bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncologic drug repository programs in the United States: a review and comparison
Authors: Heater Natalie K , Kircher Sheetal , Weldon Christine , Trosman Julia , Benson Al
Published: March 2024

As cancer affects 40% of all Americans during their lifetime, the financial burden of cancer care represents a significant contribution towards the overall cost of health care in the United States. Cancer drug repository programs offer a unique solution for patients who have limited financial ability to access medications while reducing medical waste. We reviewed all state legislation in the United States regarding cancer drug repository programs. Five states have oral anticancer drug (OACD)–specific drug repository programs, while 28 states have generalized drug repository programs. Iowa's statewide, mail-order OACD repository program is the preeminent example of an effective and efficient program, which should be replicated across the country. Many states have passed legislation allowing for drug repository programs but have struggled to translate such legislation into active programs due to lack of funding and management. We offer recommendations across policy, manufacturing, institutional, health care professional, and patient domains in order provide optimal patient care.
MAPK20-mediated ATG6 phosphorylation is critical for pollen development in Solanum lycopersicum L.
Authors: Wang Yu , Xie Dongling , Zheng Xuelian , Guo Mingyue , Qi Zhenyu , Yang Ping , Yu Jingquan , Zhou Jie
Published: March 2024

In flowering plants, male gametogenesis is tightly regulated by numerous genes. Mitogen-activated protein kinase (MAPK) plays a critical role in plant development and stress response, while its role in plant reproductive development is largely unclear. The present study demonstrated MAPK20 phosphorylation of ATG6 to mediate pollen development and germination in tomato (Solanum lycopersicum L.). MAPK20 was preferentially expressed in the stamen of tomato, and mutation of MAPK20 resulted in abnormal pollen grains and inhibited pollen viability and germination. MAPK20 interaction with ATG6 mediated the formation of autophagosomes. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis showed that ATG6 was phosphorylated by MAPK20 at Ser-265. Mutation of ATG6 in wild-type (WT) or in MAPK20 overexpression plants resulted in malformed and inviable pollens. Meanwhile, the number of autophagosomes in mapk20 and atg6 mutants was significantly lower than that of WT plants. Our results suggest that MAPK20-mediated ATG6 phosphorylation and autophagosome formation are critical for pollen development and germination.
Escape Velocity—the Launch of Microbiome Therapies
Authors: Kelly Brendan J , Kwon Jennie H , Woodworth Michael H
Published: March 2024

Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation’s (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.
Nitrous oxide inhibition of methanogenesis represents an underappreciated greenhouse gas emission feedback
Authors: Yin Yongchao , Kara-Murdoch Fadime , Murdoch Robert W , Yan Jun , Chen Gao , Xie Yongchao , Sun Yanchen , Löffler Frank E
Published: March 2024

Methane (CH4) and nitrous oxide (N2O) are major greenhouse gases that are predominantly generated by microbial activities in anoxic environments. N2O inhibition of methanogenesis has been reported, but comprehensive efforts to obtain kinetic information are lacking. Using the model methanogen Methanosarcina barkeri strain Fusaro and digester sludge-derived methanogenic enrichment cultures, we conducted growth yield and kinetic measurements and showed that micromolar concentrations of N2O suppress the growth of methanogens and CH4 production from major methanogenic substrate classes. Acetoclastic methanogenesis, estimated to account for two-thirds of the annual 1 billion metric tons of biogenic CH4, was most sensitive to N2O, with inhibitory constants (KI) in the range of 18–25 μM, followed by hydrogenotrophic (KI, 60–90 μM) and methylotrophic (KI, 110–130 μM) methanogenesis. Dissolved N2O concentrations exceeding these KI values are not uncommon in managed (i.e. fertilized soils and wastewater treatment plants) and unmanaged ecosystems. Future greenhouse gas emissions remain uncertain, particularly from critical zone environments (e.g. thawing permafrost) with large amounts of stored nitrogenous and carbonaceous materials that are experiencing unprecedented warming. Incorporating relevant feedback effects, such as the significant N2O inhibition on methanogenesis, can refine climate models and improve predictive capabilities.
The influence of steroidal implants and manganese sulfate supplementation on growth performance, trace mineral status, hepatic gene expression, hepatic enzyme activity, and circulating metabolites in feedlot steers
Authors: Smerchek Dathan T , Rients Emma L , McLaughlin Amy M , Henderson Jacob A , Ortner Brock M , Thornton Kara J , Hansen Stephanie L
Published: March 2024

