bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of antipsychotic use with breast cancer: a systematic review and meta-analysis of observational studies with over 2 million individuals
Authors: Leung Janice Ching Nam , Ng Dora Wai Yee , Chu Rachel Yui Ki , Chan Edward Wai Wa , Huang Lei , Lum Dawn Hei , Chan Esther Wai Yin , Smith Daniel J. , Wong Ian Chi Kei , Lai Francisco Tsz Tsun 
Published: September 2022

Abstract

Aims
Despite reports of an elevated risk of breast cancer associated with antipsychotic use in women, existing evidence remains inconclusive. We aimed to examine existing observational data in the literature and determine this hypothesised association.

Methods
We searched Embase, PubMed and Web of Science™ databases on 27 January 2022 for articles reporting relevant cohort or case-control studies published since inception, supplemented with hand searches of the reference lists of the included articles. Quality of studies was assessed using the Newcastle-Ottawa Scale. We generated the pooled odds ratio (OR) and pooled hazard ratio (HR) using a random-effects model to quantify the association. This study was registered with PROSPERO (CRD42022307913).

Results
Nine observational studies, including five cohort and four case-control studies, were eventually included for review (N = 2 031 380) and seven for meta-analysis (N = 1 557 013). All included studies were rated as high-quality (seven to nine stars). Six studies reported a significant association of antipsychotic use with breast cancer, and a stronger association was reported when a greater extent of antipsychotic use, e.g. longer duration, was operationalised as the exposure. Pooled estimates of HRs extracted from cohort studies and ORs from case-control studies were 1.39 [95% confidence interval (CI) 1.11–1.73] and 1.37 (95% CI 0.90–2.09), suggesting a moderate association of antipsychotic use with breast cancer.

Conclusions
Antipsychotic use is moderately associated with breast cancer, possibly mediated by prolactin-elevating properties of certain medications. This risk should be weighed against the potential treatment effects for a balanced prescription decision.
Dehydroepiandrosterone Sulfate and Colorectal Cancer Risk: A Mendelian Randomization Analysis
Authors: Jayarathna Dulari K. , Rentería Miguel E. , Kho Pik Fang , Batra Jyotsna , Gandhi Neha S. 
Published: September 2022

AbstractColorectal cancer is the third most common and second most deadly type of cancer worldwide, with approximately 1.9 million cases and 0.9 million deaths worldwide in 2020. Previous studies have shown that estrogen and testosterone hormones are associated with colorectal cancer risk and mortality. However, the potential effect of their precursor, dehydroepiandrosterone sulfate (DHEAS), on colorectal cancer risk has not been investigated. Therefore, evaluating DHEAS’s effect on colorectal cancer will expand our understanding of the hormonal contribution to colorectal cancer risk. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal effect of DHEAS on colorectal cancer. We obtained DHEAS and colorectal cancer genomewide association study (GWAS) summary statistics from the Leipzig Health Atlas and the GWAS catalog and conducted MR analyses using the TwoSampleMR R package. Our results suggest that higher DHEAS levels are causally associated with decreased colorectal cancer risk (odds ratio per unit increase in DHEAS levels z score = 0.70; 95% confidence interval [0.51, 0.96]), which is in line with previous observations in a case–control study of colon cancer. The outcome of this study will be beneficial in developing plasma DHEAS-based biomarkers in colorectal cancer. Further studies should be conducted to interpret the DHEAS-colorectal cancer association among different ancestries and populations.
The Martian Boulder Automatic Recognition System, MBARS
Authors: Hood Don R. , Sholes S. F. , Karunatillake S. , Fassett C. I. , Ewing R. C. , Levy J. 
Published: September 2022

AbstractBoulder‐sized clasts are common on the surface of Mars, and many are sufficiently large to be resolved by the high resolution imaging science experiment (HiRISE) camera aboard the Mars reconnaissance orbiter. The size, number, and location of boulders on the surface and their spatial distribution can reveal the processes that have operated on the surface, including boulder erosion, burial, impact excavation, and other mechanisms of boulder transport and generation. However, quantitative analysis of statistically significant boulder populations, which could inform these processes, entails prohibitively laborious manual segmentation, granulometry, and morphometry measurements over large areas. Here, we develop, describe, and validate an automated tool to locate and measure boulders on the Martian surface: the Martian Boulder Automatic Recognition System (MBARS). Our open‐source Python‐based toolkit automatically measures boulder diameter and height in HiRISE images enabling rapid and accurate assessments of boulder populations. We compare our algorithm with existing boulder‐counting methods, manual analyses, and objects of known size to verify accuracy and precision. Additionally, we test how MBARS quantitatively characterizes boulders around an impact crater in the Martian northern lowlands. We compare this to previous work on rock excavation during impact cratering using manually counted boulders around lunar craters.
Variations of the Intensity of the Siberian High During the Last Glacial Revealed by the Sorting Coefficient of Loess‐Paleosol Deposits in Eastern Central Asia
Authors: Cheng Liangqing , Song Yougui , Yang Linhai , Chang Hong , Wu Yubin , Long Hao , Miao Xiaodong , Dong Zhibao 
Published: September 2022

