bluuebunny/crossref_metadata_2025 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

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

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

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

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

The 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

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

BACKGROUND: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.
Urine sodium in acute heart failure: Time for reappraisal
Authors: Belal Amer A. , Kazory Amir
Published: June 2024

Congestion is the primary reason for hospital admission in patients with acute heart failure and is the key target of therapy in this setting. Urine sodium excretion has emerged as an objective and clinically relevant marker of response to decongestive therapies that portend prognostic value. While diuretics remain the mainstay of therapy in these patients, a significant subset of them experiences suboptimal response (e.g. diuretic resistance) and lingering congestion that is known to be associated with adverse outcomes. Herein, we provide an overview of several strategies that have been explored to enhance urinary sodium excretion, with the goal of improving congestion and possibly the overall outcomes. While some of these options have had suboptimal results (e.g. dopamine), the preliminary data on other methods seem to be encouraging (e.g. hypertonic saline solution). Sequential nephron blockade of sodium absorption is a widely used option that has had several advancements in recent years especially with new clinical trials targeting proximal tubular sodium absorption (e.g. sodium-glucose cotransporter-2 inhibitors). While kidney-sparing mechanical extraction of sodium (ultrafiltration therapy) is being actively investigated, several other trials focusing on natriuresis-guided decongestive therapy are on the way. The findings of these studies are expected to help clinicians refine current strategies to further enhance urinary sodium excretion and decongestion.
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.
Hyperostosis frontalis interna on fluorine-18 sodium fluoride PET/computed tomography of obese cancer patients: a potential mimicker of metastasis
Authors: Alenezi Saud , Dannoon Shorouk , Alnafisi Naheel , Elgazzar Abdelhamid , Khalafalla Khaled
Published: June 2024

Objective

The objective of this retrospective study was to identify the uptake patterns and suggest a quantitative method to detect hyperostosis frontalis interna (HFI) on fluorine-18 sodium fluoride ([18F]NaF) PET/computed tomography (CT).

Methods

Between January 2019 and December 2021, patients who underwent [18F]NaF PET/CT with a BMI of 30 and above, were included. Three nuclear medicine consultants reviewed the studies to determine the presence and identify the uptake patterns of HFI. Quantitative evaluation was performed on PET images using the total number of counts over the frontal bone and the ratio of counts between the frontal bone and iliac crest.

Results

A total of 105 out of 249 cases were included in this study. Among these scans, there were 67 positive HFI in [18F]NaF PET scans representing 64% of the studied population. As for the [18F]NaF PET uptake pattern, there were 53 with uniformly diffused and 14 with heterogeneous uptake pattern. There were 17 out of 67 with positive HFI in [18F]NaF PET scans but negative CT scans.

Conclusion

HFI is a common finding on [18F]NaF PET in obese patients and is probably underdiagnosed. HFI may present with a heterogeneous and diffuse pattern of uptake on [18F]NaF PET. The proposed quantitative analysis using the count ratios is in agreement with the visual evaluation of [18F]NaF PET images regardless of the CT findings. Awareness of this condition and its scintigraphic patterns is warranted since it can have clinical significance and may mimic other pathologies including metastasis in cancer patients.
Effect of insole on postural control and gait of stroke patients: a systematic review and meta-analysis
Authors: Hozein Menna , Mortada Hossam , Hamed Maged , Abdelhaleem Naglaa , Elshennawy Shorouk
Published: June 2024

This systematic review aims to examine the evidence of adding postural insole to traditional physical therapy to improve weight distribution, gait, mobility, balance, and postural control in stroke survivors. Five databases were searched to retrieve all related randomized controlled trials examining the effect of insole on stroke patients. Two independent authors checked the potential articles against eligibility criteria according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A meta-analysis was conducted for available outcomes and the statistical heterogeneity was examined using the I
2 test. Of 762 articles, only 15 with 448 patients were included after they met the inclusion criteria with most of them including participants exceeding 6 months of stroke incidence. When insole was used as compelled body weight shifting method, pooled statistical analysis revealed significant improvement in gait velocity [standardized mean difference (SMD) = 0.67; 95% confidence interval (CI): 0.31, 1.02; P = 0.0003], cadence (SMD = 0.67; 95% CI: 0.16, 1.18; P = 0.01] and stride length (SMD = 1.11; 95% CI: 0.57, 1.65; P < 0.0001), while no significant effect on step length (SMD = 0.48; 95% CI: −0.37, 1.33; P = 0.27). Pooled statistical analysis of balance outcomes revealed significant improvement in weight-bearing symmetry balance (SMD = 0.82; 95% CI: 0.25, 1.39; P = 0.005) and long-term improvement in Berg Balance Scale (SMD = 1.19; 95% CI: 0.19, 2.20; P = 0.02), while no difference was observed in balance confidence (SMD = 0.44; 95% CI: −0.15, 1.04; P = 0.14) and sensorimotor functions (SMD = 0.36; 95% CI −0.39, 1.11; P = 0.35). Insoles significantly improved spatiotemporal gait parameters, gait symmetry, and static balance compared with traditional physical therapy alone.
Demystifying the Technology Barriers of Nurse Educators
Authors: Brewer Will , Brown Neysa , Davenport Nikki , Irons Ann Marie , Floren Michael , Russell Beverly , Looser Melanie , Martin W. Paige , Hunt Amanda
Published: June 2024