Angus-cross steers (n = 144; 359 kg ± 13.4) were used to assess the effect of dietary Mn and steroidal implants on performance, trace minerals (TM) status, hepatic enzyme activity, hepatic gene expression, and serum metabolites. Steers (n = 6/pen) were stratified by BW in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (experimental unit = steer; n = 24/treatment). Dietary treatments included (MANG; 8 pens/treatment; Mn as MnSO4): (1) no supplemental Mn (analyzed 14 mg Mn/kg DM; Mn0); (2) 20 mg supplemental Mn/kg DM (Mn20); (3) 50 mg supplemental Mn/kg DM (Mn50). Within MANG, steers received a steroidal implant treatment (IMP) on day 0: (1) no implant; NO; or (2) combination implant (Revalor-200; REV). Liver biopsies for TM analysis and qPCR, and blood for serum glucose, insulin, non-esterified fatty acids, and urea-N (SUN) analysis were collected on days 0, 20, 40, and 77. Data were analyzed as a randomized complete block with a factorial arrangement of treatments including fixed effects of Mn treatment (MANG) and implant (IMP) using PROC MIXED of SAS 9.4 using initial BW as a covariate. Liver TM, serum metabolite, enzyme activity, and gene expression data were analyzed as repeated measures. No MANG × IMP effects were noted (P ≥ 0.12) for growth performance or carcass characteristic measures. Dietary Mn did not influence final body weight, overall ADG, or overall G:F (P ≥ 0.14). Liver Mn concentration increased with supplemental Mn concentration (MANG; P = 0.01). An IMP × DAY effect was noted for liver Mn (P = 0.01) where NO and REV were similar on day 0 but NO cattle increased liver Mn from days 0 to 20 while REV liver Mn decreased. Relative expression of MnSOD in the liver was greater in REV (P = 0.02) compared to NO and within a MANG × IMP effect (P = 0.01) REV increased liver MnSOD activity. These data indicate current NASEM Mn recommendations are adequate to meet the demands of finishing beef cattle given a steroidal implant. Despite the roles of Mn in metabolic pathways and antioxidant defense, a basal diet containing 14 mg Mn/kg DM was sufficient for the normal growth of finishing steers. This study also provided novel insight into how implants and supplemental Mn influence genes related to arginine metabolism, urea synthesis, antioxidant capacity, and TM homeostasis as well as arginase and MnSOD activity in hepatic tissue of beef steers.
Osteoporosis under psychological stress: mechanisms and therapeutics
Authors: Xu Hao-Kun , Liu Jie-Xi , Zhou Ze-Kai , Zheng Chen-Xi , Sui Bing-Dong , Yuan Yuan , Kong Liang , Jin Yan , Chen Ji
Published: March 2024

Psychological stress has been associated with the onset of several diseases, including osteoporosis. However, the underlying pathogenic mechanism remains unknown, and effective therapeutic strategies are still unavailable. Growing evidence suggests that the sympathetic nervous system regulates bone homeostasis and vascular function under psychological stress, as well as the coupling of osteogenesis and angiogenesis in bone development, remodeling, and regeneration. Furthermore, extracellular vesicles (EVs), particularly mesenchymal stem cell extracellular vesicles (MSC–EVs), have emerged as prospecting therapies for stimulating angiogenesis and bone regeneration. We summarize the role of sympathetic regulation in bone homeostasis and vascular function in response to psychological stress and emphasize the relationship between vessels and bone. Finally, we suggest using MSC–EVs as a promising therapeutic method for treating osteoporosis in psychological stress.
Probability and natural deduction
Authors: Boričić Joksimović Marija , Ikodinović Nebojša , Stojanović Nenad
Published: March 2024

We develop a system of basic probability reasoning founded on two great logical concepts, Gentzen’s natural deduction systems and Carnap–Popper probability of sentences. Our system makes it possible to manipulate with probabilized sentences and justify their causal relationships: if probabilities of sentences $A$ and $B$ are in $[r,1]$ and $[s,1]$, respectively, then the probability of sentence $C$ belongs to $[t,1]$, i.e. $A^{r},B^{s}\vdash C^{t}$, for $r,s,t\in [0,1]$. We prove that our system is sound and complete with respect to the traditional Carnap–Popper type probability semantics. This approach opens up a new perspective of proof-theoretic treatment of sentence probability, potentially allowing immediate algorithmic use of the pure syntactic convenience of natural deductions in programming.
Hiding in John Rechy’s Closet
Authors: Miranda Joseph Isaac
Published: March 2024

John Rechy is not interested in representation. Yet Rechy’s refusal to engage with identity using the terms offered to ethnic and queer writers has puzzled critics of his work. This article contends with John Rechy’s evasive novel, City of Night (1963), to reconsider Rechy’s attachment to refusal as a formal and political project that confounds any effort to portray a stable transparent minority subject. Through the novel’s rejection of disclosure and recognition, City of Night moves against forms of political stability (normative coupling, categorical identification, and property ownership) to feature ephemeral spaces in which minoritized people gather and shift around at the very moment the US state is restricting and criminalizing Mexican movement and sedimenting heteronormativity into law. By attending to evasion and refusal, I push the boundaries of Rechy criticism that have found City of Night devoid of politics or attachments to ethnic identity. Rather, I argue that the novel moves against individuation to offer ephemeral moments of entanglement with queer racialized Others through the composite form and figure of the “outsider.” Located in the unincorporated mass or crowd, City of Night’s attachment to the “outsider” thinks across difference to reveal the ways racialization underpins the policing of movement, heteronormativity, and citizenship in the mid-twentieth century. Ultimately, Rechy’s aesthetics of refusal registers the under-examined affinities between migrant, laborer, queer, and brown at the very moment the United States sought to restrict how we think about identity and politics in public.
The role of carbon in red giant spectro-seismology
Authors: Banks Kirsten A , Martell Sarah L , Tinney C G , Stello Dennis , Hon Marc , Reyes Claudia , Priest James , Buder Sven , Montet Benjamin T
Published: March 2024

