bluuebunny/crossref_metadata_2025 huggingface dataset:
The Getting It right First Time (GIRFT) programme in urology; rationale and methodology
Authors: John Joseph B. , Gray William K. , O'Flynn Kieran , Briggs Tim W.R. , McGrath John S.
Published: April 2024

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data‐driven insights and clinically‐led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data‐driven, and specialty specific. Each specialty workstream conducts deep‐dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep‐dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT‐advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.
Unemployment volatility in a generalized staggered Nash wage bargaining framework
Authors: Kara Engin
Published: April 2024

Micro evidence on wages suggests that there is heterogeneity across wage contract durations. While, on average, wages are sticky, a non‐negligible proportion of wages are flexible. I generalize the Gertler and Trigari model to match this heterogeneity and show that the new model closely matches observed unemployment volatility. This finding deviates from the literature proposing an alternative calibration of the standard model and arguing that large unemployment fluctuations require a small surplus from an employment relationship. However, in the multi‐sector model I present, unemployment volatility arises even with the standard calibration, where the surplus is relatively large.
Efficacy and biomarker analysis of second‐line nab‐paclitaxel plus sintilimab in patients with advanced biliary tract cancer
Authors: Li Xiaofen , Zhou Nan , Yang Yu , Lu Zijian , Gou Hongfeng
Published: April 2024

Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second‐line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second‐line nab‐paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first‐line chemotherapy were enrolled. Subjects received nab‐paclitaxel 125 mg/m2 on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR). The secondary end points were progression‐free survival (PFS), overall survival (OS), and adverse reactions. Simultaneously, next‐generation sequencing, programmed cell death ligand 1 immunohistochemistry and multiplex immunofluorescence of tumor‐infiltrating lymphocytes were applied to explore potential biomarkers. Twenty‐six subjects were consecutively enrolled. The ORR was 26.9% (7/26), including two complete responses and five partial responses, which met the primary end point. The disease control rate was 61.5% (16/26). The median PFS was 169 days (about 5.6 months, 95% confidence interval [CI] 60–278 days). The median OS was 442 days (about 14.7 months, 95% CI 298–586 days). Grade 3 treatment‐related adverse events (TRAEs) were mainly anemia (27%), leukopenia (23%), neutropenia (19%), and peripheral sensory neuropathy (8%). No grade 4 or 5 TRAEs occurred. Biomarker analysis suggested that positive PD‐L1 and high proportions of CD8+ T‐cell infiltration were correlated with improved clinical outcome. Nab‐paclitaxel plus sintilimab is a potentially effective and tolerable second‐line regimen for advanced BTC that deserves to be studied in large‐scale trials. PD‐L1 status and CD8+ T cell infiltration might be promising biomarkers for efficacy prediction.
Positive effects of fragmentation per se on the most iconic metapopulation
Authors: Galán‐Acedo Carmen , Fahrig Lenore , Riva Federico , Schulz Torsti
Published: April 2024

While habitat loss is a major threat to species, the effects of habitat fragmentation independent of habitat loss (fragmentation per se) are debated. Metapopulation studies often assert negative fragmentation effects, but they do not measure fragmentation per se. We evaluate the effects of fragmentation per se (patch density) across 20 years of patch occupancy patterns of the Åland Islands Glanville fritillary butterfly, Finland, a famous model system in metapopulation studies. Fragmentation per se had mainly positive effects on patch occupancy, the proportion of years occupied per patch, and patch colonization, and negative effects on patch extinction. These results suggest that fragmentation per se does not threaten persistence of the Åland Islands Glanville fritillary butterfly. Our results support the growing body of research challenging the paradigm that habitat fragmentation per se is mostly negative for species, highlighting the value of small patches for species conservation.
Identification of diagnostic biomarkers used in the diagnosis of cardiovascular diseases and diabetes mellitus: A systematic review of quantitative studies
Authors: Wilson Megan , Al‐Hamid Abdullah , Abbas Ismail , Birkett Jason , Khan Iftikhar , Harper Matthew , Al‐Jumeily OBE Dhiya , Assi Sulaf
Published: April 2024

Aims

To perform a systematic review of studies that sought to identify diagnostic biomarkers for the diagnosis of cardiovascular diseases (CVDs) and diabetes mellitus (DM), which could be used in low‐ and middle‐income countries (LMICs) where there is a lack of diagnostic equipment, treatments and training.

