bluuebunny/crossref_metadata_2025 huggingface dataset:
How Immunocompromised Hosts Were Left Behind in the Quest to Control the COVID-19 Pandemic
Authors: Boeckh Michael , Pergam Steven A , Limaye Ajit P , Englund Janet , Corey Lawrence , Hill Joshua A
Published: June 2024

The immunocompromised population was disproportionately affected by the severe acute respiratory syndrome coronavirus 2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. Although the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here, we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises.
From microcosm to macrocosm: adaptive radiation of Darwin’s finches
Authors: Grant Peter R , Grant B Rosemary
Published: June 2024

In this Perspective we show the value of studying living organisms in the field to understand their history. Darwin’s finches are an iconic example of the early stages of speciation in a young adaptive radiation that produced 18 species in little more than a million years. The question they pose is how and why so many species originated and diversified rapidly. A long-term study of four species of finches on the small island of Daphne Major, combined with genomic investigations, provide some answers in terms of extrinsic and intrinsic factors. Beak size and shape, as well as body size, are key heritable features involved in both ecological and reproductive isolation, and their evolution by natural selection was caused by competitor species during prolonged droughts. Introgressive hybridization of related species is rare but recurring, apparently widespread, increases genetic variation, and does not incur a fitness cost. Hybridization can produce a new species. We use a phylogeny based on whole genome sequences of the four finches to infer morphological transitions in their radiation. Several lines of evidence indicate that some species are missing from the early phase of the radiation due to extinction. Combining these results, we re-cast the classical allopatry-then-sympatry theory of adaptive radiation as a competition-selection-hybridization process that generates a diversity of species.
Acquisitions of behavioral health treatment facilities from 2010 to 2021
Authors: Thornburg Ben , McGinty Emma B , Eddelbuettel Julia , Kennedy-Hendricks Alene , Braun Robert T , Eisenberg Matthew D
Published: June 2024

Private equity (PE) and other for-profit ownership of behavioral health (mental health and substance use) treatment facilities have become increasingly prevalent, but data on these acquisitions are not readily available. In this study, we describe a novel database that contains information on the universe of behavioral health acquisitions that occurred between 2010 and 2021. We found that the frequency of behavioral health facilities involved in acquisitions increased substantially, from 32 facilities in 2010 to 1330 in 2021. The total number of facilities involved in acquisitions was 2806. Most of these facilities provided outpatient services only (N = 2073) and offered only mental health services (N = 1428). Private equity-backed acquisitions accounted for around 60% of all acquisition activity (N = 1678 facilities PE, N = 1128 facilities other for-profit). 25% of acquired facilities were located within 20 miles of one another (N = 561), 50% occurred within 80 miles (N = 1403), and 75% occurred within 319 miles (N = 2104). Future research should evaluate the effects of this consolidation on behavioral healthcare access, quality, spending, and patient outcomes.
Metabolome profiling and transcriptome analysis unveiling the crucial role of magnesium transport system for magnesium homeostasis in tea plants
Authors: Li Jing , Wen Ting , Zhang Ruiming , Hu Xinlong , Guo Fei , Zhao Hua , Wang Pu , Wang Yu , Ni Dejiang , Wang Mingle
Published: June 2024

Magnesium (Mg2+) is a crucial nutrient for the growth and development of Camellia sinensis and is closely related to the quality of tea. However, the underlying mechanisms responding to low-Mg 2+ stress in tea plants remain largely unknown. In this study, photosynthetic parameters, metabolomics, and transcriptomics were utilized to explore the potential effects of low Mg2+ on the growth and metabolism of C. sinensis. Low-Mg2+ treatment increased the ratio of shoot dry weight to root dry weight but decreased the photosynthesis of C. sinensis. Forty and thirty metabolites were impacted by Mg2+ shortage in C. sinensis shoots and roots, respectively. Integrated transcriptome and metabolome analyses revealed the possible reasons for the decreased contents of chlorophyll and catechins and the increased theanine content in C. sinensis roots. Weighted gene co-expression network analysis indicated that the Mg2+ transport system was essential in the regulation of Mg2+ homeostasis in C. sinensis, in which CsMGT5 was identified to be the key regulator according to CsMGT5-overexpressing and complementary assays in Arabidopsis thaliana. Moreover, silencing of CsMGT5 in vivo reduced the content of chlorophyll in C. sinensis shoots. In addition, CsMGT5 might collaborate with ammonium transporters to keep the amino acid content steady, suggesting its potential application for tea quality improvement. All these findings demonstrate the key roles of CsMGTs for Mg2+ homeostasis in C. sinensis, providing a theoretical basis for Mg2+ efficient utilization in plants.
Soil microbial community response to corrinoids is shaped by a natural reservoir of vitamin B12
Authors: Hallberg Zachary F , Nicolas Alexa M , Alvarez-Aponte Zoila I , Mok Kenny C , Sieradzki Ella T , Pett-Ridge Jennifer , Banfield Jillian F , Carlson Hans K , Firestone Mary K , Taga Michiko E
Published: June 2024

