bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive analysis of the KLRB1 expression and its clinical implication in testicular germ cell tumors: A review
Authors: Li Luyu , Hu Yaorui , Li Xiao , Ju Baojun
Published: April 2024

Testicular germ cell tumors (TGCT) are the most common testicular malignancies. KLRB1 is considered to influence the development and progression of a number of cancers. However, it is unclear how the KLRB1 gene functions in TGCT. First, it was determined the expression level of KLRB1 in TGCT using The Cancer Genome Atlas (TCGA) (The Cancer Genome Atlas) dataset and GTEx (Genotype-Tissue Expression) dataset. The clinical significance and biological functions of KLRB1 were explored using the TCGA dataset, and we analyzed the correlation of the KLRB1 gene with tumor immunity and infiltrating immune cells using gene set variation analysis and the TIMER database. We found that the expression level of KLRB1 was upregulated in TGCT malignant tissues with the corresponding normal tissues as controls, and KLRB1 expression correlated with clinicopathologic features of TGCT. Functional enrichment analysis suggested that KLRB1 might be involved in immune response and inflammatory response. KLRB1 was highly positively correlated with natural killer cell activation in immune response and positively correlated with tumor-infiltrating immune cells. This study demonstrated for the first time the role of KLRB1 in TGCT, which may serve as a new biomarker associated with immune infiltration and provide a potential therapeutic target for the treatment of TGCT.
The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer
Authors: Yuan Hui , Liang Yu , Hu Shaorun , Chen Jinxiang , You Jingcan , Jiang Jun , Luo Mao , Zeng Min
Published: April 2024

Breast cancer is a common malignancy with the highest mortality rate among women worldwide. Its incidence is on the rise year after year, accounting for more than one-tenth of new cancers worldwide. Increasing evidence suggests that forkhead box (FOX) transcription factors play an important role in the occurrence and development of breast cancer. However, little is known about the relationship between the expression, prognostic value, function, and immune infiltration of FOX transcription factors in tumor microenvironment. We used bioinformatics to investigate expression and function of FOX factor in breast cancer. Our results revealed the expression levels of FOXA1 and FOXM1 were significantly higher in breast cancer tissues than in normal tissues. The high expression of mRNA in FOXA1 (P < .05), FOXM1 (P < .01), and FOXP1 (P < .05) groups was related to tumor stage. Survival analysis results showed that increased FOXP1 mRNA levels were significantly associated with overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) in all patients with breast cancer (P < .05). Patients with the FOXA1 high-expression group had better RFS and DMFS than the low-expression group (P < .05), while patients with FOXM1 high-expression group had worse RFS, OS, and DMFS than the low-expression group (P < .05). Meanwhile, mutation analysis showed that genetic alterations in FOX transcription factors were significantly associated with shorter OS and progression-free survival (P < .05), but not with disease-free survival (P = .710) in patients with breast cancer. FOXP1, FOXA1, and FOXM1 may be used as potential biomarkers to predict the prognosis of patients with breast cancer. Functional enrichment indicated that FOX was mainly involved in cell division, cell senescence, cell cycle, and prolactin signaling pathway. In patients with breast cancer, FOXC2 expression was negatively correlated with the infiltration of B cells and positively correlated with the infiltration of neutrophils and dendritic cells. However, FOXM1 was negatively correlated with the infiltration of CD8 + T cells and macrophages and positively correlated with the infiltration of neutrophils and dendritic cells. These findings provided novel insights into the screening of prognostic biomarkers of the FOX family in breast cancer and laid a foundation for further research on the immune infiltration of the FOX transcription factor family members in tumors.
Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model
Authors: Liu Zhang-hong , Wang Li-yong , Hu Zhen-fen
Published: April 2024

This study aimed to investigate the risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model. A cross-sectional survey was conducted in a hospital in Zhejiang province, China from January 1, 2020, to November 31, 2022 among patients undergoing hemodialysis. Dietary intake was assessed applying a Food Frequency Questionnaire. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index. Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis was using a nomogram model. This study included 201 patients and 87 individuals (43.3%, 87/201) exhibited sleep disorders. The average age of included patients was 51.1 ± 9.0 years, with males accounting for 55.7% (112/201). Results from nomogram model exhibited that potential risk factors for sleep disorders in patients undergoing hemodialysis included female, advanced age, increased creatinine and alanine aminotransferase levels, as well as higher red meat consumption. Inversely, protective factors against sleep disorders in these patients included higher consumption of poultry, fish, vegetables, and dietary fiber. The C-index demonstrated a high level of discriminative ability (0.922). This study found that age, sex, and dietary factors were associated with sleep disorders in hemodialysis patients. Hemodialysis patients with sleep disorders require urgent dietary guidance.
Proposing the potential of utilizing the CAT score for early detection of COPD in asymptomatic patients, shifting towards a patient-centered approach: A review
Authors: Vaezi Atefeh , Mirsaeidi Mehdi
Published: April 2024