Background: Technology is pivotal in nursing education, with methods such as the flipped classroom, active learning, and patient simulation becoming integral. Despite this, persistent barriers hinder technology’s full integration.

Methods: An online survey collected data from nursing faculty members (n = 1761) in prelicensure nursing programs. The survey assessed their views on technology, barriers, training needs, and importance in classroom and simulation settings.

Results: Participants highlighted financial support, commitment, and administrative support as critical for technology adoption. Statistical analysis of the results revealed differences in the rankings of the importance of technology, emphasizing the significance of these factors. Additionally, time in the classroom was noted as a significant barrier.

Conclusions: Technology’s role in nursing education continues to expand. Overcoming financial constraints and enhancing faculty buy-in are essential for successful technology integration, ultimately, improving informatics competencies and advancing technological nursing education.
A Multidisciplinary Approach to Enhancing Sterilization Processes for Pleuravideoscopes in a Pulmonary Clinic
Authors: Atwood Bethany I. , Eaddy Mia , Downey Alaina , Eberhardt Gina L. , Smith Joshua D. , Romito Kenneth
Published: June 2024

Purpose/Objectives

The Centers for Disease Control and Prevention has highlighted the strong association between healthcare-associated infections and the reprocessing of flexible endoscopes. This process improvement project provided an evidence-based workflow analysis of pleuravideoscope reprocessing to validate and implement safe practices in the pulmonary clinic and sterile processing department.

Description of the Project/Program

A multidisciplinary team created an audit tool to complete infection control risk assessment using Lean Six Sigma methodology.

Outcome

The risk assessment identified gaps in clinical practice, prompting corrective measures using a shared decision-making approach. The organization updated standard operating procedures, provided training and competency assessments, and purchased single-use pleuravideoscopes. These initiatives addressed the deficiencies and reinforced a culture of continuous process improvement and patient safety.

Conclusion

Multidisciplinary teams should perform comprehensive reviews of facility processes and assess the risks related to infection control to identify optimal pleuravideoscope workflows for the healthcare institution. The involvement of a clinical nurse specialist is advantageous, as they possess the expertise necessary to facilitate collaborative efforts among team members spanning various departments. By leveraging the insights and skills of diverse professionals, healthcare organizations can optimize their reprocessing programs and enhance patient safety.
The Lupus Foundation of America—Rapid Evaluation of Activity in Lupus Clinician-Reported Outcome Predicts Damage in Patients With Systemic Lupus Erythematosus. Data From the Almenara Lupus Cohort
Authors: Ugarte-Gil Manuel F. , Gamboa-Cárdenas Rocío V. , Reátegui-Sokolova Cristina , Pimentel-Quiroz Victor R. , Elera-Fitzcarrald Claudia , Pastor-Asurza César , Rodriguez-Bellido Zoila , Perich-Campos Risto , Alarcón Graciela S.
Published: June 2024

Objective

To evaluate the predictive value of the LFA-REAL ClinRO (Lupus Foundation of America Rapid Evaluation of Activity in Lupus clinician-reported outcome) on damage accrual in systemic lupus erythematosus patients.

Methods

Data from a prevalent lupus cohort were used. The LFA-REAL ClinRO includes 9 domains: mucocutaneous (global and 3 subdomains), musculoskeletal (global and 2 subdomains), cardiorespiratory, neuropsychiatric, renal, hematological, constitutional, vasculitis, and other (it allows for other or rare manifestations). For each domain, a 0- to 100-mm visual analog scale is used, and global domains are included except for the mucocutaneous and musculoskeletal domains where the subdomains are included; it allows for 3 manifestations under “other,” so the score ranges from 0 to 1400 (sum of 14 in the visual analog scale). Damage was assessed with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index. Generalized estimating equations were performed, being the outcome the increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index; confounders from the previous visit were included; adjusted multivariable models were done. Incidence rate ratios per 10-unit increase in the LFA-REAL ClinRO were reported. Similar models were performed to evaluate the impact of the SLEDAI-2K (SLE Disease Activity Index) and physician global assessment on damage to determine which measure would better predict damage accrual.

