bluuebunny/crossref_metadata_2025 huggingface dataset:
CircASPH Enhances Exosomal STING to Facilitate M2 Macrophage Polarization in Colorectal Cancer
Authors: Zhang Yuting , Guo Jiakun , Zhang Liyin , Li Ying , Sheng Kangliang , Zhang Yawei , Liu Liu , Gong Wenbin , Guo Kun
Published: August 2023

Exosomes are considered a mediator of communication within the tumor microenvironment (TME), which modulates cancer progression through transmitting cargos between cancer cells and other cancer-related cells in TME. Circular RNAs (circRNAs) have emerged to be regulators in colorectal cancer (CRC) progression, but most of them have not been discussed in CRC. This study aims to investigate the role of circRNA aspartate beta-hydroxylase (circASPH) in CRC progression and its correlation with exosome-mediated TME. At first, we determined that circASPH was upregulated in CRC samples and cell lines. Functionally, the circASPH deficiency suppressed the malignant processes of CRC cells and also inhibited in vivo tumor growth via enhancing antitumor immunity. Mechanically, circASPH facilitated macrophage M2 polarization by upregulating exosomal stimulator of interferon genes (STING). CircASPH interacted with insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize IGF2BP2 protein, therefore enhancing the stability of m6A-modified STING mRNA. In turn, coculture of STING-overexpressed macrophages recovered the suppression of silenced circASPH on the malignancy of CRC cells both in vitro and in vivo. Our study demonstrated that circASPH enhances exosomal STING to facilitate M2 macrophage polarization, which further accelerates CRC progression. The findings support circASPH as a promising therapeutic target for CRC treatment.
Monovalent SARS-CoV-2 mRNA Vaccine Does not Boost Omicron-Specific Immune Response in Diabetic and Control Pediatric Patients
Authors: Sariol Alan , Vickers Molly A , Christensen Shannon M , Weiskopf Daniela , Sette Alessandro , Norris Andrew W , Tansey Michael J , Pinnaro Catherina T , Perlman Stanley
Published: August 2023

While the immunogenicity of SARS-CoV-2 vaccines has been well described in adults, pediatric populations have been less studied. In particular, children with type 1 diabetes are generally at elevated risk for more severe disease after infections, but are understudied in terms of COVID-19 and SARS-CoV-2 vaccine responses. We investigated the immunogenicity of COVID-19 mRNA vaccinations in 35 children with type 1 diabetes (T1D) and 23 controls and found that these children develop levels of SARS-CoV-2 neutralizing antibody titers and spike protein-specific T cells comparable to nondiabetic children. However, in comparing the neutralizing antibody responses in children who received 2 doses of mRNA vaccines (24 T1D; 14 controls) with those who received a third, booster dose (11 T1D; 9 controls), we found that the booster dose increased neutralizing antibody titers against ancestral SARS-CoV-2 strains but, unexpectedly, not Omicron lineage variants. In contrast, boosting enhanced Omicron variant neutralizing antibody titers in adults.
Novel insights into genetic susceptibility for colorectal cancer from transcriptome-wide association and functional investigation
Authors: Chen Zhishan , Song Wenqiang , Shu Xiao-Ou , Wen Wanqing , Devall Matthew , Dampier Christopher , Moratalla-Navarro Ferran , Cai Qiuyin , Long Jirong , Van Kaer Luc , Wu Lan , Huyghe Jeroen R , Thomas Minta , Hsu Li , Woods Michael O , Albanes Demetrius , Buchanan Daniel D , Gsur Andrea , Hoffmeister Michael , Vodicka Pavel , Wolk Alicja , Marchand Loic Le , Wu Anna H , Phipps Amanda I , Moreno Victor , Ulrike Peters , Zheng Wei , Casey Graham , Guo Xingyi
Published: August 2023

Background

Transcriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations.

Methods

We analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed in vitro functional assays for 3 selected genes in multiple CRC cell lines.

Results

We identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P value less than .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL, and a recently reported gene, C14orf166.

Conclusion

This study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development.
Cracking the enigma: understanding strigolactone signalling in the rhizosphere
Authors: Clark Jed , Bennett Tom
Published: August 2023

The rhizosphere is a complex physical and chemical interface between plants and their underground environment, both biotic and abiotic. Plants exude a large number of chemicals into the rhizosphere in order to manipulate these biotic and abiotic components. Among such chemicals are strigolactones, ancient signalling molecules that in flowering plants act as both internal hormones and external rhizosphere signals. Plants exude strigolactones to communicate with their preferred symbiotic partners and neighbouring plants, but at least some classes of parasitic organisms are able to ‘crack’ these private messages and eavesdrop on the signals. In this review, we examine the intentional consequences of strigolactone exudation, and also the unintentional consequences caused by eavesdroppers. We examine the molecular mechanisms by which strigolactones act within the rhizosphere, and attempt to understand the enigma of the strigolactone molecular diversity synthesized and exuded into the rhizosphere by plants. We conclude by looking at the prospects of using improved understanding of strigolactones in agricultural contexts.
Sirtuin 2 inhibition modulates chromatin landscapes genome-wide to induce senescence in ATRX-deficient malignant glioma
Authors: Malgulwar Prit Benny , Danussi Carla , Dharmaiah Sharvari , Johnson William , Singh Anand , Rai Kunal , Rao Arvind , Huse Jason T
Published: August 2023

Background

Functional inactivation of ATRX characterizes large subgroups of malignant gliomas in adults and children. ATRX deficiency in glioma induces widespread chromatin remodeling, driving transcriptional shifts and oncogenic phenotypes. Effective strategies to therapeutically target these broad epigenomic sequelae remain undeveloped.

