bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating network pharmacology and bioinformatics to explore the mechanism of Xiaojian Zhongtang in treating major depressive disorder: An observational study
Authors: Jiang Huaning , Zhang Jian , Li Quan , Zhou Yanyan
Published: September 2024

Major depressive disorder (MDD) is a common mental illness. The traditional Chinese medicine compound Xiaojian Zhongtang (XJZT) has a good therapeutic effect on MDD, but the specific mechanism is not clear. The aim of this study is to explore the molecular mechanism of XJZT in the treatment of MDD through network pharmacology and bioinformatics. The traditional Chinese medicine system pharmacology database was used to screen the chemical components and targets of XJZT, while the online Mendelian inheritance in man, DisGeNET, Genecards, and therapeutic target database databases were used to collect MDD targets and identify the intersection targets of XJZT and MDD. A “drugs-components-targets” network was constructed using the Cytoscape platform, and the STRING was used for protein-protein interaction analysis of intersecting targets. Gene Ontology and Kyoto encyclopedia of genes and genomes analysis of intersecting targets was performed using the DAVID database. Obtain serum and brain transcriptome datasets of MDD from the gene expression omnibus database, and perform differentially expressed genes, weighted gene co-expression network analysis, gene set enrichment analysis, and receiver operating characteristic analysis. A total of 127 chemical components and 767 targets were obtained from XJZT, among which quercetin, kaempferol, and maltose are the core chemical components, and 1728 MDD targets were screened out, with 77 intersecting targets between XJZT and MDD. These targets mainly involve AGE-RAGE signaling pathway in diabetic complexes, epidermal growth factor receptor tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway, and these core targets have strong binding activity with core components. In addition, 1166 differentially expressed genes were identified in the MDD serum transcriptome dataset, and weighted gene co-expression network analysis identified the most relevant gene modules (1269 genes), among which RAC-alpha serine/threonine-protein kinase (AKT1), D(4) dopamine receptor (DRD4), and kynurenine 3-monooxygenase (KMO) were target genes for the treatment of MDD with XJZT, these 3 genes are mainly related to the ubiquitin-mediated proteolysis, arachidonic acid (AA) metabolism, and Huntington disease pathways, and the expression of AKT1, DRD4, and KMO was also found in the MDD brain transcriptome dataset, which is significantly correlated with the occurrence of MDD. We have identified 3 key targets for XJZT treatment of MDD, including AKT1, KMO, and DRD4, and they can be regulated by the key components of XJZT, including quercetin, maltose, and kaempferol. This provides valuable insights for the early clinical diagnosis and development of therapeutic drugs for MDD.
Immunoprognostic analysis of indoleamine 2,3-dioxygenase 1 in patients with cervical cancer
Authors: Xu Cong , Wang Min , Chen Chaowen , Xu Yonghong , Liu Fang , Wang Guangming
Published: September 2024

The incidence of cervical cancer is increasing. Immunotherapies show better patient outcomes than monotherapies; however, the mainstay treatment for cervical cancer remains surgery and chemotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) acts on multiple tryptophan substrates, exhibiting antitumor, immunomodulatory, and antioxidant activities. Despite the association of elevated IDO1 expression with unfavorable outcomes in various cancers, its precise function in cervical cancer remains ambiguous. Here, we explored the prognostic significance of IDO1 in cervical carcinoma. Gene expression datasets were obtained from The Cancer Genome Atlas. Gene Expression Omnibus datasets were used for differential expression and functional correlation analyses. Using Human Protein Atlas alongside Tumor-Immune System Interaction Database, we assessed the association of IDO1 with survival rates. Given the link between cervical cancer prognosis and immune invasion, CIBERSORT was used to assess the connection between immune cells and IDO1, while the percentage of tumor-penetrating immune cells based on IDO1 expression in cervical cancer patients was analyzed using Tumor-Immune System Interaction Database. Incorporating a clinicopathological characteristic-based risk score model with IDO1 risk score, we devised a nomogram to predict cervical cancer patient survival. The effects of IDO1 in immune regulation and its prognostic significance were validated using data from patients with cervical cancer obtained from The Cancer Imaging Archive database. Compared with that in normal cervical tissues, IDO1 expression was significantly upregulated in cervical cancer tissues and significantly correlated with cervical cancer progression and prognosis. IDO1 expression showed a positive association with monocyte and macrophage abundance, while exhibiting a negative correlation with that of endothelial cells and eosinophils. Cox regression analyses highlighted IDO1 as the core immune gene implicated in cervical cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed an association of IDO1 with the metabolic pathways of tryptophan, phenylalanine, and tyrosine. Univariate and multivariate analyses revealed that elevated IDO1 expression correlates markedly with cervical cancer outcomes, suggesting it as a promising therapeutic target. The Cancer Imaging Archive data analysis revealed that the impact of anti-PD1 and CTLA4 therapy is more pronounced in cervical cancer patients exhibiting elevated IDO1 expression. IDO1 is a potential target for immunotherapy for cervical cancer.
Clinical observation of low temperature plasma ablation combined with collagenase injection in lumbar disc herniation
Authors: Zhang Yulin , Fang Qifan , Zhao Yongming , Yang Ying
Published: September 2024