Chronic obstructive pulmonary disease (COPD) constitutes a significant public health challenge, with delayed diagnosis and underdiagnosis being pervasive issues. The United States Preventive Service Task Force recommends restricting COPD screening to symptomatic smokers, a focus that has exhibited limitations, leading to delayed diagnoses, and imposing a substantial burden on patients, their families, and the healthcare system. This paper explores an alternative approach, highlighting the potential utility of the COPD assessment test (CAT) score as a prescreening tool. A CAT score of 10 or higher could serve as an appropriate threshold for further diagnostic procedures, given its robust correlation with pulmonary function test parameters and is valuable capacity to quantify patients’ symptoms. The utilization of CAT as a prescreening tool in primary care signifies a transition towards a more patient-centered and comprehensive approach to COPD diagnosis and care.
Transverse spinal cord infarction following immunoglobulin treatment in a patient with exfoliative dermatitis: A case report
Authors: Zhang Lili , He Lanying , Huang Jing , Ren Sixie , Wang Jian
Published: April 2024

Rationale:

Transverse spinal cord infarction (SCI) is rare but highly disabling. Aortic thrombosis was described as one of the most common etiologies. Thromboembolic complications associated with intravenous immunoglobulin (IVIG) have been reported.

Patient concerns:

A previously well, 64-year-old man who was given the treatment of IVIG (0.4 g/kg/d for 5 days) for exfoliative dermatitis 2 weeks before, progressively developed flaccid paraplegia of lower extremities, loss of all sensations below T3 level and urinary incontinence within 50 minutes.

Diagnoses:

A diagnosis of SCI and pulmonary embolism was made. IVIG was considered the possible cause.

Interventions:

Anticoagulation treatment and continuous rehabilitation were administered.

Outcomes:

The neurologic deficiency of the patient was partially improved at the 3-year follow-up.

Lessons:

The rapid development of severe deficits within 4 hours mostly contributes to the diagnosis of SCI. Heightened awareness of possible thrombotic events is encouraged for a month-long period following IVIG therapy.
A degradome-related signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma based on machine learning procedure
Authors: Deng Ziqing , Feng Qian , Zhao Dan , Huang Zhihao
Published: April 2024

Stomach adenocarcinoma (STAD) is one of the subtype of gastric cancer with high invasiveness, extreme heterogeneity, high morbidity, and high mortality. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity and carcinogenesis. An integrative machine learning procedure including 10 methods was performed to develop a prognostic degradome-based prognostic signature (DPS) in TCGA, GSE15459, GSE26253, and GSE62254 datasets. Investigations of the DPS concerning immune infiltration, immunotherapy benefits, and drug priority were orchestrated. The DPS developed by Enet [alpha = 0.3] method was regarded as the optimal prognostic model. The DPS had a stable and powerful performance in predicting the clinical outcome of STAD and served as an independent risk factor in training and testing cohorts. The C-index of DPS was higher than that of age, sex, and clinical stage. STAD patients with low DPS scores had a higher abundance of B cells, CD8+ T cells, higher cytolytic scores, and T cell co-stimulation scores. Moreover, low DPS score indicated a lower tumor immune dysfunction and exclusion score, lower T cell dysfunction and exclusion score, higher PD1&CTLA4 immunophenoscore, and higher tumor mutation burden score in STAD, demonstrating a better immunotherapy response. STAD patients with a high DPS score had a lower IC50 value of common chemotherapy and targeted therapy regimens (Cisplatin, Docetaxel, Gefitinib, etc). Our study developed an optimal DPS for STAD. The DPS could predict the prognosis, risk stratification and guide treatment for STAD patients.
Chemical shift-encoded MRI with compressed sensing combined with parallel imaging for proton density fat fraction measurement of the lumbar vertebral bone marrow
Authors: Misaka Tomofumi , Hashimoto Yukihiko , Ashikaga Ryuichiro , Ishida Takayuki
Published: April 2024

We aimed to investigate the accuracy of proton density fat fraction (PDFF) measurement of the lumbar vertebral bone marrow using chemical shift-encoded magnetic resonance imaging (CSE-MRI) with compressed sensing combined with parallel imaging (CSPI). This study recruited a commercially available phantom, and 43 patients. Fully sampled data without CSPI and under-sampled data with CSPI acceleration factors of 2.4, 3.6, and 4.8 were acquired using a 1.5T imaging system. The relationships between PDFF measurements obtained with the no-CSPI acquisition and those obtained with each CSPI acquisition were assessed using Pearson correlation coefficient (r), linear regression analyses, and Bland–Altman analysis. The intra- and inter-observer variabilities of the PDFF measurements were evaluated using the intraclass correlation coefficient. PDFF measurements obtained with all acquisitions showed a significant correlation and strong agreement with the reference PDFF measurement of the phantom. PDFF measurements obtained using CSE-MRI with and without CSPI were positively correlated (all acquisitions: r = 0.99; P < .001). The mean bias was −0.31% to −0.17% with 95% limits of agreement within ±2.02%. The intra- and inter-observer agreements were excellent (intraclass correlation coefficient: 0.988 and 0.981, respectively). A strong agreement and positive correlation were observed between the PDFF measurements obtained using CSE-MRI with and without CSPI. PDFF measurement of the lumbar vertebral bone marrow using CSE-MRI with CSPI can be acquired with a maximum reduction of approximately 75% in the acquisition time compared with a fully sampled acquisition.
Experiences of women with gestational diabetes about fear of having diabetes in their babies: A qualitative study
Authors: Topaloğlu Ören Ekin Dila , Ünsal Avdal Elif , Polat Gökşen , Sofulu Funda , Düzgün Gönül , Pamuk Gülseren
Published: April 2024

