bluuebunny/crossref_metadata_2025 huggingface dataset:
The cullin Rtt101 promotes ubiquitin-dependent DNA−protein crosslink repair across the cell cycle
Authors: Noireterre Audrey , Soudet Julien , Bagdiul Ivona , Stutz Françoise
Published: July 2024

DNA−protein crosslinks (DPCs) challenge faithful DNA replication and smooth passage of genomic information. Our study unveils the cullin E3 ubiquitin ligase Rtt101 as a DPC repair factor. Genetic analyses demonstrate that Rtt101 is essential for resistance to a wide range of DPC types including topoisomerase 1 crosslinks, in the same pathway as the ubiquitin-dependent aspartic protease Ddi1. Using an in vivo inducible Top1-mimicking DPC system, we reveal the significant impact of Rtt101 ubiquitination on DPC removal across different cell cycle phases. High-throughput methods coupled with next-generation sequencing specifically highlight the association of Rtt101 with replisomes as well as colocalization with DPCs. Our findings establish Rtt101 as a main contributor to DPC repair throughout the yeast cell cycle.
The complete pathway for co-transcriptional mRNA maturation within a large protein of a non-segmented negative-strand RNA virus
Authors: Ogino Minako , Green Todd J , Ogino Tomoaki
Published: July 2024

Non-segmented negative-strand (NNS) RNA viruses, such as rabies, Nipah and Ebola, produce 5′-capped and 3′-polyadenylated mRNAs resembling higher eukaryotic mRNAs. Here, we developed a transcription elongation-coupled pre-mRNA capping system for vesicular stomatitis virus (VSV, a prototypic NNS RNA virus). Using this system, we demonstrate that the single-polypeptide RNA-dependent RNA polymerase (RdRp) large protein (L) catalyzes all pre-mRNA modifications co-transcriptionally in the following order: (i) 5′-capping (polyribonucleotidylation of GDP) to form a GpppA cap core structure, (ii) 2′-O-methylation of GpppA into GpppAm, (iii) guanine-N7-methylation of GpppAm into m7GpppAm (cap 1), (iv) 3′-polyadenylation to yield a poly(A) tail. The GDP polyribonucleotidyltransferase (PRNTase) domain of L generated capped pre-mRNAs of 18 nucleotides or longer via the formation of covalent enzyme–pre-mRNA intermediates. The single methyltransferase domain of L sequentially methylated the cap structure only when pre-mRNAs of 40 nucleotides or longer were associated with elongation complexes. These results suggest that the formation of pre-mRNA closed loop structures in elongation complexes via the RdRp and PRNTase domains followed by the RdRp and MTase domains on the same polypeptide is required for the cap 1 formation during transcription. Taken together, our findings indicate that NNS RNA virus L acts as an all-in-one viral mRNA assembly machinery.
A phased small interfering RNA-derived pathway mediates lead stress tolerance in maize
Authors: Li Zhaoling , Jiang Li , Long Ping , Wang Chen , Liu Peng , Hou Fengxia , Zhang Minyan , Zou Chaoying , Huang Yongcai , Ma Langlang , Shen Yaou
Published: July 2024

Phased small interfering RNAs (phasiRNAs) are a distinct class of endogenous small interfering RNAs, which regulate plant growth, development, and environmental stress response. To determine the effect of phasiRNAs on maize (Zea mays L.) tolerance to lead (Pb) stress, the roots of 305 maize lines under Pb treatment were subjected to generation of individual databases of small RNAs. We identified 55 high-confidence phasiRNAs derived from 13 PHAS genes (genes producing phasiRNAs) in this maize panel, of which 41 derived from 9 PHAS loci were negatively correlated with Pb content in the roots. The potential targets of the 41 phasiRNAs were enriched in ion transport and import. Only the expression of PHAS_1 (ZmTAS3j, Trans-Acting Short Interference RNA3) was regulated by its cis-expression quantitative trait locus and thus affected the Pb content in the roots. Using the Nicotiana benthamiana transient expression system, 5′-rapid amplification of cDNA ends, and Arabidopsis heterologously expressed, we verified that ZmTAS3j was cleaved by zma-miR390 and thus generated tasiRNA targeting ARF genes (tasiARFs), and that the 5′ and 3′ zma-miR390 target sites of ZmTAS3j were both necessary for efficient biosynthesis and functional integrity of tasiARFs. We validated the involvement of the zma-miR390–ZmTAS3j–tasiARF–ZmARF3–ZmHMA3 pathway in Pb accumulation in maize seedlings using genetic, molecular, and cytological methods. Moreover, the increased Pb tolerance in ZmTAS3j-overexpressed lines was likely attributed to the zma-miR390–ZmTAS3j–tasiARF–ZmARF3–SAURs pathway, which elevated indole acetic acid levels and thus reactive oxygen species-scavenging capacity in maize roots. Our study reveals the importance of the TAS3-derived tasiRNA pathway in plant adaptation to Pb stress.
E3 ligase SlCOP1-1 stabilizes transcription factor SlOpaque2 and enhances fruit resistance to Botrytis cinerea in tomato
Authors: Gao Guangtong , Zhou Leilei , Liu Jinying , Wang Peiwen , Gong Pichang , Tian Shiping , Qin Guozheng , Wang Weihao , Wang Yuying
Published: July 2024

CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a pivotal repressor in plant photomorphogenesis, has been extensively studied in various plant processes. However, the specific roles of COP1 in fruit remain poorly understood. Here, we functionally characterized SlCOP1-1 (also known as LeCOP1), an Arabidopsis (Arabidopsis thaliana) COP1 ortholog, in tomato (Solanum lycopersicum) fruit ripening and disease resistance. Despite the clear upregulation of SlCOP1-1 during fruit ripening, knockout or overexpression (OE) of SlCOP1-1 in tomatoes only minimally affected ripening. Intriguingly, these genetic manipulations substantially altered fruit resistance to the fungal pathogen Botrytis cinerea. Proteomic analysis revealed differential accumulation of proteins associated with fruit disease resistance upon SlCOP1-1 knockout or OE. To unravel the mechanism of SlCOP1-1 in disease resistance, we conducted a screen for SlCOP1-1-interacting proteins and identified the stress-related bZIP transcription factor SlOpaque2. We provide evidence that SlOpaque2 functions in tomato resistance to B. cinerea, and SlCOP1-1-mediated mono-ubiquitination and stabilization of SlOpaque2 contributes to fruit resistance against B. cinerea. Our findings uncover a regulatory role of COP1 in controlling fruit disease resistance, enriching our understanding of the regulatory network orchestrating fruit responses to disease.
From global diffusion to local semantics: unpacking the scientization of central banks
Authors: Ibrocevic Edin
Published: July 2024

This article investigates the scientization of central banks and analyzes the evolving knowledge production. Existing literature suggests that scientized knowledge production either becomes globally more similar over time or is driven by local political economy considerations. However, research on the structure of central bank knowledge production is lacking. To address this, I conduct semantic network analysis on 75 000 central bank working papers and articles from top economics journals. Findings show global organizational forms of knowledge production have diffused, but semantics remain localized. The semantic structure becomes increasingly clustered over time, with a notable division between the Federal Reserve System (FED) and non-FED clusters. Only Federal Reserve produces knowledge aligned with top academic journals. Cluster differences are not solely due to mandates or political contexts but depend on specific policy environments. This research illuminates the evolution of knowledge production within central banks and underscores the influence of organizational and policy contexts.
Bridging Divides or Reinforcing Distance? The Interplay of Individual and Organizational Factors in Shaping Volunteers’ Relationships with Criminalized Women
Authors: Quinn Kaitlyn
Published: July 2024

As governments cut funding for social welfare programs and shift toward neoliberal, marketized alternatives, non-profits have taken on a large and growing role in the provision of services to marginalized people. This paper examines how volunteers approach their relationships with service users in non-profits, as well as the consequences of and explanations for variation in their approaches. This research explores these questions ethnographically within Canadian non-profits offering social services to criminalized women. This paper offers three interrelated contributions. The first is a typology of different volunteer approaches within the penal voluntary sector—constructing volunteers as bystanders, tourists, visitors, or apprentices in their relationships with criminalized women. The second highlights how some of these approaches entrench social distance and inequality, whereas others encourage greater proximity and equity between volunteers and criminalized women. The third demonstrates how variation in volunteers’ approaches is the product of a dynamic interplay of individual and organizational factors. Together, these findings provide new insights about the conditions under which volunteers can do “good” or “bad” within non-profits. These insights could enhance the quality of volunteer work, reduce the reproduction of inequalities, and support the operation of organizations delivering vital services to marginalized people.
Removal of historical taxonomic bias and its impact on biogeographic analyses: a case study of Neotropical tardigrade fauna
Authors: Ugarte Pedro Danel de Souza , Garraffoni André Rinaldo Senna
Published: July 2024

