bluuebunny/crossref_metadata_2025 huggingface dataset:
tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus
Authors: Bruch Alexander , Lazarova Valentina , Berg Maximilian , Krüger Thomas , Schäuble Sascha , Kelani Abdulrahman A , Mertens Birte , Lehenberger Pamela , Kniemeyer Olaf , Kaiser Stefanie , Panagiotou Gianni , Gsaller Fabio , Blango Matthew G
Published: December 2024

Increasing antifungal drug resistance is a major concern associated with human fungal pathogens like Aspergillus fumigatus. Genetic mutation and epimutation mechanisms clearly drive resistance, yet the epitranscriptome remains relatively untested. Here, deletion of the A. fumigatus transfer RNA (tRNA)-modifying isopentenyl transferase ortholog, Mod5, led to altered stress response and unexpected resistance against the antifungal drug 5-fluorocytosine (5-FC). After confirming the canonical isopentenylation activity of Mod5 by liquid chromatography-tandem mass spectrometry and Nano-tRNAseq, we performed simultaneous profiling of transcriptomes and proteomes to reveal a comparable overall response to 5-FC stress; however, a premature activation of cross-pathway control (CPC) genes in the knockout was further increased after antifungal treatment. We identified several orthologues of the Aspergillus nidulans Major Facilitator Superfamily transporter nmeA as specific CPC-client genes in A. fumigatus. Overexpression of Mod5-target tRNATyrGΨA in the Δmod5 strain rescued select phenotypes but failed to reverse 5-FC resistance, whereas deletion of nmeA largely, but incompletely, reverted the resistance phenotype, implying additional relevant exporters. In conclusion, 5-FC resistance in the absence of Mod5 and i6A likely originates from multifaceted transcriptional and translational changes that skew the fungus towards premature CPC-dependent activation of antifungal toxic-intermediate exporter nmeA, offering a potential mechanism reliant on RNA modification to facilitate transient antifungal resistance.
An exploration of recurring early intervention (EI) alerts to address at-risk officers through the lens of police reform
Authors: Gullion Christi L
Published: December 2024

Police reform, including transparency and officer and agency accountability, is a top priority. In response to patterns of excessive force and misconduct, reform agreements have been instituted, and consistently require early intervention (EI) systems, a supervision and accountability tool to address at-risk officers. Yet little is known about the likelihood and timing of recurring EI alerts. This study examines EI data from a large, metropolitan police agency in the southwestern USA. Results indicate officer race, division, time to initial alert, type of performance indicator, and year of the alert were significant for the likelihood and timing of subsequent EI alerts. Supervisor tenure was also significant for timing to a subsequent EI alert. For officers with a subsequent EI alert, half recurred within 6 months of their initial EI alert and intervention, and 90 per cent did so within 2 years. Implications for police reform include enhanced supervision and accountability with EI systems.
Memory Moves Markets
Authors: Charles Constantin
Published: December 2024

I show that memory-induced attention can distort prices in financial markets. I exploit rigid earnings announcement schedules to identify which firms are associated in investors’ memory. Firms with randomly overlapping earnings announcements are associated in memory because many investors experience them in the same context. Months later, when only one of the two firms announces earnings, this context is cued, and triggers the recall of the other, associated firm. On such days, I find that memory-induced attention leads to buying pressure in the associated firm’s stock. The strength of this effect varies as predicted by associative memory theory.
Total-body positron emission tomography: a tool for systemic, quantitative evaluation of the inflammatory burden of psoriatic arthritis
Authors: Raychaudhuri Siba P , Abdelhafez Yasser G , Mazza Dario F , Raychaudhuri Smriti K , Cherry Simon R , Nardo Lorenzo , Badawi Ramsey D , Chaudhari Abhijit J
Published: December 2024

Objectives

To test the hypothesis that recently-developed total body-positron emission tomography (TB-PET) imaging with integrated computed tomography (CT) will enable low-dose, quantitative, domain-specific evaluation of the total inflammatory burden of psoriatic arthritis (PsA) and associate with established outcome measures of the clinical domains of PsA.

Methods

Seventy-one adult participants (40 with PsA, 16 with rheumatoid arthritis (RA), and 15 with osteoarthritis (OA)) underwent 20-min TB-PET/CT scans using [18F]FDG, a glucose analogue radiotracer. [18F]FDG uptake was assessed qualitatively and quantitatively. Rheumatological examinations were performed prior to the scan. For both evaluations, domain-specific assessments included 68 joints, 6 entheses, 20 nails, axial disease and dactylitis.

Results

[18F]FDG PET uptake consistent with joint involvement and enthesitis was noted in 100% of participants with PsA. Other features included nail matrix pathology (53%), spinal involvement (60%), active sacroiliitis (13%) and dactylitis (10%). Patterns of [18F]FDG uptake in PsA differed from those in participants with RA or OA. There was a high concordance between TB-PET measures and the domain-specific assessments of the joint (75%), entheseal (79%) and nail (65%) pathology. TB-PET was positive for an additional 15% of joints, 20% of entheses and 13% of nails that were negative on clinical assessments.