To observe the effect of low temperature plasma ablation combined with collagenase injection on lumbar disc herniation. 90 patients with lumbar disc herniation admitted to the pain department of our hospital and receiving surgical treatment from April 2021 to April 2023 were included in this retrospective study, and were divided into 2 groups according to different treatment plans. One group was treated with low-temperature plasma ablation combined with collagenase injection, and the other group was treated with low-temperature plasma ablation alone. The sample size of both groups was 80 cases. Peripheral blood was collected by fasting in the morning at 5 time points before surgery, 1, 3, 7 and 14 days after surgery, and 5 mL of whole venous blood was collected by disposable vacuum blood collection device. Serum levels of pro-inflammatory factor interleukin (IL)-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α and anti-inflammatory factor IL-4, IL-10 were detected by ELISA. VAS scores were used to evaluate postoperative low back pain. ODI and Lehmann Lumbar Function Scale were used to evaluate postoperative lumbar function. The contents of IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α and anti-inflammatory factor IL-4, IL-10 in the cryo-plasma ablation combined with collagenase injection group were significantly lower than those in the cryo-plasma ablation group alone (P < .05). The VAS score of cryo-plasma ablation combined with collagenase injection group was significantly lower than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The ODI score of cryo-plasma ablation combined with collagenase injection group was significantly lower than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The Lehmann score of cryo-plasma ablation combined with collagenase injection group was significantly higher than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The overall efficacy of low-temperature plasma ablation combined with collagenase injection is better than that of low-temperature plasma ablation alone. Low temperature plasma ablation combined with collagenase injection in the treatment of patients with lumbar disc herniation has less pain, faster recovery.
Clinical study on the establishment of radio-cephalic autogenous arteriovenous fistulas in small blood vessels by multi-segment balloon dilation technique
Authors: Kang Qiyu , Hao Yajie , Zhang Huifeng , Yu Weimin , Huang Xiaoguang
Published: September 2024

Background:

To investigate the effect of dilating small blood vessels using a balloon dilation (BD) technique on the occurrence of radio-cephalic autogenous arteriovenous fistulas in terms of patency, blood flow, and vein diameter (VD).

Methods:

The subjects included in this study were all patients with chronic renal failure and required radio-cephalic arteriovenous fistula surgery for the first time and had not received dialysis before. Patients with VDs <2 mm were included as study subjects. They were either assigned treatment using a BD group or a control group that received hydrostatic dilation. The differences between the 2 groups were analyzed in terms of patency, blood flow, and VD.

Results:

A total of 22 patients were enrolled in the balloon dilatation group and 20 patients in the control group. The diameters of cephalic veins (mm) of the experimental and control group were compared at various time points: immediately postoperation, 2.89 ± 0.42 versus 1.99 ± 0.28 (P < .001); 1 week later, 3.16 ± 0.59 versus 2.66 ± 0.60 (P = .022); 1 month later, 3.76 ± 0.91 versus 3.18 ± 0.83 (P = .087); and 2 months later, 4.08 ± 1.15 versus 3.38 ± 1.13 (P = .169). Brachial artery flows (mL/min) of the 2 groups at various time points were given as follows: immediately postoperation, 413.49 ± 145.09 versus 235.61 ± 87.77 (P < .001); 1 week later, 563.26 ± 206.83 versus 331.30 ± 126.78 (P < .001); 1 month later, 679.34 ± 218.56 versus 376.79 ± 156.25 (P < .001); and 2 months later, 736.31 ± 202.61 versus 394.60 ± 161.96 (P < .001). The primary patency at 1 year for the experimental group was 61.9% compared to 11.1% for the control group (P = .045). Similarly, the secondary patency rates at 1 year were 90.5% for the experimental group and 55.6% for the control group (P = .030). The results showed that the functional primary patency rate within 1 year was 57.1% versus 16.7% (P = .032), and the functional secondary patency rate within 1 year was 85.7% versus 50.0% (P = .038).

