bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population
Authors: Park Hyung-Bok , Arsanjani Reza , Hong Sung-Jin , Yi Jee-Jeon , Yi Sang-Wook
Published: October 2023

Aims

The aim of this study was to assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population.

Methods and results

From the Korean National Health Insurance Service database, 15 672 028 participants aged 18–99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean of 8.8 years of follow-up, 105 174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold [ischaemic heart disease (IHD)], 1.24-fold [acute myocardial infarction (AMI)], and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of hypertriglyceridaemia (HTG) on CVD weakened but remained present in persons with LDL-C < 100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18–44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population.

Conclusion

Hypertriglyceridaemia independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.
The crustal structure of the western Amundsen Basin, Arctic Ocean, derived from seismic refraction/wide-angle reflection data
Authors: Castro Carlos F , Funck Thomas , Hopper John R
Published: October 2023

Two geophysical expeditions (LOMROG II and III) were carried out in 2009 and 2012 to acquire seismic data in the western Amundsen Basin in the Arctic Ocean, a basin formed by ultraslow seafloor spreading at the Gakkel Ridge. Previous studies show alternating magmatic and amagmatic segments at the ridge but it is unclear if such segmentation persisted throughout the entire opening history of the basin. The seismic refraction data were used to develop P-wave velocity models down to the uppermost mantle using forward modelling of traveltimes. The coincident seismic reflection data were used to constrain the geometry of the sedimentary layers and for characterizing the acoustic basement. 2-D gravity modelling was used to determine the Moho depth in areas when data quality was insufficient to resolve a Moho reflection. The models distinguish three different basement types: oceanic crust with layers 2 and 3, oceanic crust that is lacking a layer 3 and exhumed and serpentinized mantle. The maximum observed crustal thickness is 6 km. Areas with thin crust (<3 km) may be underlain by partially serpentinized mantle. Where exhumed mantle is observed, a serpentinization front separates highly serpentinized mantle at the top from partially serpentinized mantle below. The presence of oceanic crust off-axis of the presently amagmatic sector of the Gakkel Ridge indicates that there is both a spatial and temporal variation of crustal accretion processes at the ridge.
Bayesian estimation of non-linear centroid moment tensors using multiple seismic data sets
Authors: Hamidbeygi Mahdi , Vasyura-Bathke Hannes , Dettmer Jan , Eaton David W , Dosso Stan E
Published: October 2023

Centroid moment tensor (CMT) parameters of earthquakes are routinely estimated to gain information on structures and regional tectonics. However, for small earthquakes (M < 4), it is still challenging to determine CMTs due to the lack of high-quality waveform data. In this study, we propose to improve solutions for small earthquakes by incorporating multiple seismic data types in Bayesian joint inversion: polarities picked on broad-band signals, amplitude spectra for intermediate frequency bands (0.2–2.0 Hz), and waveforms at low frequencies (0.05–0.2 Hz). Both measurement and theory errors are accounted for by iterative estimation of non-Toeplitz covariance matrices, providing objective weightings for the different data types in the joint parameter estimation. Validity and applicability of the method are demonstrated using simulated and field data. Results demonstrate that combinations of data, such as a single high-quality waveform, a few amplitude spectra and many waveform polarities, are able to resolve CMT parameters to comparable quality as if many high-quality waveforms were available. Results of 10 induced seismic events that occurred in northeastern British Columbia, Canada, between January 2020 and February 2022 indicate predominantly strike-slip focal mechanisms with low non-double-couple components. These events appear to be located at shallow depths with short time duration, as expected for induced seismicity. These results are consistent with previous studies, indicating that this method reduces the dependence of source inversion on high-quality waveforms, and can provide resolution of CMT parameters for earthquakes as small as ML 1.6.
Funnel control of linear systems with arbitrary relative degree under output measurement losses
Authors: Berger Thomas , Lanza Lukas
Published: October 2023

We consider tracking control of linear minimum phase systems with known arbitrary relative degree which are subject to possible output measurement losses. We provide a control law which guarantees the evolution of the tracking error within a (shifted) prescribed performance funnel whenever the output signal is available. The result requires a maximal duration of measurement losses and a minimal time of measurement availability, which both strongly depend on the internal dynamics of the system, and are derived explicitly. The controller is illustrated by a simulation of a mass-on-car system.
The Arenaviridae Family: Knowledge Gaps, Animal Models, Countermeasures, and Prototype Pathogens
Authors: Hastie Kathryn M , Melnik Lilia I , Cross Robert W , Klitting Raphaëlle M , Andersen Kristian G , Saphire Erica Ollmann , Garry Robert F
Published: October 2023