Large-scale databases are crucial for macroecology research, yet not entirely bias-free. Studying the biogeography of metazoan microfauna utilizing such databases is challenging, and added biases can further hinder them. Incidence data of tardigrade species from Central and South America are geographically biased, comprising mostly species erroneously considered cosmopolitan. The impact of these biases on macroecological studies is still unknown. This paper evaluates how biased distribution records affect understanding of non-marine tardigrade distribution patterns in the Neotropical region. Using two datasets (including and excluding dubious records of allegedly cosmopolitan species), we assess how well biogeographic regions are sampled, estimate tardigrade species’ richness, and analyse whether including dubious records can alter our comprehension of their macroecology. We demonstrate how biogeographic regions are still not fully sampled, and that including unreliable records influences how many species remain to be discovered. Since records of ‘false cosmopolitan species’ represent most records, their removal increases uncertainty while yielding distribution patterns more likely to be accurate. Disregarding untrustworthy distribution records of ‘false cosmopolitan species’ is the first step to better understanding tardigrade macroecology in the Neotropics, and probably worldwide. However, additional, preferably systematic sampling is required before we can infer general tardigrade biodiversity patterns in under-sampled regions.
Building Accelerated Plant Breeding Pipelines: Screening to Evaluate Lima Bean Resistance to Root-Knot Nematode in Diverse Inbred Lines and Segregating Breeding Populations
Authors: Traverso Eboni R. , Ernest Emmalea G. , Emanuel Isabel B. , Betts Alyssa K.
Published: July 2024

Lima beans ( Phaseolus lunatus) are a cornerstone crop of Delaware's processing vegetable industry. Root-knot nematodes (RKNs; Meloidogyne spp.) cause galling of root systems, which severely reduces yield. Durable host resistance is an effective management strategy for RKNs, but availability of resistant lima bean cultivars is limited. To overcome these challenges, breeding pipelines must simultaneously advance precommercial lines and identify new resistance sources with potential for incorporation into the breeding program. Inoculated field trials were conducted in 2021 and 2022 to evaluate three M. incognita-resistant, precommercial experimental lines for resistance traits and yield potential in comparison with commercial standards ‘Cypress’ and ‘C-Elite Select’. DE1306635 had the highest yield and reduced galling and reproduction compared with ‘Cypress’ and is a candidate for commercial release. To continue the breeding pipeline, 256 lima bean inbred accessions from around the world were assessed from 2022 to 2023 in greenhouse and field screenings to identify novel sources of resistance in the lima bean gene pool. This method allows for evaluation and/or advancement of three generations per year. The full panel was initially evaluated for root galling, and 60 accessions were selected for additional field and greenhouse screening: 25 large- and 25 small-seeded with the lowest gall ratings, 5 high-gall controls, and 5 commercial standards. Seven accessions with reduced M. incognita galling and reproduction were identified, including two known resistant lines and five newly identified genotypes. The resistance carried by these genotypes will be further characterized to assess their potential use in lima bean RKN-resistance breeding.
Experimental Infection of California Ripe Olive Cultivars with Xylella fastidiosa Subspecies pauca De Donno and Acquisition by Glassy-Winged Sharpshooter
Authors: Burbank Lindsey , Rogers Elizabeth E. , Sechler Aaron J. , Magdeleno Mayra , Krugner Rodrigo
Published: July 2024

Strains of Xylella fastidiosa subspecies pauca can infect olive trees, and an introduction of this pathogen has caused significant damage to the olive industry in Europe. Although this subspecies is not known to be present in North America, the environment, plant hosts, and insect vectors in the United States olive-growing regions (mainly California) are conducive to X. fastidiosa spread and disease damage. This study evaluated several risk factors for X. fastidiosa disease in the California olive industry, including infection of the common cultivars and acquisition by insect vectors. Olive cultivars Manzanillo, Sevillano, and Mission all exhibited disease symptoms after inoculation with X. fastidiosa strain De Donno obtained from the olive disease outbreak in southern Italy. Glassy-winged sharpshooters were able to acquire X. fastidiosa De Donno from infected olive plants as soon as 30 days after plant inoculation. This information is valuable for risk assessment and disease management planning in the event of a future introduction of olive-pathogenic strains of X. fastidiosa to the United States.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Implementation of a Mental Health Objective Structured Clinical Examination (OSCE) Using Standards of Best Practice
Authors: Stockmann Cherrill , Adelman-Mullally Theresa , Willett Joanna , Dyck Mary J.
Published: July 2024

The objective structured clinical examination (OSCE) is effective for the evaluation of clinical competence. Studies examining the use of OSCEs in undergraduate mental health nursing education in the United States are limited. A pilot study and a follow-up study were conducted to establish the reliability and validity of a mental health OSCE to evaluate the clinical competence of prelicensure nursing students. International Nursing Association for Clinical Simulation and Learning Standards of Best Practice were used to guide the design and implementation. Results from both studies provide evidence for the use of OSCE in undergraduate mental health nursing education.
Preoperative Bilateral External Oblique Intercostal Plus Rectus Sheath Block for Postoperative Pain Management Following Laparoscopic Cholecystectomy
Authors: Mo Ke , Kong Weirong , Chen Jiaxin , Zhao Shuhua , Zhu Qianqian
Published: July 2024

Objectives:

The transversus abdominis plane (TAP) block has proven efficacy and is an important component of multimodal analgesia in laparoscopic cholecystectomy (LC). The external oblique intercostal (EOI) block can provide a dermatomal sensory blockade of T6 to T10 using an anterior axillary line injection. The bilateral rectus sheath (RS) block can significantly reduce early postoperative pain caused by umbilical or periumbilical incisions. The current study aimed to compare the analgesic efficacies of ultrasound-guided subcostal TAP (UG-TAP) combined with the RS block and ultrasound-guided EOI (UG-EOI) combined with the RS block for LC.

