bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordance among apoB, non–high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention
Authors: Sniderman Allan D , Dufresne Line , Pencina Karol M , Bilgic Selin , Thanassoulis George , Pencina Michael J
Published: May 2024

Background and Aims

Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care.

Methods

A sample of 293 876 UK Biobank adults (age: 40–73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C.

Results

ApoB was highly correlated with LDL-C and non-HDL-C (Pearson’s r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8–108.8 md/dL when LDL-C 130 mg/dL, 88.3–112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8–147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean − 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0–1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03–1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12–1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model.

Conclusions

High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.
Robust and heritable knockdown of gene expression using a self-cleaving ribozyme in Drosophila
Authors: Nyberg Kevin G , Navales Fritz Gerald , Keles Eren , Nguyen Joseph Q , Hertz Laura M , Carthew Richard W
Published: May 2024

The current toolkit for genetic manipulation in the model animal Drosophila melanogaster is extensive and versatile but not without its limitations. Here, we report a powerful and heritable method to knockdown gene expression in D. melanogaster using the self-cleaving N79 hammerhead ribozyme, a modification of a naturally occurring ribozyme found in the parasite Schistosoma mansoni. A 111-bp ribozyme cassette, consisting of the N79 ribozyme surrounded by insulating spacer sequences, was inserted into 4 independent long noncoding RNA genes as well as the male-specific splice variant of doublesex using scarless CRISPR/Cas9-mediated genome editing. Ribozyme-induced RNA cleavage resulted in robust destruction of 3′ fragments typically exceeding 90%. Single molecule RNA fluorescence in situ hybridization results suggest that cleavage and destruction can even occur for nascent transcribing RNAs. Knockdown was highly specific to the targeted RNA, with no adverse effects observed in neighboring genes or the other splice variants. To control for potential effects produced by the simple insertion of 111 nucleotides into genes, we tested multiple catalytically inactive ribozyme variants and found that a variant with scrambled N79 sequence best recapitulated natural RNA levels. Thus, self-cleaving ribozymes offer a novel approach for powerful gene knockdown in Drosophila, with potential applications for the study of noncoding RNAs, nuclear-localized RNAs, and specific splice variants of protein-coding genes.
High parasite diversity maintained after an alga–virus coevolutionary arms race
Authors: Lievens Eva J P , Kühn Samuel , Horas Elena L , Le Pennec Guénolé , Peter Sarah , Petrosky Azade D , Künzel Sven , Feulner Philine G D , Becks Lutz
Published: May 2024

Arms race dynamics are a common outcome of host–parasite coevolution. While they can theoretically be maintained indefinitely, realistic arms races are expected to be finite. Once an arms race has ended, for example due to the evolution of a generalist-resistant host, the system may transition into coevolutionary dynamics that favour long-term diversity. In microbial experiments, host–parasite arms races often transition into a stable coexistence of generalist-resistant hosts, (semi-)susceptible hosts, and parasites. While long-term host diversity is implicit in these cases, parasite diversity is usually overlooked. In this study, we examined parasite diversity after the end of an experimental arms race between a unicellular alga (Chlorella variabilis) and its lytic virus (PBCV-1). First, we isolated virus genotypes from multiple time points from two replicate microcosms. A time-shift experiment confirmed that the virus isolates had escalating host ranges, i.e., that arms races had occurred. We then examined the phenotypic and genetic diversity of virus isolates from the post-arms race phase. Post-arms race virus isolates had diverse host ranges, survival probabilities, and growth rates; they also clustered into distinct genetic groups. Importantly, host range diversity was maintained throughout the post-arms race phase, and the frequency of host range phenotypes fluctuated over time. We hypothesize that this dynamic polymorphism was maintained by a combination of fluctuating selection and demographic stochasticity. Together with previous work in prokaryotic systems, our results link experimental observations of arms races to natural observations of long-term host and parasite diversity.
Performance and preference of larval parasitoid, Microplitis pallidipes (Hymenoptera: Braconidae), on 2 Spodoptera pest species
Authors: Xu Wei , Lyu Baoqian , Yan Sanqiang , Song Yaoyao , Tang Jihong , Zhou Xiaojuan , Wang Chongtian
Published: May 2024