Lassa virus (LASV), Junin virus (JUNV), and several other members of the Arenaviridae family are capable of zoonotic transfer to humans and induction of severe viral hemorrhagic fevers. Despite the importance of arenaviruses as potential pandemic pathogens, numerous gaps exist in scientific knowledge pertaining to this diverse family, including gaps in understanding replication, immunosuppression, receptor usage, and elicitation of neutralizing antibody responses, that in turn complicates development of medical countermeasures. A further challenge to the development of medical countermeasures for arenaviruses is the requirement for use of animal models at high levels of biocontainment, where each model has distinct advantages and limitations depending on, availability of space, animals species-specific reagents, and most importantly the ability of the model to faithfully recapitulate human disease. Designation of LASV and JUNV as prototype pathogens can facilitate progress in addressing the public health challenges posed by members of this important virus family.
Developing a Prototype Pathogen Plan and Research Priorities for the Alphaviruses
Authors: Powers Ann M , Williamson Lauren E , Carnahan Robert H , Crowe James E , Hyde Jennifer L , Jonsson Colleen B , Nasar Farooq , Weaver Scott C
Published: October 2023

The Togaviridae family, genus, Alphavirus, includes several mosquito-borne human pathogens with the potential to spread to near pandemic proportions. Most of these are zoonotic, with spillover infections of humans and domestic animals, but a few such as chikungunya virus (CHIKV) have the ability to use humans as amplification hosts for transmission in urban settings and explosive outbreaks. Most alphaviruses cause nonspecific acute febrile illness, with pathogenesis sometimes leading to either encephalitis or arthralgic manifestations with severe and chronic morbidity and occasional mortality. The development of countermeasures, especially against CHIKV and Venezuelan equine encephalitis virus that are major threats, has included vaccines and antibody-based therapeutics that are likely to also be successful for rapid responses with other members of the family. However, further work with these prototypes and other alphavirus pathogens should target better understanding of human tropism and pathogenesis, more comprehensive identification of cellular receptors and entry, and better understanding of structural mechanisms of neutralization.
A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures
Authors: Kuhn Richard J , Barrett Alan D T , Desilva Aravinda M , Harris Eva , Kramer Laura D , Montgomery Ruth R , Pierson Theodore C , Sette Alessandro , Diamond Michael S
Published: October 2023

Flaviviruses are a genus within the Flaviviridae family of positive-strand RNA viruses and are transmitted principally through mosquito and tick vectors. These viruses are responsible for hundreds of millions of human infections worldwide per year that result in a range of illnesses from self-limiting febrile syndromes to severe neurotropic and viscerotropic diseases and, in some cases, death. A vaccine against the prototype flavivirus, yellow fever virus, has been deployed for 85 years and is highly effective. While vaccines against some medically important flaviviruses are available, others have proven challenging to develop. The emergence and spread of flaviviruses, including dengue virus and Zika virus, demonstrate their pandemic potential. This review highlights the gaps in knowledge that need to be addressed to allow for the rapid development of vaccines against emerging flaviviruses in the future.
Chinese Foreign Real Estate Investment and Local Voting in US Presidential Elections
Authors: Liao Steven
Published: October 2023

Despite the increasing globalization of housing markets, little is known about its political implications. This study investigates whether rising Chinese investments in US homes influenced local voting in recent US presidential elections. Building on pocketbook/sociotropic voting and nativism theories, I develop hypotheses on the electoral consequences of foreign real estate investment through greater home demand and equity, improved local economies, and changing neighborhoods. Using difference-in-differences designs that combine a unique shock to Chinese capital outflows in 2013 with county-level measures of local attractiveness to Chinese investments, I find that greater exposure reduced Democratic vote shares in both the 2016 and 2020 presidential elections. Furthermore, an initially larger white population strengthened this effect, while a larger college-educated population weakened it. In contrast, local equity gains, housing competition, or economic strength did not systematically influence the effect. Together, the results appear more consistent with the pro-conservative effects of nativism.
R&D location in dynamic industry environments
Authors: Colombo Luca , Dawid Herbert , Harting Philipp
Published: October 2023

We study firms’ optimal R&D location strategies in a dynamic industry model with competition in product quality. In light of potential future inwards and outwards spillovers firms make their location choices relying on heuristic strategies that are based on the expected present values associated with alternative location patterns. Using a simulation analysis, we show how the strategies of innovators and imitators differ and how they depend on whether firms operate in strongly or weakly innovative industry environments. We also characterize how firms’ location choices should account for the innovativeness of the competitors active in a location.
Black cancer patients navigating a health-care system of racial discrimination
Authors: Garrett Elleyse , Ma Cindy , Ochoa-Dominguez Carol Y , Navarro Stephanie , Yoon Paul , Hughes Halbert Chanita , Farias Albert J
Published: October 2023

Background

Exposure to racial discrimination may exacerbate disparities throughout the cancer care continuum. Therefore, we explored how experiences of racial discrimination in the health-care setting manifest for Black cancer patients and how it contributes to racial disparities in cancer care.

Methods

This qualitative analysis used semistructured in-depth interviews with Black cancer survivors not on active treatment from May 2019 to March 2020. All interviews were audio recorded, professionally transcribed, and uploaded into Dedoose software for analysis. We identified major themes and subthemes that highlight exposure to racial discrimination and its consequences for Black cancer patients when receiving cancer care.

