bluuebunny/crossref_metadata_2025 huggingface dataset:
Tirofiban influences serum inflammatory factors and neurotransmitter levels in acute cerebral infarction patients
Authors: Gbayisomore Tolulope Judah , Okon Inibehe Ime , Ajayi Oluwafunmbi Ayomiposi , Inusah Abdul-Hanan Saani , Ziblim Andrew Mpagwuni , Ajayi Rufus Oluwagbemileke , Elesho Oluwagbemisola Elizabeth , Ike-Okpe Onyekachi Innocent , Muoneke Nonso Joachin , Bankole Nourou Dine Adeniran
Published: July 2024

This study investigated the effects of tirofiban on serum inflammatory factors and neurotransmitter levels in 122 patients with acute cerebral infarction (ACI) at a Nigerian teaching hospital from January 2021 to December 2023. Patients were divided into conventional and study groups, with the study group receiving tirofiban in addition to standard treatment. Clinical efficacy and levels of Interleukin 6 (IL-6), serum tumor necrosis factor (TNF-α), 5-hydroxytryptamine (5-HT), dopamine (DA), and glutamic acid (Glu) were compared. Result findings showed that the research group (RG) had a significantly higher total effective rate of treatment (93.44%) compared to the conventional group. While IL-6 and TNF-α levels were similar between groups initially and at 7 days post-treatment, they were lower in the study group at 14 days post-treatment. Levels of 5-HT, DA, and Glu did not differ initially and at 7 days post-treatment but were higher in the study group at 14 days for 5-HT and DA, while Glu was lower. In conclusion, tirofiban improved clinical efficacy, reduce serum inflammatory responses, and impact neurotransmitter levels in patients with ACI.
Sequential Presentation of Obsessive-Compulsive Disorder and Narcolepsy in a 10-Year-Old Girl With Wolfram Syndrome 1
Authors: Ravindren Rajith K. , Veettil Rajesh Thaliyil , Athimannil Shibila , Balaram Neetha , Veedu Prasad Thotton , Veetil Sajin Appadam , Ayoor Arun Kumar , Mathew Suja , Padinharath Krishnakumar , Balan Shabeesh
Published: July 2024

Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness resulting from loss-of-function genetic variants in the WFS1 gene. Individuals with WS1 manifest a spectrum of neuropsychiatric disorders. Here, we report a pediatric case of WS1, which stemmed from a novel biallelic WFS1 loss-of-function genetic variant. The individual initially presented with obsessive-compulsive disorder, which was successfully managed by fluvoxamine. After 2 months, the child manifested excessive daytime sleepiness. Clinical evaluation and sleep recordings revealed a diagnosis of narcolepsy type 2. Excessive daytime sleepiness was improved with methylphenidate. To the best of our knowledge, this is the first report of narcolepsy in WS1, which possibly arose during a progressive neurodegenerative process. We emphasize the need for in-depth screening for neuropsychiatric phenotypes and sleep-related disorders in WS1, for clinical management, which significantly improves the quality of life.
Creation and Validation of a Novel 3-Dimensional Pediatric Hip Ultrasound Model
Authors: Nichols Francesca R. , Ryan Justin R. , Skinner John A. , Morris Jonathan M. , Nguyen Mylinh T. , Ekpenyong Atim , Pade Kathryn H.
Published: July 2024

Objectives

The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint.

Methods

A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference.

Results

A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model.

Conclusions

In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.
Data to Care Pilot Program in Chicago: Experience, Outcomes, and Direction for the Future
Authors: Schmitt Jessica , Devlin Samantha A. , Mason Joseph A. , Lauritsen Jeff , Tabidze Irina , Friedman Eleanor E. , Massey Ruby A. , Winkler Nolan , Ridgway Jessica P.
Published: July 2024

Context:

Data to Care (D2C) involves sharing HIV surveillance data between health care facilities and health departments to improve continuity of care for people living with HIV (PLWH). The Chicago Department of Public Health (CDPH) initiated a D2C pilot program at the University of Chicago Medicine (UCM) from June 2016 to September 2019.

Objectives:

To describe the proportion of patients reported by UCM as not in care who were able to be matched to CDPH enhanced HIV/AIDS Reporting System (eHARS) and to report the individual-level factors associated with matching and viral suppression.

Design:

Retrospective program evaluation.

Setting:

UCM, an academic health care center that provides HIV care to adults via a Ryan White clinic on the south side of Chicago.

Participants:

Adult PLWH who had received care at UCM but did not have current documented HIV care visit(s).

Main Outcome Measure:

Proportion of matched patients; factors associated with matching and viral suppression.