Methods

We utilized integrated multiomics and the Broad Institute Connectivity Map (CMAP) to identify drug candidates that could potentially revert ATRX-deficient transcriptional changes. We then employed disease-relevant experimental models to evaluate functional phenotypes, coupling these studies with epigenomic profiling to elucidate molecular mechanism(s).

Results

CMAP analysis and transcriptional/epigenomic profiling implicated the Class III HDAC Sirtuin2 (SIRT2) as a central mediator of ATRX-deficient cellular phenotypes and a driver of unfavorable prognosis in ATRX-deficient glioma. SIRT2 inhibitors reverted Atrx-deficient transcriptional signatures in murine neuroepithelial progenitor cells (mNPCs), impaired cell migration in Atrx/ATRX-deficient mNPCs and human glioma stem cells (GSCs), and increased expression of senescence markers in glioma models. Moreover, SIRT2 inhibition impaired growth and increased senescence in ATRX-deficient GSCs in vivo. These effects were accompanied by genome-wide shifts in enhancer-associated H3K27ac and H4K16ac marks, with the latter in particular demonstrating compelling transcriptional links to SIRT2-dependent phenotypic reversals. Motif analysis of these data identified the transcription factor KLF16 as a mediator of phenotype reversal in Atrx-deficient cells upon SIRT2 inhibition.

Conclusions

Our findings indicate that SIRT2 inhibition selectively targets ATRX-deficient gliomas for senescence through global chromatin remodeling, while demonstrating more broadly a viable approach to combat complex epigenetic rewiring in cancer.
A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors
Authors: Haberberger James F , Pegram Worthy , Britt Nicholas , Schiavone Kelsie , Severson Eric , Sharaf Radwa , Albacker Lee A , Williams Erik , Lechpammer Mirna , Hemmerich Amanda , Lin Douglas , Huang Richard S P , Hiemenz Matthew , Elvin Julia , Graf Ryon , Lesser Glenn , Kram David , Strowd Roy , Bi Wenya Linda , Ramkissoon Lori A , Cohen Michael B , Reddy Prasanth , Creeden James , Ross Jeffrey S , Alexander Brian M , Ramkissoon Shakti H
Published: August 2023

The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young adult glioblastomas. The authors relate these molecular classes to current World Health Organization guidelines and reference current literature to give therapeutic and prognostic descriptions where possible.
Machine learning reveals the waggle drift’s role in the honey bee dance communication system
Authors: Dormagen David M , Wild Benjamin , Wario Fernando , Landgraf Tim
Published: August 2023

The honey bee waggle dance is one of the most prominent examples of abstract communication among animals: successful foragers convey new resource locations to interested followers via characteristic “dance” movements in the nest, where dances advertise different locations on different overlapping subregions of the “dance floor.” To this day, this spatial separation has not been described in detail, and it remains unknown how it affects the dance communication. Here, we evaluate long-term recordings of Apis mellifera foraging at natural and artificial food sites. Using machine learning, we detect and decode waggle dances, and we individually identify and track dancers and dance followers in the hive and at artificial feeders. We record more than a hundred thousand waggle phases, and thousands of dances and dance-following interactions to quantitatively describe the spatial separation of dances on the dance floor. We find that the separation of dancers increases throughout a dance and present a motion model based on a positional drift of the dancer between subsequent waggle phases that fits our observations. We show that this separation affects follower bees as well and results in them more likely following subsequent dances to similar food source locations, constituting a positive feedback loop. Our work provides evidence that the positional drift between subsequent waggle phases modulates the information that is available to dance followers, leading to an emergent optimization of the waggle dance communication system.
Making ends meet – relating a self-reported indicator of financial hardship to health status
Authors: Homer Kate , Taylor Jayne , Miller Alexander , Pickett Kate , Wilson Lucy , Robson John
Published: August 2023

Background

Area-based index of multiple deprivation (IMD) indicators of financial hardship lack individual specificity and sensitivity. This study compared self-reports of hardship with area measures in relation to health status.

Methods

Interviews in one London Borough, reported financial hardship and health status. Associations of health status with most and least deprived quintiles of the IMD 2015 were compared with self-reported hardship; always or sometimes ‘having difficulty making ends meet at the end of the month’ in relation to never.

