bluuebunny/crossref_metadata_2025 huggingface dataset:
ZEBRA: a hierarchically integrated gene expression atlas of the murine and human brain at single-cell resolution
Authors: Flotho Matthias , Amand Jérémy , Hirsch Pascal , Grandke Friederike , Wyss-Coray Tony , Keller Andreas , Kern Fabian
Published: November 2023

The molecular causes and mechanisms of neurodegenerative diseases remain poorly understood. A growing number of single-cell studies have implicated various neural, glial, and immune cell subtypes to affect the mammalian central nervous system in many age-related disorders. Integrating this body of transcriptomic evidence into a comprehensive and reproducible framework poses several computational challenges. Here, we introduce ZEBRA, a large single-cell and single-nucleus RNA-seq database. ZEBRA integrates and normalizes gene expression and metadata from 33 studies, encompassing 4.2 million human and mouse brain cells sampled from 39 brain regions. It incorporates samples from patients with neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Multiple sclerosis, as well as samples from relevant mouse models. We employed scVI, a deep probabilistic auto-encoder model, to integrate the samples and curated both cell and sample metadata for downstream analysis. ZEBRA allows for cell-type and disease-specific markers to be explored and compared between sample conditions and brain regions, a cell composition analysis, and gene-wise feature mappings. Our comprehensive molecular database facilitates the generation of data-driven hypotheses, enhancing our understanding of mammalian brain function during aging and disease. The data sets, along with an interactive database are freely available at https://www.ccb.uni-saarland.de/zebra.
Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults
Authors: Wu Gan , Hu Qiong , Huang Zhenhe , Lai Zhihan , Wang Xiaojie , Cai Miao , Lin Hualiang
Published: November 2023

Background

Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain.

Methods

This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as estimated glomerular filtration rate between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis.

Results

During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12–1.19; HR 1.29, 95% CI 1.20–1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR 1.61, 95% CI 1.52–1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI 0.05–0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function.

Conclusions

The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.
Increased Levels of Caspase-1 and IL-1β Among Adults With Persistent Immune Activation After 12 Years of Suppressive Antiretroviral Therapy in the Infectious Diseases Institute HIV Treatment Cohort
Authors: Nabatanzi Rose , Ssekamatte Phillip , Castelnuovo Barbara , Kambugu Andrew , Nakanjako Damalie
Published: November 2023

Background

We sought evidence of activated pyroptosis and the inflammasome pathways among human immunodeficiency virus (HIV)–infected adults after 12 years of suppressive antiretroviral therapy (ART) and persistent immune activation in the Infectious Diseases Institute HIV treatment cohort in Uganda.

Methods

In a cross-sectional study, using peripheral blood mononuclear cells of HIV-infected individuals with high and low immune activation (CD4/CD8+CD38+HLA-DR+ cells) relative to HIV-negative reference group, caspase-1 expression was measured using flow cytometry and plasma interleukin 18 and interleukin 1β (IL-1β) levels using enzyme-linked immunosorbent assay.

Results

There was higher expression of caspase-1 by CD4 T cells of ART-treated individuals with high immune activation relative to those with lower immune activation (P = .04). Similarly, plasma levels of IL-1β were higher among ART-treated individuals with high immune activation levels relative to those with low immune activation levels (P = .009). We observed a low positive correlation between caspase-1 expression by CD4/CD8 T cells and immune activation levels (r  = 0.497 and r  = 0.329, respectively).

Conclusions

Caspase-1 and IL-1β were high among individuals with high immune activation despite 12 years of suppressive ART. There is a need to further understand the role of persistent abortive infection and the latent HIV reservoir characteristics as drivers of persistent activation and inflammation and to subsequently intervene to prevent the complications of chronic immune activation during long-term ART.
Interprofessional Education: An Innovative Approach to Increase the Human Immunodeficiency Virus Workforce
Authors: Person Anna K , Harris Sadie J , Burdge Jennifer , Blue Amy V , Leedy Nicole E , Villacorta Evelyn , Justo Julie Ann , Black Erik , Janelle Jennifer , Ahuja Divya , Chastain Cody A
Published: November 2023

Ending the human immunodeficiency virus (HIV) epidemic relies on a robust clinical workforce. The Southeast AIDS Education and Training Center's interprofessional education program is a novel approach to increasing the interest and ability of early health professional learners to provide high-quality, comprehensive, person-first care for people with HIV.

Key Points: Interprofessional education (IPE) focusing on multidisciplinary care for people with HIV can serve as a novel way to increase the HIV workforce. This brief report describes the IPE program of the Southeast AIDS Education and Training Center.
Impact of In-house Candida auris Polymerase Chain Reaction Screening on Admission on the Incidence Rates of Surveillance and Blood Cultures With C. auris and Associated Cost Savings
Authors: Rosa Rossana , Jimenez Adriana , Andrews David , Dinh Huy , Parra Katiuska , Martinez Octavio , Abbo Lilian M
Published: November 2023

Background

The impact of strategies for rapid diagnostic screening of Candida auris on hospital operations has not been previously characterized. We describe the implementation of in-house polymerase chain reaction (PCR) testing on admission for screening of colonization with C. auris, associated process improvements, and financial impact.

