bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of mitochondrial energy production leads to reorganization of the plant endomembrane system
Authors: Wang Taotao , Li Xinjing , Yu Hongying , Zhang Heng , Xie Zhiping , Gong Qingqiu
Published: January 2025

Mitochondria have generated the bulk of ATP to fuel cellular activities, including membrane trafficking, since the beginning of eukaryogenesis. How inhibition of mitochondrial energy production will affect the form and function of the endomembrane system and whether such changes are specific in today's cells remain unclear. Here, we treated Arabidopsis thaliana with antimycin A (AA), a potent inhibitor of the mitochondrial electron transport chain (mETC), as well as other mETC inhibitors and an uncoupler. We investigated the effects of AA on different endomembrane organelles connected by vesicle trafficking via anterograde and retrograde routes that heavily rely on ATP and GTP provision for SNARE and RAB/GEF function, respectively, in root cells. Similar to previous reports, AA inhibited root growth mainly by shortening the elongation zone (EZ) in an energy- and auxin-dependent way. We found that PIN-FORMED 2 (PIN2) and REQUIRES HIGH BORON 1 (BOR1), key proteins for EZ establishment and cell expansion, undergo accelerated endocytosis and accumulate at enlarged multivesicular bodies (MVBs) after AA treatment. Such accumulation is consistent with the observation that the central vacuole becomes fragmented and spherical and that the Arabidopsis Rab7 homolog RABG3f, a master regulator of MVB and vacuolar function, localizes to the tonoplast, likely in a GTP-bound form. We further examined organelles and vesicle populations along the secretory pathway and found that the Golgi apparatus—in particular, the endoplasmic reticulum–Golgi intermediate compartment (ERGIC)—cannot be maintained when mETC is inhibited. Our findings reveal the importance and specific impact of mitochondrial energy production on endomembrane homeostasis.
Steady-State Solutions for a Geometrically Thin Accretion Disk with Magnetically Driven Winds
Authors: Tamilan Mageshwaran , Hayasaki Kimitake , Suzuki Takeru K
Published: January 2025

We present steady-state solutions for a one-dimensional, magnetically driven accretion disk wind model based on magnetohydrodynamic equations. We assume a geometrically thin, gas-pressure-dominated accretion disk, incorporating both magnetic braking and turbulent viscosity introduced by an extended alpha-viscosity prescription. Additionally, the vertical stress parameter is assumed to scale with the disk aspect ratio. We confirm that the derived solutions result in standard disk solutions when the wind is absent. We find that the mass accretion rate decreases as the disk mass falls inward, while the mass loss rate increases with radius. The disk spectrum emitted from the magnetically driven disk wind can be observed without interference from the wind medium because the wind is significantly optically thin. The spectral luminosity is proportional to $\nu ^{1/3}$ in the intermediate, multicolor-blackbody wavebands, in the absence of wind, as predicted by standard disk theory. However, in the presence of wind, it follows a different power-law dependence on frequency over the same range. A deviation from the spectral slope of $1/3$, particularly a negative spectral slope, is a clear indicator of the presence of a magnetically driven wind. We also discuss an observational strategy to test our model with multiwavelength observations.
A predictive model based on the gut microbiota improves the diagnostic effect in patients with rheumatoid arthritis
Authors: Wang Qi , Li Chen-Long , Yu Si-Yuan , Dong Hui-Jing , Yang Lei , Liu Yang , He Pei-Feng , Zhang Sheng-Xiao , Yu Qi
Published: January 2025

Objectives

Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disorder predominantly targeting the joints, with gut microbiota dysbiosis being intricately associated with its progression. The aim of the present study is to develop effective early diagnostic methods for early RA based on gut microbiota.

Methods

A cohort comprising 262 RA patients and 475 healthy controls (HCs) was recruited. Faecal samples were collected from all participants, and microbial DNA was subsequently extracted. The V3-V4 region of the 16S rRNA gene was amplified via polymerase chain reaction (PCR) and subjected to high-throughput sequencing using the Illumina MiSeq platform. Additionally, a dataset with the accession number PRJNA450340 from the European Nucleotide Archive (ENA) was incorporated into the study. The sequencing data underwent processing and analysis utilizing QIIME2. To construct microbiome-based diagnostic models, Random Forest (RF), Support Vector Machine (SVM) and Generalized Linear Model (GLM) methodologies were employed, with the self-test data functioning as the training set and the PRJNA450340 dataset serving as the validation set.

Result

The results indicated that patients with RA exhibited a significantly reduced gut microbial α-diversity compared with the HCs group. The β-diversity analysis demonstrated notable distinctions in the gut microbiota structure between RA patients and HCs. Variations in the gut microbiome composition between RA patients and HCs were evident at both the phylum and genus levels. LEfSe analysis revealed a substantial number of significantly different microbiota between RA patients and HC, and seven key genera were obtained by intersection of the different flora in the two data sets: Ruminococcus_gnavus_group, Fusicatenibacter, Butyricicoccus, Subdoligranulum, Erysipelotrichaceae_UCG-003, Romboutsia and Dorea. Utilizing these seven core genera, RA diagnostic models were developed employing RF, SVM and GLM methodologies. The GLM model exhibited consistent performance, achieving an area under the curve (AUC) of 71.03% in the training set and 74.71% in the validation set.