Gestational Diabetes Mellitus is an important public health problem that often occurs during pregnancy. This study aimed to reveal the experiences of women with gestational diabetes regarding the fear of having diabetes in their babies. A qualitative research method was carried out with a phenomenological approach. The interviews had a semi-structured form and were recorded on an online/face-to-face voice recorder, and thematic content analysis was performed on the MAXQDA22. Following the inclusion criteria, 12 women with gestational diabetes from the 2 hospitals in the study were included, and in this way, the study reached saturation. As a result of the interviews, 4 main themes and one subtheme were obtained from coding. The main themes were “sugar baby,” “risky child,” “raising a fearful baby,” and “problematic gene carrier.” From the main theme of “problematic gene carrier,” the subtheme of “pregnancies with problematic genes” was created. This research sheds light on the problems women with gestational diabetes experience with themselves and their babies, and how they deal with these problems. Women with gestational diabetes try to accept and cope with the diagnosis. This research shows that the women were worried about both themselves and their babies. Illuminating the experiences of women with gestational diabetes is part of an integrative care approach that will help increase quality care and treatment in endocrine clinics. More qualitative studies are needed to learn more about the experiences of women with gestational diabetes in endocrine clinics.
Tuberculosis prevalence and demographic characteristics of population in Azad Jammu and Kashmir (Pakistan): A retrospective study
Authors: Khursheed Soffia , Wazir Samia , Saleem Muhammad Khurram , Majeed Ayesha Isani , Ahmad Mumtaz , Khan Qudsia Umaira , Jadoon Arzu , Akbar Amna , Jadoon Sarosh Khan , Tasneem Sabahat , Saleem Humayun , Khan Mohammad Saleem , Alvi Sarosh
Published: April 2024

Tuberculosis (TB) remains a serious problem for public health and a leading cause of death after COVID-19 and superior to even HIV/AIDS. It is a social health issue and can cause stigma and economic loss as the person cannot perform professionally due to lethargy caused by disease. It is a retrospective study done on data from National TB program Muzaffarabad chapter. The details were noted on SPSS and analysis was done to find important demographic characteristics. The total number of patients was 3441; among which 48.76% were males. Most of them (81.11%) belonged to the Muzaffarabad division of Azad Jammu and Kahmir (AJK). The microbiologically or culture positive cases were 440. Rifampicin resistance was present in 147 cases, further categorized as high (n = 143), very high (n = 3), or true positive (n = 1) resistance. Muti drug resistance was found in 19 cases. The microscopy culture is more sensitive (AUC = 0.511) than MTB/RIF or serology (AUC = 0.502) according to ROC. The rate of positive smear results is not very satisfactory in the present study as it cannot detect dormant or latent cases. There is a need to establish more sensitive tests for detection of cases and more research to combat the disease.
A challenging issue in COVID-19 infection: The relationship between PA1-1 and TAFI levels in patients with coagulation disorder: A retrospective and observational study
Authors: Altin Nilgun , Tiğlioğlu Pinar , Ulusoy Tulay Unver , Aydin Fevzi Nuri , Kar İrem , Karakoc Busra , Utebey Gulten
Published: April 2024

COVID-19 disrupts the balance between coagulation and fibrinolysis. Especially in the clinical course of serious disease, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and tissue plasminogen activator levels increase in association with hypercoagulable state and hypofibrinolysis. This explains the increased incidence of thrombosis seen in COVID-19 infection. In this study, we aimed to examine the changes in PAI-1 and TAFI levels of COVID-19 patients. Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Dişkapi Yildirim Beyazit Training and Research Hospital—Ankara Turkey, between April 1 and May 7, 2021. Patients who were diagnosed with COVID-19 were included in this retrospective study. TAFI and PAI-1 levels were analyzed from the samples that had been stored at –80 °C formerly. One hundred thirty-five patients diagnosed with COVID-19 and followed up in the service or intensive care unit were included in the study. Thirty-four (25.2%) patients required follow-up in the intensive care unit. Mortality rate was 10.4%, the coagulation tests of these patients were also compared. PA1-1 levels were found to be statistically significantly higher in intensive care unit patients (median: 133 pg/mL vs 31 pg/mL; P < .001), and there was no significant difference in TAFI levels (median:7.31 ng/mL vs 9.80 ng/mL; P = .171) between the 2 groups. TAFI levels were found to be higher in patients who died. In COVID-19 infection, as the severity of the disease increases, the coagulation balance deteriorates and eventually a hypercoagulable state occurs with an increase in PAI-1 and TAFI levels. Markers such as PAI and TAFI can be illuminating in further studies in determining prognosis and mortality and developing new treatment options.
The relationship between red cell distribution width, serum calcium ratio, and in-hospital mortality among patients with acute respiratory failure: A retrospective cohort study of the MIMIC-IV database
Authors: Dai Jun , Guo Yafen , Zhou Quan , Duan Xiang-Jie , Shen Jinhua , Zhang Xueqing
Published: April 2024