Methods:

Patients were randomly assigned to TAP or EOI group. Patients in TAP group received UG-TAP combined with an RS block. Patients in EOI group received UG-EOI combined with an RS block. The primary outcome was postoperative 24-hour sufentanil consumption.

Results:

A total of 49 patients were included in the final analysis. The postoperative 24-hour sufentanil consumption in the EOI group was significantly lower than that in the TAP group (9.79±10.22 vs. 18.67±12.58 µg; P [noninferiority] <0.01; noninferiority confirmed). Fewer patients in the EOI versus TAP group had a numerical rating score of >3 during motion. Furthermore, the mean postoperative 48-hour sufentanil consumption was lower in the EOI versus TAP group (11.54±11.70 vs. 23.04±17.10 µg; P=0.01). The mean postoperative 24-hour Quality of Recovery-15 score was higher in the EOI versus TAP group (135.21±4.40 vs. 131.91±5.11; P=0.02).

Discussion:

These findings suggest that UG-EOI combined with an RS block was superior to UG-TAP combined with an RS block for postoperative pain management in patients undergoing LC.
Impact of Spinal Deformity and Surgery on Health-Related Quality of Life in Cerebral Palsy: A Multicenter Prospective Controlled Trial
Authors: Cahill Patrick J. , Narayanan Unni , Bowen Margaret , Sarkar Sulagna , Pahys Joshua M. , Miyanji Firoz , Yaszay Burt , Shah Suken A. ,   Harms Study Group, Sponseller Paul D.
Published: July 2024

Background:

Spinal fusion for scoliosis associated with cerebral palsy (CP) is challenging to study because specialized outcome measures are needed. Therefore, evidence in favor of the benefits of surgery has not been firmly established. This study aimed to determine if corrective spinal fusion improves health-related quality of life (HRQoL) in children with CP scoliosis at 2 years.

Methods:

Children with CP and scoliosis who met the criteria for posterior spinal fusion were offered enrollment at 16 US and Canada centers. Participants’ families selected either operative intervention (OP) or nonoperative treatment (NON) in discussion with their surgeon with no influence by the decision to participate in the research study. Demographic, clinical data (function level, magnitude of deformity, comorbidities), and HRQoL (CPCHILD Questionnaire) were collected at baseline and 2 years. Change (from baseline) in total CPCHIL scores was the primary outcome.

Results:

Three hundred one OP and 34 NON subjects had complete baseline and 2-year data. At baseline, both groups were comparable in function level, comorbid status, and CPCHILD scores (52.1 ±15.3 vs. 53.4 ±14.5; P=0.66). The OP group had a larger spinal deformity magnitude (84.5˚ ± 21.8˚ vs. 66.3˚ ± 18.1˚) (P=0.001). The total CPCHILD score improved in the OP group by 6.6 points (P<0.001). NON scores were unchanged (+1.2; P=0.65) during follow-up. There were also significant score increases in the OP group for 5 of 6 CPCHILD domains. The change in CPCHILD scores from enrollment to 2 years was more significant in the OP group (P=0.05).

Conclusion:

For children with CP who undergo spinal fusion, HRQoL improved over preoperative levels and an unchanged nonoperative control group.

Level of Evidence:

Level II.
Pelvic Incidence As a Predictor of Proximal Junctional Kyphosis in Patients with Lenke type 5 Adolescent Idiopathic Scoliosis
Authors: Kitagawa Takahiro , Suzuki Satoshi , Takeda Kazuki , Okubo Toshiki , Ozaki Masahiro , Takahashi Yohei , Tsuji Osahiko , Nagoshi Narihito , Yagi Mitsuru , Matsumoto Morio , Nakamura Masaya , Watanabe Kota
Published: July 2024

Study Design.

Retrospective comparative study.

Objective.

To evaluate the relationship between pelvic incidence (PI) and proximal junctional kyphosis (PJK) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

Although PJK is a common complication of sagittal malalignment after posterior correction and fusion surgery (PSF), few studies have assessed its risk factors. The significance of pelvic morphology in relation to PJK has been suggested but remains unclear in Lenke type 5 AIS patients.

Methods.

A total of 92 patients with Lenke type 5 AIS who underwent selective thoracolumbar PSF with a minimum follow-up of two years were included. Patients were divided into PJK and non-PJK groups based on postoperative radiographs. The influence of PI on PJK occurrence was evaluated through binary logistic analysis. Subgroup analysis was performed based on the PI value (low PI,<45°; high PI, ≥ 45°) to identify factors affecting PJK occurrence.

Results.