Conclusion

Notable differences in gut microbiota exist between RA patients and healthy individuals. Diagnostic models based on key microbial genera hold potential for aiding in the early identification of individuals at risk for developing RA, thereby suggesting new avenues for its diagnosis.
Tofacitinib treatment for active dermatomyositis and anti-synthetase syndrome: a prospective cohort pilot study
Authors: Xing Xiaoyan , Li Yuhui , Liu Qinghong , Wang Naidi , Zhang Kai , Mo Wanxing , Zhao Liang , Zhang Jian , Ma Ke , Zhao Xuyang , Lu Dan , He Jing
Published: January 2025

Objectives

The objective of this study was to evaluate the efficacy and safety of tofacitinib in the treatment of active dermatomyositis (DM) and anti-synthetase syndrome (ASS).

Methods

Tofacitinib was administered at a dose of 5 mg twice daily to patients who exhibited inadequate response to conventional treatments. The primary end point was the reduction in T follicular helper (Tfh) cells at week 24. Key secondary end points included clinical scores. Moreover, we analysed the immunological profiles and conducted RNA sequencing (RNAseq) on peripheral blood samples from four patients.

Results

A total of 26 patients were enrolled, with 21 completing the study. Both DM and ASS patients demonstrated significant improvements in disease activity. Among these patients, the percentage of Tfh cells in peripheral blood decreased in 81.0% (17/21) of them (P = 0.003). Significant reductions in Th17 cells were observed in vivo in the peripheral blood mononuclear cells (PBMCs) of these patients (P = 0.017). In vitro, Tfh cells (2.88 ± 1.13 vs 2.28 ± 0.92, P< 0.001), Th17 cells (1.42 ± 0.92 vs 1.01 ± 0.74, P = 0.016), Treg cells (2.06 ± 1.26 vs 0.98 ± 0.65, P = 0.019) and Tfh17 cells (33.38 ± 15.14 vs 30.28 ± 4.89, P = 0.014) were inhibited. RNAseq analysis revealed significant downregulation of genes associated with the ‘herpes simplex virus 1 infection’ and ‘IL-17 signalling’ pathway. Myositis Disease Activity Assessment Tool (MDAAT) scores improved in 21 out of 24 patients. Fifteen (62.5%) patients met the criteria for International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI). Importantly, no severe adverse events necessitated treatment discontinuation.

Conclusion

Tofacitinib demonstrated significant immunologic and clinical effectiveness in DM and ASS patients, reducing key immune cell populations and downregulating immune activation pathways.
Radon in schools of Montenegro
Authors: Vukotic Perko , Zekic Ranko , Svrkota Nikola , Andjelic Tomislav , Dlabac Aleksandar , Mrdak Radivoje , Svrkota Ranko
Published: January 2025

During the school year, radon (222Rn) was continuously measured with passive detectors in all public schools in Montenegro—345 primary and 47 secondary schools. Measurements were taken in all ground-floor classrooms and offices (2336 rooms in total), as well as in 182 first-floor rooms across 91 schools. On the first floor, the arithmetic mean (AM) of radon concentrations was 100 Bq/m3, and the median (MED) was 65 Bq/m3, with only five schools having rooms where radon levels exceeded 300 Bq/m3. On the ground floor of all 392 schools, the AM was 276 Bq/m3, and the MED was 146 Bq/m3. In 188 schools, some rooms had radon levels above 300 Bq/m3, and in 43 schools, certain rooms exceeded 1000 Bq/m3. An assessment of the effective annual doses from radon inhalation for pupils was also conducted. On average, the dose was 0.66 mSv per school year, although in some classrooms it reached up to 11 mSv.
Ivanishvili v Credit Suisse Trust: (not) limiting trustee’s liability
Authors: Holcombe Sophie , Randall Jamie
Published: January 2025

The decision in Ivanishvili v Credit Suisse Trust Ltd (“Credit Suisse Trust”) is an important reminder of the high standards expected of trustees and the circumstances in which a trustee will be liable for loss to the trust fund. This article focuses on three ways in which Credit Suisse Trust sought to avoid liability. Two of these are concepts that are prevalent in modern trust deeds: anti-Bartlett clauses and the reservation of powers. The third is an import from the law of tort: the application of the scope of duty principle to claims for breach of fiduciary duty.
Transcriptomic analysis reveals potential roles of polyamine and proline metabolism in waterlogged peach roots inoculated with Funneliformis mosseae and Serendipita indica
Authors: Liang Sheng-Min , Abeer Hashem , Elsayed Fathi Abd_Allah , Wu Qiang-Sheng
Published: January 2025