To investigate the impact of RDW/CA (the ratio of red cell distribution width to calcium) on in-hospital mortality in patients with acute respiratory failure (ARF). This retrospective cohort study analyzed the data of 6981 ARF patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database 2.0. Critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. The primary outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether the RDW/CA ratio independently correlated with in-hospital mortality. The Kaplan–Meier method was used to plot the survival curves of the RDW/CA. Subgroup analyses were performed to measure the mortality across various subgroups. After adjusting for potential covariates, we found that a higher RDW/CA was associated with an increased risk of in-hospital mortality (HR = 1.17, 95% CI: 1.01–1.35,P = .0365) in ARF patients. A nonlinear relationship was observed between RDW/CA and in-hospital mortality, with an inflection point of 1.97. When RDW/CA ≥ 1.97 was positively correlated with in-hospital mortality in patients with ARF (HR = 1.554, 95% CI: 1.183–2.042,P = .0015). The Kaplan–Meier curve indicated the higher survival rates for RDW/CA < 1.97 and the lower for RDW/CA ≥ 1.97 after adjustment for age, gender, body mass index, and ethnicity. RDW/CA is an independent predictor of in-hospital mortality in patients with ARF. Furthermore, a nonlinear relationship was observed between RDW/CA and in-hospital mortality in patients with ARF.
Toward early intervention based on age-specific vision checkups: A vision impairment survey in Yantai, China
Authors: Sun Yuelin , Zhang Xiaoyu , Zheng Zhong , Dong Fengguang , Wang Fei , Zhou Zilin , Wang Guiqiang
Published: April 2024

The prevalence of myopia among children and adolescents is currently rising to alarming levels (>80%) in China. This study used several routinely collected demographic factors to quantify myopia and glass-wearing rates for primary and secondary school students. We identified myopia risk factors and proposed new aspects for early intervention. This study was a cross-sectional survey of myopia and glass-wearing rates for students (6–18 years old) in Yantai, China. We collected both vision (vision acuity [VA] and spherical equivalence [SE]) and glass-wearing information to establish respective logistic models for quantifying myopia and glass-wearing rate. We further propose a joint decision region (VA, SE, age) to guide early intervention. Among 10,276 children, 63% had myopia (65% wore glasses). The prevalence of myopia increases with age and levels off during adulthood. Females had a higher overall prevalence rate than males (P < .001). The rural age mode (≈15.5) is about 2 years larger than the urban age (≈13.5) for myopia students. For the myopia rate, in the age ≤14.5, the linear age effect was significant (odds ratio [OR] = 1.73, P < .0001), males had a significant negative baseline effect at the start of schooling (vs. females) (OR = 0.68, P < .0001), and the urban group had a significant positive baseline effect (vs. rural) (OR = 1.39, P < .0001). The correlation between VA and SE increases with age and has a directional shift (from negative to positive) at ages 8 to 9. For the glass-wearing rate, age had a significant positive effect (OR = 1.25, P < .0001), VA had a significant negative effect (OR = 0.002, P < .0001), and body mass index had a slightly significant positive effect (OR = 1.02, P = .03). Urban female have a higher myopia rate than rural male at the start of schooling, and vocational high school has improved vision upon high school. Body mass index was not a significant factor for myopia. The myopia rate model is specific to age range (separated at 14.5 years old). Students of lower ages are less likely to wear glasses for correction, and this may require intervention. The temporal age-specific (VA, SE) correlations and joint distributions strengthen the speculation in the literature that age 8 to 9 is a critical intervention period and motivates us to propose a rigorous intervention decision region for (age, VA, and SE) which mainly applies for this tight age period.
Knowledge of cancer symptoms and risk factors: A cross-sectional study from a developing country
Authors: Al Bashir Samir , AlBarakat Majd M. , Alabedalhalim Karam K. , Al-Khalaileh Ali , Alassaf Amer , Saleh Othman , Ayyad Asmaa W. , Alzoubi Karem H.
Published: April 2024