Results

Participants included 18 Black cancer survivors, aged 29-88 years. Most patients experienced racial discrimination when seeking care. Participants experienced racial discrimination from their interactions with health-care staff, medical assistants, front desk staff, and health insurance administrators. Exposure to overt racial discrimination in the health-care setting was rooted in racial stereotypes and manifested through verbal insults such as physicians using phrases such as “you people.” These experiences impacted the ability of the health-care delivery system to demonstrate trustworthiness. Patients noted “walking out” of their visit and not having their health issues addressed. Despite experiences with racial discrimination, patients still sought care out of necessity believing it was an inevitable part of the Black individual experience.

Conclusion

We identified that exposure to racial discrimination in the health-care setting is pervasive, affects health-seeking behaviors, and degrades the patient–clinician relationship, which may likely contribute to racial disparities in cancer care.
Appendicitis mimicry of dolichocolon
Authors: Brown Kayla K , Jolley Mercedes C , Kocay Dean A
Published: October 2023

Dolichocolon is an under-reported, under-diagnosed etiology of chronic constipation that is often overlooked as being a primary diagnosis. We present a case of an undiagnosed dolichocolon in a young adult female whose initial presentation was concerning of appendicitis. Eventually, the patient underwent a subtotal colectomy as a definitive treatment for chronic constipation. Dolichocolon is an anatomical variant that can have severe lifelong consequences, such as chronic constipation, which greatly affects a patient’s quality of life and overall health if undiagnosed. The purpose of this case report is to raise awareness among the surgical community regarding the significance of early dolichocolon diagnosis, prevent misdiagnosis, and ultimately improve patient outcomes, including reducing complications associated with chronic constipation.
Bouveret syndrome: two approaches one stone
Authors: Satchithanandha Vysheki , Lau Ngee-Soon , Galevska Ana , Sandroussi Charbel
Published: October 2023

Bouveret syndrome is a rare cause of gastric outlet obstruction, a consequence of a large impacted gallstone leading to the formation of a bilioenteric fistula. We present a case of a 79-year-old female who presented with a history of persistent nausea and vomiting. Computed tomography of the abdomen revealed a large gallstone impacted in the second part of the duodenum, complicated by a cholecystoduodenal fistula, leading to gastric outlet obstruction. After nasogastric decompression, the patient underwent an upper gastrointestinal endoscopy and attempted stone retrieval which was unsuccessful. Consequently, she underwent laparotomy, gastrotomy, and extraction of the stone. This case highlights the pitfalls of managing Bouveret syndrome via an endoscopic or an open surgical approach.
Adult intussusception of the small intestine caused by cystic fibrosis: a case report, review of the literature, and guide for management
Authors: Adu Yaw , Wolkober Brianna , Nesiama Esere , Thompson Lori , Laswi Mujahed , Obokhare Izi
Published: October 2023

Intussusception, an uncommon but potentially severe condition primarily associated with infants and young children, can also present in adults, posing distinct challenges in diagnosis and treatment. This report presents the case of a 22-year-old male with cystic fibrosis, who developed intussusception due to severe constipation in his distal gastrointestinal tract. The patient’s initial presentation included abdominal pain, constipation, and abnormal laboratory results. Computed tomography scans revealed intussusception affecting the ascending colon and cecum, necessitating surgical intervention and subsequent bowel resection. In adults, the presence of intussusception often triggers suspicion of underlying pathological lead points. However, in this instance, the root cause was attributed to cystic fibrosis induced constipation. Current evidence suggests limited efficacy with conservative treatment, with bowel resection being the most definitive treatment option. Further research is warranted to establish comprehensive guidelines for managing this uncommon condition, particularly when intertwined with cystic fibrosis.
Facial kinship verification and searching for genetic origins in gamete/embryo donor conception—an overview of potential legal and ethical issues
Authors: Łukasiewicz Rafał , Frith Lucy , Redhead Caroline
Published: October 2023

The aim of Facial Kinship Verification (FKV) technologies is to determine, by comparing images of their faces, whether two people are related genetically. FKV is developing rapidly, and it could be used to search for genetic relatives in a variety of ways and settings, such as searching for missing children or unknown parents. In this article, we focus on one area where this technology might have significant implications, the searching for gamete (egg and sperm) and embryo donor(s) by donor-conceived people. In many jurisdictions, donor-conceived people do not have access to information about their donor’s identity, and laws differ significantly in this area. We offer an initial overview of the legal and related ethical issues raised by FKV in this context, and touch on other areas where it might be used to find genetic relatives, as a starting point for further analysis and research.
In Situ Transmission Electron Microscopy Study of Bubble Behavior Near the Surface of Ice Crystals by Using a Liquid Cell With a Peltier Cooling Holder
Authors: Yamazaki Tomoya , Yashima Yuga , Katsuno Hiroyasu , Miyazaki Hiroya , Gondo Takashi , Kimura Yuki
Published: October 2023