Root-associated endophytic fungi can create symbiotic relationships with trees to enhance stress tolerance, but the underlying mechanisms, especially with regard to waterlogging tolerance, remain unclear. This study aimed to elucidate the effects of Funneliformis mosseae and Serendipita indica on the growth, root cross-section structure, and root transcriptional responses of peach under waterlogging stress, with a focus on polyamine and proline metabolism. Genes and transcription factors associated with secondary cell wall biosynthesis were selected, and their expression profiles were analyzed. F. mosseae significantly increased the height, stem diameter, and leaf number of peach seedlings subjected to two weeks of waterlogging stress, whereas S. indica only significantly improved stem diameter. Both fungal species substantially increased root diameter, stele diameter, the number of late metaxylem inside the stele, and late metaxylem diameter, thus improving aeration within inoculated roots under waterlogging stress. Transcriptomic analysis of waterlogged roots identified 5425 and 5646 differentially expressed genes following inoculation with F. mosseae and S. indica, respectively. The arginine and proline metabolism and arginine biosynthesis pathways were enriched following fungal inoculations. Both fungi reduced the conversion of glutamate and ornithine for proline synthesis. However, S. indica promoted peptide-to-proline conversion by up-regulating the expression of PIPs. Although both fungi promoted the expression of genes involved in arginine and ornithine synthesis pathway, only F. mosseae led to increased levels of arginine and ornithine. Additionally, F. mosseae promoted the accumulation of putrescine and maintained polyamine homeostasis by down-regulating PAO2 and SAMDC. Moreover, F. mosseae facilitated the metabolism of cadaverine. In conclusion, both F. mosseae and S. indica formed symbiotic relationships with peach, with F. mosseae primarily improving polyamine accumulation and S. indica predominantly facilitating proline accumulation for enhanced waterlogging resistance.
Inhibition of triglyceride metabolism‐associated enhancers alters lipid deposition during adipocyte differentiation
Authors: Zeng Sha , Li Ziqi , Li Xiaokai , Du Qinjiao , Zhang Yu , Zhong Zhining , Wang Haoming , Zhang Songling , Li Penghao , Li Haohuan , Chen Li , Jiang Anan , Shang Peng , Li Mingzhou , Long Keren
Published: January 2025

Triglyceride (TG) metabolism is a complex and highly coordinated biological process regulated by a series of genes, and its dysregulation can lead to the occurrence of disorders in lipid metabolism. However, the transcriptional regulatory mechanisms of crucial genes in TG metabolism mediated by enhancer–promoter interactions remain elusive. Here, we identified candidate enhancers regulating the Agpat2, Dgat1, Dgat2, Pnpla2, and Lipe genes in 3T3‐L1 adipocytes by integrating epigenomic data (H3K27ac, H3K4me1, and DHS‐seq) with chromatin three‐dimensional interaction data. Luciferase reporter assays revealed that 11 enhancers exhibited fluorescence activity. The repression of enhancers using the dCas9‐KRAB system revealed the functional roles of enhancers of Dgat2 and Pnpla2 in regulating their expression and TG metabolism. Furthermore, transcriptome analyses revealed that inhibition of Dgat2‐En4 downregulated pathways associated with lipid metabolism, lipid biosynthesis, and adipocyte differentiation. Additionally, overexpression and motif mutation experiments of transcription factor found that two TFs, PPARG and RXRA, regulate the activity of Agpat2‐En1, Dgat2‐En4, and Pnpla2‐En5. Our study identified functional enhancers regulating TG metabolism and elucidated potential regulatory mechanisms of TG deposition from enhancer–promoter interactions, providing insights into understanding lipid deposition.
Subtype-Specific Patterns of Tumor Purity and Mutation Load Suggest Treatment Implications
Authors: Schneider Daniel , Brown Ethan D.L. , Gluski Jacob , Mishra Akash , Shah Harshal A. , Sciubba Daniel M. , Lo Sheng-Fu Larry
Published: January 2025

Objectives:

Sarcomas are complex mesenchymal malignancies whose molecular characteristics can significantly influence treatment strategies. This study aimed to investigate the relationship between tumor purity, mutation load, and clinical characteristics across sarcoma subtypes, focusing on potential implications for therapeutic stratification.

Methods:

This study analyzed the molecular characteristics of 7494 sarcoma cases from the Soft Tissue and Bone Sarcoma (MSK, Nat Commun 2022) data set using available case analysis. Correlations between tumor purity, mutation load, age, and sex were analyzed using nonparametric methods, with subtype-specific analyses conducted using Kruskal-Wallis tests and Bonferroni-corrected post hoc comparisons. A comprehensive analysis of mutation patterns was performed using microsatellite instability (MSI) status.

Results:

Significant correlations between mutation load and tumor purity (ρ=0.320, P<0.001) were identified, with marked heterogeneity across subtypes. Tumor purity ranged from 20.0% in brain sarcomas to 78.5% in dermatofibrosarcoma protuberans. Age-related molecular changes were observed in brain (ρ=0.711, P=0.006) and skin sarcomas (ρ=0.450, P=0.006), suggesting distinct evolutionary patterns. A subset of hypermutated, microsatellite stable cases (0.15%) with mutation loads exceeding 100 mutations/mb were identified, suggesting alternative mechanisms of genomic instability. MSI-high status was rare (0.24%) but associated with higher mutation loads (median: 25.84 vs. 2.42, P<0.001), particularly in uterine sarcomas (0.7% prevalence).

