bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximity-activated guide RNA of CRISPR–Cas12a for programmable diagnostic detection and gene regulation
Authors: Hu Zhian , Ling Shen , Duan Jialin , Yu Zixiao , Che Yanfei , Wang Song , Zhang Sichun , Zhang Xinrong , Li Zhengping 
Published: January 2025

Abstract
The flexibility and programmability of CRISPR–Cas technology have made it one of the most popular tools for biomarker diagnostics and gene regulation. Especially, the CRISPR–Cas12 system has shown exceptional clinical diagnosis and gene editing capabilities. Here, we discovered that although the top loop of the 5′ handle of guide RNA can undergo central splitting, deactivating CRISPR–Cas12a, the segments can dramatically restore CRISPR function through nucleic acid self-assembly or interactions with small molecules and aptamers. This discovery forms the basis of an engineered Cas12a system with a programmable proximity-activated guide RNA (PARC–Cas12a) that links targets of interest to dsDNA. Leveraging the efficient trans- and cis-cleavage of Cas12, our findings further inspired a detection platform design for RNAs or non-nucleic acid biomarkers, enabling highly sensitive and multiplexed analysis. We further demonstrated the feasibility of RNA-controllable gene knockout/knockdown in Escherichia coli. Notably, we successfully validated the gene regulatory capabilities of the PARC–Cas12a system within mammalian cell systems by utilizing the classical theophylline molecule–aptamer system. Our results introduce a programmable toolbox for precise diagnostics and cell regulation, allowing the development of versatile diagnostic tools, complex synthetic biological circuits, and cellular biosensors.
Unveiling the power duo: agriculture and social science take center stage in the evolution of climate change adaptation research in South Africa
Authors: Nondlazi Basanda Xhantilomzi , Mantlana Brain Khanyisa , Naidoo Sasha , Ramoelo Abel 
Published: January 2025

Abstract
Global changes in climatic conditions threaten the world’s socio-economic development, including South Africa (SA). Climate change adaptation (CCA) research in SA has grown in number (publication rate) and importance (influence on different sectors) over time. A growing body of research uses systematic literature reviews to examine themes within this rapidly evolving field. However, there is still a lack of analysis on the current state of CCA science literature in SA and its evolution over time. This paper fills this gap by providing a cross-validated bibliometric review of scientific literature on CCA in SA using Scopus and Web of Science (WoS) databases. The review is constructed across time, between databases, within databases and on most preferred journals. This transdisciplinary analysis of CCA literature and dominant research themes and priorities spanning 1966–2022 examines how they relate to SA’s adaptation strategy in response to climate change. CCA research has evolved in South Africa. Since 2011/12, publication rates have grown exponentially, averaging between 5% and 26% yearly. Term diversity peaked in 2018 when the publication rate reached 100 publications per year. This exponential development can be explained using themes of clustered terms over time, i.e. biodiversity emerging around 2015/16, Climate & Yield around 2017, and Agriculture & CCA, respectively, in 2018, with 41% similarity between Scopus and Web of Science. Future research needs to advance the monitoring of activities and outcomes on adaptation throughout the thematic evolution period.
Nitro-fatty acids modulate germination onset through S-nitrosothiol metabolism
Authors: Mata-Pérez Capilla , Begara-Morales Juan C , Padilla María N , Chaki Mounira , Sánchez-Calvo Beatriz , Carreras Alfonso , Aranda-Caño Lorena , Melguizo Manuel , Valderrama Raquel , Sánchez-Vicente Inmaculada , Lorenzo Óscar , Barroso Juan B 
Published: January 2025

