bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Link of Lipschitz Normally Embedded Sets
Authors: Mendes Rodrigo , Sampaio José Edson
Published: September 2023

A path-connected subanalytic subset in $\mathbb{R}^{n}$ is naturally equipped with two metrics: the inner and the outer metrics. We say that a subset is Lipschitz normally embedded (LNE) if these two metrics are equivalent. In this article, we give some criteria for a subanalytic set to be LNE. It is a fundamental question to know if the LNE property is conical, that is, if it is possible to describe the LNE property of a germ of a subanalytic set in terms of the properties of its link. We answer this question by introducing a new notion called link Lipschitz normally embedding. We prove that this notion is equivalent to the LNE notion in the case of sets with connected links.
Light, Lamps, and Material Religion in Early Rabbinic Judaism
Authors: Gardner Gregg E
Published: September 2023

Recent scholarship on material religion has demonstrated how decentralizing texts, focusing on objects, and using material culture to shape our research inquiries enhances our understanding of religious traditions. This article seeks to initiate a conversation on material religion and ancient Judaism by applying methods from the former to archaeological finds from Roman-era Palestine and the numerous references to objects in late antique rabbinic texts. Focusing on ceramic oil lamps as a test case, I argue that attention to objects and how they were manufactured illuminates the influence of materiality on early rabbinic thought. Manufacturing was an important component of the Galilee’s material environment, which had a generative influence on its inhabitants. This paper shows how focusing on material culture and broad conceptualizations of materiality (including production, performance, and sensation) can enhance our understanding of late antique Judaism and rabbinic teachings that would later become central to Jewish tradition.
Development and Validation of Novel Quality Evaluation Methods to Differentiate Two Closely Related Species of Tinospora: A Rapid HPTLC- and HPLC-Based Assessment with MS/MS Characterization
Authors: Girme Aboli , Saste Ganesh , Balasubramaniam Arun Kumar , Ghule Chetana , Mulay Vallabh , Hingorani Lal
Published: September 2023

Background

The sympatric occurrence of the species that often resulted in different gatherings of plant material, ambiguous history on traditional use, and taxonomic flux due to similarities within the Tinospora (Menispermaceae) taxa are some of the reasons that triggered the necessity to develop robust analytical methods for efficient QC, especially to recognize dry and powder forms.

Objective

To develop novel HPTLC-based fingerprinting of two closely resembling Tinospora species followed by HPTLC–MS analysis and identification of compounds differentiating Tinospora crispa (TCP) and Tinospora cordifolia (TCR) and a rapid and quantitative assessment by HPLC with a photodiode array detector (HPLC–PDA) with MS/MS characterization of specific TCP and TCR analytical markers.

Methods

An HPTLC-based method was developed using chloroform–toluene–methanol–formic acid (7 + 4 + 2 + 0.2, by volume). The TCP compounds could be distinguished and isolated using successive column chromatography with complete characterization. Further these used in the reverse phase (RP)-HPLC–PDA coupled with LC–ESI (electrospray ionization)-MS/MS to quantify and confirmation in TCP and TCR.

Results

The fingerprinting showed distinct bands in TCP stems, confirmed as clerodane- furanoditerpenoids with indirect profiling by the HPTLC–MS technique. Systematic isolation confirmed these compounds as borapetosides B and E. Thus, the RP-HPLC–PDA method was developed for these borapetosides B and E, with tinosporide to differentiate these two species. The quantitation method was well validated with good linearity (r2 >0.99) with sensitive LOD (0.49–3.71 mcg/mL) and LOQ (1.48–11.23 mcg/mL) with recoveries of 92.34–96.19%.

Conclusion

A novel, validated HPLC–PDA method showed good resolution and reliability (up to 1% adulteration) in quantification for targeted major analytical markers from TCP to differentiate TCR. Thus, HPTLC and HPLC–PDA-based techniques are helpful with MS/MS-based characterization to identify and quantify these analytical markers from TCP (borapetoside B and E) and TCR (tinosporide) in dry and powder form.

