. , Chand M. , Groves N. , Myers R. , Hope R. , Ashano E. , Lopez-Bernal J. , De Angelis D. , Dabrera G. , Presanis A. M. , Thelwall S.
Published: October 2022

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71–0.90), hospital admission (HR = 0.88, 95% CI 0.83–0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95–1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.
Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis
Authors: Qin Le , Cui Yuanbin , Yuan Tingjie , Chen Dongmei , Zhao Ruocong , Li Shanglin , Jiang Zhiwu , Wu Qiting , Long Youguo , Wang Suna , Tang Zhaoyang , Pan Huixia , Li Xiaoping , Wei Wei , Yang Jie , Luo Xuequn , Zhang Zhenfeng , Tang Qiannan , Liu Pentao , Weinkove Robert , Yao Yao , Qin Dajiang , Thiery Jean Paul , Li Peng
Published: October 2022

Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain. We show that CARP T cells enhance the antitumor activity of anti-mesothelin CAR (CARMz) T cells in vitro and in vivo. In addition, confocal microscopy indicates that PD-L1 molecules on CARMz T cells accumulate at cell-cell contacts with CARP T cells. Using single-cell RNA-sequencing analysis, we reveal that CARP T cells promote CARMz T cells differentiation into central memory-like T cells, upregulate genes related to Th1 cells, and downregulate Th2-associated cytokines through the CD70-CD27 axis. Moreover, these effects are not restricted to PD-L1, as CAR19 T cells expressing anti-CD19 CSR exhibit similar effects on anti-PSCA CAR T cells with truncated CD19 expression. These findings suggest that target trans-recognition by CSRs on CAR T cells may improve the efficacy and persistence of CAR T cells via the CD70-CD27 axis.
Inversions of landslide strength as a proxy for subsurface weathering
Authors: Alberti Stefano , Leshchinsky Ben , Roering Josh , Perkins Jonathan , Olsen Michael J.
Published: October 2022

Distributions of landslide size are hypothesized to reflect hillslope strength, and consequently weathering patterns. However, the association of weathering and critical zone architecture with mechanical strength properties of parent rock and soil are poorly-constrained. Here we use three-dimensional stability to analyze 7330 landslides in western Oregon to infer combinations of strength - friction angles and cohesion - through analysis of both failed and reconstructed landslide terrain. Under a range of conditions, our results demonstrate that the failure envelope that relates shear strength and normal stress in landslide terrain is nonlinear owing to an exchange in strength with landslide thickness. Despite the variability in material strength at large scales, the observed gradient in proportional cohesive strength with landslide thickness may serve as a proxy for subsurface weathering. We posit that the observed relationships between strength and landslide thickness are associated with the coalescence of zones of low shear strength driven by fractures and weathering, which constitutes a first-order control on the mechanical behavior of underlying soil and rock mass.
Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors
Authors: Lee Seonghyun , Lee Hyunji , Baek Gayoung , Kim Jin-Soo
Published: October 2022

Bacterial toxin DddA-derived cytosine base editors (DdCBEs)—composed of split DddAtox (a cytosine deaminase specific to double-stranded DNA), custom-designed TALE (transcription activator-like effector) DNA-binding proteins, and a uracil glycosylase inhibitor—enable mitochondrial DNA (mtDNA) editing in human cells, which may pave the way for therapeutic correction of pathogenic mtDNA mutations in patients. The utility of DdCBEs has been limited by off-target activity, which is probably caused by spontaneous assembly of the split DddAtox deaminase enzyme, independent of DNA-binding interactions. We engineered high-fidelity DddA-derived cytosine base editors (HiFi-DdCBEs) with minimal off-target activity by substituting alanine for amino acid residues at the interface between the split DddAtox halves. The resulting domains cannot form a functional deaminase without binding of their linked TALE proteins at adjacent sites on DNA. Whole mitochondrial genome sequencing shows that, unlike conventional DdCBEs, which induce hundreds of unwanted off-target C-to-T conversions in human mtDNA, HiFi-DdCBEs are highly efficient and precise, avoiding collateral off-target mutations, and as such, they will probably be desirable for therapeutic applications.
Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion
Authors: Ablain Julien , Al Mahi Amira , Rothschild Harriet , Prasad Meera , Aires Sophie , Yang Song , Dokukin Maxim E. , Xu Shuyun , Dang Michelle , Sokolov Igor , Lian Christine G. , Zon Leonard I.
Published: October 2022