Results

1024 interviews reported hardship status in 1001 (98%). 392 people (39%) reported they ‘always’ or ‘sometimes’ had hardship. In multivariate analysis, self-reported hardship was more strongly associated with smoking; odds ratio = 5.4 (95% CI: 2.8–10.4) compared with IMD, odds ratio = 1.9 (95% CI: 1.2–3.2). Health impairment was also more likely with self-reported hardship, odds ratio = 11.1 (95% CI: 4.9–25.4) compared with IMD; odds ratio = 2.7 (95% CI: 1.4–5.3). Depression was similarly related; odds ratio = 2.4 (95% CI: 1.0–5.6) and 2.7 (95% CI: 1.2–6.6), respectively.

Conclusions

Self-reported hardship was more strongly related to health status than area-based indicators. Validity and implementation in routine health care settings remains to be established.
Significant nailfold capillary loss and late capillaroscopic pattern are associated with pulmonary arterial hypertension in systemic sclerosis
Authors: De Angelis Rossella , Riccieri Valeria , Cipolletta Edoardo , Del Papa Nicoletta , Ingegnoli Francesca , Bosello Silvia , Spinella Amelia , Pellegrino Greta , de Pinto Marco , Papa Silvia , Armentaro Giuseppe , Giuggioli Dilia
Published: August 2023

Objective

To evaluate differences in nailfold videocapillaroscopy (NVC) findings between SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH).

Methods

One hundred and ten SSc patients were enrolled in this cross-sectional, case–control, multicentre study. Patients were divided into cases (SSc-PAH confirmed by right heart catheterization) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system.

Results

SSc-PAH patients showed higher frequencies of late pattern (P < 0.01), non-specific abnormalities (P < 0.01), lower capillary density (P < 0.01), higher avascular areas (P < 0.01) and a higher mean NVC score (P < 0.01). Contrarily, the early/active pattern (P < 0.01) and a higher rate of micro-haemorrhages (P = 0.04) were more frequent in non-PAH patients. By a multivariate analysis, SSc-PAH patients, compared with non-PAH, had more non-specific abnormalities [27/55, 49.1% vs 10/55, 18.2%; adjusted odd ratio (OR) 16.89; 95% CI: 3.06, 93.16], a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%; adjusted OR 38.33; 95% CI: 2.34, 367.80) and avascular areas (18/55, 32.7% vs 10/55, 18.2%; adjusted OR 16.90; 95% CI: 2.64, 44.35). A correlation was found between the mean pulmonary arterial pressure and avascular areas (P < 0.01), capillary density (P < 0.01) and non-specific abnormalities (P < 0.01). A clinical model including the NVC variables may be able to predict a diagnosis of PAH.

Conclusion

Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e. capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH.
Improved Cryopreservation of Human Induced Pluripotent Stem Cell (iPSC) and iPSC-derived Neurons Using Ice-Recrystallization Inhibitors
Authors: Alasmar Salma , Huang Jez , Chopra Karishma , Baumann Ewa , Aylsworth Amy , Hewitt Melissa , Sandhu Jagdeep K , Tauskela Joseph S , Ben Robert N , Jezierski Anna
Published: August 2023

Human induced pluripotent stem cells (iPSCs) and iPSC-derived neurons (iPSC-Ns) represent a differentiated modality toward developing novel cell-based therapies for regenerative medicine. However, the successful application of iPSC-Ns in cell-replacement therapies relies on effective cryopreservation. In this study, we investigated the role of ice recrystallization inhibitors (IRIs) as novel cryoprotectants for iPSCs and terminally differentiated iPSC-Ns. We found that one class of IRIs, N-aryl-D-aldonamides (specifically 2FA), increased iPSC post-thaw viability and recovery with no adverse effect on iPSC pluripotency. While 2FA supplementation did not significantly improve iPSC-N cell post-thaw viability, we observed that 2FA cryopreserved iPSC-Ns re-established robust neuronal network activity and synaptic function much earlier compared to CS10 cryopreserved controls. The 2FA cryopreserved iPSC-Ns retained expression of key neuronal specific and terminally differentiated markers and displayed functional electrophysiological and neuropharmacological responses following treatment with neuroactive agonists and antagonists. We demonstrate how optimizing cryopreservation media formulations with IRIs represents a promising strategy to improve functional cryopreservation of iPSCs and post-mitotic iPSC-Ns, the latter of which have been challenging to achieve. Developing IRI enabling technologies to support an effective cryopreservation and an efficiently managed cryo-chain is fundamental to support the delivery of successful iPSC-derived therapies to the clinic.
A predictive score for severity in patients with confirmed dengue fever in a tertiary care hospital in Kerala, India
Authors: Haridas Sruthi , M Gopalakrishna Pillai , Bhaskaran Renjitha
Published: August 2023

Background

The study aimed to identify predictors of severe dengue during the 2017 epidemic and to develop and validate a simple predictive score for severity.

