bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ_0089282 inhibits carbon black nanoparticle-induced DNA damage by promoting DNA repair protein in the lung
Authors: Zhang Han , Zhou Hanyu , Zhang Nan , Jia Yangyang , Qiu Miaoyun , Yao Shuwei , Chen Xintong , Qiu Lan , Li Saifeng , Jiang Yiguo , Zhou Yun 
Published: January 2023

AbstractInhalation of carbon black nanoparticles (CBNPs) can impair lung tissue and cause DNA damage, but the epigenetic mechanism responsible for these effects is still unclear. We explored the role of circular RNAs (circRNAs) in DNA damage induced by CBNPs in the lung. Human bronchial epithelial cell lines (16HBE and BEAS-2B) were treated with 0, 5, 10, 20, 40, or 80 μg/ml CBNPs for 24, 48, and 72 h, and BALB/c mice were exposed to 8 and 80 μg/d CBNPs for 14 days to establish in vitro and vivo models of CBNP exposure, respectively. We found that CBNPs caused DNA double-strand breaks in the lung. Using high-throughput sequencing and quantitative real-time PCR to identify CBNP-related circRNAs, we identified a novel circRNA (circ_0089282) that was overexpressed in the CBNP-exposed group. We used gain-/loss-of-function approaches, RNA pulldown assays, and silver staining to explore the regulatory function of circ_0089282 and its interactions with targeted proteins. We found that circ_0089282 interference could increase CBNP-induced DNA damage, whereas overexpression resulted in the opposite. Circ_0089282 could directly bind to the fused in sarcoma (FUS) protein and positively regulate downstream DNA repair protein DNA ligase 4 (LIG4) through FUS. This regulatory effect of circRNA on DNA damage via promotion of LIG4 illustrated the interactions between genetics and epigenetics in toxicology.
Anellovirus evolution during long-term chronic infection
Authors: Kaczorowska Joanna , Timmerman Anne L , Deijs Martin , Kinsella Cormac M , Bakker Margreet , van der Hoek Lia 
Published: January 2023

Abstract
Human anelloviruses (AVs) are extremely genetically diverse, are widespread in the human population, and cause chronic infections. However, the evolutionary dynamics of AVs within single hosts is currently unknown, and it is unclear whether these changes have an implication on the long-term persistence of AVs in the host. Here, we assessed the evolutionary dynamics of six AV lineages during 30 years of chronic infection at single host resolution. The total number of substitutions and the number of variable sites increased over time. However, not all substitutions reached population fixation, showing that AV lineages form heterogeneous swarms within the host. Most substitutions occurred within a hypervariable region (HVR) located between nucleotide positions 800 and 1,300 of ORF1, which is known to be located within the spike domain. Different regions of the ORF1 gene undergo either positive or negative selection pressure. Sites under strong diversifying selection pressure were detected in the HVR, while the majority of the sites under purifying selection were detected outside this region. The HVR may play the role of an immunological decoy that prevents antibodies from binding to more vulnerable parts of ORF1. Moreover, the frequent substitutions in this region may increase the chances of AV particles escaping immune recognition.
Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine
Authors: Lanier William L. 
Published: January 2023

Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87–95. Reprinted with permission.
By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.
The Middle Rectal Artery: Revisited Anatomy and Surgical Implications of a Neglected Blood Vessel
Authors: Heinze Tillmann , Fletcher Jordan , Miskovic Danilo , Stelzner Sigmar , Bayer Andreas , Wedel Thilo 
Published: January 2023

BACKGROUND:
Although the middle rectal artery is a relevant anatomical landmark for rectal resection and lateral lymph node dissection, descriptions of this entity are highly divergent.

OBJECTIVE:
Dissection, visualization, morphometry, and 3-dimensional reconstruction of the middle rectal artery to facilitate its management in surgery.

DESIGN:
Macroscopic dissection, histologic study, morphometric measurements, and virtual modeling.

SETTING:
University laboratory of applied surgical anatomy.

PATIENTS:
This study includes formalin-fixed hemipelvis specimens (n=37) obtained from body donors (age, 67–97 y).

MAIN OUTCOME MEASURES:
The main outcome measures are photo documentation of origin, trajectory, diameter, and branching pattern; immunolabeling of lymphatics; and 3-dimensional reconstruction of the middle rectal artery.