Results

Three-hundred thirty-one patients and 1425 visits were included, 1.9 (SD 1.2) years of follow-up. Disease duration at baseline was 10.7 (7.4) years. The mean LFA-REAL ClinRO was 18.2 (SD 30.7). During the follow-up visits, 63 (17.9%) patients accrued damage once; 4 (1.1%) accrued damage twice. The LFA-REAL ClinRO was predictive of damage accrual even after adjustment for possible confounders (incidence rate ratio 1.10 (95% confidence interval 1.04–1.16; p < 0.001). Similar results were obtained using the SLEDAI-2K and the physician global assessment.

Conclusion

The LFA-REAL ClinRO is predictive of damage accrual, even after adjusting for possible confounders.
Cardiovascular Events, Malignancies, and Efficacy Outcomes in Latin American Patients With Rheumatoid Arthritis Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors
Authors: Citera Gustavo , Mysler Eduardo , Kakehasi Adriana Maria , Pascual-Ramos Virginia , Masson Walter , Cadatal Mary Jane , Rivas Jose L. , Sheibanie Farzad , Helling Claudia , Ponce de Leon Dario
Published: June 2024

Background/Objective

To assess safety/efficacy of tofacitinib and tumor necrosis factor inhibitors (TNFi) in patients from Latin America (LATAM) in ORAL Surveillance.

Methods

In ORAL Surveillance, 4362 patients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily or TNFi. This post hoc analysis stratified patients by geographical location (LATAM, n = 1202; non-LATAM, n = 3160). Incidence rates (IRs; patients with first event/100 patient-years) and hazard ratios for adverse events of special interest were reported. Efficacy outcomes included Clinical Disease Activity Index and American College of Rheumatology 20/50/70 responses.

Results

Risk factors associated with cardiovascular disease and malignancies were less prevalent in the LATAM cohort compared with the non-LATAM cohort. IRs for patients receiving tofacitinib (combined doses) versus TNFi were 0.54 versus 0.28 (LATAM) and 1.14 versus 0.92 (non-LATAM) for major adverse cardiovascular events; 0.58 versus 0.27 (LATAM) and 1.33 versus 0.95 (non-LATAM) for malignancies excluding nonmelanoma skin cancer; and 0.69 versus 0.35 (LATAM) and 0.63 versus 0.33 (non-LATAM) for all-cause death. IRs for nonmelanoma skin cancer and venous thromboembolism were also numerically higher with tofacitinib versus TNFi and in the non-LATAM cohort versus LATAM. Efficacy was similar across treatment groups within each cohort.

Conclusions

Adverse events of special interest were generally less frequent in LATAM versus non-LATAM patients, reflecting differences in baseline characteristics, and higher with tofacitinib versus TNFi in both cohorts, consistent with the overall findings of ORAL Surveillance. Our findings emphasize the importance of assessing individual risk factors to guide benefit/risk assessment and treatment decisions.

Clinical trial registration number

NCT02092467
Mesangial Expansion by Morphometry at 5 y After Kidney Transplantation: Incidence, Risk Factors, and Association With Graft Loss
Authors: Denic Aleksandar , Buglioni Alessia , Turkevi-Nagy Sandor , Mejia Mateo Velasquez , Smith Byron H. , Park Walter D. , Subramani Rashmi , Kukla Aleksandra , Diwan Tayyab S. , Grande Joseph P. , Stegall Mark D.
Published: June 2024

Background.

Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss.

Methods.

We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME
mm
(%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss.

Results.

From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME
mm
increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME
mm
was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872).

Conclusions.

Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.
Optic Nerve T2 Signal Intensity and Caliber Reflect Clinical Severity in Genetic Optic Atrophy
Authors: Nagy M. Aurel , Cunnane Mary E. , Juliano Amy F. , Wiggs Janey L. , Caruso Paul A. , Gaier Eric D.
Published: June 2024

Background:

Genetic optic atrophies comprise phenotypically heterogenous disorders of mitochondrial function. We aimed to correlate quantitative neuroimaging findings of the optic nerves in these disorders with clinical measures.

Methods:

From a retrospective database of 111 patients with bilateral optic atrophy referred for genetic testing, 15 patients diagnosed with nonglaucomatous optic atrophy of genetic origin (7 patients with pathogenic variants in OPA1, 3 patients with Wolfram syndrome, and 5 patients with Leber hereditary optic neuropathy) who had accessible magnetic resonance (MR) images of the orbits and/or brain were analyzed. The primary outcome measures of T2 short Tau inversion recovery (STIR) signal and optic nerve caliber were quantified according to a standardized protocol, normalized to internal standards, and compared between cases and controls. Inter-rater reliability was assessed and clinical features were analyzed according to MRI features.