Results:

Overall, 72.4% (n = 813/1123) of patients reported by UCM were matched by CDPH to eHARS. Individuals aged 40 to 49 years (odds ratio [OR] = 1.99; 95% confidence interval [CI], 1.10-3.62), 50 to 59 years (OR = 2.47; 95% CI, 1.37-4.47), and 60 years or older (OR = 6.18; 95% CI, 3.18-12.32) were more likely to match in eHARS. People who lived outside of Chicago (OR = 0.09; 95% CI, 0.05-0.15) or with unknown zip codes (OR = 0.08; 95% CI, 0.05-0.12) were less likely to match. Men who have sex with men and persons older than 50 years were more likely to be virally suppressed.

Conclusions:

D2C is an evidence-based strategy for reengagement of PLWH; however, program implementation relies on successful data matching. We found that a large proportion of patients from UCM were not matched, particularly those who were younger or lived outside of Chicago. Additional research is needed to understand ways to improve data matching to facilitate reengagement in HIV care.
Collaboration for Health Equity: A Qualitative Assessment of Local Leaders in Community-Based Organizations, Health Care, and Public Health in Michigan
Authors: Bora Nirali S. , Brummel Maris L. , O’Donnell Janine E. , Smith Katherine C.
Published: July 2024

A qualitative study was conducted using semi-structured interviews leaders in community-based organizations, health care, and local public health to understand organizational perspectives of collaboration for health equity and identify opportunities to improve collaboration. Twelve leaders were interviewed from March through May 2023 in Kent County, Michigan. All leaders saw collaboration as valuable for advancing health equity. Key themes that affected collaboration and could be a facilitator or barrier to advancing health equity in the community were inclusion, power, relationships, resources, and organizational traits. Leaders articulated the following factors as those that support collaboration for health equity: authentic inclusion, shared decision-making, taking time to foster trusting relationships, adequate resources to support the infrastructure needed for collaborations, organizational flexibility, and individual commitment. Building partnerships with these facilitators in mind may result in more robust, sustainable, and resilient collaboratives.
Patient Falls in the Operating Room: Why Is This Still a Problem in 2024?
Authors: Pellegrino Allison , Brook Karolina
Published: July 2024

Despite advances in patient safety, perioperative patient falls continue to be a persistent and preventable harm. Patient falls in procedural areas have been associated with multiple postoperative complications such as additional falls, functional decline, and hospital readmissions. Although fall-related databases exist, the specific number of periprocedural falls is difficult to ascertain, and the causes of such falls also remain elusive. We explore various solutions and recommend the creation of a national, focused database of periprocedural falls that will allow institutions to track numbers of falls in patients receiving anesthetic care and to identify the most common etiologies to enable the implementation of targeted strategies to prevent falls. Lacking this, we suggest specific screening and procedural recommendations during all phases of anesthetic care to increase providers’ awareness and vigilance surrounding patient falls.
Cervical cancer screening integrated in routine clinical care of women with HIV
Authors: Gram Emma J.P.N. , Moseholm Ellen , Nørløv Anne B. , Wilken-Jensen Charlotte , Thorsteinsson Kristina , Pedersen Birgitte T. , Jørgensen Sussie M. , Bonde Jesper , Omland Lars H. , Lebech Anne-Mette , Weis Nina
Published: July 2024

Objective:

To evaluate if integrated cervical cancer screening (CCS) for women with HIV (WWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of human papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities.

Design:

Cohort study.

Methods:

WWH who accepted the offer of combined CCS and HIV care (group 1), WWH who declined the offer (group 2), and WWH not offered CCS within HIV care (group 3) between 2013 and 2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WWH were screened annually.

Results:

A total of 804 WWH were included. WWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22–99% compared with the WWH who declined CCS (group 2; n = 232) 10–16% and WWH who were not invited for CCS (group 3; n = 354) 11–25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups.

Conclusion:

Integrating CCS for WWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WWH in HIV care into preventive services.
Geospatial and Socioeconomic Disparities Influencing the Management and Outcomes of Nonsyndromic Craniosynostosis: A Systematic Review
Authors: Belza Caitlyn C. , Sheahan Lucy , Becker Miriam , Gosman Amanda A.
Published: July 2024

Geospatial and socioeconomic health disparities are potential barriers to timely diagnosis and treatment of nonsyndromic craniosynostosis. This systematic review aims to assess published literature describing disparities in craniosynostosis care and to summarize the findings surrounding patient proximity to care centers and familial socioeconomic status as predictors of surgical management and outcomes. The data sources used include PubMed, MEDLINE, and Google Scholar. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for appraisal of the quality of the studies included. Generally, the literature reviewed suggested that socioeconomic variables including race, insurance payor, and median zip code income quartile are predictors of suboptimal craniosynostosis surgical management outcomes including older age at time of surgery and more invasive surgical approach performed. The only geospatial data element assessed was the general region of the hospital where the patient was treated. The review highlighted various knowledge gaps within published literature describing health-related disparities in patients with craniosynostosis. There is a paucity of research assessing geospatial access to craniosynostosis care centers, suggesting that further research should be performed to evaluate this potential disparity. In addition, previous studies lack granularity when assessing socioeconomic factors and only one study accounted for suture fused, which is a potential confounding variable across the other published work. These considerations should be addressed in future studies addressing this topic. The limitations of this review include potential publication bias given that unpublished work was not included. An element of reviewer bias also exists considering only one reviewer screened the articles and extracted the data.
Successful Management of Velopharyngeal Insufficiency in WAGR syndrome with Deletion of Chromosome 11p14.3
Authors: Ma I Zhen , Baek Rong-Min , Kim Baek-kyu
Published: July 2024