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) and Spodoptera litura (Fabricius) are the main pests on corn (Poaceae: Gramineae). The performance of the larval wasp, Microplitis pallidipes Szépligeti (Hymenoptera: Braconidae), was reported on S. frugiperda and S. litura. In this study, we evaluated host selectivity, constructed an age–stage, 2-sex life table, and assessed the pest control potential of M. pallidipes against these 2 pests under laboratory conditions. In a 2-choice host preference experiment, M. pallidipes exhibited a stronger preference for S. frugiperda over S. litura and a distinct preference for second instars. We also investigated the parasitism of females that were either unfed or fed with 10% honey–water solution under different host densities and found that the highest parasitism rate was observed when M. pallidipes were fed with honey–water solution on the first day after mating and a presented female wasp:host ratio of 1:90. In a nonselective assay, M. pallidipes successfully completed a full generation on both hosts. However, the parasitoids exhibited higher fitness and population growth potential when reared on S. frugiperda, with a net reproductive rate (R0) of 24.24, an intrinsic rate of increase (r) of 0.20 per day, a finite rate of increase (λ) of 1.23 per day, and a mean generation time (T) of 15.69 days. This study elucidates the performance of M. pallidipes on 2 Spodoptera host species and offers insights into its biological control potential on lepidopteran pests.
Pandemic Forms
Authors: Krishnan Lakshmi
Published: May 2024

Narrative structures, though invisible to the naked eye, guide our understanding of pandemics. Like curves and graphs, we can plot them, identify their patterns and organizing principles. These structures act upon our understanding of social and biological events just as much as the rhythms of viral replication and mutation. They order not only themselves but also social and health outcomes. This essay uses narrative precision to expand beyond Charles Rosenberg’s influential dramaturgic model and develops new pandemic forms, scaled from the level of an individual line break to the multi-part series: Arc, a form of sequence. Cycle, a form of repetition. Sequel, a form of elongation. Caesura, a form of break. It investigates the potentialities and limitations of these forms, how they intersect, collide, and contradict, and how analysis of these interactions contributes to a deeper understanding of pandemics, their effects, and the diverse perspectives defining their structures. In doing so, it prototypes how literary methods offer conceptual frameworks for pandemic historiography and how a transdisciplinary, medical humanities analysis produces novel understandings at the intersection of health, culture, and society.
Ganglioglioma with anaplastic/high-grade transformation: Histopathologic, molecular, and epigenetic characterization of 3 cases
Authors: Vizcaino M Adelita , Giannini Caterina , Lalich Daniel , Nael Ali , Jenkins Robert B , Tran Quynh , Orr Brent A , Abdullaev Zied , Aldape Kenneth , Vaubel Rachael A
Published: May 2024

Ganglioglioma (GG) with anaplasia (anaplastic ganglioglioma) is a rare and controversial diagnosis. When present, anaplasia involves the glial component of the tumor, either at presentation or at recurrence. To date, most published cases lack molecular characterization. We describe the histologic and molecular features of 3 patients presenting with BRAF p. V600E-mutant GG (CNS WHO grade 1) with high-grade glial transformation at recurrence. The tumors occurred in pediatric patients (age 9–16 years) with time to recurrence from 20 months to 7 years. At presentation, each tumor was low-grade, with a BRAFV600E-positive ganglion cell component and a glial component resembling pleomorphic xanthoastrocytoma (PXA) or fibrillary astrocytoma. At recurrence, tumors resembled anaplastic PXA or high-grade astrocytomas without neuronal differentiation. CDKN2A homozygous deletion (HD) was absent in all primary tumors. At recurrence, 2 cases acquired CDKN2A HD; the third case showed loss of p16 and MTAP immunoexpression, but no CDKN2A/B HD or mutation was identified. By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.
Evaluating Bacterial Spore Preparation Methods for Scanning Electron Microscopy
Authors: Malyshev Dmitry , Lee Cheng Choo , Andersson Magnus
Published: May 2024

Scanning electron microscopy (SEM) can reveal the ultrastructure of bacterial spores, including morphology, surface features, texture, spore damage, germination, and appendages. Understanding these features can provide a basis for adherence, how physical and environmental stressors affect spore viability, integrity, and functionality, as well as the distribution and function of surface appendages. However, the spore sample preparation method can significantly impact the SEM images’ appearance, resolution, and overall quality. In this study, we compare different spore preparation methods to identify optimal approaches for preparation time, spore appearance and resolved features, including the exosporium and spore pili, for SEM imaging. We use Bacillus paranthracis as model species and evaluate the efficacy of preparation protocols using different fixation and drying methods, as well as imaging under room- and cryogenic temperatures. We compare and assess method complexity to the visibility of the spore exosporium and spore appendages across different methods. Additionally, we use Haralick texture features to quantify the differences in spore surface appearance and determine the most suitable method for preserving spore structures and surface features during SEM evaluation. The findings from this study will help establish protocols for preparing bacterial spores for SEM and facilitating accurate and reliable analysis of spores’ characteristics.
What drives the variability in AGN? Explaining the UV-Xray disconnect through propagating fluctuations
Authors: Hagen Scott , Done Chris , Edelson Rick
Published: May 2024