Methods

This study was conducted across an integrated health system. Patients were tested based on risk factors for C. auris carriage. Pre-intervention, the PCR was sent out to a reference laboratory, and postintervention was performed in-house. Changes in the incidence rates (IRs) of C. auris present on admission (CA-POA) and C. auris hospital-onset fungemia (CA-HOF) were assessed using interrupted time series analysis. The economic impact on isolation and testing costs was calculated.

Results

Postintervention, the IR of CA-POA doubled (IRR, 2.57; 95% CI, 1.16–5.69; P = .02) compared with the pre-intervention period. The baseline rate of CA-HOF was increasing monthly by 14% (95% CI, 1.05–1.24; P = .002) pre-intervention, while during the postintervention period there was a change in slope with a monthly decrease in IR of 13% (95% CI, 0.80–0.99; P = .02). The median turnaround time (TAT) of the results (interquartile range) was reduced from 11 (8–14) days to 2 (1–3) days. Savings were estimated to be between $772 513.10 and $3 730 480.26.

Conclusions

By performing in-house PCR for screening of C. auris colonization on admission, we found a doubling of CA-POA rates, a subsequent decrease in CA-HOF rates, reduced TAT for PCR results, and more efficient use of infection control measures. In-house testing was cost-effective in a setting of relatively high prevalence among individuals with known risk factors.
Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency
Authors: Little Jessica S , Oakley Miranda S , Thorner Anna R , Johnston Demerise , Majam Victoria , Liakos Alexis D , Novack Lewis A , Zheng Hong , Meredith Scott , Chou Chao-Kai , Newton Benjamin R , Soiffer Robert J , Krause Peter J , Baden Lindsey R , Kumar Sanjai
Published: November 2023

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti–specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.
Statutes and Contracts as Founts of Formal Reasoning
Authors: Summers Robert S
Published: November 2023

In this essay, which I dedicate to my friend and co-author, Professor Patrick Atiyah, I seek to demonstrate that, in American law, the overall level of formality of those reasons for decision (or other action) that derive from contracts is generally lower than the formality of reasons deriving from statutes. I also explore the importance of this fact, and here and there speculate on the explanations for it. I provide brief accounts of the varieties of formality involved, as well. I believe these efforts, which are partially programmatic, enable us to understand somewhat more fully the distinctive nature of statutes and contracts (which I here consider to be a type of law), and the special character of the reasoning that these types of law generate.
Confucian Welfarism: Intellectual Origins of Solidarity for Health and Welfare Systems
Authors: Yeh Ming-Jui
Published: November 2023

Solidarity is presumed to underpin the redistributive health and welfare systems in modern democracies; however, it is often considered a Western—or more specifically, European—concept. While health and welfare systems have been transplanted successfully to many non-Western developed countries, whether the solidarity necessary for such systems exists or is intellectually available remains under debate. Using an East Asian country with the Confucian tradition as an illustrative case, I first argue that the Confucian tradition has special theoretical and sociological importance for health and welfare solidarity. Then, through investigating the classic Confucian writings, I propose transformed interpretations of the essential concepts of Confucian thought, namely filial piety, benevolent governance and the mandate of heaven. With these interpretations, the differentiated family-based solidarity and the people-rooted thought in Confucianism could be reimagined to fit with the modern liberal-democratic political regime and welfare arrangements. I call this model Confucian welfarism, which I argue could form the intellectual origins of solidarity for people who believe in or have an affinity to Confucian ethos.
The sustainability of trade in wild plants—A data-integration approach tested on critically endangered Nardostachys jatamansi
Authors: Smith-Hall Carsten , Pyakurel Dipesh , Meilby Henrik , Pouliot Mariève , Ghimire Puspa L , Ghimire Suresh , Madsen Sofia T , Paneru Yagya R , Subedi Bhishma P , Timoshyna Anastasiya , Treue Thorsten
Published: November 2023

While the demand for many products from wild-harvested plants is growing rapidly, the sustainability of the associated plant trade remains poorly understood and understudied. We integrate ecological and trade data to advance sustainability assessments, using the critically endangered Nardostachys jatamansi in Nepal to exemplify the approach and illustrate the conservation policy gains. Through spatial distribution modeling and structured interviews with traders, wholesalers, and processors, we upscale district-level trade data to provincial and national levels and compare traded amounts to three sustainable harvest scenarios derived from stock and yield data in published inventories and population ecology studies. We find increased trade levels and unsustainable harvesting focused in specific subnational geographical locations. Data reported in government records and to CITES did not reflect estimated trade levels and could not be used to assess sustainability. Our results suggest that changing harvesting practices to promote regeneration would allow country-wide higher levels of sustainable harvests, simultaneously promoting species conservation and continued trade of substantial economic importance to harvesters and downstream actors in the production network. The approach can be applied to other plant species, with indication that quick and low-cost proxies to species distribution modeling may provide acceptable sustainability estimates at aggregated spatial levels.
Engineering of a phosphotriesterase with improved stability and enhanced activity for detoxification of the pesticide metabolite malaoxon
Authors: Job Laura , Köhler Anja , Testanera Mauricio , Escher Benjamin , Worek Franz , Skerra Arne
Published: November 2023

