bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary Microvascular Dysfunction Is Present Among Well-Treated Asymptomatic Persons With HIV and Similar to Those With Diabetes
Authors: Srinivasa Suman , Walpert Allie R , Huck Daniel , Thomas Teressa S , Dunderdale Carolyn N , Lee Hang , Dicarli Marcelo F , Adler Gail K , Grinspoon Steven K
Published: April 2024

Background

Coronary microvascular dysfunction (CMD) could be a potential underlying mechanism for myocardial disease in HIV.

Methods

Comparisons of coronary flow reserve corrected for heart rate-blood pressure product (CFRCOR) were made among people with HIV (PWH) with no known history of cardiovascular disease (CVD) or diabetes mellitus, persons without HIV (PWOH), and persons with diabetes (PWDM) and no known history of CVD or HIV.

Results

PWH (n = 39, 74% male, age 55 [7] years, body mass index [BMI] 32.3 (26.8-34.9) kg/m2, duration of antiretroviral therapy 13 [5] years, CD4+ count 754 [598-961] cells/μL) were similar to PWOH (n = 69, 74% male, age 55 [8] years, BMI 32.2[25.6-36.5] kg/m2) and PWDM (n = 63, 63% male, age 55 [8] years, BMI 31.5 [28.6-35.6] kg/m2). CFRCOR was different among groups: PWOH 2.76 (2.37-3.36), PWH 2.47 (1.92-2.93), and PWDM 2.31 (1.98-2.84); overall P = .003. CFRCOR was reduced comparing PWH to PWOH (P = .04) and PWDM to PWOH (P = .007) but did not differ when comparing PWH to PWDM (P = .98). A total 31% of PWH had CFRCOR < 2.0, a critical cutoff for CMD, compared to 14% of PWOH and 27% with PWDM. A total 40% of women with HIV had a CFRCOR < 2.0 compared to 6% of women without HIV (P = .02).

Conclusions

Subclinical CMD is present among chronically infected and well-treated, asymptomatic PWH who are immunologically controlled. This study demonstrates CFR is reduced in PWH compared to PWOH and comparable to PWDM, further highlighting that well-treated HIV infection is a CVD-risk enhancing factor for CMD similar to diabetes.

Clinical Trials Registration: NCT02740179
Unusual initial presentation of prostate adenocarcinoma with inguinal lymph nodes metastases: a case report
Authors: Glavinov Maja Sofronievska , Jovanovic Rubens , Majstorov Venjamin , Burneski Jovo , Nikolovski Andrej
Published: April 2024

The presence of lymph node metastases in prostate adenocarcinoma is a poor prognostic sign, and mortality rates are often high. Inguinal lymph node metastases are an unusual presentation of advanced disease, and they can be easily misinterpreted with other diseases. We present a case of a 63-year-old patient with no previous symptoms and signs of prostate disorder with a right-sided inguinal lump and abdominal pain. The CT scan showed right inguinal and retroperitoneal lymphadenopathy. Elevated PSA serum levels, digital rectal examination, and skeletal scintigraphy with 99mTc-MDP favored the diagnosis of metastatic prostate adenocarcinoma. Since the patient denied prostate biopsy, a dissection of the right inguinal nodes was performed. Histopathological findings confirmed metastatic prostate adenocarcinoma. The treatment was hormonal and bisphosphonate therapy, with objective posttreatment improvement. Based on this case, it can be concluded that inguinal and generalized lymphadenopathy are potential initial manifestations of metastatic prostate adenocarcinoma in male patients.
The role of cardiac computed tomography in diagnostic and prognostic assessment of pregnancy related spontaneous coronary artery dissection: a case report
Authors: Luciano Alessandra , Cerimele Cecilia , Mecchia Daniele , Mozzani Marcello , Steffani Simone , D’Errico Francesca , Di Donna Carlo , De Stasio Vincenzo , Garaci Francesco , Chiocchi Marcello
Published: April 2024