Intensive broad-band reverberation mapping campaigns have shown that AGN variability is significantly more complex than expected from disc reverberation of the variable X-ray illumination. The UV/optical variability is highly correlated and lagged, with longer lags at longer wavelengths as predicted, but the observed time-scales are longer than expected. Worse, the UV/optical light curves are not well correlated with the X-rays, which should drive them. Instead, we consider an intrinsically variable accretion disc, where slow mass accretion rate fluctuations are generated in the optical-UV disc, propagating down to modulate intrinsically faster X-ray variability from the central regions. We match our model to Fairall 9, a well-studied AGN with L ∼ 0.1LEdd, where the spectrum is dominated by the UV/EUV. Our model produces light curves where the X-rays and UV have very different fast variability, yet are well correlated on longer time-scales, as observed. It predicts that the intrinsic variability has optical/UV leading the X-rays, but including reverberation of the variable EUV from an inner wind produces a lagged bound-free continuum that matches the observed UV-optical lags. We conclude that optical/UV AGN variability is likely driven by intrinsic fluctuations within the disc, not X-ray reprocessing: the observed longer than expected lags are produced by reverberation of the EUV illuminating a wind, not by X-ray illumination of the disc: the increasing lag with increasing wavelength is produced by the increased contribution of the (constant lag) bound-free continuum to the spectrum, rather than indicating intrinsically larger reverberation distances for longer wavelengths.
Highly mass-loaded hot galactic winds are unstable to cool filament formation
Authors: Nguyen Dustin D , Thompson Todd A , Schneider Evan E , Tarrant Ashley P
Published: May 2024

As cool clouds are entrained by a hot supersonic galactic wind, they may be shredded by hydrodynamical instabilities and incorporated into the hot flow. One-dimensional steady-state calculations show how cool cloud entrainment affects the bulk thermodynamics and kinematics of the hot gas: mass-loading decelerates the hot flow and changes its entropy. Here, we investigate the stability of mass-loaded hot winds using both perturbation analysis and 3D time-dependent radiative hydrodynamical simulations. We show that mass-loading is stable over a broad range of parameters and that the 1D time-steady analytic solutions exactly reproduce the 3D time-dependent calculations, provided that the flow does not decelerate sufficiently to become subsonic. For higher values of the mass-loading, the flow develops a second sonic point, with the first being at the edge of the wind-driving region. Strong deceleration increases the wind density and the flow becomes radiative, undergoing a thermal instability to form elongated dense cometary filaments. We explore the mass-loading parameters required to trigger this behaviour. For certain approximations, we can derive analytic criteria. In general, a mass-loading rate similar to the initial hot-mass outflow rate is required. In this sense, the destruction of small cool clouds by a hot flow may ultimately spontaneously generate fast cool filaments, as observed in starburst winds. Lastly, we find that the kinematics of filaments is sensitive to the slope of the mass-loading function. Filaments move faster than the surrounding wind if mass-loading is over long distances whereas filaments move slower than their surroundings if mass-loading is abrupt.
CRISPR/Cas9-generated mutations in a sugar transporter gene reduce cassava susceptibility to bacterial blight
Authors: Elliott Kiona , Veley Kira M , Jensen Greg , Gilbert Kerrigan B , Norton Joanna , Kambic Lukas , Yoder Marisa , Weil Alex , Motomura-Wages Sharon , Bart Rebecca S
Published: May 2024

Bacteria from the genus Xanthomonas are prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing the expression of host susceptibility (S) genes. Xanthomonas phaseoli pv. manihotis (Xpm) causes bacterial blight on the staple food crop cassava (Manihot esculenta Crantz). The Xpm effector TAL20 induces ectopic expression of the S gene Manihot esculenta Sugars Will Eventually be Exported Transporter 10a (MeSWEET10a), which encodes a sugar transporter that contributes to cassava bacterial blight (CBB) susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to the MeSWEET10a TAL20 effector binding site and/or coding sequence. In several of the regenerated lines, MeSWEET10a expression was no longer induced by Xpm, and in these cases, we observed reduced CBB disease symptoms post Xpm infection. Because MeSWEET10a is expressed in cassava flowers, we further characterized the reproductive capability of the MeSWEET10a promoter and coding sequence mutants. Lines were crossed to themselves and to wild-type plants. The results indicated that expression of MeSWEET10a in female, but not male, flowers is critical to produce viable F1 seed. In the case of promoter mutations that left the coding sequence intact, viable F1 progeny were recovered. Taken together, these results demonstrate that blocking MeSWEET10a induction is a viable strategy for decreasing cassava susceptibility to CBB and that ideal lines will contain promoter mutations that block TAL effector binding while leaving endogenous expression of MeSWEET10a unaltered.
Belief Updating, Childhood Maltreatment, and Paranoia in Schizophrenia-Spectrum Disorders
Authors: Sloan Ali F , Kittleson Andrew R , Torregrossa Lénie J , Feola Brandee , Rossi-Goldthorpe Rosa , Corlett Philip R , Sheffield Julia M
Published: May 2024