Cancer genetics has uncovered many tumor-suppressor and oncogenic pathways, but few alterations have revealed mechanisms involved in tumor spreading. Here, we examined the role of the third most significant chromosomal deletion in human melanoma that inactivates the adherens junction gene NECTIN1 in 55% of cases. We found that NECTIN1 loss stimulates melanoma cell migration in vitro and spreading in vivo in both zebrafish and human tumors specifically in response to decreased IGF1 signaling. In human melanoma biopsy specimens, adherens junctions were seen exclusively in areas with low IGF1 levels, but not in NECTIN1-deficient tumors. Our study establishes NECTIN1 as a major determinant of melanoma dissemination and uncovers a genetic control of the response to microenvironmental signals.
Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial
Authors: Carvajal Richard D. , Butler Marcus O. , Shoushtari Alexander N. , Hassel Jessica C. , Ikeguchi Alexandra , Hernandez-Aya Leonel , Nathan Paul , Hamid Omid , Piulats Josep M. , Rioth Matthew , Johnson Douglas B. , Luke Jason J. , Espinosa Enrique , Leyvraz Serge , Collins Laura , Goodall Howard M. , Ranade Koustubh , Holland Chris , Abdullah Shaad E. , Sacco Joseph J. , Sato Takami
Published: October 2022

In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% with a median overall survival of 7.8 months. We conducted a multicenter, single-arm, open-label phase 2 study of tebentafusp, a soluble T cell receptor bispecific (gp100×CD3), in 127 patients with treatment-refractory metastatic uveal melanoma (NCT02570308). The primary endpoint was the estimation of objective response rate based on RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Secondary objectives included safety, overall survival, progression-free survival and disease control rate. All patients had at least one treatment-related adverse event, with rash (87%), pyrexia (80%) and pruritus (67%) being the most common. Toxicity was mostly mild to moderate in severity but was greatly reduced in incidence and intensity after the initial three doses. Despite a low overall response rate of 5% (95% CI: 2–10%), the 1 year overall survival rate was 62% (95% CI: 53–70%) with a median overall survival of 16.8 months (95% CI: 12.9–21.3), suggesting benefit beyond traditional radiographic-based response criteria. In an exploratory analysis, early on-treatment reduction in circulating tumour DNA was strongly associated with overall survival, even in patients with radiographic progression. Our findings indicate that tebentafusp has promising clinical activity with an acceptable safety profile in patients with previously treated metastatic uveal melanoma, and data suggesting ctDNA as an early indicator of clinical benefit from tebentafusp need confirmation in a randomized trial.
Brain de novo transcriptome assembly of a toad species showing polymorphic anti-predatory behavior
Authors: Chiocchio Andrea , Libro Pietro , Martino Giuseppe , Bisconti Roberta , Castrignanò Tiziana , Canestrelli Daniele
Published: October 2022

