bluuebunny/crossref_metadata_2025 huggingface dataset:
PSXI-14 Effect of a Sensory Additive to Maximize Sow Feed Intake and Performance of Piglets During Lactation Under Heat Stress Conditions
Authors: López-Vergé Sergi , He Maolong , Lv Jiaqi , Wang Haifeng , Tedó Gemma , Otto-Tice Emily
Published: November 2023

Longevity of the sows is a major concern in pig production, which is negatively affected when the sow body condition is not properly restored shortly after weaning. Therefore, feed intake (FI) becomes crucial to prevent the excessive body reserve mobilization during lactation, but also in promoting milk production and therefore maximizing litter performance. This situation is more exacerbated under heat stress conditions, in which FI is severely affected. The aim of the present study was to increase the sow FI and to maximize litter performance during lactation under heat stress conditions. A total of 20 Landrace x Large White sows were used. Animals were individually caged in farrowing crates one week before parturition according to their body weight, backfat thickness and parity and randomly assigned to two treatments (10 sows/treatment): Control diet, (C) or a diet containing a sensory additive (SA) included at 0.075% (Luctamax Sows, Lucta S.A., Barcelona, Spain). All diets were offered restricted from entry to the farrowing unit until parturition and ad libitum afterwards until weaning. For the sows’ body weight (BW, kg) a scale was used; back fat (BF, mm) was registered by ultrasound echography (in mm). Both measurements were performed at the entry to the farrowing unit and at weaning. Piglets’ performance was also monitored from birth to weaning (21 d of life). Higher temperature during the trial was over 30ºC (reaching a maximum of 37ºC). Data were analyzed by using the TTEST procedure of SAS. Results showed that SA sows increased up to 6.2% their FI compared with the C group (5.86 kg/d vs 5.52 kg/d, P = 0.08) from farrowing to weaning. Regarding the body reserves mobilization, BW (-24.7 kg vs -29.4 kg) and BF (-1.00 mm vs -3.30 mm) loses were numerically less in SA sows compared with C sows, respectively (P > 0.05). Finally, concerning performance of piglets, the inclusion of the SA tended to increase the growth during the first week after farrowing (0.174 kg/d vs 0.156 kg/d, P = 0.06) compared with the C group, respectively with no significant differences for the whole lactation period. Similarly, piglets weaning BW was slightly numerically greater for piglets born from SA sows compared with the control group (5.62 kg vs. 5.53, P > 0.05), respectively. Results suggest that the dietary inclusion of the sensory additive Luctamax Sows at 0.075% in the lactation diet from entry to the farrowing unit until weaning increased sows FI and prevented body reserves mobilization, having also benefits in the offspring, specially one week after farrowing. These results prove the potential of a sensory additive in helping the sows to cope with the lactation phase, especially under heat stress conditions.
Five cases of unintentional exposure to BZO-4en-POXIZID among nightclub attendees in New York City
Authors: Palamar Joseph J , Massano Marta , Salomone Alberto
Published: November 2023

A new class of synthetic cannabinoids called OXIZIDs has emerged in recent years. This class consists of compounds with oxindole cores and hydrazide/hydrazone linker moieties and has often been described as being designed to circumvent a Chinese class-wide ban that was effective as of 1 July 2021. However, through hair testing of nightclub attendees in New York City—a high-risk population for recreational drug use—we have evidence suggesting exposures to an OXIZID called BZO-4en-POXIZID (4en-pentyl MDA-19) prior to the effective ban. Through analysis of 6 cm segmented hair samples from attendees collected in 2021, we detected five cases of exposure. Specifically, we detected a cluster of three cases based on hair samples collected on 20 June 2021, and then two additional cases from samples collected on 16 July 2021. Four of these hair samples were long enough to analyze two 6 cm hair segments (representing approximately two 6-month timeframes) and three of four of these cases tested positive for repeated exposure (for an estimated exposure over 6 months prior to hair collection). All cases included young adult females reporting past-year cannabis use but all tested negative for tetrahydrocannabinol exposure. Three cases also reported past-year use of cocaine, ecstasy, and/or ketamine, and four cases tested positive for exposure to cocaine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine and/or eutylone. These subjects were exposed to BZO-4en-POXIZID—likely as an adulterant in other drugs, and these cases are among the first documented cases which occurred approximately half a year before the Chinese legislative ban.
Prognostic evaluation of stage I lung adenocarcinoma based on systematic inflammatory response
Authors: Qian Jia-Yi , Wu Lei-Lei , Zhang Li-Yan , Li Kun , Li Zhi-Xin , Zhao Yong , Xie Dong
Published: November 2023

Background

This study aimed to construct an effective nomogram based on the clinical and laboratory characteristics to predict the prognosis of stage I lung adenocarcinoma with EGFR alteration.