PJK was observed in 17.4% of the whole cohort. Binary logistic regression analysis identified low PI and large TL/L curve as a risk factor for PJK (PI, odds ratio, 0.933; TL/L curve, odds ratio, 1.080). Subgroup analysis showed that the postoperative increase in the upper instrumented vertebra slope in PJK cases was comparable in both the low and high PI groups. Meanwhile, lordotic changes in the fused area in the PJK cases were observed only in the low PI group. No difference in the Scoliosis Research Society 22 scores were observed between the two groups.

Conclusion.

From this study a low PI was identified as a risk factor for the occurrence of PJK in Lenke type 5 AIS patients. The occurrence of PJK is influenced by lordotic changes in the fused area and the limited compensatory capacity of the pelvis in patients with a low PI.
Upregulation of CDC25B by transcription factor TEAD4 drives invasion and inhibits cisplatin sensitivity through cell adhesion in stomach adenocarcinoma
Authors: Zhang Tao , Chen Lijian , Li Shuang , Shen Chao
Published: July 2024

Cisplatin is crucial in management of advanced stomach adenocarcinoma, whereas development of chemotherapy resistance hinders overall efficacy of cisplatin. This work aims to explore role of CDC25B in cisplatin sensitivity in stomach adenocarcinoma and offer a possible mechanism for explaining its function. By using bioinformatics approaches, CDC25B and TEAD4 expression levels in stomach adenocarcinoma tissues and enriched pathways of CDC25B were analyzed. qRT-PCR of CDC25B and TEAD4 expression in stomach adenocarcinoma cells, CCK-8 detection of cell viability and IC50 values, and colony formation assay on cell proliferation were performed. Cell adhesion experiment detected cell adhesion ability. Western blot detected expression of proteins related to cell adhesion, specifically Muc-1, ICAM-1, VCAM-1. Dual luciferase assay and ChIP experiment verified binding relationship between TEAD4 and CDC25B. CDC25B was upregulated in stomach adenocarcinoma tissues and cells, enriched in focal adhesion pathway. Treatment with cell adhesion inhibitors revealed that CDC25B overexpression inhibits the sensitivity of stomach adenocarcinoma to cisplatin through the cell adhesion pathway. CDC25B has an upstream transcription factor TEAD4, which targeted and bound to CDC25B and was highly expressed in stomach adenocarcinoma. Rescue experiment revealed that knocking down TEAD4 weakened suppressive impact of CDC25B overexpression on sensitivity of stomach adenocarcinoma cells to cisplatin. Transcription factor TEAD4 could activate the transcription of CDC25B through cell adhesion to drive cell invasion and reduce sensitivity of stomach adenocarcinoma to cisplatin. TEAD4 and CDC25B may become new targets for management of stomach adenocarcinoma.
Corneal Transplant Rejection Following Durvalumab Therapy in a Patient With NSCLC: A Case Report
Authors: Froessl Luise , Panwar Puja , Bhatia Subir , Dowell Jonathan
Published: July 2024

We report the case of corneal transplant rejection in a 77-year-old male receiving durvalumab as consolidative therapy for stage IIIB non–small cell lung cancer (NSCLC). Following successful chemoradiation and initiation of durvalumab, the patient underwent a right corneal transplant for corneal dystrophy. Six months after an initially stable post-transplant course, he developed progressive visual decline culminating in graft failure 1 year later despite treatment with prednisone eye drops. This case adds to the limited evidence implicating immune checkpoint inhibitors (ICIs) in corneal graft rejection, emphasizing the need for multidisciplinary evaluation and close monitoring of corneal transplant recipients undergoing ICI therapy.
Association and its population heterogeneities between low-density lipoprotein cholesterol and all-cause and cardiovascular mortality: A population-based cohort study
Authors: Lu Jiapeng , Zhang Haibo , Chen Bowang , Yang Yang , Cui Jianlan , Xu Wei , Song Lijuan , Yang Hao , He Wenyan , Zhang Yan , Peng Wenyao , Li Xi
Published: July 2024

Background:

The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.

Methods:

A total of 2,968,462 participants aged 35–75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014–2019) were included. Cox proportional hazard models and Fine–Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0–99.9, 100.0–129.9 [reference group], 130.0–159.9, 160.0–189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality.

Results:

During a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality (P for non-linearity <0.001). Compared with the reference group (100.0–129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06–1.14) and HS mortality (HR: 1.37, 95% CI: 1.29–1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40–1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92–2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people.

