bluuebunny/crossref_metadata_2025 huggingface dataset:
Previous Hip or Knee Arthroplasty is Associated With Less Favorable Patient-reported Outcomes of Lumbar Surgery
Authors: Duculan Roland , Mancuso Carol A. , Hambrecht Jan , Cammisa Frank P. , Sama Andrew A. , Hughes Alexander P. , Lebl Darren R. , Girardi Federico P.
Published: November 2024

Study Design:

Review of cohort studies.

Objective:

To ascertain if previous hip (THA) or knee (TKA) arthroplasty was associated with patients’ outcomes assessments of subsequent lumbar surgery, specifically overall satisfaction, less disability due to pain, and an affective appraisal reflecting emotional assessment of results.

Background:

Hip, knee, and lumbar symptoms often co-exist and increasingly are managed with surgery. Whether previous total joint arthroplasty (TJA) impacts patients’ perspectives of results of subsequent lumbar surgery is not known.

Methods:

Identical and systematically acquired preoperative and postoperative data from 3 studies assessing psychosocial characteristics and outcomes of lumbar surgery were pooled. Data obtained during interviews included preoperative demographic and clinical variables and 2-year postoperative global overall assessment (very satisfied/satisfied, neither, dissatisfied/very dissatisfied) and global affective assessment (delighted/pleased, mostly satisfied/mixed/mostly dissatisfied, unhappy/terrible). Patients completed the ODI and preoperative to postoperative change was analyzed according to an MCID (15 points). At 2 years patients also reported any untoward events since surgery (ie, fracture, infection, or repeat lumbar surgery). Associations with outcomes were assessed with multivariable logistic ordinal regression controlling for untoward events. Type of arthroplasty was evaluated in subanalyses.

Results:

Among 1227 patients (mean: 59 y, 50% women), 12% had arthroplasty (+TJA) and 88% did not (-TJA). In multivariable analysis, +TJA was associated with less global satisfaction (OR: 1.9, CI: 1.3–2.7, P=0.0007), worse global affective assessment (OR: 1.6, CI: 1.1–2.2, P=0.009), and not meeting MCID15 (OR: 1.5, CI: 1.0–2.3, P=0.05). Covariables associated with less favorable outcomes were not working, positive depression screen, and prior lumbar surgery. Compared with -TJA, patients with THA had worse affective assessments and patients with TKA had less satisfaction and were less likely to meet MCID15.

Conclusions:

Previous hip or knee arthroplasty was associated with less favorable patient-reported outcomes of lumbar surgery. Surgeons and patients should discuss differences between procedures preoperatively and during shared postoperative outcome assessment.

Level of Evidence:

Level II.
Addressing Cross-Specialty Clinical Genetics Education Needs
Authors: Lindquist Karla J. , Ryan Matthew J. , Scheuner Maren T. , Tamraz Bani , Flowers Elena , Harris-Wai Julie , Biswas Sawona , Hyland Katherine
Published: November 2024

Introduction:

Advances in genomics are transforming clinical practice, but there are too few genetics professionals to meet increasing demand. Moreover, many nongeneticist clinicians feel unprepared to incorporate genetics into practice. This study assessed clinicians' unmet genomics educational needs at a single academic institution.

Methods:

Qualitative interviews with Department and Division leaders informed a survey distributed to all clinicians at the institution. Survey questions focused on current practices, confidence, and desired educational resources around genetics and genomics. Data were analyzed using descriptive statistics and Fisher exact tests. Results were shared with an expert panel of Genetics-Genomics Champions to help meet educational needs across specialties.

Results:

Of the 215 survey respondents, 72% were faculty, 24% were trainees, and 4% were clinical staff, representing 18 departments. Less than half felt confident using genetics in the clinic. About 81% desired more training, which did not differ by role (P = .27) or department (P = .98). The Genetics-Genomics Champions proposed delivering just-in-time content via e-consults, online materials, and departmental meetings.

Discussion:

This study highlights clinicians' need and desire for more genetics training. It also underscores the importance of consulting genetics-savvy clinicians to identify challenges and solutions for addressing cross-specialty genetics education needs.
Using Theory and Technology to Build an Interprofessional Community of Human Trafficking Educators
Authors: Farrell Susan E. , Bosson Rahel , Stoklosa Hanni M.
Published: November 2024

Introduction:

Human trafficking, a global health crisis, requires interprofessional responses. Skilled teachers are needed to train health care providers about human trafficking.

Methods:

To promote nonhierarchical interprofessional collaborative learning, we applied social cognitive and experiential learning theories within a dialectical constructivist program design to scaffold participants' knowledge and leveraged technology to build and sustain the program's community. WhatsApp and Flipgrid connected participants and faculty prior to the program. Participants' reflections on experiences were used to inform confidential and respectful information sharing. Live case presentations were interwoven with prerecorded didactics, Zoom break-out case analyses, and Q&A sessions with trafficking survivors. Participants used learning theories to cocreate and teach about labor and sex trafficking, disclosure, and the law. A reciprocal teaching activity facilitated participants' integration of new knowledge with authentic work responsibilities. Constructive peer feedback on the content, clarity, and engagement of their teaching reinforced participants' self-efficacy in expanding their education work in their home organizations.

Results:

As of 2021, 156 physicians, nurses, social workers, advanced practice providers, psychologists, and public health workers, from the United States, United Kingdom, Canada, and Trinidad/Tobago, have graduated from the program. Three-month postprogram surveys indicated lasting knowledge and skills changes in use of the Stop, Observe, Ask, Refer framework, teaching with adult learning principles, and creating organizational trafficking protocols.