Background and Hypothesis

Exposure to childhood maltreatment—a risk factor for psychosis that is associated with paranoia—may impact one’s beliefs about the world and how beliefs are updated. We hypothesized that increased exposure to childhood maltreatment is related to volatility-related belief updating, specifically higher expectations of volatility, and that these relationships are strongest for threat-related maltreatment. Additionally, we tested whether belief updating mediates the relationship between maltreatment and paranoia.

Study Design

Belief updating was measured in 75 patients with schizophrenia-spectrum disorders and 76 nonpsychiatric controls using a 3-option probabilistic reversal learning (3PRL) task. A Hierarchical Gaussian Filter (HGF) was used to estimate computational parameters of belief updating, including prior expectations of volatility (μ03). The Childhood Trauma Questionnaire (CTQ) was used to assess cumulative maltreatment, threat, and deprivation exposure. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS).

Results

Greater exposure to childhood maltreatment is associated with higher prior expectations of volatility in the whole sample and in individuals with schizophrenia-spectrum disorders. This was specific to threat-related maltreatment, rather than deprivation, in schizophrenia-spectrum disorders. Paranoia was associated with both exposure to childhood maltreatment and volatility priors, but we did not observe a significant indirect effect of volatility priors on the relationship between maltreatment and paranoia.

Conclusions

Our study suggests that individuals with schizophrenia-spectrum disorders who were exposed to threatening experiences during childhood expect their environment to be more volatile, potentially facilitating aberrant belief updating and conferring risk for paranoia.
Androgen synthesis cell‐specific CREBZF deficiency alters adrenal cortex steroid secretion and develops behavioral abnormalities in adult male mice
Authors: Niu Hongyu , Li Chao , Zhang Hexin , Liu Haokun , Shang Chunmei , Jia Yanni , Wuenjiya  , Li Zuhui , Wang Aihua , Jin Yaping , Lin Pengfei
Published: May 2024

The global challenge of male infertility is escalating, notably due to the decreased testosterone (T) synthesis in testicular Leydig cells under stress, underscoring the critical need for a more profound understanding of its regulatory mechanisms. CREBZF, a novel basic region‐leucine zipper transcription factor, regulates testosterone synthesis in mouse Leydig cells in vitro; however, further validation through in vivo experiments is essential. Our study utilized Cyp17a1‐Cre to knock out CREBZF in androgen‐synthesis cells and explored the physiological roles of CREBZF in fertility, steroid hormone synthesis, and behaviors in adult male mice. Conditional knockout (cKO) CREBZF did not affect fertility and serum testosterone level in male mice. Primary Leydig cells isolated from CREBZF‐cKO mice showed impaired testosterone secretion and decreased mRNA levels of Star, Cyp17a1, and Hsd3b1. Loss of CREBZF resulted in thickening of the adrenal cortex, especially X‐zone, with elevated serum corticosterone and dehydroepiandrosterone levels and decreased serum dehydroepiandrosterone sulfate levels. Immunohistochemical staining revealed increased expression of StAR, Cyp11a1, and 17β‐Hsd3 in the adrenal cortex of CREBZF‐cKO mice, while the expression of AR was significantly reduced. Along with the histological changes and abnormal steroid levels in the adrenal gland, CREBZF‐cKO mice showed higher anxiety‐like behavior and impaired memory in the elevated plus maze and Barnes maze, respectively. In summary, CREBZF is dispensable for fertility, and CREBZF deficiency in Leydig cells promotes adrenal function in adult male mice. These results shed light on the requirement of CREBZF for fertility, adrenal steroid synthesis, and stress response in adult male mice, and contribute to understanding the crosstalk between testes and adrenal glands.
The Union Army’s Surgical Handbook and the Positive Story of Civil War Surgery
Authors: Harris John M.
Published: May 2024

