bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet enhances the effects of oxycodone in mice
Authors: Trinko R. , Diaz D. M. , Foscue E. , Thompson S. L. , Taylor J. R. , DiLeone R. J. 
Published: May 2023

AbstractOpioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.
An assessment of microvascular hemodynamics in human macula
Authors: Yu Dao-Yi , Mehnert Andrew , Balaratnasingam Chandrakumar , Yu Paula K. , Hein Martin , An Dong , Cringle Stephen J. 
Published: May 2023

AbstractAn adequate blood supply to meet the energy demands is essential for any tissue, particularly for high energy demand tissues such as the retina. A critical question is: How is the dynamic match between neuronal demands and blood supply achieved? We present a quantitative assessment of temporal and spatial variations in perfusion in the macular capillary network in 10 healthy human subjects using a non-invasive and label-free imaging technique. The assessment is based on the calculation of the coefficient of variation (CoV) of the perfusion signal from arterioles, venules and capillaries from a sequence of optical coherence tomography angiography images centred on the fovea. Significant heterogeneity of the spatial and temporal variation was found within arterioles, venules and capillary networks. The CoV values of the capillaries and smallest vessels were significantly higher than that in the larger vessels. Our results demonstrate the presence of significant heterogeneity of spatial and temporal variation within each element of the macular microvasculature, particularly in the capillaries and finer vessels. Our findings suggest that the dynamic match between neuronal demands and blood supply is achieved by frequent alteration of local blood flow evidenced by capillary perfusion variations both spatially and temporally in the macular region.
Morphological and morphometric study of the scapulae of Korean wild deer
Authors: Kang Myung-Cheon , Kwon Jun , Kim In-Shik , Park Byung-Yong , Tae Hyun-Jin , Jang Young-Jin , Sim Jeoungha , Ahn Dongchoon 
Published: May 2023

AbstractKorean water deer (Hydropotes inermis argyropus; Heude, 1884) and Siberian roe deer (Capreolus pygargus; Pallas, 1771) are Korean wild deer classified in the tribe Capreolini. C. pygargus in Korea were previously considered a single species; however, it was recently suggested that roe deer living on Jeju Island (Jeju roe deer; Capreolus pygargus jejuensis) is a distinct subspecies from roe deer living on the Korean peninsula (mainland roe deer; Capreolus pygargus tianschanicus) based on several studies demonstrating genetic and morphological features. In this study, we suggests that the scapular morphology and osteometric data can be used for interspecies discrmination between Korean wild deer. To compare the morphological characteristics of scapula among the three groups of deer, we analyzed the features and nine osteomorphological measurements of 31 H. i. argyropus (14 males and 17 females), 18 C. p. jejuensis (4 males and 14 females), and 23 C. p. tianschanicus (16 females and 7 males). The estimated ages of the deer were over 32–35 months. Data were analyzed by one-way repeated measures analysis of variance with post hoc Duncan test and discriminant functional analysis (DFA). H. i. argyropus and C. p. tianschanicus had the smallest and largest scapulae, respectively. The scapulae of the three Korean wild deer had a similar triangular shape, which was obscured by the tuber of the scapular spine, pointed acromion, broad infraspinous fossa, narrow supraspinous fossa, and partial ossification of scapular cartilage in older deer. H. i. argyropus had certain distinctive features, including a caudally pointed acromion, a notch between the supraglenoid tubercle and glenoid cavity (NBSG), a glenoid notch, and no sexual dimorphism, except for the longest dorsal length (Ld) and the scapular index (SI). C. p. jejuensis had a larger scapular index (SI) (61.74 ± 0.74%), compared with the SIs of H. i. argyropus and C. p. tianschanicus. The unique features of the scapula in C. p. jejuensis include its S-shaped cranial border. The C. p. jejuensis had a cranially pointed acromion, less frequent presence of glenoid notch and NBSG, short length of supraglenoid tubercle, and no sexual dimorphism. The C. p. tianschanicus had elevated cranial margin of the glenoid cavity, and frequent presence of glenoid notch and NBSG, similar to the H. i. argyropus. Similar to C. p. jejuensis, C. p. tianschanicus had a cranially pointed acromion. However, sexual dimorphism was observed in C. p. tianschanicus. DFA using osteometric data showed 97.22% of specimens were classified correctly into their species, meaning the osteometric parameters can be used for interspecies discrimination of Korean wild deer. Our findings indicate that the scapular morphologies of the three Korean wild deer have certain similarities and differences, suggesting that C. p. jejuensis are distinct from C. p. tianschanicus.
The impact of surgical volume on hospital ranking using the standardized infection ratio
Authors: Ye Shangyuan , Li Daniel , Yu Tingting , Caroff Daniel A. , Guy Jeffrey , Poland Russell E. , Sands Kenneth E. , Septimus Edward J. , Huang Susan S. , Platt Richard , Wang Rui 
Published: May 2023