Highlights

This article reports on the systemic use of HPTLC–MS for separating and identifying analytical markers in Tinospora species, distinguishing TCR and TCP with quantitative HPLC–PDA and MS/MS assessment.
Research Progress of Photodynamic Therapy in Wound Healing: A Literature Review
Authors: Zhao Hongqing , Sun Jiachen , Yang Yuguang
Published: September 2023

Light is an efficient technique that has a significant influence on contemporary medicine. Photodynamic therapy (PDT), which involves the combined action of photosensitizers (PSs), oxygen, and light, has emerged as a therapeutically promising method for treating a broad variety of solid tumors and infectious diseases. Photodynamic therapy is minimally invasive, has few side effects, lightens scars, and reduces tissue loss while preserving organ structure and function. In particular, PDT has a high healing potential for wounds (PDT stimulates wound healing by enhancing re-epithelialization, promoting angiogenesis as well as modulating skin homeostasis). Wound healing involves interactions between many different processes, including coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Poor wound healing with diabetes or extensive burns remains a difficult challenge. This review emphasizes PDT as a potential research field and summarizes PDT’s role in wound healing, including normal wounds, chronic wounds, and aging wounds.
Factors influencing abundance of 3 tick species across a gradient of urban development intensity in the US Great Plains
Authors: Noden Bruce H , Roselli Megan A , Loss Scott R
Published: September 2023

Urbanization alters abiotic conditions, vegetation, and wildlife populations in ways that affect tick abundance and tick-borne disease prevalence. Likely due to such changes, tick abundance has increased in many US urban areas. Despite growing public health importance of tick-borne diseases, little is known about how ticks are influenced by urbanization in North America, especially in the central United States where several pathogens occur at or near their highest incidences. To identify factors influencing tick abundance across a gradient of urbanization intensity, we used CO2 traps and flagging to sample ticks at 16 parks across Oklahoma City, Oklahoma, USA over 2 yr, conducted vegetation surveys, and used trail cameras to estimate a deer abundance index. Our results indicate there is a risk of encountering ticks across the entire urbanization gradient from exurban areas to the urban core, although some species (Dermacentor variabilis (Say)) appear less-common in heavily-urbanized areas. Vegetation variables were also associated with tick abundance. For example, Amblyomma maculatum Koch decreased with increasing woody plant and leaf litter cover, and there was a weak positive relationship between D. variabilis abundance and cover of understory eastern redcedar (Juniperus virginiana L.), indicating this native encroaching tree may increase tick populations in urban areas of the Great Plains. The deer abundance index was positively correlated with A. maculatum and D. variabilis abundance but unrelated to A. americanum (L.) abundance. Public health officials and land managers can use such information about parks/greenspaces and their surroundings to focus public education and land management efforts designed to reduce tick-borne disease prevalence.
Public and Private Sanctions for Corporate Misconduct: Evidence From Listed Companies
Authors: Cardone-Riportella Clara , García-Olalla Myriam , Vázquez-Ordás Camilo J
Published: September 2023

This paper aims to evaluate the impact that the application of competition legislation exerts on financial markets. The sanctioning process is classified into three key moments: the announcement of an investigation when a case of corporate misconduct is suspected; the imposition of a fine, if applicable; and, finally, the rectification or ratification of the sanction. The impact of these announcements on share prices between 2013 and 2021 is analyzed using the event study methodology. This research focuses on companies listed on the Spanish stock exchange, yielding 22 firms with 95 observations. The results show a negative and significant market reaction to the series of announcements. While this reaction intensifies if the fine is ratified, the response becomes positive when the sanction is rectified and annulled. In conclusion, the evidence found allows us to state that the market does in effect penalize corporate misconduct. Furthermore, the public sanction imposed by the competent authority is then followed by a private sanction, which manifests itself as a drop in market value. This is consistent with a hypothetical effect of reputational loss, especially in those cases in which the sanction is more significant in relation to the company’s market value.
Improving Delivery of the Social Safety Net: The Role of Stigma
Authors: Lasky-Fink Jessica , Linos Elizabeth
Published: September 2023

Many low-income households in the United States miss out on social safety net benefits because of the information, compliance, and psychological costs associated with take-up of government assistance. Yet, the empirical evidence on the impact of learning and psychological costs on take-up, and how to reduce them, is mixed. Leaning on an administrative burden framework, this article measures the role of reducing learning costs and stigma on demand for rental assistance in two field experiments (N = 117,073) conducted in two US cities. We find that providing information about emergency rental assistance increased program application requests by 52% compared to a no-communication control group. Moreover, subtle framing changes aimed at destigmatizing rental assistance increased engagement with the communication by 36% and increased application requests by about 18% relative to an information only group, with potentially larger effects for renters of color. In two subsequent online experiments (N = 1,258), we document that the destigmatizing framing reduces internalized stigma, without affecting perceptions of the program itself.
Spatial confidence regions for combinations of excursion sets in image analysis
Authors: Maullin-Sapey Thomas , Schwartzman Armin , Nichols Thomas E
Published: September 2023

