bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of post-operative iron biomarkers in colorectal cancer: population-based patient cohort
Authors: Gwenzi Tafirenyika , Schrotz-King Petra , Anker Sophie C. , Schöttker Ben , Hoffmeister Michael , Brenner Hermann 
Published: August 2024

Abstract
Background
Post-operative anaemia is linked to iron deficiency. We investigated the prognostic value of post-operative iron biomarkers in colorectal cancer (CRC).

Methods
Ferritin, transferrin, iron, and transferrin saturation (TS%) were measured from blood collected at a single time-point post-surgery in 2769 CRC patients. Associations between iron biomarkers with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox regression with hazard ratios (HR), stratified by post-operative time of blood collection (<1-month/≥1-month).

Results
After a median follow-up of 9.5 years, 52.6% of patients had died. For iron biomarkers assessed <1-month post-surgery, higher compared to normal TS% was associated with shorter CSS (HR [95% CI] = 2.36 [1.25–4.46]), and higher iron levels with better OS (upper vs. median tertile: HR [95% CI] = 0.79 [0.65–0.97]). When assessed ≥1-month post-surgery, elevated ferritin was associated with poor CSS (high vs. normal: HR [95% CI] = 1.44 [1.10–1.87]), and low TS% with worse CSS (low vs. normal: HR [95% CI] = 1.60 [1.24–2.06]). Similar but weaker associations were observed for OS.

Conclusion
Monitoring of serum ferritin and TS% beyond 1-month post-surgery may be relevant for risk stratification of patients with operable CRC. Future studies should validate our findings.
Intention to have blood-based multi-cancer early detection (MCED) screening: a cross-sectional population-based survey in England
Authors: Schmeising-Barnes Ninian , Waller Jo , Marlow Laura A. V. 
Published: August 2024

Abstract
Background
Trials assessing the clinical utility of blood-based multi-cancer early detection (MCED) tests are underway. Understanding public attitudes towards MCED screening is essential if these tests are to be used. We aimed to quantify MCED screening intention and potential barriers and facilitators to uptake.

Methods
Adults aged 50–77 (n = 958) completed an online survey. The primary outcome was intention to have MCED screening if offered. Psychological variables including barriers and facilitators were assessed. We used logistic regressions to explore associations between socio-demographics and psychological factors and intention.

Results
93.8% of participants said they would ‘definitely’ or ‘probably’ have MCED screening if offered. Intention was significantly associated with previous screening participation and general cancer attitudes but not with socio-demographic factors. Participants were more likely to be intenders if they had higher health motivation, and perceived greater benefits of blood tests. Participants were less likely to be intenders if they perceived greater disadvantages of blood tests, more practical barriers, were more worried about the outcome and more concerned about a positive result.

Conclusions and implications
MCED screening intention was high. The lack of socio-demographic variation suggests equitable interest in this type of screening; however, future research should consider how intention translates to uptake.
TRPA1 aggravates osteoclastogenesis and osteoporosis through activating endoplasmic reticulum stress mediated by SRXN1
Authors: Zhu Pengfei , Tao Huaqiang , Chen Kai , Chu Miao , Wang Qiufei , Yang Xing , Zhou Jun , Yang Huilin , Geng Dechun 
Published: August 2024

