bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular stable intronic RNAs possess distinct biological features and are deregulated in bladder cancer
Authors: Rasmussen Asta M , Okholm Trine Line H , Knudsen Michael , Vang Søren , Dyrskjøt Lars , Hansen Thomas B , Pedersen Jakob S 
Published: August 2023

Abstract
Until recently, intronic lariats were regarded as short-lasting splicing byproducts with no apparent function; however, increasing evidence of stable derivatives suggests regulatory roles. Yet little is known about their characteristics, functions, distribution, and expression in healthy and tumor tissue. Here, we profiled and characterized circular stable intronic sequence RNAs (sisRNAs) using total RNA-Seq data from bladder cancer (BC; n = 457, UROMOL cohort), healthy tissue (n = 46), and fractionated cell lines (n = 5). We found that the recently-discovered full-length intronic circles and the stable lariats formed distinct subclasses, with a surprisingly high intronic circle fraction in BC (∼45%) compared to healthy tissues (0–20%). The stable lariats and their host introns were characterized by small transcript sizes, highly conserved BP regions, enriched BP motifs, and localization in multiple cell fractions. Additionally, circular sisRNAs showed tissue-specific expression patterns. We found nine circular sisRNAs as differentially expressed across early-stage BC patients with different prognoses, and sisHNRNPK expression correlated with progression-free survival. In conclusion, we identify distinguishing biological features of circular sisRNAs and point to specific candidates (incl. sisHNRNPK, sisWDR13 and sisMBNL1) that were highly expressed, had evolutionary conserved sequences, or had clinical correlations, which may facilitate future studies and further insights into their functional roles.
Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study
Authors: Retzer Ameeta , Baddeley Elin , Sivell Stephanie , Scott Hannah , Nelson Annmarie , Bulbeck Helen , Seddon Kathy , Grant Robin , Adams Richard , Watts Colin , Aiyegbusi Olalekan Lee , Kearns Pamela , Rivera Samantha Cruz , Dirven Linda , Calvert Melanie , Byrne Anthony 
Published: August 2023

Abstract

Background
Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods
A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results
In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions
A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.
A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice
Authors: Zhao Han-Zhi , Guo Zi-Wei , Wang Zhang-Li , Wang Chen , Luo Xian-Yu , Han Ning-Ning , Li Chen-Rui , Zheng Hua-Dong , Hui Zi-Yi , Long Yang , Zhao Yan-Lei , Li Qiu-Jin , Wang Sheng-Yu , Zhang Guang-Wei 
Published: August 2023

Abstract

Introduction
Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms.

Methods
A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells.

Results
Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α.

Conclusions
The findings of the present study indicate that the safety of E-cig should be further evaluated.

Implications
Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.
Effects of Nicotine Content and Preferred Flavor on Subjective Responses to E-cigarettes: A Randomized, Placebo-controlled Laboratory Study
Authors: Bremmer Michael P , Campbell Alana M , Xia Kai , Tarran Robert , Girdler Susan S , Hendershot Christian S 
Published: August 2023

Abstract

Introduction
Evidence suggests that e-liquid flavor and nicotine concentration are important factors in the initiation and maintenance of e-cigarette use (vaping). Flavors may increase the initiation and maintenance of vaping, and nicotine content is a factor in e-cigarette dependence and the efficacy of e-cigarettes for cigarette smoking cessation. Few human laboratory studies have assessed the joint and interactive effects of flavor and nicotine on subjective responses to e-cigarettes.

Methods
Regular e-cigarette users (N = 89) completed a multi-session study involving a paced vaping procedure with e-liquid cartridges containing their preferred flavor (berry, menthol, or tobacco) or no flavor, with or without nicotine (18 mg). Subjective effects of vaping (satisfaction, reward, aversion, airway sensations, and craving relief) were assessed.