The analysis of excursion sets in imaging data is essential to a wide range of scientific disciplines such as neuroimaging, climatology, and cosmology. Despite growing literature, there is little published concerning the comparison of processes that have been sampled across the same spatial region but which reflect different study conditions. Given a set of asymptotically Gaussian random fields, each corresponding to a sample acquired for a different study condition, this work aims to provide confidence statements about the intersection, or union, of the excursion sets across all fields. Such spatial regions are of natural interest as they directly correspond to the questions ‘Where do all random fields exceed a predetermined threshold?’, or ‘Where does at least one random field exceed a predetermined threshold?’. To assess the degree of spatial variability present, our method provides, with a desired confidence, subsets and supersets of spatial regions defined by logical conjunctions (i.e. set intersections) or disjunctions (i.e. set unions), without any assumption on the dependence between the different fields. The method is verified by extensive simulations and demonstrated using task-fMRI data to identify brain regions with activation common to four variants of a working memory task.
On the Etymology of Biblical Hebrew טֶרֶם Ṭɛrɛm ‘before, not yet’
Authors: Sjörs Ambjörn
Published: September 2023

This paper argues that the Biblical Hebrew grammatical morpheme טֶרֶם ṭɛrɛm ‘before, not yet’ is derived from a noun *tִVrm- meaning ‘(big) lip’.1
Brain tumors in United States military veterans
Authors: Bihn John R , Cioffi Gino , Waite Kristin A , Kruchko Carol , Neff Corey , Price Mackenzie , Ostrom Quinn T , Swinnerton Kaitlin N , Elbers Danne C , Mooney Michael A , Rachlin Jacob , Stein Thor D , Brophy Mary T , Do Nhan V , Ferguson Ryan E , Priemer David S , Perl Daniel P , Hickman Richard A , Nabors Burt , Rusiecki Jennifer , Barnholtz-Sloan Jill S , Fillmore Nathanael R
Published: September 2023

Background

Comprehensive analysis of brain tumor incidence and survival in the Veteran population has been lacking.

Methods

Veteran data were obtained from the Veterans Health Administration (VHA) Medical Centers via VHA Corporate Data Warehouse. Brain tumor statistics on the overall US population were generated from the Central Brain Tumor Registry of the US data. Cases were individuals (≥18 years) with a primary brain tumor, diagnosed between 2004 and 2018. The average annual age-adjusted incidence rates (AAIR) and 95% confidence intervals were estimated per 100 000 population and Kaplan–Meier survival curves evaluated overall survival outcomes among Veterans.

Results

The Veteran population was primarily white (78%), male (93%), and between 60 and 64 years old (18%). Individuals with a primary brain tumor in the general US population were mainly female (59%) and between 18 and 49 years old (28%). The overall AAIR of primary brain tumors from 2004 to 2018 within the Veterans Affairs cancer registry was 11.6. Nonmalignant tumors were more common than malignant tumors (AAIR:7.19 vs 4.42). The most diagnosed tumors in Veterans were nonmalignant pituitary tumors (AAIR:2.96), nonmalignant meningioma (AAIR:2.62), and glioblastoma (AAIR:1.96). In the Veteran population, survival outcomes became worse with age and were lowest among individuals diagnosed with glioblastoma.

Conclusions

Differences between Veteran and US populations can be broadly attributed to demographic composition differences of these groups. Prior to this, there have been no reports on national-level incidence rates and survival outcomes for Veterans. These data provide vital information that can drive efforts to understand disease burden and improve outcomes for individuals with primary brain tumors.
Prognostic Association of Liposomal Amphotericin B Doses Above 5 mg/kg/d in Mucormycosis: A Nationwide Epidemiologic and Treatment Analysis in Japan
Authors: Tashiro Masato , Namie Hotaka , Ito Yuya , Takazono Takahiro , Kakeya Hiroshi , Miyazaki Yoshitsugu , Mukae Hiroshi , Mikamo Hiroshige , Tomoo Fukuda , Shibuya Kazutoshi , Izumikawa Koichi
Published: September 2023

Background

Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B.

Methods

A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome.

Results

The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28–2.68; P = .796) compared with 5 mg/kg/d.

Conclusions

This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.
Beach recreationists perceive a lack of knowledge about shorebirds’ needs as a constraint to walking around shorebird flocks
Authors: Comber Carolyn A , Dayer Ashley A
Published: September 2023