AbstractOsteoporosis (OP) is a disorder of bone remodeling caused by an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, inhibiting excessive osteoclast activity is one of the promising strategies for treating OP. A major transient receptor potential cation channel, known as transient receptor potential ankyrin 1 (TRPA1), was found to alleviate joint pain and cartilage degeneration in osteoarthritis. However, little research has focused on TRPA1 function in OP. As a result, this study aimed to explore the TRPA1 characteristics and its potential therapeutic function during osteoclastogenesis. The TRPA1 expression gradually increased in the osteoclast differentiation process; however, its suppression with small interfering RNA and an inhibitor (HC030031) significantly controlled the osteoclast count and the expression of osteoclast characteristic genes. Its suppression also inhibited endoplasmic reticulum (ER) stress-related pancreatic ER kinase (PERK) pathways. An ER stress inhibitor (thapsigargin) reversed the down-regulated levels of ER stress and osteoclast differentiation by suppressing TRPA1. Transcriptome sequencing results demonstrated that TRPA1 negatively regulated reactive oxygen species (ROS) and significantly increased the expression of an antioxidant gene, SRXN1. The osteoclast differentiation and the levels of ER stress were enhanced with SRXN1 inhibition. Finally, TRPA1 knockdown targeting macrophages by adeno-associated virus-9 could relieve osteoclast differentiation and osteopenia in ovariectomized mice. In summary, silencing TRPA1 restrained osteoclast differentiation through ROS-mediated down-regulation of ER stress via inhibiting PERK pathways. The study also indicated that TRPA1 might become a prospective treatment target for OP.
Enantiospecificity in NMR enabled by chirality-induced spin selectivity
Authors: Georgiou T. , Palma J. L. , Mujica V. , Varela S. , Galante M. , Santamaría-García V. J. , Mboning L. , Schwartz R. N. , Cuniberti G. , Bouchard L.-S. 
Published: August 2024

AbstractSpin polarization in chiral molecules is a magnetic molecular response associated with electron transport and enantioselective bond polarization that occurs even in the absence of an external magnetic field. An unexpected finding by Santos and co-workers reported enantiospecific NMR responses in solid-state cross-polarization (CP) experiments, suggesting a possible additional contribution to the indirect nuclear spin-spin coupling in chiral molecules induced by bond polarization in the presence of spin-orbit coupling. Herein we provide a theoretical treatment for this phenomenon, presenting an effective spin-Hamiltonian for helical molecules like DNA and density functional theory (DFT) results on amino acids that confirm the dependence of J-couplings on the choice of enantiomer. The connection between nuclear spin dynamics and chirality could offer insights for molecular sensing and quantum information sciences. These results establish NMR as a potential tool for chiral discrimination without external agents.
Neuromorphic overparameterisation and few-shot learning in multilayer physical neural networks
Authors: Stenning Kilian D. , Gartside Jack C. , Manneschi Luca , Cheung Christopher T. S. , Chen Tony , Vanstone Alex , Love Jake , Holder Holly , Caravelli Francesco , Kurebayashi Hidekazu , Everschor-Sitte Karin , Vasilaki Eleni , Branford Will R. 
Published: August 2024

AbstractPhysical neuromorphic computing, exploiting the complex dynamics of physical systems, has seen rapid advancements in sophistication and performance. Physical reservoir computing, a subset of neuromorphic computing, faces limitations due to its reliance on single systems. This constrains output dimensionality and dynamic range, limiting performance to a narrow range of tasks. Here, we engineer a suite of nanomagnetic array physical reservoirs and interconnect them in parallel and series to create a multilayer neural network architecture. The output of one reservoir is recorded, scaled and virtually fed as input to the next reservoir. This networked approach increases output dimensionality, internal dynamics and computational performance. We demonstrate that a physical neuromorphic system can achieve an overparameterised state, facilitating meta-learning on small training sets and yielding strong performance across a wide range of tasks. Our approach’s efficacy is further demonstrated through few-shot learning, where the system rapidly adapts to new tasks.
Tropical peat composition may provide a negative feedback on fire occurrence and severity
Authors: Crawford Alastair J. , Belcher Claire M. , New Stacey , Gallego-Sala Angela , Swindles Graeme T. , Page Susan , Blyakharchuk Tatiana A. , Cadillo-Quiroz Hinsby , Charman Dan J. , Gałka Mariusz , Hughes Paul D. M. , Lähteenoja Outi , Mauquoy Dmitri , Roland Thomas P. , Väliranta Minna 
Published: August 2024

