bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cu(I) binds to Zn7-MT2 via two parallel pathways
Authors: Melenbacher Adyn , Stillman Martin J 
Published: September 2023

Abstract
Metallothionein proteins are essential for Cu(I) and Zn(II) homeostasis as well as heavy metal detoxification. The metallation properties of MT2 are of great interest due to their wide patterns of expression and correlation with multiple diseases including cancers, neurological disorders, and respiratory diseases. Use of isotopically pure 63Cu(I) and 68Zn(II) eliminates the complexity of the Cu, Zn-MT2 mass spectral peaks due to significant overlap of naturally abundant isotopes. This allows for the resolution of the precise Cu(I) and Zn(II) stoichiometries when both Cu(I) and Zn(II) are bound to MT2 at physiological pH as expected in vivo. Exact Cu: Zn ratios were determined from mass spectral simulations carried out for every point in the titration. We report that Cu(I) metallation of Zn7-MT2 can only be understood in terms of two pathways occurring in parallel with pathway ① resulting in Cu5Zn5-MT2 and Cu9Zn3-MT2. Pathway ② results in Cu6Zn4-MT2 and Cu10Zn2-MT2, which are the major products of the reaction. From the electrospray ionization (ESI)–mass spectral data we report a series of formation constants (KF) for species starting from Zn7-MT2 up to Cu11Zn2-MT2. Room temperature phosphorescence and circular dichroism (CD) spectra were measured in parallel with the ESI–mass spectrometry data allowing for the assignment of specific species to specific spectral bands. Through analysis of the CD spectral bands, we propose that Cu(I) binds to the β domain first to form a Cu5Zn1 cluster or Cu6 cluster with emission at 670 and 750 nm, respectively, leaving the Zn4 cluster in the α domain.
Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation
Authors: Gao Zeqian , Smith Alastair L , Scott James N F , Bevington Sarah L , Boyes Joan 
Published: September 2023

AbstractTranscription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3′ Igλ domain, Eλ3–1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and antisense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3–1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.
Characterization of a promiscuous DNA sulfur binding domain and application in site-directed RNA base editing
Authors: Hu Wenyue , Yang Bingxu , Xiao Qingjie , Wang Yuli , Shuai Yuting , Zhao Gong , Zhang Lixin , Deng Zixin , He Xinyi , Liu Guang 
Published: September 2023

Abstract
Phosphorothioate (PT)-modification was discovered in prokaryotes and is involved in many biological functions such as restriction-modification systems. PT-modification can be recognized by the sulfur binding domains (SBDs) of PT-dependent restriction endonucleases, through coordination with the sulfur atom, accompanied by interactions with the DNA backbone and bases. The unique characteristics of PT recognition endow SBDs with the potential to be developed into gene-targeting tools, but previously reported SBDs display sequence-specificity for PT-DNA, which limits their applications. In this work, we identified a novel sequence-promiscuous SBDHga from Hahella ganghwensis. We solved the crystal structure of SBDHga complexed with PT-DNA substrate to 1.8 Å resolution and revealed the recognition mechanism. A shorter L4 loop of SBDHga interacts with the DNA backbone, in contrast with previously reported SBDs, which interact with DNA bases. Furthermore, we explored the feasibility of using SBDHga and a PT-oligonucleotide as targeting tools for site-directed adenosine-to-inosine (A-to-I) RNA editing. A GFP non-sense mutant RNA was repaired at about 60% by harnessing a chimeric SBD-hADAR2DD (deaminase domain of human adenosine deaminase acting on RNA), comparable with currently available RNA editing techniques. This work provides insights into understanding the mechanism of sequence-specificity for SBDs and for developing new tools for gene therapy.
Lifeworlds in pain: a principled method for investigation and intervention
Authors: Tabor Abby , Constant Axel 
Published: September 2023