Spontaneous coronary artery dissection (SCAD) is the most common cause of myocardial infarction during pregnancy or the postpartum period and has a major impact on cardiovascular morbidity and death in pregnant women. A 38-year-old woman with sudden cardiac arrest ten days postpartum urgently underwent coronarography, which showed an intraparietal hematoma of the left anterior descending (LAD) artery. Two days later, coronary computed tomography angiography (CCTA) was performed, which showed the evidence of SCAD in the mid-distal tract of LAD and the presence of transmural ischemic infarction in the apex and mid antero-septal wall in delayed acquisition. The patient was treated with a beta-blocker. Four months later CCTA showed complete resolution of SCAD and evolution of the infarcted areas. Given the high accuracy and noninvasiveness of CCTA, our case highlights the potential role of this imaging modality in the diagnosis and follow-up of pregnancy associated SCAD.
Buschke-Lowenstein tumor in the penis and anorectal region: case report
Authors: Kabila Badr , Imrani Kaoutar , Kaddouri Soufiane , Boujida Ismail , Zouaidia Fouad , Billah Nabil Moatassim , Nassar Itimad
Published: April 2024

The Buschke-Lowenstein Tumor is a giant condyloma acuminatum caused by human papillomavirus, most commonly types 6 or 11. It is a rare condition with an estimated frequency of 0.1% in the general population. Transmission primarily occurs through sexual contact. It particularly affects men, predominantly appearing on the penis, characterized by its deep-seated growth, potential for degeneration, and tendency to recur after treatment. Surgery is the preferred treatment. We present the case of a50-year-old patient with a history of recurrent urethritis and multiple sexual partners. The patient sought medical attention for a swelling on the penis that had been progressively developing over the past 10 years. An MRI was performed for a locoregional study, revealing a perineal and penile mass with polylobed contours resembling a cauliflower, along with a sizable perineal mass Histological examination of a biopsy sample from the penis confirmed the diagnosis. Unfortunately, due to the tumor’s characteristics and the patient’s condition, surgery was contraindicated.
A novel cause of erythromelalgia due to pseudoephedrine
Authors: Kravvas Georgios , Aboukhatwah Nada , Ali Lana , Bray Adam P
Published: April 2024

Objective

Erythromelalgia is a rare, highly debilitating disorder characterised by severe episodes of discomfort, erythema, and desquamation of the extremities. Its causes include genetic factors, medications, and several underlying medical conditions. This paper describes a novel cause of erythromelalgia through a case report and literature review.

Case description

A 47-year-old Caucasian man presented with a two-year history of intermittent pain, redness and desquamation of the hands. He experienced several such episodes, each lasting 3-4 weeks. A skin biopsy confirmed the diagnosis of erythromelalgia. After several recurrences, he admitted to the intermittent use of pseudoephedrine as a nasal decongestant, which coincided with the episodes of erythromelalgia. Complete resolution of symptoms was reported on cessation of this medication.

Conclusion

Pseudoephedrine has been reported to cause a wide range of cutaneous reactions but has not been known to precipitate erythromelalgia. Recognition of this rare side effect may offer early diagnosis and reduced morbidity.
Co-infection with plasmodium falciparum and COVID-19 with lethal outcome. First clinical case from Bulgaria
Authors: Velev Valeri , Atanassova Maria , Aksentieva Yana , Ahmet Fatme Melbahtin , Yordanova Ralica , Harizanov Rumen
Published: April 2024

The symptoms of COVID-19 include febrility and mainly catarrhal symptoms. In severe cases, patients present with progression to lower respiratory tract and acute respiratory distress (ARDS) and multi-organ dysfunction. Malaria caused by P. falciparum is a severe, endemic parasitosis, mainly in Africa. In some cases, it can be complicated with ARDS. We present a case of a patient who returned from Nigeria with respiratory symptoms, in which both COVID-19 infection and tropical malaria were proven; with a fatal outcome.
Perception of Polish patients with cancer of the ethical and legal issues related to biobank research
Authors: Domaradzki Jan , Czekajewska Justyna , Walkowiak Dariusz
Published: April 2024

Background

Although biobanks have become fundamental to many research centers and contribute to medical development, they generate many ethical and legal issues that may discourage patients from donating.

Materials and Methods

To understand patients’ perception of ethical and legal issues related to biobanks we conducted a survey among 548 Polish patients with cancer.

Results

While 93.1% of patients with cancer declared themselves willing to donate biospecimens left over after a medical procedure to a biobank, most opted for one-time consent or study-specific consent, blanket consent being less frequently preferred. Many patients believed that future use of previously collected tissues require second contact. Most patients preferred pseudonymization over anonymization of the data, and supported donors’ right to withdraw informed consent at any given moment. Finally, while personal health information was the most expected form of compensation for donation, most patients suggested that all parties, including the biobank concerned, the sponsors of the research, and the donors, should own the rights to cancer tissues donated and profit from the biobank research. Patients’ opinions on the ethical and legal issues related to biobank research were associated with age, sex, religiosity, education level, and place of residence.