Understanding the genomic underpinnings of antipredatory behaviors is a hot topic in eco-evolutionary research. Yellow-bellied toad of the genus Bombina are textbook examples of the deimatic display, a time-structured behavior aimed at startling predators. Here, we generated the first de novo brain transcriptome of the Apennine yellow-bellied toad Bombina pachypus, a species showing inter-individual variation in the deimatic display. Through Rna-Seq experiments on a set of individuals showing distinct behavioral phenotypes, we generated 316,329,573 reads, which were assembled and annotated. The high-quality assembly was confirmed by assembly validators and by aligning the contigs against the de novo transcriptome with a mapping percentage higher than 91.0%. The homology annotation with DIAMOND (blastx) led to 77,391 contigs annotated on Nr, Swiss Prot and TrEMBL, whereas the domain and site protein prediction made with InterProScan led to 4747 GO-annotated and 1025 KEGG-annotated contigs. The B. pachypus transcriptome described here will be a valuable resource for further studies on the genomic underpinnings of behavioral variation in amphibians.
First direct evidence of adult European eels migrating to their breeding place in the Sargasso Sea
Authors: Wright Rosalind M. , Piper Adam T. , Aarestrup Kim , Azevedo Jose M. N. , Cowan George , Don Andy , Gollock Matthew , Rodriguez Ramallo Sara , Velterop Randolph , Walker Alan , Westerberg Håkan , Righton David
Published: October 2022

The European eel (Anguilla anguilla) is critically endangered (according to the most recent IUCN assessment) and has suffered a 95% decline in recruitment since the 1980s, attributed in part to factors occurring during the marine phases of its life-cycle. As an adult, the European eel undertakes the longest spawning migration of all anguillid eels, a distance of 5000 to 10,000 km across the Atlantic Ocean to the Sargasso Sea. However, despite the passage of almost 100 years since Johannes Schmidt proposed the Sargasso Sea as the breeding place of European eels on the basis of larval surveys, no eggs or spawning adults have ever been sampled there to confirm this. Fundamental questions therefore remain about the oceanic migration of adult eels, including navigation mechanisms, the routes taken, timings of arrival, swimming speed and spawning locations. We attached satellite tags to 26 eels from rivers in the Azores archipelago and tracked them for periods between 40 and 366 days at speeds between 3 and 12 km day−1, and provide the first direct evidence of adult European eels reaching their presumed breeding place in the Sargasso Sea.
Birdsongs alleviate anxiety and paranoia in healthy participants
Authors: Stobbe E. , Sundermann J. , Ascone L. , Kühn S.
Published: October 2022

The present study investigated the effect of urban (traffic noise) vs. natural (birdsongs) soundscapes on mood, state paranoia, and cognitive performance, hypothesizing that birdsongs lead to significant improvements in these outcomes. An additional goal was to explore the differential impact of lower vs. higher diversity of the soundscapes by manipulating the number of different typical traffic sounds or songs of different bird species within the respective soundscapes. In a randomized online experiment, N = 295 participants were exposed to one out of four conditions for 6 min: traffic noise low, traffic noise high, birdsong low, and birdsong high diversity soundscapes. Before and after the exposure, participants performed a digit-span and dual n-back task, and filled out depression, anxiety, and paranoia questionnaires. The traffic noise soundscapes were associated with a significant increase in depression (small effect size in low, medium effect size in high diversity condition). Concerning the birdsong conditions, depression exclusively decreased after exposure to the high diversity soundscape (small effect size). Anxiety and paranoia significantly decreased in both birdsong conditions (medium effect sizes). For cognition, no effects were observed. In sum, the present study suggests that listening to birdsongs regardless of diversity improves anxiety, while traffic noise, also regardless of diversity, is related to higher depressiveness. Moreover, for the first time, beneficial, medium-sized effects of birdsong soundscapes were demonstrated, reducing paranoia. Overall, the results bear interesting implications for further research, such as actively manipulating soundscapes in different environments or settings (e.g., psychiatric wards) and testing their effect on subclinical or even clinical manifestations of anxiety and paranoia.
Constrained quantum optimization for extractive summarization on a trapped-ion quantum computer
Authors: Niroula Pradeep , Shaydulin Ruslan , Yalovetzky Romina , Minssen Pierre , Herman Dylan , Hu Shaohan , Pistoia Marco
Published: October 2022