Methods

A retrospective study was performed of 913 eligible patients with EGFR alteration after surgery at Shanghai Pulmonary Hospital. The peripheral blood indicators were included in the nomogram. Calibration plots, concordance index, decision curve analysis, and X-tile software were used in this study. Recurrence-free survival (RFS) and overall survival were estimated by the Kaplan-Meier method and compared using the log-rank test.

Results

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were independent risk factors for RFS. The calibration curves for RFS probabilities showed good agreement between the nomogram prediction and actual observation. Furthermore, the nomogram, including neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had a higher concordance index (0.732, 95% confidence interval = 0.706 to 0.758) than that without neutrophil to lymphocyte ratio or platelet to lymphocyte ratio (0.713, 95% confidence interval = 0.686 to 0.740), and decision curve analysis plots showed that the nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio had better clinical practicability. Additionally, the patients were divided into 2 groups according to cutoff values of risk points, and statistically significant differences in RFS and overall survival were observed between the high-risk and low-risk groups (P < .001).

Conclusions

High pretreatment levels of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were strongly associated with a worse prognosis in stage I EGFR-altered lung adenocarcinomas. Besides, the proposed nomogram with neutrophil to lymphocyte ratio and platelet to lymphocyte ratio presented a better prediction ability for the survival of those patients.
Clinical Practice Guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 Guideline on Diagnosis and Management of Acute Bacterial Arthritis in Pediatrics
Authors: Woods Charles R , Bradley John S , Chatterjee Archana , Kronman Matthew P , Arnold Sandra R , Robinson Joan , Copley Lawson A , Arrieta Antonio C , Fowler Sandra L , Harrison Christopher , Eppes Stephen C , Creech C Buddy , Stadler Laura P , Shah Samir S , Mazur Lynnette J , Carrillo-Marquez Maria A , Allen Coburn H , Lavergne Valéry
Published: November 2023

This clinical practice guideline for the diagnosis and treatment of acute bacterial arthritis (ABA) in children was developed by a multidisciplinary panel representing the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with ABA, including specialists in pediatric infectious diseases and orthopedics. The panel’s recommendations for the diagnosis and treatment of ABA are based upon evidence derived from topic-specific systematic literature reviews.

Summarized below are the recommendations for the diagnosis and treatment of ABA in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) (see Figure 1). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.
Characterizing Attitudes Toward Maternal RSV Vaccines Among Pregnant and Lactating Persons in Kenya: Key Considerations for Demand Generation Efforts for Vaccine Acceptance
Authors: Limaye Rupali J , Sauer Molly , Njogu Rosemary , Singh Prachi , Fesshaye Berhaun , Karron Ruth A
Published: November 2023

This study examined attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya. First pregnancy was associated with higher vaccine hesitancy among pregnant and lactating people, and social norms were associated with higher vaccine hesitancy among lactating people. Understanding maternal RSV attitudes is critical for vaccine acceptance.
Predictions of DNA mechanical properties at a genomic scale reveal potentially new functional roles of DNA flexibility
Authors: Back Georg , Walther Dirk
Published: November 2023

Mechanical properties of DNA have been implied to influence many of its biological functions. Recently, a new high-throughput method, called loop-seq, which allows measuring the intrinsic bendability of DNA fragments, has been developed. Using loop-seq data, we created a deep learning model to explore the biological significance of local DNA flexibility in a range of different species from different kingdoms. Consistently, we observed a characteristic and largely dinucleotide-composition-driven change of local flexibility near transcription start sites. In the presence of a TATA-box, a pronounced peak of high flexibility can be observed. Furthermore, depending on the transcription factor investigated, flanking-sequence-dependent DNA flexibility was identified as a potential factor influencing DNA binding. Compared to randomized genomic sequences, depending on species and taxa, actual genomic sequences were observed both with increased and lowered flexibility. Furthermore, in Arabidopsis thaliana, mutation rates, both de novo and fixed, were found to be associated with relatively rigid sequence regions. Our study presents a range of significant correlations between characteristic DNA mechanical properties and genomic features, the significance of which with regard to detailed molecular relevance awaits further theoretical and experimental exploration.
Association of Insomnia, Sleep Quality, and Sleep Duration With Risk of Physical Frailty in Middle-aged and Older People With HIV
Authors: Zhou Qionggui , Ding Yingying , Chen Xiaoxiao , Wang Shanling , Lin Haijiang , He Na
Published: November 2023

Background

Frailty is one of the major concerns among aging people with HIV (PWH). Evidence regarding the association between sleep disorders and physical frailty in PWH is limited.

