bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acetaminophen versus indomethacin for patent ductus arteriosus management in premature infants: systematic review and meta-analysis of randomized controlled trials
Authors: Bitar Eyad , Hyderi Abbas , Campbell Sandra M , Kumar Manoj 
Published: April 2023

Abstract

Objectives
Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants.

Methods
We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3.

Results
Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], P-value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], P-value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], P-value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], P-value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use.

Conclusions
Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use.
LP342, a novel histone deacetylase inhibitor, decreases nitro-oxidative stress, mitochondrial dysfunction and hepatic ischaemia/reperfusion injury in mice
Authors: Samuvel Devadoss J , Krishnasamy Yasodha , Li Li , Lemasters John J , Chou C James , Zhong Zhi 
Published: April 2023

Abstract

Objectives
Some histone deacetylase (HDAC) isoforms contribute to ischaemia/reperfusion (IR) injury (IRI). Here, we examined whether LP342, the lead candidate of a new generation of hydrazide-based HDAC inhibitors (HDACi), decreases hepatic IRI.

Methods
IR was induced by clamping blood vessels to ~70% of the livers of mice for 1 h.

Key findings
At 6 h after reperfusion, ALT markedly increased, and wide-spread necrosis, leukocyte infiltration, and apoptosis occurred. LP342 treatment (1 mg/kg, ip) at 20 h or 1 h before ischaemia markedly decreased IRI whereas LP342 treatment upon reperfusion was marginally protective. Nitro-oxidative stress, c-Jun-N-terminal kinase (JNK) activation, and mitochondrial dysfunction contribute to IRI. 4-Hydroxynonenal, 3-nitrotyrosine, inducible nitric oxide synthase (iNOS), JNK activation and Sab binding increased markedly after IR, which LP342 blunted. LP342 also induced thioredoxin-1 expression before and after IR. LP342 also decreased mitochondrial depolarisation as detected by intravital microscopy at 2 h after IR. Lastly, LP342 increased acetylation of both histone-3 (class I HDAC substrate) and NFκB p65 but not tubulin (class II HDAC substrate) before and after IR.

Conclusions
This novel HDACi protects against IRI most likely by epigenetic upregulation of antioxidant proteins and post-translational modifications of NFκB thus inhibiting iNOS expression and inflammatory responses.
Targeting Disease Susceptibility Genes in Wheat Through wide Hybridization with Maize Expressing Cas9 and Guide RNA
Authors: Karmacharya Anil , Li Dandan , Leng Yueqiang , Shi Gongjun , Liu Zhaohui , Yang Shengming , Du Yang , Dai Wenhao , Zhong Shaobin 
Published: April 2023

Two genes ( TaHRC and Tsn1) conferring susceptibility to Fusarium head blight and tan spot, Septoria nodorum blotch, and spot blotch in wheat were targeted through wide hybridization with maize expressing Cas9 and guide RNA (gRNA). For each gene, two target sites were selected and corresponding gRNA expression cassettes were synthesized and cloned into a binary vector carrying the CRISPR/Cas9-mediated genome editing machinery. The constructed binary vectors were used to transform the hybrid maize Hi-II through an Agrobacterium-mediated approach to generate T0 and T1 plants, which were used to cross with wheat variety Dayn for targeting Tsn1 or the susceptible allele ( TaHRC-S) of TaHRC as well as with the near-isogenic line (Day- Fhb1) of Dayn for targeting the resistant allele ( TaHRC-R) of TaHRC. Haploid embryos were rescued in vitro from the wide crosses to generate haploid plants. PCR amplification and sequencing indicated that 15 to 33% of the haploid plants contained the target gene with mutations at the target sites. This wheat × maize hybridization combined with genome editing approach provides a useful alternative tool, not only for targeting susceptibility genes to improve disease resistance without regulatory issues, but also for understanding gene function in wheat. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Measures for the Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS)
Authors: Rose Louise , Blackwood Bronagh , Needham Dale M. , Devlin John W. , Clarke Mike , Burry Lisa D. ,   for the Del-COrS group
Published: April 2023

OBJECTIVES:
To gain consensus on measurement methods for outcomes (delirium occurrence, severity, time to resolution, mortality, health-related quality of life [HrQoL], emotional distress including anxiety, depression, acute stress, and post-traumatic stress disorder, and cognition) of our Core Outcome Set (COS) for trials of interventions to prevent and/or treat delirium in critically ill adults.