AbstractEastern Central Asia has an arid environment and experiences frequent dust storms. Modern observations indicate that the dust storm frequency in eastern Central Asia is modulated mainly by the intensity of the Siberian High (SH). However, a lack of knowledge about the process influencing the variation of the SH limits our ability to understand the genesis of dust storms and their predictions. In this study, we present data on heavy mineral assemblages and sediment grain size in a loess section in eastern Central Asia, spanning the last glacial. Combined with previously published results, we propose that the sorting coefficient in loess‐paleosol sequences is a more sensitive proxy for wind intensity—and thus for the intensity of the SH—than the commonly used proxies of the mean grain size and grain size fractions, which are also influenced by changes in dust source and vegetation cover. Our sorting coefficient series clearly reveals Heinrich events, as well as the prominent ∼5 kyr Bond cycle. Larger sorting coefficients correspond to more depleted Sanbao Cave stalagmite δ18O values, revealing an antiphase relationship between the intensity of the SH and the East Asian Summer Monsoon during the last glacial. The sorting coefficient series also support the significant influence of Arctic sea‐ice cover on the intensity of the SH.
Computational psychiatry: from synapses to sentience
Authors: Friston Karl 
Published: September 2022

AbstractThis review considers computational psychiatry from a particular viewpoint: namely, a commitment to explaining psychopathology in terms of pathophysiology. It rests on the notion of agenerative modelas underwriting (i) sentient processing in the brain, and (ii) the scientific process in psychiatry. The story starts with a view of the brain—from cognitive and computational neuroscience—as an organ of inference and prediction. This offers a formal description of neuronal message passing, distributed processing and belief propagation in neuronal networks; and how certain kinds of dysconnection lead to aberrant belief updating and false inference. The dysconnections in question can be read as a pernicious synaptopathy that fits comfortably with formal notions of how we—or our brains—encode uncertainty or its complement,precision. It then considers how the ensuing process theories are tested empirically, with an emphasis on the computational modelling of neuronal circuits and synaptic gain control that mediates attentional set, active inference, learning and planning. The opportunities afforded by this sort of modelling are considered in light of in silico experiments; namely, computational neuropsychology, computational phenotyping and the promises of a computational nosology for psychiatry. The resulting survey of computational approaches is not scholarly or exhaustive. Rather, its aim is to review a theoretical narrative that is emerging across subdisciplines within psychiatry and empirical scales of investigation. These range from epilepsy research to neurodegenerative disorders; from post-traumatic stress disorder to the management of chronic pain, from schizophrenia to functional medical symptoms.
Smoldering multiple myeloma current treatment algorithms
Authors: Rajkumar S. Vincent , Kumar Shaji , Lonial Sagar , Mateos Maria Victoria 
Published: September 2022

AbstractSmoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rather represents a heterogeneous clinically defined condition in which some patients (approximately two-thirds) have MGUS (pre-malignancy), and some (approximately one-third) have MM (biologic malignancy). Unfortunately, no single pathologic or molecular feature can reliably distinguish these two groups of patients. For purposes of practice and clinical trials, specific risk factors are used to identify patients with SMM in whom malignant transformation has already likely occurred (high risk SMM). Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3–4 months.
ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation
Authors: Adhikary Santanu , Singh Vipin , Choudhari Ramesh , Yang Barbara , Adhikari Swagata , Ramos Enrique I. , Chaudhuri Soumi , Roy Siddhartha , Gadad Shrikanth S. , Das Chandrima 
Published: September 2022

AbstractZinc Finger transcription factors are crucial in modulating various cellular processes, including differentiation. Chromatin reader Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), an All-Trans Retinoic Acid (ATRA)-responsive gene, was previously shown to play a crucial role in promoting the expression of neuronal-lineage committed genes. Here, we report that ZMYND8 promotes neuronal differentiation by positively regulating canonical MAPT protein-coding gene isoform, a key player in the axonal development of neurons. Additionally, ZMYND8 modulates gene-isoform switching by epigenetically silencing key regulatory regions within the MAPT gene, thereby suppressing the expression of non-protein-coding isoforms such as MAPT213. Genetic deletion of ZMYND8 led to an increase in the MAPT213 that potentially suppressed the parental MAPT protein-coding transcript expression related to neuronal differentiation programs. In addition, ectopic expression of MAPT213 led to repression of MAPT protein-coding transcript. Similarly, ZMYND8-driven transcription regulation was also observed in other neuronal differentiation-promoting genes. Collectively our results elucidate a novel mechanism of ZMYND8-dependent transcription regulation of different neuronal lineage committing genes, including MAPT, to promote neural differentiation.
A Cryptochrome adopts distinct moon- and sunlight states and functions as sun- versus moonlight interpreter in monthly oscillator entrainment
Authors: Poehn Birgit , Krishnan Shruthi , Zurl Martin , Coric Aida , Rokvic Dunja , Häfker N. Sören , Jaenicke Elmar , Arboleda Enrique , Orel Lukas , Raible Florian , Wolf Eva , Tessmar-Raible Kristin 
Published: September 2022