AbstractThe Centers for Medicare and Medicaid Services require hospitals to report on quality metrics which are used to financially penalize those that perform in the lowest quartile. Surgical site infections (SSIs) are a critical component of the quality metrics that target healthcare-associated infections. However, the accuracy of such hospital profiling is highly affected by small surgical volumes which lead to a large amount of uncertainty in estimating standardized hospital-specific infection rates. Currently, hospitals with less than one expected SSI are excluded from rankings, but the effectiveness of this exclusion criterion is unknown. Tools that can quantify the classification accuracy and can determine the minimal surgical volume required for a desired level of accuracy are lacking. We investigate the effect of surgical volume on the accuracy of identifying poorly performing hospitals based on the standardized infection ratio and develop simulation-based algorithms for quantifying the classification accuracy. We apply our proposed method to data from HCA Healthcare (2014–2016) on SSIs in colon surgery patients. We estimate that for a procedure like colon surgery with an overall SSI rate of 3%, to rank hospitals in the HCA colon SSI dataset, hospitals that perform less than 200 procedures have a greater than 10% chance of being incorrectly assigned to the worst performing quartile. Minimum surgical volumes and predicted events criteria are required to make evaluating hospitals reliable, and these criteria vary by overall prevalence and between-hospital variability.
Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53
Authors: Palanichamy Jayanth Kumar , Tran Tiffany M. , King Jennifer K. , Katzman Sol , Ritter Alexander J. , Sharma Gunjan , Tso Christine , Contreras Jorge R. , Fernando Thilini R. , Sanford Jeremy R. , Rao Dinesh S. 
Published: May 2023

AbstractLoss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.
Label-free intraoperative nerve detection and visualization using ratiometric diffuse reflectance spectroscopy
Authors: Throckmorton Graham A. , Haugen Ezekiel , Thomas Giju , Willmon Parker , Baba Justin S. , Solórzano Carmen C. , Mahadevan-Jansen Anita 
Published: May 2023

AbstractIatrogenic nerve injuries contribute significantly to postoperative morbidity across various surgical disciplines and occur in approximately 500,000 cases annually in the US alone. Currently, there are no clinically adopted means to intraoperatively visualize nerves beyond the surgeon’s visual assessment. Here, we report a label-free method for nerve detection using diffuse reflectance spectroscopy (DRS). Starting with an in vivo rat model, fiber- and imaging-based DRS independently identified similar wavelengths that provided optimal contrast for nerve identification with an accuracy of 92%. Optical property measurements of rat and human cadaver tissues verify that the source of contrast between nerve and surrounding tissues is largely due to higher scattering in nerve and differences in oxygenated hemoglobin content. Clinical feasibility was demonstrated in patients undergoing thyroidectomies using both probe-based and imaging-based approaches where the nerve were identified with 91% accuracy. Based on our preliminary results, DRS has the potential to both provide surgeons with a label-free, intraoperative means of nerve visualization and reduce the incidence of iatrogenic nerve injuries along with its detrimental complications.
A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4+ cell distribution in the human rectal mucosa
Authors: Franzén Boger Mathias , Benhach Nora , Hasselrot Tyra , Brand Rhonda M. , Rohan Lisa C. , Wang Lin , McGowan Ian , Edick Stacey , Ho Ken , Meyn Leslie , Matoba Nobuyuki , Palmer Kenneth E. , Broliden Kristina , Tjernlund Annelie 
Published: May 2023