Materials and Methods

Papers were sourced from six databases: the British Nursing Index, Google Scholar, PubMed, Sage, Science Direct and Scopus. Articles published between January 2002 and January 2023 were systematically reviewed by three reviewers and appropriate search terms and inclusion/exclusion criteria were applied.

Results

A total of 18 studies were yielded, as well as 234 diagnostic biomarkers (74 for CVD and 160 for DM). Primary biomarkers for the diagnosis of CVDs included growth differentiation factor 15 and neurogenic locus notch homologue protein 1 (Notch1). For the diagnosis of DM, alpha‐2‐macroglobulin, C‐peptides, isoleucine, glucose, tyrosine, linoleic acid and valine were frequently reported across the included studies. Advanced analytical techniques, such as liquid chromatography mass spectrometry, enzyme‐linked immunosorbent assays and vibrational spectroscopy, were also repeatedly reported in the included studies and were utilized in combination with traditional and alternative matrices such as fingernails, hair and saliva.

Conclusions

While advanced analytical techniques are expensive, laboratories in LMICs should carry out a cost–benefit analysis of their use. Alternatively, laboratories may want to explore emerging techniques such as infrared, Fourier transform‐infrared and near‐infrared spectroscopy, which allow sensitive noninvasive analysis.
Association between sleep traits and sarcopenia‐related traits: A two‐sample bidirectional Mendelian randomization study
Authors: Ye Ruifan , Pan Jiajia , Hu Xinying , Xie Jinxiao , Li Pengfei
Published: April 2024

Aim

Despite limited evidence regarding the impact of sleep quality on sarcopenia, it is widely recognized as being associated with various diseases. This study aimed to explore the causal relationship between sleep traits and sarcopenia‐related traits.

Methods

This study utilized a two‐sample bidirectional Mendelian randomization analysis. Genetic genome‐wide summary data of sleep quality indicators, including chronotype, morning wake‐up time, sleep duration, daytime napping, insomnia and daytime dozing, were used. Data on sarcopenia‐related traits, such as appendicular lean mass, grip strength of both hands, walking pace and waist circumference, were collected from a large cohort study. The primary method used was the inverse‐variance weighted analysis.

Results

A causal association was found between chronotype and appendicular lean mass (odds ratio [OR] 1.019, 95% confidence interval [CI] 1.016–1.211, P = 0.021). Napping during the day was connected with walking pace (OR 0.879, 95% CI 0.834–0.928, P = 2.289 × 10−6) and waist circumference (OR 1.234, 95% CI 1.081–1.408, P = 0.002). Insomnia was related to lower grip strength of the right hand (OR 0.844, 95% CI 0.747–0.954, P = 0.007), left hand (OR 0.836, 95% CI 0.742–0.943, P = 0.003), as well as walking pace (OR 0.871, 95% CI 0.798–0.951, P = 0.002). Furthermore, the reverse Mendelian randomization analysis showed associations between certain sarcopenia‐related traits and poor sleep quality.

Conclusions

Some sleep traits were associated with the occurrence of sarcopenia. These findings emphasized the significance of prioritizing sleep quality as a preventive measure against sarcopenia. Geriatr Gerontol Int 2024; 24: 537–545.
Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single‐cell sequencing
Authors: Zhai Luna , Hu Wangling , Li Jingyong , Li Dan , Xia Ni , Tang Tingting , Nie Shaofang , Zhang Min , Jiao Jiao , Lv Bingjie , Yang Fen , Lu Yuzhi , Zha Lingfeng , Gu Muyang , Hu Xiajun , Wen Shuang , Hu Desheng , Zhang Li , Wang Weimin , Cheng Xiang
Published: April 2024

Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue‐specific; however, the time, location, and mechanism of acquiring the tissue‐specific phenotype are still unknown. Using single‐cell RNA sequencing (scRNA‐seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue‐specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.
Gluteal femoral subcutaneous and dermal adipose tissue in female
Authors: Conti Giamaica , Zingaretti Nicola , Busato Alice , Quintero Sierra Lindsey , Amuso Domenico , Scarano Antonio , Iorio Eugenio Luigi , Amore Roberto , Ossanna Riccardo , Negri Alessandro , Conti Anita , Veronese Sheila , De Francesco Francesco , Riccio Michele , Parodi Pier Camillo , Sbarbati Andrea
Published: April 2024

Background

During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region.

Methods

This study has been performed using 7 T‐magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed.

Results

The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles.