Soil microbial communities perform critical ecosystem services through the collective metabolic activities of numerous individual organisms. Most microbes use corrinoids, a structurally diverse family of cofactors related to vitamin B12. Corrinoid structure influences the growth of individual microbes, yet how these growth responses scale to the community level remains unknown. Analysis of metagenome-assembled genomes suggests that corrinoids are supplied to the community by members of the archaeal and bacterial phyla Thermoproteota, Actinobacteria, and Proteobacteria. Corrinoids were found largely adhered to the soil matrix in a grassland soil, at levels exceeding those required by cultured bacteria. Enrichment cultures and soil microcosms seeded with different corrinoids showed distinct shifts in bacterial community composition, supporting the hypothesis that corrinoid structure can shape communities. Environmental context influenced both community- and taxon-specific responses to specific corrinoids. These results implicate corrinoids as key determinants of soil microbiome structure and suggest that environmental micronutrient reservoirs promote community stability.
Whole-genome resequencing reveals the uniqueness of Subei yak
Authors: Guo Shaoke , Yu Tianjun , Wang Xingdong , Zhao Shuangquan , Zhao Erjun , Ainierlitu  , Ba Teer , Gan Manyu , Dong Cunmei , Naerlima  , Yin Lian , Ke Xikou , Dana Dawuti , Guo Xian
Published: June 2024

Subei yak is an essential local yak in the Gansu Province, which genetic resource has recently been discovered. It is a meat-milk dual-purpose variety with high fecundity and relatively stable population genetic structure. However, its population genetic structure and genetic diversity are yet to be reported. Therefore, this study aimed to identify molecular markers of Subei yak genome by whole-genome resequencing, and to analyze the population structure and genetic diversity of Subei yak. This study screened 12,079,496 single nucleotide polymorphism (SNP) molecular markers in the 20 Subei yaks genome using whole-genome resequencing technology. Of these SNPs, 32.09% were located in the intronic region of the genome. Principal component analysis, phylogenetic analysis, and population structure analysis revealed that the Subei yak belonged to an independent group in the domestic yak population. A selective clearance analysis was carried out on Subei yak and other domestic yaks, and the genes under positive selection were annotated. The functional enrichment analysis showed that Subei yak possessed prominent selection characteristics in terms of external environment perception, hypoxia adaptation, and muscle development. Furthermore, Subei yak showed excellent muscle fat deposition and meat quality traits. Thus, this study will serve as a reference for discovering population structure, genetic evolution, and other unique traits of Subei yak and for expanding the genetic variation catalog of yaks.
Structural analysis of code-based algorithms of the NIST post-quantum call
Authors: González de la Torre M A , Encinas L Hernández , García J I Sánchez
Published: June 2024

Code-based cryptography is currently the second most promising post-quantum mathematical tool for quantum-resistant algorithms. Since in 2022 the first post-quantum standard Key Encapsulation Mechanism, Kyber (a latticed-based algorithm), was selected to be established as standard, and after that the National Institute of Standards and Technology post-quantum standardization call focused in code-based cryptosystems. Three of the four candidates that remain in the fourth round are code-based algorithms. In fact, the only non-code-based algorithm (SIKE) is now considered vulnerable. Due to this landscape, it is crucial to update previous results about these algorithms and their functioning. The Fujisaki-Okamoto transformation is a key part of the study of post-quantum algorithms and in this work we focus our analysis on Classic McEliece, BIKE and HQC proposals, and how they apply this transformation to obtain IND-CCA semantic security. Since after security the most important parameter in the evaluation of the algorithms is performance, we have compared the performance of the code-based algorithms of the NIST call considering the same architecture for all of them.
Primary pericardial synovial sarcoma requiring emergency salvage right atrial debulking: a case report
Authors: Ravishankar Ramanish , Makam Rishab , Loubani Mahmoud , Chaudhry Mubarak , Hussain Azar
Published: June 2024

A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion between the heart and diaphragm with a right atrial (RA) filling defect, pericardial thickening and pulmonary metastasis. An RA debulking salvage operation confirmed this to be a pericardial tumour and further cytology and immunohistochemistry testing confirmed a primary synovial sarcoma. After 12 days in intensive care for ventilation, the patient was successfully discharged on warfarin and underwent oncology follow-up for chemotherapy. Following a 15-month follow-up, no mortality was observed despite the aggressive nature of the tumour.
DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces
Authors: Miron Simona , Legrand Pierre , Dupaigne Pauline , van Rossum-Fikkert Sari E , Ristic Dejan , Majeed Atifa , Kanaar Roland , Zinn-Justin Sophie , Zelensky Alex N
Published: June 2024

