bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA biogenesis is broadly disrupted by inhibition of the splicing factor SF3B1
Authors: Downie Ruiz Velasco Angela , Parsons Aimee L , Heatley Matthew C , Martin Athena R G , Smart Alfredo D , Shah Niraj , Jopling Catherine L 
Published: June 2024

Abstract
In animals, microRNA (miRNA) biogenesis begins with cotranscriptional cleavage of the primary (pri-)miRNA by the Microprocessor complex. Cotranscriptional splicing has been shown to influence Microprocessor cleavage when miRNAs are hosted in introns of protein-coding pri-miRNAs, but the impact of splicing on production of miRNAs hosted in long non-coding (lnc)RNAs is largely unknown. Here, we investigated the role of splicing in the biogenesis of miR-122, an lncRNA-hosted, highly expressed, medically important, liver-specific miRNA. We found that splicing inhibition by the SF3B1 inhibitor pladienolide B (PlaB) led to strong and rapid reduction in transcription of endogenous, but not plasmid-encoded, pri-miR-122, resulting in reduced production of mature miR-122. To allow detection of rapid changes in miRNA biogenesis despite the high stability of mature miRNAs, we used SLAMseq to globally quantify the effects of short-term splicing inhibition on miRNA synthesis. We observed an overall decrease in biogenesis of mature miRNAs following PlaB treatment. Surprisingly, miRNAs hosted in exons and introns were similarly affected. Together, this study provides new insights into the emerging role of splicing in transcription, demonstrating novel biological importance in promotion of miR-122 biogenesis from an lncRNA, and shows that SF3B1 is important for global miRNA biogenesis.
Nanopores map the acid-base properties of a single site in a single DNA molecule
Authors: Smith Drew C , Thomas Christopher A , Craig Jonathan M , Brinkerhoff Henry , Abell Sarah J , Franzi Michaela C , Carrasco Jessica D , Hoshika Shuichi , Benner Steven A , Gundlach Jens H , Laszlo Andrew H 
Published: June 2024

Abstract
Nanopores are increasingly powerful tools for single molecule sensing, in particular, for sequencing DNA, RNA and peptides. This success has spurred efforts to sequence non-canonical nucleic acid bases and amino acids. While canonical DNA and RNA bases have pKas far from neutral, certain non-canonical bases, natural RNA modifications, and amino acids are known to have pKas near neutral pHs at which nanopore sequencing is typically performed. Previous reports have suggested that the nanopore signal may be sensitive to the protonation state of an individual moiety. We sequenced ion currents with the MspA nanopore using a single stranded DNA containing a single non-canonical DNA base (Z) at various pH conditions. The Z-base has a near-neutral pKa ∼ 7.8. We find that the measured ion current is remarkably sensitive to the protonation state of the Z-base. We demonstrate how nanopores can be used to localize and determine the pKa of individual moieties along a polymer. More broadly, these experiments provide a path to mapping different protonation sites along polymers and give insight in how to optimize sequencing of polymers that contain moieties with near-neutral pKas.
TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations
Authors: Markowski Mark C , Sternberg Cora N , Wang Hao , Wang Tingchang , Linville Laura , Marshall Catherine H , Sullivan Rana , King Serina , Lotan Tamara L , Antonarakis Emmanuel S 
Published: June 2024

Abstract

Background
The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Methods
This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate.

Results
Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected.

Conclusion
Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.
Comparison of tissue response and lifting effect induced by non-absorbable elastic thread and commercialized threads in rat model
Authors: Lee Dae Hyung , Choi Yeji , Lee Mi Hee , Park Jong-Chul 
Published: June 2024

Abstract
As we age, our skin loses elasticity and wrinkles form. To prevent this, most people try to improve skin wrinkles by performing procedures such as fillers, and absorbable lifting threads. Another way to solve this structural problem is to use an elastic thread. Although elastic sutures made of polymer materials (such as silicone) are widely used, data regarding their properties and potential effectiveness are lacking. This study aimed to investigate the effects of inserting non-absorbable elastic threads, with different manufacturing requirements and methods, on the skin and subcutaneous tissue. In this study, non-absorbable elastic threads ELATENS and Elasticum using different manufacturing methods were compared. Each thread was transplanted into the subcutaneous layer of the back of a rat to induce wrinkles. After inducing wrinkles in the skin of rat, the degree of skin maintenance by each thread and the thickness of the capsule formed around the suture were measured. Through ex-vivo experiments on each thread, the fixation force in the tissue was confirmed. In a comparison of inflammatory response and collagen formation through histological analysis, it was confirmed that there was no significant difference from the equivalent comparative product. In conclusion, the degree of encapsulation between tissues and collagen fiber formation for improving skin wrinkles was superior in elastic threads compared to non-elastic threads. It is believed that this provides certain elasticity to the skin layer and can induce cell influx to improve wrinkles.
Bmal1 regulates female reproduction in mice via the hypothalamic–pituitary–ovarian axis
Authors: Zhang Ayuan , Li Shiping , Huang Lingyi , Jiang Yin , Chen Yan , Zhu Shuyao , Xiong Fu , Luo Zemin , Ou Mingcai , Ying Junjie , Wang Shaopu , Mu Dezhi , Qu Yi 
Published: June 2024