Walking through shorebird flocks can have negative impacts on shorebird populations. Understanding human behavior is essential for minimizing disturbance. As such, we used a mixed methods approach consisting of phone interviews and a survey to explore (1) recreationists’ perceived benefits and constraints to voluntarily walk around shorebird flocks, (2) recreationists’ intentions to walk around shorebird flocks, (3) differences in behavioral intention by sociodemographic variables, and (4) differences in norms, benefits, and constraints among recreationists who intend to walk around flocks and recreationists who do not intend to walk around flocks. We found that perceived benefits to walking around flocks were maintaining undisturbed conditions for shorebirds and reducing harm to people and their dogs, whereas perceived constraints related to a lack of knowledge about shorebirds’ needs. The majority of recreationists were willing to walk around flocks, rather than through them. Intention to walk around flocks can vary by sociodemographic groups. Recreationists who intended to walk around flocks had stronger personal and social norms than recreationists who did not intend to walk around flocks. Recreationists who intended to walk around flocks generally agreed more strongly that maintaining undisturbed conditions for shorebirds and reduced harm to people and their dogs were benefits, compared to participants who did not intend to walk around flocks. Recreationists who did not intend to walk around flocks agreed more strongly that a lack of knowledge about shorebirds’ needs was a constraint compared to participants who intended to walk around flocks. Our findings could be used in the strategy development phase of a community-based social marketing campaign (CBSM) aimed at encouraging recreationists to voluntarily walk around shorebird flocks. Using behavior change techniques, benefits uncovered in this study can be emphasized and constraints uncovered in this study can be reduced for the purpose of promoting less disturbance to shorebirds.
A CYP78As–small grain4–coat protein complex Ⅱ pathway promotes grain size in rice
Authors: Zhou Chunlei , Lin Qibing , Ren Yulong , Lan Jie , Miao Rong , Feng Miao , Wang Xin , Liu Xi , Zhang Shengzhong , Pan Tian , Wang Jiachang , Luo Sheng , Qian Jinsheng , Luo Wenfan , Mou Changling , Nguyen Thanhliem , Cheng Zhijun , Zhang Xin , Lei Cailin , Zhu Shanshan , Guo Xiuping , Wang Jie , Zhao Zhichao , Liu Shijia , Jiang Ling , Wan Jianmin
Published: September 2023

CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex Ⅱ (COPⅡ) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As–SMG4–COPⅡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.
Orbital-free density functional theory: Differences and similarities between electronic and nuclear systems
Authors: Colò Gianluca , Hagino Kouichi
Published: September 2023

Orbital-free density functional theory (OF-DFT) has been used when studying atoms, molecules, and solids. In nuclear physics, applications of OF-DFT have been quite scarce so far, as DFT has been widely applied to the study of many nuclear properties mostly within the Kohn–Sham (KS) scheme. There are many realizations of nuclear KS-DFT, but computations become very demanding for heavy systems, such as superheavy nuclei and the inner crust of neutron stars, and it is hard to describe exotic nuclear shapes using a finite basis made with a limited number of orbitals. These bottlenecks could, in principle, be overcome by an orbital-free formulation of DFT. This work is a first step towards the realistic application of OF-DFT to nuclei. In particular, we have implemented possible choices for an orbital-free kinetic energy and solved the associated Schrödinger equation either with simple potentials or with simplified nuclear density functionals. While the former choice sheds light on the differences between electronic and nuclear systems, the latter choice allows us to discuss the practical applications to nuclei as well as open questions.
Identifying the public health needs of a UK probation cohort: a cross-sectional analysis
Authors: Williams O , Gray B J , Perrett S E
Published: September 2023

Background

The health needs of those under probation are likely high, but they have received very little public health attention. Limited evidence exists on the public health needs and interventions to support this cohort.

Methods

Surveys were completed by 257 people on probation as part of a local health needs assessment. Results were compared with the general population responses from the National Survey for Wales (2021–22).

Results

People on probation were 4.2 times more likely to self-report not-good general health (fair, bad or very bad) than the general population (adjusted Odds Ratio [aOR] 4.2, 95% Confidence Intervals [CI] 3.2–5.4). The odds of having a mental health condition were over eight times higher than the general population (aOR 8.8, 95% CI 6.8–11.4). Prevalence of smoking (52%), drug use (60%), attention-deficit hyperactivity disorder (21%), autism (4%) and dyslexia (15%) were all higher than the general population. General Practitioner usage and hospital stays were higher, but dentist or optician usage lower than the general population (P < 0.05). Emergency departments were accessed by 35%, with 9% frequenting them three or more times.