DESIGN:
International consensus process.

SETTING:
Three virtual meetings (April 2021).

PATIENTS/SUBJECTS:
Critical illness survivors/family, clinicians, and researchers from six Countries.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Measures (selected based on instrument validity, existing recommendations, and feasibility) and measurement time horizons were discussed. Participants voted on instruments and measurement timing (a priori consensus threshold ≥ 70%). Eighteen stakeholders (28% ICU survivors/family members) participated. We achieved consensus on the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist to measure delirium occurrence and delirium resolution (100%), Hospital Anxiety and Depression Scale for emotional distress (71%), and Montreal Cognitive Assessment-Blind for cognition (83%). We did not achieve consensus on EQ-5D five-level for HrQoL (69%) or its measurement at 6 months. We also did not achieve consensus on the Impact of Event Scale (IES)–Revised or IES-6 for post-traumatic stress (65%) or on measurement instruments for delirium severity incorporating delirium-related emotional distress. We were unable to gain consensus on when to commence and when to discontinue assessing for delirium occurrence and time to resolution, when to determine mortality. We gained consensus that emotional distress and cognition should be measured up to 12 months from hospital discharge.

CONCLUSIONS:
Consensus was reached on measurement instruments for four of seven outcomes in the COS for delirium prevention or treatment trials for critically ill adults. Further work is required to validate instruments for delirium severity that include delirium-related emotional distress.
Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury
Authors: Wang Tingting , Liu Jinmin , Hu Chenchen , Wei Xin , Han Linlin , Zhu Afang , Wang Rong , Chen Zhijun , Xia Zhengyuan , Yao Shanglong , Mao Weike 
Published: April 2023

Abstract

Background:
Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.

Methods:
Male Sprague–Dawley rats were infected with PIASy short hairpin RNA (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.

Results:
Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.

Conclusion:
PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rapid Detection of Lithium Concentrations in Oral Fluid
Authors: Granger Douglas A. , Parkin Georgia M. , Buspavanich Pichit , Findeisen Peter , Rietschel Marcella , McCarthy Michael J. , Thomas Elizabeth A. 
Published: April 2023

Background:
Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels. The aim of this study was to evaluate the analytical performance of rapid assays for lithium measurements in oral fluid.

Methods:
Levels of lithium in oral fluid from psychiatric patients (n = 108 in total) taking lithium medications were quantified using 2 rapid techniques: an automated clinical chemistry analyzer and a novel, commercially available colorimetric lithium assay. These results were compared with those obtained using inductively coupled plasma optical emission spectrometry (ICP-OES).

Results:
The mean and median oral fluid lithium levels in this cohort were 1.43–1.61 mM and 1.32–1.52 mM, respectively, depending on the method, with the overall range, across all methods, being 0.213–4.42 mM. Linear regression analysis showed excellent agreement between the oral fluid values measured using ICP-OES and the colorimetric method (r2 value = 0.926; P < 0.0001; slope = 1.084 ± 0.038). Similarly, excellent agreement was observed between ICP-OES and the automated method (r2 = 0.872; P < 0.0001; slope = 1.019 ± 0.057).

Conclusions:
These results demonstrate that lithium levels in oral fluid can be rapidly and reliably quantified using colorimetric approaches. These findings may facilitate the development of point-of-care lithium monitoring systems for use in oral fluid.
Impact of CYP2D6 Genotype on Paroxetine Serum Concentration
Authors: Hole Kristine , Haslemo Tore , Molden Espen 
Published: April 2023

Background:
Paroxetine is a selective serotonin reuptake inhibitor metabolized by cytochrome P450 (CYP)2D6. Only small-scale studies have reported the impact of CYP2D6 genotype on paroxetine exposure, and international guidelines differ in their recommendations on whether paroxetine should be administered according to CYP2D6 genotype. To clarify this issue, the aim of the present study was to investigate the impact of CYP2D6 genotype on paroxetine serum concentration in a large population of patients after adjusting for CYP2C19 genotype, age, and sex.

Methods:
Patients from a therapeutic drug monitoring database with records on their paroxetine serum concentrations and CYP2D6 and CYP2C19 genotyping between 2010 and 2021 were included in the study. The impact of CYP2D6 and CYP2C19 genotypes, age, and sex on the paroxetine concentration-to-dose (C/D) ratio was investigated by multiple linear regression analysis. Patients treated with relevant CYP inhibitors or inducers were excluded.