Liquid cell transmission electron microscopy (LC-TEM) is a unique technique that permits in situ observations of various phenomena in liquids with high spatial and temporal resolutions. One difficulty with this technique is the control of the environmental conditions in the observation area. Control of the temperature ranging from room temperature to minus several tens of degrees Celsius, is desirable for controlling the supersaturation in various materials and for observing crystallization more easily. We have developed a cooling transmission electron microscopy specimen holder that uses Peltier devices, and we have combined it with a liquid cell to realize accurate temperature control in LC-TEM. We evaluated this system by using water as a specimen. Motionless bubbles, shown to be voids containing pressurized gas, formed in the specimen sometime after the temperature had reached −12°C. An electron diffraction pattern showed that the specimen turned into ice Ih after the formation of these bubbles, confirming that our system works properly and can induce crystallization. In addition, we analyzed the behavior of bubbles formed in the ice Ih, and we discussed the formation of these bubbles and their internal pressure.
Dark Energy Survey Year 3 results: redshift calibration of the MagLim lens sample from the combination of SOMPZ and clustering and its impact on cosmology
Authors: Giannini G , Alarcon A , Gatti M , Porredon A , Crocce M , Bernstein G M , Cawthon R , Sánchez C , Doux C , Elvin-Poole J , Raveri M , Myles J , Lin H , Amon A , Allam S , Alves O , Andrade-Oliveira F , Baxter E , Bechtol K , Becker M R , Blazek J , Camacho H , Campos A , Rosell A Carnero , Kind M Carrasco , Choi A , Cordero J , De Vicente J , DeRose J , Diehl H T , Dodelson S , Drlica-Wagner A , Eckert K , Fang X , Farahi A , Fosalba P , Friedrich O , Gruen D , Gruendl R A , Gschwend J , Harrison I , Hartley W G , Huff E M , Jarvis M , Krause E , Kuropatkin N , Lemos P , MacCrann N , McCullough J , Muir J , Pandey S , Prat J , Rodriguez-Monroy M , Ross A J , Rykoff E S , Samuroff S , Secco L F , Sevilla-Noarbe I , Sheldon E , Troxel M A , Tucker D L , Weaverdyck N , Yanny B , Yin B , Zhang Y , Abbott T M C , Aguena M , Bacon D , Bertin E , Bocquet S , Brooks D , Burke D L , Carretero J , Castander F J , Costanzi M , da Costa L N , Pereira M E S , Desai S , Doel P , Ferrero I , Flaugher B , Friedel D , Frieman J , García-Bellido J , Gerdes D W , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kent S , Kuehn K , Lahav O , Lidman C , Lima M , Melchior P , Mena-Fernández J , Menanteau F , Miquel R , Ogando R L C , Paterno M , Paz-Chinchón F , Pieres A , Malagón A A Plazas , Roodman A , Sanchez E , Scarpine V , Smith M , Suchyta E , Swanson M E C , Tarle G , Thomas D , To C , Vincenzi M ,   (DES Collaboration)
Published: October 2023

We present an alternative calibration of the MagLim lens sample redshift distributions from the Dark Energy Survey (DES) first 3 yr of data (Y3). The new calibration is based on a combination of a self-organizing-map-based scheme and clustering redshifts to estimate redshift distributions and inherent uncertainties, which is expected to be more accurate than the original DES Y3 redshift calibration of the lens sample. We describe in detail the methodology, and validate it on simulations and discuss the main effects dominating our error budget. The new calibration is in fair agreement with the fiducial DES Y3 n(z) calibration, with only mild differences (<3σ) in the means and widths of the distributions. We study the impact of this new calibration on cosmological constraints, analysing DES Y3 galaxy clustering and galaxy–galaxy lensing measurements, assuming a Lambda cold dark matter cosmology. We obtain Ωm = 0.30 ± 0.04, σ8 = 0.81 ± 0.07, and S8 = 0.81 ± 0.04, which implies a ∼0.4σ shift in the Ω − S8 plane compared to the fiducial DES Y3 results, highlighting the importance of the redshift calibration of the lens sample in multiprobe cosmological analyses.
Response of gravitationally coupled gaseous and stellar components to asymmetric warp in disc galaxies
Authors: Goyary Sagar S , Singh H Shanjit
Published: October 2023

The outer disc region of most spiral galaxies (approximately 50 per cent of all disc galaxies) shows warping above the galactic mid-plane and is primarily asymmetric by nature. In this work, we explore analytically the effect of the gas component on asymmetric warps in a realistic self-gravitating collision-less disc residing in a cold oblate dark matter halo’s potential field. We consider the disc to be composed of gravitationally coupled stars and gas components. The quadratic eigenvalue equation describing the shape and frequency of the bending mode is formulated and solved numerically. Two stable ground-state bending modes m = 0 and m = 1, representing the U-shape and the mostly observed S-shaped warp in the galactic disc are superimposed linearly to generate and examine the asymmetric warps in the disc. The resulting asymmetry in warp is measured by asymmetric index (Aasym) by varying physical parameters such as the mass of the gas components and the halo flattening parameter. It is shown that the gas fraction in the disc has a negligible contribution to the generation of asymmetric warp in the disc. The disc residing in a spherical dark matter halo is found to be more asymmetry than that in the counterpart oblate halo.
GMRT observations of the radio trail from CXOU J163802.6−471358
Authors: Green D A , Roy S
Published: October 2023