Methods

A retrospective analytical study was conducted using clinical and laboratory data from adult dengue patients with a confirmed microbiological diagnosis. The study included patients who presented to a tertiary care centre in Kerala, India, during the febrile phase (≤4 d) between June 2017 and February 2019. Using appropriate statistical tests, we derived predictors of severe disease and computed a risk score model.

Results

Of the 153 patients (mean age 50±17 y; 64% males), 31 (20%) had severe dengue and 4 (3%) died. Petechial lesions, hypoalbuminemia (<3.5 g/dl), elevated alanine aminotransferase (>40 IU/l) and urea >40 IU/l were significant predictors. Our scoring system (cut-off: 2) showed excellent performance, with an area under the receiver operating characteristics curve of 0.9741, sensitivity of 100%, specificity of 96% and accuracy of 98%. The risk score was secondarily validated on 48 patients hospitalized from March 2019 to June 2019.

Conclusion

Our scoring system is easy to implement and will help primary healthcare practitioners in promptly identifying severe dengue cases upon hospital presentation.
“Dangerous in the Minds of Barrio People”: Empowering Bicultural Latino Identity on Spanish-Language Television in Los Angeles, 1960–1990
Authors: Parra Carlos Francisco
Published: August 2023

This article focuses on the bicultural Latino identity-building discourses promoted by TV stations KMEX Channel 34 (Spanish International Network/Univision) and KVEA Channel 52 (Telemundo) through news and public affairs programming in metropolitan Los Angeles, home of the United States’s largest concentration of Latinas and Latinos. The two stations’ news and public affairs shows are historically significant for being their most extensive locally produced content and offering a valuable audio/visual representation of Latino Southern California’s cultural development from the early 1960s to late 1980s. Both stations reflected their social context, broadcasting to an overwhelmingly Mexican-heritage audience; but producers and investors at KMEX-34 and KVEA-52 also consciously sought a wider Spanish-speaking audience in Southern California by framing viewers as politically empowered bicultural U.S. Latino subjects defined by a positive affirmation of their cultural background (broadly inclusive of all of Latin America) and their integration into U.S. life through participation in electoral politics and other civic processes. Combining archival research consisting of early scripts, office memoranda, program reviews, viewer letters, oral history interviews, and analysis of extant video recordings preserved in the UCLA Film and Television Archive’s News and Public Affairs Collection, I historicize the ways locally produced programming on Spanish-language TV framed and promoted notions of an additive and empowering bicultural U.S. Latino identity.
Inheritance of Resistance to Bacterial Halo Blight and Bacterial Leaf Spot in Arabica Coffee
Authors: Rodrigues Lucas Mateus Rivero , Andrade Vinícius Teixeira , Destéfano Suzete Aparecida Lanza , Braghini Masako Toma , Caixeta Larissa Brito , Guerreiro-Filho Oliveiro
Published: August 2023

Developing coffee cultivars resistant to multiple diseases by combining resistance genes is a top priority in breeding programs. To create cultivars resistant to diseases and nematodes, we transferred genes for resistance to bacterial infections caused by Pseudomonas coronafaciens pv. garcae, which causes bacterial halo blight (BHB), and P. amygdali pv. tabaci, which causes bacterial leaf spots (BLS), into Arabica coffee. Genetic analyses were conducted on breeding populations to estimate the number and function of genes that confer resistance to BHB and BLS. In total, 2,109 plants in the F2 generation and reciprocal backcrosses were inoculated with P. coronafaciens pv. garcae, while 1,996 plants were inoculated with P. amygdali pv. tabaci. Results showed that resistance to both pathogens had a heritability of 0.99, and the segregations of resistance indicated that each disease was controlled by a single dominant gene. The analyses also revealed that the resistance genes for BHB and BLS were linked, with an average distance of 10.75 cM between them on the same chromosome.
Recent advances in precision medicine for acute myeloid leukemia
Authors: Hernández-Sánchez Alberto , Bullinger Lars
Published: August 2023

Purpose of review

Acute myeloid leukemia (AML) is a heterogeneous disease, in which treatment response and patient survival are highly conditioned by the leukemia biology. The aim of this review is to summarize recent advances in AML classification, risk stratification models, measurable residual disease (MRD) and the increasing number of treatment options that are paving the way towards precision medicine in AML.

Recent findings

AML classification and risk stratification were recently updated by incorporating novel molecular markers that are important for diagnosis and outcome prediction. In addition, the impact of co-mutational patterns is under investigation and novel approaches using machine learning algorithms are starting to be used for individualized risk estimation. Molecular markers are also becoming useful in predicting response to non-intensive treatments. MRD informs of treatment response with high sensitivity, allowing dynamic patient risk assessment and early intervention. Finally, important advances were made in AML therapy, with an increasing number of targeted therapies becoming available and many novel treatment approaches being under development with promising early results.