AbstractLoss of peat through increased burning will have major impacts on the global carbon cycle. In a normal hydrological state, the risk of fire propagation is largely controlled by peat bulk density and moisture content. However, where humans have interfered with the moisture status of peat either via drainage, or indirectly via climate change, we hypothesise that its botanical composition will become important to flammability, such that peats from different latitudes might have different compositionally-driven susceptibility to ignition. We use pyrolysis combustion flow calorimetry to determine the temperature of maximum thermal decomposition (Tmax) of peats from different latitudes, and couple this to a botanical composition analysis. We find that tropical peat has higher Tmax than other regions, likely on account of its higher wood content which appears to convey a greater resistance to ignition. This resistance also increases with depth, which means that loss of surface peat in tropical regions may lead to a reduction in the subsequent ignitability of deeper peat layers as they are exposed, potentially resulting in a negative feedback on increased fire occurrence and severity.
Extensive hydrogen incorporation is not necessary for superconductivity in topotactically reduced nickelates
Authors: Balakrishnan Purnima P. , Ferenc Segedin Dan , Chow Lin Er , Quarterman P. , Muramoto Shin , Surendran Mythili , Patel Ranjan K. , LaBollita Harrison , Pan Grace A. , Song Qi , Zhang Yang , El Baggari Ismail , Jagadish Koushik , Shao Yu-Tsun , Goodge Berit H. , Kourkoutis Lena F. , Middey Srimanta , Botana Antia S. , Ravichandran Jayakanth , Ariando A. , Mundy Julia A. , Grutter Alexander J. 
Published: August 2024

AbstractA key open question in the study of layered superconducting nickelate films is the role that hydrogen incorporation into the lattice plays in the appearance of the superconducting state. Due to the challenges of stabilizing highly crystalline square planar nickelate films, films are prepared by the deposition of a more stable parent compound which is then transformed into the target phase via a topotactic reaction with a strongly reducing agent such as CaH2. Recent studies, both experimental and theoretical, have introduced the possibility that the incorporation of hydrogen from the reducing agent into the nickelate lattice may be critical for the superconductivity. In this work, we use secondary ion mass spectrometry to examine superconducting La1−xXxNiO2 / SrTiO3 (X = Ca and Sr) and Nd6Ni5O12 / NdGaO3 films, along with non-superconducting NdNiO2 / SrTiO3 and (Nd,Sr)NiO2 / SrTiO3. We find no evidence for extensive hydrogen incorporation across a broad range of samples, including both superconducting and non-superconducting films. Theoretical calculations indicate that hydrogen incorporation is broadly energetically unfavorable in these systems, supporting our conclusion that extensive hydrogen incorporation is not generally required to achieve a superconducting state in layered square-planar nickelates.
DNA polymerase α-primase facilitates PARP inhibitor-induced fork acceleration and protects BRCA1-deficient cells against ssDNA gaps
Authors: Machacova Zuzana , Chroma Katarina , Lukac David , Protivankova Iva , Moudry Pavel 
Published: August 2024

AbstractPARP inhibitors (PARPi), known for their ability to induce replication gaps and accelerate replication forks, have become potent agents in anticancer therapy. However, the molecular mechanism underlying PARPi-induced fork acceleration has remained elusive. Here, we show that the first PARPi-induced effect on DNA replication is an increased replication fork rate, followed by a secondary reduction in origin activity. Through the systematic knockdown of human DNA polymerases, we identify POLA1 as mediator of PARPi-induced fork acceleration. This acceleration depends on both DNA polymerase α and primase activities. Additionally, the depletion of POLA1 increases the accumulation of replication gaps induced by PARP inhibition, sensitizing cells to PARPi. BRCA1-depleted cells are especially susceptible to the formation of replication gaps under POLA1 inhibition. Accordingly, BRCA1 deficiency sensitizes cells to POLA1 inhibition. Thus, our findings establish the POLA complex as important player in PARPi-induced fork acceleration and provide evidence that lagging strand synthesis represents a targetable vulnerability in BRCA1-deficient cells.
Computing the alpha complex using dual active set quadratic programming
Authors: Carlsson Erik , Carlsson John 
Published: August 2024

AbstractThe alpha complex is a fundamental data structure from computational geometry, which encodes the topological type of a union of balls $$B(x;r) \subset {\mathbb {R}}^m$$

B

(
x
;
r
)