AbstractThe hypothalamic–pituitary–gonadal axis (HPG) is the key neuroendocrine axis involved in reproductive regulation. Brain and muscle ARNT‐like protein 1 (Bmal1) participates in regulating the metabolism of various endocrine hormones. However, the regulation of Bmal1 on HPG and female fertility is unclear. This study aims to explore the regulation of female reproduction by Bmal1 via the HPG axis in mice. Bmal1‐knockout (Ko) mice were generated using the CRISPR/Cas9 technology. The structure, function, and estrous cycle of ovarian in Bmal1 Ko female mice were measured. The key genes and proteins of the HPG axis involved in regulating female reproduction were examined through transcriptome analysis and then verified by RT‐PCR, immunohistochemistry, and western blot. Furthermore, the fertility of female mice was detected after intervening prolactin (PRL) and progesterone (Pg) in Bmal1 ko mice. The number of offspring and ovarian weight were significantly lower in Bmal1‐Ko mice than in wild‐type (Wt) mice. In Bmal1‐Ko mice, ovarian cells were arranged loosely and irregularly, and the total number of follicles was significantly reduced. No corpus luteum was found in the ovaries. Vaginal smears revealed that Bmal1‐Ko mice had an irregular estrus cycle. In Bmal1‐Ko mice, Star expression was decreased, PRL and luteinizing hormone (LH) levels were increased, and dopamine (DA) and Pg levels were decreased. Inhibition of PRL partially recovered the estrous cycle, corpus luteum formation, and Star expression in the ovaries. Pg supplementation promoted embryo implantation in Bmal1‐Ko female mice. Bmal1 Ko increases serum PRL levels in female mice likely by reducing DA levels, thus affecting luteal formation, resulting in decreased Star expression and Pg production, hindering female reproduction. Inhibition of PRL or restoration of Pg can partially restore reproductive capacity in female Bmal1‐Ko mice. Thus, Bmal1 may regulate female reproduction via the HPG axis in mice, suggesting that Bmal1 is a potential target to treat female infertility.
Association Between High Preoperative White Blood Cell-to-Hemoglobin Ratio and Postoperative Symptomatic Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Shin Kyung Won , Park Eun Bi , Jo Woo-Young , Lee Hyung-Chul , Park Hee-Pyoung , Oh Hyongmin 
Published: June 2024

Background:Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (ASAH) is a serious complication and has a strong relationship with systemic inflammatory responses. Given previously reported relationships between leukocytosis and anemia with ASAH-related cerebral vasospasm, this study examined the association between the preoperative white blood cell-to-hemoglobin ratio (WHR) and postoperative symptomatic cerebral vasospasm (SCV) in patients with ASAH.Methods:Demographic, preoperative (comorbidities, ASAH characteristics, laboratory findings), intraoperative (operation and anesthesia), and postoperative (SCV, other neurological complications, clinical course) data were retrospectively analyzed in patients with ASAH who underwent surgical or endovascular treatment of the culprit aneurysm. Patients were divided into high-WHR (n=286) and low-WHR (n=257) groups based on the optimal cutoff value of preoperative WHR (0.74), and stabilized inverse probability weighting was performed between the 2 groups. The predictive power of the WHR and other preoperative systemic inflammatory indices (neutrophil-to-albumin, neutrophil-to-lymphocyte, platelet-to-lymphocyte, platelet-to-neutrophil, platelet-to-white blood cell ratios, and systemic immune-inflammation index) for postoperative SCV was evaluated.Results:Postoperative SCV was more frequent in the high-WHR group than in the low-WHR group before (33.2% vs. 12.8%;P<0.001) and after (29.4% vs. 19.1%;P=0.005) inverse probability weighting. Before weighting, the predictive power for postoperative SCV was the highest for the WHR among the preoperative systematic inflammatory indices investigated (area under receiver operating characteristics curve 0.66,P<0.001). After weighting, preoperative WHR ≥0.74 was independently associated with postoperative SCV (odds ratio 1.76;P=0.006).Conclusions:High preoperative WHR was an independent predictor of postoperative SCV in patients with ASAH.
Two AIS Cases, 2 Surgeons, 1 Operating Room, 1 Day: Faster and Safer Than 1 Case in a Day
Authors: Warren Jonathan R. , Link Robert C. , Bonanni Sean , Noe McKenna C. , Anderson John T. , Schwend Richard M. 
Published: June 2024