Abstract
Nitro-fatty acids (NO2-FAs) have emerged as key components of nitric oxide (NO) signaling in eukaryotes. We previously described how nitro-linolenic acid (NO2-Ln), the major NO2-FA detected in plants, regulates S-nitrosoglutathione (GSNO) levels in Arabidopsis (Arabidopsis thaliana). However, the underlying molecular mechanisms remain undefined. Here, we used a combination of physiological, biochemical, and molecular approaches to provide evidence that NO2-Ln modulates S-nitrosothiol (SNO) content through S-nitrosylation of S-nitrosoglutathione reductase1 (GSNOR1) and its impact on germination onset. The aer mutant (a knockout mutant of the alkenal reductase enzyme; AER) exhibits higher NO2-Ln content and lower GSNOR1 transcript levels, reflected by higher SNO content and S-nitrosylated proteins. Given its capacity to release NO, NO2-Ln mediates the S-nitrosylation of GSNOR1, demonstrating that NO2-FAs can indirectly modulate total SNO content in plants. Moreover, the ectopic application of NO2-Ln to dormant seeds enhances germination success similarly to the aer germination rate, which is mediated by the degradation of master regulator ABSCISIC ACID INSENSITIVE 5 (ABI5). Our results establish that NO2-FAs regulate plant development through NO and SNO metabolism and reveal a role of NO2-FAs in plant physiology.
Officer-Involved: The Media Language of Police Killings
Authors: Moreno-Medina Jonathan , Bayer Aurelie Ouss Patrick , Ba Bocar A 
Published: January 2025

Abstract
This paper examines language patterns in US television news coverage of police killings. We first document that the media use semantic structures—such as passive voice, nominalizations, and intransitive verbs—that obscure responsibility more often in cases of police killings than in cases of civilian killings. Through an online experiment, we demonstrate the significance of these semantic differences, revealing that participants are less likely to hold police officers morally responsible and demand penalties when exposed to obfuscatory language, particularly in cases involving unarmed victims. Further analysis of news data shows greater use of obfuscatory language when the victims are unarmed or video footage is available—situations where obfuscation may have the greatest impact. Exploring the causes of this differential obfuscation, we do not find evidence that it is driven by either demand-side factors or supply-side factors associated with TV station ownership and political leaning. Instead, our results suggest that narratives crafted by police departments are a more likely driver of media obfuscation. Our study underscores the importance of semantic structures in how media shape perceptions, extending beyond considerations of coverage volume and bias.
The Impact of Being Denied a Wanted Abortion on Women and Their Children
Authors: Londoño-Vélez Juliana , Saravia Estefanía 
Published: January 2025

Abstract
This article examines the impact of denying a wanted abortion on women and children in Colombia using high-quality administrative microdata and credibly exogenous variation in abortion access. Women can seek legal abortions through a tutela, with cases randomly assigned to judges. Female judges are 20 percentage points (32%) less likely to deny abortion cases than are male judges, and we use the judge’s sex as an instrument for abortion denial. Denial of a wanted abortion has both immediate and lasting effects. It increases a woman’s risk of death by 2.5 percentage points within nine months, mainly due to unsafe abortion procedures, and raises the likelihood of carrying the pregnancy to term by 31 percentage points. Tracking outcomes up to 15 years later, we find that women denied an abortion experience more health issues, lower educational attainment, reduced labor force participation, and higher rates of single motherhood, poverty, and reliance on government assistance. Existing children, born before their mother sought an abortion, are less likely to attend school and are more likely to work.
Utilization of Potentially Inappropriate Sedative-Hypnotic and Atypical Antipsychotic Medications among Elderly Individuals with Insomnia and Alzheimer’s Disease
Authors: Chekani Farid , Mirchandani Kirti , Zaki Saba , Goswami Swarnali , Sharma Manvi 
Published: January 2025

Abstract

Study Objectives
This study assessed the utilization of potentially inappropriate medications (PIM) including oral sedative-hypnotic and atypical antipsychotic (OSHAA), healthcare resource utilization (HCRU), and costs among elderly individuals with insomnia and in the subpopulation with Alzheimer’s Disease (AD) who also had a diagnosis of insomnia.

Methods
Using claims database containing International Classification of Diseases, 10th Revision (ICD-10) codes, the cohort included individuals aged ≥ 65 with incident insomnia (EI, N=152,969) and AD insomnia subpopulation (ADI, N=4,888). Proportion of patients utilizing atypical antipsychotics or oral sedative-hypnotic medications, namely z-drugs, benzodiazepines, doxepin, Dual Orexin Receptor Antagonists (DORAs), and melatonin agonists, were assessed. Inappropriate OSHAA utilization was defined as per the American Geriatrics Society (AGS) Beers criteria. Multivariable models were utilized to compare HCRU and costs between PIM-OSHAA and no PIM-OSHAA groups.