Conclusions

This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology.
Rent or Buy? Inflation Experiences and Homeownership within and across Countries
Authors: MALMENDIER ULRIKE , WELLSJO ALEXANDRA STEINY
Published: April 2024

We show that past inflation experiences strongly predict homeownership within and across countries. First, we collect novel survey data, which reveal inflation protection to be a key motivation for homeownership, especially after high inflation experiences. Second, using household data from 22 European countries, we find that higher exposure to historical inflation predicts higher homeownership rates. We estimate similar associations among immigrants to the United States who experienced different past inflation in their home countries but face the same U.S. housing market. Consistent with the experience effects model, the relationship is strongest in countries with predominantly fixed‐rate mortgages.
Burden of obstructive sleep apnea in patients with lung cancer and its effect on performance status
Authors: Zidan Mohamed H. , Shaarawy Hany M. , Gharraf Heba S. , Helal Suzan F. , Hassan Maged , Rizk Rana
Published: April 2024

The association between lung cancer and obstructive sleep apnea has remained a matter of debate for years. Obstructive sleep apnea is thought to increase the incidence of lung cancer due to intermittent hypoxaemia and sleep fragmentation. The aim of this study is to assess the prevalence of obstructive sleep apnea in patients with lung cancer and its effect on those patients' performance status. This is a prevalence study that was conducted at Chest Diseases Department, Alexandria Main University Hospitals. We enrolled 153 patients with lung cancer. All patients underwent cardiorespiratory monitoring using a home sleep‐testing device. Performance status was assessed using Karnofsky performance status scale. The study included 120 (78.4%) males and 33 (21.6%) females newly diagnosed with lung cancer. The mean age was 59.98 ± 11.11 years. Obstructive sleep apnea (apnea–hypopnea index ≥ 5) was present in 134 (87.6%) patients. Eighty‐five (63.4%) patients had mild obstructive sleep apnea, 39 (29.1%) patients had moderate obstructive sleep apnea, and 10 (7.46%) patients had severe obstructive sleep apnea. Prolonged nocturnal oxygen desaturation as demonstrated by time of oxygen saturation spent below 90% (T90%) during total sleep time > 30% was present in 25 (16.3%) patients. There was a significant difference in the median value of Karnofsky performance status scale between patients with lung cancer and associated obstructive sleep apnea and those without obstructive sleep apnea. In conclusion, obstructive sleep apnea is highly prevalent among patients with lung cancer. Performance status is worse among patients with lung cancer in the presence of obstructive sleep apnea. Screening patients with lung cancer for obstructive sleep apnea is important regardless of the presence of classical symptoms of obstructive sleep apnea.
A case of myxopapillary ependymoma with predominant giant cell morphology: A rare entity with comprehensive genomic profiling and review of literature
Authors: Morales‐Vargas Bryan , Saad Hassan , Refai Daniel , Schniederjan Matthew , Abdullaev Zied , Aldape Kenneth , Abedalthagafi Malak
Published: April 2024

In the evolving landscape of ependymoma classification, which integrates histological, molecular, and anatomical context, we detail a rare case divergent from the usual histopathological spectrum. We present the case of a 37‐year‐old man with symptomatic spinal cord compression at the L3–L4 level. Neuroradiological evaluation revealed an intradural, encapsulated mass. Histologically, the tumor displayed atypical features: bizarre pleomorphic giant cells, intranuclear inclusions, mitotic activity, and a profusion of eosinophilic cytoplasm with hyalinized vessels, deviating from the characteristic perivascular pseudorosettes or myxopapillary patterns. Immunohistochemical staining bolstered this divergence, marking the tumor cells positive for glial fibrillary acidic protein and epithelial membrane antigen with a characteristic ring‐like pattern, and CD99 but negative for Olig‐2. These markers, alongside methylation profiling, facilitated its classification as a myxopapillary ependymoma (MPE), despite the atypical histologic features. This profile underscores the necessity of a multifaceted diagnostic process, especially when histological presentation is uncommon, confirming the critical role of immunohistochemistry and molecular diagnostics in classifying morphologically ambiguous ependymomas and exemplifying the histological diversity within MPEs.
Co‐occurring intertidal ecosystem engineers with opposing growth strategies show opposite responses to environmental gradients during establishment
Authors: van de Ven Clea N. , van der Heide Tjisse , Bouma Tjeerd J. , van Ijzerloo Lennart , Lindhout Djeli D. , Reijers Valérie C.
Published: April 2024