Although red clump stars function as reliable standard candles, their surface characteristics (i.e. Teff, log g, and [Fe/H]) overlap with those of red giant branch stars, which are not standard candles. Recent results have revealed that spectral features containing carbon (e.g. CN molecular bands) carry information correlating with the ‘gold-standard’ asteroseismic classifiers that distinguish red clump from red giant branch stars. However, the underlying astrophysical processes driving the correlation between these spectroscopic and asteroseismic quantities in red giants remain inadequately explored. This study aims to enhance our understanding of this ‘spectro-seismic’ effect by refining the list of key spectral features predicting red giant evolutionary state. In addition, we conduct further investigation into those key spectral features to probe the astrophysical processes driving this connection. We employ the data-driven The Cannon algorithm to analyse high-resolution (R ∼ 80 000) Veloce Rosso spectra from the Anglo-Australian Telescope for 301 red giant stars (where asteroseismic classifications from the TESS mission are known for 123 of the stars). The results highlight molecular spectroscopic features, particularly those containing carbon (e.g. CN), as the primary indicators of the evolutionary states of red giant stars. Furthermore, by investigating CN isotopic pairs (that is, 12C14N and 13C14N), we find suggestions of statistically significant differences in the reduced equivalent widths of such lines, suggesting that physical processes that change the surface abundances and isotopic ratios in red giant stars, such as deep mixing, are the driving forces of the ‘spectro-seismic’ connection of red giants.
Inferring the dark matter splashback radius from cluster gas and observable profiles in the FLAMINGO simulations
Authors: Towler Imogen , Kay Scott T , Schaye Joop , Kugel Roi , Schaller Matthieu , Braspenning Joey , Elbers Willem , Frenk Carlos S , Kwan Juliana , Salcido Jaime , van Daalen Marcel P , Vandenbroucke Bert , Altamura Edoardo
Published: March 2024

The splashback radius, coinciding with the minimum in the dark matter radial density gradient, is thought to be a universal definition of the edge of a dark matter halo. Observational methods to detect it have traced the dark matter using weak gravitational lensing or galaxy number counts. Recent attempts have also claimed the detection of a similar feature in Sunyaev–Zel’dovich (SZ) observations of the hot intracluster gas. Here, we use the FLAMINGO simulations to investigate whether an extremum gradient in a similar position to the splashback radius is predicted to occur in the cluster gas profiles. We find that the minimum in the gradient of the stacked 3D gas density and pressure profiles, and the maximum in the gradient of the entropy profile, broadly align with the splashback feature though there are significant differences. While the dark matter splashback radius varies with specific mass accretion rate, in agreement with previous work, the radial position of the deepest minimum in the log-slope of the gas density is more sensitive to halo mass. In addition, we show that a similar minimum is also present in projected 2D pseudo-observable profiles: emission measure (X-ray), Compton-y (SZ), and surface mass density (weak lensing). We find that the latter traces the dark matter results reasonably well albeit the minimum occurs at a slightly smaller radius. While results for the gas profiles are largely insensitive to accretion rate and various observable proxies for dynamical state, they do depend on the strength of the feedback processes.
The X-ray enhancements of radio-loud quasars at high redshift: new results at z = 4–7
Authors: Zuo Zihao , Zhu Shifu , Brandt W N , Garmire Gordon P , Vito F , Wu Jianfeng , Xue Yongquan
Published: March 2024

Highly radio-loud quasars (HRLQs; log R > 2.5) at z ≳ 4 show apparent enhanced X-ray emission compared to matched HRLQs at lower redshifts, perhaps due to a redshift-dependent fractional contribution to the X-ray luminosity from inverse-Compton scattering of cosmic microwave background photons (IC/CMB). Using new Chandra observations and archival X-ray data, we investigate this phenomenon with an optically flux-limited sample of 41 HRLQs at z = 4–5.5 all with sensitive X-ray coverage, the largest sample utilized to date by a wide margin. X-ray enhancements are assessed using X-ray-to-optical flux ratios and spectral energy distributions. We confirm the presence of X-ray enhancements at a 4.9–5.3σ significance level, finding that the median factor of enhancement is ≈1.8 at our sample median redshift of z ≈ 4.4. Under a fractional IC/CMB model, the expected enhancement at lower redshifts is modest; e.g. ≈4 per cent at z ≈ 1.5. We also investigate a sample of seven radio-loud quasars (RLQs; log R > 1) at even higher redshifts of z = 5.6–6.8, using new and archival X-ray data. These RLQs also show evidence for X-ray enhancements by a median factor of ≈2.7 at a 3.7–4.9σ significance level. The X-ray spectral and other properties of these z = 5.6–6.8 RLQs, however, pose challenges for a straightforward fractional IC/CMB interpretation of their enhancements.
Optical spectroscopy of comets using Hanle Echelle Spectrograph (HESP)
Authors: Aravind K , Venkataramani Kumar , Ganesh Shashikiran , Surya Arun , Sivarani Thirupathi , Sahu Devendra , Unni Athira , Bhardwaj Anil
Published: March 2024

