bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal circBBS2 inhibits ferroptosis by targeting miR‐494 to activate SLC7A11 signaling in ischemic stroke
Authors: Hong Ting , Zhao Tingting , He Wei , Xia Jian , Huang Qing , Yang Jie , Gu Wenping , Chen Changqing , Zhang Ning , Liu Yunhai , Feng Jie
Published: August 2023

Umbilical cord‐mesenchymal stem cells (UC‐MSCs)‐derived exosomes have been considered as an effective treatment for ischemic stroke. CircRNA BBS2 (circBBS2) was demonstrated to be down‐regulated in patients with ischemic stroke. However, the role of UC‐MSCs‐derived exosomal circBBS2 in ischemic stroke and potential mechanisms remain unclear. Hypoxia/reperfusion (H/R)‐exposed SH‐SY5Y cells and middle cerebral artery occlusion (MCAO)‐treated rats were served as in vitro and in vivo models of ischemic stroke. Target gene expression was detected by qRT–PCR. Cell viability was assessed by MTT assay. Ferroptosis was determined by iron, MDA, GSH, and lipid ROS levels. Protein levels were measured by Western blotting. The target relationships among circBBS2, miR‐494, and SLC7A11 were validated by RNA‐pull down, RIP, and dual‐luciferase reporter assays. TTC and HE staining were performed to evaluate cerebral infarction volume and neuropathological changes. circBBS2 was lowly expressed and ferroptosis was triggered in MCAO rats and H/R‐stimulated SH‐SY5Y cells. UC‐MSCs‐derived exosomes enhanced cell viability and restrained ferroptosis via increasing circBBS2 expression in SH‐SY5Y cells. Mechanistically, circBBS2 sponged miR‐494 to enhance the SLC7A11 level. Knockdown of miR‐494 or SLC7A11 reversed the effects of silencing circBBS2 or miR‐494 on ferroptosis of SH‐SY5Y cells, respectively. Furthermore, UC‐MSCs‐derived exosomes attenuated ischemic stroke in rats via delivering circBBS2 to inhibit ferroptosis. UC‐MSCs‐derived exosomal circBBS2 enhanced SLC7A11 expression via sponging miR‐494, therefore repressing ferroptosis and relieving ischemic stroke. Our findings shed light on a novel mechanism for UC‐MSCs‐derived exosomes in the treatment of ischemic stroke.
Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment
Authors: Deng Xinpeng , Sun Xiaoke , Hu Ziliang , Wu Yiwen , Zhou Chenhui , Sun Jie , Gao Xiang , Huang Yi
Published: August 2023

Although the role of N6‐Methyladenosine (m6A) methylation factors has been established in multiple cancer types, its involvement in glioblastoma multiforme (GBM) remains limited. This study aims to explore the involvement of m6A regulators in GBM and examine their association with the tumor immune microenvironment (TIME). A comprehensive set of 24 candidate m6A RNA regulators was procured. Consensus clustering was performed based on these regulators to identify distinct GBM clusters. PD‐L1 and PD‐1 levels, immune cell infiltration, and immune scores were evaluated between two clusters. Prognostic signatures and correlation analysis with TIME were analyzed using Lasso and Spearman's analysis. GBM tissue was collected to verify the correlations. Eighteen m6A regulators (WTAP, YTHDF2, HNRNPC, CAPRIN1, YTHDF3, METTL14, GNL3, ZCCHC4, HNRNPD, YTHDF1, RBM15, PCIF1, RBM27, KIAA1429, MSI2, FTO, ALKBH5, and METTL3), PD‐L1, and PD‐1 were significantly upregulated in GBM tissue. These regulators were divided into two distinct molecular subtypes (clusters 1 and 2). Cluster 2 exhibited a significant increase in immune score, monocytes, M1 macrophages, activated mast cells, and eosinophils. HNRNPC, YWHAG, and ALKBH5 were significantly associated with TIME and positively correlated with PD‐L1. Immune cell invasiveness profiles dynamically changed with copy number changes of these three m6A regulators. Finally, YWHAG and ALKBH5 were found to be independent prognostic indicators of GBM through risk analysis and were experimentally verified with clinical samples. YWHAG and ALKBH5 may be used as prognostic markers for patients with GBM. m6A methylation regulators may play an important role in regulating PD‐L1/PD‐1 expression and immune infiltration, thus having a significant impact on GBM TIME.
Variations in the Management of Closed Salter-Harris II Distal Tibia Fractures
Authors: Swarup Ishaan , Pearce Robert , Sanborn Ryan ,   Children’s Orthopaedic Trauma and Infection Consortium for Evidence Based Studies (CORTICES), Shore Benjamin J.
Published: August 2023

Background:

There are no formal practice guidelines for the surgical management of closed, Salter-Harris (SH) II distal tibia fractures. The purpose of this study was to survey the indications for operative and nonoperative management of this injury across pediatric tertiary care centers.

Methods:

We surveyed pediatric orthopedic surgeons at 20 tertiary care level-1 pediatric trauma centers. Surgeons were provided with 16 clinical scenarios that varied based on patient age and sex, and highlighted the following surgical indications: translation <3 mm, translation ≥3 mm, sagittal plane angulation >5 degrees, and coronal plane angulation >5 degrees. Each case’s scenario and radiographs after closed reduction were presented in a randomized manner. Consensus was defined as 80% agreement, and descriptive statistics were used to summarize the results.