Results
Among the EI cohort, z-drugs (13.39%) were the most commonly utilized OSHAA, and in the ADI cohort, it was AAPs (29.97%). PIM-OSHAA was utilized by 20% of the EI and 35% of the ADI cohorts. Patients with PIM-OSHAA use among the EI cohort had a higher annualized adjusted mean HCRU (pharmacy visits: 31.21 vs. 23.68; ambulatory & outpatient visits: 18.55 vs. 16.85) and costs, primarily due to medical costs (mean total cost: $36,676.08 vs. $31,346.54) compared to those without.

Conclusions
Substantial utilization of PIM-OSHAA was observed in EI and ADI cohorts. PIM-OSHAA use was associated with higher HCRU and costs. These findings underscore the importance of appropriate treatment strategies for insomnia in the elderly population especially in those with concurrent AD.
Effects of administering local anesthesia immediately before surgical castration on indicators of pain and discomfort of beef calves
Authors: Bernier Amanda F , Erickson Nathan , Campbell John , Moya Diego 
Published: January 2025

Abstract
Forty Hereford cross calves (mean and SD of 47.9 ± 10.43 d old) were used to assess the efficacy of lidocaine administered immediately before surgical castration on physiological and behavioral indicators of pain and discomfort. Calves were assigned by age to one of two treatments: surgical castration following subcutaneous injection of 2.5 mL/100 kg body weight of meloxicam (Metacam 20 mg/mL, Boehringer Ingelhein, Burlington, ON, Canada) per kg body weight (MEX, n = 19); or the same treatment preceded 90 s before by a nerve block of the spermatic cord using 8 mL of buffered (1 mL:10 mL of 8.4% sodium bicarbonate USP, Hospira Inc., Lake Forest, IL, USA) lidocaine (4 mL per cord; 20 mg/mL, LIDO-2 with epinephrine, Rafter Products, Calgary, AB, Canada) (LID, n = 21). During the castration procedure, two observers scored how much pain each animal was experiencing (visual analog score, VAS), number of body shakes and leg kicks for each calf. Blood samples and exit scores were collected the day of castration and on d 7, and 14 to assess the neutrophil-to-lymphocyte ratio (N:L) and calf temperament, respectively. Hair samples were collected the day of castration and on d 14 to determine cortisol levels. Scrotal circumference, swelling, and healing scores were determined on d 7 and 14 to assess healing. An accelerometer (HOBO Pendant® G Data Logger, Onset, Cape Cod, MA) was placed on the left hind leg to measure lying behavior until d 6 after castration. Calves were video recorded for 1 hour after the castration procedure to observe behaviors indicative of pain and discomfort. Surveillance cameras were also used to assess the mobility of the calves when cow-calf pairs were moved from the holding pen to the pasture. The VAS, number of tail flicks and foot stamps were greater (P &lt; 0.01) in MEX than in LID calves. During the first hour after castration, LID calves spent more time lying (P = 0.03) and less time standing (P = 0.01) than MEX calves. When moved from the holding pen, LID calves moved faster (P &lt; 0.01) and closer to their dams (P &lt; 0.05) than MEX calves. Hair cortisol was greater (P &lt; 0.05) in LID than MEX calves on d 14. Results suggest that using lidocaine for local anesthesia immediately before surgical castration reduced behaviors indicative of pain and improved mobility post-castration.
Phylogenetic systematics of the keratin-feeding genus Polynoncus Burmeister, 1876 (Coleoptera: Scarabaeoidea: Trogidae)
Authors: da Costa-Silva Vinícius , Strümpher Werner P , Thyssen Patricia J , Vaz-de-Mello Fernando Z 
Published: January 2025