Deletions in the 11p region can lead to severe outcomes, such as WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome. However, velopharyngeal insufficiency is little known, and its treatment guideline is yet to be established. Here, we present a velopharyngeal insufficiency case of a Korean patient with a 493kb deletion of chromosome 11p14.3. The patient was successfully managed with a posterior pharyngeal flap. Posterior pharyngeal flap should be considered in velopharyngeal insufficiency patients with WAGR syndrome.
Ligamentum Teres Augmentation for Hiatus Hernia Repair After Bariatric Surgery: A Systematic Review and Meta-analysis
Authors: Chaudhry Shahrukh , Farsi Soroush , Nakanishi Hayato , Parmar Chetan , Ghanem Omar M. , Clapp Benjamin
Published: July 2024

Objective:

Hiatal hernia (HH) and symptomatic gastroesophageal reflux disease are common complications after metabolic bariatric surgery. This meta-analysis aims to investigate the safety and efficacy of ligamentum teres augmentation (LTA) for HH repair after metabolic and bariatric surgeries (MBS).

Materials and Methods:

CENTRAL, Embase, PubMed, and Scopus were searched for articles from their inception to September 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis system.

Results:

Five studies met the eligibility criteria, with a total of 165 patients undergoing LTA for HH repair after MBS. The distribution of patients based on surgical procedures included 63% undergoing sleeve gastrectomy, 21% Roux-en-Y gastric bypass, and 16% having one anastomosis gastric bypass. The pooled proportion of reflux symptoms before LTA was 77% (95% CI: 0.580-0.960; I
2 = 89%, n = 106). A pooled proportion of overall postoperative symptoms was 25.6% (95% CI: 0.190-0.321; I
2 = 0%, n = 44), consisting of reflux at 14.5% (95% CI: 0.078-0.212; I
2 = 0%, n = 15). The pooled proportion of unsuccessful LTA outcomes was 12.5% (95% CI: 0.075-0.175; I
2 = 0%, n = 21).

Conclusion:

Our meta-analysis demonstrated that LTA appears to be a safe and efficacious procedure in the management of HH after MBS.
Modified supine (Giusti) percutaneous nephrolithotomy is noninferior to standard prone procedure for renal calculi: A single-center prospective randomized study
Authors: Ratkal Jaideep , Patel Azharuddin Sharif , Manjuprasad G. B. , Sampathkumar R. N. , Raykar Raviraj
Published: July 2024

Purpose:

The objective is to compare operative times, safety, effectiveness, postoperative pain, and need for analgesia for percutaneous nephrolithotomy (PCNL) in the modified supine (Giusti) versus the standard prone position.

Materials and methods:

A prospective randomized study of 82 patients was conducted from August 2021 to August 2022 at a tertiary medical teaching hospital. The cohort was divided into modified supine and prone PCNL groups (40 and 42 patients in supine and prone). The measured variables included age, sex, body mass index, stone size, comorbidities, procedure time, stone-free rate, pain severity/Visual Analog Scale, analgesia requirement, hospital stay, and complications (modified Clavien-Dindo grading).

Results:

The 2 groups were comparable in mean age, male-to-female ratio, stone size, residual calculi, and postoperative fever. The mean procedure time was 72.24 versus 90.12 minutes in favor of the modified supine PCNL (P < 0.001). The absolute stone-free rate showed no significant difference (82.5% versus 80.95%; P = 0.91) in both the groups. The severity of postoperative pain according to Visual Analog Scale was 2.9 (2–5) and 5.1 (3–7) in the modified supine and prone groups (P < 0.001). Patients undergoing supine PCNL needed analgesics fewer times and in lesser dosage than the prone PCNL group (1.27 versus 3.93; P < 0.001). Hospital stay was shorter in the supine group than the prone group (2.87 versus 4.40 days; P < 0.001). No differences in septic or bleeding complications were found.

Conclusion:

The modified supine PCNL is safe and noninferior to prone PCNL with shorter operative time, reduced postoperative pain, lesser need for analgesia, and shorter hospital stay, with the additional benefit of minimal physiological changes during anesthesia.
Treatment response for nocturnal enuresis in Taiwanese children: A comparison of medical departments
Authors: Ng Kuan Chong , Hung Fan-Ching , Huang Kuo-How , Chang Hong-Chiang , Chiang I-Ni
Published: July 2024

Purpose:

This retrospective study aims to evaluate the medical treatment response, treatment choice, and medication adjustment during a clinical follow-up in Taiwanese children with nocturnal enuresis (NE).