Conclusions

People on probation have poorer self-reported health, higher prevalence of unhealthy behaviours and higher accessing of reactive health services than the general population.
Evaluating the Accuracy of Counterfactuals: Heterogeneous Survival Expectations in a Life Cycle Model
Authors: de Bresser Jochem
Published: September 2023

This article shows that individual-level heterogeneity in survival expectations derived from subjective survey information improves the out-of-sample predictions of a dynamic model of retirement and saving. We consider three approaches to modelling survival: life tables, average subjective expectations, and individual-specific estimates based on reported survival probabilities. The models are estimated using Dutch data from the 1990s, a period during which workers could retire from age 59 at no penalty to pension benefits. Actuarial adjustments were introduced in the early 2000s, and we use data from the period 2006–16 to evaluate the accuracy of the counterfactual predictions. While the three models yield different preference estimates, their within-sample fit is similar. Out-of-sample forecasts do differ markedly. The models with homogeneous expectations anticipate a 4- or 5-year increase in the average retirement age in the new regime, compared with an observed increase of 2.6 years. The model with heterogeneous expectations predicts a more realistic increase of 2.7 years. Expectations matter when it comes to counterfactual predictions, even if different combinations of preferences and expectations appear equivalent within a given institutional setting.
Exploiting Growth Opportunities: The Role of Internal Labour Markets
Authors: Cestone Giacinta , Fumagalli Chiara , Kramarz Francis , Pica Giovanni
Published: September 2023

We explore how business groups use internal labour markets (ILMs) in response to changing economic conditions. We show that following the exit of a large industry competitor, group-affiliated firms expand, and gain market share by increasing their reliance on the ILM to ensure swift hiring, especially of technical managers and skilled blue collar workers. The ability to take advantage of this shock to growth opportunities is greater in firms with closer access to their affiliates’ human capital, as geographical proximity facilitates employee relocations across units. Overall, our findings point to the ILM as a prominent mechanism making affiliation with a business group valuable at times of change. For the ILM to perform its role in the face of industry shocks, group sectoral diversification must be combined with geographical proximity between affiliates.
Listing quality: Chinese journal lists in incoherent valuation regimes
Authors: Wang Jing , Halffman Willem , Horbach Serge P J M
Published: September 2023

Lists of endorsed and discouraged scholarly publications recently emerged as an important transition in Chinese journal evaluation. Among the targeted users of these lists are researchers, who are to avoid publishing in discouraged journals and focus efforts on endorsed journals. However, it is unclear how these lists affect researchers’ valuations when choosing publication outlets. This explorative study investigates the reception of such journal lists in Chinese scientists’ research practices. Our findings suggest that three logics interact in respondents’ journal valuations: institutional evaluation regimes, differing epistemic cultures, and the influence of the commercial publishing industry. The reactive effects of both endorsed and discouraged journal lists appear to differ with the ranking status of universities, the seniority of scholars, and research fields. Apart from the new institutional evaluation regimes in this interplay, there appear to be more predominant factors than journal lists that inform publishing choices: quantitative indicators, publishers’ branding, epistemic cultures, and editorial procedures and publishing models.
Rethinking moral hazard: government protection and bank risk-taking
Authors: Pernell Kim , Jung Jiwook
Published: September 2023

Why do firms take excessive risks that result in failure? Moral hazard theorists argue that the answer lies in the risk-boosting effects of the government safety net, which insulates firms from market discipline. We revisit this conventional wisdom by examining how exposure to government protection has contributed to recent trends in bank risk-taking in the USA. Drawing from insights from economic sociology, we highlight an additional way that exposure to government protection can shape organizational behavior: by reducing resource-based profitability pressures that can spur risky behavior. Using panel data analysis of risky US bank behavior between 1994 and 2015, we find that bank exposure to government protection was more often associated with less risk-taking than more of it. This pattern contradicts the predictions of moral hazard theory but aligns with the predictions of our own institutional-resource theory. We discuss implications for economic sociology and financial economics.
A nomogram proposal for early prediction of intensive care unit admission in patients with acute antipsychotic poisoning
Authors: El-Gharbawy Doaa M , Kabbash Ibrahim Ali , Ghonem Mona M
Published: September 2023

Background

Early identification of antipsychotic poisoned patients who may have a potential risk for intensive care unit (ICU) admission is crucial especially when resources are limited. Nomograms were previously used as a practical tool to predict prognosis and planning the treatment of some diseases including some poisoning conditions. However, they were not previously investigated in antipsychotic poisoning.

Aim

The current study aimed to construct a nomogram to predict the need for ICU admission in acute antipsychotic poisoning. Patients and methods: This 2-year study included 140 patients acutely intoxicated with antipsychotics and admitted at Tanta University Poison Control Centre throughout July 2019 to June 2021. Personal and toxicological data, findings of clinical examination and electrocardiography, as well as, results of laboratory investigations at time of admission were recorded. According to the outcome, patients were divided into ICU-admitted and ICU-not admitted groups.

Results

The results of this study provided a proposed nomogram that included five significant independent predictors for ICU admission in acute antipsychotic intoxications; the presence of seizures (OR: 31132.26[108.97-Inf]), corrected QT interval (OR: 1.04[1.01–1.09]), mean arterial blood pressure (OR: 0.83[0.70–0.92]), oxygen saturation (OR: 0.62[0.40 to 0.83)], and Glasgow Coma Scale (OR: 0.25 [0.06–0.56]).