Results:

In total, 33 of 37 surgeons completed the survey (89% response rate). All surgeons took trauma call at a level-1 pediatric trauma center and had an average of 8.8 years (SD: 6.5 y) of experience. Consensus was reached in 4 of 16 scenarios. Specifically, nonoperative management was recommended for all scenarios showing <3 mm of translation after closed reduction. The majority of surgeons recommended operative management in scenarios showing coronal plane angulation after closed reduction, but none of these scenarios reached consensus. There was a near-equal split in operative and nonoperative management in 8 of 16 scenarios. These scenarios showed ≥3 mm translation after closed reduction and sagittal plane angulation after closed reduction. Surgeons with 6 to 10 years in practice were the most likely to recommend surgery, especially in the case of >5 degrees coronal plane angulation postreduction (P<0.05).

Conclusions:

There is considerable variation regarding the indications for operative and nonoperative management of closed, SHII distal tibia fractures. Consensus was reached for nonoperative management in patients with <3 mm of translation after closed reduction; however, with greater deformity consensus regarding optimal treatment was unable to be achieved. The variation in the management of distal tibia SHII fractures is significant, suggesting that perhaps clinical equipoise exists between operative and nonoperative management.

Level of Evidence:

V.
Cardiovascular and Pulmonary Entry-Level Physical Therapist Competencies: Update by Academy of Cardiovascular & Pulmonary Physical Therapy Task Force
Authors: Johanson Morgan , Bartlo Pamela , Bauer Naomi , Campbell Angela , Everett Sagan , Smith Nancy
Published: August 2023

Purpose:

Competency-based education and creation of profession-based entrustable professional activities are current trends in physical therapist (PT) education. The purpose of this project is to determine the current entry-level PT competencies for cardiovascular & pulmonary (CVP) physical therapy.

Methods:

The Academy of Cardiovascular & Pulmonary Physical Therapy Competency Task Force was established to update and expand previous competencies. A mixed method approach of Subject Matter Expert (SME) consensus (modified Delphi process) and a broader survey process was used to develop these entry-level competencies. With SME guidance, a modified version of the levels of competence, None-to-Proficient, was adopted based on previous competency work by the American Council of Academic Physical Therapy.

Results:

Twenty-nine SME members engaged in the consensus process, and 268, 194, 305, and 222 respondents completed the 4 surveys, respectively. Six hundred fifty-one competency items were rated across most Commission on the Accreditation of Physical Therapy Education Standard 7 Curriculum areas, following the patient–client management model.

Conclusions:

These competencies establish specific expected levels of knowledge, skills, and behaviors essential for entry-level CVP PT practice. Adopting these competencies will help lay the groundwork for future competency-based PT education and aid in the development of the physical therapy profession's core entrustable professional activities.
Efficacy and Safety of Anxiolytics in Mohs Micrographic Surgery: A Randomized, Double-Blinded, Placebo-Controlled Trial
Authors: Guo Danny , Zloty David M. , Kossintseva Irèn
Published: August 2023

BACKGROUND

Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient satisfaction. Despite the use of anxiolytic medications in outpatient procedures, there is limited comparative evidence on the efficacy and safety of these agents in Mohs micrographic surgery.

OBJECTIVE

To compare the effectiveness and safety of different preprocedural anxiolytic agents in Mohs surgery on perioperative patient anxiety and patient satisfaction.

MATERIALS AND METHODS

A double-blinded, randomized, placebo-controlled trial was conducted of 6 different preprocedural anxiolytic agents (lorazepam, diazepam, alprazolam, gabapentin, pregabalin, and melatonin) in 350 patients undergoing Mohs surgery. Anxiety and vital signs were recorded.

RESULTS

Diazepam demonstrated a statistically significant, sustained reduction in anxiety levels compared with placebo (p = .03). Gabapentin significantly reduced early anxiety (p = .02). Alprazolam showed a trend to early anxiety reduction (p = .08). Lorazepam (p = .73), pregabalin (p = .53), and melatonin (p = .24) failed to reduce patient anxiety compared with placebo at any time point. No anxiolytic significantly impacted any patient vital sign or cognition.

CONCLUSION

Although short-acting benzodiazepines and gamma-aminobutyric acid medications may have transient anxiolytic effects, a single oral dose of 5 mg of diazepam can provide a sustained anxiolytic effect in Mohs surgery, with excellent patient safety.
A Wealth and Investment Primer for Plastic Surgeons: The Two Pillar Framework
Authors: Janis Brett A. , Tanna Neil , Janis Jeffrey E.
Published: August 2023

Sound investing, analogous to maintaining good health, is a long-term process that must be continuously nurtured and strengthened. This article will describe how adhering to a simple, two-pillar framework can help plastic surgeons secure superior wealth generation. Our first pillar is anchored on developing a consistent savings plan geared to circumstances and lifestyle goals at each career stage. Each plastic surgeon’s path is unique, but there are common drivers based on substantial upfront educational costs and high life-time wage incomes. The second pillar is focused on generating strong after-tax investment performance over many market cycles. This primer presents pragmatic steps plastic surgeons should consider for financial planning, approaching capital markets, and selecting advisors. Strong financial planning, combined with a more active and transparent investing approach, can deliver superior financial outcomes. This is an introduction only focused on investing in public securities versus illiquid assets (an asset that cannot be converted to cash in a short period, usually defined as less than 7 days, like real estate or art collectibles, for instance) and is not meant to be exhaustive or constitute investment advice regarding any asset class, strategy, or examples cited herein.
Treatment Options for the Clinical Management of Axillary Breast Tissue
Authors: Kurtzman Joey S. , Pinkasovic Elana , Preminger B. Aviva
Published: August 2023

Background:

Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%–6% of women and 1%–3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue.