Conclusion:

The strategic application of learning theory and technology has enabled us to foster a nonhierarchical community of interprofessional learners, cultivating a dynamic network of educators who continue to make international impacts on people with an experience of human trafficking.
Advanced Approaches to Generating High-validity Real-world Evidence in Asthma
Authors: Kilpatrick Karynsa , Cahill Katherine , Chandran Urmila , Riskin Daniel
Published: November 2024

Background:

Asthma is a phenotypically complex disease requiring nuanced data to generate clinically and scientifically robust real-world evidence. A quantitative measure of data quality is important for variables key to the research questions at hand. Using electronic health record (EHR) data, this study compared accuracy for asthma features between traditional real-world evidence approaches using structured data and advanced approaches applying artificial intelligence technologies to unstructured clinical data.

Methods:

We extracted 18 protocol-defined features from 6037 healthcare encounters among 3481 patients. Features included asthma severity subtypes, comorbidities, symptoms, findings, and procedures. We created a manual reference standard through chart abstraction, with two annotators reviewing each record. We assessed interrater reliability using Cohen’s kappa score and accuracy against the reference standard as an F1-score.

Results:

In the traditional study arm, average recall was 40.8%, precision 72.5%, and F1-score across features was 52.2%. In the advanced study arm, average recall was 95.7%, precision 93.8%, and F1-score was 94.7%. There was an absolute increase of 42.5% and a relative increase of 81.4% in the F1-score between traditional and advanced approaches. Cohen’s kappa score indicated 0.80 inter-rater reliability, reflecting a credible reference standard.

Conclusions:

Use of advanced approaches can enable high-quality real-world data sets in asthma, including granular clinical features such as disease subtypes and symptomatic outcomes. Data quality can be measured and, when high, can support generation of high-validity real-world evidence using routinely collected healthcare data.
Parameterization of Beta Distributions for Bias Parameters of Binary Exposure Misclassification in Probabilistic Bias Analysis
Authors: Zhang Qi , MacLehose Richard F. , Collin Lindsay J. , Ahern Thomas P. , Lash Timothy L.
Published: November 2024

Background:

To account for misclassification of dichotomous variables using probabilistic bias analysis, beta distributions are often assigned to bias parameters (e.g., positive and negative predictive values) based on data from an internal validation substudy. Due to the small sample size of validation substudies, zero-cell frequencies can occur. In these scenarios, it may be helpful to assign prior distributions or apply continuity corrections to the predictive value estimates.

Methods:

We simulated cohort studies of varying sizes, with a binary exposure and outcome and a true risk ratio (RR) = 2.0, as well as internal validation substudies, to account for exposure misclassification. We conducted bias adjustment under five approaches assigning prior distributions to the positive and negative predictive value parameters: (1) conventional method (i.e., no prior), (2) uniform prior beta (α = 1, β = 1), (3) Jeffreys prior beta (α = 0.5, β = 0.5), (4) using Jeffreys prior as a continuity correction only when zero cells occurred, and (5) using the uniform prior as a continuity correction only when zero cells occurred. We evaluated performance by measuring coverage probability, bias, and mean squared error.

Results:

For sparse validation data, methods (2)–(5) all had better coverage and lower mean squared error than the conventional method, with the uniform prior (2) yielding the best performance. However, little difference between methods was observed when the validation substudy did not contain zero cells.

Conclusion:

If sparse data are expected in a validation substudy, using a uniform prior for the beta distribution of bias parameters can improve the validity of bias-adjusted measures.
Association of oxidative balance score with blood pressure, all-cause and cardiovascular disease mortality among hypertensive patients: a prospective study
Authors: Yuan Menghan , Zhang Yingyue , Zuo Nina , Lei Haoying , Zhao Xuming , Xu Yong
Published: November 2024

Objective:

The oxidative balance score (OBS) has emerged as a novel marker for assessing oxidative stress status. This study aimed to investigate the association of OBS with systolic blood pressure (SBP), diastolic blood pressure (DBP), all-cause, and cardiovascular disease mortality in hypertensive patients.

Methods:

We conducted an analysis of data from 7602 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Multiple linear regression, Cox proportional hazards models, Kaplan–Meier survival curves, restricted cubic spline, and subgroup analysis were used to examine the association between OBS and SBP, DBP, estimated pulse wave velocity (ePWV), and mortality risk.

Results:

The results showed that individuals in the highest OBS quartile (27 ≤ OBS ≤ 40) had a significant 2.41 mmHg reduction in SBP compared to the lowest quartile (5 ≤ OBS ≤ 15) (P
trend < 0.001). Compared to the lowest quartile, individuals in the highest OBS quartile had a 29% lower risk of all-cause mortality and a 44% lower risk of cardiovascular disease mortality (P
trend < 0.001). This inverse association persisted irrespective of antihypertensive medication use. OBS is inversely associated with SBP, all-cause, and cardiovascular disease mortality in hypertensive patients.

Conclusion:

This finding provides new evidence and suggestions for those with poor blood pressure control and low OBS (<15) to adjust their diet and lifestyle reasonably.
The Effect of Latanoprostene Bunod 0.024% on Optical Coherence Tomography Angiography in Newly Diagnosed Open Angle Glaucoma
Authors: Özer Ömer , Baysal Zeki , Yildirim Biçer Gamze , Doğan Levent
Published: November 2024

Précis:

Treatment with LBN ophthalmic solution 0.024% reduced IOP by an average of 29.9% and 31.8% in patients with POAG and PXG, respectively, and improved VD in different quadrants in all slabs. Therefore, the importance of LBN in the treatment of glaucoma is likely to be that it increases macular microcirculation, possibly through NO, independent of its IOP-reducing effect.