RESULTS:
The middle rectal artery was present in 71.4% of body donors (21.4% bilateral, 50% unilateral), originated from the anterior division of the internal iliac artery, and branched either from the internal pudendal artery (45.5%), the inferior gluteal artery (22.7%), the gluteal-pudendal trunk (22.7%), or a trifurcation (9.1%). One to 3 branches of varying diameters (0.5–3.5 mm) entered the mesorectum from the ventrolateral (35.7%), lateral (42.9%), or dorsolateral (21.4%) aspect. The middle rectal artery was accompanied by podoplanin-immunoreactive lymphatic vessels and gave off additional branches (81.8%) to the urogenital pelvic organs. Three-dimensional reconstruction revealed the complex course of the middle rectal artery from the pelvic sidewall through the pelvic nerve plexus and parietal pelvic fascia into the mesorectum.

LIMITATIONS:
Findings retrieved from body donors may be prone to age- and fixation-related processes.

CONCLUSIONS:
The investigation disclosed the rather high prevalence of the middle rectal artery, its 3-dimensional topographic anatomy, and its proximity to the autonomic pelvic nerves. These features play a role in the surgical management of this blood vessel. The data provide the anatomical rationale for the lateral lymphatic spread of rectal cancer and an anatomical basis for nerve-preserving lateral lymph node dissection.
Adaptation of prokaryotic toxins for negative selection and cloning-independent markerless mutagenesis (CIMM) inStreptococcusspecies
Authors: Li Lena , Qin Hua , Zou Zhengzhong , Kreth Jens , Merritt Justin 
Published: January 2023

AbstractTheStreptococcus mutansgenetic system offers a variety of strategies to rapidly engineer targeted chromosomal mutations. Previously, we reported the firstS. mutansnegative selection system that functions in a wild-type background. This system utilizes induced sensitivity to the toxic amino acid analogp-chlorophenylalanine (4-CP) as a negative selection mechanism, and was developed for counterselection-based cloning-independent markerless mutagenesis (CIMM). While we have employed this system extensively for our ongoing genetic studies, we have encountered a couple limitations with the system, mainly its narrow host range and the requirement for selection on a toxic substrate. Here, we report the development of a new negative selection system that addresses both limitations, while still retaining the utility of the previous 4-CP-based markerless mutagenesis system. We placed a variety of toxin-encoding genes under the control of the xylose-inducible Xyl-S expression cassette and found the Fst-sm and ParE toxins to be suitable candidates for inducible negative selection. We combined the inducible toxins with an antibiotic resistance gene to create several different counterselection cassettes. The most broadly useful of these contained a wild-typefst-smopen reading frame transcriptionally fused to a point mutant form of the Xyl-S expression system, which we subsequently named as IFDC4. IFDC4 was shown to exhibit exceptionally low background resistance, with 3 – 4 log reductions in cell number observed when plating on xylose-supplemented media. IFDC4 also functioned similarly in multiple strains ofS. mutansas well as withS. gordoniiandS. sanguinis. We performed CIMM with IFDC4 and successfully engineered a variety of different types of markerless mutations in all three species. The counterselection strategy described here provides a template approach that should be adaptable for the creation of similar counterselection systems in many other bacteria.
Modelling the Longitudinal Dynamics of Paranoia in Psychosis: A Temporal Network Analysis Over 20 Years
Authors: Barnby J.M. , Haslbeck J.M.B. , Sharma R. , Rosen C. , Harrow M. 
Published: January 2023

AbstractParanoia is a highly debilitating, core element of psychosis, although is poorly managed. Theories of paranoia mostly interface with short-scale or cross-sectional data models, leaving the longitudinal course of paranoia underspecified. Here, we develop an empirical characterisation of two aspects of paranoia - persecutory and referential delusions - in individuals with psychosis over 20 years. We examine delusional dynamics by applying a Graphical Vector Autoregression Model to data collected from the Chicago Follow-up Study (n=135 with a range of psychosis-spectrum diagnoses). We adjusted for age, sex, IQ, and antipsychotic use. We found that referential and persecutory delusions are central themes, supported by other primary delusions, and are strongly autoregressive – the presence of referential and persecutory delusions is predictive of their future occurrence. In a second analysis we demonstrate that social factors influence the severity of referential, but not persecutory, delusions. We suggest that persecutory delusions represent central, resistant states in the cognitive landscape, whereas referential beliefs are more flexible, offering an important window of opportunity for intervention. Our data models can be collated with prior biological, computational, and social work to contribute toward a more complete theory of paranoia and provide more time-dependent evidence for optimal treatment targets.Graphical AbstractHighlightsPersecutory and referential delusions are central themes amongst primary delusions in chronic psychosis.Persecutory and referential delusions share a recursive relationship and are both strongly and positively autoregressive.Greater number and quality of friends reduce referential, but not persecutory, delusions.Our formal data model can be used as a test bed and framework for clinical intervention.
Hepatitis B virus infection status and associated factors among health care workers in selected hospitals in Kisumu County, Kenya: a cross-sectional study
Authors: Mboya Frankline Otieno , Daud Ibrahim I. , Ondondo Raphael , Onguru Daniel 
Published: January 2023