Western armies have relied on surgical field manuals to help physicians deal with unfamiliar combat medical conditions from the Napoleonic wars to the present day, but there has been little discussion of whether these handbooks have been used or improved outcomes. Recent research shows that the Union Army’s American Civil War (1861–1865) surgical case fatality rates improved as the war progressed, much like the US Army’s experience in later wars, and were generally superior to comparable European results. These positive Civil War outcomes have been attributed to field experience, adoption of best practices, and enhanced communication, without consideration of New York surgeon Stephen Smith’s widely-used Hand-Book of Surgical Operations. The Army of the Potomac added Smith’s pocket-sized Hand-Book to its supply table in 1862. Northern medical journals applauded it, and Smith’s contemporaries documented its wide use. Smith’s handbook explained and demonstrated surgical techniques that were adopted as the war progressed, such as the use of general anesthesia and limb-sparing resection (debridement) of gunshot wounds. It offered pithy, well-documented advice from recognized experts along with numerous illustrations, which allowed untrained physicians to visualize anatomical relationships and see contemporary best practices in a way that no other wartime publication provided, making it an exemplar of a mass-media surgical improvement change agent.
Systematic Review of Surgical Care in the Incarcerated Population: Identifying Knowledge Gaps for Future Research
Authors: Dhimal Totadri , Cupertino Paula , Ghaffar Aqsa , Li Yue , Cai Xueya , Soto Cristopher , Ramaswamy Megha , Herdman Bruce W. , Fleming Fergal J. , Loria Anthony
Published: May 2024

Objective:

This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for informing future health services research and interventions.

Background:

The US prison system detains around 2 million individuals, mainly young, indigent males from ethnic and racial minorities. The constitutional right to healthcare does not protect this population from unique health challenges and disparities. The scarcity of literature on surgical care necessitates a systematic review to stimulate research, improve care quality, and address health issues within this marginalized community.

Methods:

A systematic review, pre-registered with the International Prospective Register of Systematic Reviews (CRD42023454782), involved searches in PubMed, Embase, and Web of Science. Original research on surgical care for incarcerated individuals was included, excluding case reports/series (<10 patients), abstracts, and studies involving prisoners of war, plastic surgeries for recidivism reduction, transplants using organs from incarcerated individuals, and nonconsensual surgical sterilization.

Results:

Out of 8209 studies screened, 118 met inclusion criteria, with 17 studies from 16 distinct cohorts reporting on surgical care. Predominantly focusing on orthopedic surgeries, supplemented by studies in emergency general, burns, ophthalmology, and kidney transplantation, the review identified delayed hospital presentations, a high incidence of complex cases, and low postoperative follow-up rates. Notable complications, such as nonfusion and postarthroplasty infections, were more prevalent in incarcerated individuals compared with nonincarcerated individuals. Trauma-related mortality rates were similar, despite lower intraabdominal injuries following penetrating abdominal injuries in incarcerated patients.

Conclusion:

While some evidence suggests inferior surgical care in incarcerated patients, the limited quality of available studies underscores the urgency of addressing knowledge gaps through future research. This is crucial for patients, clinicians, and policymakers aiming to enhance care quality for a population at risk of surgical complications during incarceration and postrelease.
Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children
Authors: Aziz Muhammad , Haghbin* Hossein , Gangwani Manesh K. , Fatima Rawish , Sohail Amir H. , Ali Hassam , Alyousif Zakaria A. , Dahiya Dushyant S. , Lee-Smith Wade , Beran Azizullah , Kamal Faisal , Nawras Ali
Published: May 2024

Introduction:

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children.

Methods:

We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes.

Results:

Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5 mg twice daily, fluticasone 3 mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3 mg daily, cendakimab 180 mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5 mg daily, OVB low dose, reslizumab 3 mg/kg, reslizumab 1 mg/kg, and reslizumab 2 mg/kg.

Conclusions:

Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.
Cost-effectiveness of medication therapy management among Medicare population and across racial/ethnic groups
Authors: Tsang Chi Chun Steve , Wang Junling , Shih Ya-Chen Tina
Published: May 2024

Background:

Inappropriate medication utilization among older adults is a pressing concern in the United States, owing to its high prevalence and the consequential detrimental impact it engenders. The adverse effects stemming from the inappropriate use of medication may be unequally borne by racial/ethnic minority populations, calling for greater efforts towards promoting equity in healthcare. The study objective was to assess the cost-effectiveness of Medication Therapy Management (MTM) services among Medicare beneficiaries and across racial/ethnic groups.