Results:

Compared with control patients, the 15 genetic optic atrophy patients demonstrated significantly increased T2 STIR signal (fold-change 1.6, P = 0.0016) and decreased optic nerve caliber (fold-change 0.72, P = 0.00012) after internal normalization. These metrics were reliable (inter-reader reliability correlation coefficients of 0.98 [P = 0.00036] and 0.74 [P = 0.0025] for normalized STIR and nerve caliber, respectively) and significantly correlated with visual acuity, cup-to-disc ratio, and visual field testing.

Conclusion:

Normalized optic nerve STIR signal and optic nerve caliber significantly correlate with visual acuity, cup-to-disc ratio, and perimetric performance in patients with genetic optic atrophy. A formalized protocol to characterize these differences on MRI may help to guide accurate and expedient diagnostic evaluation.
Gemmobacter denitrificans sp. nov., a denitrifying bacterium, isolated from pond water for Litopenaeus vannamei
Authors: Zhang Mingxia , Zhang Yulian , Yang Fan , Yao Qing , Zhu Honghui
Published: June 2024

A novel Gram-stain-negative strain, designated JM10B15T, was isolated from pond water for Litopenaeus vannamei collected from Jiangmen City, Guangdong province, south PR China. Cells of the strain were aerobic, rod-shaped, and motile by lateral flagella. JM10B15T could grow at 15–40 °C, pH 6.0–9.5, and in 0–3.0 % NaCl, with optimal growth at 25–35 °C, pH 7.5–8.5, and in 0 % NaCl, respectively. Furthermore, this strain grew well on Reasoner's 2A agar but not on nutrient broth agar or Luria–Bertani agar. JM10B15T was a denitrifying bacterium capable of removing nitrites and nitrates, and three key functional genes, nasA, nirS, and nosZ, were identified in its genome. The results of phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that JM10B15T belonged to the genus Gemmobacter. JM10B15T showed the highest 16S rRNA sequence similarity to Gemmobacter lutimaris YJ-T1-11T (98.8 %), followed by Gemmobacter aquatilis IFAM 1031T (98.6 %) and Gemmobacter serpentinus HB-1T (98.1 %). The average nucleotide identity and digital DNA–DNA hybridization values between JM10B15T and the other type strains of genus Gemmobacter were 78.1–82.1 % and 18.4–22.1 %, respectively. The major fatty acids of strain JM10B15T were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c) and C18 : 1
 ω7c 11-methyl. In addition, the major respiratory quinone of this novel strain was Q-10, and the predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, four unidentified phospholipids, three unidentified lipids, and an unidentified aminophospholipid. Results of analyses of the phylogenetic, genomic, physiological, and biochemical characteristics indicated that JM10B15T represents a novel species of the genus Gemmobacter, for which the name Gemmobacter denitrificans sp. nov. is proposed. The type strain is JM10B15T (=GDMCC 1.4148T=KCTC 8140T).
Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis
Authors: Vukadinović Davor , Lauder Lucas , Kandzari David E. , Bhatt Deepak L. , Kirtane Ajay , Edelman Elazer R. , Schmieder Roland E. , Azizi Michel , Böhm Michael , Mahfoud Felix
Published: June 2024

Background

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.

Aim

To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.

Methods

We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data.

Results

Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI −6.1, −2.7, p<0.00001) and 6.6 mmHg (95%CI −9.7, −3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (−2.6 mmHg, 95%CI - 3.6, −1.5, p<0.00001; −3.5 mmHg, 95%CI −5.4, −1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials.

Conclusions

RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication.

Clinical Perspective

What is new?

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.

This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.

Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.

What are the clinical implications?

This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.
Integrating Multi-Modal Cancer Data Using Deep Latent Variable Path Modelling
Authors: Ing Alex , Andrades Alvaro , Cosenza Marco Raffaele , Korbel Jan O.
Published: June 2024

Cancers are commonly characterised by a complex pathology encompassing genetic, microscopic and macroscopic features, which can be probed individually using imaging and omics technologies. Integrating this data to obtain a full understanding of pathology remains challenging. We introduce a new method called Deep Latent Variable Path Modelling (DLVPM), which combines the representational power of deep learning with the capacity of path modelling to identify relationships between interacting elements in a complex system. To evaluate the capabilities of DLVPM, we initially trained a foundational model to map dependencies between SNV, Methylation, miRNA-Seq, RNA-Seq and Histological data using Breast Cancer data from The Cancer Genome Atlas (TCGA). This method exhibited superior performance in mapping associations between data types compared to classical path modelling. We additionally performed successful applications of the model to: stratify single-cell data, identify synthetic lethal interactions using CRISPR-Cas9 screens derived from cell-lines, and detect histologic-transcriptional associations using spatial transcriptomic data. Results from each of these data types can then be understood with reference to the same holistic model of illness.