In vertebrates, the BRCA2 protein is essential for meiotic and somatic homologous recombination due to its interaction with the RAD51 and DMC1 recombinases through FxxA and FxPP motifs (here named A- and P-motifs, respectively). The A-motifs present in the eight BRC repeats of BRCA2 compete with the A-motif of RAD51, which is responsible for its self-oligomerization. BRCs thus disrupt RAD51 nucleoprotein filaments in vitro. The role of the P-motifs is less studied. We recently found that deletion of Brca2 exons 12–14 encoding one of them (the prototypical ‘PhePP’ motif), disrupts DMC1 but not RAD51 function in mouse meiosis. Here we provide a mechanistic explanation for this phenotype by solving the crystal structure of the complex between a BRCA2 fragment containing the PhePP motif and DMC1. Our structure reveals that, despite sharing a conserved phenylalanine, the A- and P-motifs bind to distinct sites on the ATPase domain of the recombinases. The P-motif interacts with a site that is accessible in DMC1 octamers and nucleoprotein filaments. Moreover, we show that this interaction also involves the adjacent protomer and thus increases the stability of the DMC1 nucleoprotein filaments. We extend our analysis to other P-motifs from RAD51AP1 and FIGNL1.
Site-specific regulation of RNA editing with ribose-modified nucleoside analogs in ADAR guide strands
Authors: Jauregui-Matos Victorio , Jacobs Olivia , Ouye Randall , Mozumder Sukanya , Salvador Prince J , Fink Kyle D , Beal Peter A
Published: June 2024

Adenosine Deaminases Acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine to inosine in RNA duplexes. These enzymes can be harnessed to correct disease-causing G-to-A mutations in the transcriptome because inosine is translated as guanosine. Guide RNAs (gRNAs) can be used to direct the ADAR reaction to specific sites. Chemical modification of ADAR guide strands is required to facilitate delivery, increase metabolic stability, and increase the efficiency and selectivity of the editing reaction. Here, we show the ADAR reaction is highly sensitive to ribose modifications (e.g. 4′-C-methylation and Locked Nucleic Acid (LNA) substitution) at specific positions within the guide strand. Our studies were enabled by the synthesis of RNA containing a new, ribose-modified nucleoside analog (4′-C-methyladenosine). Importantly, the ADAR reaction is potently inhibited by LNA or 4′-C-methylation at different positions in the ADAR guide. While LNA at guide strand positions −1 and −2 block the ADAR reaction, 4′-C-methylation only inhibits at the −2 position. These effects are rationalized using high-resolution structures of ADAR-RNA complexes. This work sheds additional light on the mechanism of ADAR deamination and aids in the design of highly selective ADAR guide strands for therapeutic editing using chemically modified RNA.
Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception
Authors: Dou Yan-Nong , Liu Yuan , Ding Wen-Qun , Li Qing , Zhou Hua , Li Ling , Zhao Meng-Ting , Li Zheng-Yi-Qi , Yuan Jing , Wang Xiao-Fei , Zou Wang-Yuan , Li Anan , Sun Yan-Gang
Published: June 2024

Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEAMOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEAMOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms.
Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome
Authors: Chanh Ho Quang , Trieu Huynh Trung , Tran Kim Hung , Huynh Ngoc Thien Vuong , Huyen Vu Ngo Thanh , Moncada Alexandra , Thanh Nguyen Thi Kieu , Duyen Huynh Thi Le , Nguyen-Lyle Ngan , Vuong Nguyen Lam , Lam Phung Khanh , McBride Angela , Phan Tu Qui , Dong Thi Hoai Tam , Wills Bridget , Yacoub Sophie
Published: June 2024

Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. We performed a prospective cohort study in Viet Nam. Children ≥5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7–10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumourigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock. Ninety DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage haemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P < 0.01 (OR = 1.82, 95% CI 1.07–3.35, P = 0.038). Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.
Critical Differences between Typical Arc Magmas and Giant Porphyry Cu ± Au Systems: Implications for Exploration
Authors: Hao Hongda , Campbell Ian H , Park Jung-Woo
Published: June 2024