Purpose:

The aim of this study was to investigate the effect of topical latanoprostene bunod 0.024% applied once daily on intraocular pressure and macular vessel density in newly diagnosed primary and pseudoexfoliative open angle glaucoma patients.

Methods:

A total of 66 patients with newly diagnosed open angle glaucoma were included in this study (group 1). Thirty-four patients had primary (POAG, group 1A) and 32 patients had secondary (pseudoexfoliative glaucoma, PXG, group 1B) open angle glaucoma. Thirty-two healthy participants (group 2) were included in this single-center, prospective study.

Results:

In group 1, the mean IOP decrease in first month of treatment with LBN was 7.7 mm  Hg and IOP change was -30.8%. In the superficial slab, the vessel density (VD) in the superior and nasal quadrants was lower in group 1B compared with group 1A in the first month of treatment (P=0.038, 0.019, respectively). In the choriocapillaris slab, the VD in the superior quadrant at baseline (before treatment) was statistically lower in both groups compared with the VD in the superior quadrant in the first month of treatment (P<0.001, for both).

Conclusion:

In conclusion, treatment with LBN ophthalmic solution 0.024% reduced IOP by an average of 29.9% and 31.8% in patients with POAG and PXG, respectively, and improved VD in different quadrants in all slabs. Therefore, the importance of LBN in the treatment of glaucoma is likely to be that it increases macular microcirculation, possibly through NO, independent of its IOP-reducing effect.
The local molecular signature of human peripheral neuropathic pain
Authors: Sandy-Hindmarch Oliver P. , Chang Pao-Sheng , Scheuren Paulina S. , De Schoenmacker Iara , Hubli Michèle , Loizou Constantinos , Wirth Stephan , Mahadevan Devendra , Wiberg Akira , Furniss Dominic , Calvo Margarita , Bennett David L.H. , Denk Franziska , Baskozos Georgios , Schmid Annina B.
Published: November 2024

Focal nerve injuries are often associated with neuropathic pain. Preclinical research suggests altered neuroimmune signalling underlies such neuropathic pain; however, its cause remains poorly understood in humans. In this multicentre cohort study, we describe the local cellular and molecular signature of neuropathic pain at the lesion site, using Morton's neuroma as a human model system of neuropathic pain (n = 22; 18 women) compared with nerves from participants without nerve injury (n = 11; 4 women). Immunofluorescent staining revealed demyelination and chronic infiltration of immune cells in Morton's neuroma. RNA bulk sequencing identified 3349 differentially expressed genes between Morton's neuroma and controls. Gene ontology enrichment analysis and weighted gene co-expression network analyses revealed modules specific for host defence and neurogenesis. Deconvolution analysis confirmed higher densities of macrophages and B cells in Morton's neuroma than control samples. Modules associated with defence response, neurogenesis, and muscle system development as well as macrophage cell populations identified by deconvolution correlated with patients' paroxysmal or evoked pain. Of note, we identified a consistently differentially expressed gene signature (MARCO, CD163, STAB1), indicating the presence of a specific M(GC) subset of macrophages. MARCO gene expression correlated with paroxysmal pain. Targeted immunofluorescent analyses confirmed higher densities of intraneural CD163+MARCO+ macrophage subsets in Morton's neuroma. Our findings provide detailed insight into the local molecular signature in the context of human focal nerve injury. There is clear evidence for an ongoing role of the immune system in chronic peripheral neuropathic pain in humans, with macrophages and specifically the M(GC) MARCO+ subset implicated.
Predictors of Resolution and Recurrence of Anal High-Grade Squamous Intraepithelial Lesions in People With HIV
Authors: Zhang Joy C. , Geba Maria C. , Newberry Yvonne , Quass-Ferdinand Laura , Thomas Tania A. , Hoang Sook
Published: November 2024

Objective

High-resolution anoscopy (HRA) with ablation of high-grade squamous intraepithelial lesions (HSIL) can prevent the development of anal cancer in people with HIV (PWH). We sought to characterize factors associated with successful HSIL resolution or local or metachronous recurrence.

Methods

We conducted a retrospective study of 62 PWH who underwent HRAs from December 1, 2017 to July 1, 2022. Participants were ≥30 years old with ≥2 HRAs and ≥1 HSIL lesions. Poisson and logistic regressions were used to assess factors associated with HSIL resolution and local or metachronous recurrence of HSIL.

Results

Of 62 PWH, 85.5% had resolution of at least 1 HSIL. Undergoing ≥5 HRAs with thermoablation was associated with HSIL resolution (adjusted rate ratio [aRR] = 2.82) (confidence interval [CI] = 1.55–5.15), p < .001). Tobacco use was negatively associated with resolution (aRR = 0.62 (CI = 0.43–0.90), p = .01). Of this cohort, 58.1% had HSIL recurrence. Having more HRAs (adjusted odds ratio [aOR] = 2.77 (CI = 1.27–6.06), p = .01) and female sex (aOR = 9.66 (CI = 1.14–81.85), p = .04) were associated with recurrence. Non-White race was negatively associated with recurrence (aOR = 0.12 (CI = 0.02–0.68), p = .04). Our study was primarily limited by its retrospective nature and small sample size.