AbstractTo reduce HIV transmission, locally applied pre-exposure prophylaxis (PrEP) products for anorectal use will be important complements to oral and injectable PrEP products already available. It is critical to preserve an intact rectal epithelium and avoid an influx of mucosal HIV target cells with such product use. In this phase 1 clinical trial, we evaluated application of a topical rectal douche product containing Q-Griffithsin (Q-GRFT). Colorectal tissue samples were obtained via sigmoidoscopy at baseline, 1 and 24 h after single-dose exposure in 15 healthy volunteers. In situ staining for epithelial junction markers and CD4+ cells were assessed as an exploratory endpoint. A high-throughput, digitalized in situ imaging analysis workflow was developed to visualize and quantify these HIV susceptibility markers. We observed no significant differences in epithelial distribution of E-cadherin, desmocollin-2, occludin, claudin-1, or zonula occludens-1 when comparing the three timepoints or Q-GRFT versus placebo. There were also no differences in %CD4+ cells within the epithelium or lamina propria in any of these comparisons. In conclusion, the rectal epithelium and CD4+ cell distribution remained unchanged following topical application of Q-GRFT. In situ visualization of HIV susceptibility markers at mucosal sites could be useful to complement standard product safety assessments.
The 15-year national trends of endocrine cancers incidence among Iranian men and women; 2005–2020
Authors: Balajam Narges Zargar , Mousavian Amir-Hossein , Sheidaei Ali , Gohari Kimiya , Tavangar Seyed Mohammad , Ghanbari-Motlagh Ali , Ostovar Afshin , Shafiee Gita , Heshmat Ramin 
Published: May 2023

AbstractCancer is one of the important health problems in Iran, which is considered as the third cause of death. Endocrine cancers are rare but mostly curable. Thyroid cancer, the most common endocrine tumors, includes about one percent of malignant cancer. In this study, we examined the 15-year national trend of endocrine cancer incidence in Iranian men and women. The data in each province were evaluated based on age, gender, and cancer type according to International Classification of Disease Codes version 10 (ICD-10) from 2005 to 2020 in Iran. All data were obtained from the reports of the Statistics Center of Iran (SCI), 6 phases of the step-by-step approach to monitoring the risk factors of chronic diseases over 18 years old (STEPs), and 3 periods of the CASPIAN study (survey of non-communicable diseases in childhood and adolescence). Statistical analyzes and graph generation were done using R statistical software. Poisson regression with mixed effects was used for data modeling and incidence rate estimation. The incidence of thyroid gland malignancy is higher in women than in men. On the other hand, the incidence of adrenal gland cancer is slightly higher in men than in women. The same pattern is observed for other endocrine neoplasms and related structures. The incidence rate of these types of cancers has generally increased from 2005 to 2020 in Iran. This increase is more in women than in men. In addition, in the middle of the country, there is a strong region in terms of the occurrence of these types of cancers. The incidence rate in these provinces is relatively higher for both sexes and all studied periods. We conducted a study to observe the changing trends for various types of endocrine cancers over 15 years in men and women. Considering the increasing trend of thyroid cancers in Iran, therefore, creating essential policies for the management of these types of cancers for prevention, rapid diagnosis, and, timely treatment is particularly important.
Anthropogenic change decouples a freshwater predator’s density feedback
Authors: Sinclair J. S. , Briland R. , Fraker M. E. , Hood J. M. , Frank K. T. , Faust M. D. , Knight C. , Ludsin S. A. 
Published: May 2023