The X-ray source CXOU J163802.6−471358 is thought to be a pulsar wind nebula (PWN), as it shows an extended, ≈40 arcsec trail from a compact source. Here, we present Giant Metrewave Radio Telescope observations of this source at 330 and 1390 MHz, which reveal a remarkable linear radio trail ≈90 arcsec in extent. Although the radio trail points back to the supernova remnant (SNR) G338.1+0.4, ≈50 arcmin from CXOU J163802.6−471358, associating it with this remnant would require a very large velocity for the pulsar. There are no known Galactic SNRs close to the PWN and radio trail. No pulsar has yet been identified in CXOU J163802.6−471358, but if one could be found, this would allow more quantitative studies of the PWN and radio trail to be made.
An information theory approach to identifying signs of life on transiting planets
Authors: Vannah Sara , Gleiser Marcelo , Kaltenegger Lisa
Published: October 2023

Can information theory provide insights into whether exoplanets are habitable? Here, we apply information theory to a range of simulated exoplanet transmission spectra as a diagnostic tool to search for potential signatures of life on Earth-analogue planets. We test the algorithms on three epochs of evolution for Earth-like planets orbiting a range of host stars. The JWST and upcoming ground- and space-based missions promise to achieve sufficient high-resolution data that information theory can be applied to assess habitability. This approach provides a framework and a tool for observers to assess whether an exoplanet shows signs of habitability.
Hypoxia stabilizes SETDB1 to maintain genome stability
Authors: Park Sungryul , Cho Jin Hwa , Kim Jong-Hwan , Park Mijin , Park Seulki , Kim Seon-Young , Kim Seon-Kyu , Kim Kidae , Park Sung Goo , Park Byoung Chul , Moon Jeong Hee , Lee Gaseul , Kim Sunhong , Kim Jung-Ae , Kim Jeong-Hoon
Published: October 2023

Von Hippel–Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
Unprecedented reactivity of polyamines with aldehydic DNA modifications: structural determinants of reactivity, characterization and enzymatic stability of adducts
Authors: Gusti Ngurah Putu Eka Putra , Cattiaux Laurent , Lavergne Thomas , Pommier Yves , Bombard Sophie , Granzhan Anton
Published: October 2023

Apurinic/apyrimidinic (AP) sites, 5-formyluracil (fU) and 5-formylcytosine (fC) are abundant DNA modifications that share aldehyde-type reactivity. Here, we demonstrate that polyamines featuring at least one secondary 1,2-diamine fragment in combination with aromatic units form covalent DNA adducts upon reaction with AP sites (with concomitant cleavage of the AP strand), fU and, to a lesser extent, fC residues. Using small-molecule mimics of AP site and fU, we show that reaction of secondary 1,2-diamines with AP sites leads to the formation of unprecedented 3′-tetrahydrofuro[2,3,4-ef]-1,4-diazepane (‘ribodiazepane’) scaffold, whereas the reaction with fU produces cationic 2,3-dihydro-1,4-diazepinium adducts via uracil ring opening. The reactivity of polyamines towards AP sites versus fU and fC can be tuned by modulating their chemical structure and pH of the reaction medium, enabling up to 20-fold chemoselectivity for AP sites with respect to fU and fC. This reaction is efficient in near-physiological conditions at low-micromolar concentration of polyamines and tolerant to the presence of a large excess of unmodified DNA. Remarkably, 3′-ribodiazepane adducts are chemically stable and resistant to the action of apurinic/apyrimidinic endonuclease 1 (APE1) and tyrosyl-DNA phosphoesterase 1 (TDP1), two DNA repair enzymes known to cleanse a variety of 3′ end-blocking DNA lesions.
Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae
Authors: Schrott Simon , Osman Christof
Published: October 2023

The mitochondrial genome, mtDNA, is present in multiple copies in cells and encodes essential subunits of oxidative phosphorylation complexes. mtDNA levels have to change in response to metabolic demands and copy number alterations are implicated in various diseases. The mitochondrial HMG-box proteins Abf2 in yeast and TFAM in mammals are critical for mtDNA maintenance and packaging and have been linked to mtDNA copy number control. Here, we discover the previously unrecognized mitochondrial HMG-box protein Cim1 (copy number influence on mtDNA) in Saccharomyces cerevisiae, which exhibits metabolic state dependent mtDNA association. Surprisingly, in contrast to Abf2’s supportive role in mtDNA maintenance, Cim1 negatively regulates mtDNA copy number. Cells lacking Cim1 display increased mtDNA levels and enhanced mitochondrial function, while Cim1 overexpression results in mtDNA loss. Intriguingly, Cim1 deletion alleviates mtDNA maintenance defects associated with loss of Abf2, while defects caused by Cim1 overexpression are mitigated by simultaneous overexpression of Abf2. Moreover, we find that the conserved LON protease Pim1 is essential to maintain low Cim1 levels, thereby preventing its accumulation and concomitant repressive effects on mtDNA. We propose a model in which the protein ratio of antagonistically acting Cim1 and Abf2 determines mtDNA copy number.
TheMarker: a comprehensive database of therapeutic biomarkers
Authors: Zhang Yintao , Zhou Ying , Zhou Yuan , Yu Xinyuan , Shen Xinyi , Hong Yanfeng , Zhang Yuxin , Wang Shanshan , Mou Minjie , Zhang Jinsong , Tao Lin , Gao Jianqing , Qiu Yunqing , Chen Yuzong , Zhu Feng
Published: October 2023