Conclusion

It could be concluded that the developed nomogram is a promising tool for easy and rapid decision making to predict the need for ICU admission in acute antipsychotic poisoning.
Effects of Rosmarinus officinalis L. (Laminaceae) essential oil on adult and larvae of Drosophila melanogaster
Authors: Pedroso Aline Lucca , Schonwald Miryane Knapp , Dalla Corte Cristiane Lenz , Soares Felix Alexandre Antunes , Sperança Adriane , Godoi Benhur , de Carvalho Nélson Rodrigues
Published: September 2023

Rosmarinus officinalis (Lamiaceae family), also known as “alecrim,” is a perennial herb, typical of the Mediterranean region and widely distributed in Brazilian territory. Despite having demonstrated several properties of human interest, insecticide/larvicidal effect of essential oil from R. officinalis on insects remains unclear. In this study, we tested the effects of R. officinalis essential oil on biomarkers of oxidative damage in Drosophila melanogaster. Exposure to R. officinalis essential oil increased adult mortality and decreased geotaxis behavior in adult fruit flies. In addition, essential oil increased of larval mortality and impaired the developmental success in D. melanogaster. R. officinalis essential oil showed a significant repellent effect, with duration time of about 6 h. To understand the mechanism underlying the toxicity of essential oil both pro-oxidant effects and biomarkers of oxidative damage were evaluated in exposed flies. Exposure to essential oil caused a significant redox imbalance with impairment of both enzymatic and non-enzymatic antioxidant system and increased the lipid peroxidation levels. These results suggest that R. officinalis essential oil can be used as a bioinsecticide and/or larvicide as well as an alternative insect repellent.
Melatonin treatment prevents carbon-tetrachloride induced rat brain injury
Authors: Stojanović Nikola M , Maslovarić Aleksandra , Mihajlović Ivana , Marković Aleksandar , Randjelović Pavle J , Sokolović Dušan
Published: September 2023

Introduction

Herein the neuroprotective properties of melatonin, a highly effective antioxidant, administered in a single dose 50 mg/kg intraperitoneally, were investigated in the brain tissue of Wistar rats acutely exposed to the toxin carbon-tetrachloride (1 mL/kg, intraperitoneally).

Methods

To assess the degree of whole encephalic mass damage, biochemical parameters related to lipid and protein oxidation, antioxidant enzymes (catalase and superoxide dismutase), glutathione and inducible nitric oxide/arginase pathways were determined.

Results

The results showed that carbon-tetrachloride impaired the function of antioxidant enzymes (reduced catalase and superoxide dismutase activities) and reduced glutathione-metabolizing enzymes (reduced glutathione, glutathione S-transferase and peroxidase activity). Furthermore, carbon-tetrachloride increased lipid peroxidation and protein oxidative damage in the brain tissue, as well as myeloperoxidase and inducible nitric oxide synthase content/activities.

Conclusions

The application of a single dose of melatonin post intoxication has been able to reverse the disturbance in the function of antioxidant enzymes and alleviate the tissue damage caused by oxidative stress, indicating that melatonin could be a potential therapeutic agent in oxidative-damage related neurodegenerative disorders.
Freeze dehydration vs supercooling in tree stems: physical and physiological modelling
Authors: Bozonnet Cyril , Saudreau Marc , Badel Eric , Améglio Thierry , Charrier Guillaume
Published: September 2023

Frost resistance is the major factor affecting the distribution of plant species at high latitude and elevation. The main effects of freeze–thaw cycles are damage to living cells and formation of gas embolism in tree xylem vessels. Lethal intracellular freezing can be prevented in living cells by two mechanisms, such as dehydration and deep supercooling. We developed a multiphysics numerical model coupling water flow, heat transfer and phase change, considering different cell types in plant tissues, to study the dynamics and extent of cell dehydration, xylem pressure changes and stem diameter changes in response to freezing and thawing. Results were validated using experimental data for stem diameter changes of walnut trees (Juglans regia). The effect of cell mechanical properties was found to be negligible as long as the intracellular tension developed during dehydration was sufficiently low compared with the ice-induced cryostatic suction. The model was finally used to explore the coupled effects of relevant physiological parameters (initial water and sugar content) and environmental conditions (air temperature variations) on the dynamics and extent of dehydration. It revealed configurations where cell dehydration could be sufficient to protect cells from intracellular freezing, and situations where supercooling was necessary. This model, freely available with this paper, could easily be extended to explore different anatomical structures, different species and more complex physical processes.
Modeling the response of Norway spruce tree-ring carbon and oxygen isotopes to selection harvest on a drained peatland forest
Authors: Tikkasalo Olli-Pekka , Leppä Kersti , Launiainen Samuli , Peltoniemi Mikko , Mäkipää Raisa , Rinne-Garmston Katja T , Sahlstedt Elina , Young Giles H F , Bokareva Aleksandra , Lohila Annalea , Korkiakoski Mika , Schiestl-Aalto Pauliina , Lehtonen Aleksi
Published: September 2023