Methods:

A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence.

Results:

A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications.

Conclusions:

Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal.
Treatment of Symptomatic Lymphedema in the Hand with Omental Flow-through Flap
Authors: Dozier Peaches A. , Reid Adam J. , Mailey Brian A.
Published: August 2023

Vascularized lymph node transfer (VLNT) is a surgical option to improve physiologic lymphatic drainage. This technique transfers healthy vascularized lymphatic tissue from various available donor sites to the existing lymphatics of the affected area. Here, we present a successful case halting the size progression and reversing lymphedema symptoms in a patient treated with vascularized omental lymph node transfer. A 56-year-old man presented with stage III malignant sarcoma of his left medial upper arm. Two-years after excision, flap reconstruction, and radiation brachytherapy, worsening diffuse left arm edema developed, causing pain, decreased range of motion, and paresthesia. A vascularized omental lymph node transfer was performed. The omental flap required a flow-through design, requiring anastomosis of both gastroepiploic arteries to obtain Dopplerable signals. The patient experienced progressive relief of lymphedema symptoms after this transfer. Treatment outcomes with the use of VLNT have been largely encouraging; however, objective measures of improvement and timing of neolymphangiogenesis in recipient lymph node sites still need to be defined. Understanding omental VLNT flow dynamics and expected time point changes during the postoperative course will define expected outcomes and allow for treatment of a greater number of patients affected by lymphedema.
CONGENITAL RETINAL MACROVESSEL AND CAVERNOUS HEMANGIOMA IN COWDEN SYNDROME: A CASE REPORT AND REVIEW OF LITERATURE
Authors: Cohen Devin C. , Tsui Jonathan C. , Scoles Drew
Published: August 2023

Purpose:

To describe a case of unilateral congenital retinal macrovessel with a retinal cavernous hemangioma in a patient with Cowden syndrome (CS). In addition, we summarize previously reported cases of ocular findings in CS in the literature.

Methods:

Observational case report and literature review.

Results:

A 45-year-old White female patient with Cowden syndrome presented for routine ocular examination. She had a history of thyroid carcinoma, fallopian paratubal cyst, chromophobe-type renal cell carcinoma, multiple benign skin lesions, and macrocephaly. At presentation, she was asymptomatic with good vision. On dilated fundus examination, the right eye revealed a congenital retinal macrovessel and retinal cavernous hemangioma. Previously performed genetic testing revealed a pathogenic c.46dupT mutation in the PTEN gene, which was consistent with CS.

Conclusion:

Our patient had a history of multiple malignancies and hamartomas consistent with her genetic diagnosis of CS. We incidentally discovered a congenital retinal macrovessel with a retinal cavernous hemangioma. Patients with CS should be referred for interdisciplinary evaluation, including routine ocular examinations.
Combined Use of Therapeutic Hyper-CL Soft Contact Lens and Insulin Eye Drops for the Treatment of Recalcitrant Neurotrophic Keratopathy
Authors: Giannaccare Giuseppe , Coco Giulia , Rossi Costanza , Borselli Massimiliano , Lucisano Andrea , Vaccaro Sabrina , Verdiglione Mario , Scorcia Vincenzo
Published: August 2023

Purpose:

The aim of this study was to report the successful clinical outcome of recalcitrant neurotrophic keratopathy (NK) treated with insulin eye drops associated with therapeutic Hyper-CL soft contact lens (CL) (EyeYon Medical, Ness Ziona, Israel).

Methods:

This study is a case report.

Results:

A 40-year-old man was referred to our clinic for the management of severe recalcitrant NK developed after surgical and adjuvant radiotherapy treatment of adenoid cystic carcinoma of the nasal cavity with basicranial involvement. The patient presented with severe conjunctival hyperemia, a large (7 × 4 mm) central epithelial defect, corneal opacity and thinning, and deep corneal neovascularization. Unpreserved tear substitutes, vitamin A ointment, punctal plug, bandage CL, and autologous serum had been used for the previous 3 months without success. Patient was prescribed insulin eye drops (1 unit per mL), and therapeutic Hyper-CL soft CL was applied to increase the contact time between insulin eye drops and the corneal surface. Follow-up visits were performed at day 10 (T1) and day 20 (T2). A marked reduction in the epithelial defect size was noted at T1 and complete healing was reached at T2. Simultaneously, conjunctival hyperemia and corneal opacity markedly reduced over time with treatment.

Conclusions:

The combination of insulin eye drops and therapeutic Hyper-CL soft CL was effective in determining healing of recalcitrant NK not responsive to standard treatments and bandage CL. It is unclear whether the positive outcomes were determined by insulin eye drops, Hyper-CL, or the combination of both, and future randomized clinical trials are warranted to determine the contribution of each treatment.
Nature of the work correlated to overweight and obesity for nurses: A 10-year hospital-based cohort study
Authors: Huang Chih-Kang , Huang Ching-Feng , Liu Zheying , Li Shih-Kuan , Chiu Yu-Hua , Chiu Hsiao-Hui , Wu Shang-Liang
Published: August 2023

Background:

Nurses are a high-risk group for overweight and obesity due to high stress, low-labor medical work, irregular diet, and lack of exercise. There is scarce information on relationship between job characteristics and overweight and obesity among nurses. This study aimed to answer the question. Does the nature of the work including job position, seniority relate to overweight and obesity among nurses? Their incidence was also investigated.