Conclusion

Our study supports the utility of HRA/ablation for HSIL treatment with >85% of participants experiencing resolution of at least 1 HSIL. We found that having more HRAs was associated with a higher likelihood of resolution. However, the high rate of recurrence and progression to HSIL highlights the need for continued surveillance after treatment.
Recompensation features and prognosis in hepatitis B virus-related acute-on-chronic liver failure patients
Authors: Zhang Junchao , Lin Yehong , Zhu Yueyong
Published: November 2024

Objective

This study aimed to investigate the characteristics and prognosis of recompensation in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Methods

A total of 136 patients with HBV-related ACLF were followed up until the end of the study. Patients were categorized into recompensation and non-recompensation groups based on whether recompensation occurred in the first year. The survival rate and incidence of recompensation were calculated using the Kaplan–Meier method.

Results

According to the BAVENO VII consensus criteria, 56 (41.18%) of these patients with ACLF regained recompensation in the 1-year follow-up. The recompensated group had less severe liver damage, higher alpha-fetoprotein, lower age, and lower model for end-stage liver disease score. Specifically, in terms of complications, the recompensated group showed a lower incidence compared with the non-recompensated group (P < 0.05). The 3-, 6-, 12-, 36-, and 60-month cumulative survival rates of ACLF were 44.9, 43.4, 43.4, 40.4, and 40.4% respectively. Among the patients who survived beyond 90 days, 57/61 (93.44%) patients showed recompensation of ACLF (with one patient recovering to recompensation after more than 1 year of follow-up), the 3-, 6-, 12-, and 24-month cumulative recompensation rates were 56.5, 90.9, 94.6, and 97.3%, respectively. Among the 57 patients with recompensation of ACLF, 87.7% maintained a stable condition, and 10.5% were diagnosed with hepatocellular carcinoma (HCC).

Conclusion

Milder necrosis, less inflammation, and more vigorous hepatic regeneration are conducive to recompensation and a better long-term prognosis in ACLF. However, the occurrence of HCC cannot be avoided and regular monitoring is necessary in the recompensation of ACLF.
Efficacy and safety of resmetirom for the treatment of nonalcoholic steatohepatitis: a GRADE assessed systematic review and meta-analysis
Authors: Talha Muhammad , Ali Mohammad Haris , Nadeem Zain Ali , Akram Umar , Saravanan Praveen Bharath , Khalid Muhammad Hamza Awais
Published: November 2024

There are no Food and Drug Administration (FDA)-approved treatment options for nonalcoholic steatohepatitis (NASH) which is a prevailing disease that leads to fibrosis, cirrhosis, or hepatocellular carcinoma. Hence, this systematic review and meta-analysis aims to determine the efficacy and safety of resmetirom, the first FDA-approved drug, for the treatment of NASH. A Grading of Recommendations, Assessment, Development, and Evaluation assessed systematic search of Cochrane Library, MEDLINE, Scopus, and Google Scholar database was conducted from inception till 31 March 2024. Meta-analyses were carried out in accordance with the PRISMA statement. Heterogeneity was determined to be significant if found above 50%. This meta-analysis encompasses three randomized clinical trials, including a total of 2231 patients. The findings show resmetirom’s significant efficacy in several key outcomes, including improvement in fibrosis risk ratios, 1.67 [95% confidence intervals (CI), 1.26–2.20], reductions in liver fat content (95% CI, −39.58 to −23.5), and enhanced liver fibrosis score (95% CI, −0.37 to −0.13) along with improved levels of liver enzymes. Resmetirom was found to be associated with nausea and diarrhea. This is the first systematic review and meta-analysis to determine the safety and efficacy of resmetirom which showed significant positive results in fibrosis improvement, liver fat content, lipid profiles, and liver enzymes in comparison to placebo. Moreover, moderate side effects, such as diarrhea and nausea, were seen in few patients indicating a satisfactory safety profile.
Leveraging Narrative Reflective Writing to Teach Nursing Students About Social Determinants of Health by Harnessing “Small Moments”
Authors: Kaligotla Lalita , Bhat Shankar , Chicas Roxana , Irish Jasmine , McDermott Carrie , Chance-Revels Rebekah
Published: November 2024

Background:

There is increasing recognition that social determinants of health (SDOH) profoundly affect health outcomes. Frontline nurses must grasp how SDOH shape health disparities and inequities.

Purpose:

This paper describes an innovative pedagogical approach that leverages didactic, experiential, and reflective methods, specifically a “small moments” writing activity, to enhance students’ understanding of SDOH.

Methods:

Nursing students (n = 135) from a southeastern U.S. university participated in the activity, and 72 provided consent for inclusion in this analysis. Themes related to students’ understanding of SDOH were identified, and implications for nursing practice were considered.

Results:

This integrative approach deepened students’ understanding of SDOH. Narratives highlighted economic instability, cultural barriers, and systemic inequities as drivers of health disparities. Students described greater awareness, empathy, and culturally competent care.

Conclusion:

Student narratives showed evidence of critical thinking, empathy, and advocacy, crucial skills for addressing health disparities.
A Pilot Study of a Simulation-Based Mastery Learning Procedural Curriculum for Pediatric Emergency Medicine Fellows
Authors: Mitzman Jennifer , Reynolds Maegan , Panchal Ashish , Yee Jennifer
Published: November 2024

Objectives

Pediatric emergency medicine (PEM) fellows are expected to perform high-risk procedures across a wide range of patient age, size, and physiology including procedures that are no longer required during pediatric residency training. Examples include central venous catheter (CVC) placement, endotracheal intubation of children and adolescents, and tube thoracostomy placement. Simulation-based mastery learning has demonstrated decreased patient morbidity. In this study, we describe implementation of a simulation-based mastery learning (SBML) procedural curriculum for PEM fellows.