Coastal vegetated ecosystems including mangroves, seagrasses, and salt marshes are often shaped by positive plant–environment feedbacks. Plants improve their own living conditions with increasing patch size and density by attenuating hydrodynamics and stabilizing sediments. As these habitat modifications are critical for survival and growth, the positive density‐dependent nature of these feedbacks can lead to establishment thresholds for young plants in absence of mature conspecifics. Although feedback strength is known to depend on hydrodynamic exposure and plant traits (e.g. stiff versus flexible stems), it remains unclear how 1) opposing morphological plant traits affect establishment in contrasting environments, and 2) whether trait plasticity influences establishment success. Here, we investigate this by transplanting two tidal species with opposing growing strategies – Spartina anglica forms tussocks of stiff stems while Zostera noltii forms patches of stress‐avoiding flexible shoots – from two different donor sites in eight experimental locations. Results show that the survival and growth of both species was most successful at field locations with diverging environmental characteristics, while overall survival was highest for Z. noltii. Mainly, S. anglica survival was highest at locations with high organic matter and silt content and higher elevation relative to the tidal amplitude. In contrast, Z. noltii survival was highest at locations with larger grainsize and lower relative elevations. Furthermore, despite initial differences in plant traits between the two donor sites of Z. noltii, we found no effects of donor origin. Contrastingly, we found a significant effect of donor origin on S. anglica growth, even though transplants from the two donor sites showed no initial trait differences. Collectively, these results suggest that the stress‐tolerance strategy of S. anglica hampers establishment in exposed conditions, whereas the stress‐avoiding Z. noltii appears to be more susceptible to stress from desiccation and silty sediments.
The relationship between neighborhood social capital and health from a biopsychosocial perspective: A systematic review
Authors: Magro‐Montañés Beatriz , Pabón‐Carrasco Manuel , Romero‐Castillo Rocío , Ponce‐Blandón José Antonio , Jiménez‐Picón Nerea
Published: April 2024

Background

The Social Determinants of Health (SDH) influence the health of people throughout their lives, and can be positive, protective or risk factors for the population and, in turn, biological, psychological, or social. The social environment conditions the health status of the neighborhood, population, and social group, which can be a health asset due to its strong psychosocial and socio‐cultural influence. Social capital is a community asset of the healthy neighborhood that must be known in order to promote community health.

Objectives

The objective is to determine the relationship between social capital and neighborhood biopsychosocial health.

Methods

A systematic review was conducted based on PRISMA: PubMed, Wos, Scopus, Embase, and Cochrane databases. The search was conducted from January to March 2023. Three authors independently extracted data using a structured form.

Results

Out of 527 records, 17 results passed the inclusion and exclusion criteria. The positive and statistically significant relationship between neighborhood social capital (NSC) and the physical and mental health of neighbors is confirmed, that is, the higher the NSC, the more exercise, better oral health in children and physical health in pregnant women, lower tobacco consumption and lower prevalence of human immunodeficiency virus. At the psychological level, greater NSC leads to better mental health, mental well‐being, life satisfaction, quality of life, self‐perceived health, higher cognitive function, and less depression.

Conclusions

In conclusion, social capital is an important SDH and health asset that influences neighborhood biopsychosocial health and should be known and researched for health promotion in community settings. More evidence is needed to support the results obtained.
The treatment of behavioural and psychological symptoms in dementia: pragmatic recommendations
Authors: Mercier Camille , Rollason Victoria , Eshmawey Mohamed , Mendes Aline , Frisoni Giovanni B.
Published: April 2024

Behavioural and psychological symptoms of dementia (BPSD) are a clinical challenge for the lack of a sound taxonomy, frequent presentation with comorbid BPSD, lack of specific pharmacologic interventions, poor base of methodologically sound evidence with randomized clinical trials, contamination from the treatment of behavioural disturbances of young and adult psychiatric conditions, and small efficacy window of psychotropic drugs. We present here a treatment workflow based on a concept‐driven literature review based on the notions that (i) the aetiology of BPSD can be mainly neurobiological (so‐called ‘primary’ symptoms) or mainly environmental and functional (‘secondary’ symptoms) and that this drives treatment; (ii) the clinical efficacy of psychotropic drugs is driven by their specific profile of receptor affinity; (iii) drug treatment should follow the rules of ‘start low–go slow, prescribe and revise’. This article argues in support of the distinction between primary and secondary BPSD, as well as their characteristics, which until now have been just sketchily described in the literature. It also offers comprehensive and pragmatic clinician‐oriented recommendations for the treatment of BPSD.
National assessments of money laundering risks: Stumbling at the start
Authors: Ferwerda Joras , Reuter Peter
Published: April 2024