Methods:

Medicare administrative data from 2016 to 2017 linked to Area Health Resources Files were used to analyze Medicare fee-for-service patients aged 65 or above with continuous Parts A/B/D coverage. The intervention group included new MTM enrollees in 2017; the control group referred to patients who met the general MTM eligible criteria but did not enroll in 2016 or 2017. The 2 groups were matched using a propensity score method. Effectiveness was evaluated as the proportion of appropriate medication utilization based on performance measures developed by the Pharmacy Quality Alliance. Costs were computed as total healthcare costs from Medicare perspective. A multivariable net benefit regressions with a classic linear model and Bayesian analysis were utilized. Net benefit was calculated based on willingness-to-pay thresholds at various multiples of the gross domestic product in 2017. Three-way interaction terms among dummy variables for MTM enrollment, 2017, and racial/ethnic minority groups were incorporated in a difference-in-differences study design.

Results:

After adjusting for patient characteristics, the findings indicate that MTM receipt was associated with incremental net benefit among each race and ethnicity. For instance, the net benefit of MTM among the non-Hispanic White patients was $2498 (95% confidence interval = $1609, $3386) at a willingness-to-pay value of $59,908. The study found no significant difference in net benefits for MTM services between minority and White patients.

Conclusion:

The study provides evidence that MTM is a cost-effective tool for managing medication utilization among the Medicare population. However, MTM may not be cost-effective in reducing racial/ethnic disparities in medication utilization in the short term. Further research is needed to understand the long-term cost-effectiveness of MTM on racial/ethnic disparities.
The effect of massage on patients with chronic fatigue syndrome: A systematic review and meta-analysis
Authors: Li Jingnan , Piao Feng , Zeng Qiaoqiao , Yan Huixin , Bi Yunpeng , Zhang Shaobo , Song Bailin
Published: May 2024

Background:

Chronic fatigue syndrome (CFS) is a long-term and complex chronic disease that seriously affects the physical and mental health and quality of life of patients. Massage, as one of the methods in traditional Chinese medicine, can treat both symptoms and root causes and is widely used to treat CFS. The main purpose is to systematically evaluate the impact of massage therapy on the efficacy and safety of CFS patients, providing a reference for clinical practice.

Methods:

By searching for literature published in PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, VIP Database, and China National Knowledge Infrastructure Database until November 2023, randomized controlled trial studies were selected according to the established inclusion and exclusion criteria. The Cochrane system evaluation manual was used to evaluate the quality of the included studies, and RevMan5.4 software was used for meta-analysis.

Results:

32 randomized controlled trials were included, with a total of 2594 CFS patients. Meta-analysis showed that the total score of the fatigue scale (FS-14) in the treatment group, MD = −1.59, 95% CI (−1.84, −1.34), P < .00001; Physical fatigue score, MD = −1.30, 95% CI (−1.60, −1.00), P < .00001; Mental fatigue score, MD = −0.84, 95% CI (−0.99, −0.72), P < .0001]; Effective rate [RR = 1.23, 95% CI (1.19,1.28), P < .00001]; all indicators were superior to the control group, Only one study reported adverse reactions, including local swelling, skin bruising, and nausea.

Conclusion:

Our research findings suggest that massage therapy has a significant therapeutic effect on CFS, avoiding adverse reactions and improving fatigue symptoms. Therefore, massage therapy for chronic fatigue syndrome should be further promoted and applied.
Finite element analysis of modified Slongo’s external fixation in the treatment of supracondylar humeral fractures in older children
Authors: Zhao Jingxin , Yao Wuyi , Ma Jianxiong , Lu Bin , Ma Xinlong
Published: May 2024