Methods

Our PEM fellows underwent an SBML procedural curriculum for lumbar puncture (LP), CVC placement, endotracheal intubation, and tube thoracostomy placement. These procedures are mandatory for fellows to learn, have known association with potential iatrogenic injury, and are widely available commercial task trainers. Fellows underwent baseline assessments, group demonstration, deliberate practice, and then postassessments. For both pre- and postassessments, we used internally developed checklists with minimum passing scores (MPSs) calculated by the Mastery-Angoff technique.

Results

Nineteen pediatrics residency-trained PEM fellows underwent this curriculum over a 2-year period. Six fellows (31.58%) achieved the MPS on all four procedures during their first posttest attempt. All fellows achieved the MPS on all four procedures by the second posttest attempt. Most fellows (17/19 or 89.47%) did not achieve the MPS on baseline LP assessments, despite inclusion of this procedure as an Accreditation Council of Graduate Medical Education (ACGME) requirement during their pediatric residency training.

Conclusions

All participating PEM fellows demonstrated competency after training on four procedures associated with iatrogenic injuries. Using an SBML framework is a feasible method to teach procedural skills to PEM fellows, allowing them to demonstrate objective measures of competency in the simulation laboratory.
Use of nonbarrier contraceptives among women with HIV
Authors: Paulsen Fie W. , Tetens Malte M. , Gerstoft Jan , Kronborg Gitte , Johansen Isik S. , Larsen Carsten S. , Wiese Lothar , Dalager-Pedersen Michael , Lunding Suzanne , Nielsen Lars N. , Pinborg Anja B. , Weis Nina , Omland Lars H. , Obel Niels , Lebech Anne-Mette
Published: November 2024

Objective:

The aim of this study was to investigate the use of nonbarrier contraceptives among women with HIV (WWH) compared to women from the general population (WGP) in Denmark.

Design:

A nationwide, population-based, matched cohort study.

Methods:

We included WWH aged 16–50 years, treated at an HIV specialized clinic, and included in The Danish HIV Cohort Study between 1995 and 2021 and an age-matched comparison cohort of WGP. We examined use of hormonal contraception, intrauterine devices (IUDs), and sterilization from 10 years before to 20 years after study inclusion. Additionally, we calculated age-standardized proportions and incidences over calendar time.

Results:

We included 1720 WWH and 17 720 WGP. Median age was 33 years and almost half of WWH had African origin (41%). Nonbarrier contraceptive use was lower among WWH (8.5%) compared to WGP (32.1%) at study inclusion. Before and after inclusion, WWH had nearly half the nonbarrier contraceptive use of WGP, with notably lower hormonal contraception and IUD use. Initially, fewer WWH were sterilized, but 5 years after inclusion, sterilization became the preferred method among WWH. HC use increased among WWH after 2010 but decreased among WGP after 2005. IUD use increased among both groups during 1995–2021 but remained lower among WWH. Incidence of sterilizations remained stable in both groups.

Conclusion:

Use of nonbarrier contraceptives was lower among WWH compared to WGP. For WWH, sterilization became the preferred nonbarrier method few years after study inclusion. hormonal contraception and IUD use increased among WWH after 2010 but remained lower than for WGP. Improved contraceptive counseling is recommended to support reproductive health among WWH.
Basal Cell Carcinoma of the Head With Intense [68Ga]OncoFAP Uptake
Authors: Ventura David , Ernst Iris , Timma Barbara , Schäfers Michael , Backhaus Philipp
Published: November 2024

A 72-year-old man with advanced locally invasive basal cell carcinoma of the forehead failed several pretreatments including surgery and radiation. MRI was not feasible because of the presence of facial implants. CT scan did not provide clear evidence of vital/avital tumor sites as a result of slow progression and previous radiation treatments. Due to limited treatment options, the patient underwent evaluation with 68Ga-OncoFAP PET/CT for potential stereotactic body radiation therapy. We present a rare case of advanced and metastasized basal cell carcinoma with vigorous FAP (fibroblast activation protein) expression.
Pediatric Solitary Epithelioid Histiocytoma of the Face
Authors: Yuksel Selcen S. , North Paula E. , Y.K. Lin Kant
Published: November 2024

Background:

Solitary epithelioid histiocytoma, also known as reticulohistiocytoma, is a rare benign histiocytic proliferation with an unreported incidence that commonly presents as a superficial nodule involving the trunk and extremities of adults. Pathology shows dermal histiocytic infiltration composed of large, eosinophilic histiocytes with “glassy” cytoplasm and oncocytic macrophages. When presenting as part of a systemic disorder, it is called multicentric reticulohistiocytosis, a rare and more aggressive condition characterized by multiple skin and mucosal lesions and arthritis.

Clinical Case:

A 5-year-old African American male patient presented to the pediatric plastic surgery clinic with a lesion of his lower lip 3 months after its initial appearance. Ultrasound identified a hypoechoic heterogenous nodule with increased vascularity. The lesion was excised in the operating room. Pathology revealed a highly cellular nodular proliferation of large epithelioid histiocytes with abundant glassy, lightly eosinophilic cytoplasm and mildly pleomorphic, generally eccentric, round-to-elongated nuclei. The large epithelioid cells were strongly and consistently positive for CD163 and CD68. The diagnosis was determined to be a benign histiocytic proliferation most consistent with solitary epithelioid histiocytoma. At 2-week and 2-month follow-up, the area was healing well and there was no evidence of recurrence.