Organophosphorus (OP) pesticides are still widely applied but pose a severe toxicological threat if misused. For in vivo detoxification, the application of hydrolytic enzymes potentially offers a promising treatment. A well-studied example is the phosphotriesterase of Brevundimonas diminuta (BdPTE). Whereas wild-type BdPTE can hydrolyse pesticides like paraoxon, chlorpyrifos-oxon and mevinphos with high catalytic efficiencies, kcat/KM >2 × 107 M−1 min−1, degradation of malaoxon is unsatisfactory (kcat/KM ≈ 1 × 104 M−1 min−1). Here, we report the rational engineering of BdPTE mutants with improved properties and their efficient production in Escherichia coli. As result, the mutant BdPTE(VRNVVLARY) exhibits 37-fold faster malaoxon hydrolysis (kcat/KM = 4.6 × 105 M−1 min−1), together with enhanced expression yield, improved thermal stability and reduced susceptibility to oxidation. Therefore, this BdPTE mutant constitutes a powerful candidate to develop a biocatalytic antidote for the detoxification of this common pesticide metabolite as well as related OP compounds.
Carbon dynamics in long-term starving poplar trees—the importance of older carbohydrates and a shift to lipids during survival
Authors: Helm Juliane , Muhr Jan , Hilman Boaz , Kahmen Ansgar , Schulze Ernst-Detlef , Trumbore Susan , Herrera-Ramírez David , Hartmann Henrik
Published: November 2023

Carbon (C) assimilation can be severely impaired during periods of environmental stress, like drought or defoliation, making trees heavily dependent on the use of C reserve pools for survival; yet, the dynamics of reserve use during periods of reduced C supply are still poorly understood. We used stem girdling in mature poplar trees (Populus tremula L. hybrids), a lipid-storing species, to permanently interrupt the phloem C transport and induced C shortage in the isolated stem section below the girdle and monitored metabolic activity during three campaigns in the growing seasons of 2018, 2019 and 2021. We measured respiratory fluxes (CO2 and O2), non-structural carbon concentration, the respiratory substrate (based on isotopic analysis and CO2/O2 ratio) and the age of the respiratory substrate (based on radiocarbon analysis). Our study shows that poplar trees can survive long periods of reduced C supply from the canopy by switching in metabolism from recent carbohydrates to older storage pools with a potential mixture of respiratory substrates, including lipids. This mechanism of stress resilience can explain why tree decline may take many years before death occurs.
Bladder Repair with Irrigation and Debridement and Open Reduction Internal Fixation of the Anterior Pelvic Ring is Safe and Decreases Risk of Infection in Pelvic Ring Injuries with Extraperitoneal Bladder Ruptures
Authors: Saiz Augustine M. , O’Donnell Edmond , Kellam Patrick , Cleary Courtney , Moore Ximia , Schultz Blake J , Mayer Ryan , Amin Adeet , Gary Joshua , Warner Stephen J , Routt Milton L. , Eastman Jonathan G.
Published: November 2023

Objective:

To determine the incidence of infection in nonoperative versus operative management of extraperitoneal bladder ruptures in patients with pelvic ring injuries.

Setting:

Two level 1 trauma centers.

Design:

A retrospective cohort study of two prospectively collected trauma registries.

Patients/Participants: Of 1127 patients with operative pelvic ring injuries, 68 (6%) had extraperitoneal bladder ruptures.

Main Outcome Measurements:

Primary outcome was the incidence and associated risk factors of deep pelvic infection requiring return to OR for surgical debridement. Secondary outcomes included quality of reduction, other complications, and radiographic union.

Results:

Of the 68 patients with extraperitoneal bladder ruptures in the setting of an operative pelvic ring injury, 55 had bladder repair and 13 did not. Of those 13 without repair, none had ORIF of the anterior pelvic ring. Patients without bladder repair had an increased odds of infection 17-fold compared to patients who did have a repair performed (OR 16.9, 95% CI 1.75 – 164, P = 0.01). Other associated factors for deep pelvic infection included use of suprapubic catheter (P < 0.02) and a closed reduction of the anterior ring (P < 0.01). Patients undergoing anterior ring ORIF and bladder repair had improved reductions and no increased infection risk.

Conclusions:

Operative repair of extraperitoneal bladder ruptures decreases risk of infection in patients with pelvic ring injuries. Additionally, ORIF of the anterior pelvic ring does not increase risk of infection and results in better reductions compared to closed reduction. Treatment algorithms for these combined injuries should consider recommending early bladder repair and anterior pelvic ORIF.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Effect of Cervicothoracic Junction LIV Selection on Posterior Cervical Fusion Mechanical Failure
Authors: Labrum Joseph T. , Waddell William H. , Gupta Rishabh , Coronado Rogelio A. , Hymel Alicia , Steinle Anthony , Abtahi Amir M. , Stephens Byron F.
Published: November 2023

Study Design:

Systematic review and Meta-analysis.