Conclusion

TB-PET/CT identified inflammatory pathologies characteristic to all clinical domains of PsA and thus provided an in vivo evaluation of systemic PsA inflammatory burden. This promising tool may further contribute to identifying pathologies that may be occult, provide biomarkers to diagnose and differentiate PsA at an early stage, and to monitor early treatment response.
Immune checkpoint inhibitors-associated vasculitis: a heterogeneous condition with possible severe disease course
Authors: Chanson Noemie , Galvagni Alexandre , Ramos-Casals Manuel , Ruiz Juan Ignacio , Suijkerbuijk Karijn P M , Gente Karolina , Kerschen Philippe , Karam Jean Denis , Belkhir Rakiba , Outh Rodereau , Closs-Prophette Fabienne , Garcia Morillo Jose Salvador , Robles-Marhuenda Ángel , Michot Jean-Marie , Voisin Anne Laure , Messayke Sabine , Laparra Arianne , Robert Caroline , Suarez-Almazor Maria , Mariette Xavier , Lambotte Olivier ,   for the ICIR, Ramos-Casals Manuel , Mariette Xavier , Lambotte Olivier , Kostine Marie , Khamashta Munther A , Calabrese Leonard , Suárez-Almazor Maria , Baldini Chiara , Bingham Clifton O , Gottenberg Jacques-Eric , Radstake Timothy R D , Schaeverbeke Thierry , Schulze-Koops Hendrik , Brito-Zerón Pilar , Flores-Chávez Alejandra , Acar-Denizli Nihan
Published: December 2024

Objective

To describe presentation, treatment and outcome of immune checkpoint inhibitor (ICI) associated-vasculitis in cancer patients in a multicentre study.

Methods

Thanks to the ImmunoCancer International Registry (ICIR), a multidisciplinary network focused on the research of the immune related adverse events related to cancer immunotherapies, patients presenting with a clinical and/or radiological suspicion of vasculitis and histological evidence of vasculitis after being exposed to ICIs were retrospectively identified.

Results

Twenty-eight cases were identified in the ICIR registry. The median interval between starting ICI treatment and vasculitis diagnosis was 4 months. Small vessel vasculitis was predominant (n = 21), followed by large vessel (n = 4) and medium vessel (n = 3). The small vessel vasculitis included 10 unclassified vasculitis either with limited cutaneous involvement (n = 6) or systemic involvement (n = 4), five IgA vasculitis, three cryoglobulinemic vasculitis, and three ANCA+ vasculitis. At presentation or during the evolution, renal and neurologic manifestations were evidenced in seven cases each (25%). Renal biopsies documented immune glomerulopathies in six cases. Only seven patients (25%) fulfilled the 2022 ACR/EULAR classification criteria (four giant cell arteritis, two EGPA and one GPA). Most patients (90%) required systemic corticosteroid and an additional drug was given in 10 patients (36%). Vasculitis outcome was good: 22 patients had vasculitis complete response, no patient died due to vasculitis. Nine patients (32%) were rechallenged with immunotherapy with only one relapse.

Conclusion

ICI-associated vasculitis are rare, heterogeneous, but can be severe requiring urgent multidisciplinary management with aggressive treatment.
The cognition, behaviours and social environment related to Clonorchis sinensis infection in China: a qualitative study
Authors: He Yun-Ting , Zeng Qing-Sheng , Huang Si-Yue , Li Lai-De , Shi Cong-Xing , Chen Yin-Fang , Qian Men-Bao , Fang Yue-Yi , Lai Ying-Si
Published: December 2024

Background

Cognition, behaviours and social environment are associated with Clonorchis sinensis infection, a prevalent liver fluke disease in China. This study aimed to use social cognitive theory (SCT) to investigate these three aspects and their interaction in an endemic area.

Methods

We conducted three semi-structured focus group discussions in Da'ao town, Jiangmen city, Guangdong Province, China. Thematic analysis was used to extract themes.

Results

Twenty-four people were interviewed. The participants exhibited inadequate knowledge about C. sinensis infection and were unaware of the health risks. Although some have reduced their consumption of raw fish, some continue to consume it frequently. Compared with stopping eating raw fish, receiving tests and taking medicines were easier behaviours to adopt. Guided by the SCT, we considered the reciprocal determinism between people and the social environment as the basis of the persistent raw fish consumption behaviour. While the social environment could influence the cognition and behaviours of people, people also can reshape the social environment. Based on the reciprocal determinism, we proposed an integrated intervention framework.

Conclusions

Our study unveiled a reciprocal determinism between the cognition, behaviours and social environment related to C. sinensis infection in high-endemic areas of China, providing insights for establishing control strategies.
Isolated Corrective Saccades in the Bilateral Posterior Canal Stimulation During the Video Head Impulse Test: A Marker of Central Vestibulopathy?
Authors: Hurtado Genoveva , Poth Elizabeth A. , Monaghan Neil P. , Nguyen Shaun A. , Rizk Habib G.
Published: December 2024

Objectives:

This study aimed to determine if the presence of corrective saccades during video head impulse test (vHIT) stimulation of the bilateral posterior semicircular canals (PSCs) correlated with other vestibular test results, demographics, symptoms, or diagnoses.

Design:

This study was a retrospective chart review where 1006 subjects’ vHIT records were screened with 17 subjects meeting inclusion criteria for isolated bilateral PSC saccades.

Results:

Of the 1006 patients undergoing vHIT testing, only 1.7% had isolated bilateral PSC saccades. The median age of subjects was 73 years, with a range of 61 to 85 years. Statistical significance was identified between groups with abnormal PSC vHIT gain and abnormal ocular vestibular evoked myogenic potential results as well as those with 1 to 2 diagnoses.