Results
Nicotine significantly increased psychological reward and craving relief, whereas flavor significantly increased vaping satisfaction and taste. Nicotine dependence severity moderated the effect of nicotine on reward, such that those with the greatest dependence severity reported the greatest reward.

Conclusions
These findings support differential and noninteractive effects of e-liquid nicotine content and flavor on reinforcing effects of e-cigarettes.

Implications
E-liquid flavor and nicotine content have independent, non-interactive effects on subjective responses to vaping under controlled laboratory conditions. Among regular e-cigarette users, vaping a preferred flavor increased taste and satisfaction, but did not interact with nicotine to alter reward or craving. Further research on the ways in which these subjective effects may motivate vaping behavior among different populations of e-cigarette users would be useful to inform regulatory policy of ENDS products.
A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors
Authors: Garralda Elena , Schram Alison M , Bedard Philippe L , Schwartz Gary K , Yuen Eunice , McNeely Samuel C , Ribeiro Silvia , Cunningham Jason , Wang Yi , Urunuela Arantxa , Xu Xiaojian , LoRusso Patricia 
Published: August 2023

Abstract

Background
This study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors.

Materials and Methods
LY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity.

Results
Fifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n = 3; 35 mg: n = 3; 25 mg: n = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed.

Conclusion
The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development.

ClinicalTrials.gov Identifier
NCT03770494.
Early Tumor Shrinkage and Depth of Response as Predictors of Survival for Advanced Biliary Tract Cancer: An Exploratory Analysis of JCOG1113
Authors: Okano Naohiro , Morizane Chigusa , Okusaka Takuji , Sadachi Ryo , Kataoka Tomoko , Kobayashi Satoshi , Ikeda Masafumi , Ozaka Masato , Mizutani Tomonori , Sugimori Kazuya , Todaka Akiko , Shimizu Satoshi , Mizuno Nobumasa , Yamamoto Tomohisa , Sano Keiji , Tobimatsu Kazutoshi , Katanuma Akio , Gotoh Kunihito , Yamaguchi Hironori , Ishii Hiroshi , Ohba Akihiro , Furuse Junji , Ueno Makoto ,   Hepatobiliary and Pancreatic Oncology Group of Japan Clinical Oncology Group (JCOG)
Published: August 2023

Abstract

Background
Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer.

Material and Methods
In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model.

Results
The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark.

Conclusion
As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.
COVID-19 and Hospital-Acquired Pressure Injuries: A Systematic Review
Authors: Bourkas Adrienn N. , Zaman Michele , Sibbald R. Gary 
Published: August 2023

ABSTRACT

OBJECTIVE
To investigate the relationship between COVID-19-related variables and hospital-acquired pressure injury (HAPI) incidence.

DATA SOURCES
The authors searched four databases: Cochrane, MEDLINE, EMBASE, and CINAHL. The literature search contained key terms such as “COVID-19,” “hospital-acquired pressure injuries,” “pressure ulcer,” “pressure injury,” “decubitus ulcer,” and “hospitalization.”

STUDY SELECTION
The systematic search of the literature identified 489 publications that matched the inclusion criteria. Articles were included in the review if they were peer-reviewed publications that reported HAPI incidence for patients who were hospitalized and COVID-19 positive. Two reviewers performed the screen simultaneously, and 19 publications were included.

DATA EXTRACTION
Two reviewers followed a standardized extraction form that included study and patient characteristics, COVID-19 status, HAPI characteristics, prone positioning, length of hospitalization, and HAPI prevention and treatment strategies.

DATA SYNTHESIS
The authors carried out a narrative synthesis of the extracted data because the data obtained were too heterogeneous for meta-analysis. The primary outcome was HAPI incidence.