The delayed presentation of cancer patients to healthcare facilities for diagnosis is a pressing issue, as late-stage cancer cases are often more challenging to treat effectively. In low-resource settings, such as those with limited access to healthcare facilities, the impact of inadequate awareness of cancer signs and symptoms can be particularly severe. Therefore, this study aimed to evaluate public knowledge of cancer signs and symptoms and risk factors in the context of Jordan. This cross-sectional study was conducted among participants from all settings. Data was obtained from an Arabic version of the cancer awareness measure (CAM), which was answered online. It described demographic data and knowledge of cancer prevalence, age-related risk, signs, symptoms, and risk factors in recall and recognition-type questions. Participants (n = 1998) completed the questionnaire with a Median age of 35 and an interquartile range of 24. About half (n = 1070) thought that cancer is unrelated to age. Most participants identified breast cancer as the most common cancer among women (81%). Awareness of cancer signs/symptoms significantly differed in the level of knowledge in favor of females. The symptom “unexplained weight loss” was most commonly recognized (66.3%) and “persistent difficulty swallowing” the least (42.6%). As for risk factors, “smoking” was the most identified (76.9%) and “eating less than 5 portions of fruits and vegetables a day” was the least (19%), and “doing <30 minutes of moderate physical activity 5 times a week” as a close second least (19.95%). Females identified “smoking,” “passive smoking,” “HPV infection,” and “having a close relative with cancer” as risk factors significantly more than males. Those with good economic status were more aware that smoking is a cancer risk factor by 1.51 times compared to those with poor economic status. To enhance early diagnosis and presentation in Jordan, there is a need for increased public awareness of the signs, symptoms, and risk factors of cancer. One effective strategy to achieve this goal is to conduct targeted public campaigns that cater to different population groups, such as the youth, to improve their understanding and ensure that the message resonates.
Association between neck circumference and pulmonary function in Korean adults
Authors: Hwang In Cheol , Lee Chung-Woo , Lee Yoo Jeong , Ahn Hong Yup
Published: April 2024

Neck circumference (NC) is associated with various diseases. However, its association with pulmonary diseases remains unclear. This study aimed to investigate the association between NC and pulmonary function in Korean adults. Data from the 2019 Korean National Health and Nutrition Examination Survey were used, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). A total of 3818 adults aged 40 to 79 years were included in the analysis. Multivariable logistic regression models were used to examine factors associated with low pulmonary function (<80% of the predicted value) and calculate odds ratios (ORs) and 95% confidence intervals (CIs) for decreased lung function per 1-cm increase in NC. A negative correlation was observed between the NC and pulmonary function in both sexes. In multivariate logistic regression analyses, in contrast to men, women exhibited a notable relationship between increased NC and impaired pulmonary function, with a more pronounced effect observed in FVC (OR, 1.14; 95% CI, 1.05–1.24). Central obesity may play a role in pulmonary function decline. Understanding this relationship can inform preventive strategies and interventions to improve the respiratory health of individuals with central obesity.
A Practical guide to selecting and using new Crohn's disease therapies
Authors: Scoville Elizabeth A. , Horst Sara N.
Published: April 2024

Purpose of review

This review details the three new agents, including two novel mechanisms of action, approved to treat Crohn's disease in recent years. We review efficacy, safety, prescribing information, and available data on positioning these new therapies.

Recent findings

Risankizumab and upadacitinib are novel mechanisms of action approved to treat moderate to severe Crohn's disease. Risankizumab targets the cytokine interleukin-23. Upadacitinib is a selective Janus kinase-1 inhibitor approved for use in individuals who have previously failed or are intolerant to an anti-TNF agent. Subcutaneous infliximab provides a novel method of administering maintenance dosing of a longstanding and efficacious therapy.

Risankizumab has shown efficacy in both biologic naïve and biologic experienced populations. The SEQUENCE trial shows superiority of risankizumab over ustekinumab for disease response in patients who have previously failed an anti-tumor necrosis factor agent. Upadacitinib has shown good efficacy in clinical trials even in the setting of a mandated steroid taper during induction. Subcutaneous infliximab maintenance therapy appears noninferior to i.v. infliximab and shows good treatment persistence in real world transitions. Additional data is needed to better understand how to position these therapies.
Comparing Video Head Impulse Testing in Patients With Acute Vestibular Dysfunction
Authors: Mochizuki Fumihiro , Ito Yusuke , Sasano Yoshiyuki , Williams Erin , Hoffer Michael E. , Komori Manabu , Koizuka Izumi
Published: April 2024

Objective:

The video head impulse test (v-HIT) can evaluate the function of all semicircular canals (SCCs) in a short period. In this work, we sought to compare v-HIT results among 2 commercially available devices, the ICS impulse (Otometrics, Denmark) (ICS) and Eye See Cam (Interacoustics, Denmark) (ESC), among individuals with unilateral vestibular disorders.

Design:

Retrospective study (n = 15).

Setting:

St. Marianna University School of Medicine Hospital.