Conclusions:

Our study confirms the rarity of isolated bilateral PSC vHIT saccades and as well as association with central vestibulopathy. Correlations with other vestibular test results, demographics, symptoms, or diagnoses may be strengthened with future large-scale studies. Further understanding of the clinical utility of isolated bilateral PSC vHIT saccades is needed. Patients with bilateral PSC vHIT abnormalities may benefit from a comprehensive neurological evaluation and consultation.
Comparing Patient-Reported Outcomes in Patients Undergoing Lumbar Fusion for Degenerative Spondylolisthesis With Predominant Back Pain Versus Predominant Leg Pain Symptoms
Authors: Kaul Aayush , Wolf Jacob C. , Anwar Fatima N. , Roca Andrea M. , Khosla Ishan , Loya Alexandra C. , Medakkar Srinath S. , Jacob Kevin C. , Patel Madhav R. , Pawlowski Hanna , Parsons Alexander W. , Vanjani Nisheka N. , Prabhu Michael C. , Federico Vincent P. , Sayari Arash J. , Lopez Gregory D. , Singh Kern
Published: December 2024

Study Design:

Retrospective review.

Objective:

This study aims to compare postoperative patient-reported outcome measures (PROMs) in predominant back pain (PBP) versus predominant leg pain (PLP) patients following lumbar fusion for degenerative spondylolisthesis (DS).

Summary of Background Data:

Prior studies comparing PROMs in patients undergoing lumbar fusion with PBP versus PLP symptoms have included heterogeneous spinal pathology and restricted analysis to posterior fusion techniques.

Methods:

Demographics, perioperative characteristics, complications, and PROMs from a retrospective single-surgeon database were collected for primary, elective, and single-level lumbar fusion for DS. Preoperative/postoperative PROMs included visual analog scale (VAS)-back/leg pain (VAS-BP/VAS-LP), Oswestry disability index (ODI), 12-Item Short Form Physical and Mental Composite Score (SF-12 PCS/MCS), and Patient-Reported Outcome Measurement Information System-Physical Function (PROMIS-PF). Preoperative VAS-BP>VAS-LP established the PBP cohort and VAS-LP>VAS-BP established the PLP cohort. The average follow-up was 23.4±2.8 months. Improvement in PROMs (ΔPROM) at 6 weeks (ΔPROM-6W) and final follow-up (ΔPROM-FF) were calculated. χ2 and the Student t test analyzed categorical and continuous variables, respectively. Postoperative PROMs, ΔPROMs, and MCID achievement rates were compared between groups with multivariate linear or logistic regression.

Results:

In total, 166 patients were selected with 108 in the PBP cohort. Both cohorts saw improvements in all PROM scores over time. The PBP cohort reported significantly greater ΔPROM-6W and ΔPROM-FF for VAS-BP (P<0.003). The PLP cohort reported greater ΔPROM-6W and ΔPROM-FF for VAS-LP and ΔPROM-FF for SF-12 PCS (P<0.014). MCID achievement rates for VAS-BP were higher in the PBP cohort, and VAS-LP MCID achievement rates were higher in the PLP cohort (P<0.015).

Conclusion:

Regardless of predominant pain location, patients-reported improvements in all PROs at the final follow-up. Patients with PLP-reported greater improvement in leg pain and physical function and patients with PBP-reported greater back pain improvement.
DIEP Flap Weights in Immediate 1-stage and 2-stage Breast Reconstruction: Considering Chest Wall Deformity
Authors: Inoue Mariko , Aoki Hironobu , Kamegai Mina , Ogawa Rei
Published: December 2024

Background:

There are advantages and disadvantages to both immediate 1-stage and 2-stage autologous-breast reconstruction. The 2-stage procedure may suffer from a hitherto overlooked difficulty: the tissue expander may induce chest wall depression that may require using a heavier-than-expected flap to generate symmetrical breasts. We conducted a retrospective observational study to assess this phenomenon.

Methods:

Consecutive patients who underwent 1-stage or 2-stage unilateral autologous-breast reconstruction with a deep inferior epigastric perforator flap were included. The 2 groups were compared in terms of age, body mass index, mastectomized tissue weight, inset-flap weight, and percentage additional flap weight (defined as [inset-mastectomy]/mastectomy × 100). The latter reflects the amount of additional flap tissue relative to mastectomized tissue that was needed to generate symmetrical breasts. The chest wall deformity after tissue expansion in the 2-stage patients was quantitated with computed tomography.

Results:

Patients’ healthy and affected breasts were symmetrical before surgery (P > 0.05). Compared with the 1-stage patients (n = 37), the 2-stage patients (n = 31) only differed in terms of a significantly higher mean percentage additional flap weight (28% versus 12%, P = 0.0077). Relative to preoperative values, nearly all 2-stage patients had mild (74%) or moderate (19%) chest wall deformity before tissue expander removal.

Conclusions:

Due to tissue expander-induced chest wall deformity, 2-stage breast reconstruction may require a larger flap volume than is anticipated on the basis of preoperative volumetric measurements. Considering this phenomenon when choosing between immediate 1-stage and 2-stage reconstruction could potentially help improve patient outcomes.
Chromosomal Mosaicism in the Placenta
Authors: Baptiste Caitlin , Grati Francesca R. , Levy Brynn
Published: December 2024

The clinical implications of placental chromosomal mosaicism can be challenging for patients and health care providers. Key considerations include the specific characteristics of the chromosomal abnormality (such as size, gene content, and copy number), the timing of the mosaicism’s onset during embryogenesis or fetal development, the types of tissues involved, and the level of mosaicism (the ratio of normal to abnormal cells within those tissues). Genetic counseling can help inform patients about the chances of having a live-born child with a chromosomal abnormality. Each case requires individual assessment to provide accurate guidance. This chapter will explore the clinical implications of detecting mosaicism at 3 critical diagnostic stages: (1) chorionic villus sampling (CVS); (2) amniocentesis; and (3) cell-free DNA (cfDNA) testing.
PATHOGENESIS, PROGNOSIS, AND SURGICAL OUTCOMES OF FULL-THICKNESS MACULAR HOLES IN MACULAR TELANGIECTASIA TYPE 2
Authors: Carlà Matteo Mario , Cusato Mattia , Hu Lorenzo , Rizzo Stanislao
Published: December 2024

Purpose:

Macular telangiectasia type 2 (MacTel2) is a rare disorder, affecting retina's vascular structure, and MacTel2-associated full-thickness macular holes (MHs) are extremely rare in general population. Since their management is still controversial, this literature review was aimed to gather evidences on the surgical management of MacTel2-associated MHs.