A better understanding of AML biology is leading to improved risk stratification and important advances in treatments, which are allowing the development of precision medicine in AML at an unprecedented pace.
Surrogate endpoints for HTA decisions of breast cancer drugs: utility and pitfalls
Authors: Wright Kristin , Mittal Abhenil , Gyawali Bishal
Published: August 2023

Purpose of review

Health technology assessment (HTA) of cancer drugs is important to identify whether drugs should be publicly funded. With increasing use of surrogate end points in clinical trials including breast cancer, a review of literature was done to synthesize evidence for validation of these surrogate end points and their potential role in HTA decisions pertaining to breast cancer.

Findings

Disease free survival (DFS) in human epidermal receptor 2 (HER2) positive early breast cancer remains the only validated surrogate end point. Other surrogate end points like pathological complete response (pCR) and event free survival (EFS) in early breast cancer (EBC) and objective response rate (ORR) and progression free survival (PFS) in advanced disease have not been validated for overall survival (OS). Moreover, surrogate end points for quality of life (QOL) have not been established and drugs that improve PFS can have detrimental effect on QOL. End points like pCR have excellent prognostic utility in individual patients but have weak correlation with survival at trial level.

Most surrogate end points used in breast cancer do not predict OS or QOL which makes it challenging to use them for decisions regarding public funding of cancer drugs. These findings are relevant to HTA agencies prior to making drug reimbursement decisions.
Clinical utility of genomic signatures for the management of early and metastatic triple-negative breast cancer
Authors: Castellano Grazia , Giugliano Federica , Curigliano Giuseppe , Marra Antonio
Published: August 2023

Purpose of review

This comprehensive review aims to provide timely and relevant insights into the current therapeutic landscape for triple-negative breast cancer (TNBC) and the molecular features underlying this subtype. It emphasizes the need for more reliable biomarkers to refine prognostication and optimize therapy, considering the aggressive nature of TNBC and its limited targeted treatment options.

Recent findings

The review explores the multidisciplinary management of early TNBC, which typically involves systemic chemotherapy, surgery, and radiotherapy. It highlights the emergence of immune checkpoint inhibitors (ICIs), poly(ADP-ribose) polymerase (PARP) inhibitors, and antibody–drug conjugates (ADCs) as promising therapeutic strategies for TNBC. Recent clinical trials investigating the use of ICIs in combination with chemotherapy and the approval of pembrolizumab and atezolizumab for PD-L1-positive metastatic TNBC are discussed. The efficacy of PARP inhibitors and ADCs in treating TNBC patients with specific genetic alterations is also highlighted.

The findings discussed in this review have significant implications for clinical practice and research in TNBC. The identification of distinct molecular subtypes through gene expression profiling has enabled a better understanding of TNBC heterogeneity and its clinical implications. This knowledge has the potential to guide treatment decisions, as different subtypes display varying responses to neoadjuvant chemotherapy. Furthermore, the review emphasizes the importance of developing reliable genomic and transcriptomic signatures as biomarkers to refine patient prognostication and optimize therapy selection in TNBC. Integrating these signatures into clinical practice may lead to more personalized treatment approaches, improving outcomes for TNBC patients.
Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Authors: Meng Wenbo , Leung Joseph W. , Wang Zhenyu , Li Qiyong , Zhang Leida , Zhang Kai , Wang Xuefeng , Wang Meng , Wang Qi , Shao Yingmei , Zhang Jijun , Yue Ping , Zhang Lei , Zhu Kexiang , Zhu Xiaoliang , Zhang Hui , Hou Senlin , Cai Kailin , Sun Hao , Xue Ping , Liu Wei , Wang Haiping , Zhang Li , Ding Songming , Yang Zhiqing , Zhang Ming , Weng Hao , Wu Qingyuan , Chen Bendong , Jiang Tiemin , Wang Yingkai , Zhang Lichao , Wu Ke , Yang Xue , Wen Zilong , Liu Chun , Miao Long , Wang Zhengfeng , Li Jiajia , Yan Xiaowen , Wang Fangzhao , Zhang Lingen , Bai Mingzhen , Mi Ningning , Zhang Xianzhuo , Zhou Wence , Yuan Jinqiu , Suzuki Azumi , Tanaka Kiyohito , Liu Jiankang , Nur Ula , Weiderpass Elisabete , Li Xun
Published: August 2023

Background:

Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery.

Methods:

This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle.

Results:

The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ
2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ
2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ
2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models.

Conclusion:

Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.

Trail Registration:

ClinicalTrials.gov, No. NCT03075280.
Refractory hepatic hydrothorax is associated with increased mortality with death occurring at lower MELD-Na compared to cirrhosis and refractory ascites
Authors: Chin Allison , Bastaich Dustin R. , Dahman Bassam , Kaplan David E. , Taddei Tamar H. , John Binu V.
Published: August 2023

Background and Aims:

Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized Model for End-stage Liver Disease (MELD) exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA).