Patients:

Fifteen patients with acute unilateral vestibular disorders.

Intervention:

Two v-HIT devices were conducted across patients to compare the results of the 2 models.

Main Outcome Measures:

Gain values and pathological saccades for each SCC were compared across the 2 models. Monothermal caloric testing was performed to compare alongside v-HIT gain values.

Results:

There was no difference between the 2 models for the evaluation of the horizontal SCCs. There was a significant negative correlation (ESC: r = −0.52, ICS: r = −0.53) between caloric testing and the gain values of the 2 models. In the vertical SCCs, the gain values of ESC were significantly higher than the gain values of ICS. Detection of catch-up saccades in vertical SCCs was similar across the 2 models.

Conclusion:

For the horizontal SCCs, there was no difference in test results between the 2 models. However, in the vertical SCCs, gain values were variable across the 2 devices. Larger scale studies are needed to develop normative ranges for the vertical canals.
The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation
Authors: Kotton Camille N. , Kamar Nassim , Wojciechowski David , Eder Michael , Hopfer Helmut , Randhawa Parmjeet , Sester Martina , Comoli Patrizia , Tedesco Silva Helio , Knoll Greg , Brennan Daniel C. , Trofe-Clark Jennifer , Pape Lars , Axelrod David , Kiberd Bryce , Wong Germaine , Hirsch Hans H. ,   on behalf of The Transplantation Society International BK Polyomavirus Consensus Group
Published: April 2024

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.
Hantavirus infection in central Sri Lanka – an unusual clinical presentation: a case report
Authors: Pattiyakumbura T. T. , Pathirathne S. H. , Muthugala M. A. R. V.
Published: April 2024

Hantavirus infections are emerging zoonoses. In Asia, the hantavirus commonly manifests as haemorrhagic fever with renal syndrome (HFRS), apparent with fever, thrombocytopenia and acute kidney injury. There are a few cases with the atypical clinical course with cardiopulmonary symptoms in Asia including Sri Lanka. Here, we report a case of hantavirus infection with an atypical cardiopulmonary syndrome-like illness with serological evidence of the Puumala/Puumala-like virus.
Bioisosteric analogs of MDMA with improved pharmacological profile
Authors: Alberto-Silva Ana Sofia , Hemmer Selina , Bock Hailey A. , Alves da Silva Leticia , Scott Kenneth R. , Kastner Nina , Bhatt Manan , Niello Marco , Jäntsch Kathrin , Kudlacek Oliver , Bossi Elena , Stockner Thomas , Meyer Markus R. , McCorvy John D. , Brandt Simon D. , Kavanagh Pierce , Sitte Harald H.
Published: April 2024

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is re-emerging in clinical settings as a candidate for the treatment of specific psychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile.In vitromethods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubation with isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry.In silicomethods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin and dopamine transporters (hSERT and hDAT, respectively) but decreased activity at 5-HT2A/2B/2Creceptors. Regarding their hepatic metabolism, they differed from MDMA, withN-demethylation being the only metabolic route shared, and without forming phase II metabolites. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA analogs might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT and hDAT, but displaying a reduced activity at 5-HT2A/2B/2Creceptors and reduced hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.
Somatic embryogenesis of grapevine (Vitis vinifera) expresses a transcriptomic hourglass
Authors: Koska Sara , Leljak-Levanić Dunja , Malenica Nenad , Villi Kian Bigović , Futo Momir , Čorak Nina , Jagić Mateja , Tušar Anja , Kasalo Niko , Domazet-Lošo Mirjana , Vlahoviček Kristian , Domazet-Lošo Tomislav
Published: April 2024

At the molecular level, multicellular eukaryotic lineages and bacterial biofilms show predictable evolutionary footprints in their development. For instance, the zygotic embryogenesis ofArabidopsis, which is initiated by gamete fusion, shows hourglass-shaped ontogeny-phylogeny correlations at the transcriptome level. However, many plants are capable of yielding a fully viable next generation by somatic embryogenesis — a comparable developmental process that usually starts by the embryogenic induction of a diploid somatic cell. This leads to the question: is the hourglass-shaped ontogeny-phylogeny correlation preserved in somatic embryogenesis? To explore the correspondence between ontogeny and phylogeny in this alternative developmental route in plants, we developed a new and highly efficient model of somatic embryogenesis in grapevine (Vitis vinifera) and sequenced its developmental transcriptomes. By combining the evolutionary properties of grapevine genes with their expression values, which were recovered from early induction until the formation of juvenile plants, we found a strongly supported hourglass-shaped developmental trajectory. However, in contrast to zygotic embryogenesis inArabidopsiswhere the torpedo stage was evolutionary the most inert, we found that in the somatic embryogenesis of grapevine the heart stage expressed evolutionary the oldest and the most conserved transcriptome. This is a surprising finding because it suggests a better evolutionary system-level analogy between animal development and plant somatic embryogenesis than zygotic embryogenesis. We conclude that macroevolutionary logic is deeply hardwired in plant ontogeny and that somatic embryogenesis is likely a primordial embryogenic program in plants.
Punctuational evolution is pervasive in distal site metastatic colonization
Authors: Butler George , Amend Sarah R. , Axelrod Robert , Venditti Chris , Pienta Kenneth J.
Published: April 2024

The evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence. By measuring punctuational effects across the metastatic cascade, we show that punctuational effects contribute more to the molecular diversity at distal site metastases compared to the paired primary tumor, suggesting qualitatively different modes of evolution may drive primary and metastatic tumor progression. This is the first empirical evidence for distinct patterns of molecular evolution at early and late stages of metastasis and demonstrates the complex interplay of cell intrinsic and extrinsic factors that shape lethal cancer.
Respiration and gas exchange under negative pressure breathing during simulated microgravity
Authors: Semenov Yury S. , Gorbunova Aleksandra A. , Popova Julia A. , Dyachenko Alexander I.
Published: April 2024

The research considers the effect of inspiratory negative pressure breathing (NPBin, -20 cmH2O relative to barometric pressure) on respiration and gas exchange in healthy humans under various conditions: in the sitting and supine positions as well as during simulating the physiological effects of a long stay in conditions of microgravity (dry immersion and head-down bed rest). Under NPBin, respiratory rate significantly decreased (by 7 min-1on average, in some volunteers up to two or three cycles per minute), tidal volume increased (by an average of 0.3 l), while minute ventilation decreased (on average by 1.8 l/min), and respiratory exchange ratio increased (on average by 0.09). The response of respiratory and gas exchange parameters to NPBin in all the considered conditions was almost the same (there were no significant differences in parameters changes induced by NPBin between the conditions). Despite the decrease in minute ventilation, the results indicate CO2washout from the body under NPBin.
Collateral damage of NUDT15 deficiency in cancer provides a cancer pharmacogenetic therapeutic window with thiopurines
Authors: Massey Jacob C. , Magagnoli Joseph , Sutton S. Scott , Buckhaults Phillip J. , Wyatt Michael D.
Published: April 2024

Genome instability is a hallmark of cancer and are driven by mutations in oncogenes and tumor suppressor genes. Despite successes seen with select targeted therapeutics, this type of personalized medicine is only beneficial for a small subpopulation of cancer patients who have one of a few actionable genetic changes. Most tumors also contain hundreds of passenger mutations that offered no fitness advantage or disadvantage during tumor evolution. Mutations in known pharmacogenetic (PGx) loci for which germline variants encode variability in drug response can cause somatically acquired drug sensitivity. TheNUDT15gene is a known PGx locus that participates in the rate-limiting metabolism of thiopurines. People with two defective germline alleles of NUDT15 are hypersensitive to the toxic effects of thiopurines.NUDT15is located adjacent to the Retinoblastoma (RB1) tumor suppressor gene, which often undergoes homozygous deletion in retinoblastomas and other epithelial cancers. We observed thatRB1undergoes homozygous deletions in 9.4% of prostate adenocarcinomas and 2.5% of ovarian cancers, and in nearly all of these casesNUDT15is also lost. Moreover, 44% of prostate adenocarcinomas and over 60% of ovarian cancers have lost one allele of NUDT15, which predicts that a majority of all prostate and ovarian cancers have somatically acquired hypersensitivity to thiopurine treatment. We performed a retrospective analysis of >16,000 patients in the US Veterans Administration health care system and found concurrent xanthine oxidase inhibition (XOi) and thiopurine usage for non-cancer indications is significantly associated with reduced incidence of prostate cancer. The hazard ratio for the development of prostate cancer in patients treated with thiopurines and XOi was 0.562 (0.301-1.051) for the unmatched cohort and 0.389 (0.185-0.819) for the propensity score matched cohort. We experimentally depleted NUDT15 from ovarian and prostate cancer cell lines and observed a dramatic sensitization to thiopurine-induced and DNA damage-dependent toxicity. These results indicate that somatic loss of NUDT15 predicts therapeutic sensitivity to a low cost and well tolerated drug with a broad therapeutic window.
Spatial motifs reveal patterns in cellular architecture of complex tissues
Authors: Samadi Zainalabedin , Askary Amjad
Published: April 2024