Porphyry Cu, and porphyry Cu–Au deposits, are associated with arc magmatism and their ore-forming systems generally follow the magmatic evolution of typical arcs. However, most arc magmas are barren and giant economic porphyry Cu ± Au deposits are rare. In this study, we model variations in rare earth element concentrations in evolving arc magmas and giant porphyry Cu ± Au systems to quantify the percentage of the fractionating minerals required to produce the observed changes. We find that, during the andesitic stage of fractionation, ore-forming systems in thick crusts fractionate ~35% more amphibole than an average of thick arc magma systems (the thick-crust reference suite) and that ore-forming systems in thin crusts fractionate twice as much amphibole as their equivalent thin-arc magma reference suite. Thick-crust ore-forming suites also fractionate ~50% less plagioclase, and thin-crust ore systems ~40% less plagioclase, than their associated reference suites during the same andesitic stage of fractionation. Taken together, these observations imply that ore-producing magmas are appreciably wetter than their associated barren reference suites. Our modeling also shows that ~80% more amphibole is required to reproduce the andesite stage of fractionation in the thick-crust reference suite than in its thin-crust equivalent, suggesting that magmas produced under thick crusts are wetter than those produced under thin crusts. On the other hand, the chalcophile element contents of the thick- and thin-crust ore-forming systems are similar to and higher than those of the thick- and thin-crust reference suites, respectively. Therefore, we suggest that the high water content plays a critical role in the formation of giant porphyry Cu ore in thick crusts, whereas both high chalcophile contents and high water contents are required to form giant porphyry Cu–Au deposits in thin crusts. The high fraction of amphibole fractionation in giant economic porphyry suites, compared with their relevant reference suites, results in lower Y in the ore-associated suites and this difference increases with fractionation. As a consequence, plots of Y against MgO can be used to identify porphyries that have economic potential and are preferred to Sr/Y plots because they are less affected by the intense alteration associated with giant porphyry Cu ± Au deposits.
Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration
Authors: Kim Woo-Jin , Ryu Jeong-Hyun , Kim Ji Won , Kim Ki-Tae , Shin Hye-Rim , Yoon Heein , Ryoo Hyun-Mo , Cho Young-Dan
Published: June 2024

Clinical bone-morphogenetic protein 2 (BMP2) treatment for bone regeneration, often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems, necessitates research into improved biomaterials for better BMP2 stability and retention. To tackle this challenge, we introduced a groundbreaking bone-targeted, lipoplex-loaded, three-dimensional bioprinted bilayer scaffold, termed the polycaprolactone-bioink-nanoparticle (PBN) scaffold, aimed at boosting bone regeneration. We encapsulated BMP2 within the fibroin nanoparticle based lipoplex (Fibroplex) and functionalized it with DSS6 for bone tissue-specific targeting. 3D printing technology enables customized, porous PCL scaffolds for bone healing and soft tissue growth, with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex, shown to support effective nutrient exchange and cell growth at specific pore sizes. The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue, a finding validated by in vitro osteogenic differentiation assays. The PBN scaffold was evaluated for critical calvarial defects, focusing on sustained BMP2 delivery, prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo. The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge, promoting osteogenic differentiation and bone regeneration in a calvarial defect animal. Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation, thereby reducing the risk of heterotopic ossification.
Sociodemographic and Health Factors of the Alcohol Treatment-seeking Population in New South Wales, Australia
Authors: Heijstee Nathan , Black Eleanor , Black Emma , Demirkol Apo , Mammen Kristie , Mills Llewellyn , Deacon Rachel , Ezard Nadine , Montebello Mark , Reid David , Bruno Raimondo , Shakeshaft Anthony , Siefried Krista J. , Farrell Michael , Lintzeris Nicholas
Published: June 2024

Objectives

Although factors associated with alcohol use have been researched at a population level, descriptions of the alcohol and other drug (AOD) treatment-seeking population in New South Wales (NSW), Australia, are limited. This study addresses this gap by analyzing sociodemographic and health characteristics in the NSW AOD treatment-seeking population.

Methods

Self-reported Australian Treatment Outcomes Profile data on substance use, health ratings, and sociodemographic factors were acquired from public AOD services (offering services from counseling to ambulatory/inpatient withdrawal management) in 6 administrative health districts from 2016 to 2019 (n = 14,287). Gaussian and multiple logistic regressions were conducted to examine associations between these factors and alcohol consumption quantity.

Results

Data were analyzed for patients seeking treatment for alcohol consumption specifically (n = 5929; median age, 44 years; 65% male). Valid alcohol consumption data were available for 5460 patients, among whom the mean volume of alcohol consumed was 311 standard drinks (3110 grams of ethanol) over the past 28 days and 15 standard drinks (150 grams of ethanol) per occasion. Higher volumes were consumed by males and those with recent experiences of violence and/or injecting drug use. Caring for children younger than 5 years and having above-median health ratings were associated with lower alcohol consumption.