Methods:

We conducted a retrospective cohort study of nurses who underwent annual checkups during 2007 to 2016 in a medical center. Overweight was defined as a body mass index between 24 and 27 kg/m2. Obesity was defined as a body mass index higher than 27 kg/m2. We calculated the prevalence and incidence of overweight and obesity and estimated relative risks using logistic regression.

Results:

Overall, 4253 participants were enrolled for the incidence of overweight and obesity. We found that junior staff, administrative directors, working in intensive care units, and old age had a high possibility of overweight. Junior staff, administrative directors, old age, and male sex tend to be obesity. Overweight and obesity occurred rapidly in the first 2 years of their career.

Conclusion:

Our findings suggest that policies should be set up to achieve the goal of workplace health promotion. Health plans focusing on these factors may help nurses avoid obesity and overweight. The director of the hospital should keep track of the health checkup database to confirm the benefits of its long-term implementation.
Relationship between the Presence of Nystagmus in the Fourth Position of the Epley Maneuver and Treatment Efficacy for PSC BPPV: A Prospective Study
Authors: Pimentel de Morais Catarina , Correia Filipe , Branco Pedro , Castelhano Luís , Escada Pedro
Published: August 2023

Objective

To investigate whether a specific nystagmus observed during the Epley maneuver can enable immediate reassessment of patients, eliminating the need for deferred diagnosis.

Study Design

Prospective cohort.

Setting

Tertiary center.

Patients

Patients with posterior semicircular canal (PSC) benign paroxysmal positional vertigo (BPPV) diagnosed by the Dix–Hallpike test between March 2022 and March 2023.

Interventions

All patients were treated with the Epley maneuver. The presence and the characteristics of the nystagmus were recorded in each of the four intermediate positions of the maneuver. Fifteen minutes later, all patients were reevaluated with the Dix–Hallpike test to determine the therapeutic success.

Main Outcome Measures

Outcome of the Epley maneuver and its relationship with nystagmus characteristics during the four positions of the maneuver.

Results

Sixty-six patients (77.3% female) were included in the study, of which 66.7% exhibited right PSC BPPV. Therapeutic success of the first Epley maneuver was 74.2%. Almost one third (30.3%) of patients presented with nystagmus in the second and third positions of the Epley maneuver. All patients with down-beating and torsional nystagmus toward the opposite direction of the diagnostic nystagmus in the fourth position of the Epley maneuver needed a second rehabilitative maneuver. None of the patients without nystagmus in this fourth position remained with active BPPV after the first Epley maneuver.

Conclusions

The presence of nystagmus in the fourth position of the Epley maneuver appears to have a high predictive value, reducing waiting time for a second diagnostic maneuver. Its absence may exempt subsequent reevaluation.
Key Genes and Endoscopic Radical Surgery in Primary Middle Ear Oncocytic Papillomas
Authors: Lyu Jihan , Wang Wei , Chen Binjun , Wang Yanmei , Sun Haojie , Yuan Yasheng , Ren Dongdong
Published: August 2023

Objective

Papillomas originating from the Schneiderian epithelium within the middle ear are extremely rare and may be associated with a high rate of recurrence and malignant transformation. Oncocytic papillomas represent the rarest pathological subtype of such tumors. The current investigation aimed to determine whether there exists a distinct mechanism underlying the incidence of oncocytic papillomas arising primarily within the middle ear, and to explore potential treatment strategies to ensure complete removal and prevent recurrence.

Study Design

Search of the English literature for cases of middle ear papilloma and RNA sequencing analysis of three samples from one new case presenting at the Eye and ENT Hospital, Fudan University (Shanghai, China), with recurrent middle ear oncocytic papilloma, along with two normal mucosal samples.

Setting

Academic, tertiary referral hospital.

Patient and interventions

The patient underwent open mastoidectomy and endoscopic tympanoplasty twice in 6 years. Histopathology confirmed oncocytic papilloma in middle ear. The patient has been free of the disease at 18 months of follow-up without radiation, whereas the RNA-seq analysis of the samples in endoscopic operations remained nonmalignant.

Results

Only four cases of primary middle ear oncocytic papillomas have been reported. Recurrent masses usually originate from around the eustachian tube, which may explain the pathogenesis of this lesion. RNA-seq analysis was used to identify 1,317 (UP, 239; DOWN, 1078) differentially expressed genes between papillomas and normal mucosa. The involvement of some hub proteins (e.g., FN1, CXCL8, L10, JUN, and FOS) in the pathogenesis of primary middle ear papillomas was found to align with the observed clinical features.

Conclusion

The middle ear oncocytic papillomas were extremely rare and remained incompletely understood. The findings of this first RNA-seq analysis of this rare tumor may serve to enhance comprehension of and aid in the management of middle ear papillomas.
Effects of Teduglutide on Diarrhea in Pediatric Patients with Short Bowel Syndrome-Associated Intestinal Failure
Authors: Fifi Amanda , Raphael Bram P. , Terreri Brian , Uddin Sharif , Kaufman Stuart S.
Published: August 2023

Objectives:

This post-hoc analysis evaluated the effect of teduglutide treatment on diarrhea in patients with short bowel syndrome-associated intestinal failure (SBS-IF).