Conclusions:

The identification of distinct molecular patterns across sarcoma subtypes challenge existing morphology-based classification systems and may hold implications for therapeutic stratification. These findings may help inform future immunotherapeutic and molecular-guided approaches to treatment in sarcoma patients, particularly for elderly patients with brain sarcomas or females with uterine sarcomas.
Factors Determining the Need for Ultrafiltration in Cardiorenal Syndrome
Authors: Coşkuner Muhammed Ali , İnci Ayça , Köker Gökhan , Yilmaz Üstün , Arslan Şakir
Published: January 2025

This study investigates the factors determining the need for ultrafiltration (UF) in patients with cardiorenal syndrome presenting with hypervolemia-related symptoms and signs. A total of 88 patients hospitalized for hypervolemia were treated according to current guidelines, with UF employed as a rescue therapy when diuretic treatment failed to achieve adequate decongestion. Data collected included medical history, laboratory findings, blood pressures, diuretic doses, spot urine sodium (measured 6 hours after diuretic therapy), response to diuretics, postdischarge creatinine levels, rehospitalization rates, and mortality rates. UF was required in 23.90% of patients due to insufficient response to diuretics, with a higher rate observed in men (34.10%) compared with women (13.64%). Patients needing UF had lower systolic blood pressure, higher initial serum creatinine levels, and elevated pro-B-type natriuretic peptide levels. Statistical analysis showed that an increase in initial creatinine levels raised the risk of requiring UF by 6.443 times, while a one-unit decrease in urine sodium increased the risk by 1.037 times. These findings suggest that male gender, high pro-B-type natriuretic peptide levels, low spot urine sodium, low systolic blood pressure, and high initial creatinine levels may predict the need for UF. Further research involving larger patient cohorts is necessary to refine these criteria and develop a risk score.
Biodegradable Temporizing Matrix in Postoncological Scalp Reconstruction: A Case Series
Authors: Calderbank Tom , Turner Emma , Mohamed Mohaned , Kanakopoulos Dimitrios , Kelemen Noemi
Published: January 2025

Biodegradable temporizing matrix (BTM) is a synthetic biodegradable dermal matrix that helps develop a non–skin graft amenable wound bed (eg, over tendon or bone) into a graftable wound bed, by acting as an inert scaffold for angiogenesis and formation of granulation tissue. There is currently a paucity of evidence to encourage its use in scalp defects following skin malignancy excision. This retrospective analysis aimed to evaluate the utility of BTM in this patient subset. This is a case series of patients undergoing BTM reconstruction for scalp defects following skin malignancy excision between January 2022 and January 2024. Data collected included demographics, as well as oncological and reconstructive outcomes. Thirteen distinct BTM cases were identified in 12 patients. All patients were male with a median age of 85 years. Of 13 lesions, 10 were confirmed squamous cell carcinoma, with 3 confirmed as malignant melanoma. Of 13 cases, 12 required excision down to the calvaria, with 1 down to pericranium. Of 13 cases, 11 went on to receive a split-thickness skin graft (STSG) after BTM application, with a median interval of 46 days. All these patients had complete take of their subsequent STSG. Two cases did not receive STSG, 1 had satisfactorily healed upon delamination of the BTM, and 1 had failure of BTM due to bacterial colonization. This study demonstrates the utility of BTM as a successful, low morbidity reconstructive option in patients undergoing skin cancer excision on the scalp.
A Study of Radium Content and Radon Exhalation Rates in Soil Samples from Abi-Adi Town, Ethiopia, Using LR-115 Type-II
Authors: Alene Assefa Nigus , Arbese Yisak
Published: January 2025

In the present study, we are presenting the results of radium content, radon concentration, and radon exhalation rates (both mass and area) for 32 soil samples collected from different locations of Abi-Adi Town, Ethiopia, by using the sealed can technique containing a LR-115 Type-II plastic detector. The values of radium content from soil samples were found to vary from 35.26 Bq kg−1 to 101.78 Bq kg−1, with a mean value of 70.25 Bq kg−1. The mass and area exhalation rates of radon were found to be from 2.72 × 10−6 Bq kg−1 d−1 to 7.87 × 10−6 Bq kg−1 d−1 and from 0.76 × 10−4 Bq m−2 d−1 to 2.20 × 10−4 Bq m−2 d−1, with a mean value of 5.43 × 10−6 Bq kg−1 d−1 and 1.52 × 10−4 Bq m−2 d−1, respectively. The outdoor and indoor annual effective dose equivalent varied from 0.24 mSv y−1 to 0.68 mSv y−1 and from 0.06 mSv y−1 to 0.17 mSv y−1 with a mean value of 0.37 mSv y−1 and 0.09 mSv y−1, respectively. The working level varied from 2.50 mWL to 7.21 mWL with a mean value of 3.94 mWL. From the results of this study, we found that there was a positive correlation between radium content and radon exhalation rates in soil samples. The radium content values determined in soil samples are less than the permissible value of 370 Bq kg−1 recommended by Organization for Economic Cooperation and Developments as acceptable for safe use. Thus, results reveal that the area under investigation is safe as far as the health hazards of radon are concerned.
Radiation Dose to Occupational Dosimeters Brought on Commercial Air Travel
Authors: Chang Lienard , Kim Daniel
Published: January 2025

Occupational radiation dosimeters that return high readings cannot always be explained by circumstances in the workplace. For this experiment, a series of optically stimulated luminescence (OSL) dosimeters were brought to airports to estimate the radiation dose OSLs would receive should a worker accidentally bring their dosimeter with them during travel. The OSLs returned readings between 0.77 and 3.70 mSv. While factors such as scanning times, machine modality and model, flight duration, and elevation changes can all affect dosimeter readings, this small experiment provides a general range of dose readings to dosimeters to assist radiation safety program managers in quantifying true radiation dose from the workplace.
A Sneaky Culprit: Secondary Infectious Keratitis Due to Brevundimonas diminuta
Authors: Thareja Suma K. , Luo Susan , Carballo Sarah
Published: January 2025

Purpose:

To describe a rare case of infectious keratitis secondary to Brevundimonas diminuta, a gram-negative bacillus with fluoroquinolone resistance and rare clinical isolation.