Older children over 8 years old are at higher risk of elbow joint stiffness after treatment of supracondylar humeral fractures. The objective of this study was to improve the Slongo’s external fixation system for treating supracondylar humeral fractures in older children. This would be achieved by increasing fixation strength and providing a theoretical basis through finite element analysis and mechanical testing. A 13-year-old female patient with a history of previous fracture was selected for CT data processing to create a three-dimensional model of the distal humerus fracture. Two internal fixation models were established, using the Slongo’s external fixation method with Kirschner wire (Group A) and modifying the Slongo’s external fixation (Kirschner wire tail fixation) (Group B). The fracture models were then subjected to mechanical loading analysis using Finite Element Analysis Abaqus 6.14 software to simulate separation, internal rotation, and torsion loads. A PVC humeral bone model was used to create a supracondylar fracture model, and the A and B internal fixation methods were applied separately. The anterior–posterior and torsional stresses were measured using the Bose Electroforce3510 testing system, followed by a comparative analysis. The finite element simulation results showed that under the same tensile, torsion, and inversion forces, the osteotomy model fixed with Kirschner wire at the distal end in Group B exhibited smaller tensile stress and deformation compared to the unfixed osteotomy model in Group A. This indicated that the fixation strength of Group B was superior to that of Group A. According to the test results of the Bose Electroforce3510 testing system, a simple linear regression analysis was conducted using SPSS software. The K values of rotation angle-torque tests and front and rear displacement-stress tests were calculated for Groups A and B, with Group B showing higher values than Group A. The results of this study supported the significantly enhanced biomechanical reliability and stability of fracture fixation in Group B, which utilized the modified Slongo’s external fixation (Kirschner wire tail fixation). This optimized method provides a new choice for the clinical treatment of supracondylar humeral fractures in older children, backed by both clinical evidence and theoretical basis.
How artificial intelligence can provide information about subdural hematoma: Assessment of readability, reliability, and quality of ChatGPT, BARD, and perplexity responses
Authors: Gül Şanser , Erdemir İsmail , Hanci Volkan , Aydoğmuş Evren , Erkoç Yavuz Selim
Published: May 2024

Subdural hematoma is defined as blood collection in the subdural space between the dura mater and arachnoid. Subdural hematoma is a condition that neurosurgeons frequently encounter and has acute, subacute and chronic forms. The incidence in adults is reported to be 1.72–20.60/100.000 people annually. Our study aimed to evaluate the quality, reliability and readability of the answers to questions asked to ChatGPT, Bard, and perplexity about “Subdural Hematoma.” In this observational and cross-sectional study, we asked ChatGPT, Bard, and perplexity to provide the 100 most frequently asked questions about “Subdural Hematoma” separately. Responses from both chatbots were analyzed separately for readability, quality, reliability and adequacy. When the median readability scores of ChatGPT, Bard, and perplexity answers were compared with the sixth-grade reading level, a statistically significant difference was observed in all formulas (P < .001). All 3 chatbot responses were found to be difficult to read. Bard responses were more readable than ChatGPT’s (P < .001) and perplexity’s (P < .001) responses for all scores evaluated. Although there were differences between the results of the evaluated calculators, perplexity’s answers were determined to be more readable than ChatGPT’s answers (P < .05). Bard answers were determined to have the best GQS scores (P < .001). Perplexity responses had the best Journal of American Medical Association and modified DISCERN scores (P < .001). ChatGPT, Bard, and perplexity’s current capabilities are inadequate in terms of quality and readability of “Subdural Hematoma” related text content. The readability standard for patient education materials as determined by the American Medical Association, National Institutes of Health, and the United States Department of Health and Human Services is at or below grade 6. The readability levels of the responses of artificial intelligence applications such as ChatGPT, Bard, and perplexity are significantly higher than the recommended 6th grade level.
Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study
Authors: Ding Wenjing , Chen Liangliang , Xia Jianguo , Pei Bei , Song Biao , Li Xuejun
Published: May 2024

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264–0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056–1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234–2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022–1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382–0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085–0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.
The role of platelet large cell ratio in determining mortality in COVID-19 patients
Authors: Çelik Onur , Laloğlu Esra , Çelik Neslihan
Published: May 2024

Inflammatory mechanisms have been implicated and have been subject to research in the clinical course of COVID-19 patients. In this study, platelet large cell ratio (P-LCR) has been examined as a novel prognostic and inflammatory parameter. A total of 1992 COVID-19-positive patients admitted to COVID-19 unit of Infectious Diseases were included. In order to identify a potential relationship between P-LCR and mortality, surviving patients were compared with subjects who died as a result of the disease. Although P-LCR levels showed a steady increase in all COVID-19 patients after admission, they were significantly higher in those who eventually died (P < .001), indicating a positive correlation between mortality and P-LCR. The P-LCR levels of patients followed up in the intensive care unit were statistically significantly higher than those followed up in the ward (P < .001). P-LCR levels of patients intubated in intensive care unit were statistically significantly higher than those who were not intubated (P < .001). Also, P-LCR levels were subdivided into 3 categories as normal, low, and elevated. Elevated P-LCR was found to be positively correlated with leukocyte count, neutrophil count, D-dimer, troponin, ferritin, and C-Reactive Protein (CRP) and showed negative correlation with fibrinogen, lymphocyte count, and platelet count. As P-LCR was correlated with the severity of inflammation in all COVID-19 patients, it was significantly higher in those patients who died. Elevated P-LCR was considered to be associated with the risk of severe disease and death. This inexpensive, readily available test may be incorporated into our clinical practice as a novel marker of poor prognosis in addition to other valuable laboratory parameters.
Efficacy and safety of transarterial chemoembolization combined with targeted therapy and immunotherapy versus with targeted monotherapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Feng Jingwen , Zhao Yi , Zhai Lin , Zhou Jingxu
Published: May 2024

Background and objective:

The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma (HCC) has gained increasing attention. However, there are variations in the efficacy and safety outcomes between TACE-T-I versus TACE combined with targeted drugs (TACE-T). This study aims to systematically evaluate the efficacy and safety of TACE-T-I versus TACE-T in unresectable HCC.