Observing the vibrational/rotational lines in a comet’s optical spectrum requires high-resolution spectroscopy, as they are otherwise seen as a blended feature. To achieve this, we have obtained medium and high-resolution (R (λ/Δλ) = 30 000 and 60 000) spectra of several comets, including C/2015 V2 (Johnson), 46P/Wirtanen, 41P/Tuttle–Giacobini–Kresák, and 38P/Stephan–Oterma, using the Hanle Echelle Spectrograph (HESP) mounted on the 2-m Himalayan Chandra Telescope (HCT) in India. The spectra effectively cover the wavelength range 3700–10 000 Å, allowing us to probe the various vibrational bands and band sequences to identify the rotational lines in the cometary molecular emission. We were also able to separate the cometary Oxygen lines from the telluric lines and analyse the green-to-red (G/R) forbidden oxygen [O i] ratios in a few comets. For comets C/2015 V2, 46P, and 41P, the computed G/R ratios, 0.04 ± 0.01, 0.04 ± 0.01, and 0.08 ± 0.02, respectively, point to H2O being a major source of Oxygen emissions. Notably, in the second fibre pointing at a location 1000 km away from the photocentre of comet 46P, the G/R ratio reduced by more than half the value observed in the first fibre, indicating the effects of quenching within the inner coma. We also measured the NH2 ortho-to-para ratio of comet 46P to be about 3.41 ± 0.05 and derived an ammonia ratio of 1.21 ± 0.03 corresponding to a spin temperature of ∼26 K. With these, we present the results of the study of four comets from different cometary reservoirs using medium and high-resolution optical spectroscopy, emphasizing the capabilities of the instrument for future cometary studies.
ARGONAUTE1-binding Tudor domain proteins function in small interfering RNA production for RNA-directed DNA methylation
Authors: Takei Takahito , Tsukada Michio , Tamura Kentaro , Hara-Nishimura Ikuko , Fukao Yoichiro , Kurihara Yukio , Matsui Minami , Saze Hidetoshi , Tsuzuki Masayuki , Watanabe Yuichiro , Hamada Takahiro
Published: March 2024

Transposable elements (TEs) contribute to plant evolution, development, and adaptation to environmental changes, but the regulatory mechanisms are largely unknown. RNA-directed DNA methylation (RdDM) is 1 TE regulatory mechanism in plants. Here, we identified that novel ARGONAUTE 1 (AGO1)-binding Tudor domain proteins Precocious dissociation of sisters C/E (PDS5C/E) are involved in 24-nt siRNA production to establish RdDM on TEs in Arabidopsis thaliana. PDS5 family proteins are subunits of the eukaryote-conserved cohesin complex. However, the double mutant lacking angiosperm-specific subfamily PDS5C and PDS5E (pds5c/e) exhibited different developmental phenotypes and transcriptome compared with those of the double mutant lacking eukaryote-conserved subfamily PDS5A and PDS5B (pds5a/b), suggesting that the angiosperm-specific PDS5C/E subfamily has a unique function in angiosperm plants. Proteome and imaging analyses revealed that PDS5C/E interact with AGO1. The pds5c/e double mutant had defects in 24-nt siRNA accumulation and CHH DNA methylation on TEs. In addition, some lncRNAs that accumulated in the pds5c/e mutant were targeted by AGO1-loading 21-nt miRNAs and 21-nt siRNAs. These results indicate that PDS5C/E and AGO1 participate in 24-nt siRNA production for RdDM in the cytoplasm. These findings indicate that angiosperm plants evolved a new regulator, the PDS5C/E subfamily, to control the increase in TEs during angiosperm evolution.
Contingent Claims and Hedging of Credit Risk with Equity Options
Authors: Avino Davide E , Salvador Enrique
Published: March 2024

Using contingent-claims valuation, we introduce novel hedge ratios for credit exposures using put options. Option hedge ratios are generally in line with the empirical sensitivities of credit spread changes to put option returns and, relative to stock hedge ratios, produce further reductions in volatility for a portfolio of North American firms. We show that option hedge ratios capture option-specific credit exposure related to the VIX index and the default spread, which is unaccounted for by Merton’s (1974) equity hedge ratios alone. Combining stocks and put options for credit risk hedging can be done effectively using the volatility smirk. (JEL E43, E44, G10)
Ecological Predictors of Organelle Genome Evolution: Phylogenetic Correlations with Taxonomically Broad, Sparse, Unsystematized Data
Authors: Giannakis Konstantinos , Richards Luke , Johnston Iain G
Published: March 2024

