bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological risk assessment of heavy metals in tea plantation soil around Tai Lake region in Suzhou, China
Authors: Xu Xiaohan , Yang Jiahui , Zhang Yang , Sui Xueyan , Gong Zelong , Liu Shujing , Chen Xuan , Li Xinghui , Wang Yuhua
Published: February 2024

Tea plant [Camellia sinensis (L.) O. Kuntze] is one of the important foliar cash crops in China, and its root system absorbs heavy metal (HM) elements enriched in the soil and transports them to the over ground part. In order to ensure the safety of the soil ecological environment and tea raw materials in the tea production area, the HM contents of soil and tea plant leaves in Suzhou tea plantations were detected, the relationship between HMs and soil physicochemical properties was analyzed, and the ecological risk of HMs in tea plantation soils was evaluated by using relevant detection techniques and evaluation models. The results showed that the average pH of tea plantation soils around Tai Lake in Suzhou was within the range suitable for the growth of tea plants. The pH, soil organic matter, total nitrogen, available phosphorus and available potassium of tea plantation soil satisfying the requirements of high quality, high efficiency and high yield (‘3H’) tea plantation accounted for 47.06%, 26.47%, 8.82%, 79.41% and 67.65%, respectively. Site 2 fully met the requirements of ‘3H’ tea plantation. In addition, the contents of cadmium (Cd) and mercury (Hg) were extremely variable, and the average contents exceeded the background value of soil in Jiangsu Province, but the HM contents of tea leaves all met the pollution-free standard, and the HM contents of tea leaves around Tai Lake in Suzhou were generally at a safe level. The composite ecological risk index ranged from 0.05 to 0.60, and 32 of the 34 sample sites (except site 21 and site 23) are the most suitable agricultural land for tea plantations.
High Prevalence of Non-typeable Haemophilus influenzae and Haemophilus haemolyticus Among Vaccinated Children with Community-Acquired Pneumonia in Vietnam
Authors: Tran Xuan Duong , Hoang Van Thuan , Dao Thi Loi , Marty Pierre , Gautret Philippe
Published: February 2024

Among 467 children under five hospitalized with community-acquired pneumonia, the prevalence of Haemophilus influenzae or Haemophilus haemolyticus was 60.8%, all cases were non-typable H. influenzae (NTHi) or H. haemolyticus. NTHi/H. haemolyticus PCR detection was associated with about twice the risk for severe disease. The results highlight the need for increased awareness and research efforts to investigate the role of NTHi/H. haemolyticus in severe CAP among children.
Adding MYC/BCL2 double expression to NCCN-IPI may not improve prognostic value to an acceptable level
Authors: Warnnissorn Naree , Kanitsap Nonglak , Niparuck Pimjai , Boonsakan Paisarn , Kulalert Prapasri , Limvorapitak Wasithep , Bhoopat Lantarima , Saengboon Supawee , Suriyonplengsaeng Chinnawut , Chantrathammachart Pichika , Puavilai Teeraya , Chuncharunee Suporn
Published: February 2024

Background

MYC/BCL2 double expression (DE) is associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). This study aimed to determine whether the addition of DE to the National Comprehensive Cancer Network Internal Prognostic Index (NCCN-IPI) could improve the prediction of disease progression in patients with DLBCL treated with R-CHOP.

Methods

This confirmatory prognostic factor study retrospectively recruited patients with newly diagnosed DLBCL between January 1, 2014, and January 31, 2018, at Ramathibodi Hospital (RA) and Thammasat University Hospital (TU). The follow-up period ended on July 1, 2022. Tumors expressing MYC ≥ 40% and BCL2 ≥ 50% were classified as DE. We calculated the hazard ratios (HR) for progression-free survival (PFS) from the date of diagnosis to refractory disease, relapse, or death. Discrimination of the 5-year prediction was based on Cox models using Harrell’s concordance index (c-index).

Results

A total of 111 patients had DE (39%), NCCN-IPI (8%), and disease progression (46%). The NCCN-IPI adjusted HR of DE was 1.6 (95% confidence interval [CI]: 0.9–2.8; P = 0.117). The baseline NCCN-IPI c-index was 0.63. Adding DE to the NCCN-IPI slightly increased Harrell’s concordance index (c-index) to 0.66 (P = 0.119).