Approach and Results:

This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (adjusted HR [aHR] 4.63, 95% CI 3.31–6.48) than RA overall and within all MELD-sodium (MELD-Na) strata (<10 aHR 4.08, 95% CI 2.30–7.24, 10–14.9 aHR 5.68, 95% CI 2.63–12.28, 15–24.9 aHR 4.14, 95% CI 2.34–7.34, ≥25 aHR 7.75, 95% CI 2.99–20.12). LRD was higher among participants requiring 1 (aHR 3.54, 95% CI 2.29–5.48), 2–3 (aHR 4.39, 95% CI 2.91–6.63), and ≥4 (aHR 7.89, 95% CI 4.82–12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p=0.002) but higher MELD 3.0 (27.85 vs. 22.48, p<0.0001).

Conclusions:

RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.
Examination of the Corneal Endothelium in Pediatric Patients With COVID-19
Authors: Soysal Gizem Gürbostan , Seyyar Sevim Ayça , Kimyon Sabit , Mete Alper , Güngör Kıvanç
Published: August 2023

Purpose:

To investigate the effects of coronavirus disease 2019 (COVID-19) infection on the corneal endothelium in children.

Methods:

This retrospective study included 46 pediatric patients with COVID-19 infection and 38 healthy controls. Specular microscopy measurements were analyzed, and measurements were obtained from images showing at least 100 cells with clear borders. Mean endothelial cell density, mean hexagonal cell percentage (HEX), mean coefficient of variation (CV), central corneal thickness, and mean cell area were evaluated.

Results:

Specular microscopy data showed that the CV values were 2.442±6.517 in the healthy control group (HCG) and 2.659±5.119 in the COVID-19–affected group (CAG) (P=0.003). The hexagonality of the HCG and CAG were 6.916±8.271 and 6.683±5.885, respectively (P=0.011).

Conclusion:

A decrease in the HEX and an increase in the CV were observed in the corneal specular microscopic examination of children with COVID-19 infection. These results are important in demonstrating the corneal effects of COVID-19 infection in children.
Osteoarticular Infections: Younger Children With Septic Arthritis and Low Inflammatory Patterns Have a Better Prognosis in a European Cohort
Authors: Gouveia Catarina , Subtil Ana , Aguiar Pedro , Canhão Helena , Norte Susana , Arcangelo Joana , Varandas Luís , Tavares Delfin
Published: August 2023

Background:

Osteoarticular infections (OAI) are associated with complications and sequelae in children, whose prediction are of great importance in improving outcomes. We aimed to design risk prediction models to identify early complications and sequelae in children with OAI.

Methods:

This observational study included children (>3 months–17 years old) with acute OAI admitted to a tertiary-care pediatric hospital between 2008 and 2018. Clinical treatment, complications and sequelae were recorded. We developed a multivariable logistic predictive model for an acute complicated course (ACC) and another for sequelae.

Results:

A total of 240 children were identified, 17.5% with ACC and 6.0% and 3.6% with sequelae at 6 and 12 months of follow-up, respectively. In the multivariable logistic predictive model for ACC, predictors were fever at admission [adjusted odds ratio (aOR): 2.98; 95% confidence interval (CI): 1.10–8.12], C-reactive protein ≥100 mg/L (aOR: 2.37; 95% CI: 1.05–5.35), osteomyelitis (aOR: 4.39; 95% CI: 2.04–9.46) and Staphylococcus aureus infection (aOR: 3.50; 95% CI: 1.39–8.77), with an area under the ROC curve of 0.831 (95% CI: 0.767–0.895). For sequelae at 6 months, predictors were age ≥4 years (aOR: 4.08; 95% CI: 1.00–16.53), C-reactive protein ≥110 mg/L (aOR: 4.59; 95% CI: 1.25–16.90), disseminated disease (aOR: 9.21; 95% CI: 1.82–46.73) and bone abscess (OR: 5.46; 95% CI: 1.23–24.21), with an area under the ROC curve of 0.887 (95% CI: 0.815–0.959).

Conclusions:

In our model we could identify patients at low risk for complications and sequelae, probably requiring a less aggressive approach.
Interpretation bias and the transition from acute to chronic pain
Authors: Todd Jemma , Pickup Brydee , Sharpe Louise
Published: August 2023

Most theories of pain emphasize cognitive factors in the development of chronicity, but they have rarely been studied in the context of the transition from acute to chronic pain. The aim of the present study was to assess the role of interpretation bias, pain anxiety, and pain avoidance in acute and chronic pain and the transition from acute to chronic pain. Study 1 recruited a sample of N = 85 adults with chronic pain. Study 2 recruited a sample of N = 254 adults with acute pain and followed them up 3 months later. Both studies assessed interpretation bias with the word association task, as well as measuring pain-related anxiety, pain avoidance, pain severity, and pain interference. In study 2, pain outcomes at 3 months were also assessed. Across both acute and chronic pain samples, interpretation bias was associated with pain interference, but not pain severity. Path analysis mediation models for study 2 showed that interpretation bias was associated with increased pain anxiety, which predicted both pain severity and pain interference 3 months later. Pain anxiety was also associated with pain avoidance, but pain avoidance did not predict pain outcomes. This research provides further insight into the transition from acute to chronic pain, suggesting that interpretation bias in acute pain may play a role in pain-related anxiety that drives pain interference, thus maintaining chronic pain. These findings hold promise for further research into potential large-scale preventative interventions targeting interpretation bias and pain anxiety in acute pain.
Longitudinal Auditory Benefit for Elderly Patients After Cochlear Implant for Bilateral Hearing Loss, Including Those Meeting Expanded Centers for Medicare & Medicaid Services Criteria
Authors: Shen Sarek , Sayyid Zahra , Andresen Nicholas , Carver Courtney , Dunham Rachel , Marsiglia Dawn , Yeagle Jennifer , Della Santina Charley C. , Bowditch Steve , Sun Daniel Q.
Published: August 2023