Conclusions:

People with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.
Bioinformatics tools and resources for cancer and application
Authors: Huang Jin , Mao Lingzi , Lei Qian , Guo An-Yuan
Published: July 2024

Tumor bioinformatics plays an important role in cancer research and precision medicine. The primary focus of traditional cancer research has been molecular and clinical studies of a number of fundamental pathways and genes. In recent years, driven by breakthroughs in high-throughput technologies, large-scale cancer omics data have accumulated rapidly. How to effectively utilize and share these data is particularly important. To address this crucial task, many computational tools and databases have been developed over the past few years. To help researchers quickly learn and understand the functions of these tools, in this review, we summarize publicly available bioinformatics tools and resources for pan-cancer multi-omics analysis, regulatory analysis of tumorigenesis, tumor treatment and prognosis, immune infiltration analysis, immune repertoire analysis, cancer driver gene and driver mutation analysis, and cancer single-cell analysis, which may further help researchers find more suitable tools for their research.
Robot-assisted laparoscopic retroperitoneal lymph node dissection in testicular cancer using a single-position supine approach: A case report and literature review
Authors: Zhou Lei , Yao Kun , Li Chao , Xiong Wei , Hou Weibin , Wang Bingzhi , Xu Long , Wang Long
Published: July 2024

This case study demonstrates a single-position supine approach for robotic retroperitoneal lymph node dissection for the treatment of nonseminomatous germ cell tumors and residual masses after chemotherapy. We performed a bilateral robotic retroperitoneal lymph node dissection in a 33-year-old man with nonseminomatous germ cell tumors and residual postchemotherapy masses. For this approach, the patient was placed in a steep Trendelenburg position, and a 5-port transperitoneal technique was used, with the robot docked so that the arms were oriented cephalad. This approach allowed simultaneous access to both sides of the retroperitoneum, thereby eliminating the need for bilateral lymphadenectomy and patient repositioning. Bilateral R-RPLDN was performed using a single-position supine approach. This versatile approach offers a less invasive, more efficient, and safer solution for removing residual postchemotherapy testicular cancer masses.
Association of the dopamine D2 receptor gene SNP rs1800497 with postoperative nausea and vomiting
Authors: Stegen Maike , Bachmann Hagen S. , Belani Grazina , Mohamed Ahmed , Breuing Björn , Brenner Thorsten , Klenke Stefanie
Published: July 2024

BACKGROUND

Postoperative nausea and vomiting (PONV) are the most frequent complications in the context of anaesthesia. Several studies suggest a contribution of genetic traits to PONV disposition. Single nucleotide polymorphisms (SNPs) located in the cholinergic receptor muscarinic 3 gene CHRM3 (rs2165870) and the potassium voltage-gated channel subfamily B member 2 KCNB2 (rs349358) have been described as independent risk factors for the occurrence of PONV. In addition, further SNPs might be associated with an increased PONV risk, for example a dopamine D2 receptor (DRD2) SNP (rs1800497).

OBJECTIVE

The primary aim of our study was the development of a new PONV prediction score which includes genetic information of SNPs in the genes CHRM3 and KCNB2, which have been already associated with PONV. The secondary aim of our study was to investigate the association of five additional SNPs with PONV.

DESIGN

Prospective cohort study.

SETTING

Single centre study in Germany.

RESULTS

We could not establish a new PONV prediction score that includes genetic information, due to limited association of the KCNB2 SNP and CHRM3 SNP with PONV. Interestingly, the GA and AA genotypes of the DRD2 rs1800497 in the dopamine D2 receptor gene were associated with PONV 24 h postoperatively, with a relative risk (RR) of GA/AA genotype vs. GG genotype of 1.5 [95% confidence interval (CI) 1.06 to 2.01, P = 0.02]. This association was independent from the Apfel score in a multivariate logistic regression analysis (RR 1.4, 95% CI 1.03 to 1.90, P = 0.03).

CONCLUSION

The construction of a new PONV prediction score including genetic information was not possible due to limited association of the CHRM3 and KCNB2 SNPs. However, the DRD2 GA and AA genotypes (rs1800497) were associated with PONV and this SNP might be a future candidate for further validation studies aiming for molecular-derived PONV prediction models.

TRIAL REGISTRATION

German Clinical Study Register – DRKS00021051.
The degree of respiratory depression according to the effect-site concentration in remimazolam target-controlled infusion
Authors: Park Soo Jung , Min Sang Kee , Choi Gyubin , Kim Ji Eun , Kim Ha Yeon
Published: July 2024

BACKGROUND

Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression.

OBJECTIVE

We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion.

DESIGN

A prospective, double-blind, randomised controlled study.

SETTING

Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022.

PARTICIPANTS

One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) (n = 36), 1000 (RMZ-1000) (n = 35) and 1500 ng ml−1 (RMZ-1500) (n = 36).

INTERVENTIONS

Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO2 less than 97%, 100% oxygen delivery for SpO2 less than 93% and assisted ventilation for SpO2 less than 90%.

MAIN OUTCOME MEASURES

The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion.

RESULTS

Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) (P < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients (P = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups (P < 0.001).

CONCLUSIONS

Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation.