Conclusions

This study contributes to the characterization of the NSW public AOD treatment population and identifies associations between alcohol consumption, sociodemographic factors, and health ratings among people seeking treatment for alcohol consumption. Findings point towards multilevel assessment and comprehensive interventions for people engaging in treatment for alcohol use. Future research should address barriers to treatment.
Kava Withdrawal Treated With Phenobarbital—A Case Report and Literature Review
Authors: Cassidy Ryan Michael , Burdick Kalli , Anesi Trevor , Daunis Daniel
Published: June 2024

Kava consumption is a traditional practice in Polynesian and Micronesian cultures. It has recently gained popularity in the United States for therapeutic and recreational use. We report the following case. A man presented to the emergency department after a fall while intoxicated on kava. He was medically admitted for altered mental status, facial and clavicle fractures, and hyponatremia. Psychiatry was consulted for management of delirium. On interview, he reported consuming escalating amounts of kava for weeks despite attempts to stop. He was diagnosed with acute kava withdrawal with hyperactive delirium, treated with phenobarbital load (860 mg) and taper (390 mg). Continuous dexmedetomidine drip to hospital day 3 treated sympathetic activation and breakthrough agitation. By day 4, his delirium resolved and remained in remission until discharge. We performed a systematic review for reports of kava withdrawal, returning 9 studies. Eight assessed withdrawal symptoms after cessation of a low controlled dose of kava extract with no symptoms noted. One reported a case series of heavy kava users with seizure-like events. No publications discussed treatment of kava withdrawal. To our knowledge, this is the first publication to describe kava withdrawal syndrome and its effective treatment with phenobarbital.
Quick Estimation of Minimum Hearing Levels Using a Binaural Multifrequency Stimulus Paradigm: Proof of Concept
Authors: Gargeshwari Aditi , Krishnan Ananthanarayan , Delgado Rafael E.
Published: June 2024

Objectives:

Objective estimation of minimum hearing levels using auditory brainstem responses (ABRs) elicited by single frequency tone-bursts presented monaurally is currently considered the gold standard. However, the data acquisition time to estimate thresholds (for both ears across four audiometric frequencies) using this method usually exceeds the sleep time (ranging between 35 and 49 minutes) in infants below 4 months, thus providing incomplete information of hearing status which in turn delays timely clinical intervention. Alternate approaches using faster rate, or tone-burst trains have not been readily accepted due to additional hardware and software requirements. We propose here a novel binaural multifrequency stimulation paradigm wherein several stimuli of different frequencies are presented binaurally in an interleaved manner. The rationale here is that the proposed paradigm will increase acquisition efficiency, significantly reduce test time, and improve accuracy by incorporating an automatic wave V detection algorithm. It is important to note that this paradigm can be easily implemented in most commercial ABR systems currently used by most clinicians.

Design:

Using this binaural multifrequency paradigm, ear specific ABRs were recorded in 30 normal-hearing young adults to both tone-bursts, and narrow-band (NB) iChirps at 500, 1000, 2000, and 4000 Hz. Comparison of ABRs elicited by tone-bursts and narrow-band chirps allowed us to determine if NB iChirps elicited a more robust wave V component compared with the tone-bursts. ABR data were characterized by measures of minimum hearing levels; wave V amplitude; and response detectability for two electrode configurations (high forehead-C7; and high forehead-linked mastoids).

Results:

Consistent with the research literature, wave V response amplitudes were relatively more robust for NB iChirp stimuli compared with tone-burst stimuli. The easier identification and better detectability of wave V for the NB iChirps at lower stimulus levels contributed to their better thresholds compared with tone-burst elicited responses. It is important to note that binaural multifrequency hearing levels close to minimum hearing levels were determined in approximately 22 minutes using this paradigm—appreciably quicker than the 45 to 60 minutes or longer time required for threshold determination using the conventional single frequency method.

Conclusions:

Our novel and simple paradigm using either NB iChirps or tone-bursts provides a reliable method to rapidly estimate the minimum hearing levels across audiometric frequencies for both ears. Incorporation of an automatic wave V detection algorithm increases objectivity and further reduce test time and facilitate early hearing identification and intervention.
The Effect of Intraoperative Overdistraction on Subsidence Following Anterior Cervical Discectomy and Fusion
Authors: Duey Akiro H. , Gonzalez Christopher , Hoang Timothy , Geng Eric A. , Ferriter Pierce J. , Rosenberg Ashley M. , Zaidat Bashar , Zapolsky Ivan J. , Kim Jun S. , Cho Samuel K.
Published: June 2024

Study Design:

Retrospective cohort.

Objective:

The purpose of this study was to evaluate the effect of overdistraction on interbody cage subsidence.

Background:

Vertebral overdistraction due to the use of large intervertebral cage sizes may increase the risk of postoperative subsidence.

Methods:

Patients who underwent anterior cervical discectomy and fusion between 2016 and 2021 were included. All measurements were performed using lateral cervical radiographs at 3 time points – preoperative, immediate postoperative, and final follow-up >6 months postoperatively. Anterior and posterior distraction were calculated by subtracting the preoperative disc height from the immediate postoperative disc height. Cage subsidence was calculated by subtracting the final follow-up postoperative disc height from the immediate postoperative disc height. Associations between anterior and posterior subsidence and distraction were determined using multivariable linear regression models. The analyses controlled for cage type, cervical level, sex, age, smoking status, and osteopenia.