Methods:

PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 21, 2023, for comparative studies on TACE-T-I versus TACE-T for unresectable HCC. Outcome measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (TRAEs). OS was the primary outcome of this study. Weighted mean difference (WMD) or hazard ratio (HR) was used as the pooled statistic for OS and PFS. Relative risk (RR) was employed as the pooled statistic for ORR, DCR and the incidence of TRAEs. And 95% confidence intervals (CIs) were calculated for all effect measures. Data analysis was conducted using Stata 14.0 software.

Results:

The meta-analysis included 14 studies with 2144 patients. The pooled results showed that compared with patients in the TACE-T group, patients in the TACE-T-I group had higher ORR (RR = 1.61; 95%CI: 1.38–1.89) and DCR (RR = 1.17; 95%CI: 1.09–1.26). Patients in the TACE-T-I group experienced prolonged PFS (WMD = 3.08; 95%CI: 2.63–3.53) and OS (WMD = 5.76; 95%CI: 4.68–6.84). And the risk of disease progression (HR = 0.45; 95%CI: 0.37–0.55) and death (HR = 0.43; 95%CI: 0.38–0.49) was lower in the TACE-T-I group. Common TRAEs included fever, pain, abdominal pain, nausea, vomiting, elevated ALT, elevated AST, hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence and severity of TRAEs in the TACE-T-I group were similar to those in the TACE-T group, with no significant differences (P > .05).

Conclusion:

Current evidence suggests that, on the basis of TACE combined with targeted therapy, the addition of immunotherapy provides better clinical efficacy and survival benefits for unresectable HCC patients, with good tolerability.
In vitro antileishmanial activities of hydro-methanolic crude extracts and solvent fractions of Clematis simensis fresen leaf, and Euphorbia abyssinica latex
Authors: Worku Kassahun Misgana , Araya Dawit , Tesfa Habtie , Birru Eshetie Melese , Hailu Asrat , Aemero Mulugeta
Published: May 2024

As a result of increasing drug resistance, crossover resistance development, prolonged therapy, and the absence of different agents with innovative methods for implementation, the efficacy of recent antileishmanial medications is severely declining. So, it is vital to look for other medications from botanical remedies that have antileishmanial activity. The latex of Euphorbia abyssinica (E abyssinica) and the leaves of Clematis simensis fresen (C simensis) were macerated in methanol (80%). In vitro antileishmanial activity of the preparation was tried on promastigotes of Leishmania aethiopica (L aethiopica) and Leishmania donovani (L donovani) using resazurin assay, and fluorescence intensity was measured. One percent of dimethyl sulfoxide (DMSO) and media as negative control and amphotericin B as positive control were used. Additionally, hemolytic & phytochemical tests of the preparation were done. The mean and standard errors of each extract were evaluated and interpreted for statistical significance using one-way analysis of variance. From sigmoidal dose-response curves of % inhibition, half maximal inhibitory concentration (IC50) values were determined by GraphPad Prism and Microsoft Excel; outcomes were presented as mean ± standard error of mean of triplicate trials. P < .05 was statistical significance. The phytochemical screening of C simensis and E abyssinica confirmed the existence of steroids, phenols, tannins, saponins, alkaloids, terpenoids, flavonoids and glycosides. C simensis possesses antileishmanial activity with IC50 outcomes of 46.12 ± 0.03 and 8.18 ± 0.10 µg/mL on the promastigotes of L aethiopica and L donovani, respectively. However, E abyssinica showed stronger activity with IC50 outcomes of 16.07 ± 0.05 µg/mL and 4.82 ± 0.07 µg/mL on L aethiopica and L donovani, respectively. C simensis and E abyssinica have a less hemolytic effect on human red blood cells at low concentrations. The outcomes from this investigation demonstrated that the preparation of C simensis and E abyssinica indicated significant antileishmanial activity. Therefore, further in vivo assessment of antileishmanial, cytotoxicity activity and quantitative identification of secondary metabolites are highly recommended.