Background:
To lessen surgical times for patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and fusion (PSIF), our department developed a quality improvement initiative where 2 AIS cases were completed in 1 day by the same 2 surgeons operating together in 1 operating room (OR). We describe the results of this initiative, comparing operative times and outcomes to cases of these surgeons operating individually.

Methods:
From 2017 to 2023, patients aged 10 to 18 years with AIS undergoing PSIF were prospectively enrolled for “Two Spine Tuesday.” Patients were matched by age, sex, curve severity, and number of levels fused to historical AIS controls. Outcomes included surgery time, total OR time, estimated blood loss (EBL), volume of cell saver transfused, allogenic blood transfusion, length of stay, 90-day readmissions, Clavien-Dindo-Sink Complication Classification System complication rates, and percentage who achieved the minimal clinically important difference (MCID) for SRS-22.

Results:
Fifty-five patients composing the 2-spine group (group 2) were compared with 55 historical sex-matched and age-matched controls (group 1). Major coronal curve and average number of levels fused were similar between groups. Overall surgery time (203 vs. 296 min, P<0.001), total OR time (P<0.001), and EBL (400 vs. 550 mL, P<0.001) were lower for group 2. Group 2 had fewer complications [n=17 (31%) vs. n=28 (51%), P=0.03].

Conclusions:
Performing 2 AIS cases in 1 OR by 2 surgeons the same day resulted in shorter surgery times, less total time in the operating room, lower complication rates, and less blood loss compared with single-surgeon matched controls.

Level of Evidence:
Level III—retrospective comparative study.
Has Health Physics Contributed to an 80-Y False Narrative about the Trinity Nuclear Test?
Authors: Shonka Joseph J. 
Published: June 2024

Abstract
This paper discusses the various analyses of the Trinity Nuclear Test, including how they might apply to the issue of infant mortality. This paper was first drafted as a response to a letter by Rice, who commented on my earlier letter on that issue. My earlier letter commented on the National Cancer Institute’s 2020 series of papers in the October Issue of Health Physics on the impact of the Trinity Nuclear Test that was conducted on unoccupied government lands on 16 July 1945. The Journal editors requested that my response to Rice be edited and submitted as a paper to ensure adequate technical review and suggested that the article also add material summarizing the series of exchanges that were published in the Journal. This article suggests that significant differences exist between various summaries of the offsite impact of the Trinity Nuclear Test and offers that Trinity might be the largest nuclear accident in terms of the impact on uninvolved civilians who were downwind following the test. It suggests areas for further study to resolve these significant differences. It also asserts that until the estimated exposures of downwind residents are resolved and an appropriate study is made of infant deaths following the Trinity Nuclear Test, the issue of infant mortality remains an unanswered, 80-y-old question.
Improving Safety and Satisfaction in the Safety Monitoring Unit
Authors: Welch Dani Lynn 
Published: June 2024

ABSTRACTBACKGROUND:The safety monitoring unit (SMU) is a 4-bed unit designated for patients who require continual observation. Most experience some form of dementia, and agitation and aggression are not uncommon. When deescalation techniques do not work, request for help may be necessary. Referred to as Security Alert: Behavioral Assist (SABA), this system-wide message requires response from designated personnel. An increase in SABA events prompted this quality improvement project.METHODS:A survey sent to all unit staff members identified a need for specialized training on the care and management of SMU patients. Education on dementia care and deescalation techniques was provided by a certified dementia specialist and a psychiatry advanced practice registered nurse. Staff expressed a need for defined SMU admission criteria and the establishment of patient care guidelines. Patient care guidelines were developed. A structured schedule was implemented, and dedicated staff were hired to provide familiarity for patients.RESULTS:A postproject survey indicated a nonsignificant increase in staff satisfaction. Security Alert: Behavioral Assist events in the SMU decreased from an average of 3.6 to 1.75 episodes per month.CONCLUSION:Caring for SMU patients creates unique challenges to staff. Staff confidence and satisfaction were higher after implementing new SABA policies. This project could be replicated on similar units with ongoing leadership support and staff education.
Prognostic role of unmeasured anions determined by the Stewart approach in septic shock: A prospective cohort study
Authors: Roukhomovsky-Moretti Mathilde , Uberti Thomas , Giai Joris , Cerro Valérie , Crozon-Clauzel Jullien , Duclos Antoine , Girardot Thibaut , Grégoire Arnaud , Hernu Romain , Huriaux Laetitia , Leray Véronique , Marcotte Guillaume , Monard Céline , Argaud Laurent , Rimmelé Thomas 
Published: June 2024