CONCLUSIONS
This review identified that HAPI incidence was high among men who were COVID-19 positive, had longer hospital stays, experienced prone positioning, and had care teams without a skin and wound care expert. Future research should use more robust methodology and focus on quantitative modeling to iteratively improve inpatient HAPI guidelines.
One-Year Outcomes of Patients Requiring Tracheostomy Placement Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Abunasser Jafar J. , Perez Oscar , Wang Xiaofeng , Wang Yifan , Khouli Hassan , Duggal Abhijit 
Published: August 2023

BACKGROUND:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes (COVID-19) have resulted in an increase in critical illness and in the prevalence of acute respiratory failure with the need for tracheostomy. The characteristics and long-term outcomes of this patient cohort are not well identified.

RESEARCH QUESTION:
What are the characteristics of patients who develop the need for tracheostomy due to SARS-CoV-2 with acute respiratory distress syndrome (ARDS)? What is their 90-day and 1-year survival and are there any identifiable risk factors for mortality and ventilator dependency?

STUDY DESIGN AND METHODS:
Retrospective, follow-up cohort study of adult patients with COVID-19 infection and ARDS who required tracheostomy placement in a large healthcare system.

RESULTS:
One hundred sixty-four consecutive patients with SARS-CoV-2 admitted to ICUs for ARDS who required tracheostomy placement between March 2020 and March 2021 were identified. One hundred nine (66.5%) were male. Average age was 63.5 years. The most common comorbidities were obesity, hypertension, diabetes mellitus, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), atrial fibrillation, and asthma. The most common complications during hospitalization were delirium, secondary infections, acute kidney injury, pneumothorax, and venous thromboembolism. Ninety-day and 1-year mortality were 29.9% and 44.5%, respectively. Ninety-six patients (58.5%) were liberated from the ventilator, and 84 (51.2%) had the tracheostomy tube decannulated. Asthma, COPD, atrial fibrillation, and renal replacement therapy requirement in the ICU correlated with increased risk of ventilator dependency. Among survivors at 1 year, 71 patients (43.3%) were residing at home and 20 patients (12.2%) remained in a skilled nursing facility.

INTERPRETATION:
COVID-19 has resulted in a significant burden of acute critical illness and acute respiratory failure with the need for tracheostomy. A significant percentage of patients with SARS-CoV-2 requiring tracheostomy were alive and at home 1 year after tracheostomy placement. Long-term care support, including tracheostomy, beyond 90 days appears to be beneficial in this patient population and warrants further investigation.
Recommendations for Patient-Reported Outcomes Measurement Information System pediatric measures in youth with chronic pain: a COnsensus-based Standards for the selection of health Measurement INstruments systematic review of measurement properties
Authors: Li Rui , Gibler Robert C. , Rheel Emma , Slack Katherine , Palermo Tonya M. 
Published: August 2023

Abstract
The Patient-Reported Outcome Measurement Information System (PROMIS) pediatric measures assess physical, emotional, and social health among children and adolescents. However, their measurement properties have not been systematically examined in youth with chronic pain. A systematic review applying the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) methodology was conducted to evaluate self-reported PROMIS pediatric measures in youth with chronic pain, assessing 8 measurement properties across all versions (item bank, short form, and computer adaptive testing) from 63 studies covering 25 measures. Moderate or high-quality evidence was most available for content validity, structural validity, internal consistency (measurement precision), and construct validity. Four short-form PROMIS pediatric measures—mobility, anxiety, depressive symptoms, and physical stress experiences—achieved recommendation for the use in chronic pain clinical trials; 7 approached recommendation and 14, including the commonly used PROMIS Pediatric Pain Interference Scale, would be recommended with further evidence. Recommendations were also provided for the use of each measure in observational studies. Overall, based on the existing evidence, a total of 11 self-reported PROMIS pediatric short-form measures, including pain intensity, pain behavior, mobility, sleep disturbance, sleep-related impairment, anxiety, depressive symptoms, psychological stress experiences, physical stress experiences, family relationships, and positive effect, are recommended or approaching recommendation for use in youth ages 8 to 19 years with chronic pain. Research is needed to further establish test–retest reliability, measurement errors, cross-cultural validity, and responsiveness. Future work should expand the evaluation of PROMIS pediatric measures in subpopulations of youth with chronic pain, particularly young children and those with neurodevelopmental disabilities.
Early effects of very early cochlear implant activation on tinnitus
Authors: Chau Ivy Yenwen , Li Sophia Yung-Hsia , Shiao An-Suey , Islam Albina S. , Coelho Daniel H. 
Published: August 2023