The Financial Action Task Force (FATF) requires national governments to demonstrate an understanding of the distribution of money laundering risks across different sectors of the financial system. Such understanding is the foundation for effective control of money laundering under the risk‐based approach called for by the FATF. We analyzed the National Risk Assessments (NRAs) of eight systemically important countries before 2020 to test whether these demonstrated that basic understanding. The eight show very different conceptualizations, analytic approaches, and products. None showed more than minimal competence at risk assessment. For example, most relied largely on expert opinion, solicited, however, in ways that violated the well‐developed methodology for eliciting expert opinion. They consistently misinterpreted Suspicious Activity Reports, the most fine‐grained quantitative data available on money laundering, and failed to provide risk assessments relevant for policymakers. Only one described the methodology employed. Although conducting strong money laundering risk assessments is challenging, given the difficulty of estimating the extent of laundering in any sector, existing practices can be improved. We offer some potential explanations for the failure of governments to take this task seriously. The lack of involvement of risk assessment professionals is an important contributing factor to the weaknesses of the current NRAs.
The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population
Authors: Kong Yujie , Xiao Jie , Tian Li , Xu Ying
Published: April 2024

Background and Objectives

Anti‐E alloantibody is the most common and important red blood cell (RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA) allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population.

Study Design and Methods

All individuals included in our study were RhE‐negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti‐E (responders) and non‐anti‐E‐producing group (non‐responders). The class I and II classical HLA genotyping were determined using next‐generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non‐responders.

Results

In total, 76 responders and 94 non‐responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 phenotypes than non‐responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA‐DRB1*09:01‐DQA1*03:02‐DQB1*03:03 in the RhE responders was significantly higher than in the non‐responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823–5.456; pc value, 1.25 × 10−3).

Conclusion

Our findings indicated that HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three‐locus haplotype in the RhE responders and collaborated to RhE alloimmunization.
Investigating the effects of dopamine on short‐ and long‐latency afferent inhibition
Authors: Foglia Stevie D. , Adams Faith C. , Ramdeo Karishma R. , Drapeau Chloe C. , Turco Claudia V. , Tarnopolsky Mark , Ma Jinhui , Nelson Aimee J.
Published: April 2024

Short‐ and long‐latency afferent inhibition (SAI and LAI respectively) are phenomenon whereby the motor evoked potential induced by transcranial magnetic stimulation (TMS) is inhibited by a sensory afferent volley consequent to nerve stimulation. It remains unclear whether dopamine participates in the genesis or modulation of SAI and LAI. The present study aimed to determine if SAI and LAI are modulated by levodopa (l‐DOPA). In this placebo‐controlled, double‐anonymized study Apo‐Levocarb (100 mg l‐DOPA in combination with 25 mg carbidopa) and a placebo were administered to 32 adult males (mean age 24 ± 3 years) in two separate sessions. SAI and LAI were evoked by stimulating the median nerve and delivering single‐pulse TMS over the motor hotspot corresponding to the first dorsal interosseous muscle of the right hand. SAI and LAI were quantified before and 1 h following ingestion of drug or placebo corresponding to the peak plasma concentration of Apo‐Levocarb. The results indicate that Apo‐Levocarb increases SAI and does not significantly alter LAI. These findings support literature demonstrating increased SAI following exogenous dopamine administration in neurodegenerative disorders.

image

Key points

Short‐ and long‐latency afferent inhibition (SAI and LAI respectively) are measures of corticospinal excitability evoked using transcranial magnetic stimulation.

SAI and LAI are reduced in conditions such as Parkinson's disease which suggests dopamine may be involved in the mechanism of afferent inhibition.

125 mg of Apo‐Levocarb (100 mg dopamine) increases SAI but not LAI.

