bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical presentation and outcomes of Mooren’s ulcer: a 2-year retrospective cohort study
Authors: Atima Mayor Orezime , Idakwo Ugbede , Komolafe Oyeronke , Shimizu Eisuke , Shintaro Nakayama , Balogun Emmanuel Oluwadare , Dingwoke Emeka John , Orugun Ayodele Jacob 
Published: April 2024

Background:
Mooren’s ulcer is a chronic, painful, unrelenting, peripheral ulcerative keratitis with atypical geographic presentation and distribution. This study aimed to retrospectively investigate the clinical presentation and outcomes of patients with Mooren’s ulcer over a 2-year period at the Evangelical Church Winning All (ECWA) Eye Hospital, Kano, Nigeria.

Methods:
The theatre records of 24 patients with Mooren’s ulcer were retrospectively reviewed, with a focus on those who had up to 2 years of follow-up. The surgical treatment followed a standard procedure of 3 ml of 2% xylocaine and 0.01% adrenaline were administered for peribulbar anaesthesia. The periorbital area was cleaned with 10% povidone iodine, draped, and a lid speculum was inserted to part the lids. The conjunctiva was excised 2 mm from the edge of the ulcer, and the area was lightly cauterized. This was followed by a combination of subconjunctival injection of 2 mg of dexamethasone and 20 mg of gentamycin and a drop of 0.3% of ciprofloxacin and 1% of atropine. Data were analyzed using a social science statistical package (IBM SPSS Inc. Chicago V 19.0) with 95% confidence.

Results:
The results revealed that Mooren’s ulcer was predominant in an age range of 11 and 30 years. A total number of 24 patients were seen in the two years of review, with an average age of 27.3±13.7 years. There were 19 male and 5 female patients, with a male-to-female ratio of 3.8:1. At presentation, patients had poor preoperative vision, with acuity values of less than 6/60–3/60 range. Postoperatively, 15

eyes had a borderline outcome (cannot see 6/18 but can see 6/60), 12

eyes had good vision (VA 6/18) and 4

eyes ended up with the same presenting vision (VA<6/60) after treatment. One patient had iris prolapse and three patients had evisceration.

Conclusions:
This study provided the clinical characteristics of patients with Mooren’s corneal ulcer. A comparison of preoperative and postoperative visual acuity showed that early presentation and intervention improved visual outcomes. Although most eyes maintained or improved vision, nearly half demonstrated a borderline result that fell short of the target vision threshold. The retrospective nature of this study limited its ability to review complete patient information. The small sample size also constrained the analysis due to the low incidence of Mooren’s ulcer. Further research is needed to better understand increased susceptibility in younger populations. This will help inform prevention and treatment efforts to address this public health challenge.
A randomized controlled trial of a postdischarge nursing intervention for patients with decompensated cirrhosis
Authors: Barfod O’Connell Malene , Brødsgaard Anne , Matthè Maria , Hobolth Lise , Wullum Laus , Bendtsen Flemming , Kimer Nina 
Published: April 2024

Background:
Few randomized trials have evaluated the effect of postdischarge interventions for patients with liver cirrhosis. This study assessed the effects of a postdischarge intervention on readmissions and mortality in patients with decompensated liver cirrhosis.

Methods:
We conducted a randomized controlled trial at a specialized liver unit. Adult patients admitted with complications of liver cirrhosis were eligible for inclusion. Participants were allocated 1:1 to standard follow-up or a family-focused nurse-led postdischarge intervention between December 1, 2019, and October 31, 2021. The 6-month intervention consisted of a patient pamphlet, 3 home visits, and 3 follow-up telephone calls by a specialized liver nurse. The primary outcome was the number of readmissions due to liver cirrhosis.

Results:
Of the 110 included participants, 93% had alcohol as a primary etiology. We found no significant differences in effects in the primary outcomes such as time to first readmission, number of patients readmitted, and duration of readmissions or in the secondary outcomes like health-related quality of life and 6- and 12-month mortality. A post hoc exploratory analysis showed a significant reduction in nonattendance rates in the intervention group (RR: 0.28, 95% CI: 0.13–0.54, p=0.0004) and significantly fewer participants continuing to consume alcohol in the intervention group (p=0.003). After 12 months, the total number of readmissions (RR: 0.76, 95% CI: 0.59–0.96, p=0.02) and liver-related readmissions (RR: 0.55, 95% CI: 0.36–0.82, p=0.003) were reduced in the intervention group.