Objective:

Analyze and summarize literature evaluating the role of C7, T1, and T2 lowest instrumented vertebra (LIV) selection in posterior cervical fusion (PCF) and if this affects the progression of mechanical failure and revision surgery.

Summary of Background Data:

Literature evaluating mechanical failure and adjacent segment disease in the setting of PCF at or nearby the cervicothoracic junction (CTJ) remains limited with studies reporting conflicting results.

Materials and Methods:

Two reviewers conducted a detailed systematic review using EMBASE, PubMed, Web of Science, and Google Scholar on June 28, 2021, for primary research articles comparing revision and complication rates for posterior fusions ending in the lower cervical spine (C7) and upper thoracic spine (T1–T2). The initial systematic database yielded 391 studies, of which 10 met all inclusion criteria. Random effects meta-analyses compared revision and mechanical failure rates between patients with an LIV above the CTJ and patients with an LIV below the CTJ.

Results:

Data from 10 studies (total sample=2001, LIV above CTJ=1046, and LIV below CTJ=955) were meta-analyzed. No differences were found between the 2 cohorts for all-cause revision [odds ratio (OR)=0.75, 95% CI=0.42–1.34, P<0.0001] and construct-specific revision (OR=0.62, 95% CI=0.25–1.53, P<0.0001). The odds of total mechanical failure in the LIV below CTJ cohort compared with the LIV above CTJ cohort were significantly lower (OR=0.38, 95% CI=0.18–0.81, P<0.0001).

Conclusion:

The results show patients with PCFs ending below the CTJ have a lower risk of undergoing total mechanical failure compared with fusions ending above the CTJ. This is important information for both physicians and patients to consider when planning for operative treatment.

Level of Evidence:

Level I.
Different Anti-inflammatory Drugs on High-Sensitivity C-Reactive Protein in Patients After Percutaneous Coronary Intervention: A Pilot Randomized Clinical Trial
Authors: Yu Miao , Zhu Zheng-Feng , Yang Fen , Yuan Yuan-Fan , Liao Shu-De , Liu Mei-Lin , Cheng Xiang
Published: November 2023

Colchicine reduces atherothrombotic cardiovascular events in coronary artery disease because of its anti-inflammatory effect. However, the effects of the other anti-inflammatory drugs in coronary artery disease remain unclear. This study included 132 patients aged 18–80 years who completed the planned percutaneous coronary interventions and were treated with aggressive secondary prevention strategies for 4 weeks. The subjects were randomly assigned to 1 of the following treatment groups for 4 weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in high-sensitivity C-reactive protein (hsCRP) levels at the end of 4 weeks. In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male, and 28 (25.69%) were female. The percentage changes in hsCRP after 4 weeks of treatment were −11.62%, −48.28%, −21.60%, and −7.81%, in the control, colchicine, tranilast, and the oridonin groups, respectively. Compared with the control group, only the colchicine group showed significantly greater reduction in hsCRP levels (P = 0.022). In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin, myeloperoxidase, and myeloblastin), platelet aggregation (glycoprotein VI), and endothelial damage (galectin-3) were reduced with colchicine therapy. These results show that of 3 anti-inflammatory drugs only colchicine could reduce hsCRP in patients after percutaneous coronary interventions.
A public health perspective on mitigating the global burden of chronic liver disease
Authors: Balakrishnan Maya , Rehm Jürgen
Published: November 2023

Chronic liver disease is a significant global health problem. Epidemiological trends do not show improvement in chronic liver disease incidence but rather a shift in etiologies, with steatotic liver disease (SLD) from metabolic dysfunction and alcohol becoming increasingly important causes. Consequently, there is a pressing need to develop a comprehensive public health approach for SLD. To that end, we propose a public health framework for preventing and controlling SLD. The framework is anchored on evidence linking physical inactivity, unhealthy dietary patterns, alcohol use, and obesity with both incidence and progression of SLD. Guided by the framework, we review examples of federal/state-level, community-level, and individual-level interventions with the potential to address these determinants of SLD. Ultimately, mitigating SLD’s burden requires primary risk factor reduction at multiple socioecological levels, by scaling up the World Health Organization’s “best buys,” in addition to developing and implementing SLD-specific control interventions.
Scheimpflug Corneal Tomography Anterior Chamber Depth in Descemet Stripping Endothelial Keratoplasty Recipients
Authors: Mandell Jordan , Pajek Sarah , Vanner Elizabeth A. , Santiago-Leon Andrea C. , Zhang Crystal L. , Koo Ellen H.
Published: November 2023

Purpose:

Our study investigates whether preoperative anterior chamber depth (ACD) measured by Scheimpflug tomography could serve as a potential predictor of graft failure in eyes undergoing Descemet stripping endothelial keratoplasty (DSEK).