Methods

PWH and HIV-negative individuals aged ≥40 years were included and frequency-matched in a 1:2 ratio by sex and age. Logistic regression models were used to estimate the odds ratios (ORs) and 95% CIs of the association between sleep disorders and physical frailty, and restricted cubic splines were used to describe the dose–response association. The contribution of depression to the association was estimated by mediation analysis.

Results

A total of 1526 PWH and 3052 HIV-negative individuals were included. Logistic regression indicated that insomnia (OR, 3.05; 95% CI, 1.63–5.72) and poor sleep quality (OR, 2.32; 95% CI, 1.21–4.45) were significantly associated with physical frailty in middle-aged and older PWH, especially in those with current CD4+ T-cell counts <350 cells/µL, but not in HIV-negative participants. A U-shaped and J-shaped dose–response relation between sleep duration and physical frailty was observed in PWH and HIV-negative participants, respectively. Shorter and longer sleep duration was associated with an increased risk of physical frailty in PWH. However, in HIV-negative participants, only longer sleep duration was associated with physical frailty. Mediation analysis revealed that depression mediated the relation between sleep disorders and frailty among PWH.

Conclusions

Sleep disorders including insomnia, poor sleep quality, and short and long sleep duration were significantly associated with physical frailty among middle-aged and older PWH. Depression may play a mediating role in the sleep–frailty association.
Improving the language of migratory bird science in North America
Authors: Albert Steven K , Siegel Rodney B
Published: November 2023

Several long-accepted terms are widely misused in ornithology and have led to a misperception of important concepts in the ecology of Nearctic–Neotropical migratory birds. The term “North America” (and its ancillary terms “North American species,” “North American habitats,” etc.) is widely used to refer to the United States and Canada, when in fact it should include all of the continent from the Arctic through Panama. In a similar vein, the terms “wintering” and “over-wintering” (whether used to describe the status of individual birds or species, or as a modifier for terms like habitats, ecology, or behavior), “spring migration” and “fall migration” are inappropriate for Nearctic–Neotropical migrants because they explicitly reference conditions in the temperate zone of the continent, even as most such species spend the majority of their annual cycle elsewhere, where these terms are inaccurate and unhelpful. We discuss the pitfalls of using these terms and suggest several alternatives and replacements. In particular, we urge more precision in the use of the term “North America”; for Nearctic–Neotropical migratory species (especially long-distance migrants), we suggest retiring the terms “wintering” and “over-wintering” in favor of “nonbreeding”; and for the same group of species we suggest retiring the terms “spring migration” and “fall migration” in favor of “pre-breeding,” “post-breeding,” or “post-natal” migration.
Pre-contractual Duties of Disclosure
Authors: Waddams S M
Published: November 2023

In 1871 Chief Justice Cockburn, considering a hypothetical case of a sale of land under which were valuable mineral deposits known to the purchaser but not to the vendor, said that it was a case in which ‘a man of tender conscience and high honour would be unwilling to take advantage of the ignorance of the seller; but there can be no doubt that the contract … would be binding’. On the basis of this statement, and many others to similar effect, it is usually asserted that there is, in English law, no general duty in one party to disclose material facts to the other party to a proposed contract. This legal position is sometimes referred to by the latin expression caveat emptor, but the principle is not confined to buyers, nor to contracts of sale. The principle is also often referred to by saying that silence is not equivalent to a misrepresentation, and that there is no general duty of good faith in pre-contractual negotiations. Another way of putting it is that the law permits one party to take advantage of another’s unilateral mistake. All these formulations point in the same direction, but as will be seen, there are significant differences among them.
Libel and Constitutional Free Speech
Authors: Fleming John
Published: November 2023

Actions for defamation and invasion of privacy present a peculiar tension between a plaintiff’s personality (dignitary) interests and the defendant’s freedom of speech. These respective interests, especially the latter, are widely viewed as of constitutional significance, and often specifically protected by written constitutions. The purpose of this essay is to explore the effect this perception has on resolving the conflict between these interests: one the speaker’s, the other that of the victim of speech. In particular, modern constitutional provisions guaranteeing freedom of speech and the press are apt to collide with traditional civil-law protection of individuals’ reputation and honour, reflecting change from a value system of chivalry to one of democratic ideals. In several instances this clash has resulted in substantial modifications of the conventional private law.
Germany
Authors: Körber Stefanie
Published: November 2023