Continuous cover forestry (CCF) has gained interest as an alternative to even-aged management particularly on drained peatland forests. However, relatively little is known about the physiological response of suppressed trees when larger trees are removed as a part of CCF practices. Consequently, studies concentrating on process-level modeling of the response of trees to selection harvesting are also rare. Here, we compared, modeled and measured harvest response of previously suppressed Norway spruce (Picea abies) trees to a selection harvest. We quantified the harvest response by collecting Norway spruce tree-ring samples in a drained peatland forest site and measuring the change in stable carbon and oxygen isotopic ratios of wood formed during 2010–20, including five post-harvest years. The measured isotopic ratios were compared with ecosystem-level process model predictions for ${\kern0em }^{13}$C discrimination and ${\kern0em }^{18}$O leaf water enrichment. We found that the model predicted similar but lower harvest response than the measurements. Furthermore, accounting for mesophyll conductance was important for capturing the variation in ${\kern0em }^{13}$C discrimination. In addition, we performed sensitivity analysis on the model, which suggests that the modeled ${\kern0em }^{13}$C discrimination is sensitive to parameters related to CO2 transport through stomata to the mesophyll.
TGF‐β1 reduces the differentiation of porcine IgA‐producing plasma cells by inducing IgM+ B cells apoptosis via Bax/Bcl2‐Caspase3 pathway
Authors: Wang Caiying , Yang Shanshan , Huang Xin , Lu Yabin , Zhang Yue , Li Maolin , Zhao Jing , Li Shuxian , Savelkoul Huub , Jansen Christine , Liu Guangliang
Published: September 2023

Transforming growth factor β1 (TGF‐β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF‐β1 expression via activating Tregs. Besides, recombinant porcine TGF‐β1 decreased the percentage of CD21+ B cells within the lymphocyte population in vitro. We further found that TGF‐β1 reduced the IgA‐secreting B cell numbers and also inhibited plasma cell differentiation. Additional investigations revealed that TGF‐β1 induced the apoptosis of IgM+ B cells in both peyer's patches (PPs) and peripheral blood (PB) through the activation of the Bax/Bcl2‐Caspase3 pathway. Conversely, the application of the TGF‐β1 signaling inhibitor SB431542 significantly antagonized the TGF‐β1‐induced reduction of IgA secretion and B cell apoptosis and restored plasma cell differentiation. Collectively, TGF‐β1 plays an important role in regulating the survival and differentiation of porcine IgA‐secreting B cells through the classical mitochondrial apoptosis pathway. These findings will facilitate future mucosal vaccine designs that target the regulation of TGF‐β1 for the control of enteric pathogens in the pig industry.
Identifying risk factors for osteonecrosis after talar fracture
Authors: Alley Maxwell C. , Vallier Heather A. , Tornetta Paul ,   and the Orthopaedic Trauma Research Consortium
Published: September 2023

Objective:

To identify patient, injury, and treatment factors associated with development of avascular necrosis (AVN)

following talar fractures, with particular interest in modifiable factors.

Design:

Retrospective chart review.

Setting:

21 US trauma centers and 1 UK trauma center.

Patients:

2,220 patients with talar neck and/or body fractures.

Intervention:

Open reduction internal fixation of talar neck and body fractures.

Main Outcome Measurements:

Development of AVN. Infection, nonunion, and arthritis were secondary outcomes.

Results:

796 patients (408 M; 388 F; age 18-81, avg 38.6) with 796 (532R; 264L) fractures were included and were classified as Hawkins 1(51), IIA(71), IIB(113), III(158), IV(40), neck plus body (177), body (188). 336/798 developed AVN (42%), more commonly following any neck fracture (47.0%) vs isolated body fracture (26.1%, p<0.001). More severe Hawkins’ classification, combined neck and body fractures, body mass index (BMI), tobacco smoking, right-sided fractures, open fracture, dual anteromedial and anterolateral surgical approaches, and associated medial malleolus fracture were associated with AVN. After multivariate regression, fracture type, tobacco smoking, open fractures, dual approaches, age, and BMI remained significant.Excluding late cases (>7 days), time to joint reduction for Hawkins type IIB-IV neck injuries was no different for those who developed AVN or not. AVN rates for reduction of dislocations within 6 hours of injury vs >6 hours were 48.8% and 57.5%, respectively. Complications included 60 (7.5%) infections and 70 (8.8%) nonunions.