Conclusion subsections:

BD has obvious advantages over hydrostatic dilation for chronic renal failure patients with small veins in establishing arteriovenous fistula in terms of patency and blood flow.
Effect of targeted temperature management on systemic inflammatory responses after out-of-hospital cardiac arrest: A prospective cohort study
Authors: Chen Dalong , Lin Yukai , Ko Poyen , Lin Jenjyh , Huang Chihyang , Wang Gueijane , Chang Kuan-Cheng
Published: September 2024

Background:

Interleukin (IL)-6 is a major inflammatory cytokine that predicts mortality after out-of-hospital cardiac arrest (OHCA). Targeted temperature management (TTM) is associated with improved all-cause mortality in patients with OHCA. However, the effect of TTM on IL-6 production remains unclear. This study investigated whether TTM has additional anti-inflammatory effects after OHCA.

Methods:

This prospective cohort study included a total of 141 hospitalized patients with OHCA who were treated between January 2015 and June 2023. The study was conducted in the intensive care unit of China Medical University Hospital, Taichung. Postcardiac arrest care included TTM or the control approach (no TTM). The primary outcomes included the 90-day mortality rate and neurologic outcomes after OHCA. Differences between the TTM and control groups were examined using Student t test, chi-square test, and Kaplan–Meier survival curve analysis. Multivariate analysis of variance model was used to examine interaction effects.

Results:

Plasma IL-6 and IL-6/soluble IL-6 receptor complex levels were measured at 6 and 24 hours after resuscitation. IL-6 and IL-6/soluble IL-6 receptor complex production was lower in the TTM group than in the control group (−50.0% vs +136.7%, P < .001; +26.3% vs +102.40%, P < .001, respectively). In addition, the 90-day mortality rate and poor neurologic outcomes were lower in the TTM group than in the control group (36.8% vs 63.0%, relative risk 0.39, 95% confidence interval 0.24–0.64, P < .001; 65.5% vs 81.5%, relative risk 0.80, 95% confidence interval 0.66–0.98, P = .04).

Conclusion:

TTM improves both the mortality rate and neurologic outcomes in patients resuscitated from OHCA, possibly by reducing IL-6-induced proinflammatory responses.
Insights into multilevel tissue-level collateral status using ColorViz maps from dual data sources in acute ischemic cerebrovascular diseases: A STARD-compliant retrospective study
Authors: Zhang Xiaoxiao , Liu Qingyu , Guo Luxin , Guo Xiaoxi , Zhou Xinhua , Lv Shaomao , Lin Yu , Wang Jinan
Published: September 2024

This study aims to explore the utility of ColorViz mapping from dual data sources for assessing arterial collateral circulation and predicting cerebral tissue-level collateral (TLC) in patients with acute ischemic cerebrovascular diseases. A retrospective study was conducted at a single center on a cohort of 79 patients diagnosed with acute ischemic cerebrovascular diseases between November 2021 and April 2022, who had undergone both multi-phase CT angiography (mCTA) and computed tomography perfusion (CTP). The quality of images and arterial collateral status depicted on ColorViz maps from dual data-sets (mCTA and CTP) were assessed using a “5-point scale” and a “10-point scale,” respectively. The status of TLC was evaluated by analyzing multilevel hypoperfusion volume and the hypoperfusion intensity ratio (HIR). The Spearman correlation coefficient was employed to examine the association between arterial collateral status derived from dual data sources and TLC. Receiver operating characteristic curve analysis was used to determine the diagnostic efficacy in detecting large vessel occlusive acute ischemic stroke (LVO-AIS). The ColorViz maps derived from dual data sources facilitated comparable image quality, with over 95% of cases meeting diagnostic criteria, for the evaluation of arterial level collateral circulation. Patients with robust arterial collateral circulation, as determined by dual data sources, were more likely to exhibit favorable TLC status, as evidenced by reductions in hypoperfusion volume (Tmax > 4 seconds, Tmax > 6 seconds, Tmax > 8 seconds, and Tmax > 10 seconds, P < .05) and HIR (Tmax > 6 seconds/4 seconds, Tmax > 8 seconds/4 seconds, Tmax > 10 seconds/4 seconds, and Tmax > 8 seconds/6 seconds, P < .05). The sensitivity and specificity in detecting LVO-AIS was 60.00% and 97.73% for mCTA source maps, while 74.29% and 72.73% for CTP source maps (P > .05 based on De-Long test). In conclusion, this study indicates that ColorViz maps derived from both data sources are equally important in evaluating arterial collateral circulation and enhancing diagnostic efficiency in patients with LVO-AIS, as well as offering insights into the TLC status based on hypoperfusion volume and HIR.
Incidence of associated anomalies in children with anorectal malformation: A 1-year prospective observational study in a low-income setting
Authors: Wondemagegnehu Belachew Dejene , Asfaw Solomon Wubetu , Mamo Tihtina Nigussie , Aklilu Woubedel Kiflu , Robelie Amezene Tadess , Gebru Fisseha Temesgen , Gebreselassie Hanna Getachew
Published: September 2024