Methods:

Data from 2 open-label, multicenter, phase 3 pediatric SBS-IF clinical trials of teduglutide (NCT01952080 and NCT02682381) were pooled where possible. The primary objective was to evaluate the change in stool consistency, frequency, and volume from baseline to weeks 12 and 24 of treatment in patients who received any teduglutide dose from both studies (“total teduglutide”). Safety assessments included gastrointestinal adverse event reporting.

Results:

Overall, 101 patients were analyzed. Among the total teduglutide group (n = 87), there were significant changes from baseline to weeks 12 and 24 in mean (standard error) Bristol Stool Form Scale (BSFS) score [−1.8 (0.26; P < 0.0001) and −2.2 (0.27; P < 0.0001), respectively], parenteral nutrition and/or intravenous fluid (PN/IV) volume [−16.9 (1.7; P < 0.0001) and −20.1 (2.3; P < 0.0001) mL/kg/day, respectively], and enteral nutrition volume [9.2 (1.7; P < 0.0001) and 9.6 (2.3; P = 0.0002) mL/kg/day, respectively]. Among patients in the standard of care group (n = 14) there were numerical changes in BSFS score, and enteral nutrition volume at weeks 12 and 24; significant changes in PN/IV volume [−6.9 (1.5) mL/kg/day; P = 0.0041] were observed at 24 weeks, but not at 12 weeks.

Conclusion:

In this post-hoc analysis, short-term treatment with teduglutide was associated with improved stool consistency, as well as trends towards reductions in PN/IV requirements and advancements in enteral nutrition volume in children with SBS-IF. Further research assessing the impact of patient-level factors on stool characteristics when using teduglutide is warranted.
Pediatric Malignant Pelvic Paraganglioma—A Diagnostic and Surgical Challenge
Authors: Al-Shafei Tariq Rashid Salim , Ali Farman , Dawood Bashar , Al-Balushi Zainab , Al Sulaimi Jawaher , Mittal Alok , Ghosh Dhruva N.
Published: August 2023

Pheochromocytoma are chromaffin cell-derived tumors that have an exceptionally high genetic predisposition. The presentation of extra-adrenal and pelvic paraganglioma (PGL) in children is uncommon. Due to the relative rarity, PGL tumors’ presentation and disease behavior may vary. Genetic testing, imaging, and biochemical investigation are employed to diagnose PGL. Surgical resection with preoperative angioembolization has been practiced in alleviating the burden of torrential intraoperative bleeding.
Detection of multidrug-resistant pathogens as a risk for patients in healthcare settings
Authors: Pantano Daniele , Friedrich Alexander W.
Published: August 2023

Purpose of review

Healthcare-acquired Infections and antimicrobial resistance are major challenges for both healthcare management and patient safety. Every year, resistant microorganisms seem to outperform our ability to develop new interventions to counteract this escalation. This review, focusing mainly on bacteria, aims to provide an update on the recent advances in diagnostics and on the strategies to manage healthcare-acquired infections.

Recent findings

Both phenotypic and molecular methods are profitably growing in recent years. In addition to these classical techniques, new methodologies are continuously developed with more focus on other methods like the use of nanotechnologies, the implementation of computational analysis, and the machine-learning approach. An increasing effort is also given to developing alternatives to antibiotics such as phage therapy and the use of probiotics or other antagonizing microorganisms.

Unfortunately, even if new methods are developed each year, on the surveillance and infection prevention side of the problem, the main approach is still based on observational and descriptive studies. A shift in how we implement infection control measures by using modern diagnostic tools and novel typing approaches is essential in resolving the problem.
Spontaneous Recovery of Pathological Fracture Caused by Medication-Related Osteonecrosis of the Jaw
Authors: Jung Joon Hyeok , Kim Je Seong , Kim Bong Chul , Lee Jun , Lim Hun Jun
Published: August 2023

Pathological fracture is one of the most serious complications in medication-related osteonecrosis of the jaw (MRONJ). This case is a report of an 87-year-old woman who had been diagnosed with pathological fracture due to MRONJ. The authors performed minimally invasive and conservative treatment, such as intraoral dressing, antibiotic therapy, and simple debridement, for patients with pathologic fractures due to MRONJ. After 1 year, the inflammatory symptoms disappeared and pathological fractures spontaneously recovered.
Knowledge of Pelvic Floor Dysfunction in African American and Afro-Caribbean Women Seeking Medical Care in a Primary Care Ambulatory Setting
Authors: Soyemi Sarin A. , Sheu Joanne , Hahm Emily , Noriega Dominique , Kristoferson Eva , Li Jiamin , Chan Luanna , Zhen Dong , Calixte Rose , Gil Patricia
Published: August 2023

Importance

Approximately one fourth of U.S. community-dwelling women will develop a pelvic floor dysfunction (PFD) within their lifetimes. Prior research has revealed that knowledge of PFD was low to moderate in the general population and lower among Black patients.

Objective

This study aimed to assess the proficiency of urinary incontinence and pelvic organ prolapse (POP) in self-identified African American and Afro-Caribbean adult (age ≥ 18 years) female patients seeking medical care in our ambulatory setting.