Conclusions

Since biobanks generate ethical and legal issues related to informed consent, data protection and storage, as well as the sharing of biosamples, tissue ownership, and profit sharing, that may discourage patients from donation, when asking a patient for a donation, healthcare professionals should communicate in a donor-centered manner and address patients’ ethical and moral concerns related to donation and offer resources to help manage these concerns.
Drought-induced circular RNAs in maize roots: Separating signal from noise
Authors: Xu Jie , Wang Qi , Tang Xin , Feng Xiaoju , Zhang Xiaoyue , Liu Tianhong , Wu Fengkai , Wang Qingjun , Feng Xuanjun , Tang Qi , Lisch Damon , Lu Yanli
Published: April 2024

Circular RNAs (circRNAs) play an important role in diverse biological processes; however, their origin and functions, especially in plants, remain largely unclear. Here, we used 2 maize (Zea mays) inbred lines, as well as 14 of their derivative recombination inbred lines with different drought sensitivity, to systematically characterize 8,790 circRNAs in maize roots under well-watered (WW) and water-stress (WS) conditions. We found that a diverse set of circRNAs expressed at significantly higher levels under WS. Enhanced expression of circRNAs was associated with longer flanking introns and an enrichment of long interspersed nuclear element retrotransposable elements. The epigenetic marks found at the back-splicing junctions of circRNA-producing genes were markedly different from canonical splicing, characterized by increased levels of H3K36me3/H3K4me1, as well as decreased levels of H3K9Ac/H3K27Ac. We found that genes expressing circRNAs are subject to relaxed selection. The significant enrichment of trait-associated sites along their genic regions suggested that genes giving rise to circRNAs were associated with plant survival rate under drought stress, implying that circRNAs play roles in plant drought responses. Furthermore, we found that overexpression of circMED16, one of the drought-responsive circRNAs, enhances drought tolerance in Arabidopsis (Arabidopsis thaliana). Our results provide a framework for understanding the intricate interplay of epigenetic modifications and how they contribute to the fine-tuning of circRNA expression under drought stress.
RNA editing factor SlORRM2 regulates the formation of fruit pointed tips in tomato
Authors: Yang Yongfang , Ji Yajing , Wang Keru , Li Jinyan , Zhu Guoning , Ma Liqun , Ostersetzer-Biran Oren , Zhu Benzhong , Fu Daqi , Qu Guiqin , Luo Yunbo , Zhu Hongliang
Published: April 2024

Domestication of tomato (Solanum lycopersicum) has led to large variation in fruit size and morphology. The development of the distal end of the fruit is a critical factor in determining its overall shape. However, the intricate mechanisms underlying distal fruit development require further exploration. This study aimed to investigate the regulatory role of an organelle RNA recognition motif (RRM)-containing protein SlORRM2 in tomato fruit morphology development. Mutant plants lacking SlORRM2 exhibited fruits with pointed tips at the distal end. However, this phenotype could be successfully restored through the implementation of a “functional complementation” strategy. Our findings suggest that the formation of pointed tips in the fruits of the CR-slorrm2 mutants is linked to alterations in the development of the ovary and style. We observed a substantial decrease in the levels of indole-3-acetic acid (IAA) and altered expression of IAA-related response genes in the ovary and style tissues of CR-slorrm2. Moreover, our data demonstrated that SlORRM2 plays a role in regulating mitochondrial RNA editing sites, particularly within genes encoding various respiratory chain subunits. Additionally, the CR-slorrm2 mutants exhibited modified organellar morphology and increased levels of reactive oxygen species. These findings provide valuable insights into the mechanisms underlying the formation of fruit pointed tips in tomato and offer genetic resources for tomato breeding.
Tissue equivalent conversion of silicon-based microdosemeters in hadron therapy
Authors: Yu Songke , Shi Hui , Zhong Xiaojuan
Published: April 2024