Conclusion:

42% of all patients developed AVN, with talar neck fractures, more displaced fractures and open injuries having higher rates. Injury-related factors are most prognostic of AVN risk. Surgical technique to emphasize anatomical reduction, without iatrogenic damage to remaining blood supply is essential.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion
Authors: Iyer Sravisht , Steinhaus Michael E. , Kazarian Gregory S. , Zgonis Evangelia M. , Cunningham Matthew E. , Farmer James C. , Kim Han Jo , Lebl Darren R. , Huang Russel C. , Lafage Virginie , Schwab Frank J. , Qureshi Sheeraz , Girardi Federico P. , Rawlins Bernard A. , Beckman James D. , Carrino John A. , Chazen J. Levi , Varghese Jeffrey J. , Muzammil Hamna , Lafage Renaud , Sandhu Harvinder S.
Published: September 2023

Study Design.

A randomized, double-blinded, placebo-controlled trial.

Objective.

To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A).

Summary of Background Data.

Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study.

Patients and Methods.

Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours.

Results.

A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A (P = 0.025) and IV-P (P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance (P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst (P = 0.004), best (P = 0.001), average (P = 0.001), and current pain (P = 0.002) on postoperative day 1, and significantly shorter LOS (P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates.

Conclusions.

By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of “enhanced recovery after surgery” protocols.
The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma
Authors: Boudreau Matthew W. , Tonogai Emily J. , Schane Claire P. , Xi Min X. , Fischer James H. , Vijayakumar Jayanthi , Ji Yan , Tarasow Theodore M. , Fan Timothy M. , Hergenrother Paul J. , Dudek Arkadiusz Z.
Published: September 2023

The treatment of metastatic uveal melanoma remains a major clinical challenge. Procaspase-3, a proapoptotic protein and precursor to the key apoptotic executioner caspase-3, is overexpressed in a wide range of malignancies, and the drug PAC-1 leverages this overexpression to selectively kill cancer cells. Herein, we investigate the efficacy of PAC-1 against uveal melanoma cell lines and report the synergistic combination of PAC-1 and entrectinib. This preclinical activity, tolerability data in mice, and the known clinical effectiveness of these drugs in human cancer patients led to a small Phase 1b study in patients with metastatic uveal melanoma. The combination of PAC-1 and entrectinib was tolerated with no treatment-related grade ≥3 toxicities in these patients. The pharmacokinetics of entrectinib were not affected by PAC-1 treatment. In this small and heavily pretreated initial cohort, stable disease was observed in four out of six patients, with a median progression-free survival of 3.38 months (95% CI 1.6–6.5 months). This study is an initial demonstration that the combination of PAC-1 and entrectinib may warrant further clinical investigation. Clinical trial registration: Clinical Trials.gov: NCT04589832.
Usefulness of Ultrasound in Verrucous Venous Malformation: a Series of 103 Cases
Authors: Gong Xia , Chang Shih-Jen , Xiong Ping , Lin Xiaoxi , Wang Lizhen
Published: September 2023

BACKGROUND

Verrucous venous malformation (VVM), previously called “verrucous hemangioma,” is a rare type of vascular malformation.

OBJECTIVE

Little is known about the ultrasonographic characteristics of VVM. The present study aimed to show the conventional US and elastographic features of a VVM.

MATERIALS AND METHODS

The US findings in 103 patients with VVMs were retrospectively evaluated.

RESULTS

On gray-scale ultrasound images, 98 (95.1%) lesions showed subcutaneous fat infiltration from skin across muscle to deep fascia. The other 5 (4.9%) sat in the subcutaneous layer with no skin involvement. Most (96.1%) lesions were hyperechoic. Furthermore, 71.8% of lesions were heterogeneous, 68.9% of which were with ill-defined margins. Calcifications and visible vessels were present in 5.7% and 10.7% of the VVM cases, respectively. By color Doppler ultrasound, all lesions were found with low vascular density and 4.9% showed enhanced blood flow after compression. Venous spectrum was observed in 67.0% of lesions. The elasticity score was 2.66 ± 0.48.

CONCLUSION

Diagnosis of a VVM is challenging in the clinic. However, we found that most VVM lesions present distinctive ultrasound imaging characteristics. These ultrasound findings may well contribute to the accuracy of VVM diagnosis, especially in those with the absence of epidermal changes and the lack of dermal involvement.