Conclusions

Adding DE to the NCCN-IPI may not improve the prognostic value to an acceptable level in resource-limited settings. Multiple independent confirmatory studies from a large cohort of lymphoma registries have provided additional evidence for the clinical utility of DE.
Economic Burden of Livestock Abortions in Northern Tanzania
Authors: Semango George , Yoder Jonathan , Kibona Tito , Claxton John R. , Buza Joram , Mmbaga Blandina T. , Johnson Stephanie Sikavitsas , Cleaveland Sarah , Lankester Felix
Published: February 2024

Livestock abortion is a source of economic loss for farmers, but its economic impact has not been estimated in many Low and Middle-Income Countries. This article presents an estimation methodology and estimates for the gross and net cost of an abortion based on a sample of livestock-owning households in three regions of northern Tanzania and market data. We then generate aggregate estimates of abortion losses across Tanzania. We estimate annual gross and net annual losses of about $263 Million (about TZS 600 billion) and $131 million (about TZS 300 billion), respectively.
Care and Crisis: Making Beds in the National Health Service
Authors: Arnold-Forster Agnes , Bates Victoria
Published: February 2024

In July 1979, the Sunday Mirror published an article with the headline: “HOSPITALS AT CRISIS POINT: Jobs and beds to go in cash curbs.” In this article we explore the role of hospital beds in such public discussions of “crisis” within the British National Health Service (NHS). In the 1970s, the media and politicians paid increasing attention to bed numbers as an indicator of resource scarcity within the NHS. While this in part reflected a genuine trend, it was also a powerful narrative device. The hospital bed has become a cipher for NHS resourcing and resilience, but throughout the twentieth century, there has been a tension between stories of declining bed numbers as a sign of “crisis,” and declining bed numbers as a marker of more efficient, high-quality healthcare. This article will show that the hospital bed was an extremely important political device because it was imbued with rich social and cultural symbolism, and that stories of declining bed numbers were not as straightforward as they first appear. While discussions in the public sphere tended to focus on bed numbers and waiting times, discussions in the healthcare sector and among policymakers attended to what beds could—and should—do for both patients and staff. Public rhetoric about decline was less about the object itself, and more about the role of the hospital bed as a symbol of care and as a politically pertinent shorthand for the health of the NHS as an institution.
Credit Cars: Or How I Learned to Stop Worrying and Love Auto Loans
Authors: Reyes Nicholas Tucker , Headworth Spencer
Published: February 2024

Drawing on trade publications, contemporaneous newspaper stories, and other historical sources from the early twentieth-century United States, this article explains how installment plans overcame moral and business concerns to become the standard way people bought cars. Prominent figures in the automobile industry and financial institutions initially denounced the idea of selling cars on credit, and many banks declined to extend credit to would-be auto buyers. However, the relevant legal infrastructure heavily favored creditors, allowing them to circumvent usury laws and guaranteeing their right to repossess assets if borrowers missed payments. When the profit-making that these aspects of the law enabled became clear, moral objections to the idea of selling cars on credit yielded to a new moral consensus among powerful actors that valorized buying cars on credit and concentrated disapprobation on just those borrowers who defaulted on their payments. Thus, the characteristics of the legal infrastructure functionally presupposed the resolution of the erstwhile debate about the fundamental morality of selling cars on credit. Ultimately, lending practices building on the legal and moral foundation established in the early twentieth century led to the establishment of subprime auto lenders whose business model revolves around exorbitant interest rates, high fees, and aggressive repossession.
Reflections on a Counter-Humanist Archaeology: A Commentary on Greer 2023
Authors: Montgomery Lindsay M.
Published: February 2024

In ‘Humanist Missteps’, Matthew Greer makes the pointed observation that non-anthropocentric frameworks, including symmetrical, object-oriented and posthuman feminist archaeologies, have primarily focused on deconstructing the human–non-human binary while failing to problematize humanist assumptions about who counts as Human. At the core of Greer's argument is the matter of citational practice: which social theorists are archaeologists referencing in their efforts to craft relational approaches to humans, things, animals and plants? In answering this question, the author points to a notable lack of Black Studies theorists, particularly the work of Sylvia Wynter, Zakkiyah Jackson and Tiffany King, in posthumanist archaeologies. While I agree with Greer's critiques, his essay stops short of explaining this citational silence. In this brief commentary, I suggest that this absence of Black Studies scholarship reflects the fact that the discipline of archaeology remains a ‘white public space’ (Brodkin et al.2011: 545) and maintains an artificial division between analysis and activism.
Development of the conversation tool “I-HARP for COPD” for early identification of palliative care needs in patients with chronic obstructive pulmonary disease
Authors: Huijten Daniël C.M. , Hofstede Laura , Simons Sami O. , Ament Stephanie C.M. , Gunnink-Boonstra Nicolette , van den Beuken-van Everdingen Marieke H.J. , Janssen Daisy J.A.
Published: February 2024

Objectives

This study aimed to develop the conversation tool “I-HARP for COPD” for timely identification of palliative care needs in Dutch patients with chronic obstructive pulmonary disease (COPD).