Realizing the potential of near-term quantum computers to solve industry-relevant constrained-optimization problems is a promising path to quantum advantage. In this work, we consider the extractive summarization constrained-optimization problem and demonstrate the largest-to-date execution of a quantum optimization algorithm that natively preserves constraints on quantum hardware. We report results with the Quantum Alternating Operator Ansatz algorithm with a Hamming-weight-preserving XY mixer (XY-QAOA) on trapped-ion quantum computer. We successfully execute XY-QAOA circuits that restrict the quantum evolution to the in-constraint subspace, using up to 20 qubits and a two-qubit gate depth of up to 159. We demonstrate the necessity of directly encoding the constraints into the quantum circuit by showing the trade-off between the in-constraint probability and the quality of the solution that is implicit if unconstrained quantum optimization methods are used. We show that this trade-off makes choosing good parameters difficult in general. We compare XY-QAOA to the Layer Variational Quantum Eigensolver algorithm, which has a highly expressive constant-depth circuit, and the Quantum Approximate Optimization Algorithm. We discuss the respective trade-offs of the algorithms and implications for their execution on near-term quantum hardware.
Whole farm planning raises profit despite burgeoning climate crisis
Authors: Muleke Albert , Harrison Matthew Tom , Eisner Rowan , de Voil Peter , Yanotti Maria , Liu Ke , Yin Xiaogang , Wang Weilu , Monjardino Marta , Zhao Jin , Zhang Feng , Fahad Shah , Zhang Yunbo
Published: October 2022

The climate crisis challenges farmer livelihoods as increasingly frequent extreme weather events impact the quantum and consistency of crop production. Here, we develop a novel paradigm to raise whole farm profit by optimising manifold variables that drive the profitability of irrigated grain farms. We build then invoke a new decision support tool—WaterCan Profit—to optimise crop type and areas that collectively maximise farm profit. We showcase four regions across a climate gradient in the Australian cropping zone. The principles developed can be applied to cropping regions or production systems anywhere in the world. We show that the number of profitable crop types fell from 35 to 10 under future climates, reflecting the interplay between commodity price, yield, crop water requirements and variable costs. Effects of climate change on profit were not related to long-term rainfall, with future climates depressing profit by 11–23% relative to historical climates. Impacts of future climates were closely related to crop type and maturity duration; indeed, many crop types that were traditionally profitable under historical climates were no longer profitable in future. We demonstrate that strategic whole farm planning of crop types and areas can yield significant economic benefits. We suggest that future work on drought adaptation consider genetic selection criteria more diverse than phenology and yield alone. Crop types with (1) higher value per unit grain weight, (2) lower water requirements and (3) higher water-use efficiency are more likely to ensure the sustainability and prosperity of irrigated grain production systems under future climates.
Low functional vulnerability of fish assemblages to coral loss in Southwestern Atlantic marginal reefs
Authors: Luza André L. , Quimbayo Juan P. , Ferreira Carlos E. L. , Floeter Sergio R. , Francini-Filho Ronaldo B. , Bender Mariana G. , Longo Guilherme O.
Published: October 2022

Marginal reefs sustain coral assemblages under conditions considered suboptimal for most corals, resulting in low coral abundance. These reefs are inhabited by numerous fishes with a generally unknown degree of association with corals that might lead to the assumption that corals play minor roles in determining fish occurrence, when corals could be actually sustaining diverse and resilient assemblages. Using site-occupancy models fitted to data of 113 reef fish species of different life stages (adults and juveniles) from 36 reefs distributed across the Southwestern Atlantic (0.87–27.6°S) we first assessed fish assemblage’s response to coral and turf algal cover, and identified coral-associated fish. Then, we simulated the loss of coral-associated fishes and contrasted it with random losses, providing inferences on the resilience of fish assemblage’s functional trait space to species loss. The entire fish assemblage responded more positively to coral than to turf algae, with 42 (37%) species being identified as coral-associated fish. The simulated loss of coral-associated fish reduced up to 5% the functional trait space and was not different from the random loss. These results reveal that marginal reefs of Southwestern Atlantic reefs host resilient fish assemblages that might preserve fundamental ecological functions and ecosystem services even with coral declines.
Protein delivery to living cells by thermal stimulation for biophysical investigation
Authors: Torricella Francesco , Barbieri Letizia , Bazzurro Virginia , Diaspro Alberto , Banci Lucia
Published: October 2022