Background:
Unlike standard methods for the analysis of acid-base disturbances, the Stewart approach allows for a precise quantification of unmeasured anions (strong ion gap, SIG). The prognostic value of these unmeasured anions has been reported in various clinical situations in the intensive care unit (ICU), but not specifically in septic shock. The aim of the present study was to assess whether or not the SIG could be a prognostic marker for 28-day mortality in critically ill patients admitted to the ICU for septic shock.

Methods:
This prospective cohort study was conducted from June 2016 to December 2017 in three ICUs of a French teaching hospital. All patients admitted to the ICU for septic shock and equipped with an arterial blood line were eligible. Oral consent was collected after delivering oral and written information to the patient or his/her family. The SIG was calculated from a complete blood sampling (blood electrolytes and arterial blood gas) collected immediately upon ICU admission. Receiver operating characteristics (ROC) curves were determined to assess the ability of SIG to predict 28-day mortality.

Results:
A total of 116 patients were analyzed. The 28-day mortality rate was 41.4%. Median (interquartile range [IQR]) SIG at admission was 7.1 (4.6-9.6) mEq/L for the 28-day survivors and 8.0 (6.1-10.3) mEq/L for non-survivors (P = 0.051). The area under ROC of SIG at admission for 28-day mortality prediction was 0.607 (95% confidence interval [CI] 0.504-0.710; P = 0.051).

Conclusion:
SIG is not a relevant prognostic marker for mortality in septic shock.
Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging
Authors: Ivanick Nathaniel M. , Kunadharaju Rajesh , Bhura Sajeer , Mengiste Hiwot , Saeed Musa , Saradna Arjun , Grover Harshwant , Kalvapudi Sukumar , Yendamuri Sai , Yu Han , Shafirstein Gal , Reid Mary 
Published: June 2024

Background:
The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020.

Methods:
We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years.

Results:
The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001).

Conclusion:
This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.
Evaluation of the metabolic activity of the torn rotator cuff muscles by 18F-2-deoxy-d-glucose PET-computed tomography scan
Authors: MLV Sai Krishna , Mittal Ravi , Chauhan Nitin , Kumar Rakesh , KV Siva Sankar , Chattopadhyay Aritra , Gamangatti Shivanand 
Published: June 2024

Objectives
Fatty atrophy and fatty infiltration have been considered as limiting factors for rotator cuff repair. The metabolic activity of the muscle can be measured noninvasively by PET. In our study, we aim to compare the metabolic activity between the shoulders with rotator cuff tears and normal shoulders.

Methods
All the patients with unilateral full-thickness rotator cuff tears were included. The patients were divided into two groups based on fatty atrophy and the metabolic activities of the rotator cuff muscles, trapezius, and deltoid were calculated using an 18F-2-deoxy-d-glucose PET-computed tomography scan for comparison.

Results
A total of 17 patients were included. The standardized uptake values were compared between the affected shoulder and the normal shoulders. There was a significant increase in uptake in the insertion sites and musculotendinous junctions in the rotator cuff torn group. The standardized uptake values showed no significant difference between the low-grade and high-grade groups.

Conclusion
Our first hypothesis was also proven wrong; when we found that there was no statistically significant difference in the metabolic activity in muscle bellies of normal shoulders and those with rotator cuff tears. Our second hypothesis was proven wrong when found that there was no statistically significant difference in the metabolic activities of rotator cuff muscles between high-grade and low-grade fatty atrophy groups. The metabolic activities of the middle deltoid and trapezius are inversely related. Based on the findings of our study, fatty atrophy or fatty infiltration alone cannot be considered a limiting factor for rotator cuff repair.