AbstractBackgroundPoorly managed medical waste produced at the health facilities are potential source of infections including occupational exposure to Hepatitis B Virus (HBV). This study evaluated the prevalence of HBV infection among healthcare workers (HCW) in Kisumu County.MethodsWe determined the prevalence of HBV infections among 192 HCW from nine purposively selected high volume public hospitals in Kisumu County. A structured questionnaire was administered, and 4.0 ml of venous blood sample collected for Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and total hepatitis B core antibody (anti-HBc) testing using enzyme immunoassay (EIA).ResultsOf the 192 HCW sampled, 52.1% were males and 78.7% are married, the median participants age was 34.4 years with interquartile range (IQR) of 11 years. Most participants had between 1-5 years of service while 43.8% had ≥2 doses of HBV vaccine.The respective prevalence of HBsAg, anti HBs and anti HBc was 18.8% (95% CI: 13.5-25.0%), 63.0% (95% CI: 55.8-69.9%) and 44.8% (95% CI: 37.6-52.1%). Higher proportion of HBV positive was found in HCW who had worked for less than one year and who had not received any dose of HBV vaccine at 37.5% and 35.9 % respectively.. Significant risk of HBV lifetime exposure was noted among HCW with one vaccine dose, those with no known exposure and highest in those with knowledge on HBV transmission (aOR, 7.97; 95% CI, 2.10-153.3, p-value=0.008). HCW who had received ≥2 doses of HBV vaccine (aOR, 0.03; 95% CI, 0.01-0.10, p-value= <0.0001) had significant HBV protection. Duration of service was not associated with HBV among HCW.ConclusionPrevalence of HBV infection was high among HCW in Kisumu County. Ministry of health Kenya should strengthen comprehensive infection prevention and control practices to reduce lifetime exposure to HBV infection among HCW.
Predicting Ward Transfer Mortality with Machine Learning
Authors: Lezama Jose L. , Alterovitz Gil , Jakey Colleen E. , Kraus Ana L. , Kim Michael J. , Borkowski Andrew A. 
Published: January 2023

ABSTRACTBackgroundPredicting mortality and morbidity amongst hospitalized patients has long been a struggle for inpatient Internal Medicine physicians. To prevent physician burnout, hospital organizations are turning to shift work for the care of hospitalized patients. Such shift work frequently leads to a handoff of patients, with many physicians often being the sole provider in the hospital for close to one hundred patients.ObjectivesWe propose developing an artificial intelligence model that helps predict which patients will be most at risk of increased mortality. This model would assist providers and frontline staff in focusing their efforts on improving patient outcomes.Materials and MethodsRecords of patients who were transferred from non-intensive care units to intensive care units were queried from the Veteran Affairs Corporate Data Warehouse (CDW). Two thousand four hundred twenty-five records were identified. The patient outcome was designated a dependent variable, with bad outcome defined as the patient dying within 30 days of admission and good outcome as the patient being alive within 30 days of admission. Using twenty-two independent variables, we trained sixteen machine learning models, of which six best-performing ones were fine-tuned and evaluated on the testing dataset. Finally, we repeated this process with twenty independent variables, omitting the Length of Stay and Days to Intensive Care Unit Transfer variables which are unknown at the time of admission.ResultsThe best results were obtained with the LightGBM model with both datasets, one that included Length of Stay and Days to Intensive Care Unit Transfer variables and the other without these two variables. The former achieved Receiver Operating Characteristics Curve - Area Under the Curve (ROC-AUC) of 0.89, an accuracy of 0.72, a sensitivity of 0.97, and a specificity of 0.68, while the latter achieved a ROC-AUC of 0.86, an accuracy of 0.71, sensitivity of 0.94 and specificity of 0.67 respectively.ConclusionsOur predictive mortality model may offer providers a means for optimizing the utilization of resources when managing a large caseload, especially with shift changes.
Rapid automated 3-D pose estimation of larval zebrafish using a physical model-trained neural network
Authors: Ravan Aniket , Feng Ruopei , Gruebele Martin , Chemla Yann R. 
Published: January 2023