Methods:

A 50-year-old man with contact lens overuse presented with a large corneal ulcer and hand motion visual acuity. Initial treatment with fortified topical tobramycin and vancomycin yielded slow improvement, and initial culture grew Staphylococcus epidermidis, Staphylococcus hominis, and Corynebacterium bovis. Therapy was tapered to topical moxifloxacin. Loteprednol was added to reduce corneal inflammation after presumed sterilization. Persistent epithelial defect and worsening infiltrate after 3 weeks prompted repeat culture and corneal punch biopsy.

Results:

Repeat culture revealed B. diminuta resistant to moxifloxacin. Treatment was modified to tobramycin, and therapeutic penetrating keratoplasty was pursued to prevent further stromal loss. Four months postoperatively, the cornea remained clear without recurrence or neovascularization.

Conclusion:

To our knowledge, this is the second reported culture-positive case of secondary infectious keratitis with B. diminuta, highlighting its rarity and potential for delayed identification. The atypical response to initial therapy underscores the importance of repeat cultures and corneal biopsy in persistent cases. This case contributes to the growing understanding of rare ocular pathogens, advocating for a vigilant clinical approach.
Neuroradiological Correlates of Abnormal Pupillary Light Reflex Findings Among Patients in the Neuroscience Intensive Care Unit
Authors: Rana Chahat , Moreno Jorge H. , Marshall Jade L. , Olson DaiWai M. , Aiyagari Venkatesh
Published: January 2025

BACKGROUND: Changes in pupil reactivity secondary to cerebral mass effect are traditionally linked to compression of the oculomotor nerve by the uncus or by horizontal midbrain displacement. The neurological pupil index (NPi) is a metric to assess the pupillary light reflex. This study explores the relationship of midline shift, cisternal, and sulcal effacement or ventricular compression in patients with a new finding of abnormal pupillary light reflex. METHODS: This retrospective study identified adult patients with serial pupillometer readings between 2018 and 2023 who had a baseline head computed tomography (CT) scan, subsequent new-onset NPi worsening from normal to abnormal, and a repeat CT scan within 2 hours of the NPi changes. Those with NPi worsening were compared with those with no NPi change. RESULTS: Among 77 patients (27 with NPi worsening, 50 without), those with NPi worsening exhibited a higher incidence of midline shift on the repeat CT. Regression models revealed a significant correlation between midline shift change and abnormal NPi (r = 0.2260, P < .001). However, NPi worsening was not linked to changes in ventricular compression, nor sulcal or cisternal effacement. CONCLUSION: Midline shift, rather than cisternal or sulcal effacement, is associated with abnormal NPi values.
Dysmenorrhea, Premenstrual Syndrome, and Lifestyle Habits in Young University Students in Spain: A Cross-Sectional Study
Authors: FRANCO-ANTONIO Cristina , SANTANO-MOGENA Esperanza , CORDOVILLA-GUARDIA Sergio
Published: January 2025

Background

Menstruation is a physiological process that may be accompanied by pain, headache, edema, emotional changes, and other symptoms, all of which affect quality of life. Although the results of some studies indicate lifestyle habits can affect the menstrual cycle and associated symptoms, few have investigated this issue, and even fewer have explored the impact of these symptoms on quality of life, in Spanish women.

Purpose

The objectives of this study were to determine the prevalence of dysmenorrhea and premenstrual syndrome (PMS) among students at a Spanish university, assess the impact of these conditions on quality of life, and analyze the relationship among lifestyle habits, dysmenorrhea, and PMS.

Methods

A cross-sectional study was carried out on 743 women enrolled at the University of Extremadura in the 2021–2022 academic year. Data related to the menstrual cycle, pain, and PMS-related physical and emotional symptoms were collected. Quality of life related to menstruation was evaluated using the CVM-22 scale. Lifestyle data collected included adherence to a Mediterranean diet (PREDIMED [Prevención con Dieta Mediterránea] questionnaire), level of physical activity (International Physical Activity Questionnaire), and alcohol and tobacco consumption (Alcohol, Smoking, and Substance Involvement Screening Test Version 3). Also, other clinical data were recorded.

Results

In terms of the sample, the median age was 21 (19–23) years, the prevalence of dysmenorrhea was 57.9%, 92.7% reported premenstrual physical symptoms, and 55.6% reported experiencing premenstrual emotional changes. Having a low level of adherence to a Mediterranean diet was associated with the presence of dysmenorrhea, with an adjusted odds ratio (aOR) of 1.47 (95% CI [1.06, 2.03]). Having a low level of physical activity was strongly associated with the presence of premenstrual physical symptoms, with an aOR of 5.89 (95% CI [1.71, 20.26]). Also, an association was found between tobacco use and premenstrual emotional changes, with an aOR of 2.02 (95% CI [1.25, 3.25]). Furthermore, dysmenorrhea and PMS were both associated with a low quality of life, with pain and emotional changes being the most significantly associated factors, with ORs of 16.25 (95% CI [10.36, 25.47]) and 26.73 (95% CI [16.46, 43.40]), respectively.