Spatial organization of cells is crucial to both proper physiological function of tissues and pathological conditions like cancer. Recent advances in spatial transcriptomics have enabled joint profiling of gene expression and spatial context of the cells. The outcome is an information rich map of the tissue where individual cells, or small regions, can be labeled based on their gene expression state. While spatial transcriptomics excels in its capacity to profile numerous genes within the same sample, most existing methods for analysis of spatial data only examine distribution of one or two labels at a time. These approaches overlook the potential for identifying higher-order associations between cell types – associations that can play a pivotal role in understanding development and function of complex tissues. In this context, we introduce a novel method for detecting motifs in spatial neighborhood graphs. Each motif represents a spatial arrangement of cell types that occurs in the tissue more frequently than expected by chance. To identify spatial motifs, we developed an algorithm for uniform sampling of paths from neighborhood graphs and combined it with a motif finding algorithm on graphs inspired by previous methods for finding motifs in DNA sequences. Using synthetic data with known ground truth, we show that our method can identify spatial motifs with high accuracy and sensitivity. Applied to spatial maps of mouse retinal bipolar cells and hypothalamic preoptic region, our method reveals previously unrecognized patterns in cell type arrangements. In some cases, cells within these spatial patterns differ in their gene expression from other cells of the same type, providing insights into the functional significance of the spatial motifs. These results suggest that our method can illuminate the substantial complexity of neural tissues, provide novel insight even in well studied models, and generate experimentally testable hypotheses.
Wisent genome assembly uncovers extended runs of homozygosity and a large deletion that inactivates the thyroid hormone responsive gene
Authors: Bortoluzzi Chiara , Mapel Xena Marie , Neuenschwander Stefan , Janett Fredi , Pausch Hubert , Leonard Alexander S.
Published: April 2024

The wisent (Bison bonasus) is Europe’s largest land mammal. We produced a HiFi read-based wisent assembly with a contig N50 value of 91 Mb containing 99.7% of BUSCO genes which improves contiguity a thousand-fold over an existing assembly. Extended runs of homozygosity in the wisent genome compromised the separation of the HiFi reads into parental-specific read sets, which resulted in inferior haplotype assemblies. A bovine super-pangenome built with assemblies from wisent, bison, gaur, yak, taurine and indicine cattle identified a 1,580 bp deletion removing the protein-coding sequence ofTHRSPencoding thyroid hormone-responsive protein from the wisent and bison genomes. Analysis of 725 sequenced samples across the Bovinae subfamily showed that the deletion is fixed in bothBisonspecies but absent inBosandBubalus. TheTHRSPtranscript is abundant in adipose, fat, liver, muscle, and mammary gland tissue ofBosandBubalus, but absent in bison indicating that the deletion inactivatesTHRSPpossibly contributing to low bison milk and meat fat content. We show that super-pangenomes can reveal potentially trait-associated variation across phylogenies, but also demonstrate that haplotype assemblies from species that went through population bottlenecks warrant scrutiny, as they may have accumulated long runs of homozygosity that complicate phasing.
MicrobiomePhylo: A New Tool for Metabarcoding Data Downstream Analysis - A Real-World Data Analysis Demonstration
Authors: Tafuro Camilla Veronica
Published: April 2024

The field of microbiome research has rapidly expanded, driven by advancements in sequencing technologies that generate vast amounts of data. To navigate this complexity, MicrobiomePhylo has been developed as a web platform tailored for the downstream analysis of microbiome amplicon sequencing data. It stands out for its ability to process QIIME2 artifact files (.qza), offering an intuitive interface, extensive analytical functions, and advanced visualization features, making it indispensable for bioinformaticians and biologists alike. MicrobiomePhylo enhances the understanding of complex datasets by facilitating detailed analysis and visualization. Its effectiveness is showcased through the analysis of the “Moving Pictures” tutorial dataset from QIIME2, a benchmark in microbiome research, featuring 16S rRNA gene sequencing data from various sample types over time.

The platform supports a comprehensive workflow including data upload, pre-processing, refinement, visualization, exploration, and advanced statistical analysis. Features include data filtering, rarefaction, and diverse visualizations like barplots, boxplots, and heatmaps. Advanced analyses cover alpha and beta diversity, abundance analysis, differential abundance analysis, and correlation studies, backed by robust statistical methods.

A demonstration with the “Moving Pictures” dataset highlights MicrobiomePhylo’s capability to manage real-world data. Customization options for variables, taxonomic levels, plot dimensions, and group highlighting improve result interpretability and visual appeal. Analysis at the phylum level across different body sites reveals insights into microbial composition and diversity. The generated visualizations distinguish microbial community compositions and taxa abundance between body sites, emphasizing the site-specific nature of the human microbiome.

Importance

The significance of MicrobiomePhylo in microbiome research is profound. As sequencing technologies advance, generating vast datasets, researchers face the challenge of analyzing this data efficiently. MicrobiomePhylo, a web platform designed for microbiome amplicon sequencing data analysis, directly processes QIIME2 artifact files (.qza), offering an accessible interface for both bioinformaticians and biologists. Its comprehensive analytical and advanced visualization capabilities are crucial for understanding complex datasets, enabling deeper insights into microbial composition and diversity. The platform supports a full workflow from data upload to advanced statistical analysis, including data filtering, rarefaction, and various visualizations for taxa abundances, correlations with continuous variables, diversity and more. This facilitates a thorough investigation of microbiome data, making MicrobiomePhylo an indispensable tool in the field, enhancing our understanding of the microbiome through specialized, user-friendly analysis capabilities.