Materials and methods:

A total of 287 children diagnosed with NE were included in the study. Patients’ characteristics, treatment response, and medication adjustment after the second clinic visit were analyzed. The study also compared treatment options chosen by different medical departments.

Results:

Of the 287 children analyzed, 56.8% received medical treatment, 68.8% were older than 7 years (P < 0.001), and 45.6% were initially treated with desmopressin. The presence of daytime symptoms did not significantly affect the prescription of medication at the first clinic visit (P = 0.817). However, 76.9% of children with daytime symptoms who were initially treated with desmopressin needed medication adjustment during their second clinic visit (P = 0.01). Urologists were more likely to prescribe medications than other medical departments at the first clinic visit (P < 0.001).

Conclusion:

Almost half of the Taiwanese children with NE (46%) in this study had a satisfactory treatment response after the initial treatment. Urologists were more likely to use medications as their initial treatment strategy. The limitation included bias from heterogeneous study population and limited information of pretreatment urodynamic or imaging studies. Further education is required for both general public and medical departments to improve the treatment outcomes of children with enuresis.
Influence of urethral mucosa preservation of prostatic apex during monopolar transurethral resection of the prostate on postoperative functional outcomes: A retrospective comparative study
Authors: Irani Darioush , Saadatfar Abdullah , Aminsharifi Alireza , Ahmed Faisal , Mirzakhanlouei Ali , Afrasiabi Mohammadamin , Adib Ali , Shamohammadi Iman
Published: July 2024

Purpose:

The aim of this study is to compare the efficacy and functional outcomes of monopolar transurethral resection of the prostate (m-TURP) without and with the preservation of urethral mucosa at the prostatic apex.

Materials and methods:

In a retrospective study from June 2018 to June 2020, 53 patients with benign prostatic hyperplasia who undertook m-TURP were included in the study. The patients who underwent conventional m-TURP were considered group A (n = 26) and those who were operated by m-TURP with preserved prostate apex were considered group B (n = 27). Preoperative and operative parameters, postoperative complications, urinary incontinence (UI), postoperative 6-month functional outcomes including International Prostate Symptom Score, International Index of Erectile Function score, and peak flow rates (Q max) were assessed and compared between groups.

Results:

All preoperative parameters were similar in both groups without significant differences (P > 0.05). In group A, the mean operative time was significantly longer (40.59 ± 5.20 versus 33.84 ± 4.44 minutes), and intraoperative blood loss was significantly more (305 ± 63.4 versus 212.5 ± 65 mL) than in group B and both were statistically significant (P < 0.001 and P < 0.0001, respectively). Group B had significantly lower urge UI compared with group A (0% versus 23%; P = 0.008). Six-month follow-up data showed that the International Prostate Symptom Score, International Index of Erectile Function score, and Q max were improved in both groups with no statistically significant differences between the 2 groups (P > 0.05).

Conclusion:

Our results indicate that preservation of urethral mucosa at the prostatic apex can be associated with a lower incidence of early postoperative urge UI, less operative blood loss, and shorter operative length, thus improving surgical efficiency.
Integrated genetic analysis identifies a protective effect of MSRA against renal cell carcinoma
Authors: Chang Chi-Fen , Huang Shu-Pin , Hsueh Yu-Mei , Chen Pei-Ling , Lee Cheng-Hsueh , Geng Jiun-Hung , Huang Chao-Yuan , Bao Bo-Ying
Published: July 2024

Purpose:

Deficiencies in methionine sulfoxide reductase (MSR) enzymes, which function as a defense system against oxidative stress, have been linked to age-related diseases, including cancer and neurodegenerative diseases. This study aimed to assess the association between genetic variants in MSR genes and susceptibility to renal cell carcinoma (RCC).

Materials and methods:

We systematically evaluated the effects of 89 common MSR gene polymorphisms on the risk of developing RCC in a cohort of 630 patients and controls. Furthermore, publicly available gene expression datasets were used to analyze gene expression and patient prognosis.

Results:

After adjusting for covariates and multiple testing corrections, MSRA rs56198596 and rs11782000 showed significant associations with the risk of RCC. Analysis of expression quantitative trait loci indicated that the risk alleles of these 2 variants tended to correlate with reduced MSRA expression. Pooled analyses of 19 kidney cancer gene expression datasets revealed that RCC exhibited lower MSRA expression than did normal tissues (P < 0.001) and that higher MSRA expression was associated with improved patient prognosis (P < 0.001).