Studying biomolecules in their native environment represents the ideal sample condition for structural biology investigations. Here we present a novel protocol which allows to delivery proteins into eukaryotic cells through a mild thermal stimulation. The data presented herein show the efficacy of this approach for delivering proteins in the intracellular environment of mammalian cells reaching a concentration range suitable for successfully applying biophysical methods, such as double electron electron resonance (DEER) measurements for characterising protein conformations.
Applicability of modified weibull extension distribution in modeling censored medical datasets: a bayesian perspective
Authors: Feroze Navid , Tahir Uroosa , Noor-ul-Amin Muhammad , Nisar Kottakkaran Sooppy , Alqahtani Mohammed S. , Abbas Mohamed , Ali Rashid , Jirawattanapanit Anuwat
Published: October 2022

There are some contributions analyzing the censored medical datasets using modifications of the conventional lifetime distribution; however most of the said contributions did not considered the modification of the Weibull distribution (WD). The WD is an important lifetime model. Due to its prime importance in modeling life data, many researchers have proposed different modifications of WD. One of the most recent modifications of WD is Modified Weibull Extension distribution (MWED). However, the ability of MWED to model the censored medical data has not yet been explored in the literature. We have explored the suitability of the model in modeling censored medical datasets. The analysis has been carried out using Bayesian methods under different loss functions and informative priors. The approximate Bayes estimates have been computed using Lindley’s approximation. Based on detailed simulation study and real life analysis, it has been concluded that Bayesian methods performed better as compared to maximum likelihood estimates. In case of small samples, the performance of Bayes estimates under ELF and informative prior was the best. However, in case of large samples, the choice of prior and loss function did not affect the efficiency of the results to a large extend. The MWED performed efficiently in modeling real censored datasets relating to survival times of the leukemia and bile duct cancer patients. The MWED was explored to be a very promising candidate model for modeling censored medical datasets.
Effects of odors on sleep quality in 139 healthy participants
Authors: Sabiniewicz Agnieszka , Zimmermann Pia , Ozturk Guliz Akin , Warr Jonathan , Hummel Thomas
Published: October 2022

The present study aimed to systematically examine whether laurinal, orange odor, and a specifically designed “perfume” influence sleep quality. During sleep, healthy participants (n = 139) were presented with odor or no odor through nose clips for fourteen consecutive nights (phase one). We collected physiological parameters together with subjective reports. Later on, longer lasting effects of this manipulation were examined for the following fourteen nights (phase two) without exposition to odors. Additionally, olfactory, cognitive and non-cognitive measures were conducted before phase one, between both phases and after phase two. One-way analyses of variance for repeated measures with nights and condition (1 vs 2) as the within-subject factor and odor condition (0, 1, 2 or 3) together with odor pleasantness rating as between-subject factor, was employed to analyse data. Overall, the present results demonstrated that the odor condition in comparison to control had no consistent effect on sleep in healthy participants which can be possibly explained by exposure to odors via nose clips. However, the analyses indicated that the individual pleasantness of odors enhanced the positive assessment of sleep quality. Altogether, the present results indicate that the subjective perception of an odor’s hedonic value appears to be crucial for sleep quality, not the odors themselves.
Using the Baidu index to understand Chinese interest in thyroid related diseases
Authors: Hu Qian , Mou Yuan-lin , Yin Ruo-yun , Tang Lei , Zhang Fan
Published: October 2022