Methods

An iterative and participatory research design was used to develop “I-HARP for COPD”. There were 2 phases to the development of “I-HARP for COPD”: content development and testing. A review of current literature, parallel focus groups, and a questionnaire among experts were used to develop the content of “I-HARP for COPD”. “I-HARP for COPD” was then assessed by health-care professionals (HCPs) in clinical practice for understanding, difficulty, and relevance.

Results

A total of 46 HCPs, 6 patients, 1 informal caregiver, and 1 bereaved informal caregiver participated in this study. “I-HARP for COPD” included 14 screening questions, additional in-depth questions, and recommendations to address identified needs. The content of “I-HARP for COPD” was accepted by 86.2% of the HCPs.

Significance of results

“I-HARP for COPD” was successfully developed for providing guidance in the palliative care of Dutch patients with COPD and their informal caregivers. By supporting HCPs with “I-HARP for COPD”, they are better able to timely identify and direct palliative care needs.
Examining Mediators of the Relationship Between Subjective Age and Cognition
Authors: Siedlecki Karen L. , Kobrinsky Veronika , Aminoff Elissa
Published: February 2024

Abstract: Research has demonstrated associations between subjective age (i.e., the age that one feels) and cognitive performance, although the mechanisms underlying this relationship remain understudied. The current study examined the predictive validity of subjective age on objective and subjective cognition as well as depressive symptoms and self-rated health (SRH) as statistical mediators. We used secondary data analysis comprising the cross-sectional data of 247 adults (ages 50+) to conduct a series of hierarchical linear regressions and mediation analyses. Older subjective age was significantly associated with lower ratings of measures of subjective cognition, and depressive symptoms and SRH partially mediated these relationships. The malleability of depressive symptoms and SRH provide promising directions for future research aimed at enhancing or maintaining cognition in older adults.
On the Derivation of Closed‐Form Expressions for Displacements, Strains, and Stresses Inside Poroelastic Reservoirs
Authors: Cornelissen P. , Meulenbroek B. J. , Jansen J. D.
Published: February 2024

We critically review the derivation of closed‐form analytical expressions for elastic displacements, strains, and stresses inside a subsurface reservoir undergoing pore pressure changes using inclusion theory. Although developed decades ago, inclusion theory has been used recently by various authors to obtain fast estimates of depletion‐induced and injection‐induced fault stresses in relation to induced seismicity. We therefore briefly address the current geomechanical relevance of this method, and provide a numerical example to demonstrate its use to compute induced fault stresses. However, the main goal of our paper is to correct some erroneous assumptions that were made in earlier publications. While the final expressions for the poroelastic stresses in these publications were correct, their derivation contained conceptual mistakes due to the mathematical subtleties that arise because of singularities in the Green's functions. The aim of our paper is therefore to present the correct derivation of expressions for the strains and stresses inside an inclusion and to clarify some of the results of the aforementioned studies. Furthermore, we present two conditions that the strain field must satisfy, which can be used to verify the analytical expressions.
TEA domain transcription factor 1 (TEAD1) induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway
Authors: Song Shuai , Zhang Xiaokai , Huang Zihang , Zhao Yongchao , Lu Shuyang , Zeng Linqi , Cai Fengze , Wang Tongyao , Pei Zhiqiang , Weng Xinyu , Luo Wei , Lu Hao , Wei Zilun , Wu Jian , Yu Peng , Shen Li , Zhang Xiaochun , Sun Aijun , Ge Junbo
Published: February 2024

Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.
Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models
Authors: Antón-Galindo Ester , Adel Maja R. , García-González Judit , Leggieri Adele , López-Blanch Laura , Irimia Manuel , Norton William H. J. , Brennan Caroline H. , Fernàndez-Castillo Noèlia , Cormand Bru
Published: February 2024

RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1sa15940, a zebrafish mutant line with TL background. We found that rbfox1sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1del19, and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.
Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice
Authors: Liu Rongrong , Shang Wenjing , Liu Yingying , Xie Yi , Luan Jun , Zhang Ting , Ma Ying , Wang Zengxian , Sun Yan , Song Xicheng , Han Fengchan
Published: February 2024

The Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells. Our goal of the present study was to investigate the mechanism underlying cochlear cell death in the Fscn2 knockout mice. Microarray analysis revealed upregulation of expression of PARVB, a local adhesion protein, in the inner ears of Fscn2 knockout mice at 8 weeks of age. Further studies showed increased levels of PARVB together with cleaved-Caspase9 and decreased levels of ILK, p-ILK, p-AKT, and Bcl-2 in the inner ears of Fscn2 knockout mice of the same age. Knockdown of Fscn2 in HEI-OCI cells led to decreased cell proliferation ability and migration rate, along with increased levels of PARVB and decreased levels of ILK, p-ILK, p-AKT, Bcl-2 and activated Rac1 and Cdc42. Overexpression of Fscn2 or inhibition of Parvb expression in HEI-OC1 cells promoted cell proliferation and migration, with increased levels of ILK, p-ILK, p-AKT, and Bcl-2. Finally, FSCN2 binds with PPAR-γ to reduce its nuclear translocation in HEI-OC1 cells, and inhibition of PPAR-γ by GW9662 decreased the level of PARVB and increased the levels of p-AKT, p-ILK, and Bcl-2. Our results suggest that FSCN2 negatively regulates PARVB expression by inhibiting the entry of PPAR-γ into the cell nucleus, resulting in inhibition of ILK-AKT related pathways and of cochlear cell survival in Fscn2 knockout mice. Our findings provide new insights and ideas for the prevention and treatment of genetic hearing loss.
Onset of double subduction controls plate motion reorganisation
Authors: Zhang Kuidi , Liao Jie , Gerya Taras
Published: February 2024

Face-to-face double subduction systems, in which two oceanic plates subduct toward each other, are essential elements of plate tectonics. Two subduction zones in such systems are typically uneven in age and their spatially and temporally variable dynamics remain enigmatic. Here, with 2D numerical modelling, we demonstrate that the onset of the younger subduction zone strongly changes the dynamics of the older subduction zone. The waxing younger subduction may gradually absorb plate convergence from the older one, resulting in older subduction waning featured by the dramatic decrease in subduction rate and trench retreat. The dynamical transformation of subduction predominance alters the intraplate stress and mantle flow, regulating the relative motion among the three different plates. The process of waxing and waning of subduction zones controls plate motion reorganisation, providing a reference to interpret the past, present, and future evolution of several key double subduction regions found on the modern Earth.
Articular surface interactions distinguish dinosaurian locomotor joint poses
Authors: Manafzadeh Armita R. , Gatesy Stephen M. , Bhullar Bhart-Anjan S.
Published: February 2024

Our knowledge of vertebrate functional evolution depends on inferences about joint function in extinct taxa. Without rigorous criteria for evaluating joint articulation, however, such analyses risk misleading reconstructions of vertebrate animal motion. Here we propose an approach for synthesizing raycast-based measurements of 3-D articular overlap, symmetry, and congruence into a quantitative “articulation score” for any non-interpenetrating six-degree-of-freedom joint configuration. We apply our methodology to bicondylar hindlimb joints of two extant dinosaurs (guineafowl, emu) and, through comparison with in vivo kinematics, find that locomotor joint poses consistently have high articulation scores. We then exploit this relationship to constrain reconstruction of a pedal walking stride cycle for the extinct dinosaur Deinonychus antirrhopus, demonstrating the utility of our approach. As joint articulation is investigated in more living animals, the framework we establish here can be expanded to accommodate additional joints and clades, facilitating improved understanding of vertebrate animal motion and its evolution.
Causes of death among people living with metastatic cancer
Authors: Mani Kyle , Deng Daxuan , Lin Christine , Wang Ming , Hsu Melinda L. , Zaorsky Nicholas G.
Published: February 2024

Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients with metastatic cancer, across 13 cancer types and 25 non-cancer causes and predict the risk of death after diagnosis from the diagnosed cancer versus other causes (e.g., stroke, heart disease, etc.). Among 1,030,937 US (1992–2019) metastatic cancer survivors, 82.6% of patients (n = 688,529) died due to the diagnosed cancer, while 17.4% (n = 145,006) died of competing causes. Patients with lung, pancreas, esophagus, and stomach tumors are the most likely to die of their metastatic cancer, while those with prostate and breast cancer have the lowest likelihood. The median survival time among patients living with metastases is 10 months; our Fine and Gray competing risk model predicts 1 year survival with area under the receiver operating characteristic curve of 0.754 (95% CI [0.754, 0.754]). Leading non-cancer deaths are heart disease (32.4%), chronic obstructive and pulmonary disease (7.9%), cerebrovascular disease (6.1%), and infection (4.1%).
Rejuvenation as the origin of planar defects in the CrCoNi medium entropy alloy
Authors: Yang Yang , Yin Sheng , Yu Qin , Zhu Yingxin , Ding Jun , Zhang Ruopeng , Ophus Colin , Asta Mark , Ritchie Robert O. , Minor Andrew M.
Published: February 2024

High or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and planar fault boundaries that enhance the ductility, but this has not been verified. Here, we integrate in situ nanomechanical testing with energy-filtered four-dimensional scanning transmission electron microscopy (4D-STEM) and directly observe the rejuvenation during cyclic mechanical loading in single crystal CrCoNi at room temperature. Surprisingly, stacking faults (SFs) and twin boundaries (TBs) are reversible in initial cycles but become irreversible after a thousand cycles, indicating SF energy reduction and rejuvenation. Molecular dynamics (MD) simulation further reveals that the local breakdown of SRO in the MEA triggers these SF reversibility changes. As a result, the deformation features in HEAs/MEAs remain planar and highly localized to the rejuvenated planes, leading to the superior damage tolerance characteristic in this class of alloys.
A signal processing and deep learning framework for methylation detection using Oxford Nanopore sequencing
Authors: Ahsan Mian Umair , Gouru Anagha , Chan Joe , Zhou Wanding , Wang Kai
Published: February 2024

Oxford Nanopore sequencing can detect DNA methylations from ionic current signal of single molecules, offering a unique advantage over conventional methods. Additionally, adaptive sampling, a software-controlled enrichment method for targeted sequencing, allows reduced representation methylation sequencing that can be applied to CpG islands or imprinted regions. Here we present DeepMod2, a comprehensive deep-learning framework for methylation detection using ionic current signal from Nanopore sequencing. DeepMod2 implements both a bidirectional long short-term memory (BiLSTM) model and a Transformer model and can analyze POD5 and FAST5 signal files generated on R9 and R10 flowcells. Additionally, DeepMod2 can run efficiently on central processing unit (CPU) through model pruning and can infer epihaplotypes or haplotype-specific methylation calls from phased reads. We use multiple publicly available and newly generated datasets to evaluate the performance of DeepMod2 under varying scenarios. DeepMod2 has comparable performance to Guppy and Dorado, which are the current state-of-the-art methods from Oxford Nanopore Technologies that remain closed-source. Moreover, we show a high correlation (r = 0.96) between reduced representation and whole-genome Nanopore sequencing. In summary, DeepMod2 is an open-source tool that enables fast and accurate DNA methylation detection from whole-genome or adaptive sequencing data on a diverse range of flowcell types.
Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial
Authors: Hieken Tina J. , Nelson Garth D. , Flotte Thomas J. , Grewal Eric P. , Chen Jun , McWilliams Robert R. , Kottschade Lisa A. , Yang Lu , Domingo-Musibay Evidio , Dronca Roxana S. , Yan Yiyi , Markovic Svetomir N. , Dimou Anastasios , Montane Heather N. , Erskine Courtney L. , Piltin Mara A. , Price Daniel L. , Khariwala Samir S. , Hui Jane , Strand Carrie A. , Harrington Susan M. , Suman Vera J. , Dong Haidong , Block Matthew S.
Published: February 2024

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).
Deep photonic network platform enabling arbitrary and broadband optical functionality
Authors: Najjar Amiri Ali , Vit Aycan Deniz , Gorgulu Kazim , Magden Emir Salih
Published: February 2024