Abstract
Among the five known Trogidae genera, Polynoncus is the only one endemic to South America. Although the systematics within Trogidae is well established, the evolutionary relationships among Polynoncus species remain poorly understood. Here, we conducted a phylogenetic analysis based on maximum parsimony, using the equal and implicit weighting algorithm with all characters, in TNT v.1.5 software. The assembled data matrix consisted of 98 morphological characters scored for 48 taxa. Our results corroborate the monophyletic status of Polynoncus and its sister-group relationship with the genus Omorgus, both within Omorginae. In Polynoncus, three main lineages were recovered: (i) clade ‘pedestris’, with four species occurring mostly in the Andes; (ii) clade ‘pilularius’, whose species have been most reported in the temperate zone of South America; and (iii) clade ‘brevicollis’, whose species are distributed from the arid zones of Argentina and Chile to Peru, following through the Andes. This is the first species-level phylogeny presented for Trogidae.
Mitochondrial respiration in white adipose tissue is dependent on body mass index and tissue location in patients undergoing oncological or parietal digestive surgery
Authors: Guerrier Lisa , Bacoeur‐Ouzillou Ophélie , Touron Julianne , Mezher Sami , Cassagnes Lucie , Vieille‐Marchiset Aurélie , Chanon Stéphanie , Pereira Bruno , Pezet Denis , Pinel Alexandre , Gagnière Johan , Malpuech‐Brugère Corinne , Richard Ruddy 
Published: January 2025

AbstractAdipose tissue (AT), is a major endocrine organ that plays a key role in health and disease. However, adipose dysfunctions, especially altered energy metabolism, have been under‐investigated as white adipocytes have relatively low mitochondrial density. Nevertheless, recent studies suggest that mitochondria could play a major role in AT disorders and that AT mitochondrial activity could depend on adiposity level and location. This clinical study aimed to evaluate mitochondrial respiration and metabolism in human visceral (vAT) and subcutaneous (scAT) AT and their relationship with body mass index (BMI). This clinical study enrolled 67 patients (30 females/37 males) scheduled for digestive surgery without chemotherapy and parietal infection. BMI ranged from 15.4 to 51.9 kg·m−2 and body composition was estimated by computed tomographic images. Mitochondrial respiration was measured in situ in digitonin‐permeabilized AT using high‐resolution respirometry and a substrate/inhibitor titration approach. Protein levels of mitochondrial and lipid metabolism key elements were evaluated by Western blot. Maximal mitochondrial respiration correlated negatively with BMI (p < .01) and AT area (p < .001) regardless of the anatomical location. However, oxidative phosphorylation respiration was significantly higher in vAT (2.22 ± 0.15 pmol·sec−1·mg−1) than scAT (1.79 ± 0.17 pmol·sec−1·mg−1) (p < 0.001). In line with oxygraphy results, there were higher levels of mitochondrial respiratory chain complexes in low‐BMI patients and vAT. Mitochondrial respiration decreased with increasing BMI in both scAT and vAT, without sex‐associated difference. Mitochondrial respiration appeared to be higher in vAT than scAT. These differences were both qualitative and quantitative. Clinical Trials Registration IDNCT05417581.
Industrial air emissions and breast cancer incidence in a United States-wide prospective cohort
Authors: Ish Jennifer L. , Madrigal Jessica M. , Pearce John L. , Keil Alexander P. , Fisher Jared A. , Jones Rena R. , Sandler Dale P. , White Alexandra J. 
Published: January 2025

Background:
We evaluated air emissions of industrial compounds, many of which have carcinogenic or endocrine disrupting properties, in relation to breast cancer incidence.

Methods:
Using the United States Environmental Protection Agency’s Toxics Release Inventory, we quantified air emissions of 28 compounds near Sister Study participants’ residences during the 10 years leading up to study enrollment (2003-2006; n=46,150). We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of residential emission levels of single pollutants with incident breast cancer. We assessed pollutant mixtures using an Exposure Continuum Mapping (ECM) framework and characterized associations using a joint-exposure response function.

Results:
During follow-up (median=13.4 years), we identified 4,155 breast cancer cases. We observed non-monotonic but elevated associations with breast cancer for emissions within 3km of the residence for nickel compounds (HRquintile5vs.none = 1.3; 95% CI 1.0, 1.6) and trichloroethylene (HRquintile5vs.none = 1.3; 95% CI 1.0, 1.6). ECM identified 25 mixture profiles that explained 72% of the variance in emissions patterns, with most participants experiencing relatively low emissions profiles. The joint-exposure response function suggested that higher incidence of breast cancer occurred among individuals with relatively rare, high emissions profiles; however, the overall trend was not associated with breast cancer (p=0.09).