AbstractThe experience of pain spans biological, psychological and sociocultural realms, both basic and complex, it is by turns necessary and devastating. Despite an extensive knowledge of the constituents of pain, the ability to translate this into effective intervention remains limited. It is suggested that current, multiscale, medical approaches, largely informed by the biopsychosocial (BPS) model, attempt to integrate knowledge but are undermined by an epistemological obligation, one that necessitates a prior isolation of the constituent parts. To overcome this impasse, we propose that an anthropological stance needs to be taken, underpinned by a Bayesian apparatus situated in computational psychiatry. Here, pain is presented within the context of lifeworlds, where attention is shifted away from the constituents of experience (e.g. nociception, reward processing and fear-avoidance), towards the dynamic affiliation that occurs between these processes over time. We argue that one can derive a principled method of investigation and intervention for pain from modelling approaches in computational psychiatry. We suggest that these modelling methods provide the necessary apparatus to navigate multiscale ontology and epistemology of pain. Finally, a unified approach to the experience of pain is presented, where the relational, inter-subjective phenomenology of pain is brought into contact with a principled method of translation; in so doing, revealing the conditions and possibilities of lifeworlds in pain.
Diffuse midline glioma invasion and metastasis rely on cell-autonomous signaling
Authors: Bruschi Marco , Midjek Lilia , Ajlil Yassine , Vairy Stephanie , Lancien Manon , Ghermaoui Samia , Kergrohen Thomas , Verreault Maite , Idbaih Ahmed , de Biagi Carlos Alberto Oliveira , Liu Ilon , Filbin Mariella G , Beccaria Kevin , Blauwblomme Thomas , Puget Stephanie , Tauziede-Espariat Arnault , Varlet Pascale , Dangouloff-Ros Volodia , Boddaert Nathalie , Le Teuff Gwenael , Grill Jacques , Montagnac Guillaume , Elkhatib Nadia , Debily Marie-Anne , Castel David 
Published: September 2023

Abstract

Background
Diffuse midline gliomas (DMG) are pediatric tumors with negligible 2-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease, all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current clues as to what causes tumor infiltration circle mainly around the tumor microenvironment, but there are currently no known determinants to predict the degree of invasiveness.

Methods
In this study, we use patient-derived glioma stem cells (GSCs) to create patient-specific 3D avatars to model interindividual invasion and elucidate the cellular supporting mechanisms.

Results
We show that GSC models in 3D mirror the invasive behavior of the parental tumors, thus proving the ability of DMG to infiltrate as an autonomous characteristic of tumor cells. Furthermore, we distinguished 2 modes of migration, mesenchymal and ameboid-like, and associated the ameboid-like modality with GSCs derived from the most invasive tumors. Using transcriptomics of both organoids and primary tumors, we further characterized the invasive ameboid-like tumors as oligodendrocyte progenitor-like, with highly contractile cytoskeleton and reduced adhesion ability driven by crucial over-expression of bone morphogenetic pathway 7 (BMP7). Finally, we deciphered MEK, ERK, and Rho/ROCK kinases activated downstream of the BMP7 stimulation as actionable targets controlling tumor cell motility.

Conclusions
Our findings identify 2 new therapeutic avenues. First, patient-derived GSCs represent a predictive tool for patient stratification in order to adapt irradiation strategies. Second, autocrine and short-range BMP7-related signaling becomes a druggable target to prevent DMG spread and metastasis.
Nutrition and melanoma: the contribution of trace elements in onset, progression, and treatment of melanoma
Authors: Lei Rui , Liu Xiao , Wu Jinfeng 
Published: September 2023

Abstract
Melanoma is a highly malignant and drug-resistant disease that imposes a substantial economic burden on the world. There are many studies linking trace elements to diverse types of cancers, including melanoma. This review elucidates the relationship between trace elements exposure and melanoma. It was identified that copper, manganese, selenium, zinc, iron, and many other trace elements were associated with melanoma in humans. In terms of epidemiology, different elements have different correlations with melanoma. These trace elements affect the occurrence and development of melanoma through various mechanisms, such as oxidative stress and the MAPK pathway. The literature on the role of trace elements in the pathogenesis and treatment of melanoma depicts promising prospects for this field.
Impact of Primary Breast Surgery on Overall Survival of Patients With De Novo Metastatic Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Villacampa Guillermo , Papakonstantinou Andri , Fredriksson Irma , Matikas Alexios 
Published: September 2023

Abstract

Background
Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival.

Methods
We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials.

Results
Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74).

Conclusion
Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.
Experimental study of (p, 2p) reactions at 197 MeV on 12C, 16O, 40,48Ca, and 90Zr nuclei leading to low-lying states of residual nuclei
Authors: Noro Tetsuo , Sakaguchi Satoshi , Wakasa Tomotsugu , Dozono Masanori , Fujioka Hiroyuki , Fujita Kunihiro , Hatanaka Kichiji , Ishida Takashi , Iwamoto Chihiro , Kawase Shoichiro , Kubota Yuki , Maeda Yukie , Matsubara Hiroaki , Miki Kenjiro , Ota Shinsuke , Panin Valerii , Sakaguchi Harutaka , Sakaue Akane , Sakemi Yasuhiro , Sasano Masaki , Sekiguchi Kimiko , Shimizu Yohei , Takeda Hiroyuki , Tameshige Yuji , Tamii Atsushi , Terashima Satoru , Uesaka Tomohiro , Yang Zai-Hong , Yasuda Yusuke , Yoshida Hidetomo P , Zenihiro Juzo 
Published: September 2023