Conclusions

Similar to previous studies, the findings of this study indicate a high prevalence of dysmenorrhea and PMS among young university students in western Spain, with both of these symptoms impacting quality of life significantly and negatively. In addition, lifestyle habits, diet, physical activity, and tobacco use seem to influence the occurrence of these symptoms. Promoting lifestyle changes may be an effective strategy to reduce the incidence of dysmenorrhea and PMS and improve the quality of life of young women.
Glycosyltransferase B3GNT3 promotes immune evasion in pancreatic cancer by downregulating MHC-I levels on the surface of pancreatic cancer cells
Authors: Yin Shi-Qi , Ma Hong-Tai , Li Xia-Qing , Xiao Shu-Yu , Tulamaiti Aziguli , Zhang Zhi-Gang , Xing Xin
Published: January 2025

Objective:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging malignancies in the digestive system. Immune evasion is a crucial factor leading to poor prognosis in patients. This study aims to investigate the molecular mechanisms of immune evasion in PDAC cells.

Methods:

We utilized the TCGA & GTEx, GEO databases, and immunohistochemistry to analyze the expression patterns of B3GNT3 in normal pancreatic tissues and tumor tissues. We explored the biological pathways involving B3GNT3 through RNA-seq and GO enrichment analysis. The correlation between B3GNT3 and MHC-I levels was examined using flow cytometry. Additionally, by establishing a mouse PDAC orthotopic model, we investigated the relationship between B3GNT3, PDAC progression, and CD8+ T cell function.

Results:

B3GNT3 mRNA levels are significantly higher in tumor samples compared to normal tissue, and its expression is negatively correlated with patient prognosis. RNA-seq analysis suggests B3GNT3 may impact MHC-I-mediated antigen presentation. Knockdown of B3GNT3 increases MHC-I levels on tumor cells, while overexpression decreases them. In a mouse PDAC model, B3GNT3 knockdown inhibits tumor growth and increases CD8+ T cell infiltration.

Conclusions:

The expression level of B3GNT3 in PDAC cells is negatively correlated with MHC-I levels, thereby affecting the ability of CD8+ T cells to recognize tumor cells and exert their cytotoxic function, making tumor cells more prone to immune evasion.
Deep Learning–Powered CT-Less Multitracer Organ Segmentation From PET Images
Authors: Salimi Yazdan , Mansouri Zahra , Shiri Isaac , Mainta Ismini , Zaidi Habib
Published: January 2025

Purpose

The common approach for organ segmentation in hybrid imaging relies on coregistered CT (CTAC) images. This method, however, presents several limitations in real clinical workflows where mismatch between PET and CT images are very common. Moreover, low-dose CTAC images have poor quality, thus challenging the segmentation task. Recent advances in CT-less PET imaging further highlight the necessity for an effective PET organ segmentation pipeline that does not rely on CT images. Therefore, the goal of this study was to develop a CT-less multitracer PET segmentation framework.

Patients and Methods

We collected 2062 PET/CT images from multiple scanners. The patients were injected with either 18F-FDG (1487) or 68Ga-PSMA (575). PET/CT images with any kind of mismatch between PET and CT images were detected through visual assessment and excluded from our study. Multiple organs were delineated on CT components using previously trained in-house developed nnU-Net models. The segmentation masks were resampled to coregistered PET images and used to train 4 different deep learning models using different images as input, including noncorrected PET (PET-NC) and attenuation and scatter-corrected PET (PET-ASC) for 18F-FDG (tasks 1 and 2, respectively using 22 organs) and PET-NC and PET-ASC for 68Ga tracers (tasks 3 and 4, respectively, using 15 organs). The models’ performance was evaluated in terms of Dice coefficient, Jaccard index, and segment volume difference.

Results

The average Dice coefficient over all organs was 0.81 ± 0.15, 0.82 ± 0.14, 0.77 ± 0.17, and 0.79 ± 0.16 for tasks 1, 2, 3, and 4, respectively. PET-ASC models outperformed PET-NC models (P < 0.05) for most of organs. The highest Dice values were achieved for the brain (0.93 to 0.96 in all 4 tasks), whereas the lowest values were achieved for small organs, such as the adrenal glands. The trained models showed robust performance on dynamic noisy images as well.

Conclusions

Deep learning models allow high-performance multiorgan segmentation for 2 popular PET tracers without the use of CT information. These models may tackle the limitations of using CT segmentation in PET/CT image quantification, kinetic modeling, radiomics analysis, dosimetry, or any other tasks that require organ segmentation masks.
Beyond One-Size-Fits-All
Authors: Kang Daihun
Published: January 2025

Background

Digital nerve injuries significantly affect hand function and quality of life, necessitating effective reconstruction strategies. Autologous nerve grafting remains the gold standard due to its superior biocompatibility, despite recent advancements in nerve conduits and allogenic grafts. This study aims to propose a novel zone-based strategy for donor nerve selection to improve outcomes in digital nerve reconstruction.

Methods

A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, searching PubMed, Embase, Cochrane Library, and Web of Science for articles published from January 2004 to December 2023. Inclusion criteria included studies involving adult human subjects undergoing autologous nerve grafting for digital nerve reconstruction, with sensory recovery and donor site morbidity as primary outcome measures. Additionally, an anatomical study comparing donor nerves to digital nerves was included.