Conclusion:

These findings suggest that MSRA gene variants may affect the risk of RCC, highlighting the potential protective role of MSRA and its contribution to a favorable RCC prognosis.
Glycosaminoglycan replacement therapy in preventing women’s recurrent urinary tract infections?: A systematic review and meta-analysis
Authors: Chang Yu-Cheng , Lee Yuan-Ju , Chueh Jeff S. , Chang Shang-Jen
Published: July 2024

The aim of this study is to systematically review the published literature and pool the data to evaluate the effectiveness of glycosaminoglycans (GAGs) replacement therapy in preventing women’s recurrent urinary tract infections (rUTIs). A systematic search of PubMed was performed to identify comparative and randomized controlled trials that compared the efficacy of GAG replacement therapy with control groups (placebo/antibiotics/standard therapy) in preventing rUTI in women. The evaluated outcomes included risk of rUTI, rUTI episodes per patient-year, time to urinary tract infection recurrence, pelvic pain and urgency/frequency, and the quality of life (Short Form-36 questionnaire). The Cochrane Collaboration Review Manager software (RevMan, version 5.4) was used for statistical analysis. Seven trials, including 2 randomized control studies and 5 retrospective comparative trials, met the inclusion criteria and were enrolled into our meta-analysis. A total of 702 patients were included in the analysis. Five studies adopted intravesical instillations and 2 used oral-administered hyaluronic acid. The synthesized results revealed that GAG replacement therapy significantly reduced the risk of rUTI (odds ratio: 0.31), reduced urinary tract infection-associated symptoms on pelvic pain and urgency/frequency scores (WMD: −6.70), and contributed to nonsignificant influence in quality of life, prolongation of time to rUTI, and the risk of rUTI per patient-year. In conclusion, the current meta-analysis revealed that GAG replacement therapy might serve as an alternative treatment strategy for rUTI. Further studies should focus on the durability of the protective effect of hyaluronic acid and the optimal protocol for dosage and administration route for GAG replacement therapy.
Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study
Authors: Estrela Tais , Stiebel-Kalish Hadas , Rettenmaier Leigh , Henderson Amanda D. , Sotirchos Elias , Said Yana , Ahmadi Gelareh , Tajfirouz Deena A. , Flanagan Eoin P. , Tisavipat Nanthaya , Gise Ryan , Chwalisz Bart K. , Chen John J.
Published: July 2024

Background:

Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning.

Methods:

This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC.

Results:

Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = −0.60 and R = −0.64, respectively), inversely moderate in patients with MOGAD (R = −0.34 and R = −0.40, respectively), and weak in patients with NMOSD (R = −0.03 and R = −0.17, respectively).

Conclusions:

Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.
Antimicrobial resistance patterns of isolates from bloodstream infections at Jinja Regional Referral Hospital: A cross-sectional study
Authors: Lwigale Fahad
Published: July 2024

Purpose

This study determined the most frequent aetiologic agents responsible for bloodstream infections, their antimicrobial susceptibility patterns, and infection sources in Eastern-central Uganda.

Patients and methods

The analysis involved all non-duplicate blood culture reports from 2019 to 2021 using World Health Organization Network (WHONET 2022) desktop software.

Results

The 1364 reports showed a diagnostic yield of 114(6.8%) and a 1.5% contamination rate. Over 37% and 13% of infections were hospital-acquired and community-acquired respectively. Most etiologic agents were Gram-positive bacteria dominated by Staphylococcus aureus 39(34.2%). Polymicrobial growth existed in 4(0.3%) cases. S. aureus was mainly resistant to penicillin G but most susceptible to gentamicin. Escherichia coli and unspecified coliforms together showed high resistance to ampicillin(87.5%) and third-generation cephalosporins(100%). The least resistance was to chloramphenicol and carbapenems.

Conclusion

Empirical management of suspected sepsis cases by S. aureus in this region could have higher success with gentamicin involved in the therapy combination. Microbiology services should be routinely utilized to guide targeted antimicrobial use, monitor blood culture contamination rates and resistance trends to strengthen regional antimicrobial stewardship.
In Vitro Screening for Antitrypanosomal Potentials of Punica granatum L. Leaves Crude Extracts
Authors: Fathuddin Muhammad Muhsin , Inabo Helen Ileigo
Published: July 2024