TRIAL REGISTRATION

CRIS (https://cris.nih.go.kr), identifier: KCT0006952
Intravenous lidocaine for postoperative analgesia management in paediatrics
Authors: Pardessus Pierre , Loiselle Maud , Brouns Kelly , Horlin Anne-Laure , Bruneau Beatrice , Maroun Yara , Lagarde Martin , Deliere Maxime , Julien-Marsollier Florence , Dahmani Souhayl
Published: July 2024

BACKGROUND

The administration of intravenous lidocaine during the peri-operative period may improve pain management after paediatric surgery.

OBJECTIVE

To explore the decrease in postoperative pain intensity and opioid consumption associated with peri-operative lidocaine administration in the paediatric population.

DESIGN

A systematic review with meta-analysis of randomised controlled trials and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.

DATA SOURCES

Extensive literature review.

ELIGIBILITY CRITERIA

This study includes clinical trials conducted during surgery that examined the effect of intravenous lidocaine compared with placebo on postoperative pain management.

RESULTS

Lidocaine administration decreased pain intensity in PACU (standardised mean difference (SMD) = -1.89 [-3.75, -0.03], I
2 = 97%, P of I
2 < 0.001) and on postoperative day 1 (SMD = -2.02 [-3.37, -0.66], I
2 = 96%, P of I
2 < 0.001, number of studies = 5). Lidocaine was associated with a decrease in opioid consumption on postoperative day 1 (SMD = -1.2 [-2.19, -0.2], I
2 = 93%, P of I
2 < 0.001) but not on postoperative day 2 (SMD = -1.73 [-3.9, 0.44], I
2 = 96%, P of I
2 < 0.001). GRADE analyses resulted in low-quality results. Subgroup analyses revealed that pain intensity in PACU and opioid consumption on postoperative day 1 decreased when lidocaine was administered during both the intra-operative and postoperative periods.

CONCLUSIONS

The use of lidocaine is associated with improved pain management. However, further studies are needed to increase the level of evidence and determine the optimal administration regimen for pain management.
Mdka produced by the activated HSCs drives bipotential progenitor cell redifferentiation during zebrafish biliary-mediated liver regeneration
Authors: Zhang Xintao , Liu Huijuan , Cai Pengcheng , Huang Zhuofu , Ma Jianlong , Luo Lingfei
Published: July 2024

Background and Aims:

After extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs through trans-differentiation of biliary epithelial cells (BECs), which involves dedifferentiation of biliary epithelial cells into bipotential progenitor cells (BP-PCs) and subsequent redifferentiation of BP-PCs into nascent hepatocytes and biliary epithelial cells. Despite several studies on the redifferentiation process of BP-PCs into nascent hepatocytes, the contributions of nonparenchymal cells in this process remain poorly understood.

Approach and Results:

Using the zebrafish severe liver injury model, we observed specific expression of midkine a (Mdka) in the activated HSCs through single-cell analyses and fluorescence in situ hybridization. Genetic mutation, pharmacological inhibition, whole-mount in situ hybridizations, and antibody staining demonstrated an essential role of mdka in the redifferentiation of BP-PCs during liver regeneration. Notably, we identified Nucleolin (Ncl), the potential receptor for Mdka, specifically expressed in BP-PCs, and its mutant recapitulated the mdka mutant phenotypes with impaired BP-PC redifferentiation. Mechanistically, the Mdka-Ncl axis drove Erk1 activation in BP-PCs during liver regeneration. Furthermore, overexpression of activated Erk1 partially rescued the defective liver regeneration in the mdka mutant.

Conclusions:

The activated HSCs produce Mdka to drive the redifferentiation process of BP-PCs through activating Erk1 during the biliary-mediated liver regeneration, implying previously unappreciated contributions of nonparenchymal cells to this regeneration process.
Diagnostic Performance of Machine Learning-based Models in Neonatal Sepsis: A Systematic Review
Authors: Kainth Deepika , Prakash Satya , Sankar M. Jeeva
Published: July 2024

Background:

Timely diagnosis of neonatal sepsis is challenging. We aimed to systematically evaluate the diagnostic performance of sophisticated machine learning (ML) techniques for the prediction of neonatal sepsis.

Methods:

We searched MEDLINE, Embase, Web of Science and Cochrane CENTRAL databases using “neonate,” “sepsis” and “machine learning” as search terms. We included studies that developed or validated an ML algorithm to predict neonatal sepsis. Those incorporating automated vital-sign data were excluded. Among 5008 records, 74 full-text articles were screened. Two reviewers extracted information as per the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies) checklist. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline extension for diagnostic test accuracy reviews and used the PROBAST tool for risk of bias assessment. Primary outcome was a predictive performance of ML models in terms of sensitivity, specificity and positive and negative predictive values. We generated a hierarchical summary receiver operating characteristics curve for pooled analysis.