Conclusions:
In our study, breast cancer incidence was associated with air emissions of certain industrial carcinogens. Although the overall emissions mixture did not show a trend related to breast cancer, this may not reflect the importance of individual compounds or specific emissions sources.
New therapies in celiac disease
Authors: Santonicola Antonella , Soldaini Carlo , Ciacci Carolina 
Published: January 2025

Purpose of review
Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing.

Recent findings
Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten.

Summary
While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.
Selective degradation of BRD9 by a DCAF16-recruiting targeted glue: mode of
action elucidation and in vivo proof of concept
Authors: Hughes Scott J. , Stec Wojciech J. , Davies Colin T. R. , McGarry David , Williams Alicia , Del Barco Barrantes Ivan , Harris Rebecca , Owens Dominic D. G. , Fawcett Alexander , Hellicar John , Meier Gregor P. , Runcie Andrew C. , Greger Liliana , O’Rourke Martin , Churcher Ian , Pass Martin , Brown Giles A. , Ciulli Alessio , Modis Louise K. , Testa Andrea 
Published: January 2025

Abstract
Prospective discovery of molecular glues degraders for a specific
therapeutic target protein of interest is an emerging strategy in drug
discovery. Modification of pre-existing ligands with fragments that can alter
the protein surface can lead to the creation of novel compounds (‘’targeted
glues’’) able to induce neo-interactions between the target and an E3 ligase,
resulting in targeted protein degradation. By screening a library of potential
BRD9 targeted glue compounds, we have discovered a potent and selective,
reversibly covalent BRD9 degrader,AMPTX-1.
Co-immunoprecipitation-mass spectrometry experiments demonstrated that cell
treatment withAMPTX-1induces selective recruitment of
BRD9 to the E3 ligase DCAF16. Degradation is dependent on the engagement of the
surface Cys58 of DCAF16 and formation of a covalent adduct to DCAF16 is
facilitated by the ternary complex formation with BRD9. BRD9 degradation is
achievedin vivo after oral dosing, demonstrating
that covalent recruitment of DCAF16 is a viable strategy for targeted protein
degradation and can be achieved with drug-like, orally bioavailable compounds
with promisingin vivoactivity.
Exploring the kinetics and mechanism of phase separation in ternary lipid
mixtures containing APP C99 using atomistic vs coarse-grained MD
simulations
Authors: Pantelopulos George A. , Prusty Sangram , Bandara Asanga , Straub John E. 
Published: January 2025

Abstract
The phase separation of lipid bilayers, composed of mixtures of saturated
and unsaturated lipids and cholesterol, is a topic of fundamental importance in
membrane biophysics and cell biology. The formation of lipid domains, including
liquid-disordered domains enriched in unsaturated lipids and liquid-ordered
domains enriched in saturated lipids and cholesterol is believed to be essential
to the function of many membrane proteins. Experiment, theory, and simulation
have been used to develop a general understanding of the thermodynamic driving
forces underlying phase separation in ternary and quaternary lipid mixtures.
However, the kinetics of early events in lipid phase separation in the presence
of transmembrane proteins remain relatively understudied. Using large-scale
all-atom and coarse-grained simulations, we explore the kinetics and phase
separation of ternary lipid mixtures of saturated lipid, unsaturated lipid, and
cholesterol. Order parameters employed in the Cahn-Hilliard theory provide
insight into the kinetics and mechanism of lipid phase separation. We observe
three distinct time regimes in the phase separation process: a shorter time
exponential phase followed by a power law phase followed by a longer time
plateau phase. Comparison of lipid, protein and lipid-protein dynamics between
all-atom and coarse-grained models identifies both quantitative and qualitative
differences and similarities in the phase separation kinetics. Moreover,
timescaling of dynamics of AA and CG simulation yields a similar kinetic
mechanism of phase separation. The findings of this study elucidate fundamental
aspects of membrane biophysics and the ongoing efforts to define the role of
lipid rafts in the structure and function of cellular membrane.