Comparative analysis of variables across phylogenetically linked observations can reveal mechanisms and insights in evolutionary biology. As the taxonomic breadth of the sample of interest increases, challenges of data sparsity, poor phylogenetic resolution, and complicated evolutionary dynamics emerge. Here, we investigate a cross-eukaryotic question where all these problems exist: which organismal ecology features are correlated with gene retention in mitochondrial and chloroplast DNA (organelle DNA or oDNA). Through a wide palette of synthetic control studies, we first characterize the specificity and sensitivity of a collection of parametric and non-parametric phylogenetic comparative approaches to identify relationships in the face of such sparse and awkward datasets. This analysis is not directly focused on oDNA, and so provides generalizable insights into comparative approaches with challenging data. We then combine and curate ecological data coupled to oDNA genome information across eukaryotes, including a new semi-automated approach for gathering data on organismal traits from less systematized open-access resources including encyclopedia articles on species and taxa. The curation process also involved resolving several issues with existing datasets, including enforcing the clade-specificity of several ecological features and fixing incorrect annotations. Combining this unique dataset with our benchmarked comparative approaches, we confirm support for several known links between organismal ecology and organelle gene retention, identify several previously unidentified relationships constituting possible ecological contributors to oDNA genome evolution, and provide support for a recently hypothesized link between environmental demand and oDNA retention. We, with caution, discuss the implications of these findings for organelle evolution and of this pipeline for broad comparative analyses in other fields.
Timing of dietary zinc additions during gestation for improved piglet survival
Authors: Hammers Kelsey L , Urriola Pedro E , Schwartz Mark , Ryu Moon-Suhn , Gomez Andres , Johnston Lee J
Published: March 2024

The objectives of this study were to determine a practical approach to feeding elevated dietary zinc (Zn) to gestating sows in a commercial setting and to confirm preweaning mortality could be reduced by feeding high Zn to sows during different periods of gestation. The study was conducted at a commercial sow farm in the upper Midwest. Mixed parity sows (n = 267) over three consecutive weekly farrowing groups (sows farrowing within 1 wk) were assigned randomly to one of the three dietary treatments within parity. Treatments consisted of: (1) control sows fed a corn–soybean meal diet containing 206 mg/kg total supplemental Zn supplied by zinc hydroxychloride; (2) breed-to-farrow: as control + 147 mg/kg supplemental Zn as ZnSO4 (353 mg/kg total supplemental Zn) fed from 5 d after breeding to farrowing; and (3) day 110-to-farrow: as control fed from breeding to farrowing + 4,079 mg/kg supplemental Zn as ZnSO4 (4,285 mg/kg total supplemental Zn) starting day 110 of gestation until farrowing. At farrowing, individual piglets were weighed and identified within 12 h of birth. Data were analyzed using PROC GLIMMIX of SAS and the model considered the fixed effect of dietary treatment and random effect of farrowing group. Dietary treatments did not affect number of total pigs born per litter. For breed-to-farrow sows, there was an increase in the percentage of pigs born alive compared to sows fed the control and day 110-to-farrow treatments (P < 0.001). The number of stillborn pigs expressed as a percentage of total litter size at birth decreased for breed-to-farrow sows (P < 0.001) compared with control or day 110-to-farrow sows. Mortality of low birth weight piglets from birth to weaning did not differ among dietary treatments (P = 0.305); however, a trend for decreasing post-natal mortality (P = 0.068) of normal birth weight pigs was observed for pigs born to sows fed elevated Zn 5 d before farrowing. In conclusion, feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. Under the conditions of this study, elevated Zn intake of sows did not influence piglet post-natal survival. However, feeding high zinc throughout gestation may decrease piglet mortality during the parturition process.
Trends in Indications and Contraindications for Cervical Disk Arthroplasty from 2009 to 2019
Authors: Shafi Karim , Du Jerry Y. , Blackburn Collin W. , Kim Han Jo , Iyer Sravisht , Qureshi Sheeraz , Marcus Randall E. , Albert Todd J.
Published: March 2024

Study Design:

Cross-sectional study.

Objective:

Assess trends of indications and contraindications for the use of Cervical Disk Arthroplasty (CDA)

Summary of Background Data:

As spine surgeons become more familiar with CDA, there have been expansions in indications.

Methods:

The Medicare Provider Analysis and Review Limited Data Sets for 2009, 2014, and 2019 were utilized. Patients undergoing elective CDA were included. Diagnosis for index surgery and “contraindications” as defined by original CDA Investigative Device Exemption (IDE) criteria were assessed. Variables were identified by the International Classification of Diseases (ICD)-9 or ICD-10 diagnosis and procedural codes.