Methods:

A retrospective review was conducted on patients who underwent primary or repeat DSEK between January 2020 and August 2021 at Bascom Palmer Eye Institute. Charts from 378 primary and 192 repeat DSEK patients were reviewed and ultimately 47 primary and 21 repeat DSEK patients met criteria for inclusion. Data collection included demographics, preoperative ACD, best-corrected visual acuity, and length of follow-up.

Results:

Demographics were similar between groups, and there was no significant difference in the average best-corrected visual acuity between the single and repeat DSEK groups preoperatively. Baseline preoperative ACD was greatest in the single DSEK group (3.51 ± 0.90 mm) when compared to baseline preoperative ACD in the repeat DSEK group (3.01 ± 0.67 mm, P = 0.003). The preoperative mean ACD was smallest in the repeat DSEK group before the second DSEK (2.94 ± 0.48 mm, P = 0.001). Preoperative baseline ACD was the only variable to affect graft survival time significantly (P = 0.012). The incidence of glaucoma diagnosis was similar in both groups (42.5% vs. 42.8%, P = 0.471). The diagnosis of glaucoma and presence of incisional glaucoma surgery did not affect the graft survival time (P = 0.129, P = 0.559) or need for repeat DSEK.

Conclusions:

Smaller baseline preoperative Scheimpflug ACD measurement may be a possible predictor of the need for repeat DSEK. Our study found that Scheimpflug ACD decreases with subsequent DSEK failure.
Variations in Management of Zone 1 Open Globe Injuries Across Corneal Specialists
Authors: Foley Lindsay M. , Colby Kathryn A. , Rapuano Christopher J. , Woreta Fasika A. , Syed Zeba A.
Published: November 2023

Purpose:

The aim of this study was to describe variations in practice patterns for the management of zone 1 open globe injuries among corneal specialists worldwide.

Methods:

This cross-sectional study was performed using an online survey distributed to members of The Cornea Society. Responses were collected between September 9, 2021, and September 30, 2021.

Results:

Of 94 responses included in analysis, respondents averaged 18.2 ± 14.5 years of postfellowship experience. Among respondents, 53 (56.4%) were affiliated with an academic institution and 41 (43.6%) with private practice. Ophthalmologists practicing in the United States were significantly more likely to use an eye shield preoperatively (98.5% vs. 85.7%, P = 0.03) and less likely to perform primary lensectomy in cases of lens involvement (40.9% vs. 75.0%, P = 0.002) compared with those practicing outside the United States. Ophthalmologists in practice fewer than 10 years were more likely to administer preoperative systemic antibiotics (91.4% vs. 66.1%, P = 0.006) and tetanus prophylaxis (88.6% vs. 67.8%, P = 0.03), and to obtain preoperative computed tomography scans (85.7% vs. 54.2%, P = 0.002) compared with more senior physicians. Ophthalmologists at academic institutions were more likely to perform preoperative B-scan (30.2% vs. 9.8%, P = 0.02), use general anesthesia (90.6% vs. 70.7%, P = 0.03), and admit for postoperative antibiotics (28.3% vs. 9.8%, P = 0.04), and were less likely to perform surgery overnight (45.3% vs. 70.7%, P = 0.02) compared with private practice physicians.

Conclusions:

There is significant variation in the practice patterns for the management of zone 1 open globe injuries among corneal specialists, which presents an opportunity to investigate whether certain treatment options lead to better outcomes in these injuries.
Neuroinflammation drives sex-dependent effects on pain and negative affect in a murine model of repeated mild traumatic brain injury
Authors: Liu Shiwei (Steve) , Pickens Sarah , Barta Zack , Rice Myra , Dagher Merel , Lebens Ryan , Nguyen Theodore V. , Cummings Brian J. , Cahill Catherine M.
Published: November 2023

The Center for Disease Control and Prevention estimates that 75% of reported cases of traumatic brain injury (TBI) are mild, where chronic pain and depression are 2 of the most common symptoms. In this study, we used a murine model of repeated mild TBI to characterize the associated pain hypersensitivity and affective-like behavior and to what extent microglial reactivity contributes to these behavioral phenotypes. Male and female C57BL/6J mice underwent sham or repeated mild traumatic brain injury (rmTBI) and were tested for up to 9 weeks postinjury, where an anti-inflammatory/neuroprotective drug (minocycline) was introduced at 5 weeks postinjury in the drinking water. Repeated mild traumatic brain injury mice developed cold nociceptive hypersensitivity and negative affective states, as well as increased locomotor activity and risk-taking behavior. Minocycline reversed negative affect and pain hypersensitivities in male but not female mice. Repeated mild traumatic brain injury also produced an increase in microglial and brain-derived neurotropic factor mRNA transcripts in limbic structures known to be involved in nociception and affect, but many of these changes were sex dependent. Finally, we show that the antiepileptic drug, gabapentin, produced negative reinforcement in male rmTBI mice that was prevented by minocycline treatment, whereas rmTBI female mice showed a place aversion to gabapentin. Collectively, pain hypersensitivity, increased tonic-aversive pain components, and negative affective states were evident in both male and female rmTBI mice, but suppression of microglial reactivity was only sufficient to reverse behavioral changes in male mice. Neuroinflammation in limbic structures seems to be a contributing factor in behavioral changes resulting from rmTBI.
Multimodal covarying brain patterns mediate genetic and psychological contributions to individual differences in pain sensitivity
Authors: Zhang Huijuan , Zhao Lei , Lu Xuejing , Peng Weiwei , Zhang Li , Zhang Zhiguo , Hu Li , Cao Jin , Tu Yiheng
Published: November 2023