Methods:

A retrospective review on the Cochrane Central, PubMed, Web of Science, and ClinicalTrials.gov databases for articles regarding MacTel2 and MHs. The search period was set from January 2000 to February 2024, and any kind of article was taken into account.

Results:

We took into account 10 studies analyzing surgical outcomes of MacTel2-associated MHs, with a total number of 95 treated eyes. Different surgical techniques were used, with a better anatomical outcome after internal limiting membrane inverted flap surgery but with very controversial functional outcomes. In a comparative report, internal limiting membrane peeling alone (34 eyes) was associated with a 47% anatomical success rate, internal limiting membrane inverted flap (22 eyes) with 90% successful closure, and autologous retinal transplantation (five eyes) with a 100% success rate but without visual improvement.

Conclusion:

Since the exact pathophysiology of MacTel2 macular holes is not clear yet, even if the internal limiting membrane inverted flap technique could be an effective treatment for these patients, visual outcomes are poor. This underlines the necessity of a deeper comprehension of the pathophysiology of the disease and the development of new surgical approaches.
Glucagon-like Peptide-1 Receptor Agonists in the Management of Diabetic Retinopathy
Authors: Samanta Anindya , Bordbar Darius D. , Weng Christina Y. , Chancellor John R.
Published: December 2024

Glucagon-like peptide-1 (GLP-1) receptor agonists are a family of drugs, most well known by the third-generation once-weekly subcutaneous semaglutide, that act on the incretin pathway of metabolic, hormonal signaling to modulate pancreatic insulin release, gastric emptying, energy intake, and subjective feelings of satiety. This class of drugs’ efficacy and safety in the treatment of type 2 diabetes and obesity have been demonstrated across multiple large randomized controlled trials. These data have propelled GLP-1 receptor agonists to ubiquity in diabetic management and weight loss therapy, leading them to be frequently encountered in ophthalmic practice. The effect of GLP-1 receptor agonists like semaglutide on diabetic retinopathy (DR) is at this point unclear; some studies indicate a worsening of DR with the initiation of GLP-1 agonists, especially semaglutide. Overall, the macrovascular reduction of cardiovascular and stroke risks from GLP-1 receptor agonists should be prioritized over the potential microvascular progression of DR, as long as the patient is regularly followed by ophthalmology.
Visual and Anatomic Outcomes From Ultracomplex Retinal Detachment Repair in a Large County Hospital
Authors: Chen Ariel , Coffee Robert E. , Date Rishabh C. , Weng Christina Y.
Published: December 2024

Purpose:

To evaluate outcomes of ultracomplex retinal detachment (UCRD) repairs performed at a large county hospital.

Materials and Methods:

Retrospective chart review of patients who underwent a UCRD repair, defined as a funnel retinal detachment (RD), RD associated with ocular trauma, or RD requiring retinectomy, 5000 centistoke silicone oil or perfluorocarbon heavy liquid (PFO). The outcomes examined were visual acuity (VA), anatomic success, and phthisis development.

Results:

Fifty eyes met inclusion criteria; 7 (14%) had a funnel RD, 14 (28%) had a history of ocular trauma, 34 (68%) had a retinectomy, 19 (38%) used 5000 centistoke silicone oil, and 12 (24%) used PFO. The mean follow-up time was 10.9±6.9 months. At 3 months, vision had remained stable or improved for 64% of eyes and the macula was attached for 66% of eyes. The mean preoperative VA was 2.5±0.5 logMAR, and the mean VA at 3 months was 2.4±0.7 logMAR with no statistically significant difference (P=0.30). With multivariate regression, preoperative VA was a statistically significant predictive factor of postoperative VA at 3 months. Nine (18%) of eyes developed phthisis, a mean of 11.4±5.1 months after UCRD repair.

Conclusions:

Surgical intervention for UCRD can stabilize vision and achieve anatomic success.
Use of Home Optical Coherence Tomography for Retinal Diseases
Authors: Bordbar Darius D. , Bhatnagar Anshul , Weng Christina Y.
Published: December 2024

Modern treatment protocols for retinal diseases involve frequent in-office monitoring with optical coherence tomography (OCT) and treatment with anti-vascular endothelial growth factor injections. Monthly injections may yield the greatest visual outcomes but are the most burdensome for patients and physicians, while as-needed injections may lead to undertreatment. Hybrid protocols, such as treat-and-extend (TREX) have been conceived to bridge this gap. Device-based home monitoring protocols for retinal disease may iterate further and allow more precise treatment tailored to individualized disease activity curves. Prior non-OCT home monitoring strategies have been developed with varying efficacy. These range from the ubiquitous but low-sensitivity Amsler grid to recent innovations such as the ForeseeHome preferential hyperacuity perimeter. Most recently, home OCT devices have been studied for remote monitoring, largely for use with age-related macular degeneration (AMD). Currently, the only Food and Drug Administration (FDA) approved device that utilizes OCT for monitoring retinal disease is the SCANLY Home OCT. Paired with an artificial intelligence (AI) algorithm that allows automated monitoring and alerting of retinal fluid volumes in AMD, SCANLY has demonstrated feasibility in limited trials to date, and a multicenter randomized controlled trial is currently underway to assess its efficacy in comparison to TREX regimens. Additional non–FDA-approved devices are being developed with varying degrees of study to date. Questions remain regarding its efficacy, real-world implementation, and financial considerations; nevertheless, home OCT has the potential to address many current barriers in retinal care, including travel and treatment burdens, while facilitating increased treatment precision.
Head-mounted Devices for Low Vision: A Review
Authors: Yuan Sean M. , Rafaelof Michael , Huang Jennifer D. , Mehta Mitul C.
Published: December 2024