Conclusion:

This is an unusual presentation of a rare but benign histiocytic proliferation on the face of a young child. When pediatric patients are referred to a plastic surgery clinic for excisional biopsy of facial lesions, it is important to be aware of the broad range of differential diagnoses, including histiocytic proliferations, to treat the patient appropriately.
Naso-alveolar Asymmetry in Unilateral Cleft Lip and Palate Patients—CT Analysis of the Paranasal Region
Authors: Phua Yun , Hessenauer Maximilian
Published: November 2024

Secondary deformities to the midfacial area in adolescence and adulthood are common sequelae after primary cleft lip and palate repair and lead to significant functional, aesthetic and psychosocial challenges. Treatment for patients with normal occlusion or treated malocclusion and remaining midfacial hypoplasia includes autologous and alloplastic augmentation of the maxilla. Because of the great variation of deformities, accurate evaluation is essential for appropriate treatment planning. To provide insights in the altered midfacial anatomy in cleft patients, a retrospective computed tomography morphologic analysis of the anterior projection of the maxilla in the paranasal region, soft tissue thickness, and relation of soft tissue to bony landmarks was performed in adolescent, unilateral, non-syndromic complete cleft and palate patients. The anterior projection of the maxilla was very variable with the cleft side bone surface being more anterior relative to the non-cleft side in some patients. Soft tissue thickness was not significantly different between cleft and non-cleft side. The lateral distance from the most anterior point of the maxilla to subalare was significantly smaller on the cleft side as compared with the non-cleft side. The authors' study demonstrates that in cleft lip and palate patients midfacial anatomy with regards to maxilla projection at the pyriform aperture is very variable making accurate evaluation of the bone morphology and an individualized treatment plan a prerequisite for successful correction of nasomaxillary deformities.
Clinical Utility and Safety of an Ultrasonic Head Stimulator in Dementia With Lewy Bodies
Authors: Manabe Yuta
Published: November 2024

Background:

The potential of Ultra-Ma, an ultrasonic head stimulator, for the supplementary treatment of dementia with Lewy bodies (DLB) was evaluated in patients with various symptoms under poor control by drug therapy.

Methods:

Patients with DLB treated with choline esterase inhibitor or L-DOPA, either alone or in combination, and who met inclusion criteria were enrolled. Four weeks of placebo stimulation was followed by 8 weeks of active ultrasonic stimulation and a 4-week follow-up. Primary endpoints were the effects of ultrasonic head stimulation on both cognitive dysfunction and behavioral and psychological symptoms of dementia (BPSD). Cognitive dysfunction was evaluated using the Japanese versions of the Mini-Mental State Examination and Montreal Cognitive Assessment, and BPSD was assessed using the Neuropsychiatric Inventory Brief Questionnaire Form. For cognitive fluctuations, the Cognitive Fluctuation Inventory served as an index. Improvements in parkinsonism, activities of daily living, and caregiver burden were examined as secondary endpoints.

Results:

Twelve patients were enrolled. The primary endpoint was significantly improved during the active stimulation period, as were secondary endpoint ratings for parkinsonism and caregiver burden. No notable adverse events occurred.

Conclusions:

The findings suggest that ultrasonic head stimulation has supplementary potential when combined with drug treatment in DLB.
Efficacy of Minocycline in Depression: A Systematic Review and Meta-analysis
Authors: Huang Hua , Zou Zhuan , Chen Bin
Published: November 2024

Objectives

Traditional antidepressant therapy is associated with an inadequate response and a low remission rate. Our aim was to synthesize published randomized controlled trials on the potential effects of minocycline in patients with depression.

Methods

PubMed, Web of Science, Embase, and Cochrane Library databases were searched for studies published. Randomized controlled trials published in English that evaluated the efficacy of minocycline in patients with depression were selected for inclusion. Changes from baseline in the Hamilton Depression Rating Scale (HDRS) or Montgomery-Åsberg Depression Rating Scale (MADRS) were pooled to determine the antidepressant effect of minocycline compared with placebo. The quality of the included studies was assessed using the Cochrane risk-of-bias tool.

Results

Eight trials with 567 participants were eligible and included in the analysis. The meta-analysis did not reveal a statistically significant effect of minocycline on depression based on HDRS or MADRS scores.

Conclusions

According to the HDRS and MADRS scores, minocycline did not demonstrate effectiveness in reducing depressive symptoms.
Intravenous Ketamine to Facilitate Transport of Agitated Patients to the ECT Clinic
Authors: Dean Olivia , Byford-Brooks Anthony , Hannigan Kara , Saunders Danielle , Gamble William , Kirov George
Published: November 2024

Objectives

Electroconvulsive therapy (ECT) can be effective for a variety of psychiatric conditions, including for some patients who are very psychotic or agitated. Transferring such patients from the psychiatric ward to the ECT clinic can pose significant challenges for treating teams, as they try to minimize the use of restraint.

Methods

We developed a protocol for safe transfer of such patients using sedation with ketamine. An intravenous cannula is inserted on the ward in a low stimulus environment with gentle supportive holds. Intravenous ketamine is given in a bolus at 0.5–2.0 mg/kg. The patient is transported on a transfer bed to the ECT clinic within a few minutes, and usual ECT process is immediately followed.

Results

We describe 6 patients who were given between 1 and 11 ECT treatments using this method. All of them finished ECT courses without the need for ketamine sedation. Five of them regained capacity, provided informed consent for further ECTs, and eventually reached remission.