Expanding applications in optical communications, computing, and sensing continue to drive the need for high-performance integrated photonic components. Designing these on-chip systems with arbitrary functionality requires beyond what is possible with physical intuition, for which machine learning-based methods have recently become popular. However, computational demands for physically accurate device simulations present critical challenges, significantly limiting scalability and design flexibility of these methods. Here, we present a highly-scalable, physics-informed design platform for on-chip optical systems with arbitrary functionality, based on deep photonic networks of custom-designed Mach-Zehnder interferometers. Leveraging this platform, we demonstrate ultra-broadband power splitters and a spectral duplexer, each designed within two minutes. The devices exhibit state-of-the-art experimental performance with insertion losses below 0.66 dB, and 1-dB bandwidths exceeding 120 nm. This platform provides a tractable path towards systematic, large-scale photonic system design, enabling custom power, phase, and dispersion profiles for high-throughput communications, quantum information processing, and medical/biological sensing applications.
Effects of human disturbances on wildlife behaviour and consequences for predator-prey overlap in Southeast Asia
Authors: Lee Samuel Xin Tham , Amir Zachary , Moore Jonathan H. , Gaynor Kaitlyn M. , Luskin Matthew Scott
Published: February 2024

Some animal species shift their activity towards increased nocturnality in disturbed habitats to avoid predominantly diurnal humans. This may alter diel overlap among species, a precondition to most predation and competition interactions that structure food webs. Here, using camera trap data from 10 tropical forest landscapes, we find that hyperdiverse Southeast Asian wildlife communities shift their peak activity from early mornings in intact habitats towards dawn and dusk in disturbed habitats (increased crepuscularity). Our results indicate that anthropogenic disturbances drive opposing behavioural adaptations based on rarity, size and feeding guild, with more nocturnality among the 59 rarer specialists’ species, more diurnality for medium-sized generalists, and less diurnality for larger hunted species. Species turnover also played a role in underpinning community- and guild-level responses, with disturbances associated with markedly more detections of diurnal generalists and their medium-sized diurnal predators. However, overlap among predator-prey or competitor guilds does not vary with disturbance, suggesting that net species interactions may be conserved.
VO2 memristor-based frequency converter with in-situ synthesize and mix for wireless internet-of-things
Authors: Liu Chang , Tiw Pek Jun , Zhang Teng , Wang Yanghao , Cai Lei , Yuan Rui , Pan Zelun , Yue Wenshuo , Tao Yaoyu , Yang Yuchao
Published: February 2024

Wireless internet-of-things (WIoT) with data acquisition sensors are evolving rapidly and the demand for transmission efficiency is growing rapidly. Frequency converter that synthesizes signals at different frequencies and mixes them with sensor datastreams is a key component for efficient wireless transmission. However, existing frequency converters employ separate synthesize and mix circuits with complex digital and analog circuits using complementary metal-oxide semiconductor (CMOS) devices, naturally incurring excessive latency and energy consumption. Here we report a highly uniform and calibratable VO2 memristor oscillator, based on which we build memristor-based frequency converter using 8$$\times$$
×
8 VO2 array that can realize in-situ frequency synthesize and mix with help of compact periphery circuits. We investigate the self-oscillation based on negative differential resistance of VO2 memristors and the programmability with different driving currents and calibration resistances, demonstrating capabilities of such frequency converter for in-situ frequency synthesize and mix for 2 ~ 8 channels with frequencies up to 48 kHz for low frequency transmission link. When transmitting classical sensor data (acoustic, vision and spatial) in an end-to-end WIoT experimental setup, our VO2-based memristive frequency converter presents up to 1.45× ~ 1.94× power enhancement with only 0.02 ~ 0.21 dB performance degradations compared with conventional CMOS-based frequency converter. This work highlights the potential in solving frequency converter’s speed and energy efficiency problems in WIoT using high crystalline quality epitaxially grown VO2 and calibratable VO2-based oscillator array, revealing a promising direction for next-generation WIoT system design.
Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab
Authors: Meng Pei , Dalal Hina , Chen Yilun , Brueffer Christian , Gladchuk Sergii , Alcaide Miguel , Ehinger Anna , Saal Lao H.
Published: February 2024

HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological “ultrahigh” ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1–9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1–12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.
Computational demystification of iron carbonyls formation under syngas environment
Authors: Bentria El Tayeb , Shenai Prathamesh Mahesh , Sanvito Stefano , Park Heesoo , Béland Laurent Karim , Laycock Nicholas , El Mellouhi Fedwa
Published: February 2024