Punica granatum L. leaves were examined for potential antitrypanosomal properties. These leaves were acquired and identified at Ahmadu Bello University (ABU) Herbarium Unit in Zaria. Following drying, the following solvents—chloroform, ethyl acetate, and ethanol—were used for exhaustive Soxhlet extraction. The crude extracts phytochemical analysis and in vitro antitrypanosomal capability was performed on Trypanosoma brucei brucei, obtained from The National Research Institute for Chemical Technology (NARICT), Basawa, Zaria. In 96-round-bottom-well microtiter plates, the in vitro trypanocide activity was evaluated in duplicate. Wet and thick blood film and rapid matching were used to examine the antitrypanosomal activity under 400x magnification. The antitrypanosomal activity was determined using the chloroform, ethanol and ethyl acetate extracts ranging from 006.25 to 400.00 mg/ml. The red blood cells (RBCs) were lysed at all concentrations between 200.00 and 400.00 mg/ml, while between 006.25 and 100.00 mg/ml, the RBCs were relatively intact. It was observed that as concentrations declined, the parasite's motility decreased. The parasite's motility entirely stopped after 60 minutes, whereas it continued for an additional 80 minutes in the negative control. A standard drug that was made per the manufacturer's instructions and used as the positive control which cleared everything in less than a minute. Accordingly, the chloroform extract despite lysing the RBC, did not affect the parasite and did not kill it. At a minimum concentration of 6.25 mg/ml, the Punica granatum L. ethyl acetate and ethanol extract can potentially operate as antitrypanosomal agents. This research may help in the development of novel antitrypanosomal medications from Punica granatum L.
Investigating Combined Hypoxia and Stemness Indices for Prognostic Transcripts in Gastric Cancer: Machine Learning and Network Analysis Approaches
Authors: Mahmoudian-Hamedani Sharareh , Lotfi-Shahreza Maryam , Nikpour Parvaneh
Published: July 2024

Introduction

Gastric cancer (GC) is among the deadliest malignancies globally, characterized by hypoxia-driven pathways that promote cancer progression, including mechanisms associated with stemness facilitating invasion and metastasis. This study aimed to develop a prognostic decision tree using genes implicated in hypoxia and stemness pathways to predict outcomes in GC patients.

Material and Methods

GC RNA-seq data from The Cancer Genome Atlas (TCGA) were utilized to compute hypoxia and stemness scores via Gene Set Variation Analysis (GSVA) and mRNA expression-based stemness index (mRNAsi). Hierarchical clustering based on these scores identified clusters with distinct survival outcomes, and differentially expressed genes (DEGs) between these clusters were identified. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify modules and hub genes associated with clinical traits. Hub genes overlapping with DEGs were extracted, followed by functional enrichment, protein-protein interaction (PPI) network analysis, and survival analysis of shared genes. A prognostic decision tree was constructed using survival-associated genes.

Results

Hierarchical clustering identified six clusters among 375 TCGA GC patients, showing significant differences in survival outcomes between cluster 1 (with low hypoxia and high stemness) and cluster 4 (high hypoxia and stemness). Validation in the GSE62254 dataset corroborated these findings. WGCNA revealed modules correlating with clinical traits and survival. Functional enrichment highlighted pathways such as cell adhesion and calcium signaling. The decision tree based on survival-related genes includingAKAP6,GLRB,LINC00578,LINC00968,MIR145,NBEA,NEGR1andRUNX1T1and achieved an area under the curve (AUC) of 0.81 (training) and 0.67 (test), demonstrating the utility of combined scores in patient stratification.

Conclusion

This study introduces a novel hypoxia-stemness-based prognostic decision tree for GC. The identified genes show promise as prognostic biomarkers for GC, warranting further validation in clinical settings.
C-terminal CDC42 variants in autoinflammatory patients specifically trigger actin defects and NF-κB hyperactivation
Authors: Iannuzzo Alberto , Mertz Philippe , Delafontaine Selket , Tacine Rachida , Boursier Guilaine , Hentgen Véronique , Georgin-Lavialle Sophie , Meyts Isabelle , Delon Jérôme
Published: July 2024

Background

CDC42 belongs to the RHO GTPases family. Recently, four variants were identified in autoinflammatory patients. One variant affects the N-terminal part of the protein while the three others are located in the C-terminal region. To date, most of the functional defects were only reported for the C-terminal R186C variant. The other three variants are far less characterized at the functional level.

Objectives

We aimed to investigate whether all four CDC42 variants share common signaling alterations.

Methods

We performed in depth imaging analysis of actin cytoskeleton and NF-κB nuclear translocation, coupled to flow cytometry in cells from patients or in the monocytic THP-1 cell line.

Results

We show that the N-terminal Y64C CDC42 variant localizes normally in cells and does not exhibit any defect in actin filaments formation or NF-κB activation. By contrast, all three C-terminal CDC42 variants have aberrant subcellular localizations and share common functional alterations. They exhibit a strong reduction or complete block in their abilities to polymerize actin filaments. They also show more NF-κB nuclear translocation and phosphorylation. However, we suggest that there is no causal relationship between these two events. Artificial reduction in cellular actin content using specific pharmacologic drugs is indeed not sufficient to hyperactivate NF-κB.