This study increases our understanding of the pharmacological mechanism of SAI and LAI.
New approach of local critical dimension uniformity improvement for via/contact hole etch with direct current superposition
Authors: Hirsch Emilia W. , Metzler Dominik , Wang Peng
Published: April 2024

As feature sizes continue to shrink for more advanced nodes, local critical dimension (CD) uniformity (LCDU) control becomes more critical than ever for improving defectivity, edge placement error, and yield enhancement. In this work, we developed a new approach utilizing an Ar plasma treatment with a direct current superposition function at low-temperature post patterning stack open. Our results demonstrated that this approach was capable of breaking the trade-off between CD shrink, LCDU improvement, and defectivity reduction. We significantly reduced the LCDU from 1.64 to 1.26 nm at the same CD level (∼10 nm). In contrast, no LCDU reduction was observed with the traditional CD shrink approach through trilayer process tuning. The mechanism for the LCDU improvement was investigated, and a hypothesis was proposed. We believe both the defect mitigation of the organic planarization layer profile and the vertical loading effect together with top sealing and in situ planarization contributed to the final LCDU improvement.
Backscatter measurement of cancellous bone using the ultrasound transit time spectroscopy
Authors: Jia Yan , Han Shuai , Li Boyi , Liu Chengcheng , Ta Dean
Published: April 2024

Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%–99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = –0.87; p < 0.001) and trabecular structures (|r|=0.43–0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.
Iconicity mediates semantic networks of sound symbolism
Authors: Akita Kimi , McLean Bonnie , Park Jiyeon , Thompson Arthur Lewis
Published: April 2024

One speech sound can be associated with multiple meanings through iconicity, indexicality, and/or systematicity. It was not until recently that this “pluripotentiality” of sound symbolism attracted serious attention, and it remains uninvestigated how pluripotentiality may arise. In the current study, Japanese, Korean, Mandarin, and English speakers rated unfamiliar jewel names on three semantic scales: size, brightness, and hardness. The results showed language-specific and cross-linguistically shared pluripotential sound symbolism. Japanese speakers associated voiced stops with large and dark jewels, whereas Mandarin speakers associated [i] with small and bright jewels. Japanese, Mandarin, and English speakers also associated lip rounding with darkness and softness. These sound-symbolic meanings are unlikely to be obtained through metaphorical or metonymical extension, nor are they reported to colexify. Notably, in a purely semantic network without the mediation of lip rounding, softness can instead be associated with brightness, as illustrated by synesthetic metaphors such as yawaraka-na hizashi /jawaɾakanaçizaɕi/ “a gentle (lit. soft) sunshine” in Japanese. These findings suggest that the semantic networks of sound symbolism may not coincide with those of metaphor or metonymy. The current study summarizes the findings in the form of (phono)semantic maps to facilitate cross-linguistic comparisons of pluripotential sound symbolism.
Human-level few-shot concept induction through minimax entropy learning
Authors: Zhang Chi , Jia Baoxiong , Zhu Yixin , Zhu Song-Chun
Published: April 2024

Humans learn concepts both from labeled supervision and by unsupervised observation of patterns, a process machines are being taught to mimic by training on large annotated datasets—a method quite different from the human pathway, wherein few examples with no supervision suffice to induce an unfamiliar relational concept. We introduce a computational model designed to emulate human inductive reasoning on abstract reasoning tasks, such as those in IQ tests, using a minimax entropy approach. This method combines identifying the most effective constraints on data via minimum entropy with determining the best combination of them via maximum entropy. Our model, which applies this unsupervised technique, induces concepts from just one instance, reaching human-level performance on tasks of Raven’s Progressive Matrices (RPM), Machine Number Sense (MNS), and Odd-One-Out (O
3
). These results demonstrate the potential of minimax entropy learning for enabling machines to learn relational concepts efficiently with minimal input.
Carbon capture in polymer-based electrolytes
Authors: Wang Yang , Feric Tony G. , Tang Jing , Fang Chao , Hamilton Sara T. , Halat David M. , Wu Bing , Celik Hasan , Rim Guanhe , DuBridge Tara , Oshiro Julianne , Wang Rui , Park Ah-Hyung Alissa , Reimer Jeffrey A.
Published: April 2024