Distinct from the traditional diagnostic/prognostic biomarker (adopted as the indicator of disease state/process), the therapeutic biomarker (ThMAR) has emerged to be very crucial in the clinical development and clinical practice of all therapies. There are five types of ThMAR that have been found to play indispensable roles in various stages of drug discovery, such as: Pharmacodynamic Biomarker essential for guaranteeing the pharmacological effects of a therapy, Safety Biomarker critical for assessing the extent or likelihood of therapy-induced toxicity, Monitoring Biomarker indispensable for guiding clinical management by serially measuring patients’ status, Predictive Biomarker crucial for maximizing the clinical outcome of a therapy for specific individuals, and Surrogate Endpoint fundamental for accelerating the approval of a therapy. However, these data of ThMARs has not been comprehensively described by any of the existing databases. Herein, a database, named ‘TheMarker’, was therefore constructed to (a) systematically offer all five types of ThMAR used at different stages of drug development, (b) comprehensively describe ThMAR information for the largest number of drugs among available databases, (c) extensively cover the widest disease classes by not just focusing on anticancer therapies. These data in TheMarker are expected to have great implication and significant impact on drug discovery and clinical practice, and it is freely accessible without any login requirement at: https://idrblab.org/themarker.
scTEA-db: a comprehensive database of novel terminal exon isoforms identified from human single cell transcriptomes
Authors: Barquin Miguel , Kouzel Ian U , Ehrmann Beat , Basler Michael , Gruber Andreas J
Published: October 2023

The usage of alternative terminal exons results in messenger RNA (mRNA) isoforms that differ in their 3′ untranslated regions (3′ UTRs) and often also in their protein-coding sequences. Alternative 3′ UTRs contain different sets of cis-regulatory elements known to regulate mRNA stability, translation and localization, all of which are vital to cell identity and function. In previous work, we revealed that ∼25 percent of the experimentally observed RNA 3′ ends are located within regions currently annotated as intronic, indicating that many 3′ end isoforms remain to be uncovered. Also, the inclusion of not yet annotated terminal exons is more tissue specific compared to the already annotated ones. Here, we present the single cell-based Terminal Exon Annotation database (scTEA-db, www.scTEA-db.org) that provides the community with 12 063 so far not yet annotated terminal exons and associated transcript isoforms identified by analysing 53 069 publicly available single cell transcriptomes. Our scTEA-db web portal offers an array of features to find and explore novel terminal exons belonging to 5538 human genes, 110 of which are known cancer drivers. In summary, scTEA-db provides the foundation for studying the biological role of large numbers of so far not annotated terminal exon isoforms in cell identity and function.
The effect of B-vitamins on the prevention and treatment of cardiovascular diseases: a systematic review and meta-analysis
Authors: Miao Ya , Guo Yihan , Chen Yixin , Lin Yijia , Lu Yan , Guo Qihao
Published: October 2023

Context

Previous research evaluating the effects in B-vitamins on the prevention and treatment of cardiovascular disease (CVD) has substantial limitations and lacks recently published large prospective studies; hence, conducting an updated meta-analysis is needed.

Objective

We investigated the association between vitamin B status and human CVD development in order to provide more specific advice about vitamin B intake for those at risk of CVD.

Data Sources

Relevant articles were identified by JSTOR, PubMed, and ProQuest databases.

Data Extraction

Key words used to identify the studies included the different combinations of B-vitamins, folate, folic acid, vitamin B6, vitamin B12, homocysteine, cardiovascular disease, stroke, coronary disease, myocardial infarction, and cerebrovascular and transient ischemic attack. The database search was supplemented by hand-searching of reference lists of selected articles.

Data Analysis

Pooled estimates were calculated from the mean differences using a random-effects model.

Results

Supplementation with folic acid was reported to have a clinical benefit of significantly reducing carotid intima-media thickness. Higher intakes of folic acid, vitamin B6, and vitamin B12 were generally associated with a lower risk of CVD in the general population, except in those without normal renal function and those with unstable angina or past non–ST-elevation myocardial infarction.