Conclusions:
A family-focused postdischarge nursing intervention had no significant effects on any of the primary or secondary outcomes. In a post hoc exploratory analysis, we found reduced 6-month nonattendance and alcohol consumption rates, as well as reduced 12-month readmission rates in the intervention group.
Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1
Authors: Ates Ilayda , Stuart Callie , Rathbone Tanner , Barzi Mercedes , He Gordon , Major Angela M. , Shankar Vijay , Lyman Rachel A. , Angner Sidney S. , Mackay Trudy F.C. , Srinivasan Shanthi , Farris Alton Brad , Bissig Karl-Dimiter , Cottle Renee N. 
Published: April 2024

Background:
We previously demonstrated the successful use of in vivo CRISPR gene editing to delete 4-hydroxyphenylpyruvate dioxygenase (HPD) to rescue mice deficient in fumarylacetoacetate hydrolase (FAH), a disorder known as hereditary tyrosinemia type 1 (HT1). The aim of this study was to develop an ex vivo gene-editing protocol and apply it as a cell therapy for HT1.

Methods:
We isolated hepatocytes from wild-type (C57BL/6J) and Fah
−/− mice and then used an optimized electroporation protocol to deliver Hpd-targeting CRISPR-Cas9 ribonucleoproteins into hepatocytes. Next, hepatocytes were transiently incubated in cytokine recovery media formulated to block apoptosis, followed by splenic injection into recipient Fah

−/−
mice.

Results:
We observed robust engraftment and expansion of transplanted gene-edited hepatocytes from wild-type donors in the livers of recipient mice when transient incubation with our cytokine recovery media was used after electroporation and negligible engraftment without the media (mean: 46.8% and 0.83%, respectively; p=0.0025). Thus, the cytokine recovery medium was critical to our electroporation protocol. When hepatocytes from Fah

−/−
mice were used as donors for transplantation, we observed 35% and 28% engraftment for Hpd-Cas9 ribonucleoproteins and Cas9 mRNA, respectively. Tyrosine, phenylalanine, and biochemical markers of liver injury normalized in both Hpd-targeting Cas9 ribonucleoprotein and mRNA groups independent of induced inhibition of Hpd through nitisinone, indicating correction of disease indicators in Fah

−/−
mice.

Conclusions:
The successful liver cell therapy for HT1 validates our protocol and, despite the known growth advantage of HT1, showcases ex vivo gene editing using electroporation in combination with liver cell therapy to cure a disease model. These advancements underscore the potential impacts of electroporation combined with transplantation as a cell therapy.
Vascular adhesion protein-1 blockade in primary sclerosing cholangitis: Open-label, multicenter, single-arm, phase II trial
Authors: Hirschfield Gideon M. , Arndtz Katherine , Kirkham Amanda , Chen Yung-Yi , Fox Richard , Rowe Anna , Douglas-Pugh Jessica , Thorburn Douglas , Barnes Eleanor , Aithal Guruprasad P. , Hull Diana , Bhandal Khushpreet , Olsen Kathryn , Woodward Paul , Lax Siân , Newsome Philip , Smith David J. , Kallio Antero , Adams David H. , Homer Victoria , Weston Chris J. 
Published: April 2024

Background:
Primary sclerosing cholangitis is a progressive inflammatory liver disease characterized by biliary and liver fibrosis. Vascular adhesion protein-1 (VAP-1) is important in the inflammatory process driving liver fibrosis. We evaluated the safety and efficacy of VAP-1 blockade with a monoclonal antibody (timolumab, BTT1023) in patients with primary sclerosing cholangitis.

Methods:
BUTEO was a prospective, single-arm, open-label, multicenter, phase II trial, conducted in 6 centers in the United Kingdom. Patients with primary sclerosing cholangitis aged 18–75 years had an alkaline phosphatase value of >1.5 times the upper limit of normal. The dose-confirmatory stage aimed to confirm the safety of timolumab through the incidence of dose-limiting toxicity and sufficient trough levels of circulating antibody to block VAP-1 function. The primary outcome of the dose-expansion portion of the trial was patient’s response to timolumab at day 99, as measured by a reduction in serum alkaline phosphatase by 25% or more from baseline to day 99.