Individuals vary significantly in their pain sensitivity, with contributions from the brain, genes, and psychological factors. However, a multidimensional model integrating these factors is lacking due to their complex interactions. To address this, we measured pain sensitivity (ie, pain threshold and pain tolerance) using the cold pressor test, collected magnetic resonance imaging (MRI) data and genetic data, and evaluated psychological factors (ie, pain catastrophizing, pain-related fear, and pain-related anxiety) from 450 healthy participants with both sexes (160 male, 290 female). Using multimodal MRI fusion methods, we identified 2 pairs of covarying structural and functional brain patterns associated with pain threshold and tolerance, respectively. These patterns primarily involved regions related to self-awareness, sensory-discriminative, cognitive-evaluative, motion preparation and execution, and emotional aspects of pain. Notably, pain catastrophizing was negatively correlated with pain tolerance, and this relationship was mediated by the multimodal covarying brain patterns in male participants only. Furthermore, we identified an association between the single-nucleotide polymorphism rs4141964 within the fatty acid amide hydrolase gene and pain threshold, mediated by the identified multimodal covarying brain patterns across all participants. In summary, we suggested a model that integrates the brain, genes, and psychological factors to elucidate their role in shaping interindividual variations in pain sensitivity, highlighting the important contribution of the multimodal covarying brain patterns as important biological mediators in the associations between genes/psychological factors and pain sensitivity.
Post-colonoscopy rectal cancer in Swedish patients with Crohn’s disease 2001–2015: a population-based case review study
Authors: Stjärngrim Jessica , Ekbom Anders , Widman Linnea , Hultcrantz Rolf , Forsberg Anna
Published: November 2023

Objective

Post-colonoscopy colorectal cancer (PCCRC) is a key quality indicator of colonoscopy, and PCCRC rates are high in the IBD population. Rectal cancer, an important risk factor for PCCRC among patients with Crohn’s disease (CD), has not previously been examined.

Methods

Swedish adult patients with CD who underwent a colonoscopy within 36 months before a rectal cancer diagnosis between 2001 and 2015 were identified through the National Patient and Cancer registers. Their medical records were reviewed and a root-cause analysis and a sub-categorization according to the World Endoscopic Organization (WEO) were performed.

Results

Of 24 patients with CD and PCCRC in the rectum, 79% were men and the median age was 50 (IQR 45–59) years. The median disease duration was 21.5 (IQR 19–30) years. The cancer was located in the distal 5 cm of the rectum in 63% of the cases. Retroversion in the rectum was reported in only one case. The most common plausible explanation for PCCRC was ‘possible missed lesion, prior examination adequate’ (63%); when adding retroversion in the rectum, instead 77% of examinations were considered negative but deemed as inadequate. The most common PCCRC sub-category was non-interval type C (54%) and B (37%). Among those with type C, 38% should have been included in surveillance according to present guidelines.

Conclusion

Better adherence to surveillance guidelines and more meticulous follow-up is warranted. The importance of performing rectal palpation and retroversion in the rectum is underscored and we suggest that this is included in the WEO algorithm.
A nomogram for analyzing risk factors of poor treatment response in patients with autoimmune hepatitis
Authors: Wang Xin , Liu Hui , Wang Peng , Wang Yuqi , Yi Yunyun , Li Xin
Published: November 2023

Objective

The objective of this study was to identify biochemical and clinical predictors of poor response (including incomplete response and non-response) to standard treatment in autoimmune hepatitis (AIH) patients.

Methods

This study retrospectively collected clinical data from 297 patients who were first diagnosed with AIH in Beijing Ditan Hospital from 2010 to 2019. Finally, 149 patients were screened out. Risk factors were screened by univariate and multifactorial logistic regression. Then they were used to establish the nomogram. The ROC curve, calibration curve, decision curves analysis (DCA) and clinical impact curves (CIC) were used to evaluate the nomogram.

Results

149 patients were divided into two groups: the response group (n = 120, 80%) and the poor response group (n = 29, 20%). Multivariate logistic regression analysis found that IgG > 26.5 g/L (OR: 22.016; 95% CI: 4.677–103.640) in AIH patients increased the risk. In contrast, treatment response status was better in women (OR: 0.085; 95% CI: 0.015–0.497) aged >60 years (OR: 0.159; 95% CI: 0.045–0.564) with AST > 4.49 × ULN (OR: 0.066; 95% CI: 0.009–0.494). The C index (0.853) and the calibration curve show that the nomogram is well differentiated and calibrated; the DCA and CIC indicate that the model has good clinical benefits and implications.