Conclusions

Ketamine can be used to manage risk and transfer agitated patients to an ECT clinic for treatment.
Divergent responses of the native grassland soil microbiome to heavy grazing between spring and fall
Authors: Lupwayi Newton Z. , Hao Xiying , Gorzelak Monika A.
Published: November 2024

Grasslands are estimated to cover about 40% of the earth’s land area and are primarily used for grazing. Despite their importance globally, there is a paucity of information on long-term grazing effects on the soil microbiome. We used a 68-year-old grazing experiment to determine differences in the soil permanganate-oxidizable C (POXC), microbial biomass C (MBC), the soil prokaryotic (bacterial and archaeal) community composition and enzyme activities between no-grazing, light grazing and heavy grazing, i.e. 0, 1.2 and 2.4 animal unit months (AUM) ha−1. The grazing effects were determined in spring and fall grazing. Light grazing had little effect on soil MBC and the composition and diversity of prokaryotic communities in either grazing season, but the effects of heavy grazing depended on the grazing season. In spring, heavy grazing increased the relative abundances of copiotrophic phyla Actinomycetota, Bacillota and Nitrososphaerota, along with soil POXC contents but decreased those of oligotrophic phyla Acidobacteriota, Verrucomicrobiota and Nitrospirota. This difference in responses was not observed in fall, when grazing reduced soil POXC, MBC and the relative abundances of most phyla. The β-diversity analysis showed that the prokaryotic community structure under heavy grazing was different from those in the control and light grazing treatments, and α-diversity indices (except the Shannon index) were highest under heavy grazing in both grazing seasons. The activities of P-mobilizing and S-mobilizing soil enzymes decreased with increasing cattle stocking rate in both seasons, but the activities of the enzymes that mediate C and N cycling decreased only in the fall. The genus RB41 (phylum Acidobacteriota) was one of two core bacterial genera, and its relative abundance was positively correlated with the activity of the S-mobilizing enzyme. Therefore, light grazing is recommended to reduce negative effects on the grassland soil microbiome and its activity, and the grazing season should be considered when evaluating such grazing effects.
The Late-Stage Steps ofBurkholderia cenocepaciaProteinO-Linked Glycan Biosynthesis Are Conditionally Essential
Authors: Jebeli Leila , McDaniels Taylor A. , Ho Duncan T. T. , Tahir Hamza , Kai-Ming Nicholas L. , Mcgaw Molli , Karlic Kristian I. , Lewis Jessica M. , Scott Nichollas E.
Published: November 2024

PeriplasmicO-linked protein glycosylation is a highly conserved process observed across theBurkholderiagenus. Within Burkholderia, protein glycosylation requires the five gene cluster known as theO-glycosylationcluster (OGC,ogcXABEI) which facilitates the construction of theO-linked trisaccharide attached to periplasmic proteins. Previous studies have reported conflicting results regarding the essentiality ofogcA, predicted to be responsible for the addition of the final carbohydrate of theO-linked trisaccharide andogcX,the putativeO-linked glycan flippase. Within this work, we aimed to dissect the impact of the loss ofogcAandogcXonBurkholderia cenocepaciaviability. We demonstrate that the loss of eitherogcAorogcXare detrimental if glycosylation is initiated leading to marked phenotypic effects. Proteomic analysis supports that the loss ofogcA/ogcXboth blocks glycosylation and drives pleotropic effects in the membrane proteome, resulting in the loss of membrane integrity. Consistent with this, strains lackingogcAandogcXexhibit increased sensitivity to membrane stressors including antibiotics and demonstrate marked changes in membrane permeability. These effects are consistent with fouling of the undecaprenyl pool due to dead-endO-linked glycan intermediates, and consistent with this, we show that modulation of the undecaprenyl pool through the overexpression of undecaprenyl pyrophosphate synthase (UppS) or the OGC flippase (OgcX) restores viability while expression of early-stage OGC biosynthesis genes (ogcIandogcB) reduceB. cenocepaciaviability. These findings demonstrate disruptingO-linked glycan biosynthesis or transport appears to dramatically impactB. cenocepaciaviability, supporting the assignment ofogcAandogcXas conditionally essential.

Importance

Protein glycosylation, a conserved process inBurkholderiaspecies, utilizes glycans generated by theO-glycosylation cluster (OGC), which is composed of five genes (ogcX, ogcA,ogcB,ogcE, andogcI). In this study, we demonstrate that the loss ofogcAorogcXsignificantly affects the physiology ofBurkholderia cenocepacia. Using complementary genetic approaches and proteomic techniques, we show that the loss ofogcAorogcXblocks glycosylation, alters the cell membrane, and sensitizes cells to stressors such as antibiotics. This increased sensitivity to membrane stress is consistent with the accumulation of dead-endO-linked glycan intermediates, which sequester the limited and essential undecaprenyl pool withinB. cenocepacia. These findings highlight thatogcAandogcXare conditionally essential forB. cenocepaciasurvival and provides mechanistic insight into how protein glycosylation fidelity—the use of specific glycans for protein glycosylation—is controlled inBurkholderiaspecies.
An integrative approach prioritizes the orphan GPR61 genomic region in tissue-specific regulation of chronotype
Authors: Tchio Cynthia , Williams Jonathan , Taylor Herman , Ollila Hanna , Saxena Richa
Published: November 2024

Objectives

Chronotype, a manifestation of circadian rhythms, affects morning or evening preferences and ease of getting-up. This study explores the genetic basis of morning chronotype and ease of getting-up, focusing on the G protein-coupled receptor locus, GPR61.