Objective

To examine the effect of patient age on longitudinal speech understanding outcomes after cochlear implantation (CI) in bilateral hearing loss.

Study Design

Retrospective cohort study.

Setting

Tertiary academic center

Patients

One thousand one hundred five adult patients with bilateral hearing loss receiving a unilateral CI between 1987 and 2022

Interventions

None.

Main Outcome Measures

Postoperative speech recognition outcomes, including AzBio sentences, consonant-nucleus-consonant word, and Hearing in Noise Test in quiet were analyzed at short-term (<2 yr), medium-term (2–8 y), and long-term (>8 yr) term postoperative intervals.

Results

Eighty-six very elderly (>80 yr), 409 elderly (65–80 yr), and 709 nonelderly (18–65 yr) patients were included. Short-term postoperative AzBio scores demonstrated similar magnitude of improvement relative to preoperative scores in the very elderly (47.6, 95% confidence interval [CI], 28.9–66.4), elderly (49.0; 95% CI, 39.2–58.8), and nonelderly (47.9; 95% CI, 35.4–60.4). Scores for those older than 80 years remained stable after 2 years after implant, but in those 80 years or younger, scores continued to improve for up to 8 years (elderly: 6.2 [95% CI, 1.5–12.4]; nonelderly: 9.9 [95% CI, 2.1–17.7]) after implantation. Similar patterns were observed for consonant-nucleus-consonant word scores. Across all age cohorts, patients with preoperative Hearing in Noise Test scores between 40 and 60% had similar scores to those with preoperative scores of less than 40%, at short-term (82.4, 78.9; 95% CI, −23.1 to 10.0), medium-term (77.2, 83.9; 95% CI, −15.4 to 8.2), or long-term (73.4, 71.2; 95% CI, −18.2 to 12.2) follow-up.

Conclusions

Patients older than 80 years gain significant and sustained auditory benefit after CI, including those meeting expanded Centers for Medicare & Medicaid Service criteria for implantation. Patients younger than 80 years demonstrated continued improvement over longer periods than older patients, suggesting a role of central plasticity in mediating CI outcomes as a function of age.
Incidence of Vestibular Schwannoma in Patients with Unilateral Tinnitus: A Systematic Review and Meta-Analysis
Authors: Javed Azfar , Okoh Magnus , Mughal Zahir , Javed Faisal , Gupta Keshav
Published: August 2023

Objectives

Vestibular schwannoma (VS) is a tumor of the vestibulocochlear nerve. Current literature indicates that 1.6% of patients undergoing magnetic resonance imaging of the internal auditory meatus (MRI IAM) for audiovestibular symptoms are diagnosed with a VS. However, there is limited research reporting on patients who present with unilateral tinnitus without asymmetrical hearing loss. This study is a systematic review and meta-analysis evaluating how many of those patients had a VS diagnosed on MRI IAM.

Databases Used

Online searches of PubMed, Medline, and Embase databases were performed up to October 2022.

Methods

This meta-analysis was undertaken aligning with PRISMA guidelines. Articles reporting on patients having MRI IAM for unilateral tinnitus without asymmetrical hearing loss were included. Outcomes measures were patient demographics, VS cases, incidental findings, size, and management of tumor. A meta-analysis of proportions was performed using a random-effects model with the restricted maximum likelihood method. Quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.

Results

Seven case series were included in the review: a total of 1,394 patients. Seven patients had a VS, with a median size of 4 mm. The pooled detection rate for VS was 0.08% (95% confidence interval = 0.00–0.45). Subsequent management was reported in six cases of which four were actively monitored and two surgically excised. The most common incidental finding was sinus disease (49 patients).

Conclusion

Our findings indicate that MRI IAM has a low diagnostic yield for VS detection in patients presenting with unilateral tinnitus without asymmetrical hearing loss, with mostly small tumors that are conservatively managed.
Incomplete Partition Type II Cochlear Malformations: Delineating the Three-Dimensional Structure from Digitized Human Histopathological Specimens
Authors: Swords Chloe , Geerardyn Alexander , Zhu MengYu , O'Malley Jennifer T. , Wu Peizhe , Arenberg Julie G. , Podury Archana , Brassett Cecilia , Bance Manohar , Quesnel Alicia M.
Published: August 2023

Hypothesis

There are clinically relevant differences in scalae anatomy and spiral ganglion neuron (SGN) quantity between incomplete partition type II (IP-II) and normal cochleae.