Conclusion

The study found that male patients aged ≤ 60 years with IgG > 26.5 g/L and elevated AST ≤ 4.49 × ULN were more likely to have a non-response/incomplete response to standard treatment.
A novel risk score model of esophageal stricture for patients undergoing endoscopic submucosal dissection
Authors: Yan Jin , Yang Zhen , Gao Li , He Lu , Chen Meihong , Ding Hailong , Shen Rongrong , Gong Yaoyao , Zhang Guoxin
Published: November 2023

Background and purpose

Endoscopic submucosal dissection (ESD) is a promising technique for superficial esophageal lesions. However, stricture is a frequent adverse complication. This study was performed to develop a precise and convenient score prediction model for esophageal strictures after ESD, and compare its efficacy with a previously published predictive model.

Methods

This study enrolled clinical data of patients who underwent esophageal ESD for superficial esophageal lesions. Possible risk factors for esophageal stricture were identified by univariate and multivariate logistic regression analysis. Then we developed a prediction model according to the Framingham system for the first time and presented a convenient table containing the risk probability for each patient. In addition, we validated our score model and the previously published model in our center.

Results

A total of 838 patients were enrolled in this study and 6 variables, including age, surgery time, location of the lesion, circumference of the lesion, longitudinal resection length, and depth of infiltration were comprised in the score model. The total score ranged from 0 to 16 points and the risk probability was presented in one concise table for each patient. Areas under receiver-operator characteristic curves for the prediction model were 0.715 in derivation group and 0.804 in validation group.

Conclusion

We designed and validated a prediction score model for esophageal stricture after ESD, which can be applied conveniently to stratify the stricture risk after esophageal ESD and may facilitate appropriate clinical decision-making for these patients.
The Price of Practice Change
Authors: Lehman Valerie E.R. , Siegel Joanna E. , Chiang Ethan N.
Published: November 2023

Background:

Clinicians, health care administrators, and implementation scientists know that it takes intentional effort, resources, and implementation strategies to integrate research findings into routine clinical practice. An oft-cited concern for those considering whether and how to implement an evidence-based program is how much it will cost to implement the change. Yet information about the cost of implementation is not often available to health care decision-makers. Teams that received Implementation Award funding from PCORI are conducting implementation projects to promote the uptake of evidence-based practices in health care settings. As part of their implementation efforts, a number of teams have examined the costs of implementation. In this Topical Collection, 5 teams will report their findings on implementation costs and discuss their methods for data collection and analysis.

Discussion:

The teams’ costing efforts provide specific information about the costs sites can expect to incur in promoting the uptake of specific evidence-based programs. In addition, the papers illuminate 3 key features of the teams’ approaches to measuring the cost of implementation: (1) the use of specific micro-costing methods with time-driven activity-based costing serving as the most popular method; (2) different ways to categorize and organize costs, including a site-based and non-site-based framework; and (3) cost collection challenges experienced by the teams.

Conclusion:

The cost of implementation is a critical consideration for organizations seeking to improve practice in accordance with research findings. This Topical Collection describes detailed approaches to providing this type of cost information and highlights insights to be gained from a rigorous focus on implementation cost.
Prevalence of Curable Sexually Transmitted Infections in a Population-Representative Sample of Young Adults in a High HIV Incidence Area in South Africa
Authors: Jarolimova Jana , Chidumwa Glory , Chimbindi Natsayi , Okesola Nonhlanhla , Dreyer Jaco , Smit Theresa , Seeley Janet , Harling Guy , Copas Andrew , Baisley Kathy , Shahmanesh Maryam ,   the Isisekelo Research Group, Herbst (Carina , McGrath Nuala , Zuma Thembelihle , Khoza Thandeka , Behuhuma Ngundu , Bassett Ingrid V. , Sherr Lorraine
Published: November 2023

Background

Recent population-representative estimates of sexually transmitted infection (STI) prevalence in high HIV burden areas in southern Africa are limited. We estimated the prevalence and associated factors of 3 STIs among adolescents and young adults (AYA) in rural South Africa.

Methods

Between March 2020 and May 2021, a population-representative sample of AYA aged 16 to 29 years were randomly selected from a Health and Demographic Surveillance Site in rural KwaZulu-Natal, South Africa, for a 2 × 2 factorial randomized controlled trial. Participants in 2 intervention arms were offered baseline testing for gonorrhea, chlamydia, and trichomoniasis using GeneXpert. Prevalence estimates were weighted for participation bias, and logistic regression models were used to assess factors associated with STIs.

Results

Of 2323 eligible AYA, 1743 (75%) enrolled in the trial. Among 863 eligible for STI testing, 814 (94%) provided specimens (median age of 21.8 years, 52% female, and 71% residing in rural areas). Population-weighted prevalence estimates were 5.0% (95% confidence interval [CI], 4.2%–5.8%) for gonorrhea, 17.9% (16.5%–19.3%) for chlamydia, 5.4% (4.6%–6.3%) for trichomoniasis, and 23.7% (22.2%–25.3%) for any STI. In multivariable models, female sex (adjusted odds ratio [aOR], 2.24; 95% CI, 1.48–3.09) and urban/periurban (vs. rural) residence (aOR, 1.48; 95% CI, 1.02–2.15) were associated with STIs; recent migration was associated with lower odds of STI (aOR, 0.37; 95% CI, 0.15–0.89). Among those with an STI, 53 (31.0%) were treated within 7 days; median time to treatment was 11 days (interquartile range, 6–77 days).