For some time now, the retention of goods by customs authorities has been a significant tool used in Germany for combating the cross-border trade of goods infringing intellectual property rights. The tremendous rise in the practical significance of customs retentions in Germany in recent years is demonstrated by two sets of statistics. On the one hand, the number of applications for action filed with the customs authorities in Germany increased from 56 in 1994 to 290 in 2004. On the other hand, the number of cases involving the retention of goods by the customs authorities soared from 56 in 1994 to 8,564 in 2004.
Greece
Authors: Georganda Dimitra , Mouzaki Ekaterini
Published: November 2023

Greece does not have a long history of fighting counterfeit and pirated goods. Only in recent years have the Greek authorities accepted that activities connected with the manufacturing and marketing of counterfeit or pirated products can be considered to have important economic consequences for the businesses involved, and even lead to a financial crisis in a whole sector.
Sweden
Authors: Eliasson Bengt , Öström Helena Wassén
Published: November 2023

Before Sweden’s entry into the European Union in 1995, border measures against counterfeit and pirated goods were rather unusual. It was more common that action was taken against the goods after they had entered the country. At the time of Sweden’s entry into the European Union, a new Customs Act was introduced.This Customs Act was a supplement to the Community legislation concerning border measures, Regulation (EEC) No 3842/86.Since the Swedish Customs Act that was introduced in 1995 was rushed in order to be finalized before entry into the European Union, a new Customs Act was introduced in 2001.
Optimized APCVD method for synthesis of monolayer H-Phase VS2 crystals
Authors: Patel Amit Kumar , Borah Ashish Jyoti , Srivastava Anchal
Published: November 2023

Monolayer transition metal dichalcogenides, specifically H-phase vanadium disulfide (VS2), hold great significance as fundamental components for next-generation low-dimensional spintronic, optoelectronic, and future electronic devices. They also offer an opportunity to explore the intrinsic magnetic properties associated with monolayer H-phase VS2 crystals at room temperature. However, there have been limited experimental studies on synthesizing pure monolayer H-phase VS2 crystals using sodium metavanadate (NaVO3) and sulfur (S) as precursors for vanadium (V) and S, respectively. In this study, we present a facile atmospheric pressure chemical vapor deposition (APCVD) approach for the synthesizing monolayer H-phase VS2 crystals with a thickness of ∼0.7 nm. The lateral dimensions of monolayer VS2 crystals extends up to ∼26 µm. Additionally, we have modulated the growth parameters, such as the temperature of NaVO3 and the Ar gas flow rate, to obtain VS2 flakes with different sizes and morphologies. This significant advancement paves the way for the synthesis of monolayer H-phase VS2 crystals on SiO2/Si substrates using the APCVD technique.
Snow patch refugia benefits for species of periglacial zones—Evidence from a high-elevation obligate
Authors: Hayes Forest P , Berger Joel
Published: November 2023

Conserving Earth's most rapidly changing biomes necessitates understanding biological consequences of altered climes. Past species- and taxa-level responses to warming environs include numerous concentrated extirpations at the southern peripheries of distributions during the late Pleistocene. Less clear are localized capacities of cold-adapted species to mitigate thermal challenges against warming temperatures, especially through proximate behavioral and physiological adjustments. Whereas snow patches persist in periglacial zones and elsewhere, broad reductions in seasonal snow raise concerns about how and why species continue to use them. If snow patches play a functional role to combat increasing thermal demands, we predicted individuals would display an array of autonomic responses to increased temperatures modulated by wind, ambient temperature, and winter fur on and away from snow patches. We tested these predictions using a mammalian exemplar of high latitude and high elevation, mountain goats (Oreamnos americanus), using two sites in the northern Rocky Mountains, USA. Surprisingly, and contrary to expectations of reduced thermal stress, respiration rates were not decreased on snow patches but use of snow was strongly correlated with decreased metrics of insect harassment. As snow cover continues to decline in montane environs, the persistence of cold-adapted species depends on navigating concurrent changes in biotic communities and thermal environments and balancing competing pressures on behavioral and biological responses.
Nonassortative relationships between groups of nodes are typical in complex networks
Authors: Liu Cathy Xuanchi , Alexander Tristram J , Altmann Eduardo G
Published: November 2023