Head-mounted devices (HMDs) are wearable electronic tools designed to augment the visual experience of low-vision patients who have a decrease in vision not improved by refractive correction. They do so by addressing various principles of visual enhancement, including magnification, illumination, increased field of view, and contrast sensitivity enhancement, among others. Since the introduction of the first HMD 3 decades ago, advancements in technology have made these devices more lightweight and practical for everyday use. More sophisticated features have been developed, including augmented reality, virtual reality, text-to-speech, and blind spot remapping. However, despite these advancements, HMDs still face a host of challenges, including cost, customizability to specific patient factors, and social stigma. In this paper, we present a broad overview of HMDs, review major products available commercially, and discuss the challenges and future directions for this rapidly growing field.
Demographics of Ophthalmology and Optometry Practices and Changes in Utilization Patterns of Procedures and Services Following Private Equity Acquisition
Authors: Del Piero Juliet , Yennam Sowmya , Mukhopadhyay Anirudh , Chen Evan M. , Weng Christina Y. , Parikh Ravi
Published: December 2024

Purpose:

To characterize private equity (PE) acquisition of ophthalmology and optometry practices and compare procedural utilization before and after acquisition.

Methods:

Ophthalmologists and optometrists in practices acquired from 2012 to 2016 were identified and characterized using an internet archive with an additional search in 2017 to characterize doctor turnover. United States Census Bureau and Internal Revenue Service Data were used to determine population health insurance and adjusted gross income (AGI). Healthcare Common Procedure Coding System codes were drawn from the Medicare database.

Results:

Six platform companies acquired 36 practices between 2012 and 2016, including 518 optometrists and 136 ophthalmologists with a net doctor decrease of 3% and 7%, respectively (years 2016 to 2017). PE firm-owned practices were primarily located in metropolitan core areas with above-average AGI and insurance coverage. Diagnostic procedures, total encounters, cataract surgery, and yttrium aluminum garnet (YAG) capsulotomy volume increased per physician 1-year post-acquisition. In adjusted difference-in-difference comparisons, cataract surgery (13.3% relative increase, P<0.001) and YAG capsulotomy (35.6% relative increase, P<0.001) remained significant. PE practices demonstrated an increase in cataract surgery procedures (28,813/platform pre-acquisition to 33,930/platform post-acquisition, P=0.015).

Conclusion:

PE acquisitions of ophthalmology and optometry practices were centered in metropolitan core areas with above-average AGI and insurance coverage. PE acquisition led to less optometrists and ophthalmologists employed at the practice. Overall, they exhibited doctor turnover with a net doctor decrease. When compared to non-PE doctors, PE-acquired doctors demonstrated an increase in cataract surgery and YAG capsulotomy volume. Overall, cataract surgery volume increased among PE practices after acquisition.
PRK plus crosslinking to correct refractive error after phakic intraocular lens repeated rotation: Bioptics Xtra
Authors: Balparda Kepa , Herrera-Chalarca Tatiana , Franco-Sánchez Isabela , López-Velásquez Mariana , Escobar-Giraldo Mariana
Published: December 2024

Introduction:

Phakic intraocular lens (IOL) surgery is generally considered safe; however, spontaneous IOL rotation can occur in some patients. Repeat spontaneous rotation of the IOL presents a significant challenge that requires careful management.

Patient and Clinical Findings:

A 30-year-old man underwent bilateral phakic IOL implantation for high myopia in the context of a borderline cornea, characterized by keratometric asymmetry and anterior elevation at the location of the thinnest corneal point. The IOLs experienced spontaneous rotation, which was initially managed by surgical repositioning. However, the IOLs rotated spontaneously again less than a week after the repositioning.

Diagnosis, Intervention, and Outcomes:

The patient underwent topography-guided photorefractive keratectomy (PRK) combined with accelerated crosslinking (30 mW/cm2 for 90 seconds, totaling 2.7 J/cm2) in both eyes. 6-month post-PRK Xtra, his uncorrected vision improved to 20/20 in the right eye and 20/25 in the left eye. The IOLs have remained stable in their final rotated positions.

Conclusions:

This is the first reported case, to the authors' knowledge, of using PRK Xtra to manage residual refractive error in a patient experiencing repeated spontaneous rotation of phakic IOLs. This technique is feasible and may serve as an alternative to IOL exchange. It has been named “Bioptics Xtra.”
Postoperative complications and surgical outcomes of robotic versus laparoscopic pancreaticoduodenectomy: a meta-analysis of propensity-score-matched studies
Authors: Tang Gang , Zhang Jie , Zhang Linyu , Xia Lingying , Chen Rui , Zhou Rongxing
Published: December 2024

Background:

Robotic pancreaticoduodenectomy (RPD) is used more commonly, but high-level evidence is still scarce. This meta-analysis aimed to compare the short-term outcomes between RPD and laparoscopic pancreaticoduodenectomy (LPD) using data collected from propensity score-matched (PSM) studies.

Materials and methods:

We searched PubMed, Cochrane Library, Embase, and Web of Science databases for PSM studies comparing RPD and LPD. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals were calculated.