Conclusion

Vitamin B supplementation resulted in the greatest cardiovascular benefit in those with normal renal function and without unstable angina or non–ST-elevation myocardial infarction recently. Factors such as age, gender, and genetic polymorphisms contribute to varying effects.
Sex differences in patch-leaving foraging decisions in rats
Authors: Garcia Marissa , Gupta Sukriti , Wikenheiser Andrew M
Published: October 2023

The ubiquity, importance, and sophistication of foraging behavior makes it an ideal platform for studying naturalistic decision making in animals. We developed a spatial patch-foraging task for rats, in which subjects chose how long to remain in one foraging patch as the rate of food earnings steadily decreased. The cost of seeking out a new location was varied across sessions. The behavioral task was designed to mimic the structure of natural foraging problems, where distinct spatial locations are associated with different reward statistics, and decisions require navigation and movement through space. Male and female Long-Evans rats generally followed the predictions of theoretical models of foraging, albeit with a consistent tendency to persist with patches for too long compared to behavioral strategies that maximize food intake rate. The tendency to choose overly-long patch residence times was stronger in male rats. We also observed sex differences in locomotion as rats performed the task, but these differences in movement only partially accounted for the differences in patch residence durations observed between male and female rats. Together, these results suggest a nuanced relationship between movement, sex, and foraging decisions.
Development and Validation of a Resistance Management Model for the Soybean Cyst Nematode, Heterodera glycines
Authors: McCarville Michael T. , Williams Jayme , Daum Julia
Published: October 2023

Plant-parasitic nematodes are a key yield-limiting pest of crops around the world. Deployment of plant resistance genes are an important management tactic for many economically important plant-parasitic nematodes. The selection for virulence in nematode populations is a major threat to the effectiveness of resistance gene-based management. Little research has gone into resistance management modelling despite the importance of both plant-parasitic nematodes and resistance genes for their management. In this paper, we report on a cyst nematode resistance management model created to explore the factors which are most important for determining the durability of resistance genes to this important family of plant-parasitic nematodes. The relative dominance of virulence expression, the level of inbreeding, and the number of generations per cropping season were the most important factors in predicting resistance gene durability. Aspects of cyst nematode biology that reduce the number of generations per season for a portion of the population had a much smaller effect on the durability of resistance genes. These factors included delayed hatching within a season and early dormancy. The accuracy and utility of the model was tested using the soybean cyst nematode (SCN) rhg1-mediated resistance system. The model accurately predicted the rate at which virulence to the rhg1b resistance gene developed in Iowa over a two-decade period. The model suggested resistance gene pyramids as the most durable management solution for SCN with multiple possible avenues to obtain acceptable efficacy and durability.
The role of high serum bilirubin as a predictor of complicated appendicitis: a retrospective cohort study
Authors: Bhandari Suyog , Baral Akriti , Tiwari Ashish , Shrestha Suman K.
Published: October 2023

Introduction:

An appendectomy is one of the most common emergency surgeries. The delay in diagnosis and treatment of appendicitis can lead to complicated appendicitis. The definitive predictive factor that can diagnose complicated appendicitis is still lacking. The authors aim to assess the role of high serum bilirubin level as a predictor of complicated appendicitis.

Methods:

A retrospective cohort study was conducted among patients with acute appendicitis (AA) between March 2017 and March 2018. Appendicitis cases diagnosed with the help of the Alvarado score undergoing surgery were taken in study and based on the histopathological report, the cases were classified into two groups: uncomplicated and complicated. Preoperatively, biochemical parameters like increased white blood cell count (>11000/cubic millimeter), and level of serum bilirubin >1.4 mg/dl were studied. Informed written consent for the study was taken from the patients with AA. A χ
2 test was applied for the association between categorical variables. Statistical analysis was done with a statistical package for the social sciences (SPSS) version 20; P-value less than 0.05 was considered statistically significant.

Results:

A total of 100 patients were enrolled in the study with a mean age of 31.2±18.3 years, and 60% were male. Seventy-four (74%) had uncomplicated appendicitis and 26 (26%) had complicated appendicitis. Mean bilirubin was 1.2±0.8 mg/dl in uncomplicated and 1.8±0.8 mg/dl in complicated groups (P <0.05). The sensitivity and specificity of hyperbilirubinemia as a predictor of complicated appendicitis were 50 and 78.38%, respectively.

Conclusion:

The study revealed that patients with AA and a higher serum bilirubin level have a higher risk of having complicated appendicitis. Serum bilirubin level helps to predict complicated appendicitis and thus plan for timely and appropriate management. Thus, the study concludes that bilirubin should be used together with clinical examination and other laboratory investigations in the assessment of patients with suspected AA.
Anatomic Analysis of Masseteric-to-zygomatic Nerve Transfer in Rat and Pig Models
Authors: Millesi Elena , Suchyta Marissa , Wang Huan , Mardini Samir
Published: October 2023

Background:

Nerve transfer from the masseteric branch of the trigeminal nerve is a widely performed procedure for facial reanimation. Despite achieving powerful muscle force, clinical and aesthetic results leave room for improvement. Preclinical animal models are invaluable to establishing new therapeutic approaches. This anatomical study aimed to establish a masseteric-to-zygomatic nerve transfer model in rats and pigs.

Methods:

The masseteric branch of the trigeminal nerve and the zygomatic branch of the facial nerve were dissected in 30 swine and 40 rat hemifaces. Both nerves were mobilized and approximated to achieve an overlap between the nerve ends. Over the course of dissecting both nerves, their anatomy, length, and branching pattern were documented. At the coaptation point, diameters of both nerves were measured, and samples were taken for neuromorphometric analysis.