Decomposing a graph into groups of nodes that share similar connectivity properties is essential to understand the organization and function of complex networks. Previous works have focused on groups with specific relationships between group members, such as assortative communities or core–periphery structures, developing computational methods to find these mesoscale structures within a network. Here, we go beyond these two traditional cases and introduce a methodology that is able to identify and systematically classify all possible community types in directed multi graphs, based on the pairwise relationship between groups. We apply our approach to 53 different networks and find that assortative communities are the most common structures, but that previously unexplored types appear in almost every network. A particularly prevalent new type of relationship, which we call a source–basin structure, has information flowing from a sparsely connected group of nodes (source) to a densely connected group (basin). We look in detail at two online social networks—a new network of Twitter users and a well-studied network of political blogs—and find that source–basin structures play an important role in both of them. This confirms not only the widespread appearance of nonassortative structures but also the potential of hitherto unidentified relationships to explain the organization of complex networks.
Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study
Authors: Gumber Leher , Jackson Hannah , Gomez Nancy , Hopkins Georgina , Tucis Davis , Chakravorty Mithun , Tighe Patrick , Grainge Matthew J , Rutter Megan , Ferraro Alastair , Power Sheila , Pradère Marie-Josèphe , Lanyon Peter C , Pearce Fiona A , Fairclough Lucy
Published: November 2023

Objective

Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD).

Methods

Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls.

Results

Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8–724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8–1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose–response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03).

Conclusion

Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.
Recent progress in functional modification and crosslinking of bioprosthetic heart valves
Authors: Zheng Cheng , Yang Li , Wang Yunbing
Published: November 2023

Valvular heart disease (VHD), clinically manifested as stenosis and regurgitation of native heart valve, is one of the most prevalent cardiovascular diseases with high mortality. Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD. Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves (BHVs), implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD. However, BHVs might fail within 10–15 years due to structural valvular degeneration (SVD), which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs, including cytotoxicity, calcification, component degradation, mechanical failure, thrombosis and immune response. To prolong the service life of BHVs, much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD. In this review, we summarized and analyzed the research and progress on: (i) modification strategies based on glutaraldehyde crosslinked BHVs and (ii) nonglutaraldehyde crosslinking strategies for BHVs.
Napping and circadian sleep–wake regulation during healthy aging
Authors: Deantoni Michele , Reyt Mathilde , Baillet Marion , Dourte Marine , De Haan Stella , Lesoinne Alexia , Vandewalle Gilles , Maquet Pierre , Berthomier Christian , Muto Vincenzo , Hammad Gregory , Schmidt Christina
Published: November 2023

Study Objectives

Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance.

Methods

Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities.

Results

The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases.

Discussion

Our data indicate that napping is associated with an altered circadian sleep–wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep–wake cycle fragmentation during healthy aging. Altered circadian sleep–wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.
Identification of the mechanisms underlying per- and polyfluoroalkyl substance-induced hippocampal neurotoxicity as determined by network pharmacology and molecular docking analyses
Authors: Li Shirui , Gao Zhihui , Zhong Meihan , Bi Haoran , Li Jianan
Published: November 2023

Background

Per- and polyfluoroalkyl substances (PFASs) are a class of environmental contaminants that pose significant health risks to both animals and humans. Although the hippocampal neurotoxic effects of numerous PFASs have been reported, the underlying mechanisms of combined exposure to PFASs-induced hippocampal neurotoxicity remain unclear.

Methods

In this study, network pharmacology analysis was performed to identify the intersectional targets of PFASs for possible associations with hippocampal neurotoxicity. The evaluation of the influence of PFASs on intersectional targets was assessed using a weighted method. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the screened targets were performed, the intersected hub targets calculated by various algorithms were screened in the network and molecular docking was also used to analyze binding activities.

Results

Our results indicated that eight PFASs, which acted on key targets (MYC, ESR1, STAT3, RELA, MAPK3) impacted the NF-κB signaling pathway, STAT3 signaling pathway, and MAPK signaling pathways to exert neurotoxicity in the hippocampus. The molecular docking results revealed that PFASs have strong binding potential to the hub targets.

Conclusions

Our findings provided a basis for future studies to investigate the detailed mechanisms of PFASs-induced hippocampal neurotoxicity and to develop preventative and control strategies.
Toxicological mechanisms and potencies of organophosphate esters in KGN human ovarian granulosa cells as revealed by high-throughput transcriptomics
Authors: Wang Xiaotong , Rowan-Carroll Andrea , Meier Matthew J , Williams Andrew , Yauk Carole L , Hales Barbara F , Robaire Bernard
Published: November 2023