Study Design

In this cross-sectional study, we administered the Prolapse and Incontinence Knowledge Questionnaire to patients in primary care and gynecology ambulatory settings at an academic medical center in Central Brooklyn. We used a multivariable Poisson regression model to find characteristics of the participants that are associated with proficiency in Prolapse and Incontinence Knowledge Questionnaire domains.

Results

A total of 266 survey participants self-identified as African American or Afro-Caribbean. Overall, using a multivariable model, knowledge of POP was significantly higher among African Americans than Afro-Caribbeans, and 75.5% of our patients reported that they would seek information on urinary incontinence and POP from a medical provider (gynecologist or primary care doctor) compared with other alternatives (eg, internet, 19.6%).

Conclusions

These findings highlight subgroups that could benefit from provider-initiated education regarding PFD. Furthermore, although Black patients are often homogenized in research studies, differences may exist within subgroups likely because of varying interplays of structural racism and other social determinants of health, which may serve as an area of future research.
Accuracy of Bladder Scanner in Measuring Bladder Volumes in Postpartum Women
Authors: Zheng Veronica Jierong , Geynisman-Tan Julia , Knoll Justin , Kenton Kimberly , Brown Oluwateniola
Published: August 2023

Importance

Ultrasound bladder scanners may provide a less invasive method to measure postpartum urinary volume, but their accuracy must be validated.

Objective

The objective of this study was to evaluate the accuracy of a bladder scanner in measuring bladder volumes in postpartum women. The secondary objective was to evaluate the effect of obesity on scanner accuracy.

Study Design

This prospective cohort study included women older than 18 years who gave birth vaginally at term gestation. After delivery, we obtained 3 sequential measurements of the bladder volume using an ultrasound bladder scanner. We then measured true bladder volume by transurethral catheterization. The primary outcome was the absolute difference between the bladder scanner volume and the catheterized volume. A Wilcoxon signed-rank test was used to compare absolute median difference between the bladder scan volume and true catheter volume. Repeated-measures analysis of variance and linear regression were used to evaluate the effect of obesity on the accuracy of the bladder scanner.

Results

We enrolled 70 patients (61.4% nulliparous, 38.6% multiparous). One delivery was vacuum-assisted, 4 were forceps-assisted, and 65 were spontaneous vaginal. The median age was 34 years, and median body mass index was 30.5. Median difference between bladder scanner and catheter volume was 42.7 mL (P < 0.001), with the scanner underestimating true volume 82.9% of the time. The scanner was less accurate in patients with a body mass index ≥ 30 (P = 0.001).

Conclusions

The bladder scanner is less accurate than catheterized urine volume. However, the median difference between the bladder scanner and the catheterized volume is 42.7 mL, making it suitable for clinical use. Accuracy deteriorates in obese patients.
Patient-Specific Pessaries for Pelvic Organ Prolapse Using Three-Dimensional Printing: A Pilot Study
Authors: Hong Christopher X. , Zhang Shufei , Eltahawi Ahmed , Borazjani Ali , Kalami Hamed , San Aye Nyein , Sham Derek , Ameri Golafsoun , McDermott Colleen D.
Published: August 2023

Importance

Vaginal pessaries are an effective nonsurgical treatment for pelvic organ prolapse (POP) when properly fitted. However, pessary fitting and use are often unsuccessful or imperfect.

Objective

The objective of this study was to assess the feasibility of using patient-specific pessaries fabricated from three-dimensional (3D)-printed molds to improve POP symptoms and increase overall satisfaction of pessary treatment in patients using standard vaginal pessaries.

Study Design

Patients undergoing POP treatment with standard vaginal pessaries were enrolled in this pilot prospective study. Patient-specific pessaries were designed and fabricated for each patient using patient input, physician input, and anatomic measurements from clinical assessment. Pessary fabrication involved injection of biocompatible liquid silicone rubber into 3D-printed molds followed by a biocompatible silicone coating. Pelvic organ prolapse symptomatic distress and pessary treatment satisfaction were evaluated before and after a 3-week patient-specific pessary home trial using the validated Pelvic Organ Prolapse Distress Inventory-6 form and a visual analog scale, respectively.

Results

Eight women were included in this study. Changing from standard pessary to patient-specific pessary treatment was associated with an improvement in prolapse symptoms on the Pelvic Organ Prolapse Distress Inventory-6 (median change, −3.5; interquartile range, −5 to −2.5; P = 0.02) and an increase in overall pessary satisfaction on a visual analog scale (median change, +2.0; interquartile range, +1.0 to +3.0; P = 0.02). All patients reported either an improvement or no change in pessary ease of use, comfort, and the feeling of support provided by the pessary.

Conclusion

Patient-specific vaginal pessaries are a promising alternative to standard pessaries for alleviating POP symptoms and improving patient satisfaction with pessary use.
Combining Serum miR-144-3p and miR-652-3p as Potential Biomarkers for the Early Diagnosis and Stratification of Acute Cellular Rejection in Heart Transplantation Patients
Authors: Pérez-Carrillo Lorena , Sánchez-Lázaro Ignacio , Triviño Juan Carlos , Feijóo-Bandín Sandra , Lago Francisca , González-Juanatey José Ramón , Martínez-Dolz Luis , Portolés Manuel , Tarazón Estefanía , Roselló-Lletí Esther
Published: August 2023

Background.