Results:

A total of 1067 elective CDA patients were included. There were 230 patients in 2009, 300 patients in 2014, and 537 patients in 2019. The proportion of patients aged >65 increased from 35% to 51% (P<0.001). Incidence of CDA for radiculopathy increased from 57% to 69% (P<0.001), myelopathy increased from 23% to 78% (P<0.001), and spondylosis without radiculopathy or myelopathy decreased from 19% to 3% (P<0.001). There were increased incidences of ankylosing spondylitis (0.4% to 2.8%, P=0.007), long-term steroid use (1% to 2%, P=0.039), morbid obesity (2% to 6%, P=0.019), and osteoporosis (1% to 5%, P=0.014). The incidence of hybrid CDA and anterior cervical discectomy and fusion (ACDF) decreased from 28% to 23% (P=0.007).

Conclusion:

From 2009 to 2019, the number of CDA performed in older patients increased. An increase in the use of CDA for the treatment of myelopathy and radiculopathy and a decrease in the treatment of isolated cervical spondylosis was observed. The proportion of CDA performed in patients with original IDE trial “contraindications” increased. Further research into the efficacy of CDA for patients with contraindications is warranted.
Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway
Authors: Ni Weijie , Zhao Yajie , Shen Jinxin , Yin Qing , Wang Yao , Li Zuolin , Tang Taotao , Wen Yi , Zhang Yilin , Jiang Wei , Jiang Liangyunzi , Wei Jinxuan , Gan Weihua , Zhang Aiqing , Zhou Xiaoyu , Wang Bin , Liu Bi-Cheng
Published: March 2024

Background:

Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.

Methods:

We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett’s multiple comparison and t-test were used to analyze the data.

Results:

Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.

Conclusions:

Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Role of mitochondrial dysfunction in kidney disease: Insights from the cGAS-STING signaling pathway
Authors: Li Lu , Liu Fei , Feng Chunyue , Chen Zhenjie , Zhang Nan , Mao Jianhua
Published: March 2024

Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.
Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over −18.00 diopters
Authors: Ortega-Usobiaga Julio , González-López Félix , Peng Yanli , Bilbao-Calabuig Rafael , Beltrán-Sanz Jaime , Larrubia Juan Ramón , Llovet-Osuna Fernando
Published: March 2024

Purpose:

To explore visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at −18.00 diopters (D), with central port, followed by bioptics by laser vision correction (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) to address residual myopia or myopic astigmatism.

Setting:

Clínica Baviera (Aier Eye Hospital Group), Bilbao, Spain.

Design:

Retrospective analysis of cases.

Methods:

The study assessed uncorrected distance visual acuity, corrected distance visual acuity (CDVA), predictability, safety, efficacy, and patient satisfaction after implantation of the ICL and bioptics. The model implanted was V4c and EVO, with a correction of −18.00 D. Bioptics were performed at least 3 months after implantation, and patients were followed up for at least 3 months after LASIK or PRK.

Results:

The analysis included 125 eyes from 90 patients. Of these, 51.2% underwent LASIK and 48.8% PRK. Mean time from implantation to bioptics was 5.9 ± 9.4 months. Patients were followed up for a mean of 40.2 ± 37.9 months after bioptics. Median manifest refractive spherical equivalent was −2.89 D before bioptics and −0.49 D after. Median CDVA was 0.18 logMAR before bioptics and 0.17 after. The mean safety and efficacy indices were 2.22 ± 1.88 and 2.06 ± 1.85, respectively.

Conclusions:

Visual outcomes and safety indices after ICL implantation and subsequent LASIK or PRK in patients with extreme myopia are excellent.
Clinical efficacy of clopidogrel and ticagrelor in patients undergoing off-pump coronary artery bypass grafting: a retrospective cohort study
Authors: Wang Zi , Ma Runhua , Li Xiaoyu , Li Xiaoye , Xu Qing , Yao Yao , Wang Chunsheng , Lv Qianzhou
Published: March 2024

Background:

Ticagrelor is reportedly more effective than clopidogrel in preventing atherothrombotic events in patients with percutaneous coronary intervention. However, the optimal antiplatelet therapy strategy after off-pump coronary artery bypass grafting (OPCABG) is yet to be established.

Materials and Methods:

This study was performed using the prospectively-maintained database at our institution. Patients who underwent OPCABG were divided into the clopidogrel and the ticagrelor groups. Propensity score matching analysis was performed between the two groups. The clinical outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of vascular death, myocardial infarction, or stroke 1-year after surgery.

Results:

In total, 545 patients completed the entire follow-up assessment. After propensity score matching, 232 patients each were included in the clopidogrel and ticagrelor groups. The primary outcome occurred in 7.8 and 4.3% of patients in the clopidogrel and ticagrelor groups, respectively (P=0.113). CYP2C19 variants (*2, *3, and *17) did not impact the clinical outcomes, regardless of the use of clopidogrel or ticagrelor. The rates of MACE were significantly lower in patients carrying the ABCB1 C3435T CT/TT genotypes in the ticagrelor group than in those carrying the ABCB1 C3435T CC genotype in the clopidogrel group (1.4 vs. 9.1%, adjusted P=0.030), as well as those carrying the ABCB1 C3435T CC genotype in the ticagrelor group (1.4 vs. 8.9%, adjusted P=0.036). The ABCB1 C3435T CC genotype was significantly associated with the incidence of 1-year MACE (HR=1.558, 95% CI: 1.109–2.188, P=0.011). Patients who experienced severe perioperative bleeding exhibited a significantly higher incidence of MACE than those who did not experience severe perioperative bleeding (14.0 vs. 4.9%, adjusted P=0.007).