Despite the growing number of studies reporting potential risks associated with exposure to organophosphate esters (OPEs), their molecular mechanisms of action remain poorly defined. We used the high-throughput TempO-Seq platform to investigate the effects of frequently detected OPEs on the expression of ∼3000 environmentally responsive genes in KGN human ovarian granulosa cells. Cells were exposed for 48 h to 1 of 5 OPEs (0.1–50 μM): tris(methylphenyl) phosphate (TMPP), isopropylated triphenyl phosphate (IPPP), tert-butylphenyl diphenyl phosphate (BPDP), triphenyl phosphate (TPHP), or tris(2-butoxyethyl) phosphate (TBOEP). The sequencing data indicate that 4 OPEs induced transcriptional changes, whereas TBOEP had no effect within the concentration range tested. Multiple pathway databases were used to predict alterations in biological processes based on differentially expressed genes. At lower concentrations, inhibition of the cholesterol biosynthetic pathway was the predominant effect of OPEs; this was likely a consequence of intracellular cholesterol accumulation. At higher concentrations, BPDP and TPHP had distinct effects, primarily affecting pathways involved in cell cycle progression and other stress responses. Benchmark concentration modeling revealed that BPDP had the lowest transcriptomic point of departure. However, in vitro to in vivo extrapolation modeling indicated that TMPP was bioactive at lower concentrations than the other OPEs. We conclude that these new approach methodologies provide information on the mechanism(s) underlying the effects of data-poor compounds and assist in the derivation of protective points of departure for use in chemical read-across and decision-making.
Biliary Complications After Liver Transplantation
Authors: Pierce Lillian , Pierce Charles , Hendzel Kevin , Haney Sean , Simpson Russell , Xie Karen L.
Published: November 2023

Liver transplantation continues to be an optimal treatment choice for end-stage liver disease, acute liver failure, and primary liver cancer. An understanding and anticipation of potential complications of liver transplantation is integral to the medical and interventional management of these postoperative patients. Complications related to the biliary system are the most common posttransplant complications. Potential complications include biliary strictures, leakage, intraductal stone/sludge, and biliary cast syndrome. Multiple diagnostic imaging modalities are available including ultrasound, CT angiography, and hepatobiliary iminodiacetic acid scanning for evaluation of the biliary system and associated complications. The approach of interventional access to the biliary system after surgery is tailored based on surgical transplantation techniques. Endoscopic retrograde cholangiopancreatography remains the imaging modality of choice for evaluation and potential therapeutic intervention. If the biliary tree is not accessible by endoscopy due to postsurgical anatomy changes, interventional radiology may play a vital role in complication management and can provide percutaneous transhepatic cholangiography as a less invasive alternative to surgical intervention.
A Convolutional Neural Network for Automated Detection of Cervical Ossification of the Posterior Longitudinal Ligament using Magnetic Resonance Imaging
Authors: Qu Zhe , Deng Bin , Sun Wei , Yang Ranran , Feng Hu
Published: November 2023

Study Design:

Retrospective cohort study.

Objective:

We aimed to develop and validate a convolutional neural network (CNN) model to distinguish between cervical ossification of posterior longitudinal ligament (OPLL) and multilevel degenerative spinal stenosis using Magnetic Resonance Imaging (MRI) and to compare the diagnostic ability with spine surgeons.

Summary of Background Data:

Some artificial intelligence models have been applied in spinal image analysis and many of promising results were obtained; however, there was still no study attempted to develop a deep learning model in detecting cervical OPLL using MRI images.

Materials and Methods:

In this retrospective study, 272 cervical OPLL and 412 degenerative patients underwent surgical treatment were enrolled and divided into the training (513 cases) and test dataset (171 cases). CNN models applying ResNet architecture with 34, 50, and 101 layers of residual blocks were constructed and trained with the sagittal MRI images from the training dataset. To evaluate the performance of CNN, the receiver operating characteristic curves of 3 ResNet models were plotted and the area under the curve were calculated on the test dataset. The accuracy, sensitivity, and specificity of the diagnosis by the CNN were calculated and compared with 3 senior spine surgeons.

Results:

The diagnostic accuracies of our ResNet34, ResNet50, and ResNet101 models were 92.98%, 95.32%, and 97.66%, respectively; the area under the curve of receiver operating characteristic curves of these models were 0.914, 0.942, and 0.971, respectively. The accuracies and specificities of ResNet50 and ResNet101 models were significantly higher than all spine surgeons; for the sensitivity, ResNet101 model achieved better values than that of the 2 surgeons.

Conclusion:

The performance of our ResNet model in differentiating cervical OPLL from degenerative spinal stenosis using MRI is promising, better results were achieved with more layers of residual blocks applied.
Chemoprophylactic Anticoagulation After Spine Surgery Does Not Increase Epidural Hematoma Risk
Authors: Cloney Michael B. , Dhillon Ekamjeet , Hopkins Benjamin , El Tecle Najib , Koski Tyler R. , Dahdaleh Nader S.
Published: November 2023

Study design:

A retrospective cohort study.

Objective:

To calculate the magnitude of any increased risk of epidural hematoma (EDH) associated with chemoprophylactic anticoagulation (chemoprophylaxis), if any.