Conclusions

We identified a high prevalence of curable STIs among AYA in rural South Africa. Improved access to STI testing to enable etiologic diagnosis and rapid treatment is needed.
Advantages of a High-Powered Ultrasonic Vibration Cutting Device for Orthognathic Surgeries
Authors: Sato Akimitsu , Imai Yoshimichi
Published: November 2023

This study aimed to evaluate the advantages of using a high-powered ultrasonic vibration cutting device (HP-UVCD) in orthognathic surgeries. We analyzed 22 consecutive patients who underwent Le FortⅠosteotomy and bilateral sagittal split osteotomies for cleft lip and palate. We used conventional power instruments, such as reciprocating saws and rotating burrs in the first 10 patients, and an HP-UVCD in the remaining 12 patients. Surgical time, intraoperative blood loss, and postoperative inferior alveolar nerve affection were retrospectively investigated. The surgical time in the ultrasonic group (223±12.217 min) was significantly shorter than that in the conventional group (278±11.153 min, P=0.008). The amount of intraoperative blood loss in the ultrasonic group was an average of 230±45.154 g, and that in the conventional group was an average of 343±49.463 g. Although the blood loss in the ultrasonic group was reduced compared with that in the conventional group, this difference was not statistically significant (P=0.118). All patients in both groups recovered normal sensation by 6 months postoperatively. Our findings suggest that the HP-UVCD can be used in place of a reciprocating saw or rotating burrs in orthognathic surgeries, resulting in reduced surgical time and minimal blood loss. The use of an ultrasonic bone-cutting device may allow for a safer and less invasive orthognathic surgery.
Associated Risk Factors for Extended Length of Stay Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database
Authors: Hengartner Astrid C. , Serrato Paul , Sayeed Sumaiya , Prassinos Alexandre J. , Alperovich Michael , DiLuna Michael , Elsamadicy Aladine A.
Published: November 2023

Objectives:

The aim of this study was to identify the factors associated with extended length of stay (LOS) for pediatric patients with craniosynostosis undergoing cranial vault remodeling (CVR).

Methods:

A retrospective cohort study was performed using the 2012 to 2021 American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients below 2 years old with craniosynostosis who underwent CVR were identified using Current Procedural Terminology and International Classification of Diseases-9/10 codes. Patients were dichotomized according to whether they encountered an extended postoperative hospital LOS, which was defined as LOS greater than the 75th percentile for the entire cohort (4 days). Patient demographics, comorbidities, intraoperative variables, postoperative adverse events, and health care resource utilization were assessed. Multivariate logistic regression analysis was utilized to identify predictors of prolonged LOS.

Results:

In our cohort of 9784 patients, 1312 (13.4%) experienced an extended LOS. The extended LOS cohort was significantly older than the normal LOS cohort (normal LOS: 225.1±141.8 d vs. extended LOS: 314.4±151.7 d, P<0.001) and had a smaller proportion of non-Hispanic white patients (normal LOS: 70.0% vs. extended LOS: 61.2%, P<0.001). Overall, comorbidities and adverse events were significantly higher in the extended LOS cohort than the normal LOS cohort. On multivariate logistic regression, independent associations of extended LOS included age, race and ethnicity, weight, American Society of Anesthesiologists classification, impaired cognitive status, structural pulmonary abnormalities, asthma, and neuromuscular disorders.

Conclusions:

This study demonstrates that age, race, comorbidities, and perioperative complications contribute to extended LOS after CVR for craniosynostosis. Further investigations to further elucidate the risk factors of extended LOS is warranted to optimize patient outcomes.
Oral Rehabilitation of Marginal Maxillectomy Patient After Local Flap Reconstruction
Authors: Silva Isadora França Vieira da , Vilela Camila Rocha , Rocha Amanda Leal , Souza Leandro Napier de , Moreno Amália , Jardilino Francisca Daniele Moreira
Published: November 2023

The treatment of oral cancer can lead to various oral complications, including oral defects, tissue deformation, and trismus in patients who have undergone oral cancer surgery with resection of any part of the maxillary. Restoring the ability to chew, swallow, and maintain esthetics is essential and a significant challenge. The aim of this study was to report a successful clinical case of preprosthetic surgery and prosthetic rehabilitation of a 65-year-old man who had undergone marginal maxillectomy, resulting in tissue scarring and a significant reduction in maximal mouth opening. The oral rehabilitation was achieved using a conventional removable prosthesis. This case demonstrates that preprosthetic surgery combined with conventional removable prosthesis is an effective strategy for complex rehabilitations providing functional and esthetic improvement in the affected area for patients with marginal maxillectomies resulting from oral cancer.