Results:
Twenty-three patients were recruited: 7 into the initial dose-confirmatory stage and a further 16 into an expansion stage. Timolumab (8 mg/kg) was confirmed to be safe for the duration of administration with sufficient circulating levels. Only 2 of the 18 evaluable patients (11.1%) achieved a reduction in alkaline phosphatase levels of 25% or more, and both the proportion of circulating inflammatory cell populations and biomarkers of fibrosis remained unchanged from baseline.

Conclusions:
The BUTEO trial confirmed 8 mg/kg timolumab had no short-term safety signals and resulted in sufficient circulating levels of VAP-1 blocking timolumab. However, the trial was stopped after an interim assessment due to a lack of efficacy as determined by no significant change in serum liver tests.
A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids
Authors: Hehl Leonida , Creasy Kate T. , Vitali Cecilia , Scorletti Eleonora , Seeling Katharina S. , Vell Mara S. , Rendel Miriam D. , Conlon Donna ,   Regeneron Genetics Center, Vujkovic Marijana , Zandvakili Inuk , Trautwein Christian , Schneider Kai M. , Rader Daniel J. , Schneider Carolin V. 
Published: April 2024

Background:
Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear.

Methods:
We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank.

Results:
Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His carriers were associated with significantly higher serum levels of HDL cholesterol and alanine aminotransferase. Carriers homozygous for MLXIPL Gln241His showed a higher risk of SLD in 2 unrelated cohorts. Carriers of MLXIPL Gln241His were especially more likely to be diagnosed with SLD if they were female, obese, and/or also carried the PNPLA3 I148M variant. Furthermore, the heterozygous carriage of MLXIPL Gln241His was associated with significantly higher all-cause, liver-related, and cardiovascular mortality rates. Nuclear magnetic resonance metabolomics data indicated that carriage of MLXIPL Gln241His was significantly associated with lower serum levels of VLDL and increased serum levels of HDL cholesterol.

Conclusions:
Analyses of the MLXIPL Gln241His polymorphism showed a significant association with a higher risk of SLD diagnosis and elevated serum alanine aminotransferase as well as significantly lower serum triglycerides and apolipoprotein-B levels. MLXIPL might, therefore, be a potential pharmacological target for the treatment of SLD and hyperlipidemia, notably for patients at risk. More mechanistic studies are needed to better understand the role of MLXIPL Gln241His on lipid metabolism and steatosis development.
Precise subcellular organelle-targeted analyses of the hepatotoxicity of rhubarb
Authors: Wu Jianzhi , Ma Zhi , Zhang Yinhao , Duan Shuni , Sun Rong , Liu Runping , Li Yijie , Li Xiaojiaoyang 
Published: April 2024

Objective:
Drug-induced liver injury (DILI) is the leading cause of acute liver failure and poses a significant challenge to human health. Rhubarb (Rheum officinale Baill. DaHuang) has been clinically used for its heat-clearing and diuresis-promoting effects. However, its toxic effects on different organelles in the liver require further validation.

Methods:
We analyzed the potential targets affecting hepatotoxicity in rhubarb and the potential damage relationship with five major organelles, including microsomes, mitochondria, endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes through Integrated Traditional Chinese Medicine (ITCM)/HERB databases and network pharmacology. We isolated and purified different organelles, incubated them with different fractions and monomers of rhubarb in an adenosine triphosphate (ATP) culture system and examined the structural and functional changes in the organelles using particle size analysis and molecular biological experiments to investigate whether rhubarb affects the damage and rupture of major organelles in the liver.

Results:
By combining virtual predictions and experimental verification, our research confirmed that emodin isolated from the anthraquinone of rhubarb, catechin in the tannins of rhubarb, and palmitic acid in the organic acids of rhubarb caused the most significant functional and structural damage to the representative organelles. Among all the monomeric compounds, emodin caused the most damage to the microsome, mitochondria, ER, and lysosome; catechin induced microsome and GA damage; and palmitic acid caused the most damage to microsomes and GA in the liver, suggesting that rhubarb components may exert hepatotoxicity through multi-organelle injury.