Results:
In total, 304 patients were included in the study: 17 CYP2D6 poor metabolizers (PMs), 114 intermediate metabolizers (IMs), 168 extensive metabolizers (EMs), and 5 ultrarapid metabolizers. Multiple linear regression analysis showed that CYP2D6 IMs and PMs had 2.2-fold and 3.8-fold higher paroxetine C/D-ratios than extensive metabolizers, respectively (P < 0.001). Patients who were CYP2C19 IMs (n = 70) or PMs (n = 13) had 1.6-fold higher paroxetine C/D ratio than extensive metabolizers (P = 0.04). An age ≥65 years was associated with a 2.9-fold increased C/D ratio (P < 0.001), whereas sex was not significantly associated with paroxetine exposure.

Conclusions:
The present study showed that CYP2D6 genotype is of significant importance for paroxetine dose adjustments. For CYP2D6 PMs, 25% of the regular paroxetine starting dose may be sufficient, whereas CYP2D6 IMs could receive 50% of the regular dosage. This well-powered study shows that the guidelines should consider the importance of CYP2D6 genotype for personalized dosing of paroxetine.
Clinical Effectiveness of a Supervised Exercise Therapy Program for Treatment of Peripheral Artery Disease: A Translational Study
Authors: Salisbury Dereck L. , Brown Rebecca , Elgersma Kristin , Larson Kayla , Treat-Jacobson Diane 
Published: April 2023

Purpose:
National guidelines for the treatment and management of symptomatic peripheral artery disease (PAD) recommend supervised exercise therapy (SET) as a first line of therapy. However, it is unknown how these expert opinion–based SET guidelines work in clinical practice as SET programs become established following the 2017 Centers for Medicare & Medicaid Services coverage announcement. The purpose of this prospective, nonrandomized translational study was to evaluate the clinical effectiveness of a SET program and specifically walking exercise modalities that did not incorporate a treadmill (TM).

Methods:
Participants enrolled in a 12-wk SET program housed in four rural Midwest cardiac rehabilitation settings and were prescribed an exercise program by an exercise physiologist or nurse based on current SET guidelines. Groups included TM walking, total body recumbent stepping (TBRS), TM walking + TBRS, and multimodal. Pre- and post-tests of walking capacity, physical function, and quality of life were administered.

Results:
The sample (n = 93) was all White, with 55% female representation, age of 73.7 ± 9.0 yr, and mild-moderate PAD (ankle-brachial index = 0.71 ± 0.19). Collectively, SET significantly improved the 6-min walk test (32.1 ± 6.6 m; P < .01). Within-group changes in the 6-min walk test were seen for all groups except the multimodal group; there were no significant between-group differences in change scores (P = .30). No significant between-group changes were seen for the TM walking, TBRS, and TM walking + TBRS groups for physical function measures.

Conclusion:
This study demonstrates the clinical effectiveness of SET programs following current guidelines and potential utilization of non-TM walking modalities in SET programs.
The SCARE 2023 guideline: updating consensus Surgical CAse REport (SCARE) guidelines
Authors: Sohrabi Catrin , Mathew Ginimol , Maria Nicola , Kerwan Ahmed , Franchi Thomas , Agha Riaz A ,   Collaborators
Published: April 2023

Background:
The Surgical CAse REport (SCARE) guidelines were first published in 2016 as a tool for surgeons to document and report their surgical cases in a standardised and comprehensive manner. However, with advances in technology and changes in the healthcare landscape, it is important to revise and update these guidelines to ensure they remain relevant and valuable for surgeons.

Materials and methods:
The updated guidelines were produced through a Delphi consensus exercise. Members of the SCARE 2020 guidelines Delphi group, editorial board members, and peer reviewers were invited to participate. Potential contributors were contacted by e-mail. An online survey was completed to indicate their agreement with the proposed changes to the guideline items.

Results:
A total of 54 participants were invited to participate and 44 (81.5%) completed the survey. There was a high degree of agreement among reviewers, with 36 items (83.7%) meeting the threshold for inclusion.