Background

IP-II is a commonly implanted cochlear malformation. Detailed knowledge of intracochlear three-dimensional (3D) morphology may assist with cochlear implant (CI) electrode selection/design and enable optimization of audiologic programming based on SGN maps.

Methods

IP-II (n = 11) human temporal bone histological specimens were identified from the National Institute on Deafness and Other Communication Disorders National Temporal Bone Registry and digitized. The cochlear duct, scalae, and surgically relevant anatomy were reconstructed in 3D. A machine learning algorithm was applied to map the location and number of SGNs.

Results

3D scalae morphology of the basal turn was normal. Scala tympani (ST) remained isolated for 540 degrees before fusing with scala vestibuli. Mean ST volume reduced below 1 mm2after the first 340 degrees. Scala media was a distinct endolymphatic compartment throughout; mean ± standard deviation cochlear duct length was 28 ± 3 mm. SGNs were reduced compared with age-matched norms (mean, 48%; range, 5–90%). In some cases, SGNs failed to ascend Rosenthal's canal, remaining in an abnormal basalward modiolar location. Two forms of IP-II were seen: type A and type B. A majority (98–100%) of SGNs were located in the basal modiolus in type B IP-II, compared with 76 to 85% in type A.

Conclusion

Hallmark features of IP-II cochleae include the following: 1) fusion of the ST and scala vestibuli at a mean of 540 degrees, 2) highly variable and overall reduced SGN quantity compared with normative controls, and 3) abnormal SGN distribution with cell bodies failing to ascend Rosenthal's canal.
Rates of Delayed Postcochlear Implant Pain in the Pediatric Population—Role of Proactive Approach
Authors: Rotlevi Tomer , Ziv Oren , Hazan Itai , Cohen Oded , Al Jaar Hasan , Alkrenawi Mohamad , Kaplan Daniel M.
Published: August 2023

Objective

To investigate the rates of delayed postoperative cochlear implantation pain (DPCIP) in the pediatric population, using a “reach-out” proactive approach. Secondary aims included the possible impact of surgery extent or the patient ethnicity on DPCIP rates.

Materials and methods

A cross-sectional study was conducted at Soroka University Medical Center in Israel. Demographics and data regarding the surgery and surgical complications were collected from the medical records of the patients. A telephone questionnaire was conducted for parents of all children who underwent cochlear implantation (CI) between 2007 and 2020. The questions addressed pain at four time periods: during hospitalization after surgery, 3 months, 2 years, and 5 years after surgery.

Results

Out of 213 patients, 129 (60%) were included in this study. The mean age was 41 months (±40). Unilateral CI was performed in 72 (56%) patients. At 3 months and 2 years after surgery, 8.5% of patients reported pain (visual analog scale [VAS] ≥ 1). Five years after surgery, a slight increase in the number of patients who reported pain (12%) was observed. Of those experiencing pain 2 years and 5 years after surgery, 10/12 (83%) and 11/16 (69%), respectively, reported a new onset of the pain. Surgery extent and cultural background were not significantly associated with DPCIP rates. No correlations were found between patients complaining of pain and any surgical complications.

Conclusions

DPCIP rates may be underrecognized and higher than previously reported, reaching up to 12%. This long-term effect should be acknowledged and discussed with parents upon informed consent.
Free Flap Reconstruction in the Era of Commercial Price Transparency – What are We Paying For?
Authors: Rochlin Danielle H. , Rizk Nada M. , Mehrara Babak , Matros Evan , Sheckter Clifford C.
Published: August 2023

Background:

Commercial rates for free flap reconstruction were not known publicly prior to the 2021 Hospital Price Transparency Final Rule. The purpose of this study was to examine commercial facility payments to characterize nationwide variation for microsurgical operations and identify opportunities to improve market effectiveness.

Methods:

A cross-sectional study was performed using 2022 commercial insurance pricing merged with hospital performance data. Facility payment rates were extracted for nine CPT codes for free flap operations. Price variation was quantified via across-hospital ratios (AHRs) and within-hospital ratios (WHRs). Mixed effects linear models evaluated commercial rates relative to value, outcomes, and equity performance metrics, in addition to facility-level factors that included healthcare market concentration.

Results:

20,528 commercial rates across 675 hospitals were compiled. AHRs ranged from 5.85–7.95, while WHRs ranged from 1.00–1.71. Compared to the lowest scoring hospitals (grade D), hospitals with an outcome grade of A and equity grades of B or C were associated with higher commercial rates (p<0.04); there were no significant differences in rate based on value. Higher commercial rates were also associated with nonprofit status and more concentrated markets (p<0.006). Lower commercial rates were correlated with safety-net and teaching hospitals (p<0.001).

Conclusion:

Commercial rates for free flaps varied substantially both across and within hospitals. Associations of higher commercial rates with less competitive markets, and the lack of consistent association with value and equity, identify pricing failures. Additional work is needed to improve market efficiency for free flap operations.