⊂

R

m

for $$x\in S$$

x
∈
S

, including a weighted version that allows for varying radii. It consists of the collection of “simplices” $$\sigma =\{x_0,...,x_k\} \subset S$$

σ
=
{

x
0

,
.
.
.
,

x
k

}
⊂
S

, which correspond to nonempty $$(k+1)$$

(
k
+
1
)

-fold intersections of cells in a radius-restricted version of the Voronoi diagram $${{\,\textrm{Vor}\,}}(S,r)$$

Vor

(
S
,
r
)

. Existing algorithms for computing the alpha complex require that the points reside in low dimension because they begin by computing the entire Delaunay complex, which rapidly becomes intractable, even when the alpha complex is of a reasonable size. This paper presents a method for computing the alpha complex without computing the full Delaunay triangulation by applying Lagrangian duality, specifically an algorithm based on dual quadratic programming that seeks to rule simplices out rather than ruling them in.
Differences in macular thickness associated with peripheral retinal vessel whitening in diabetic patients
Authors: Kalaw Fritz Gerald P. , Sharma Paripoorna , Walker Evan , Borooah Shyamanga 
Published: August 2024

AbstractThis study aimed to determine the difference in macular thickness among patients with diabetes mellitus (DM) with and without peripheral retinal vessel whitening (PRVW). PRVW was defined by retinal vessel whitening outside the standard seven ETDRS fields. Subjects were divided into DM with PRVW, DM without PRVW, and normal age-matched controls. Optical coherence tomography scans were divided into total, inner, and outer retinal layer thicknesses and were compared in the macula's central, inner, and outer rings. Forty-seven eyes were included: DM with PRVW = 15, DM without PRVW = 16, and Controls = 16. Overall, the mean retinal thickness in patients with DM with PRVW was lower than in patients with DM without PRVW and controls. In the inner macula, DM patients with PRVW showed a significantly lower mean inner superior, nasal, inferior, and temporal macula compared to DM patients without PRVW (p = 0.014, 0.008, 0.005, < 0.001, respectively). DM patients with PRVW also showed a significantly lower mean outer superior, nasal, inferior, and temporal macula than controls (p = 0.005, 0.005, 0.016, 0.025, respectively). This study demonstrates that PRVW in DM patients may be associated with global structural changes to the macular region, promoting a decrease in inner and outer retinal thickness. Further studies should investigate the functional correlation with PRVW in DM patients in order to better understand its potential implications in diabetic patients.
Transcriptome analysis of Drosophila suzukii reveals molecular mechanisms conferring pyrethroid and spinosad resistance
Authors: Tabuloc Christine A. , Carlson Curtis R. , Ganjisaffar Fatemeh , Truong Cindy C. , Chen Ching-Hsuan , Lewald Kyle M. , Hidalgo Sergio , Nicola Nicole L. , Jones Cera E. , Sial Ashfaq A. , Zalom Frank G. , Chiu Joanna C. 
Published: August 2024

AbstractDrosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.
Effect of welding parameters on microstructure and mechanical properties of dissimilar AISI 304/ductile cast iron fusion welded joints
Authors: El-Shennawy M. , Abdel-Aleem H. A. , Ghanem M. M. , Sehsah A. M. 
Published: August 2024

AbstractProblems associated with dissimilar fusion welding are mainly originated from the differences in melting points, coefficients of thermal conductivity and thermal expansion, …etc., and carbon content when welding dissimilar ferrous materials. In this study, the problems associated with dissimilar fusion welding of stainless steel AISI304 with ductile cast iron DCI grade A536 were investigated. Using shielded metal arc welding (SMAW) process, various welding parameters were studied to investigate the successful/accepted dissimilar welded joint(s). Welding electrodes and welding techniques were the main studied parameters. Microstructural and mechanical investigations were carried out for welded joints under different welding parameters. Tensile, impact and hardness tests coupled with optical and scanning electron microscopic examinations with EDX analysis were made for metallurgical and mechanical evaluations of welded joints. This extensive study could solve the problem of dissimilar welding between ductile cast iron and 304 stainless steel. The main results showed that joints welded by ENiCrFe-3 electrode in root pass and ENiFe-CI in filling passes were the successful dissimilar welded joints with 422 MPa tensile strength which represents 104% of annealed DCI base metal and without any changes in toughness properties, where toughness at HAZ of DCI was 18 J. High Ni content in weld metal increased the strength, ductility and reduced the weld metal dilution.
Oxidative stress and regulation of adipogenic differentiation capacity by sirtuins in adipose stem cells derived from female patients of advancing age
Authors: Bernhardt Anne , Jamil Alan , Morshed Md. Tanvir , Ponnath Pia , Gille Veronika , Stephan Nadine , Sauer Heinrich , Wartenberg Maria 
Published: August 2024