AbstractIntraspecific interactions within predator populations can affect predator–prey dynamics and community structure, highlighting the need to better understand how these interactions respond to anthropogenic change. To this end, we used a half-century (1969–2018) of abundance and size-at-age data from Lake Erie’s walleye (Sander vitreus) population to determine how anthropogenic alterations have influenced intraspecific interactions. Before the 1980s, the length-at-age of younger walleye (ages 1 and 2) negatively correlated with older (age 3 +) walleye abundance, signaling a ‘density feedback’ in which intraspecific competition limited growth. However, after the early 1980s this signal of intraspecific competition disappeared. This decoupling of the density feedback was related to multiple anthropogenic changes, including a larger walleye population resulting from better fisheries management, planned nutrient reductions to improve water quality and transparency, warmer water temperatures, and the proliferation of a non-native fish with novel traits (white perch,Morone americana). We argue that these changes may have reduced competitive interactions by reducing the spatial overlap between older and younger walleye and by introducing novel prey. Our findings illustrate the potential for anthropogenic change to diminish density dependent intraspecific interactions within top predator populations, which has important ramifications for predicting predator dynamics and managing natural resources.
Synthesis of L-methionine-loaded chitosan nanoparticles for controlled release and their in vitro and in vivo evaluation
Authors: Nuzaiba Pallath Muhammed , Gupta Subodh , Gupta Shobha , Jadhao Sanjay Balkrishna 
Published: May 2023

AbstractTherapeutically popular controlled release-enabling technology has forayed into the nutrition sector. Polymer coated forms of L-methionine used in soy protein diets, and its intermediate metabolite, S-adenosyl-L-methionine, used in myriad of medical conditions have proved more efficacious over (highly catabolized) free forms. In this premier study, L-methionine-loaded chitosan nanoparticles (M-NPs) were synthesized using ionic gelation method and their efficacy was evaluated. Biophysical characterization of the NPs was done using a Nanopartica SZ 100 analyser, transmission electron microscopy, and Fourier transform infrared spectroscopy. The M-NPs were spherical and smooth and 218.9 ± 7.4 nm in size and in vitro testing confirmed the controlled release of methionine. A 60-days feeding trial in L. rohita fish fingerlings was conducted. A basal diet suboptimal (0.85%) in methionine was provided with one of the supplements as under: none (control), 0.8% chitosan NPs (0.8% NPs), 1.2% L-methionine (1.2% M) (crystalline free form), 0.6% M-NPs and 1.2% M-NPs. While the addition of 0.6% M-NPs to the basal diet complemented towards meeting the established dietary requirement and resulted in significantly highest (P < 0.05) growth and protein efficiency and sero-immunological test scores (serum total protein, serum globulin, serum albumin: globulin ratio, phagocytic respiratory burst/NBT reduction and lysozyme activity), 1.2% supplementation in either form (free or nano), for being 0.85% excess, was counterproductive. Liver transaminases and dehydrogenases corroborated enhanced growth. It was inferred that part of the methionine requirement in nano form (M-NPs) can confer intended performance and health benefits in animals relying on plant proteins-based diets limiting in this essential amino acid. The study also paves the way for exploring chitosan NPs-based sustained delivery of amino acids in human medical conditions.
MGMT is frequently inactivated in pancreatic NET-G2 and is associated with the therapeutic activity of STZ-based regimens
Authors: Yagi Kohei , Ono Hiroaki , Kudo Atsushi , Kinowaki Yuko , Asano Daisuke , Watanabe Shuichi , Ishikawa Yoshiya , Ueda Hiroki , Akahoshi Keiichi , Tanaka Shinji , Tanabe Minoru 
Published: May 2023