Abstract
We have measured the differential cross section and analyzing power for (p, 2p) reactions that lead to discrete states of residual nuclei at an incident energy of 197 MeV for five kinds of target nuclei, 12C, 16O, 40,48Ca, and 90Zr. The data are compared with distorted-wave impulse approximation calculations using two kinds of global optical potentials. The spectroscopic factors obtained from these calculations agree with those determined in (e, e′p) studies within 20%, except for one orbital of the 90Zr nucleus where the distortion effect is much greater than that for the other orbitals of 90Zr and for other target nuclei. We also observed a clear and visibly distinct j-dependence in the analyzing power.
Prevalence of acute kidney injury among dengue cases: a systematic review and meta-analysis
Authors: Bushi Ganesh , Shabil Muhammed , Padhi Bijaya Kumar , Ahmed Mohammed , Pandey Pratima , Satapathy Prakasini , Rustagi Sarvesh , Pradhan Keerti Bhusan , Al-qaim Zahraa Haleem , Sah Ranjit 
Published: September 2023

ABSTRACTNumerous studies have shown a correlation between dengue virus (DENV) infection and kidney disease. However, there is no existing meta-analysis on the prevalence of kidney diseases in the dengue population. A thorough systematic review and meta-analysis were undertaken to determine the prevalence of renal problems in people with DENV infection in order to fill this knowledge gap. A rigorous electronic literature search was carried out up to 25 January 2023 in a number of databases, including ProQuest, EBSCOhost, Scopus, PubMed and Web of Science. The search aimed to find articles that reported on the prevalence of kidney diseases in patients with DENV infection. Using the modified Newcastle–Ottawa Scale, the quality of the included studies was assessed. The meta-analysis included a total of 37 studies with 21 764 participants reporting on the prevalence of acute kidney injury (AKI) in individuals with DENV infection. The pooled prevalence of AKI in dengue patients was found to be 8% (95% confidence interval 6 to 11), with high heterogeneity across studies. The studies included are of moderate quality. The study revealed a high AKI prevalence in dengue patients, underlining the need for regular renal examination to detect AKI early and reduce hospitalization risk. Further research is needed to understand the dengue–kidney relationship and develop effective management strategies.
Assessing heat effects on respiratory mortality and location characteristics as modifiers of heat effects at a small area scale in Central-Northern Europe
Authors: Zafeiratou Sofia , Samoli Evangelia , Analitis Antonis , Gasparrini Antonio , Stafoggia Massimo , de’ Donato Francesca K. , Rao Shilpa , Zhang Siqi , Breitner Susanne , Masselot Pierre , Aunan Kristin , Schneider Alexandra , Katsouyanni Klea ,   on behalf of the EXHAUSTION project team
Published: September 2023

Background:
Heat effects on respiratory mortality are known, mostly from time-series studies of city-wide data. A limited number of studies have been conducted at the national level or covering non-urban areas. Effect modification by area-level factors has not been extensively investigated. Our study assessed the heat effects on respiratory mortality at a small administrative area level in Norway, Germany, and England and Wales, in the warm period (May–September) within 1996–2018. Also, we examined possible effect modification by several area-level characteristics in the framework of the EU-Horizon2020 EXHAUSTION project.

Methods:
Daily respiratory mortality counts and modeled air temperature data were collected for Norway, Germany, and England and Wales at a small administrative area level. The temperature-mortality association was assessed by small area-specific Poisson regression allowing for overdispersion, using distributed lag non-linear models. Estimates were pooled at the national level and overall using a random-effect meta-analysis. Age- and sex-specific models were also applied. A multilevel random-effects model was applied to investigate the modification of the heat effects by area-level factors.

Results:
A rise in temperature from the 75th to 99th percentile was associated with a 27% (95% confidence interval [CI] = 19%, 34%) increase in respiratory mortality, with higher effects for females. Increased population density and PM2.5 concentrations were associated with stronger heat effects on mortality.