Results:

Sixty-eight patients and 125 fused levels were included in the study. Of the 68 fusions, 22 were single-level fusions, 35 were 2-level, and 11 were 3-level. The median final follow-up interval was 368 days (range: 181–1257 d). Anterior disc space subsidence was positively associated with anterior distraction (beta = 0.23; 95% CI: 0.08, 0.38; P = 0.004), and posterior disc space subsidence was positively associated with posterior distraction (beta = 0.29; 95% CI: 0.13, 0.45; P < 0.001). No significant associations between anterior distraction and posterior subsidence (beta = 0.07; 95% CI: −0.06, 0.20; P = 0.270) or posterior distraction and anterior subsidence (beta = 0.06; 95% CI: −0.14, 0.27; P = 0.541) were observed.

Conclusions:

We found that overdistraction of the disc space was associated with increased postoperative subsidence after anterior cervical discectomy and fusion. Surgeons should consider choosing a smaller cage size to avoid overdistraction and minimize postoperative subsidence.
Physical activity and cardiac rehabilitation for the primary and secondary prevention of heart failure
Authors: Komuro Kaoruko , Komuro Jin , Ueno Kensuke , Kaneko Hidehiro , Komuro Issei
Published: June 2024

Heart failure (HF) is a mounting global health and financial concern. With the introduction of angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, outcomes for HF have improved dramatically in recent years, however, the increase in HF cases remains uncontrolled, and reliance on current medical treatment alone is no longer sufficient. Therefore, primary prevention through exercise habits and secondary prevention through cardiac rehabilitation (CR) are becoming increasingly important to reduce the number of HF cases. We have previously highlighted the benefits of adopting a healthy lifestyle in preventing cardiovascular disease (CVD), even in individuals with cancer. Our findings underscore the importance of incorporating regular exercise into lifestyle modification and highlight the critical role of exercise habits in primary prevention, especially in terms of CVD prevention. The importance of CR is emphasized in the many guidelines such as European, American, and Japanese guidelines. CR is given a Class I recommendation due to its association with improved prognosis for patients with HF. Furthermore, early initiation of CR is recommended, especially for older patients with HF, because CR has been reported to reduce the length of stay and prevent rehospitalization. In addition to the existing evidence, the Nationwide Population-Based Database in Japan has indicated the importance of CR in patients with acute HF and of enhancing gait speed in preventing HF. Although the importance of CR is recognized worldwide, actual utilization of CR by patients remains low. The challenge for the future is to raise awareness among attending physicians and patients about the importance of exercise habits and CR by actively promoting individualized rehabilitation.
Serum amylase as a novel prognostic marker of organophosphorus poisoning: a retrospective study
Authors: Guo Xinxin , Chen Zhongwei , Feng Ke , Zeng Siyao , Zhang Junfei , Ma Zhe , Yuan Changda
Published: June 2024

Background

This study aims to explore the significance of serum amylase levels in patients with organophosphorus pesticide (OP) poisoning and to provide a new perspective for evaluating the severity and prognosis of OP poisoning.

Methods

The clinical data of 67 patients with acute OP poisoning, who had been treated in the emergency department of the General Hospital of Ningxia Medical University between September 2020 and August 2022, were retrospectively analyzed. Using Spearman rank correlation, serum amylase levels during admission and severity of poisoning correlated with discharge outcomes. Based on serum amylase levels, receiver operating characteristic curves were plotted to predict the severity and mortality of patients who experience organophosphate poisoning. The optimal threshold serum amylase level at admission was determined based on the maximum Youden index.

Results

Using Spearman rank correlation analysis, serum amylase levels at admission positively correlated with the severity of poisoning and discharge outcomes, but the degree of correlation was weak (r
s: 0.344; 0.264; P < 0.05). The patients’ serum amylase levels at admission had receiver operating characteristic area under the curve values of 0.726 and 0.735 to predict the degree of severe poisoning and death, respectively. Based on the maximum Youden index, the optimal threshold of serum amylase were 97.8 and 194.1 U/L when the degree of poisoning was severe and the discharge outcome of patients was died. In comparison to patients with serum amylase levels ≤194.1 U/L at admission, the OR values of death in patients with serum amylase levels >194.1 U/L at admission was 15.944 (95% CI: 1.825–139.274).

Conclusion

Serum amylase levels in patients with organophosphate poisoning correlate with the degree of poisoning and discharge outcomes. Higher serum amylase level was a risk factor for organophosphorus poisoning death.
The Pathophysiology of Keratoconus
Authors: Vought Rita , Greenstein Steven A. , Gelles John , Hersh Peter S.
Published: June 2024

Purpose:

Keratoconus is a progressive disease characterized by changes in corneal shape, resulting in loss of visual function. There remains a lack of comprehensive understanding regarding its underlying pathophysiology. This review aims to bridge this gap by exploring structural failures and inflammatory processes involved in the etiology and progression of keratoconus.