Iron pentacarbonyl (IPC) gas forms upon the reaction of carbon monoxide with Fe containing metallic surfaces under gas reforming conditions. IPC formation can sometimes reach alarming levels that cause metal loss, pipeline thinning corrosion, catalyst poisoning, and contamination of sensitive industrial equipment. In this work, we demystify using multiscale computational modeling the mechanism of Iron pentacarbonyl formation: Density functional theory (DFT) is used to explore various catalytic reactions that involve a Fe adatom reacting with adsorbed carbon monoxide. Our calculated carbonyls desorption barriers on a perfect and clean Fe surface are too high to allow the carbonyls to form then desorb at temperatures <500 K at the rates reported experimentally. Most importantly, our calculations indicate that a high CO surface coverage, in addition to the presence of Fe adatoms, favors carbonyl formation and its desorption towards the flowing gas medium. Using insights extracted from ab initio molecular dynamics simulations, we propose that the most plausible IPC formation mechanism consists of: (1) on surface reactions of adsorbed CO molecules with an Fe adatom to form iron tricarbonyl (Fe(CO)3*) molecules; (2) an adsorbate assisted movement of iron tricarbonyl on top of the CO adlayer; and (3) the interaction of iron tricarbonyl with CO molecules from the gaseous medium eventually leading to iron adatom removal as Fe(CO)5 gas.
Mechanisms and kinetic model for steel corrosion in unsaturated cementitious materials
Authors: Tian Zushi , Fu Chuanqing , Ye Hailong
Published: February 2024

Considering the complex coupling of steel corrosion in partially saturated concrete filled with water, the quantitative description of control mechanisms is still under debate. This work provides new experimental evidence supporting that diffusion control (relative diffusion coefficient) is the dominant mechanism in controlling corrosion rate by limiting the ferrous ion migration in unsaturated concrete. Furthermore, a new mechanism-based kinetic model is developed to predict the corrosion rate in different cementitious materials and corrosion conditions. In addition, the proposed kinetic model can quantify the variation of critical [Cl−]/[OH−] with degree of saturation, classify corrosive conditions, and predict the electrical resistivity and corrosion rate relationships.
TREX reveals proteins that bind to specific RNA regions in living cells
Authors: Dodel Martin , Guiducci Giulia , Dermit Maria , Krishnamurthy Sneha , Alard Emilie L. , Capraro Federica , Rekad Zeinab , Stojic Lovorka , Mardakheh Faraz K.
Published: February 2024

Different regions of RNA molecules can often engage in specific interactions with distinct RNA-binding proteins (RBPs), giving rise to diverse modalities of RNA regulation and function. However, there are currently no methods for unbiased identification of RBPs that interact with specific RNA regions in living cells and under endogenous settings. Here we introduce TREX (targeted RNase H-mediated extraction of crosslinked RBPs)—a highly sensitive approach for identifying proteins that directly bind to specific RNA regions in living cells. We demonstrate that TREX outperforms existing methods in identifying known interactors of U1 snRNA, and reveals endogenous region-specific interactors of NORAD long noncoding RNA. Using TREX, we generated a comprehensive region-by-region interactome for 45S rRNA, uncovering both established and previously unknown interactions that regulate ribosome biogenesis. With its applicability to different cell types, TREX is an RNA-centric tool for unbiased positional mapping of endogenous RNA–protein interactions in living cells.
Shorter self-reported sleep duration is associated with worse virtual spatial navigation performance in men
Authors: Yavuz Emre , Gahnstrom Christoffer J. , Goodroe Sarah , Coutrot Antoine , Hornberger Michael , Lazar Alpar S. , Spiers Hugo J.
Published: February 2024

Sleep has been shown to impact navigation ability. However, it remains unclear how different sleep-related variables may be independently associated with spatial navigation performance, and as to whether gender may play a role in these associations. We used a mobile video game app, Sea Hero Quest (SHQ), to measure wayfinding ability in US-based participants. Wayfinding performance on SHQ has been shown to correlate with real-world wayfinding. Participants were asked to report their sleep duration, quality, daytime sleepiness and nap frequency and duration on a typical night (n = 766, 335 men, 431 women, mean age = 26.5 years, range = 18–59 years). A multiple linear regression was used to identify which self-reported sleep variables were independently associated with wayfinding performance. Shorter self-reported sleep durations were significantly associated with worse wayfinding performance in men only. Other self-reported sleep variables showed non-significant trends of association with wayfinding performance. When removing non-typical sleepers (< 6 or > 9 h of sleep on a typical night), the significant association between sleep duration and spatial navigation performance in men was no longer present. These findings from U.S.-based participants suggest that a longer self-reported sleep duration may be an important contributor to successful navigation ability in men.
Insights into gut microbiomes in stem cell transplantation by comprehensive shotgun long-read sequencing
Authors: Spohr Philipp , Scharf Sebastian , Rommerskirchen Anna , Henrich Birgit , Jäger Paul , Klau Gunnar W. , Haas Rainer , Dilthey Alexander , Pfeffer Klaus
Published: February 2024