Results:

Ten PSM studies were included, encompassing 8106 patients (RPD group: 3695 patients; LPD group: 4411 patients). Compared with LPD, RPD was associated with a lower conversion rate (RR, 0.56) and blood transfusion rate (RR, 0.49), as well as a higher number of harvested lymph nodes (MD, 2.15). There were no significant differences observed in 30-day readmission (RR, 1.02), 90-day mortality (RR, 1.01), overall morbidity (RR, 0.94), major complications (RR, 1.06), operative time (MD, −8.00 min), blood loss (MD, −19.37 mL), reoperation (RR, 0.95), bile leak (RR, 0.93), chylous leak (RR, 1.40), postoperative pancreatic fistula (RR, 1.06), delayed gastric emptying (RR, 0.92), wound infection (RR, 1.12), length of stay (MD, −0.32 days), and R0 resection (RR, 0.98) between the groups.

Conclusions:

Although LPD and RPD had similar surgical outcomes, RPD had the perioperative advantage over LPD in decreasing conversion rates and blood transfusion rates and increasing the number of lymph nodes harvested. Further randomized controlled trials evaluating the potential advantages of RPD over LPD are warranted.
The role of artificial intelligence in the diagnosis, imaging, and treatment of thoracic empyema
Authors: Zumla Adam , Ahmed Rizwan , Bakhri Kunal
Published: December 2024

Purpose of review

The management of thoracic empyema is often complicated by diagnostic delays, recurrence, treatment failures and infections with antibiotic resistant bacteria. The emergence of artificial intelligence (AI) in healthcare, particularly in clinical decision support, imaging, and diagnostic microbiology raises great expectations in addressing these challenges.

Recent findings

Machine learning (ML) and AI models have been applied to CT scans and chest X-rays to identify and classify pleural effusions and empyema with greater accuracy. AI-based analyses can identify complex imaging features that are often missed by the human eye, improving diagnostic precision. AI-driven decision-support algorithms could reduce time to diagnosis, improve antibiotic stewardship, and enhance more precise and less invasive surgical therapy, significantly improving clinical outcomes and reducing inpatient hospital stays.

ML and AI can analyse large datasets and recognize complex patterns and thus have the potential to enhance diagnostic accuracy, preop planning for thoracic surgery, and optimize surgical treatment strategies, antibiotic therapy, antibiotic stewardship, monitoring complications, and long-term patient management outcomes.
Cuproptosis: an emerging domain for copper-based nanomaterials mediated cancer therapy
Authors: Zhao Fan , Zhao Zhuangzhuang , Gao Hao , Zhang Yuxin , Qi Jiarui , Yu Hongyan , Wang Chen , Xu Junchen , Zubair Yousaf Muhammad , Che Shenglei , Yu Jing
Published: December 2024

Cuproptosis, a newly discovered copper-dependent mode of cell death, has received extensive attention in the field of cancer therapy due to its specific activation pathway. Rapid accumulation of large amounts of copper ions within the cancer cells to achieve copper overload is the key to activating cuproptosis. Advanced nanotechnology offers considerable promise for delivering ions to cancer cells, in which copper-based nanomaterials have been proposed to evoke cuproptosis-mediated cancer therapy. However, it is still a great challenge to induce copper overload specifically in tumors and efficiently activate subsequent cuproptosis-related molecular pathways. Therefore, it is necessary to summarize the strategies used to effectively activate or amplify cuproptosis based on currently developed copper-based nanomaterials, providing ideas for the design of nanomaterials in the future. In this review, copper-based nanomaterials that can be used to activate cuproptosis are systematically classified for nanomaterials selection. Subsequently, cuproptosis sensitization strategies using copper-based nanomaterials are provided to amplify the therapeutic efficiency. Meanwhile, cuproptosis-related combination therapies for maximizing treatment efficacy are delineated. Ultimately, the remaining challenges and feasible future directions in the use of cuproptosis for tumor therapy based on copper-based nanomaterials are also discussed.
Incidence of Sexually Transmitted Infections and Pregnancy Among Adolescents Experiencing Sex Trafficking
Authors: Ficker Whitney , Ehrhardt-Humbert Lauren , Reynolds Stacy
Published: December 2024

Objective:

There is a lack of data regarding the incidence of sexually transmitted infections (STIs) and pregnancy among adolescents experiencing sex trafficking. This study aimed to determine the incidence proportion of STIs and pregnancy among adolescents evaluated for sex trafficking at an urban tertiary children's hospital compared to the community adolescent population.

Methods:

This retrospective, cross-sectional study looked at adolescents aged 11 to 21 years experiencing sex trafficking from March 2019 to March 2022. Data were abstracted from the hospital's human trafficking advocacy team database and the electronic medical record (EMR), including demographics, type and setting of trafficking, presenting complaints, and STI and pregnancy test results. Using Fisher's exact test, the incidence of STIs and pregnancy among adolescents experiencing sex trafficking was compared to adolescents in the community using local county health department data.

Results:

Fifty-four patients met the eligibility criteria. Females comprised 93% (n = 50) of the group. The average age was 16 years. The racial demographics most represented were African American at 56% (n = 30) and White at 30% (n = 16). History of abuse prior to trafficking was found in 78% (n = 42). Incidence proportions of STIs, compared to county health data, are as follows: 64.8% for Chlamydia trachomatis (CT) versus 7.8% (OR, 22; 95% CI, 12–40), 51.9% for Neisseria gonorrhoeae (GC) versus 2.2% (OR, 47; 95% CI, 26–83), 9.3% for syphilis versus 0.1% (OR, 111; 95% CI, 34–283), and 5.6% for HIV versus 0.1% (OR, 83; 95% CI, 16–261). There was a high individual cumulative incidence of STIs among patients over time, and patients presented with a variety of presenting complaints. The incidence proportion for pregnancy was 11.1% compared to 1.3% (OR, 10; 95% CI, 3–22).