Conclusion:
Through a completed Delphi consensus exercise we present the SCARE 2023 guidelines. This will provide surgeons with a comprehensive and up-to-date tool for documenting and reporting their surgical cases while highlighting the importance of patient-centred care.
Vasectomy has No Impact on Future Lower Urinary Tract Symptoms Diagnoses: A Retrospective Cohort Claims Database Analysis
Authors: Venigalla Greeshma , Kohn Taylor P. , Pozzi Edoardo , Ramasamy Ranjith 
Published: April 2023

Purpose:
The aim of this study was to assess whether there is an association between vasectomy and benign prostatic hyperplasia with associated lower urinary tract symptoms (BPH/LUTS) due to inflammatory etiology.

Materials and Methods:
We assessed the incidence of BPH/LUTS in men who had undergone vasectomy in a matched cohort analysis using the TriNetX Research Network. We identified men aged 30 to 60 years who underwent vasectomy and had a follow-up visit within 6 months to 5 years after vasectomy from January 2010 through December 2022 and compared them with matched controls. Outcomes recorded include diagnoses of BPH (N40, N40.1), BPH-related medication prescriptions, and BPH-related procedures. We accounted for confounding variables through propensity score-matching for age; race; and history of comorbid medical conditions: hyperlipidemia (International Classification of Disease-10: E78), metabolic syndrome (E88.81), overweight or obesity (E66), testicular hypofunction (E29.1), hypertension (I10-I16), nicotine dependence (F17), and obstructive sleep apnea (G47.33).

Results:
There was no significant difference in BPH diagnosis between postvasectomy men vs controls (0.84% vs 0.80%, RR: 0.95, 95% CI 0.86-1.05) or BPH/LUTS diagnosis (0.48% vs 0.44%, RR: 0.92, 95% CI 0.81-1.05) within 6 months to 5 years after vasectomy, respectively. No differences in BPH medication prescription (0.94% vs 0.84%) or rate of BPH procedures (0.022% vs 0.017%) were detected between the 2 groups.

Conclusions:
This study suggests that vasectomy does not increase the risk of BPH development and/or LUTS worsening compared with the general population, providing assurance to both patients and health care providers who may consider vasectomy as a safe family planning option.
Are open access article processing charges affordable for otolaryngologists in low-income and middle-income countries?
Authors: Seguya Amina , Salano Valerie , Okerosi Samuel , Kim Eric K. , Shrime Mark G. , Viljoen Gerrit , Fagan Johannes J. 
Published: April 2023

Purpose of review
Open access articles are more frequently read and cited, and hence promote access to knowledge and new advances in healthcare. Unaffordability of open access article processing charges (APCs) may create a barrier to sharing research. We set out to assess the affordability of APCs and impact on publishing for otolaryngology trainees and otolaryngologists in low-income and middle-income countries (LMICs).

Recent findings
A cross-sectional online survey was conducted among otolaryngology trainees and otolaryngologists in LMICs globally. Seventy-nine participants from 21 LMICs participated in the study, with the majority from lower middle-income status (66%). Fifty-four percent were otolaryngology lecturers while 30% were trainees. Eighty-seven percent of participants received a gross monthly salary of less than USD 1500. Fifty-two percent of trainees did not receive a salary. Ninety-one percent and 96% of all study participants believed APCs limit publication in open access journals and influence choice of journal for publication, respectively. Eighty percent and 95% believed APCs hinder career progression and impede sharing of research that influences patient care, respectively.

Summary
APCs are unaffordable for LMIC otolaryngology researchers, hinder career progression and inhibit the dissemination of LMIC-specific research that can improve patient care. Novel models should be developed to support open access publishing in LMICs.
Robotic-assisted retroperitoneal lymph node dissection for testicular cancer
Authors: Gereta Sofia , Hung Michael , Hu Jim C. 
Published: April 2023

Purpose of review
Robotic-assisted retroperitoneal lymph node dissection (R-RPLND) is an emerging surgical option for testicular cancer with less morbidity than open RPLND. We outline the operative technique used at our center and review contemporary evidence in the advancement of R-RPLND.

Recent findings
R-RPLND is being applied effectively beyond clinical stage I testicular cancer to treat low-volume, clinical stage II disease in both the primary and postchemotherapy setting. Compared with the open approach, R-RPLND offers shorter hospitalization and less blood loss with comparably low complications and oncologic control.

Summary
With ongoing adoption and optimization of R-RPLND, future studies will assess long-term oncologic outcomes and disseminate R-RPLND in the treatment of testicular cancer.