Silicon has been developed as a microdosemeter, as it can provide sensitive volumes at submicrometric levels, does not need a gas supply, has a fast response, and has low power consumption. However, since the energy response in silicon is not the same as that in tissue, a spectral conversion from silicon to tissue is necessary to obtain the probability distribution of energy deposition in tissue. In this work, we present a method for microdosimetric spectra conversion from silicon to tissue based on the scaled Fourier transformation and the geometric scaling factor, which shows relatively good results in the spectral conversion from diamond to tissue. The results illustrate that the method can convert the energy deposition spectra from silicon to tissue with proper accuracy. Meanwhile, the inconsistency between the converted and actual spectra due to the inherent difference was also observed. Whereas, the reasons for the disagreement are different. For the plateau part of the Bragg curve, the discrepancy between the converted and actual spectra is due to the poor tissue equivalent of silicon. For the proximal part of the Bragg curve, the spectral difference is attributed to the different shapes of the energy deposition spectra obtained in silicon and water, which is the same as that in the diamond. In summary, this method can be employed in the tissue equivalent conversion of silicon microdosemeter, but the poor tissue equivalent of silicon limited the accuracy of this method. In addition, the correction for the deviation between the converted and calculated spectra due to the difference in spectral shapes is required to improve the practicality of this mod.
“It’s Complicated”: How Black and White Women Innovate with Situationships at Midlife
Authors: Armstrong Elizabeth A , Hamilton Laura T , Garrison Spencer A , Giles Kelly N , Hoffman Charity M , Perone Angela K
Published: April 2024

The sexual and romantic activities of unmarried women at midlife are often invisible in survey research based on normative categories of adult intimacy. However, women at this stage in the life course are structurally positioned to innovate with intimacy. In our interviews with 53 Black and white women between ages 33-58, outside of stable partnerships, and open to sex and intimacy with men, we find that women’s frustration with marriage and marriage-like commitment, negative experiences dating, and lack of interest in celibacy led them to experiment with a new form of intimacy. A majority engaged in ongoing liaisons in a liminal space between casual and committed—what emerging scholarship on the romantic relationships of Black women refer to as “situationships.” Black women, those with higher incomes, and queer-identified women were more likely to use situationships. We argue that women’s use of situationships challenged normative expectations that felt constraining to many at midlife and allowed women to enjoy the benefits of sexual and romantic company. Situationships enabled them to avoid casual sex and maintain autonomy and single identity. Finally, we highlight the disadvantages of situationships, emphasizing the importance of life stage and orientation to normative arrangements for situationship experiences.
Views of Intermarried Couples: Implications for Social Work Practice
Authors: Greif Geoffrey L , Woolley Michael E , Stubbs Victoria D
Published: April 2024

Intermarriage, defined here as the marriage between people of different races or different ethnicities, is on the rise in the United States, with one in six newlyweds intermarrying. While public opinion approval of interracial marriage is at an all-time high, racial and ethnic hate crimes are also on the rise, which can affect spouses differently based on their identity. Drawing on a 2022 Qualtrics sample of 287 spouses who intermarried and have children, authors of this article sought to learn what is related to their holding a positive view of intermarriage. Talking openly with one’s spouse about differences, children initiating discussions about race, and being consciously aware of the interracial or interethnic aspect of the marriage were predictors. Implications for social work practice, which are predicated on the ability to have open communication between family members and the social worker’s comfort with their own racial identity, are included for this growing population of intermarried couples.
U.S. Social Work Students and Social Media: A Descriptive Analysis of Survey Items across Four Time-Points
Authors: Ricciardelli Lauren A
Published: April 2024

Between fall 2018 and spring 2023, the author conducted four survey studies on social work students’ use, attitudes, and knowledge regarding social media: (1) a pilot study in fall 2018 (N = 57), (2) a comparative study in spring 2019 (N = 42), (3) a national survey study in fall 2019 (N = 430), and (4) a national replication survey study in spring 2023 (N = 287). The purpose of this article is to describe general observed trends across these four studies. Findings included persistent and pervasive use of social media, decreased knowledge of the impact of social media in undermining democratic processes, students’ inverted concern for others’ use of social media when compared with concern over their own use, diminished agreement with the importance of protecting personal data and treating data protection as a civil/human right, overall agreement that law enforcement should be able to use social media in the apprehension of people accused of committing a crime, decreased agreement that disinformation is a problem on social media, ambivalence toward social media’s positive impact on society, and increased strong disagreement that students wish to delete their accounts but feel unable to do so. Recommendations are shared.
Biocontrol Methods for the Management of Sclerotinia sclerotiorum in Legumes: A Review
Authors: Wang Su-Yan , Zhang Yun-Jiao , Chen Xin , Shi Xin-Chi , Herrera-Balandrano Daniela D. , Liu Feng-Quan , Laborda Pedro
Published: April 2024