Conclusion:

There was no significant difference in the 1-year MACE between patients receiving clopidogrel and those receiving ticagrelor after OPCABG. Notably, The ABCB1 C3435T CC genotype was related to a higher risk of MACE.
The STROCSS 2024 guideline: strengthening the reporting of cohort, cross-sectional, and case–control studies in surgery
Authors: Rashid Rasha , Sohrabi Catrin , Kerwan Ahmed , Franchi Thomas , Mathew Ginimol , Nicola Maria , Agha Riaz A.
Published: March 2024

Introduction:

First released in 2017, the STROCSS guidelines have become integral for promoting high-quality reporting of observational research in surgery. However, regular updates are essential to ensure they remain relevant and of value to surgeons. Building on the 2021 updates, the authors have developed the STROCSS 2024 guidelines. This timely revision aims to address residual reporting gaps, assimilate recent advances, and further strengthen observational study quality across all surgical disciplines.

Methods:

A core steering committee compiled proposed changes to update the STROCSS 2021 guidelines based on identified gaps in prior iterations. An expert panel of surgical research leaders then evaluated the proposed changes for inclusion. A Delphi consensus exercise was used. Proposals that scored between 7-9 on a nine-point Likert agreement scale, by ≥70% of Delphi participants, were integrated into the STROCSS 2024 checklist.

Results:

In total, 46 of 56 invited participants (82%) completed the Delphi survey and hence participated in the development of STROCSS 2024. All suggested amendments met the criteria for inclusion, indicating a high level of agreement among the Delphi group. All proposed items were therefore integrated into the final revised checklist.

Conclusion:

The authors present the updated STROCSS 2024 guidelines, which have been developed through expert consensus to further enhance the transparency and reporting quality of observational research in surgery.
C-reactive protein/lymphocyte ratio as a prognostic biomarker in acute pancreatitis: a cross-sectional study assessing disease severity
Authors: Chen Xinqi , Lin Zhijin , Chen Yani , Lin Chanchan
Published: March 2024

Background:

The C-reactive protein/lymphocyte ratio (CLR) is a prognostic biomarker of various diseases. However, its significance in acute pancreatitis (AP) remains unknown. The main aim of this study was to investigate the association between the CLR and disease severity in patients with AP.

Methods:

This cross-sectional study included 476 AP patients [mild acute pancreatitis (MAP), n=176; moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), n=300]. The primary exposure of interest was the baseline CLR. The primary outcome was the incidence of moderate to severe AP. Multivariate logistic regression and restricted cubic spline analyses were performed to evaluate the association between the CLR and the incidence of moderate to severe AP. Receiver operating characteristic (ROC) analysis was conducted to assess the predictive efficacy, sensitivity, and specificity of CLR in predicting the incidence of moderate to severe AP.

Results:

The mean age of the patients was 44±13.2 years, and 76.5% were male. The distribution of CLR was 31.6 (interquartile range, 4.5, 101.7). Moderate to severe AP occurred in 300 cases (63.0%). After multiple adjustments, CLR was independently associated with the incidence of moderate to severe AP (odds ratio, 1.04; 95% CI: 1.03–1.05; P< 0.001). A nonlinear relationship was found between CLR and the incidence of moderate to severe AP, with a threshold of approximately 45. The effect size and CI below and above the threshold value were 1.061 (1.033–1.089) and 1.014 (0.997–1.031), respectively. The area under the curve (AUC) for CLR was 87.577% (95% CI: 84.443– 90.710%) with an optimal cut-off value of 30.835, resulting in a sensitivity of 73.7% and a specificity of 88.6%.

Conclusions:

There was a nonlinear relationship with a saturation effect between the CLR and the incidence of moderate to severe AP. The CLR measured within 24 h of admission may serve as a promising biomarker for predicting the emergence of moderate to severe AP, thereby providing a more scientifically grounded basis for preventing such cases. Nonetheless, further research is warranted to validate and strengthen these findings.
Preliminary analysis of stimulation parameters for sacral neuromodulation in different indications: a multicenter retrospective cohort study from China
Authors: Meng Lingfeng , Yan Zehao , Wang Xinhao , Zhang Yaoguang , Zhu Zhikai , Zhu Wen , Ling Qing , Sun Xiaoke , Gu Yinjun , Lv Jianwei , Li Yan
Published: March 2024

Background:

Sacral neuromodulation (SNM) is an effective approach for treating lower urinary tract dysfunction (LUTD), and stimulation programming is essential for successful treatment. However, research on SNM programming for various indications is limited. Thus, the authors aimed to determine whether there were differences in the stimulation parameters for different SNM indications and the appropriate programming recommendations.