There is a dire need for specific, noninvasive biomarkers that can accurately detect cardiac acute cellular rejection (ACR) early. Previously, we described miR-144-3p as an excellent candidate for detecting grade ≥2R ACR. Now, we investigated the combination of miR-144-3p with miR-652-3p, other differentially expressed serum miRNA we previously described, to improve diagnostic accuracy mainly in mild rejection to avoid reaching severe stages.

Methods.

We selected miR-652-3p from a preliminary RNA-seq study to be validated by reverse transcription-quantitative polymerase chain reaction on 212 consecutive serum samples from transplantation recipients undergoing routine endomyocardial biopsies to subsequently combine them with miR-144-3p results and investigate their diagnostic capability.

Results.

We confirmed the miR-652-3p overexpression (P < 0.0001) and its capability to discriminate between patients with and without ACR of any grade (P < 0.0001). The combined serum levels of miR-144-3p and miR-652-3p were significantly higher in patients with rejection regardless of posttransplantation time (P < 0.0001). This combination resulted in a diagnostic efficacy for 1R (area under the curve = 0.794) and ≥2R (area under the curve = 0.892; P < 0.0001) that was superior to each biomarker alone. Furthermore, it was a strong independent predictor of ACR for 1R (odds ratio of 10.950; P < 0.0001) and ≥2R (odds ratio of 14.289; P < 0.01).

Conclusions.

We demonstrated that an appropriate combination of blood-based biomarkers could exhibit greater efficiency for cardiac rejection diagnosis. The combined detection of abnormal expression of miR-144-3p and miR-652-3p in the serum of ACR patients can improve the diagnostic sensitivity of rejection at an early stage and contribute to increasing the diagnostic accuracy, mainly in the lower rejection grades.
RNF4 and USP7 cooperate in ubiquitin-regulated steps of DNA replication
Authors: Chang Ya-Chu , Lin Kevin , Baxley Ryan M. , Durrett Wesley , Wang Liangjun , Stojkova Olivera , Billmann Maximilian , Ward Henry , Myers Chad L. , Bielinsky Anja-Katrin
Published: August 2023

DNA replication requires precise regulation achieved through post-translational modifications, including ubiquitination and SUMOylation. These modifications are linked by the SUMO-targeted E3 ubiquitin ligases (STUbLs). Ring finger protein 4 (RNF4), one of only two mammalian STUbLs, participates in double-strand break repair and resolving DNA–protein cross-links. However, its role in DNA replication has been poorly understood. Using CRISPR/Cas9 genetic screens, we discovered an unexpected dependency of
RNF4
mutants on
ubiquitin specific peptidase 7
(
USP7)
for survival in
TP53
-null retinal pigment epithelial cells.

TP53
−/–
/RNF4
−/–
/USP7
−/–

triple knockout (TKO) cells displayed defects in DNA replication that cause genomic instability. These defects were exacerbated by the proteasome inhibitor bortezomib, which limited the nuclear ubiquitin pool. A shortage of free ubiquitin suppressed the ataxia telangiectasia and Rad3-related (ATR)-mediated checkpoint response, leading to increased cell death. In conclusion, RNF4 and USP7 work cooperatively to sustain a functional level of nuclear ubiquitin to maintain the integrity of the genome.
Cellular dynamics in the maize leaf growth zone during recovery from chilling depends on the leaf developmental stage
Authors: Lainé Cindy M.S. , AbdElgawad Hamada , Beemster Gerrit T.S.
Published: August 2023

Zea mays, a major crop, is highly sensitive to chilling which frequently occurs during its seedling stage and negatively affects yields. Although the direct effect of chilling is well-studied, the mechanisms determining the subsequent recovery are still unknown. Our goal is to determine the cellular basis of the dynamic leaf growth response to chilling and during recovery of leaves exposed before or after their emergence. We first studied the effect of a 3-day cold spell on leaf growth at the plant level. Then, we performed a kinematic analysis to analyse the dynamics of cell division and elongation during recovery of the 4thleaf after exposure to cold before or after emergence. Our results demonstrate that cold more strongly reduced the final length of non-emerged than emerged leaves (-13 vs -18%). This was not related to growth differences during cold, but a faster and more complete recovery of the growth of emerged leaves. Kinematic analysis showed that this difference was due to a higher cell division rate on the 1stand a higher cell elongation rate on the 2nd-day of recovery, respectively. The dynamics of cell division and expansion during recovery determine developmental stage-specific differences in cold tolerance of maize leaves.
Study of the protectiveOAS1rs10774671-G allele against severe COVID-19 in Moroccans suggests a North African origin for Neanderthals
Authors: Youssfi Fatima Zohra El , Haroun Abbas Ermilo , Nebhani Chaimae , Belayachi Jihane , Askander Omar , Fahime Elmostafa El , Fares Hakima , Ennibi Khalid , Abouqal Redouane , Razine Rachid , Bouhouche Ahmed
Published: August 2023

Background

The clinical presentation of COVID-19 has shown high variability between individuals, which is partly due to genetic factors. The OAS1/2/3 cluster was found to be strongly associated with COVID-19 severity. We aimed to examine this locus for the occurrence of the critical variant, rs10774671, and its respective haplotype blocks within the Moroccan population.