Methods:

A literature review was conducted using PubMed and Google Scholar databases, screening for articles published in English using the keyword combinations of “keratoconus” with “pathophysiology,” “pathology,” “metabolism,” “inflammatory,” “oxidative stress,” “cytokines,” “enzymes,” “collagen,” and “cornea.” Articles published between January 1, 1970, and June 1, 2023, were queried and reviewed, with greater emphasis placed on more recent data. Fifty-six relevant studies were examined to develop a thorough review of the pathophysiological mechanisms at play in keratoconus.

Results:

Biomechanical structural failures in the cornea seem to be the primary militating factors in keratoconus etiology and progression. These include disruptions in the arrangement in the collagen lamellae, a decrease in collagen levels, a decrease in natural collagen crosslinking, and changes in lysosomal enzyme activity. Immunologic changes have also been identified in keratoconus, challenging the traditional view of the condition as noninflammatory. Elevated levels of proinflammatory cytokines like IL-1b, IL-6, IL-17, and TNF-α have been observed, along with increased apoptosis of keratocytes. Increased oxidative stress leads to the activation of collagenase and gelatinase enzymes.

Conclusions:

Keratoconus is a complex condition influenced by both structural defects and inflammatory processes. Understanding these mechanisms can inform clinical management and potentially lead to more effective treatments.
Prognosis and immune infiltration analysis of m6A RNA methylation regulators in cutaneous melanoma and differential analysis with cuproptosis related genes
Authors: Tian Cui-cui , Shi Hao-ze , Zhang Cong-cong , Kong Ying-qi , Chen Hao
Published: June 2024

Objective:

N6-methyladenosine (m6A) modification and cuproptosis play essential roles in the pathogenesis of various malignant tumors. However, the predictive role of m6A regulators and cuproptosis-related genes in cutaneous melanoma (CM) remains unclear. In this study, the aim was not only to explore the role of m6A modification in CM, but also to investigate the differential expression of cuproptosis-related genes in different risk group.

Methods:

We obtained transcriptome data from the XENA and GTEx databases. Univariate Cox regression analysis was performed to investigate the relationship between m6A-related genes and the outcomes of CM. LASSO regression analysis was utilized to construct a risk model. Moreover, we analyzed immune cell infiltration using CIBERSORT algorithms. Finally, we evaluated the expression levels of cuproptosis-related genes in CM samples and performed RT-qPCR to validate the expression of cuproptosis-associated genes in melanoma cells after YTHDF3 knockdown.

Results:

All m6A-related genes differed in melanoma tissues and normal tissues and a prognostic signature was developed. Immune infiltration revealed that low-risk group patients had a higher level of CD8 + T cells, memory activated CD4 + T cells, activated NK cells and M1 Macrophages than high-risk group (P<0.05). Moreover, the cuproptosis-related genes MTF-1, PDHB and FDX1 were significantly negatively associated with risk score (P=0.0007, P=0.0057 and P=0.04, respectively). We also found that downregulation YTHDF3 in melanoma cells affected the expression of cuproptosis-related genes. (P<0.01 and P<0.05).

Conclusion:

Our study demonstrated the prognostic value of m6A-related genes and cuproptosis-related genes in CM, providing new predictive models and potential therapeutic targets for CM.
To choose or not to choose a nurse practitioner fellowship: An opinion piece on why to choose
Authors: Kuhnly Nicole
Published: June 2024

New graduate nurse practitioners (NPs) often face a challenging learning curve, especially in specialized fields. The quality of clinical experiences and education varies widely across NP programs, and NP Fellowships offer an extension of formal education and clinical experiences. This editorial offers a personal perspective into the NP Fellowship experience and affirms their value to improve the standard of patient care and equip novice NPs for a sustainable career.
Association between hyperuricemia and chronic total coronary occlusion in non–chronic kidney disease populations: a cross-sectional study
Authors: Wang Jianping , Chen Xiaoli , He Zhongwei , Xiao Lian , Xiao Kaiyong , Zhao Lin , Yu Qiang , Hou Yulin , Li Qingrui , He Lei , Feng Hui , Luo Xiaowen
Published: June 2024

Background

Chronic total coronary occlusion (CTO) is an extremely hazardous condition that leads to various clinical phenomena and complications and results in social and economic burdens. Hyperuricemia (HU) is often associated with atherosclerosis. Few studies, however, have investigated the risk of CTO in individuals with HU and the role of traditional cardiovascular risk factors in this setting.

Methods

A cohort of 1245 individuals without chronic kidney disease from southwest China who underwent coronary angiography between February 2018 and June 2021 were enrolled. CTO was defined as a total occlusion of any coronary artery or arteries for more than 3 months. HU was defined as a serum uric acid level of ≥420 µmol/L in men and ≥360 µmol/L in women. Univariate and multivariate logistic regression models and subgroup analyses were applied to assess the relationship between HU and CTO.