AbstractThe moon’s monthly cycle synchronizes reproduction in countless marine organisms. The mass-spawning bristle worm Platynereis dumerilii uses an endogenous monthly oscillator set by full moon to phase reproduction to specific days. But how do organisms recognize specific moon phases? We uncover that the light receptor L-Cryptochrome (L-Cry) discriminates between different moonlight durations, as well as between sun- and moonlight. A biochemical characterization of purified L-Cry protein, exposed to naturalistic sun- or moonlight, reveals the formation of distinct sun- and moonlight states characterized by different photoreduction- and recovery kinetics of L-Cry’s co-factor Flavin Adenine Dinucleotide. In Platynereis, L-Cry’s sun- versus moonlight states correlate with distinct subcellular localizations, indicating different signaling. In contrast, r-Opsin1, the most abundant ocular opsin, is not required for monthly oscillator entrainment. Our work reveals a photo-ecological concept for natural light interpretation involving a “valence interpreter” that provides entraining photoreceptor(s) with light source and moon phase information.
Molecular basis for polysaccharide recognition and modulated ATP hydrolysis by the O antigen ABC transporter
Authors: Spellmon Nicholas , Muszyński Artur , Górniak Ireneusz , Vlach Jiri , Hahn David , Azadi Parastoo , Zimmer Jochen 
Published: September 2022

AbstractO antigens are ubiquitous protective extensions of lipopolysaccharides in the extracellular leaflet of the Gram-negative outer membrane. Following biosynthesis in the cytosol, the lipid-linked polysaccharide is transported to the periplasm by the WzmWzt ABC transporter. Often, O antigen secretion requires the chemical modification of its elongating terminus, which the transporter recognizes via a carbohydrate-binding domain (CBD). Here, using components from A. aeolicus, we identify the O antigen structure with methylated mannose or rhamnose as its cap. Crystal and cryo electron microscopy structures reveal how WzmWzt recognizes this cap between its carbohydrate and nucleotide-binding domains in a nucleotide-free state. ATP binding induces drastic conformational changes of its CBD, terminating interactions with the O antigen. ATPase assays and site directed mutagenesis reveal reduced hydrolytic activity upon O antigen binding, likely to facilitate polymer loading into the ABC transporter. Our results elucidate critical steps in the recognition and translocation of polysaccharides by ABC transporters.
High-density electrode recordings reveal strong and specific connections between retinal ganglion cells and midbrain neurons
Authors: Sibille Jérémie , Gehr Carolin , Benichov Jonathan I. , Balasubramanian Hymavathy , Teh Kai Lun , Lupashina Tatiana , Vallentin Daniela , Kremkow Jens 
Published: September 2022

AbstractThe superior colliculus is a midbrain structure that plays important roles in visually guided behaviors in mammals. Neurons in the superior colliculus receive inputs from retinal ganglion cells but how these inputs are integrated in vivo is unknown. Here, we discovered that high-density electrodes simultaneously capture the activity of retinal axons and their postsynaptic target neurons in the superior colliculus, in vivo. We show that retinal ganglion cell axons in the mouse provide a single cell precise representation of the retina as input to superior colliculus. This isomorphic mapping builds the scaffold for precise retinotopic wiring and functionally specific connection strength. Our methods are broadly applicable, which we demonstrate by recording retinal inputs in the optic tectum in zebra finches. We find common wiring rules in mice and zebra finches that provide a precise representation of the visual world encoded in retinal ganglion cells connections to neurons in retinorecipient areas.
In-sensor image memorization and encoding via optical neurons for bio-stimulus domain reduction toward visual cognitive processing
Authors: Lee Doeon , Park Minseong , Baek Yongmin , Bae Byungjoon , Heo Junseok , Lee Kyusang 
Published: September 2022