Results:

Of 19 studies (15,984 participants) with 76 ML models, the random forest algorithm was the most employed. The candidate predictors per model ranged from 5 to 93; most included birth weight and gestation. None performed external validation. The risk of bias was high (18 studies). For the prediction of any sepsis (14 studies), pooled sensitivity was 0.87 (95% credible interval: 0.75–0.94) and specificity was 0.89 (95% credible interval: 0.77–0.95). Pooled area under the receiver operating characteristics curve was 0.94 (95% credible interval: 0.92–0.96). All studies, except one, used data from high- or upper-middle-income countries. With unavailable probability thresholds, the performance could not be assessed with sufficient precision.

Conclusions:

ML techniques have good diagnostic accuracy for neonatal sepsis. The need for the development of context-specific models from high-burden countries is highlighted.
HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa
Authors: Anderson Kim , van Zyl Gert , Hsiao Nei-Yuan , Claassen Mathilda , Mudaly Vanessa , Voget Jacqueline , Heekes Alexa , Kalk Emma , Phelanyane Florence , Boulle Andrew , Sridhar Gayathri , Ragone Leigh , Vannappagari Vani , Davies Mary-Ann
Published: July 2024

Background:

Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis.

Methods:

We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021–2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug–resistance mutation lists to define mutations.

Results:

We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor–associated, nucleoside reverse transcriptase inhibitor–associated, protease inhibitor–associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations).

Conclusions:

Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor–associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.
The Retrospective Implementation of Standardized In Utero HIV Exposure Definitions Using Routinely Collected Public Sector Data Across the Western Cape Province, South Africa
Authors: de Beer Shani T. , Davies Mary-Ann , Phelanyane Florence , Jones Hayley E. , Ingle Suzanne M. , Eley Brian S. , Anderson Kim , Heekes Alexa , Kalk Emma , Mendelsohn Andrea , Boulle Andrew , Slogrove Amy L.
Published: July 2024

Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project’s standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.
Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection in Japan 2023: Executive Summary
Authors: Ito Yoshinori , Morioka Ichiro , Takahashi Naoto , Fujioka Kazumichi , Miura Kiyonori , Moriuchi Hiroyuki , Morimoto Noriko , Yoshikawa Tetsushi , Ashina Mariko , Abe Shinya , Imafuku Hitomi , Uchida Akiko , Okahashi Aya , Kakiuchi Satsuki , Kakimoto Yu , Kawata Soichiro , Kawamura Yoshiki , Kido Takumi , Kidokoro Hiroyuki , Kozawa Kei , Samejima Tomohiro , Suzuki Takako , Tanimura Kenji , Tomonaga Chiharu , Torii Yuka , Nakanishi Megumi , Nagano Nobuhiko , Nagamatsu Takeshi , Narita Hajime , Nishimura Koji , Nonobe Norie , Hasegawa Yuri , Hara Koichiro , Hijikata Midori , Fukuda Takuya , Funato Yusuke , Mimura Nobuko , Yamamoto Nobuko , Yoshitomi Ai , Kakei Yasumasa , Kodama Tomoyuki , Oka Akira
Published: July 2024

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the “Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection” was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1–1-3), diagnosis (CQs 2-1–2-6), treatment (CQs 3-1–3-7) and follow-up requirements (CQs 4-1–4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.
The Practical Management of Rhinitis in Athletes
Authors: Khalid Hesham , Tait Joanna E. , North Alexander S. , Lakhani Raj
Published: July 2024

Objective:

Exercise-induced rhinitis (EIR) is a poorly understood condition that can have a massive impact within elite sport. This was epitomized in 2019 when British cyclist and Tour de France winner Chris Froome lost control of his bike at 37 mph while wiping his nose, resulting in an admission to intensive care. We aim to produce a comprehensive resource to guide the assessment and management of rhinitis in athletes.

Design:

Rhinitis is a common condition which can be broadly divided into allergic rhinitis (AR) and non-AR (NAR), a subset of which is known as vasomotor rhinitis. Exercise-induced rhinitis is an important but understudied subcategory of NAR. The pathophysiology of the disease is broadly believed to be an imbalance of the sympathetic and parasympathetic nervous systems, leading to symptoms of watery rhinorrhea, nasal congestion, and paroxysmal sneezing. Up to 50% of people suffer from some degree of EIR, which impedes their nasal breathing and affects performance. The assessment of the athlete with rhinitis requires consideration of both allergic and vasomotor contributions to ensure optimal management is introduced. There is no clear guidance for the management of EIR, with uncertainty regarding the most effective pharmaceuticals and optimizing the timing of treatment to enable peak performance.

Setting:

N/A.

Patients/Participants:

N/A.

Interventions:

N/A.

Main Outcome Measures:

N/A.

Results and Conclusions:

Based on expert clinical experience in a busy ear, nose, and throat center and a systematic review of current literature, this article proposes a step-wise, incremental approach to the management of EIR symptoms. In an industry where marginal gains give athletes a competitive edge, optimal management of EIR is crucial.