Conclusions:
Our study strengthens the evidence of adverse heat effects on respiratory mortality in Northern Europe by identifying vulnerable subgroups and subregions. This may contribute to the development of targeted policies for adaptation to climate change.
Peripheral visual field shifts after intraocular lens implantation
Authors: van Vught Luc , Luyten Gregorius P.M. , Beenakker Jan-Willem M. 
Published: September 2023

Purpose:To assess whether intraocular lens (IOL) implantation induces shifts in the peripheral visual field.Setting:Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.Design:Ray-tracing study.Methods:Nonsequential ray-tracing simulations were performed with phakic and pseudophakic versions of the same eye model to assess potential shifts in the visual field after IOL implantation. 2 different IOL designs were evaluated and for each design 5 different axial positions and 7 different intrinsic powers were tested. The relation between the physical position of the light source and the location where the retina was illuminated was determined for each eye model. Subsequently, these relations were used to calculate whether the visual field shifts in pseudophakic eyes.Results:The pseudophakic visual field shift was below 1 degree for central vision in all evaluated models. For peripheral vision, the light rays in the pseudophakic eyes were refracted to a more central retinal location compared with phakic eyes, resulting in a central shift of the peripheral visual field. The magnitude of the shift depended on the IOL design and its axial position, but could be as high as 5.4 degrees towards central vision.Conclusions:IOL implantation tends to have little effect on the central visual field but can induce an over 5 degrees shift in the peripheral visual field. Such a shift can affect the perception of peripheral visual complaints.
Comparative evaluation of multiple nomograms for predicting postoperative vault after implantable collamer lens surgery
Authors: Moshirfar Majid , Han Kenneth D. , Jaafar Muhammed A. , Santos Jordan M. , Theis Joshua S. , Stoakes Isabella M. , Hoopes Philip C. 
Published: September 2023

Purpose:To compare the vault predictability of most available implantable collamer lens (ICL) sizing nomograms and identify which preoperative measurements are predictive of vault.Setting:Private practice in Draper, Utah.Design:Retrospective chart review.Methods:This study was a retrospective analysis of 209 eyes of 106 patients who underwent STAAR Surgical ICL implantation. Analyses were performed based on the availability of preoperative parameters, varying the number of eyes for each test. Mean absolute error (MAE) of predicted vs actual postoperative vault was calculated for each nomogram. The frequency of Kim, Rocamora (least absolute shrinkage and selection operator-optical coherence tomography), Russo, and Reinstein recommending the correct ICL size in instances when Parkhurst, optimized white-to-white (WTW), and STAAR could not recommend a definitive ICL size was determined. Univariate and multivariate linear regression analysis was performed between preoperative measurements and vault.Results:The Kim, Rocamora, Russo, and Reinstein nomograms had significantly lower MAE of predicted vs actual postoperative vault than the KSV2 and Nakamura V3 nomograms. The Russo formula most frequently recommended the correct ICL size when the Parkhurst, Optimized WTW, and STAAR nomograms could not provide ICL size recommendations. At the 0.05 significance level, anterior chamber depth (ACD), ciliary body inner diameter (CBID), and pupil diameter were the parameters found to have significant correlation with postoperative vault.Conclusions:The Kim, Rocamora, Russo, and Reinstein nomograms were the most predictive of vault. Additionally, ACD, CBID, and pupil diameter were found to be significantly correlated with vault and should be considered for use in future ICL sizing nomograms.
Effect of Enhanced Recovery After Surgery on the Prognosis of Patients With Hip Fractures: A Systematic Review and Meta-Analysis
Authors: Zhu Ruiqi , Yang Fengqiao , Li Caiying , Zhu Hongxia , Lin Lu , Zhao Xin 
Published: September 2023

BACKGROUND:
Hip fractures, predominantly occurring in the elderly, are a significant public health concern due to associated morbidity, disability, and mortality. Prolonged bed rest following the fracture often leads to complications, further threatening patient health. Enhanced recovery after surgery, a modern approach to postoperative care, is being explored for its potential to improve outcomes and quality of life in hip fracture patients.

OBJECTIVE:
This study investigates the impact of enhanced recovery after surgery on hip fracture patients.

METHODS:
In this systematic review, we addressed the PICO question: Does the enhanced recovery after surgery program reduce 1-year mortality, readmissions, and postoperative pain and improve Harris Hip Score compared with traditional care in elderly hip fracture patients? We searched key databases and gray literature and analyzed outcomes through a meta-analysis using RevMan, Stata, and the Newcastle–Ottawa Scale for quality assessment.

RESULTS:
Nine studies involving 10,359 patients were included. Compared with the control group, the enhanced recovery after surgery group showed significant reduction in length of stay (mean difference [MD] = −2.00; 95% confidence interval [CI] [−2.87, −1.14]; p < .0001) and overall complication rate (risk ratio [RR] = 0.76; 95% CI [0.67, 0.85]; p < .0001), with a lower delirium rate (RR = 0.42; 95% CI [0.26, 0.68]; p = .004). No significant differences were observed in Harris Hip Score, pain score, 1-year mortality, readmission rate, or incidences of urinary tract infection, respiratory tract infection, and deep vein thrombosis.

CONCLUSION:
Enhanced recovery after surgery is associated with reduced length of stay, complication rate, and delirium rate in hip fracture patients.