Materials and methods:

Clinical data were retrospectively collected from patients with LUTD who underwent SNM and completed internal pulse generator implantation. The parameters with the highest patient satisfaction or the most symptom improvement during the test period were considered optimal and used to set the programming after internal pulse generator implantation.

Results:

After screening, 282 patients were enrolled and categorized into four groups based on the following indications: refractory overactive bladder (OAB) (n=61), neurogenic lower urinary tract dysfunction (nLUTD) (n=162), interstitial cystitis/painful bladder syndrome (IC/BPS) (n=24), and idiopathic nonobstructive urinary retention (NOUR) (n=35). When analyzing the optimal stimulus parameters, disparities in the stimulation amplitude and pulse frequency were noted among the four groups. The stimulation amplitude in the nLUTD group was higher than that in the idiopathic NOUR group (P=0.013). Differences in pulse frequency were observed between the refractory OAB and nLUTD groups (P<0.001) and between the refractory OAB and idiopathic NOUR groups (P=0.001). No differences in the electrode configuration or pulse width settings existed among the four groups.

Conclusions:

The stimulation parameters for SNM varied among the different indications. For the initial programming of stage I, most patients are recommended to start with stimulation amplitudes below 2 V, although patients with nLUTD may benefit from higher amplitudes. A standard pulse width of 210 μs is recommended for all patients. However, for individuals experiencing nLUTD or idiopathic NOUR, the pulse frequency can begin above the standard 14 Hz but not exceed 50 Hz.
Malignant hyperthermia in a paediatric patient; managed successfully without dantrolene: a case report
Authors: Ranjit Sangina , Kharbuja Kalpana , Shrestha Ashish , Timalsina Binod , Ranjitkar Neeti , Chaudhary Ashlesha
Published: March 2024

Introduction:

Malignant hyperthermia (MH) is a potentially life-threatening pharmacogenetic syndrome triggered by volatile anaesthetics, succinylcholine, and stress such as vigorous exercise.

Case presentation:

The authors describe a case of an 8-year-old male who presented with classical symptoms of MH after induction of general anaesthesia and symptomatic treatment was done successfully due to the unavailability of Dantrolene.

Discussion:

Definitive diagnosis of MH can be done based on a contracture test in fresh muscle biopsy in the presence of halothane and caffeine. In the absence of muscle biopsy and genetic testing, diagnosis for MH can be done based on MH scoring.

Conclusion:

Anesthesiologists should be made aware that proper symptomatic management can also save the life of a patient. Also, strong advocacy should be done to ensure the availability of Dantrolene and further strengthen lab facilities to confirm diagnosis to facilitate diagnosis and management in the future.
Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model
Authors: Kobayashi Yasuyuki , Li Jing , Parker Marlee , Wang Jian , Nagy Anita , Fan Chun-Po Steve , Runeckles Kyle , Okumura Michiru , Kadowaki Sachiko , Honjo Osami
Published: March 2024

Background.

Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model.

Methods.

Sixteen DCD piglet hearts (11–14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0–5.9 g/dL; n = 8) and control (Hb, 7.5–8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t-tests or Fisher’s Exact tests.

Results.

During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption (P < 0.001), a higher arterial lactate level (P = 0.001), and worse systolic ventricular function (P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level (P = 0.031). Adjusted cardiac troponin-I (P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group (P = 0.028).

Conclusions.

Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.
Lacticaseibacillus pabuli sp. nov., isolated from fermented cattle feed
Authors: Choi Hyorim , Kim Yiseul , Kim Seunghwan , Kwon Soon-Wo , Lee Daseul , Han Byeong-Hak , Hong Seung-Beom , Naito Hanako , Yamada Tomomi , Hamada Moriyuki , Heo Jun
Published: March 2024

Strain BSF-3MT is a Gram-stain-positive, non-flagellated, facultative anaerobic and rod-shaped bacterium that was isolated from fermented feed collected at a cattle farm in the Daejeon region of the Republic of Korea. It was studied using polyphasic taxonomic methods. Using 16S rRNA gene sequences and the resulting phylogenetic tree, the strain was primarily identified as a member of the genus Lacticaseibacillus. Strain BSF-3MT contained a chromosome of 2.5 Mbp and a plasmid of 33.4 kbp. The G+C content of genomic DNA was 51.3 mol%. Strain BSF-3MT had the highest ortho-average nucleotide identity value of 73.7 % with Lacticaseibacillus songhuajiangensis 7-19T, its closest relative in the phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree based on up-to-date bacterial core genes. Based on the results of a polyphasic taxonomic study, strain BSF-3MT represents a novel species in the genus Lacticaseibacillus, for which the name Lacticaseibacillus pabuli sp. nov. is proposed. The type strain is BSF-3MT (=KACC 23028T=NBRC 116014T).