Nanoparticle organic hybrid materials (NOHMs) have been proposed as excellent electrolytes for combined CO
2
capture and electrochemical conversion due to their conductive nature and chemical tunability. However, CO
2
capture behavior and transport properties of these electrolytes after CO
2
capture have not yet been studied. Here, we use a variety of nuclear magnetic resonance (NMR) techniques to explore the carbon speciation and transport properties of branched polyethylenimine (PEI) and PEI-grafted silica nanoparticles (denoted as NOHM-I-PEI) after CO
2
capture. Quantitative
13
C NMR spectra collected at variable temperatures reveal that absorbed CO
2
exists as carbamates (RHNCOO
−
or RR′NCOO
−
) and carbonate/bicarbonate (CO
3
2−
/HCO
3
−
). The transport properties of PEI and NOHM-I-PEI studied using
1
H pulsed-field-gradient NMR, combined with molecular dynamics simulations, demonstrate that coulombic interactions between negatively and positively charged chains dominate in PEI, while the self-diffusion in NOHM-I-PEI is dominated by silica nanoparticles. These results provide strategies for selecting adsorbed forms of carbon for electrochemical reduction.
Mid-infrared single-photon upconversion spectroscopy enabled by nonlocal wavelength-to-time mapping
Authors: Cai Yujie , Chen Yu , Dorfman Konstantin , Xin Xiaoning , Wang Xiaoying , Huang Kun , Wu E
Published: April 2024

Ultrasensitive spectroscopy is an essential component in mid-infrared (MIR) technology. However, the drawbacks of MIR detectors pose challenges to robust MIR spectroscopy at the single-photon level. We propose an MIR single-photon frequency upconversion spectroscopy nonlocally mapping the MIR information to the time domain. Broadband MIR photons from spontaneous parametric downconversion are frequency-upconverted to the near-infrared band with quantum correlation preservation. Via the group delay of fiber, the MIR spectral information within a 1.18-micrometer bandwidth of 2.76 to 3.94 micrometers is then successfully projected to arrival times of correlated photon pairs. Under the conditions of 6.4 × 10
6
photons per second illumination, the transmission spectra of polymers with single-photon sensitivity are demonstrated using single-pixel detectors. The developed approach circumvents scanning and frequency selection instability, which stands out for its inherent compatibility for evolving environments and scalability for various wavelengths. Because of its high sensitivity and robustness, characterization of biochemical samples and weak measurement of quantum systems are possible to foresee.
Electric-field control of nonvolatile resistance state of perpendicular magnetic tunnel junction via magnetoelectric coupling
Authors: Zhang Yike , Sun Weideng , Cao Kaihua , Yang Xiao-Xue , Yang Yongqiang , Lu Shiyang , Du Ao , Hu Chaoqun , Feng Ce , Wang Yutong , Cai Jianwang , Cui Baoshan , Piao Hong-Guang , Zhao Weisheng , Zhao Yonggang
Published: April 2024

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field–free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.
Real-time swelling-collapse kinetics of nanogels driven by XFEL pulses
Authors: Dallari Francesco , Lokteva Irina , Möller Johannes , Roseker Wojciech , Goy Claudia , Westermeier Fabian , Boesenberg Ulrike , Hallmann Jörg , Rodriguez-Fernandez Angel , Scholz Markus , Shayduk Roman , Madsen Anders , Grübel Gerhard , Lehmkühler Felix
Published: April 2024

Stimuli-responsive polymers are an important class of materials with many applications in nanotechnology and drug delivery. The most prominent one is poly-
N
-isopropylacrylamide (PNIPAm). The characterization of the kinetics of its change after a temperature jump is still a lively research topic, especially at nanometer-length scales where it is not possible to rely on conventional microscopic techniques. Here, we measured in real time the collapse of a PNIPAm shell on silica nanoparticles with megahertz x-ray photon correlation spectroscopy at the European XFEL. We characterize the changes of the particles diffusion constant as a function of time and consequently local temperature on sub-microsecond timescales. We developed a phenomenological model to describe the observed data and extract the characteristic times associated to the swelling and collapse processes. Different from previous studies tracking the turbidity of PNIPAm dispersions and using laser heating, we find collapse times below microsecond timescales and two to three orders of magnitude slower swelling times.
TIM-3
+
CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies
Authors: Minnie Simone A. , Waltner Olivia G. , Zhang Ping , Takahashi Shuichiro , Nemychenkov Nicole S. , Ensbey Kathleen S. , Schmidt Christine R. , Legg Samuel R. W. , Comstock Melissa , Boiko Julie R. , Nelson Ethan , Bhise Shruti S. , Wilkens Alec B. , Koyama Motoko , Dhodapkar Madhav V. , Chesi Marta , Riddell Stanley R. , Green Damian J. , Spencer Andrew , Furlan Scott N. , Hill Geoffrey R.
Published: April 2024