Conclusions:
Our findings revealed that rhubarb has varying degrees of damaging effects on different organelles, which in turn affects cellular life activities by impairing organelle morphology and function. This study provides a theoretical basis and technical support for a refined analysis of the toxic components and targets of rhubarb.
Perceived Work Demands and Emergency Department Crowding as Predictors of Objective Stress Among Emergency Physicians
Authors: Britt Thomas W. , Pirrallo Ronald G. , Rosopa Patrick J. , Hirsh Emily , Moschella Phillip , Bessey Alexxa , Klinefelter Zachary , Barrows Caroline , Reddy Kaustubha , Faulkner Madisen , Fowler Lauren A. 
Published: April 2024

Objective
To understand shift-level determinants of emergency physician (EP) burnout, relationships were tested between EP shift demands, stress, and fatigue.

Method
EP (n = 16) were assessed over 114 shifts that occurred before and during the COVID-19 pandemic. Salivary cortisol (an indicator of stress) and self-reported fatigue were collected prior to and following each shift. An objective crowding score (National Emergency Department Overcrowding Scale) per shift was calculated. Shift demands were assessed at the end of each shift.

Results
Multilevel models revealed that shift demands, National Emergency Department Overcrowding Scale, and the pandemic were related to higher levels of end-of-shift cortisol, but not fatigue. Cortisol levels were higher for shifts with a higher number of demands, greater crowding, and during the pandemic.

Conclusions
Shift demands predicted objective indicators of stress, but not self-reported fatigue. Interventions are needed to decrease stress and shift demands to reduce EP burnout.
Impact of COVID-19 Pandemic on Tuberculosis and Latent Tuberculosis Infection Diagnosis in Healthcare Workers
Authors: Monaiar Luciana Rott , D'Avila Karen Gomes , Soccol Emanuelle Bianchi , Santos André Kulzer , de Braga Raimunda Sinthia Lima , Filho Fábio Fernandes Dantas , Silva Denise Rossato 
Published: April 2024

Objective
The aim of the study is to compare the prevalence of latent tuberculosis infection and tuberculosis (TB) in the prepandemic period (2017–2019) with the pandemic period (2020–2022), in a group of healthcare workers (HCWs).

Methods
This is a retrospective study. Data on TB diagnosis was retrieved from the hospital information system database. All HCWs who underwent tuberculin skin test (TST) from January 2017 to December 2022 were included in the study.

Results
In the prepandemic period (2017–2019), 163 HCWs out of 710 were TST positive (22.9%), and in the pandemic period (2020–2022), 85 HCWs out of 449 were TST positive (18.9%) (P = 0.11). There were 10 HCWs diagnosed with TB in the prepandemic period (incidence: 41.7/100,000) and 2 in the pandemic period (incidence: 8.3/100,000) (P < 0.0001).

Conclusions
This study showed that TB incidence was reduced during the pandemic period in HCWs. TST positivity was also reduced, though not statistically significant.
Transforming diabetes care with continuous glucose monitoring: Rationale for expanded eligibility criteria
Authors: Hirsch Barbara R. 
Published: April 2024

ABSTRACT
Randomized trials and large retrospective database studies have shown that individuals treated with noninsulin therapies experience the same glycemic benefits from continuous glucose monitoring (CGM) use as those treated with more intensive treatment regimens. However, many policy makers and payers are reluctant to provide CGM coverage for these patients. Although the recent American Diabetes Association guidelines have taken an important first step in recommending that CGM should be offered to all adults treated with basal insulin who are capable of using it, clinicians should consider the acute and long-term consequences of persistent hyperglycemia in all of their patients with diabetes. This article describes how the use of the FreeStyle Libre 2 CGM System (Abbott Diabetes Care, Alameda, CA) improved glycemic outcomes and facilitates personalized diabetes care in two type 2 diabetes patients treated with noninsulin therapies.
Bibliometric study and visualization of cellular senescence associated with osteoarthritis from 2009 to 2023
Authors: Ding Xueting , Huang Jingrui , Zhou Raorao , Che Xianda , Pang Yiming , Liang Dan , Lu Chengyang , Zhuo Yuhao , Cao Fuyang , Wu Gaige , Li Wenjin , Li Penghua , Zhao Litao , Rong XueQin , Li Pengcui , Wang Chunfang 
Published: April 2024