Sclerotinia sclerotiorum is an economically damaging fungal pathogen that causes Sclerotinia stem rot in legumes, producing enormous yield losses. This pathogen is difficult to control due to its wide host spectrum and ability to produce sclerotia, which are resistant bodies that can remain active for long periods under harsh environmental conditions. Here, the biocontrol methods for the management of S. sclerotiorum in legumes are reviewed. Bacillus strains, which synthesized lipopeptides and volatile organic compounds, showed high efficacies in soybean plants, whereas the highest efficacies for the control of the pathogen in alfalfa and common bean were observed when using Coniothyrium minitans and Streptomyces spp., respectively. The biocontrol efficacies in fields were under 65%, highlighting the lack of strategies to achieve a complete control. Overall, although most studies involved extensive screenings using different biocontrol agent concentrations and application conditions, there is a lack of knowledge regarding the specific antifungal mechanisms, which limits the optimization of the reported methods.
Linkage Mapping and Genome-Wide Association Study Identified Two Peanut Late Leaf Spot Resistance Loci, PLLSR-1 and PLLSR-2, Using Nested Association Mapping
Authors: Gangurde Sunil S. , Thompson Ethan , Yaduru Shasidhar , Wang Hui , Fountain Jake C. , Chu Ye , Ozias-Akins Peggy , Isleib Thomas G. , Holbrook Corley , Dutta Bhabesh , Culbreath Albert K. , Pandey Manish K. , Guo Baozhu
Published: April 2024

Identification of candidate genes and molecular markers for late leaf spot (LLS) disease resistance in peanut ( Arachis hypogaea) has been a focus of molecular breeding for the U.S. industry-funded peanut genome project. Efforts have been hindered by limited mapping resolution due to low levels of genetic recombination and marker density available in traditional biparental mapping populations. To address this, a multi-parental nested association mapping population has been genotyped with the peanut 58K single-nucleotide polymorphism (SNP) array and phenotyped for LLS severity in the field for 3 years. Joint linkage-based quantitative trait locus (QTL) mapping identified nine QTLs for LLS resistance with significant phenotypic variance explained up to 47.7%. A genome-wide association study identified 13 SNPs consistently associated with LLS resistance. Two genomic regions harboring the consistent QTLs and SNPs were identified from 1,336 to 1,520 kb (184 kb) on chromosome B02 and from 1,026.9 to 1,793.2 kb (767 kb) on chromosome B03, designated as peanut LLS resistance loci, PLLSR-1 and PLLSR-2, respectively. PLLSR-1 contains 10 nucleotide-binding site leucine-rich repeat disease resistance genes. A nucleotide-binding site leucine-rich repeat disease resistance gene, Arahy.VKVT6A, was also identified on homoeologous chromosome A02. PLLSR-2 contains five significant SNPs associated with five different genes encoding callose synthase, pollen defective in guidance protein, pentatricopeptide repeat, acyl-activating enzyme, and C2 GRAM domains-containing protein. This study highlights the power of multi-parent populations such as nested association mapping for genetic mapping and marker-trait association studies in peanuts. Validation of these two LLS resistance loci will be needed for marker-assisted breeding.
Intracranial Pressure and Cerebral Hemodynamics in Infants Before and After Glenn Procedure
Authors: Jijeh Abdulraouf M. Z. , Fatima Anis , Faraji Mohammad A. , Hamadah Hussam K. , Shaath Ghassan A.
Published: April 2024

OBJECTIVES:

This prospective cohort study aimed to investigate changes in intracranial pressure (ICP) and cerebral hemodynamics in infants with congenital heart disease undergoing the Glenn procedure, focusing on the relationship between superior vena cava pressure and estimated ICP.

DESIGN:

A single-center prospective cohort study.

SETTING:

The study was conducted in a cardiac center over 4 years (2019–2022).

PATIENTS:

Twenty-seven infants with congenital heart disease scheduled for the Glenn procedure were included in the study, and detailed patient demographics and primary diagnoses were recorded.

INTERVENTIONS:

Transcranial Doppler (TCD) ultrasound examinations were performed at three time points: baseline (preoperatively), postoperative while ventilated (within 24–48 hr), and at discharge. TCD parameters, blood pressure, and pulmonary artery pressure were measured.