AbstractPatient age is critical for mesenchymal stem cell quality and differentiation capacity. We demonstrate that proliferation and adipogenic capacity of subcutaneous adipose stem cells (ASCs) from female patients declined with advanced age, associated with reduction in cell nucleus size, increase in nuclear lamina protein lamin B1/B2, and lamin A, upregulation of senescence marker p16INK4a and senescence-associated β-galactosidase activity. Adipogenic induction resulted in differentiation of adipocytes and upregulation of adipogenic genes CCAAT enhancer binding protein alpha, fatty acid binding protein 4, lipoprotein lipase, and peroxisome proliferator-activated receptor-γ, which was not affected by the Sirt-1 activator YK-3-237 or the Sirt-1 inhibitor EX-527. Protein expression of the stem cell markers Oct4 and Sox2 was not significantly downregulated with advanced patient age. Mitochondrial reactive oxygen species were increased in ASCs from old-aged patients, whereas protein expression of NADPH oxidases NOX1 and NOX4 was downregulated, and dual oxidase isoforms remained unchanged. Generation of nitric oxide and iNOS expression was downregulated. Protein expression of Sirt-1 and Sirt-3 decreased with patient age, whereas Sirt-2 and Sirt-5 remained unchanged. Induction of adipogenesis stimulated protein expression of Sirt-1 and Sirt-3, which was not affected upon pre-incubation with the Sirt-1-activator YK-3-237 or the Sirt-1-inhibitor EX-527. The Sirt-1 inhibitor Sirtinol downregulated adiponectin protein expression and the number of adipocytes, whereas YK-3-237 exerted stimulatory effects. In summary, our data demonstrate increased oxidative stress in ASCs of aging patients, and decline of adipogenic capacity due to Sirt-1- mediated adiponectin downregulation in elderly patients.
Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are associated with insecticide resistance in the major malaria vectors Anopheles gambiae s.l. and Anopheles funestus
Authors: Logan Rhiannon Agnes Ellis , Mäurer Julia Bettina , Wapler Charlotte , Ingham Victoria Anne 
Published: August 2024

AbstractMalaria remains one of the highest causes of morbidity and mortality, with 249 million cases and over 608,000 deaths in 2022. Insecticides, which target the Anopheles mosquito vector, are the primary method to control malaria. The widespread nature of resistance to the most important insecticide class, the pyrethroids, threatens the control of this disease. To reverse the stall in malaria control there is urgent need for new vector control tools, which necessitates understanding the molecular basis of pyrethroid resistance. In this study we utilised multi-omics data to identify uridine-diphosphate (UDP)-glycosyltransferases (UGTs) potentially involved in resistance across multiple Anopheles species. Phylogenetic analysis identifies sequence similarities between Anopheline UGTs and those involved in agricultural pesticide resistance to pyrethroids, pyrroles and spinosyns. Expression of five UGTs was characterised in An. gambiae and An. coluzzii to determine constitutive over-expression, induction, and tissue specificity. Furthermore, a UGT inhibitor, sulfinpyrazone, restored susceptibility to pyrethroids and DDT in An. gambiae, An. coluzzii, An. arabiensis and An. funestus, the major African malaria vectors. Taken together, this study provides clear association of UGTs with pyrethroid resistance as well as highlighting the potential use of sulfinpyrazone as a novel synergist for vector control.