Common thyroid diseases are hyperthyroidism, hypothyroidism, thyroiditis, thyroid tumor and so on. Baidu is currently the most widely used online search tool in China, has developed an internet search trends collection and analysis tool called the Baidu Index. The aim of the present study was to understand the trend and characteristics of public’s online attention to thyroid diseases, and to explore the value of Baidu Index in monitoring online retrieval behavior of thyroid-related information. Taking the period from January 1, 2011 to December 31, 2019 as the time range into consideration, we used the big data analysis tool of Baidu Index and took “thyroid nodules”, “thyroid cancer”, “thyroiditis” “hyperthyroidism” and “hypothyroidism” as the keywords, the data of “search index” and “media index” were recorded on a weekly basis, and all information were aggregated into quarterly and annual to generate the final data which was carried out for secondary analysis. Pearson correlation analysis was used to analyze the correlation between the search index of keywords and the year. One-way Analysis of Variance was used to analyze the differences between search index and media index. Among the five keywords, thyroid nodule search index had the highest growth rate (640%), followed by thyroid cancer (298%). The media’s attention to thyroid diseases had been declining year by year. Unlike the public’s attention, the media index of hyperthyroidism was significantly higher than other keywords. Over the past nine years, the public's attention to thyroid-related diseases has been increasing gradually. Baidu Index is an effective tool to track the health information query behavior of Chinese internet users, which can provide a cost-effective supplement to traditional monitoring system.
Severity of underweight affects the development of nontuberculous mycobacterial pulmonary disease; a nationwide longitudinal study
Authors: Kang Ji Young , Han Kyungdo , Kim Mee Kyoung
Published: October 2022

Regarding to known association between underweight and non-tuberculous mycobacterial pulmonary disease (NTM-PD), the underweight was simply categorized as body mass index (BMI) less than 18.5 kg/m2, mainly because of its low prevalence. We aimed to better define the impact of BMI severity on NTM-PD development. We analysed health data from 4,332,529 individuals examined in 2009 and followed up until December 2017 to determine the incidence of NTM-PD. Based on the BMI in kg/m2, the population was categorized into mild (17.00–18.49), moderate (16.00–16.99), and severe underweight (< 16.00) groups. Using Cox proportional-hazards analyses, hazard ratios for NTM-PD were calculated according to the severity of underweight in reference to normal BMI (18.50–22.99). Over a median follow-up of 5.6 ± 1.2 years, 6223 participants developed NTM-PD. Risk of NTM-PD increased significantly with the severity of underweight: multivariate adjusted hazard ratios (95% confidence intervals) for mild, moderate, and severe underweight were 2.34 (2.17–2.52), 3.50 (3.07–3.99), and 4.35 (3.63–5.21), respectively. In subgroup analysis, being younger (< 65 years old) or male exacerbated the effect of severe underweight on the risk of NTM-PD. This study proved that as underweight categories became more severe, the risk of NTM-PD increased proportionally.
Overexpression of mouse prion protein in transgenic mice causes a non-transmissible spongiform encephalopathy
Authors: Jackson Graham S. , Linehan Jacqueline , Brandner Sebastian , Asante Emmanuel A. , Wadsworth Jonathan D. F. , Collinge John
Published: October 2022

Transgenic mice over-expressing human PRNP or murine Prnp transgenes on a mouse prion protein knockout background have made key contributions to the understanding of human prion diseases and have provided the basis for many of the fundamental advances in prion biology, including the first report of synthetic mammalian prions. In this regard, the prion paradigm is increasingly guiding the exploration of seeded protein misfolding in the pathogenesis of other neurodegenerative diseases. Here we report that a well-established and widely used line of such mice (Tg20 or tga20), which overexpress wild-type mouse prion protein, exhibit spontaneous aggregation and accumulation of misfolded prion protein in a strongly age-dependent manner, which is accompanied by focal spongiosis and occasional neuronal loss. In some cases a clinical syndrome developed with phenotypic features that closely resemble those seen in prion disease. However, passage of brain homogenate from affected, aged mice failed to transmit this syndrome when inoculated intracerebrally into further recipient animals. We conclude that overexpression of the wild-type mouse prion protein can cause an age-dependent protein misfolding disorder or proteinopathy that is not associated with the production of an infectious agent but can produce a phenotype closely similar to authentic prion disease.