The gut microbiome is a diverse ecosystem, dominated by bacteria; however, fungi, phages/viruses, archaea, and protozoa are also important members of the gut microbiota. Exploration of taxonomic compositions beyond bacteria as well as an understanding of the interaction between the bacteriome with the other members is limited using 16S rDNA sequencing. Here, we developed a pipeline enabling the simultaneous interrogation of the gut microbiome (bacteriome, mycobiome, archaeome, eukaryome, DNA virome) and of antibiotic resistance genes based on optimized long-read shotgun metagenomics protocols and custom bioinformatics. Using our pipeline we investigated the longitudinal composition of the gut microbiome in an exploratory clinical study in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT; n = 31). Pre-transplantation microbiomes exhibited a 3-cluster structure, characterized by Bacteroides spp. /Phocaeicola spp., mixed composition and Enterococcus abundances. We revealed substantial inter-individual and temporal variabilities of microbial domain compositions, human DNA, and antibiotic resistance genes during the course of alloHSCT. Interestingly, viruses and fungi accounted for substantial proportions of microbiome content in individual samples. In the course of HSCT, bacterial strains were stable or newly acquired. Our results demonstrate the disruptive potential of alloHSCTon the gut microbiome and pave the way for future comprehensive microbiome studies based on long-read metagenomics.
Guiding role of esophageal variceal diameter in treatment of endoscopic ligation: an animal experimental study
Authors: Li Zhiqun , LingHu Enqiang , Li Weimin , Zhou Licai
Published: February 2024

In this study, according to the Location, Diameter, Risk factor (LDRf) classification principle, the influence and effect of esophageal varices diameter on the degree of complete ligation of multicyclic ligator were investigated. Methods. The esophageal veins of healthy piglets were filled with methylene blue solution, and the in vitro pig esophageal varices model was made, which were divided into three groups according to the diameter of esophageal varices: D1, 0.4–1.0 cm; D2, 1.1–1.5 cm; and D3, 1.6–2.0 cm. Finally, the ligation effect of each group was analyzed statistically. A total of 407 ligations were performed on the simulated esophageal variceal model. There were 103 ligations in the D1 group and 98 were complete (95.15%, 98/103); 151 ligations in the D2 group and 47 were complete (31.13%, 47/151); and 153 ligations in the D3 group but none were complete (0%, 0/153). There was significant difference in the degree of complete ligation between the two groups (χ2 = 38.0014, P ≤ 0.001). In the varicose ligation model, the complete ligation effect was the most complete and robust when the varicose diameter was 0.4–1.0 cm. This study showed that the varicose vein diameter in LDRf classification was reasonable and feasible to guide endoscopic varicose vein ligation.
Exploring stress response’s role in executive function impairments among adults with early adverse childhood experiences
Authors: Victor Taïna Steevine , Jacquet Baptiste , El Massioui Farid
Published: February 2024

Adverse childhood experiences (ACEs) are recognised as precursors to numerous physical and mental health challenges. However, research on their impact on inhibitory control and working memory, particularly among healthy young adults, remains limited. The role played by the stress response as a moderator in these effects is likewise underexplored. Our study addresses this gap by examining cognitive impairments in non-clinical adults with early childhood trauma, specifically trauma before the age of 13 years, and by assessing the influence of the stress response on these effects. A total of 15 participants with early ACEs were compared with a control group (n = 18) using the Corsi Block Tapping Test (CBTT) and Stroop Word Colour Test (SCWT). Results showed that participants with early ACEs exhibited lower scores on the SCWT but not the CBTT. The stress response emerged as a potential factor in the relationship between early ACEs and cognitive performance. The implications of these findings are then discussed in relation to the existing literature.
Prolyl hydroxylase domain inhibitor is an effective pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock
Authors: Wu Xiaowu , Cap Andrew P. , Bynum James A. , Chance Tiffani C. , Darlington Daniel N. , Meledeo Michael A.
Published: February 2024

Pre-hospital potentially preventable trauma related deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock, acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 h following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.