Results

Five studies met the inclusion criteria: 4 clinical studies and 1 anatomical study. Analysis of the 4 included clinical studies showed that the posterior interosseous nerve had the lowest donor site morbidity (6.25%), while the lateral antebrachial cutaneous nerve (LABCN) demonstrated the best sensory recovery outcomes (mean 2-point discrimination of 5.92 mm, with 100% of patients achieving good to excellent recovery). The sural nerve exhibited acceptable donor site morbidity (15%) but showed the lowest sensory recovery outcomes (mean 2-point discrimination of 10.8 mm, with only 46% of patients reporting good to very good recovery). The anatomical study indicated that the LABCN had the closest match in cross-sectional area and fascicle count to most zones of the digital nerve, supporting its suitability as a graft source.

Conclusions

Although there are many nerve reconstruction techniques available, autologous nerve grafting remains the gold standard. Based on the analysis of five studies, this review proposes a new zone-based approach for donor nerve selection, emphasizing matching donor nerves to specific injury zones. This tailored strategy can potentially optimize both functional recovery and donor site morbidity, moving beyond the one-size-fits-all paradigm. The posterior interosseous nerve, LABCN, and SN each provide unique benefits depending on the zone of injury, suggesting that this approach may lead to improved patient outcomes. Future research is needed to validate this framework.
Surgical Outcomes for Nonmelanoma Skin Cancer of the Head and Neck
Authors: Liu Hua , Dai Xiaoming
Published: January 2025

Objectives

There is no consensus on elective lymphatic dissection of the parotid and neck for nonmelanoma skin cancer (NMSC) due to challenges in detecting occult spread to these regions. This study aimed to summarize clinical data and evaluate correlations between risk factors, nodular metastasis, and the need for elective parotidectomy in patients with cutaneous squamous cell carcinoma (CSCC), Merkel cell carcinoma (MCC), and apocrine carcinoma (AC) of the head and neck, all with clear surgical margins and negative imaging results for regional metastases.

Study Design

We retrospectively reviewed 166 patients with CSCC, one with MCC, and one with AC of the head and neck, all treated surgically between September 2006 and July 2022. The neck and parotid nodes were imaged preoperatively, and nodular metastases were verified by pathological examination. Age, maximum primary tumor dimension, and primary tumor depth were evaluated in patients with and without nodular metastases.

Results

Seven patients developed nodular metastases after primary tumor excision. Facial paralysis occurred in three of five patients with parotid spread. Age and primary tumor size differed significantly between patients with and without nodular metastases (P < 0.05). Tumor depth did not differ significantly between these groups (P > 0.50).

Conclusions

Negative imaging results of nodular metastases before primary tumor excision and clear margins did not imply exemption from nodular metastases postoperatively. Nodular spread of CSCC is associated with multiple risk factors rather than any single factor. Elective parotidectomy is recommended to prevent facial nerve invasion by occult nodular metastasis in patients with CSCCs with advanced age, large primary tumor size (≥T3), critical tumor locations, and/or pathological types with high metastatic potential.
MicroRNA-146b targets HIF-1α AND attenuates cardiomyocyte apoptosis and fibrosis in doxorubicin-induced heart failure
Authors: Wang Min , Lu Rui , Peng Liang , Xu Ling-Ling , He Shang-Fei , Guo Tao , Lu Ming-Jun , Luo Yi , Cui Tong-Tao
Published: January 2025

The global prevalence of heart failure is still growing, which imposes a heavy economic burden. The role of microRNA-146b (miR-146b) in HF remain largely unknown. This study aims to explore the role and mechanism of miR-146b in HF. Method: We applied Reverse transcription-polymerase chain reaction (RT-PCR) to search for differential microRNAs between myocardial tissues of heart failure patients and controls. We also used RT-PCR to detect the miR-146b expression in primary neonatal mouse cardiomyocytes (NMCMs) and mice models of doxorubicin induced HF. In vivo experiments, echocardiography was performed at baseline and weeks 6. After that we harvested mice’ heart and evaluated the cardiomyocyte with hematoxylin and eosin (HE), Masson trichrome staining and TUNEL staining. Through bioinformatics analysis, we found HIF-1α might be the target gene of miR-146b which validated by luciferase reporter gene assay. Subsequently, mRNA and protein expression levels of HIF-1α were detected by overexpression or inhibition of miR-146b in primary NMCMs. Results: We found that miR-146b expression was decreased in myocardial tissues of HF patients compared with controls (p < 0.01). MiR-146b levels were notably down regulated in HF models. MiR-146b knockout mice showed a more pronounced decrease in cardiac function and more severe myocardial fibrosis and apoptosis than wild type. Meanwhile, over expression or repression of miR-146b in primary neonatal mouse cardiomyocytes could inhibit or upregulate HIF-1α mRNA and protein expression. Conclusion: Our study shows that miR-146b may be a protective factor for cardiomyocytes by modulating HIF-1α.
Endothelial-specific knockout of the scramblase TMEM16F impairs in vivo clot formation
Authors: Bonson Grace , Lambert Aaron R. , Sackheim Adrian M. , Howard Abigail , Piffard Sophia H. , Lescieur-Garcia Carlos , Cleary Jade , Rubinelli Luisa , DiLorenzo Annarita , Majumdar Devdoot , Hennig Grant , Nelson Mark T. , Freeman Kalev
Published: January 2025

Objective

Loss of function of the phospholipid scramblase (PLS) TMEM16F results in Scott Syndrome, a hereditary bleeding disorder generally attributed to intrinsic platelet dysfunction. The role of TMEM16F in endothelial cells, however, is not well understood. We sought to test the hypothesis that endothelial TMEM16F contributes to hemostasis by measuring bleeding time and venous clotting in endothelial-specific knockout (ECKO) mice.