Conclusions

This study further extends the spectrum of defects observed in autoinflammatory CDC42 patients, and pinpoints a functional heterogeneity between N- and C-terminal CDC42 variants. We also show that CDC42 patients should not be necessarily classified among actinopathies. Altogether, the functional defects we report here can lead the way towards more personalized therapeutic interventions.
Validation of morphological ear classification devised by principal component analysis using three-dimensional images for human identification
Authors: Biwasaka Hitoshi , Usui Akihito , Takamiya Masataka , Angelakopoulos Nikolaos , Cameriere Roberto , Kumagai Akiko
Published: July 2024

This study attempts to classify ear morphology for human identification in forensic investigations by distinguishing between the upper auricle and lobule areas. A three-dimensional homologous model of the ear was created using 414 ear images of males aged 17–93 years reconstructed from computed tomography scans of forensic autopsy cases. Morphological changes were visualized using principal component analysis and areas of significant individual differences within the entire ear were identified. The classification criterion images for the upper auricle (ten images) and lobule (12 images) were developed by combining multiple principal component values: components 1–5 for the upper auricle and 1–6 for the lobule. Three-dimensional ear images of the upper auricle and lobule areas from 414 subjects were categorized using a measurement method based on the minimum distance between 5,507 corresponding points. The results indicate the applicability of the criterion images for the morphological classification of ears in this study.
Circadian clock disruption engages the DREAM complex in suppressing cellular health
Authors: Valentim Isabela Santos , Romero-Expósito Francisco Javier , Schwab Katjana , Bayar Melike , Riege Konstantin , Fischer Martin , Olmedo María , Hoffmann Steve , Ermolaeva Maria A.
Published: July 2024

Circadian clock disruption and lack of sleep impair health of cells and organs, but mechanisms remain elusive. Here, we used multi-omics, molecular and functional assays in three model systems (C. elegans, human retinal cells and mouse brain) to identify the DREAM complex as a ubiquitous health repressor acting downstream of clock impairment. We show that clock dysfunction aberrantly activates DREAM leading to simultaneous de-regulation of multiple cellular processes. The affected activities including translation, stress responses and OXPHOS are basic and ubiquitous, explaining pan-cellular decline induced by impaired clock and sleep. Accordingly, inhibition of DREAM restores healthy homeostasis and alleviates de-regulation of adaptive mechanisms in clock-impaired nematodes and human cells. This restorative effect occurs amid persisting clock dysfunction, suggesting that DREAM ablation uniquely uncouples circadian clock impairments from their negative effects on health. Our study coins DREAM as a new therapeutic target for preserving organismal fitness under re-current circadian dysfunction.
Hornworts reveal a spatial model for pyrenoid-based CO2-concentrating mechanisms in land plants
Authors: Robison Tanner A. , Oh Zhen Guo , Lafferty Declan , Xu Xia , A. Villarreal Juan Carlos , Gunn Laura H. , Li Fay-Wei
Published: July 2024

Pyrenoid-based CO2-concentrating mechanisms (pCCMs) turbocharge photosynthesis by saturating CO2around Rubisco. Hornworts are the only land plants with a pCCM. Owing to their closer relationship to crops, hornworts could offer greater translational potential compared to the green alga Chlamydomonas, the traditional model for studying pCCM. Here we report the first thorough investigation of a hornwort pCCM using the emerging modelAnthoceros agrestis. The pyrenoids inA. agrestisexhibit liquid-like properties similar to Chlamydomonas, but differ by lacking starch sheaths and being enclosed by multiple thylakoids. We found that the core pCCM components in Chlamydomonas, including BST, LCIB, and CAH3, are conserved inA. agrestisand likely have similar functions based on their subcellular localizations. Therefore, the underlying chassis for concentrating CO2might be shared between hornworts and Chlamydomonas, and ancestral to land plants. Our study presents the first spatial model for pCCM in a land plant, paving the way for future biochemical and genetic investigations.
Ultra-fast variant effect prediction using biophysical transcription factor binding models
Authors: Hosseini Rezwan , Balci Ali Tugrul , Kostka Dennis , Chikina Maria
Published: July 2024

Sequence variation within TF binding sites can significantly affect TF-DNA interactions, influencing gene expression and contributing to disease susceptibility or phenotypic traits. Despite recent progress in deep sequence-to-function models that predict functional output from sequence data, these methods perform inadequately on some variant effect prediction tasks, especially with common genetic variants. This limitation underscores the importance of leveraging biophysical models of TF binding to enhance interpretability of variant effect scores and facilitate mechanistic insights.