Background:
Osteoarthritis is a common degenerative joint disease that is highly prevalent in the elderly population. Along with the occurrence of sports injuries, osteoarthritis is gradually showing a younger trend. Osteoarthritis has many causative factors, and its pathogenesis is currently unknown. Cellular senescence is a stable form of cell cycle arrest exhibited by cells in response to external stimuli and plays a role in a variety of diseases. And it is only in the last decade or so that cellular senescence has gradually become cross-linked with osteoarthritis. However, there is no comprehensive bibliometric analysis in this field. The aim of this study is to present the current status and research hotspots of cellular senescence in the field of osteoarthritis, and to predict the future trends of cellular senescence in osteoarthritis research from a bibliometric perspective.

Methods:
This study included 298 records of cellular senescence associated with osteoarthritis from 2009 to 2023, with data from the Web of Science Core Collection database. CiteSpace, Scimago Graphica software, VOSviewer, and the R package “bibliometrix” software were used to analyze regions, institutions, journals, authors, and keywords to predict recent trends in cellular senescence related to osteoarthritis research.

Results:
The number of publications related to cellular senescence associated with osteoarthritis is increasing year by year. China and the United States contribute more than 70% of the publications and are the mainstay of research in this field. Central South University is the most active institution with the largest number of publications. International Journal of Molecular Sciences is the most popular journal in the field with the largest number of publications, while Osteoarthritis and Cartilage is the most cited journal. Loeser, Richard F. is not only the most prolific author, but also the most frequently cited author, contributing greatly to the field.

Conclusion:
In the last decade or so, this is the first bibliometric study that systematically describes the current status and development trend of research on cellular senescence associated with osteoarthritis. The study comprehensively and systematically summarizes and concludes the research hotspots and development trends, providing valuable references for researchers in this field.
Effect of different oral anticoagulants on cognitive function in patients with atrial fibrillation: A Bayesian network meta-analysis
Authors: Ning Wanling , Wang Shiheng , Tang Hanqing , Wu Sichu , Huang XiaoSong , Liu Baiyan , Mao Yilin 
Published: April 2024

Background:
Atrial fibrillation (AF) is 1 of the most common types of arrhythmias. At present, the treatment for patients with AF mainly includes oral anticoagulants (OACs). Studies have shown that OACs are associated with cognitive decline in patients with atrial fibrillation; however, there is a lack of relevant evidence. This study used Bayesian network meta-analysis (NMA) to investigate the effects of different oral anticoagulants on cognitive decline in patients with AF.

Methods:
We systematically searched for clinical studies on oral anticoagulants in patients with AF in PubMed, Web of Science, Embase, and the Cochrane Library as of July 3, 2023. Cochrane’s randomized controlled trial bias risk assessment tool and the Newcastle–Ottawa Scale were used to assess the bias risk of the included studies. The main outcome measure was decreased cognitive functioning.

Results:
Ten studies were included, including 2 RCTs and 7 RCSs, including 882,847 patients with AF. Five oral anticoagulants and 2 anticoagulants were included: VKAs (especially warfarin), Dabigatran, Edoxaban, Rivaroxaban, Apixaban, and Aspirin, Clopidogrel. The results of the mesh meta-analysis showed that VKAs were superior to warfarin in reducing the risk of cognitive decline in patients with AF (OR = −1.19, 95% CI (−2.35, −0.06), P < .05) (Table 5). The top 3 drugs in terms of the probability of reducing the incidence of cognitive impairment in patients with AF with different oral anticoagulants were VKAs (87%), rivaroxaban (62.2%), and dabigatran (60.8%).

Conclusion:
Based on the results of this study, VKAs may be the best intervention measure for reducing the risk of cognitive decline in patients with AF. Owing to the limitations of this study, more high-quality randomized controlled trials with large sample sizes and multiple centers are required to provide more evidence.