Results

After adjustment, HU was noted to be associated with a 1.47-fold increase in the risk of CTO [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06–2.58; P = 0.026]. As a continuous variable, uric acid was an independent predictor of CTO (OR, 1.002; 95% CI, 1.001–1.004; P = 0.047). Subgroup analyses showed that the risk of CTO was higher among individuals under 65 years of age (OR, 2.77; 95% CI, 1.3–5.89), nonobese individuals (OR, 1.9; 95% CI, 1.16–3.1), and those with dyslipidemia (OR, 1.8; 95% CI, 1.04–3.11), while sex, smoking, hypertension, and diabetes did not show similar effects. Interaction analyses revealed no interaction among subgroups.

Conclusion

Among individuals residing in southwest China, HU was associated with an increased risk of CTO in non-CKD individuals, especially those under 65 years of age and nonobese and dyslipidemic individuals.
Deficiency of adenosine deaminase 2 (DADA2) with bilateral renal subcapsular hematoma: a case report and literature review
Authors: Tuqan Anas R. , Barabrah Anas M. , Zaben Basel A. , Shehadeh Mohammad Hakam , Adas Motaz M.
Published: June 2024

Introduction and importance:

Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive genetic disorder caused by loss-of-function mutations in the adenosine deaminase 2 (ADA2) gene. This condition primarily manifests in pediatric cases before the age of 10 years, with sporadic cases reported in adults. ADA2 is a critical enzyme involved in macrophage differentiation and immune homeostasis. The clinical manifestations of DADA2 vary widely and can affect multiple organ systems. Our case uniquely highlights an infrequent DADA2 manifestation.

Case presentation:

An 18-year-old female presented with right flank pain, fever, and a history of joint pain, Raynaud’s phenomenon, livedo-like rash, and chronic abdominal pain. Physical examination revealed subcapsular hematoma in the right kidney. Further evaluation showed positive serologic tests for rheumatoid factor and antinuclear antibody (ANA). Genetic testing confirmed DADA2 homozygosity. The patient was discharged on the appropriate medications.

Clinical discussion:

DADA2 is associated with vascular dysfunction and systemic vasculopathy. The clinical manifestations of DADA2 encompass a spectrum of organ involvement, including the skin, nervous system, gastrointestinal system, renal system, and the cardiovascular system. Early recognition and diagnosis are crucial for appropriate management.

Conclusion:

This case report highlights the diverse clinical presentations of ADA2 deficiency, specifically focusing on bilateral renal subcapsular hematoma. This finding emphasizes the importance of considering DADA2 as a differential diagnosis in patients presenting with unexplained renal manifestations. Increased awareness of the varied clinical presentations of DADA2 will contribute to earlier diagnosis, appropriate management, and improved outcomes in patients affected by this rare genetic disorder.
Development and validation of the air pollution exposure protective behavior scale for toddlers
Authors: Wang Chongkun , Shen Meidi , Hu Yinchu , Li Ruiqiong , Dorj Gantuya , Gombojav Enkhjargal , Shi Yuexian , Ren Lihua
Published: June 2024

Objectives:

This study aimed to develop the Air Pollution Exposure Protective Behavior Scale for Toddlers (APP-T) and test its psychometric properties, to provide a tool for the assessment of air pollution exposure protective behaviors for toddlers.

Methods:

A draft scale containing 39 items was constructed based on an evidence summary, an interview and literature review. The scale was revised according to the comments from 16 experts in public health, environmental science and nursing through a modified Delphi method, and the results of a pilot test of air pollution exposure protective behaviors for toddlers (n=57). A formal survey was conducted using the revised scale (n=876). Factor structure and model fit of the scale were examined using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). An expert consultation was conducted to assess the content validity. Known-groups validity, internal consistency, test-retest reliability, and split-half reliability of the scale were also calculated.

Results:

A five-point Likert scale of four dimensions, consisting of 25 main items, two additional items and four validation items, was developed in this study, to assess the air pollution exposure protective behaviors for toddlers. In the formal survey, the four factors of the scale explained 63.0% of the variance, with a good model fit and acceptable convergence. The scale Cronbach’s α was 0.93. The test-retest correlation coefficients for all four dimensions and the whole scale scores were above 0.70 and statistically significant, with a Spearman-Brown coefficient of 0.85.

Conclusion:

This study developed and validated an assessment scale, the Air Pollution Exposure Protective Behavior Scale for Toddlers (APP-T), with good reliability and validity. This scale can provide a basis for clarifying the current situation of air pollution exposure protective behaviors for toddlers and for implementing precision nursing on respiratory symptoms and diseases for toddlers.