AbstractO6-methylguanine-DNA methyltransferase (MGMT) has been linked with alkylating agent resistance and tumor growth suppression. However, its role remains undetermined in pancreatic neuroendocrine tumors (Pan-NET). The MGMT expression was examined by immunohistochemistry in 142 patients to evaluate MGMT immunoreactivity and clinicopathological factors. We analyzed the relationship between MGMT expression and treatment efficacy in 19 patients who received STZ-based regimens. In 142 Pan-NET, 97 cases (68.3%) were judged as MGMT-positive and 45 cases (31.6%) as negative. MGMT negativity was significantly more common in NET-G2 (62.5%) than in NET-G1 (11.2%, p < 0.001). MGMT-negative cases were associated significantly with larger tumor size (p < 0.01), higher Ki-67 index (p < 0.01), higher mitotic index (p < 0.05), and more frequent liver metastasis (p < 0.05). Of the 19 cases treated with STZ, 6 cases were determined as SD and 4 cases as PD in MGMT-positive patients (N = 10), while 5 cases were determined as PR and 4 cases as SD in MGMT-negative patients (N = 9). Progression-free survival in MGMT-negative cases was significantly better than in MGMT-positive cases (p < 0.05). MGMT expression was lower in NET-G2 than in NET-G1, and STZ-based regimens improved the therapeutic outcomes of MGMT-negative Pan-NET. These findings indicate that NET-G2 may represent a better therapeutic target for STZ treatment.
Assessments of sarcopenia and its associated factors in community-dwelling middle-aged and older Chinese adults in Kelantan, Malaysia
Authors: Foo Leng Huat , Wen Yin Siew , Kadir Azidah Abdul 
Published: May 2023

AbstractSarcopenia is an emerging public health problem worldwide, but very limited information exits concerning the influence of lifestyle factors and inflammation on sarcopenia among community-dwelling older populations in Asia, including Malaysia. A total of 230 apparently healthy community-dwelling middle-aged and older Chinese adults were included in the study. Validated questionnaires were used to assess dietary and lifestyle practices, while pro-inflammatory cytokine status was assessed by blood interleukin-6 concentrations (IL-6). Sarcopenia risk was assessed by the newly revised diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 12.5% with similar proportions of males and females. Multivariate logistic regression analysis showed that older age and higher concentrations of pro-inflammatory cytokine levels of IL-6 were significantly associated with a greater risk of sarcopenia, after adjustments for potential known biological and body composition factors. The present findings indicate that older adults aged 70 years and above with higher inflammation levels had a significantly increased risk of sarcopenia. Hence, effective dietary and lifestyle intervention strategies should emphasize reducing the inflammation associated with aging to prevent the rapid loss of muscle mass and strength that can lead to sarcopenia.
Fim3-dependent autoagglutination of Bordetella pertussis
Authors: Otsuka Nao , Koide Kentaro , Goto Masataka , Kamachi Kazunari , Kenri Tsuyoshi 
Published: May 2023

AbstractAutoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown. Repeated single colony isolation enabled us to detect an Agg- mutant in the supernatant of an Agg+ strain of B. pertussis. Whole-genome sequencing and immunoblot analysis disclosed that the Agg- mutant had a single C-deletion in its fim3 promoter region (Pfim3) which abolished Fim3 fimbriae production. A B. pertussis fim3-knock out mutant also lacked the Agg+ phenotype. Agg+ clinical isolates were detected a higher production of Fim3 than Fim3-producing Agg- isolates. B. pertussis is known to harbor multiple Pfim3 poly(C) lengths within a single strain culture and our newly developed PCR/LDR assay revealed that Agg+ isolates harbor the highest Pfim3 poly-14C abundance. We evaluated the frequency of autoagglutination in clinical B. pertussis isolates collected in Japan between 1994 and 2018 (n = 203). Fim3 production was confirmed for 190 isolates and 74.7% of them displayed the Agg+ phenotype. The Agg+ phenotype was strongly associated with Pfim3 poly-14C abundance. Taken together, our findings demonstrated that B. pertussis autoagglutination occurs in response to high Fim3 levels and the Agg+ strain has predominated in Japan over the past two decades.