Materials and Methods

We initially evaluated the extent to which TMEM16F contributes to endothelial calcium events produced by trauma factors in vitro, using a pharmacological approach. Cultured endothelial cells were exposed to histones in the presence or absence of the PLS inhibitor, niclosamide, for live-cell calcium imaging and flow cytometry with annexin V staining. We then applied a genetic approach to specifically ablate TMEM16F in vascular endothelial cells in vivo using a murine tamoxifen-inducible cre-lox system under control of a Cdh5 promoter. Hemostasis was evaluated by measuring tail bleeding time after a distal 5 mm tail resection. Venous thrombus formation was evaluated by creating a surgical stenosis of the inferior vena cava (IVC) and harvesting the resultant clot 24 hours post-procedure for measurement. Blood samples were obtained via IVC cannulation to assay plasma-based coagulation. Mesenteric arteries were isolated and cannulated for assessment of endothelial-dependent vasodilation by pressure myography.

Results

Pretreatment with the PLS inhibitor niclosamide prevented pathological calcium signals and mitigated PS translocation in cultured endothelial cells exposed to extracellular histones. TMEM16F ECKO mice exhibited prolonged bleeding compared to controls (time, 205.6 +/- 234.5 vs. 38.1 +/- 29.11 sec; p < 0.05). The ECKO mice also generated significantly smaller IVC thrombi (length, 0.9 +/- 1.4 vs. 4.7 +/- 3.3 mm; p < 0.05). TMEM16F ablation did not impact prothrombin time or endothelial-dependent vasodilatory function.

Conclusions

Endothelial TMEM16F function is essential for normal hemostasis. ECKO of TMEM16F is sufficient to produce a coagulopathic phenotype, as shown by the prolonged bleeding time after tail transection and decreased thrombus generation in response to IVC stenosis. Because endothelial calcium events are pathologically amplified in response to trauma factors, these results suggest that TMEM16F may play a role in trauma-induced coagulopathy.
Isolated Neisseria meningitidis-associated endophthalmitis in an immunocompetent host: case report and literature review
Authors: Lo Calvin Ka-Fung , Hughes Lauren , Schonhofer Cole , Bowie William R , McCormick Iain , Kirker Andrew
Published: January 2025

Introduction

Neisseria meningitidis is a Gram-negative diplococcus with significant infectious sequelae including meningitis and disseminated meningococcal bloodstream infection. Rarely has it been reported in the context of endophthalmitis without central nervous system involvement. We report a clinical case of isolated meningococcal endophthalmitis in an immunocompetent patient and present a literature review on published cases including treatment regimens and clinical outcomes.

Case Presentation

A 51-year-old male with no significant medical history presented to the emergency department with acute vision loss in the right eye after returning from Mexico. Ophthalmic examination was consistent with endophthalmitis, presumed to be endogenous in the absence of recent ocular trauma or surgery. Vitreous culture was positive for growth of gram-negative diplococci, subsequently identified as Neisseria meningitidis. Blood and cerebrospinal fluid cultures were negative for growth of similar or implicative pathogens. There was no evidence of disseminated meningococcal infection; imaging did not demonstrate any drainable collections or sequelae of extension into the central nervous system. The patient was treated with intravitreal antibiotics as well as topical steroids and antibiotics. In addition, he completed a two-week course of systemic antibiotics. Visual outcome was unfortunately poor.

Conclusion

This case illustrates a rare case of isolated endophthalmitis secondary to meningococcus, presumably from nasopharyngeal source. In these clinical scenarios, clinicians should perform a thorough evaluation for predisposing immunodeficiencies.
Genetic score associations with birthweight in preterm-born infants compared with term-born infants
Authors: Beaumont Robin N , Kotecha Sarah J , Simpson Shannon J , Kotecha Sailesh , Freathy Rachel M
Published: January 2025

Objective

In preterm infants, lower birthweight correlates with a higher risk of neonatal complications. Understanding the factors influencing birthweight in these infants is important as it may guide future antenatal and perinatal care. Genetic variants account for at least one-quarter of variation in birthweight in term-born infants, but the genetic contribution to birthweight in preterm infants is not well understood. We aimed to compare genetic score associations with birthweight in a well-powered sample of preterm infants with those in term-born infants.

Study design

We used linear regression to test the association between birth weight and fetal genetic scores for birthweight (BW-GS) in a total of 1,416 preterm, singleton and 15,253 term, singleton infants. Analyses, adjusted for ancestry principal components were performed within each of 4 datasets and meta-analysed.

Results

In term-born infants: a 1 SD higher BW-GS was associated with a 1.20 (95% CI 1.10-1.29) SD higher birthweight. In preterm infants, there was also strong evidence of association, but with a smaller effect size (0.76SD (0.41-1.11) higher birthweight per 1-SD higher BW-GS). In preterms, when stratifying by gestational duration, we found that the associations strengthened with increasing gestational duration.

Conclusions

Genetic scores composed of variants identified in term-born infants also influenced birthweight in preterm infants. However, the associations had smaller effects in preterms and were weaker at earlier gestations. This suggests that while many of the same genetic factors influence birthweight in preterm and term-born infants, other factors (environmental, placental, different genetic) may be more important in preterms. Future well-powered studies are required to investigate this.