Methods

The frequency of SNPs at the cluster of OAS immunity genes was assessed from an in-house database in 157 unrelated individuals of Moroccan origin. TheOAS1exon 6 was sequenced by Sanger’s method in 71 asymptomatic/mild and 74 moderate/severe individuals positive for SARS-CoV-2. Genotypic, allelic, and haplotype frequencies of three SNPs were compared between the two groups. Finally, males in our COVID-19 series were genotyped for the Berber-specific marker E-M81.

Results

The prevalence of theOAS1rs10774671-G allele in present-day Moroccans was 40.4%, close to that of Europeans. However, it was found equally on both the Neanderthal GGG haplotype and the African GAC haplotype with a frequency of 20% each. These two haplotypes, and hence the rs10774671-G allele, were significantly associated with the protection against severe COVID-19 (p= 0.034,p= 0.041, andp= 0.008 respectively). Surprisingly, among Berber men, the African haplotype was absent while the prevalence of the Neanderthal haplotype was close to that of Europeans.

Conclusion

The protective rs10774671-G allele ofOAS1was found only in the Neanderthal haplotype in Berbers, the indigenous people of North Africa, suggesting that this region may have served as the stepping-stone for the passage of the hominids to the other continents.
H3-OPT: Accurate prediction of CDR-H3 loop structures of antibodies with deep learning
Authors: Chen Hedi , Fan Xiaoyu , Zhu Shuqian , Pei Yuchan , Zhang Xiaochun , Zhang Xiaonan , Liu Lihang , Qian Feng , Tian Boxue
Published: August 2023

Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model, and provides a 2.24 Å average RMSDCαbetween predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody-antigen interactions. This structural prediction tool can be used to optimize antibody-antigen binding, and to engineer therapeutic antibodies with biophysical properties for specialized drug administration route.
Single-dose epidural bupivacaine vs placebo after lumbar decompression surgery: A Randomized controlled trial
Authors: Hermans Sem M. M. , Lantinga-Zee Aniek A. G. , Droeghaag Ruud , van Santbrink Henk , van Hemert Wouter L. W. , Reinders Mattheus K. , Hoofwijk Daisy M. N. , van Kuijk Sander M. J. , Rijkers Kim , Curfs Inez
Published: August 2023

Introduction

Adequate postoperative pain management following lumbar spinal decompression surgery is important as it will lead to early mobilization, less complications and shorter hospital stay. Opioid consumption should be limited due to their frequently accompanied side effects and their addictive nature. During the final phase of lumbar decompression surgery, the epidural space becomes easily accessible. This might be an ideal moment for surgeons to administer an epidural bolus of analgesia, as a safe and effective method for post-operative pain relief.

Methods

This is a double blind randomized controlled trial comparing a single intraoperative bolus of epidural analgesia using bupivacaine 0.25% to placebo (NaCl 0,9%) and its effect on postoperative pain following lumbar spinal decompression surgery. The primary outcome was the difference in NRS pain between the intervention and placebo groups during the first 48h after surgery. It was hypothesized that the intervention group will have lower postoperative NRS pain scores.

Results

Both the intervention group and the placebo group consisted of 20 randomized patients (N=40). We observed statistically significant lower NRS pain scores in the intervention group in comparison with the control group, with a difference of −1.9 (±1.1). The average pain score was lower in the intervention group at all postoperative time-points. Opioid consumption, quality of life and satisfaction were similar between study groups. No study related complications occurred, and complications rate did not differ between study groups.

Conclusion

This randomized controlled trial shows that administrating a bolus of intraoperative epidural bupivacaine is a safe and effective method in reducing early postoperative pain following lumbar decompression surgery.
Computer vision detects inflammatory arthritis in standardized smartphone photographs in an Indian patient cohort
Authors: Phatak Sanat , Chakraborty Somashree , Goel Pranay
Published: August 2023

Introduction

Computer vision extracts meaning from pixelated images and holds promise in automating clinical tasks. Convolutional neural networks (CNN), deep learning networks used therein, have shown promise in X-ray images as well as joint photographs. We studied the performance of a CNN on standardized smartphone photographs in detecting inflammation in three hand joints.

Methods

We enrolled consecutive patients with inflammatory arthritis of less than two years duration and excluded those with deformities. Each patient was examined by a rheumatologist and the presence of synovitis in each joint was recorded. Hand photographs were taken in a standardized manner and anonymized. Images were cropped to include joints of interest. A reNrt-101 backbone modified for two class outputs (inflamed or not) was used for training. We also tested a hue augmented dataset. We report accuracy, sensitivity and specificity for three joints: wrist, index finger proximal interphalangeal (IFPIP), middle finger interphalangeal (MFPIP).

Results

The cohort had a mean age of 49.7 years; most had rheumatoid arthritis(n=68). The wrist (62.5%), MFPIP (47%) and IFPIP (41.5%) were the three most commonly inflamed joints. The CNN achieved the highest accuracy in being able to detect synovitis in the MFPIP (83%) followed by the IFPIP (74%) and the wrist (65%).

Discussion

We show that computer vision was able to detect inflammation in three joints of the hand with reasonable accuracy on standardized photographs despite a small dataset. Feature engineering was not required, and the CNN worked despite a diversity in clinical diagnosis. Larger datasets are likely to improve accuracy and help explain the basis of classification. These data suggest a potential use of computer vision in screening and follow-up of inflammatory arthritis.