AbstractAs machine vision technology generates large amounts of data from sensors, it requires efficient computational systems for visual cognitive processing. Recently, in-sensor computing systems have emerged as a potential solution for reducing unnecessary data transfer and realizing fast and energy-efficient visual cognitive processing. However, they still lack the capability to process stored images directly within the sensor. Here, we demonstrate a heterogeneously integrated 1-photodiode and 1 memristor (1P-1R) crossbar for in-sensor visual cognitive processing, emulating a mammalian image encoding process to extract features from the input images. Unlike other neuromorphic vision processes, the trained weight values are applied as an input voltage to the image-saved crossbar array instead of storing the weight value in the memristors, realizing the in-sensor computing paradigm. We believe the heterogeneously integrated in-sensor computing platform provides an advanced architecture for real-time and data-intensive machine-vision applications via bio-stimulus domain reduction.
Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids
Authors: Randriamanantsoa S. , Papargyriou A. , Maurer H. C. , Peschke K. , Schuster M. , Zecchin G. , Steiger K. , Öllinger R. , Saur D. , Scheel C. , Rad R. , Hannezo E. , Reichert M. , Bausch A. R. 
Published: September 2022

AbstractThe development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.
Structural basis for recognition of N-formyl peptides as pathogen-associated molecular patterns
Authors: Chen Geng , Wang Xiankun , Liao Qiwen , Ge Yunjun , Jiao Haizhan , Chen Qiang , Liu Yezhou , Lyu Wenping , Zhu Lizhe , van Zundert Gydo C. P. , Robertson Michael J. , Skiniotis Georgios , Du Yang , Hu Hongli , Ye Richard D. 
Published: September 2022

AbstractThe formyl peptide receptor 1 (FPR1) is primarily responsible for detection of short peptides bearing N-formylated methionine (fMet) that are characteristic of protein synthesis in bacteria and mitochondria. As a result, FPR1 is critical to phagocyte migration and activation in bacterial infection, tissue injury and inflammation. How FPR1 distinguishes between formyl peptides and non-formyl peptides remains elusive. Here we report cryo-EM structures of human FPR1-Gi protein complex bound toS. aureus-derived peptide fMet-Ile-Phe-Leu (fMIFL) andE. coli-derived peptide fMet-Leu-Phe (fMLF). Both structures of FPR1 adopt an active conformation and exhibit a binding pocket containing the R2015.38XXXR2055.42(RGIIR) motif for formyl group interaction and receptor activation. This motif works together with D1063.33for hydrogen bond formation with the N-formyl group and with fMet, a model supported by MD simulation and functional assays of mutant receptors with key residues for recognition substituted by alanine. The cryo-EM model of agonist-bound FPR1 provides a structural basis for recognition of bacteria-derived chemotactic peptides with potential applications in developing FPR1-targeting agents.
Neuromorphic device based on silicon nanosheets
Authors: Wang Chenhao , Xu Xinyi , Pi Xiaodong , Butala Mark D. , Huang Wen , Yin Lei , Peng Wenbing , Ali Munir , Bodepudi Srikrishna Chanakya , Qiao Xvsheng , Xu Yang , Sun Wei , Yang Deren 
Published: September 2022

AbstractSilicon is vital for its high abundance, vast production, and perfect compatibility with the well-established CMOS processing industry. Recently, artificially stacked layered 2D structures have gained tremendous attention via fine-tuning properties for electronic devices. This article presents neuromorphic devices based on silicon nanosheets that are chemically exfoliated and surface-modified, enabling self-assembly into hierarchical stacking structures. The device functionality can be switched between a unipolar memristor and a feasibly reset-able synaptic device. The memory function of the device is based on the charge storage in the partially oxidized SiNS stacks followed by the discharge activated by the electric field at the Au-Si Schottky interface, as verified in both experimental and theoretical means. This work further inspired elegant neuromorphic computation models for digit recognition and noise filtration. Ultimately, it brings silicon - the most established semiconductor - back to the forefront for next-generation computations.
In vivo adenine base editing reverts C282Y and improves iron metabolism in hemochromatosis mice
Authors: Rovai Alice , Chung BoMee , Hu Qingluan , Hook Sebastian , Yuan Qinggong , Kempf Tibor , Schmidt Florian , Grimm Dirk , Talbot Steven R. , Steinbrück Lars , Götting Jasper , Bohne Jens , Krooss Simon A. , Ott Michael 
Published: September 2022

AbstractHemochromatosis is one of the most common inherited metabolic diseases among white populations and predominantly originates from a homozygous C282Y mutation in the HFE gene. The G > A transition at position c.845 of the gene causes misfolding of the HFE protein, ultimately resulting in its absence at the cell membrane. Consequently, the lack of interaction with the transferrin receptors 1 and 2 leads to systemic iron overload. We screened potential gRNAs in a highly precise cell culture assay and applied an AAV8 split-vector expressing the adenine base editor ABE7.10 and our candidate gRNA in 129-Hfetm.1.1Nca mice. Here we show that a single injection of our therapeutic vector leads to a gene correction rate of >10% and improved iron metabolism in the liver. Our study presents a proof-of-concept for a targeted gene correction therapy for one of the most frequent hereditary diseases affecting humans.