Methods

We analyzed the genetic correlation between chronotype and ease of getting-up using linkage disequilibrium score regression with summary statistics from the UK Biobank (n=453,379). We prioritized shared signals between chronotype and ease of getting-up using the Human Genetic Evidence (HuGE) score. We assessed the significance of GPR61 and the lead variant rs12044778 through colocalization andin-silicoanalyses from ENCODE, Genotype-Tissue Expression, Hi-C, and Knockout Mouse Project databases to explore potential regulatory roles of causal genes.

Results

We identified a strong genetic correlation (Rg=0.80, P=4.9 x10324) between chronotype and ease of getting-up. Twenty-three genes, including three circadian core clock components, had high HuGE scores for both traits. Lead variant rs12044778 inGPR61was prioritized for its high HuGE score (45) and causal pleiotropy (posterior probability=0.98). This morningness variant influenced gene expression in key tissues: decreasingGPR61in tibial nerve, increasingAMIGO1in subcutaneous adipose, and increasingATXN7L2in the cerebellum. Functional knockout models showedGPR61knockout increased fat mass and activity,AMIGO1knockout increased activity, andATXN7L2knockout reduced body weight without affecting activity.

Conclusions

Our findings reveal pleiotropic genetic factors influencing chronotype and ease of getting-up, emphasizingGPR61’s rs12044778 and nearby genes likeAMIGO1andATXN7L2. These insights advance understanding of circadian preferences and suggest potential therapeutic interventions.

SIGNIFICANCE

This study investigates the genetic underpinnings of chronotype preferences and ease of getting up, with a focus on the orphan G protein-coupled receptor GPR61 and the locus lead variant rs12044778. By combining genomic data within silicofunctional analysis, we provide mechanistic insight into a locus for morning chronotype and ease of getting in the morning. We identified the variant rs12044778 as a key regulator ofGPR61and nearby genesAMIGO1andATXN7L2influencing circadian and metabolic traits. Our findings shed light on the intricate genetic networks governing circadian rhythms, suggesting potential therapeutic targets for disorders of the circadian rhythm.
Ustilago maydisdisrupts carbohydrate signaling networks to induce hypertrophy in host cells
Authors: Lee Yoon Joo , Stolze Sara Christina , Saridis Georgios , Ebert Malaika K. , Nakagami Hirofumi , Doehlemann Gunther
Published: November 2024

Ustilago maydisis a biotrophic fungus infecting maize, secreting effector proteins to manipulate host cellular processes and create nutrient-rich environments for its growth. Three effectors, Hap1-3 (hypertrophy-associated proteins), were identified as virulence factors promoting hypertrophic mesophyll tumor cells (HTT). Immunoprecipitation and mass spectrometry revealed interactions among Hap effectors, suggesting potential effector complex formation. CRISPR-Cas9 triple knockout of hap1-3 demonstrated Hap1’s role in HTT formation. Infection assays identified Hap1 as a key virulence factor interacting with maize Snf1-related kinase 1 (SnRK1), a central energy regulator. RNA-seq analysis showed that Hap1 promotes cell cycle and starch biosynthesis genes, while CR-hap1induced defense-related WRKY transcription factors. Phosphoproteomics revealed increased phosphorylation of SnRK1 and metabolic enzymes during SG200 infection. Our findings support a model whereU. maydisinduces hypertrophy through Hap1, targeting the SnRK1α subunit to prevent SnRK1 inhibition by high trehalose-6-phosphate (T6P), disrupting the antagonistic relationship between T6P and SnRK1. This reprograms host transcription to enhance starch metabolism and induce endoreduplication, leading to hypertrophy induction, while suppressing sugar-induced immune signaling.
Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis
Authors: Grant Olivia A. , Iacoangeli Alfredo , Zwamborn Ramona A. J. , van Rheenen Wouter , Byrne Ross , Van Eijk Kristel R. , Kenna Kevin , van Vugt Joke J.F.A. , Cooper-Knock Johnathan , Kenna Brendan , Vural Atay , Topp Simon , Campos Yolanda , Weber Markus , Smith Bradley , Dobson Richard , van Es Michael A. , Vourc’h Patrick , Corcia Philippe , de Carvalho Mamede , Gotkine Marc , Panades Monica P. , Mora Jesus S. , Mill Jonathan , Garton Fleur , McRae Allan , Wray Naomi R. , Shaw Pamela J. , Landers John E. , Glass Jonathan D. , Shaw Christopher E. , Basak Nazli , Hardiman Orla , Van Damme Philip , McLaughlin Russell L. , van den Berg Leonard H. , Veldink Jan H. , Al-Chalabi Ammar , Al Khleifat Ahmad
Published: November 2024

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females). We identified a total of 226 ALS saDMPs (sex-associated DMPs) annotated to a total of 159 unique genes. These ALS saDMPs were depleted at transposable elements yet significantly enriched at enhancers and slightly enriched at 3’UTRs. These ALS saDMPs were enriched for transcription factor motifs such as ESR1 and REST. Moreover, we identified an additional 10 genes associated with ALS saDMPs through chromatin loop interactions, suggesting a potential regulatory role for these saDMPs on distant genes. Furthermore, we investigated the relationship between DNA methylation at specific CpG sites and overall survival in ALS using Cox proportional hazards models. We identified two ALS saDMPs, cg14380013 and cg06729676, that showed significant associations with survival. Overall, our study reports a reliable catalogue of sex-associated ALS saDMPs in ALS and elucidates several characteristics of these sites using a large-scale dataset. This resource will benefit future studies aiming to investigate the role of sex in the incidence, progression and risk for ALS.