Conclusions:

Adolescents experiencing sex trafficking have a significantly higher rate of STIs and pregnancy than the community adolescent population.
Impact of Preoperative Lacrimal Sac Morphology on Postoperative Rhinostomy Shape and Prognosis in Endoscopic Dacryocystorhinostomy
Authors: Lim Kyungsu , Lee Shin Hyo , Roh Hong Gee , Shin Hyun Jin
Published: December 2024

Purpose:

To determine the association between the preoperative shape of the lacrimal sac and the postoperative shape of a rhinostomy in patients undergoing endoscopic dacryocystorhinostomy (DCR) for primary acquired nasolacrimal duct obstruction.

Material and Methods:

This retrospective study involved 180 cases among 129 patients. Preoperative dacryocystography (DCG) classified lacrimal sacs into constricted or cylindrical types based on their width relative to the nasolacrimal duct. Postoperative rhinostomy shapes were categorized into flat, ladle, and ice-scoop types according to the presence and visibility of borders between the lacrimal sac and nasal mucosa. Anatomic success required patency as verified by syringing, whereas functional success required the complete resolution of epiphora.

Results:

The 180 cases comprised 46 (25.7%) and 134 (74.3%) classified as constricted and cylindrical preoperative shapes, respectively. There were 24 flat, 92 ladle, and 64 ice-scoop types of rhinostomies observed postoperatively. The preoperative DCG shape influenced the postoperative rhinostomy shape, with constricted sacs more frequently resulting in flat-shaped rhinostomies, and cylindrical sacs more frequently resulting in ice-scoop-shaped rhinostomies. Functional success was more common in cylindrical and ladle-type sacs than in constricted types (P<0.001), and lower for flat-shaped rhinostomy than for the ladle and ice-scoop shapes (P=0.003).

Conclusions:

Lacrimal sac characteristics play a prominent role in determining the postoperative rhinostomy shape that is particularly relevant to functional outcomes. A preoperative cylindrical lacrimal sac and postoperative ice-scoop-shaped rhinostomy are predictive of functional success after endoscopic DCR. These observations will be crucial in creating a surgical plan and monitoring the postoperative rhinostomy configuration.
Residents' Exposure to Obstetric Anal Sphincter Injury: A 16-Year Temporal Trend
Authors: Pfeuti Courtney K. , Gugerty Lindsay , Occhino John A. , Chauhan Suneet P.
Published: December 2024

Importance

Exposure to the surgical management of obstetric anal sphincter injuries (OASIS) is limited during obstetrics training.

Objectives

The objective of this study was to quantify residents' exposure to OASI repair during 4-year obstetrics and gynecology (OBGYN) residency and examine temporal trends over a 16-year period.

Study Design

This was a retrospective cohort study of residents' exposure to OASIS at a community academic hospital from 2007 to 2022. Individuals with documented OASIS (third- or fourth-degree laceration) by International Classification of Diseases, Ninth and Tenth Revisions, codes during vaginal delivery (VD), spontaneous vaginal delivery (SVD), or operative vaginal delivery (OVD), were included. Delivery rates and OBGYN resident positions were examined. Temporal trends in OASIS were analyzed in 4-year epoch to determine average resident exposure during OBGYN residency.

Results

During the 16-year study period, there were 103,234 deliveries (62% VD, 4% OVD, 34% cesarean delivery). Among VDs, there were 2,344 (3.4%) OASIS with 88.5% classified as third-degree and 11.5% as fourth degree. The OASI rate decreased from 4.2% (2007–2010) to 2.9% (2019–2022), whereas OBGYN residents increased by 49% (67 to 99; P < 0.001). Average resident exposure to OASIS decreased from 11 (2007–2010) to 5 (2019–2022; P = 0.55). Subclassification revealed that residents were exposed to 5 third-degree repairs and less than 1 fourth-degree repair, on average, during 2019–2022.

Conclusions

During 4 years of training, average resident exposure was to 7 OASIS, 6 third degree, and 1 fourth degree. Limited exposure to OASIS during residency may be detrimental, as surgical treatment is a complicated yet essential obstetric procedure that carries significant risk of patient morbidity and potential long-term sequelae. Therefore, reliance on supplementation with simulation may improve surgeon competence in OASI management.
Knockout of the V-ATPase interacting protein Tldc2 in B-type kidney intercalated cells impairs urine alkalinization
Authors: Eaton Amity F. , Danielson Elizabeth C. , Tu Leona J. , Brown Dennis , Merkulova Maria
Published: December 2024

Intercalated cells (ICs) are acid-base regulatory cells in the kidney collecting duct that excrete either acid or base into the urine in response to systemic cues. A-ICs deliver protons into the tubule lumen via an apical proton pump (V-ATPase) and reabsorb base (bicarbonate) using the AE1 anion exchanger. B-ICs function in the opposite direction. They have basolateral V-ATPase and secrete bicarbonate into the lumen via the anion exchange protein, pendrin. The function of a third IC subtype, the non-A non-B IC which has apical pendrin and apical V-ATPase, is less well understood. We previously reported that members of the TLDc protein family interact with the V-ATPase and may regulate its function. TLDc proteins exhibit a distinct expression pattern in the kidney with RNAseq showing high, differential expression of Tldc2 in B-ICs. Here, we show by RNAscope imaging that Tldc2 is indeed expressed in B-ICs, but also in some non-A, non-B ICs. UsingTldc2knockout (Tldc2-/-) mice, we found that male and females had significantly lower urine pH than wild-type littermates, and their ability to increase urine pH in response to a bicarbonate load was impaired. In addition,Tldc2-/-males developed hyperbicarbonatemia.Tldc2-/-kidneys contained fewer B-ICs than wild-type mice, but more non-A, non-B ICs; therefore their sum and the number of A-ICs were unchanged. Furthermore, there was decreased basolateral accumulation of V-ATPase inTldc2/-/-B-ICs. These findings suggest thatTldc2is a novel gene involved in renal acid-base regulation and in addition, may serve as a differentiation marker for B-ICs.