AbstractQuantitative ethology requires an accurate estimation of an organism’s postural dynamics in three dimensions plus time. Technological progress over the last decade has made animal pose estimation in challenging scenarios possible with unprecedented detail. Here, we present (i) a fast automated method to record and track the pose of individual larval zebrafish in a 3-D environment, applicable when accurate human labeling is not possible; (ii) a rich annotated dataset of 3-D larval poses for ethologists and the general zebrafish and machine learning community; and (iii) a technique to generate realistic, annotated larval images in novel behavioral contexts. Using a three-camera system calibrated with refraction correction, we record diverse larval swims under free swimming conditions and in response to acoustic and optical stimuli. We then employ a convolutional neural network to estimate 3-D larval poses from video images. The network is trained against a set of synthetic larval images rendered using a 3-D physical model of larvae. This 3-D model samples from a distribution of realistic larval poses that we estimate a priori using a template-based pose estimation of a small number of swim bouts. Our network model, trained without any human annotation, performs larval pose estimation with much higher speed and comparable accuracy to the template-based approach, capturing detailed kinematics of 3-D larval swims.Author SummaryLarval zebrafish swimming has been studied extensively in 2-D environments, which are restrictive compared to natural 3-D habitats. To enable rapid capture of 3-D poses, we collect three orthogonal video projections of swim behaviors in several behavioral settings and fit poses to a physical model. We then use the physical model to generate an auto-annotated stream of synthetic poses to train a convolutional neural network. The network model performs highly accurate pose predictions on over 600 real swim bouts much faster than a physical model fit. Our results show that larvae frequently exhibit motions inaccessible in a 2-D setup. The annotated dataset could be used by ethologists studying larval swimming dynamics, and by the machine learning community interested in multi-dimensional time series and 3-D reconstruction. Using the ability to render images with multiple synthetic poses, our method can be extended to collective behavior.
DNA methylation signature inNSD2loss-of-function variants appeared similar to that in Wolf-Hirschhorn syndrome
Authors: Kawai Tomoko , Kinoshita Shiori , Takayama Yuka , Onishi Eriko , Kamura Hiromi , Kojima Kazuaki , Kikuchi Hiroki , Terao Miho , Sugawara Tohru , Migita Ohsuke , Kagami Masayo , Isojima Tsuyoshi , Yamaguchi Yu , Wakui Keiko , Ohashi Hirofumi , Shimizu Kenji , Mizuno Seiji , Okamoto Nobuhiko , Fukushima Yoshimitsu , Takada Fumio , Kosaki Kenjiro , Takada Shuji , Akutsu Hidenori , Ura Kiyoe , Nakabayashi Kazuhiko , Hata Kenichiro 
Published: January 2023

AbstractPurposeWolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome caused by the hemizygous deletion of the distal short arm of chromosome 4 whereNSD2is, reportedly exhibits specific DNA methylation signatures in peripheral blood cells. However, responsible genomic loci for signatures are unreported. The objective of the study is to define the loci of WHS-related DNA methylation signatures and to explore the role ofNSD2for the signatures.MethodsWe conducted genome-wide methylation analysis of individuals with WHS orNSD2variants using array. We studied genome-edited knock in mice or induced pluripotent stem cells to explore the function ofNSD2variants which are observed in congenital anomaly cases.ResultsThree undiagnosed cases withNSD2variants showed WHS-related DNA methylation signatures. These variants were validated to beNSD2loss-of-function in induced pluripotent stem cells or genome-edited knock-in mice. p.Pro905Leu variant decreased Nsd2 protein levels, and changed Histone H3-Lysine 36 demethylation levels in similar way in the same genomic regions asNsd2knock out mice regulated.Nsd2knock out mice exhibited common DNA methylation changes.ConclusionThese results revealed that WHS-related DNA methylation signatures are dependent onNSD2dysfunction and are useful in diagnosingNSD2variants of unknown significance.
APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia
Authors: Nair Jayakrishnan , Welch Joseph F. , Marciante Alexandria B. , Hou Tingting , Lu Qing , Fox Emily J. , Mitchell Gordon S. 
Published: January 2023

ABSTRACTRationaleAcute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability.ObjectivesIdentify individual factors (e.g., genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).MethodsAssociations of individual factors with the magnitude of AIHH (15, 1-min O2=9.5%, CO2=5% episodes) induced changes in diaphragm motor-evoked potential amplitude (MEP) and inspiratory mouth occlusion pressures (P0.1) were evaluated in 17 healthy individuals (age=27±5 years) compared to Sham. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E,APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoEknock-in rats were performed to test causality.ResultsAIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous forAPOE4(i.e., APOE3/4) alleleversusotherAPOEgenotypes (p=0.048). No significant differences were observed between any other SNPs investigated, notablyBDNFval/met(all p>0.05). Males exhibited a greater diaphragm MEP enhancementversusfemales, regardless of age (p=0.004). Age was inversely related with change in P0.1within the limited age range studied (p=0.007). InhApoE4knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3controls (p<0.05).ConclusionsAPOE4genotype, sex and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults.ADDITION TO KNOWLEDGE BASEAcute intermittent hypoxia (AIH) is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative diseases. Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH), in healthy humans. We demonstrate that genetics (particularly the lipid transporter,APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.