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T
PHEX
), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with
BATF
expression and motif accessibility. IFN-γ
+
T
PHEX
effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ
+
T
PHEX
. We also observed IFN-γ
+
T
PHEX
within CD19-targeted chimeric antigen receptor T cells, which killed CD19
+
leukemia cells. An IFN-γ
+
T
PHEX
gene signature was recapitulated in T
EX
cells from human cancers, including myeloma and lymphoma. Here, we characterize a T
EX
subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional T
EX
found in chronic viral infections. Thus, IFN-γ
+
T
PHEX
represent a potential target for immunotherapy of blood cancers.
Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis
Authors: Canales-Herrerias Pablo , Uzzan Mathieu , Seki Akihiro , Czepielewski Rafael S. , Verstockt Bram , Livanos Alexandra E. , Raso Fiona , Dunn Alexandra , Dai Daniel , Wang Andrew , Al-taie Zainab , Martin Jerome , Laurent Thomas , Ko Huaibin M. , Tokuyama Minami , Tankelevich Michael , Meringer Hadar , Cossarini Francesca , Jha Divya , Krek Azra , Paulsen John D. , Taylor Matthew D. , Nakadar Mohammad Zuber , Wong Joshua , Erlich Emma C. , Mintz Rachel L. , Onufer Emily J. , Helmink Beth A. , Sharma Keshav , Rosenstein Adam , Ganjian Danielle , Chung Grace , Dawson Travis , Juarez Julius , Yajnik Vijay , Cerutti Andrea , Faith Jeremiah J. , Suarez-Farinas Mayte , Argmann Carmen , Petralia Francesca , Randolph Gwendalyn J. , Polydorides Alexandros D. , Reboldi Andrea , Colombel Jean-Frederic , Mehandru Saurabh
Published: April 2024

Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7
+
) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7
+
IgG
+
plasmablasts in circulation, as well as IgG
+
plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.
Pseudorabies virus usurps non-muscle myosin heavy chain IIA to dampen viral DNA recognition by cGAS for antagonism of host antiviral innate immunity
Authors: Liu Yingqi , Qin Yidan , Yang Bingbing , Zheng Hongmei , Qiao Songlin , Luo Zhong , Li Rui
Published: April 2024

Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated. In our previous work, we demonstrated that non-muscle myosin heavy chain IIA (NMHC-IIA), a multifunctional cytoskeleton protein, attenuates innate immune responses triggered by RNA viruses. In the current study, we reported a previously unrecognized role of NMHC-IIA in counteracting PRV-induced cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) production. Mechanistically, PRV infection led to an elevation of NMHC-IIA, strengthening the interaction between poly (ADP-ribose) polymerase 1 (PARP1) and cGAS. This interaction impeded cGAS recognition of PRV DNA and hindered downstream signaling activation. Conversely, inhibition of NMHC-IIA by Blebbistatin triggered innate immune responses and enhanced resistance to PRV proliferation both
in vitro
and
in vivo
. Taken together, our findings unveil that PRV utilizes NMHC-IIA to antagonize host antiviral immune responses via impairing DNA sensing by cGAS. This in-depth understanding of PRV immunosuppression not only provides insights for potential PRV treatment strategies but also highlights NMHC-IIA as a versatile immunosuppressive regulator usurped by both DNA and RNA viruses. Consequently, NMHC-IIA holds promise as a target for the development of broad-spectrum antiviral drugs.

IMPORTANCE

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis plays a vital role in counteracting alphaherpesvirus infections. Alphaherpesviruses exploit various strategies for antagonizing cGAS-STING-mediated antiviral immune responses. However, limited examples of pseudorabies virus (PRV)-caused immunosuppression have been documented. Our findings reveal a novel role of non-muscle myosin heavy chain IIA (NMHC-IIA) in suppressing PRV-triggered innate immune responses to facilitate viral propagation both
in vitro
and
in vivo
. In detail, NMHC-IIA recruits poly (ADP-ribose) polymerase 1 (PARP1) to augment its interaction with cGAS, which impairs cGAS recognition of PRV DNA. Building on our previous demonstration of NMHC-IIA’s immunosuppressive role during RNA virus infections, these findings indicate that NMHC-IIA acts as a broad-spectrum suppressor of host antiviral innate immunity in response to both DNA and RNA viruses. Therefore, NMHC-IIA will be a promising target for the development of comprehensive antiviral strategies.
Supplemental Material: Niobium ore genesis in a capsule
Authors: Williams-Jones Anthony , al. et
Published: April 2024

Methods, Figures S1–S2, and Tables S1–S4.  