Summary of Background Data:

Chemoprophylaxis for the prevention of venous thromboembolic events may be associated with an increased risk of EDH after spine surgery.

Materials and Methods:

A total of 6869 consecutive spine surgeries performed at our institution were identified, and clinical and demographic data were collected. We identified cases in which symptomatic EDHs were evacuated within 30 days postoperatively. Patients receiving chemoprophylaxis and controls were matched using K-nearest neighbor propensity score matching to calculate the effect of anticoagulation on the rate of postoperative EDH.

Results:

After propensity score matching, 1071 patients who received chemoprophylaxis were matched to 1585 controls. Propensity scores were well balanced between populations (Rubin B=20.6, Rubin R=1.05), and an 89.6% reduction in bias was achieved, with a remaining mean bias of 3.2%. The effect of chemoprophylaxis on EDH was insignificant (P=0.294). Symptomatic EDH was independently associated with having a transfusion [odds ratio (OR)=7.30 (1.15, 46.20), P=0.035], having thoracic-level surgery [OR=41.19 (3.75, 452.4), P=0.002], and increasing body mass index [OR=1.44 (1.04, 1.98), P=0.028] but was not associated with chemoprophylaxis. Five out of 13 patients who developed EDH (38.5%) were receiving some form of anticoagulation, including 1 patient on therapeutic anticoagulation, 1 concurrently on aspirin and chemoprophylaxis, and 2 who were also found to have developed thrombocytopenia postoperatively. The median time on anticoagulation before EDH was 8.1 days. A higher proportion of patients who developed EDH also developed venous thromboembolic events than the general population [38.5% vs. 2.4%, OR=25.34 (9.226, 79.68), P<0.0001], and 1 EDH patient died from pulmonary embolism while off chemoprophylaxis.

Conclusions:

Chemoprophylactic anticoagulation did not cause an increase in the rate of spinal EDH in our patient population.
Alcohol-induced epigenetic changes prevent fibrosis resolution after alcohol cessation in miceresolution
Authors: Schonfeld Michael , O’Neil Maura , Weinman Steven A. , Tikhanovich Irina
Published: November 2023

Background and Aims:

Alcohol-associated liver disease is a major cause of alcohol-associated mortality. Recently, we identified hepatic demethylases lysine demethylase (KDM)5B and KDM5C as important epigenetic regulators of alcohol response in the liver. In this study, we aimed to investigate the role of KDM5 demethylases in alcohol-associated liver disease resolution.

Approach and Results:

We showed that alcohol-induced liver steatosis rapidly resolved after alcohol cessation. In contrast, fibrosis persisted in the liver for up to 8 weeks after the end of alcohol exposure. Defects in fibrosis resolution were in part due to alcohol-induced KDM5B and KDM5C-dependent epigenetic changes in hepatocytes. Using cell-type–specific knockout mice, we found that adeno-associated virus-mediated knockout of KDM5B and KDM5C demethylases in hepatocytes at the time of alcohol withdrawal promoted fibrosis resolution. Single-cell ATAC sequencing analysis showed that during alcohol-associated liver disease resolution epigenetic cell states largely reverted to control conditions. In addition, we found unique epigenetic cell states distinct from both control and alcohol states and identified associated transcriptional regulators, including liver X receptor (LXR) alpha (α). In vitro and in vivo analysis confirmed that knockout of KDM5B and KDM5C demethylases promoted LXRα activity, likely through regulation of oxysterol biosynthesis, and this activity was critical for the fibrosis resolution process. Reduced LXR activity by small molecule inhibitors prevented fibrosis resolution in KDM5-deficient mice.

Conclusions:

In summary, KDM5B and KDM5C demethylases prevent liver fibrosis resolution after alcohol cessation in part through suppression of LXR activity.
Risk Factors for Recurrence in the Treatment of Recurrent Pterygium
Authors: Kusano Yuki , Den Seika , Yamaguchi Takefumi , Nishisako Sota , Fukui Masaki , Shimazaki Jun
Published: November 2023

Purpose:

The aim of this study was to identify the postoperative recurrence rate of recurrent pterygium and to evaluate risk factors for the recurrence.

Methods:

This study was a retrospective interventional nonrandomized consecutive case series. In this single-center study, 119 eyes of patients with recurrent pterygium who underwent surgery with a follow-up period of >12 months after the surgery were analyzed. The clinical characteristics of pterygium were classified according to the length of corneal involvement and Tan grade. The main outcome was the recurrence rate. The secondary outcome was the risk factors for recurrence.