MEASUREMENTS AND MAIN RESULTS:

TCD parameters included systolic flow velocity, diastolic flow velocity (dFV), mean flow velocity (mFV), pulsatility index (PI), and resistance index. Estimated ICP and cerebral perfusion pressure (CPP) were calculated using established formulas. There was a significant postoperative increase in estimated ICP from 11 mm Hg (interquartile range [IQR], 10–16 mm Hg) to 15 mm Hg (IQR, 12–21 mm Hg) postoperatively (p = 0.002) with a trend toward higher CPP from 22 mm Hg (IQR, 14–30 mm Hg) to 28 mm Hg (IQR, 22–38 mm Hg) postoperatively (p = 0.1). TCD indices reflected alterations in cerebral hemodynamics, including decreased dFV and mFV and increased PI. Intracranial hemodynamics while on positive airway pressure and after extubation were similar.

CONCLUSIONS:

Glenn procedure substantially increases estimated ICP while showing a trend toward higher CPP. These findings underscore the intricate interaction between venous pressure and cerebral hemodynamics in infants undergoing the Glenn procedure. They also highlight the remarkable complexity of cerebrovascular autoregulation in maintaining stable brain perfusion under these circumstances.
Daptomycin Exposure Prediction With a Limited Sampling Strategy
Authors: De Gregori Simona , Seminari Elena , Capone Mara , Giordani Paola , Bruno Raffaele , De Silvestri Annalisa
Published: April 2024

Background:

Daptomycin is a cyclic lipopeptide antibiotic used to treat serious infectious endocarditis caused by Staphylococcus aureus. The pharmacodynamic parameter correlating best with efficacy is the ratio of the estimated area under the concentration (AUC0-24)–time curve to the minimum inhibitory concentration. The aim of the study is to develop a limited sampling strategy to estimate AUC0-24 using a reduced number of samples.

Methods:

Sixty-eight daptomycin AUC0-24 values were calculated for 50 White patients who underwent treatment for at least 5 consecutive days. Plasma concentrations were detected using a validated high-performance liquid chromatography–tandem mass spectrometry analytical method, with daptomycin-d5 as an internal standard. Multiple regression was used to evaluate the ability of 2 concentration–time points to predict the AUC0-24 calculated from the entire pharmacokinetic profile. Prediction bias was calculated as the mean prediction error, whereas prediction precision was estimated as the mean absolute prediction error. The development and validation datasets comprised 40 and 10 randomly selected patients, respectively.

Results:

The AUC0-24 (mg*h/L) was best estimated using the daptomycin trough concentration and plasma concentrations detected 2 hours after dosing. We calculated a mean prediction error of 1.6 (95% confidence interval, −10.7 to 10.9) and a mean absolute prediction error of 11.8 (95% confidence interval, 5.3–18.3), with 73% of prediction errors within ±15%.

Conclusions:

An equation was developed to estimate daptomycin exposure (AUC0-24), offering clinical applicability and utility in generating personalized dosing regimens, especially for individuals at high risk of treatment failure or delayed response.
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

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.
The characteristics of sexual behavior in blind men in Ganzhou, China: A cross-sectional study
Authors: Huang Shaoming , Zhu Shenghuang , Liu Renfu , Xiong Chuanchuan , Liu Lixin , Huang Jiaguo , Qian Biao
Published: April 2024

Visual stimuli play key roles in influencing men sexual behavior. However, few studies have explored the sexual behavior of blind men. To provide more information about blind men for the study of andrology by surveying the characteristics of their current sexual behavior. A questionnaire-based cross-sectional study design was performed. The questionnaire contained questions regarding demographic characteristics of participants, access to sexual knowledge, perception of the sexual partners’ beauty, and sexual arousal. Blind men were interviewed face-to-face by the trained investigator. Complete questionnaires were collected from 54 participants, with an average age of 40.57 ± 9.80 years old. Eye diseases were the most frequent cause of blindness. In terms of sexual orientation, all participants were heterosexual. Notably, 90.7% of the participants reported to have had a sexual experience. Among those who had engaged in sexual behavior, 93.6% experienced sexual pleasure and 69.4% had a normal erectile function. Overall, 16.7% of the participants received sex education. The participants obtained sexual knowledge mainly through sounds from mobile phones, peer-to-peer communication, sounds of television and radio. Voice was the most frequent perception of the sexual partners’ beauty, followed by figure, skin, and body fragrance. In terms of stimuli of sexual arousal, tactile sensation and auditory sensation in that order were the most frequent stimuli of sexual arousal. Stimuli of sexual arousal in blind men are mainly mediated by sound and touch. Blind men understand their sexual partners’ beauty through auditory, tactile, and olfactory sensations. Blind men in Ganzhou lack formal and systematic sex education.