Results:

Anatomic details and landmarks were described. Tension-free coaptation was possible in all rat and pig dissections. In rats, the masseteric branch had an average diameter of 0.36 mm (±0.06), and the zygomatic branch average diameter was 0.46 mm (±0.13). In pigs, the masseteric branch measured 0.52 (±0.16) mm and the zygomatic branch, 0.59 (±0.16) mm. No significant differences were found between the diameters and axon counts of both nerves in pigs. In rats, however, their diameters, axon counts, and fascicular areas were significantly different.

Conclusion:

Our study demonstrated the feasibility of direct masseteric-to-zygomatic nerve transfer in rats and pigs and provided general anatomic knowledge of both nerves.
Exercise training reduces arterial stiffness in women with high blood pressure: a systematic review and meta-analysis
Authors: Zaman Shadman , Raj Isaac Selva , Yang Angela Wei Hong , Lindner Robert , Denham Joshua
Published: October 2023

The acute and long-term benefits of exercise on cardiovascular health are well established, yet the optimal mode of exercise training that improves arterial stiffness in women with high blood pressure remains unclear. The aim of this systematic review and meta-analysis was to assess the influence of aerobic and resistance training on arterial stiffness in women with high blood pressure. After an extensive search of four online databases, six randomized controlled trials met the inclusion criteria and were included in meta-analyses. Data were extracted from six studies examining the influence of exercise on arterial stiffness assessed by pulse wave velocity (PWV) and were expressed as standardized mean difference (SMD). Whereas aerobic exercise significantly reduced arterial PWV in women with high blood pressure after long-term training [SMD −1.87, 95% confidence interval (CI) −2.34 to −1.40], resistance training had a more modest effect that was borderline statistically significant (SMD −0.31, 95% CI −0.65 to 0.03). These findings suggest regular long-term aerobic exercise training (i.e. 12–20 week interventions) reduces arterial stiffness in women with high blood pressure. Although not statistically significant, the modest number of included trials and lack of publication bias encourages further assessments on the efficacy of resistance exercise for improving arterial stiffness in women with high blood pressure. Given the unique benefits of aerobic and resistance training, particularly for postmenopausal women (e.g. bone health and muscular strength), both modes of training should be encouraged for women with high blood pressure to enhance arterial function and support favorable cardiovascular outcomes.
The Relationship Between Yoga Practice Dosage and Perceived Stress, Anxiety, and Self-reported Health Among Breast Cancer Survivors Who Practice Yoga
Authors: Weitz M. Velma , Bloch Joan R. , Birati Yosefa , Rundio Albert , Fisher Kathleen , Byrne Sharon , Guerra Linda
Published: October 2023

The aim of this anonymous online study was to explore the yoga practice of breast cancer survivors to determine if yoga dosage (frequency and duration of practice) was related to stress, anxiety, and self-reported health in female survivors. Participants were recruited from online breast cancer support groups during a 3-month period (June-September 2019). Demographic information, stage and treatment of breast cancer, and frequency of yoga participation, including a home yoga practice were reported. Measures include the Perceived Stress Scale, State-Trait Anxiety Inventory, and self-reported health. Cumulative yoga dosage was calculated. Thirty-five women participated (mean age = 55 years) and were divided into low and high yoga dosage groups based on the sample distribution. Low dosage of yoga was operationally defined as a cumulative dosage that fell within the lowest quartile (≤25%). Findings indicated no difference between the low-dosage group compared with the high-dosage group for perceived stress and self-reported health; but the high dosage yoga group had lower state anxiety scores (P< .05). All participants reported good self-reported health. These findings contribute to our knowledge of the psychosocial aspects of breast cancer survivorship and raise questions for further research quantifying the therapeutic dosing of yoga practice.
Acupuncture Reduces Severity of Hot Flashes in Breast Cancer
Authors: Serra Diane , Fleishman Stewart B. , White Carol , Leung Tung Ming , Chadha Manjeet
Published: October 2023

This study evaluated the effectiveness of traditional Chinese medicine-based therapeutic acupuncture (TA) in reducing the severity of hot flashes (HFs) in breast cancer patients and compared the effectiveness of TA to “sham” placebo acupuncture (SA). Subjects experiencing more than 10 episodes of HF/week were randomly assigned to TA or SA. The response was assessed by the Menopause-specific Quality of Life (MenQoL) scale, scoring the subject's perception of the severity of HFs. HFs were scored at baseline, after treatment, and 1-month follow-up. A total of 54 subjects enrolled (28 TA and 26 SA). Seven women withdrew from the study. A hot flash diary documented the number of HFs a subject experienced. Analysis included 47 subjects (27 TA and 20 SA). A statistically significant response in HF scores was noted in the TA group compared with the SA group (P = .0064.) On average HF scores dropped by 1.89 with TA, and only 0.16 with SA. At follow-up, TA subjects had a sustained response. TA is effective in reducing the intensity and severity of HF. With SA, no relative response/change in HF scores was noted. Larger studies and longer follow-up to assess durability of response to TA are needed.