Background:
Cochlear implantation (CI) has long been the standard of care for patients with severe-to-profound hearing impairment. Yet the benefits of CI extend far beyond speech understanding, with mounting recent literature supporting its role in tinnitus abatement. However, those studies have uniformly analyzed the effects of tinnitus after the traditional 3–4 weeks waiting period between CI surgery and device activation. As many clinics are shifting these waiting intervals to become shorter (in some cases within 24 hours, little is known about tinnitus abatement very early in the postoperative period. The aim of this study was to compare preoperative and postoperative tinnitus handicaps in this unique but growing population of very early-activated patients.

Methods:
Twenty-seven adults with severe-to-profound hearing impairment with chronic tinnitus (>6 months) were included. Patients with concomitant psychiatric disorders were excluded. All patients were implanted with the same array and were switched on within 24 hours after the surgery. Tinnitus Handicap Inventory (THI) was recorded preoperatively, immediately after activation at 24 hours postoperatively, at 1 week, 2 weeks, and I month after activation. Wilcoxon signed-rank test was used to compare values between preoperative assessment and respective fitting sessions.

Results:
Mean THI 24 hours after implantation increased in comparison to that assessed preoperatively (77.6 vs 72.5, p = 0.001). By 1 week after surgery, the THI had decreased to 54.9 (p < 0.001). This trend continued and was statistically significant at 2 weeks (36.0, p < 0.001) and 1 month (28.5, p < 0.001).

Conclusion:
On average, most patients with tinnitus will note a significant improvement in their tinnitus handicap when activated within 24 hours of CI. However, tinnitus does increase between surgery and 24 hours, most likely reflecting not only intracochlear changes, but modulation of the entire auditory pathway. Following this early rise, the tinnitus continues to abate over the following month. Patients with tinnitus may benefit from early activation, although should be counseled that they may experience an exacerbation during the very early postoperative period.
Technical Surgical Skill Assessment of Neurovascular Bundle Dissection and Urinary Continence Recovery After Robotic-Assisted Radical Prostatectomy
Authors: Ma Runzhuo , Cen Steven , Forsyth Edward , Probst Patrick , Asghar Aeen , Townsend William , Hui Alvin , Desai Aditya , Tzeng Michael , Cheng Emily , Ramaswamy Ashwin , Wagner Christian , Hu Jim C. , Hung Andrew J. 
Published: August 2023

Purpose:
To examine the association between the quality of neurovascular bundle dissection and urinary continence recovery after robotic-assisted radical prostatectomy.

Materials and Methods:
Patients who underwent RARPs from 2016 to 2018 in 2 institutions with ≥1-year postoperative follow-up were included. The primary outcomes were time to urinary continence recovery. Surgical videos were independently assessed by 3 blinded raters using the validated dissection assessment for robotic technique (DART) tool after standardized training. Cox regression was used to test the association between DART scores and urinary continence recovery while adjusting for relevant patient features.

Results:
One hundred twenty one RARP performed by 23 surgeons with various experience levels were included. The median follow-up was 24 months (95% confidence interval [CI] 20-28 months). The median time to continence recovery was 7.3 months (95% CI 4.7-9.8 months). After adjusting for patient age, higher scores of certain DART domains, specifically tissue retraction and efficiency, were significantly associated with increased odds of continence recovery (P < .05).

Conclusions:
Technical skill scores of neurovascular bundle dissection vary among surgeons and correlate with urinary continence recovery. Unveiling the specific robotic dissection skillsets which affect patient outcomes has the potential to focus surgical training.