We introducemotifDiff, a novel computational tool designed to quantify variant effects using mono and dinucleotide position weight matrices.motifDiffoffers several key advantages, including scalability to score millions of variants within minutes, implementation of various normalization strategies for optimal performance, and support for both dinucleotide and mononucleotide models. We demonstratemotifDiff‘s efficacy by evaluating it across diverse ground truth datasets that quantify the effects of common variants in vivo, thereby establishing robust benchmarks for the predictive value of variant effect calculations.motifDiffis available as a standalone Python application athttps://github.com/rezwanhosseini/MotifDiff.
Lethal Disruption of the Symbiotic Gut Community in Eastern Subterranean Termite Caused by Boric Acid
Authors: Ashbrook Aaron R. , Schwarz Melbert , Schal Coby , Mikaelyan Aram
Published: July 2024

Abstract

The Eastern subterranean termite,Reticulitermes flavipes(Kollar), is a significant pest, causing extensive damage to structures that amount to substantial economic losses. Traditional termite control methods have utilized boric acid, known for its broad-spectrum insecticidal properties, yet its impact on termite gut microbiomes and the implications of such effects remain understudied. Our study evaluates the dose-dependent mortality ofR. flavipesupon being provided boric acid treated filter papers and investigates the resulting dysbiosis within the termite gut microbiome. Consistent with reports from other insects, mortality increased in a dose-dependent manner, with the highest boric acid concentration (203.7 µg/cm2of filter paper) significantly reducing termite survival. 16S rRNA gene sequencing of the gut microbiome revealed notable shifts in composition, indicating boric acid-induced dysbiosis. Aside from an overall decrease in microbial diversity, the relative abundance of some symbionts essential for termite nutrition decreased in response to higher boric acid concentrations, while several putative pathogens increased. Our findings extend the understanding of boric acid’s mode of action in termites, emphasizing its effect beyond direct toxicity to include significant microbiome modulation that can have dire effects on termite biology. Considering its potential to induce dysbiosis and potentially augment the effectiveness of entomopathogens, our study supports the continued use of boric acid and related compounds for termite-resistant treatments for wood.
Loss of neurofibromin accelerates uveal and dermal melanoma formation driven by GNAQ
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D.
Published: July 2024

Neurofibromin is a very large and complex tumor suppressor, whose loss can synergize with other MAPK pathway mutations to promote melanoma in the skin. In this paper, we investigated whetherNF1loss has a role in other melanomas, such as those that form in the dermis or eye (uveal tract). We found that heterozygous 17q11.2 loss that includes theNF1locus is an uncommon, but recurrent phenomenon in human dermal and uveal melanomas described previously. We studied the effects ofNf1haploinsufficiency in mice expressing oncogenic GNAQQ209Lin melanocytes and Schwann cells of peripheral nerves using thePlp1-creERTtransgene, with tamoxifen given at 5 weeks of age.Nf1haploinsufficiency accelerated dermal and uveal melanoma formation. We studied the effects ofNf1loss in these melanomas using RNAseq. Many of the differentially expressed genes were homologous to genes whose expression correlates with prognosis in human uveal melanoma. Of particular interest was the up-regulation of cAMP signaling and its connection to protein kinase A, which is mutant in malignant melanotic nerve sheath tumors (MMNSTs). An unexpected finding was that oncogenic GNAQ was sufficient by itself to drive peripheral nerve sheath-like neoplasms in the mice. Hence, these studies reveal new insight into both melanocyte and Schwann cell transformation.
Dual roles of idling moments in past and future memories
Authors: Ghandour Khaled , Haga Tatsuya , Ohkawa Noriaki , Fung Chi Chung Alan , Nomoto Masanori , Fayed Mostafa R. , Asai Hirotaka , Sato Masaaki , Fukai Tomoki , Inokuchi Kaoru
Published: July 2024

Every day, we experience new daily episodes and store new memories. Although memories are stored in corresponding engram cells, how different sets of engram cells are selected for current and next episodes, and how they create their memories, remains unclear. We report that in mice, hippocampal CA1 neurons show an organized synchronous activity in prelearning home cage sleep that correlates with the learning ensembles only in engram cells, termed preconfigured ensembles. Moreover, after learning, a subset of nonengram cells develops population activity, which is constructed during postlearning offline periods through synaptic depression and scaling, and then emerges to represent engram cells for new learning. Together, our findings indicate that during offline periods there are two parallel processes occurring: conserving of past memories through reactivation, and preparation for upcoming ones through offline synaptic plasticity mechanisms.
LINC01432binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy
Authors: Mishra Richa , Thunuguntla Prasanth , Perkin Alani , Duraiyan Dhanusha , Bagwill Katelyn , Gonzales Savannah , Brizuela Vanessa , Daly Steve , Chang Yoon Jae , Abebe Mahdote , Rajana Yash , Wichmann Kelly , Bolick Catheryn , King Jaiyana , Fiala Mark , Fortier Julie , Jayasinghe Reyka , Schroeder Mark , Ding Li , Vij Ravi , Silva-Fisher Jessica
Published: July 2024

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression- free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA,LINC01432. We investigatedLINC01432overexpression and CRISPR/Cas9 knockdown in MM cell lines to show thatLINC01432overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show thatLINC01432directly interacts with the RNA binding protein, CELF2. Lastly, we showed thatLINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterizedLINC01432,which inhibits apoptosis.

Key points:lncRNA expression was found to be dysregulated in patients with short PFS to standard multiple myeloma therapy.LINC01432-bound CELF2 inhibits apoptosis.