NEW & NOTEWORTHY

Acid-base balance in the body is constantly changing but must be tightly controlled to be compatible with life. The kidney contains specialized cells that can excrete excess acid or base (bicarbonate) into the urine to maintain normal blood pH. The key protein involved in this process is called the V-ATPase. Here, we report that a novel V-ATPase interacting protein Tldc2 is critical for kidney bicarbonate secretion and is, therefore, a previously unrecognized acid-base regulatory gene.
Induction of hemodynamic traveling waves by glial-related vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging
Authors: Pereira Mickaël , Droguerre Marine , Valdebenito Marco , Vidal Louis , Marcy Guillaume , Benkeder Sarah , Comte Jean-Christophe , Pascual Olivier , Zimmer Luc , Vidal Benjamin
Published: December 2024

Cerebral hemodynamics are crucial for brain homeostasis and serve as a key proxy for brain activity. Although this process involves coordinated interaction between vessels, neurons and glial cells, its dysregulation in neuroinflammation is not well understood.

We used in vivo mesoscopic functional ultrasound imaging to monitor cerebral blood volume changes during neuroinflammation in rats injected with lipopolysaccharide (LPS) in the visual cortex, under resting-state or visual stimulation, combined to advanced ex vivo techniques for glial cell reactivity analysis.

Cortical neuroinflammation induced large oscillatory hemodynamic traveling waves in the frequency band of vasomotion (∼0.1 Hz) in both anesthetized and awake rats. Vasomotor waves traveled through large distances between adjacent penetrating vessels, spanning the entire cortex thickness, and even extending to subcortical areas. Moreover, vasomotion amplitude correlated with microglial morphology changes and was significantly reduced by astrocytic toxins, suggesting that both microglia and astrocytes are involved in the enhancement of vasomotion during neuroinflammation. Notably, functional connectivity was increased under this oscillatory state and functional hyperemia was exacerbated.

These findings reveal new spatiotemporal properties and cellular mechanisms of cerebral vasomotion, and suggest that this is a major component of brain hemodynamics in pathological states. Moreover, reactive microglia and astrocytes are participating to increased vasomotion during neuroinflammation. These results call for a reassessment of vasomotion and traveling waves as primary phenomena when imaging brain hemodynamic activity, particularly in conditions associated with neuroinflammation.
Cardiac fibroblasts cellular anisotropy is determined by YAP-dependent cellular contractility and ECM production
Authors: Pereira-Sousa Daniel , Guillamat Pau , Niro Francesco , Vinarský Vladimír , Fernandes Soraia , Cassani Marco , Pagliari Stefania , Trepat Xavier , Rasponi Marco , Oliver-De La Cruz Jorge , Forte Giancarlo
Published: December 2024

Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue, features which are essential for maintaining tissue integrity and function, primarily through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts, which promote maladaptive ECM remodeling, a process which may lead to heart failure. Although the mechanosensitive Yes-Associated Protein (YAP) has been implicated in CFb activation, its role in the organization of CFbs and in their ability to deposit cardiac ECM remains unexplored. We investigated the effects of YAP genetic deletion on cardiac fibroblast phenotype and function by generating CFbs from wild-type (WT) and YAP knockout (KO) human embryonic stem cells (hESCs). We found that YAP depletion impaired CFbs differentiation by reducing the expression of cardiogenic markers. Additionally, we demonstrated that YAP expression is required for monolayer alignment of CFbs. Transcriptomic analysis further revealed that YAP is essential for the regulation of ECM- and contractility-related genes, and that its absence resulted in reduced ECM deposition, diminished anisotropy, and decreased force generation. Pharmacological inhibition of contractility closely mirrored YAP KO phenotype, suggesting that YAP regulates both monolayer organization and ECM structure through its control over contractility. These findings underscore the critical role of the mechanosensor YAP in maintaining the supracellular organization of CFbs and the mechanical integrity of cardiac tissue.
Collective dynamics of DNA methylation during ageing
Authors: Hashtroud Aida , Bonder Marc , Stegle Oliver , von Meyen Ferdinand , Reik Wolf , Rulands Steffen
Published: December 2024

Ageing is the decline of physiological function over time. Statistical models termed ageing clocks can predict chronological and biological age from the longitudinal time evolution of DNA methylation. Here, we show that DNA methylation ageing is also manifest in how pairs of genomic loci evolve with respect to each other with age. Using sequencing data from a range of tissues in mouse we show that genomic correlations in DNA methylation during ageing are characterised by an enrichment of correlations between sites that are roughly 500 bp apart. We trace the origin of this behaviour to collective dynamics in the boundaries of CpG islands. We derive a simple, biophysical model that explains the origin due to a tilt in the competition between methylating and demethylating processes and an ensuing wetting-like phenomenon. Using Chip-seq data, we argue for a molecular mechanism based on a PRC2-dependent dilution of H3K27me3 during ageing. Our work gives a new perspective on epigenetic ageing, highlighting the importance of correlative as opposed to longitudinal dynamics.