Results:

The mean follow-up period was 42 ± 28.6 months. Recurrence was observed in 15 patients (12.6%). The average postoperative recurrence period was 7.7 ± 6.7 months. Twelve patients experienced a recurrence within 12 months. Eyes with recurrence had a significantly greater length of corneal involvement (2.47 ± 0.72 mm) and number of previous surgery (1.9 ± 1.3) than those without (1.97 ± 0.74 mm, and 1.3 ± 0.7, both P = 0.04). Multivariate analysis showed that recurrence was significantly associated with the length of corneal involvement (odds ratio [OR] 2.38, 95% confidence interval [CI], 1.02–5.57, P = 0.05) and the number of previous surgeries (OR: 1.91, 95% CI, 1.03–3.58, P = 0.04) but not with sex (OR: 3.71, 95% CI, 0.90–15.2, P = 0.07), age (OR: 0.99, 95% CI, 0.94–1.04, P = 0.59), and use of mitomycin C (OR: 0.31, 95% CI, 0.07–1.21, P = 0.09).

Conclusions:

The postoperative recurrence rate of recurrent pterygium was 12.6%. The preoperative length of corneal involvement and number of previous pterygium surgeries were significantly correlated with recurrence. Male sex and nonuse of mitomycin C tended to correlate with recurrence.
Behavior Intervention Response Team: Piloting an Effective Means to Manage Patient- and Family-Disruptive Behaviors
Authors: Katzenstein Jennifer M. , Boatman Sondra L. , Newman Kevin , Maier Kristin
Published: November 2023

Goal:

This article describes the development and implementation of a behavior intervention response team (BIRT). Pilot data indicate the successful implementation of BIRT interventions with patients and families and the positive staff response to these interventions.

Methods:

Patient- and family-disruptive behaviors are increasing in hospitals. Those behaviors arise from stress, financial burdens, and the mental weight of the patient's medical condition on the family. These distressed patients and their families tax an already overwhelmed staff, exacerbating the caregivers' exhaustion, depersonalization, and frustration. We recognized the need to proactively address these disruptions at our children's hospital with an interdisciplinary response. Disciplines engaged in the BIRT development included risk management, behavioral health, child life, service excellence, patient and family services, social work, and chaplaincy. Following multiple brainstorming sessions, we created a comprehensive, clear intervention strategy to engage with a disruptive patient or family. The BIRT was developed to work with both the family and their medical team to intervene at the first signs of potential disruption.

Principal Findings:

With the BIRT, we were able to reduce disruptive behaviors and limit the subsequent removal of problematic individuals from the facility. Of the families who worked with the BIRT, 75.8% required no postintervention follow-up.

Practical Applications:

The development of a BIRT can help head off disruptive behaviors and improve family–medical team relationships to support the highest quality and safest healthcare.
Do oral antiviral drugs used in the treatment of chronic hepatitis B cause erectile dysfunction?
Authors: Üzel Ali , Ebik Berat , Bucaktepe Gamze Erten , Yolaçan Ramazan , Karabulut Ümit , Uçmak Feyzullah
Published: November 2023

Objective

The effect of antiviral drugs on the erectile dysfunction (ED) problem expressed by some patients using antiviral drugs due to chronic hepatitis B infection (HBV) was investigated.

Methods

A total of 102 male patients receiving antiviral therapy for HBVinfection without any known non-cirrhotic and comorbid disease that may cause ED and whodon’t use any drugs with an ED formation potential were analyzed through the InternationalIndex of Erectile Function test.

Results

Among the patients admitted to the study, anxiety disorder was detected as 24.5% (n = 25) and depression as 46.1% (n = 47). 70.6% (n = 72) of the patients suffered ED. Severe ED was only detected in 3 (n = 2.9%) patients. ED was detected in 70.6% of the entecavir, 64.2% of tenofovir, and 80% of Tenofovir alafenamide users (P = 0.287). On the other hand, the logistics regression analysis revealed that the most important factors that increase the risk of ED are age (>55 age; RR: 2.66; P < 0.001), and anxiety disorder (RR: 2.30; P < 0.0001). The cumulative effect of antiviral drugs on ED was 5.7% (RR: 0.8; P = 0.156).

Conclusion

We could not find any mounting evidence relating to the effect ofcommonly used antiviral drugs for hepatitis B causing ED. The incidence rate of ED on ourpatients was at a similar rate with population studies in the literature based on society. It is notappropriate to terminate antiviral therapy in hepatitis B for this reason.
Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis
Authors: Tan Shufa , Ou Yan , Yang Yunyi , Huang Shuilan , Chen Shikai , Gao Qiangqiang
Published: November 2023

Background

The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs.

Methods

We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs.

Results

Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs.

Conclusion

DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.