Anorectal malformations (ARMs) consist of a range of anomalies that are often associated with other anomalies The purpose of the study is to assess the incidence of associated congenital anomalies that are seen in patients with ARMs. An observational prospective study was conducted on 162 cases with ARM from February 2019 to January 2020, and data were collected on patient demographics, type of ARM, and associated anomalies using a prestructured questionnaire and analysis done using SPSS (IBM), version 23, software. Relevant statistical analysis was done, and the results are presented in tables and charts. Of 162 cases studied, 70 of them were males and 92 were females with a male-to-female ratio of 0.76:1. The majority of male patients (45%) had rectourethral fistulas, whereas 63% of the females had rectovestibular fistula. While 76 (47%) patients presented with isolated ARM, 86 (53%) had ≥1 associated congenital malformations. Forty-eight (30%) patients presented with a single associated anomaly, whereas 20 (12%) patients had≥3 associated anomalies. The commonest associated anomalies were urologic 26.5% followed by genital (22.8%), cardiac 20.4%, and musculoskeletal 16.6%, and 12.3% of them had vertebral; anorectal; cardiac; tracheoesophageal fistula; renal; limb association. More than half of the children have other associated abnormalities. We found urogenital anomalies to be the most common associated congenital defects. A lower incidence of cardiac and spinal cord anomalies was noted suggesting a need for active workup to be in line with the latest standards of care.
Influencing factors of glycemic control in singleton pregnancies complicated by gestational diabetes mellitus in western China: A retrospective study
Authors: Zhang Jiani , Mao Chihui , Cao Qi , Huang Guiqiong , Wang Xiaodong
Published: September 2024

To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019–1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052–3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320–2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046–1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273–1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications.
A discussion on a suspected case with EGPA after maintenance hemodialysis for 5 years and related literature analysis: A case report
Authors: Zhao Lingshan , Zhang Chenli
Published: September 2024

Rationale:

Pathological featuring by necrotizing granulomatous inflammation of peripheral blood and tissues with increased eosinophils infiltrating small and medium vessels, eosinophilic granulomatosis with polyangiitis (EGPA), a family of rare antineutrophil cytoplasmic antibody (ANCA) associated with systemic vasculitis. With low morbidity, diverse clinical manifestations, and difficult early diagnosis, the majority of patients are confirmed after multiple organ damages, thus missing the best treatment time and having a poor prognosis. About 25% to 30% of EGPA cases have been reported to suffer from the renal disease, and there are few studies on EGPA complicated with kidney damage, most of them on ANCA-positive patients. Generally, the initial diagnosis of EGPA on maintenance hemodialysis is even rare. We report a case of a patient with maintenance hemodialysis for 5 years and then was diagnosed with EGPA.

Patient concerns:

The female patient, 54-year-old, having maintenance hemodialysis for 5 years consecutively, was hospitalized for the recurring rash in the past 3 years and then exacerbation in the last 2 months. With the previous history of bronchial asthma having attacked frequently recently, it could be observed from peripheral blood that the eosinophils increased, from the cardiac color ultrasound that it was prone to eosinophilic endocarditis, from 5 tests for vasculitis that P-ANCA and MPO-AB were positive.

Diagnoses:

The patient’s onset is renal dysfunction, with maintenance hemodialysis for 5 years, recurrent lung infections, combined with eye lesions, scattered skin rashes, P-ANCA positive, MPO-AB positive, asthma present, eosinophil absolute value 1.60 × 109/L, total score >6 points, diagnosis considering EGPA.

Interventions:

Due to multiple organ damage, the patient received treatment with a combination of steroids and cyclophosphamide.

Outcomes:

After 2 days, the patient’s rash significantly darkened compared to before, wheezing improved, and eosinophils returned to normal levels.

Lessons:

The ANCA test shall be put on the high agenda for patients presenting with kidney failure at first. Meanwhile, the neglected immune monitoring for patients with dialysis tells us that it is of great significance for this kind of patient to have immune monitoring in the early diagnosis of EGPA.
Eosinophilia in a Neonate With Trisomy 21, Transient Abnormal Myelopoiesis, and Neurofibromatosis Type 1
Authors: Schmittau Kayla M. , Walker Brian M. , Mittal Nupur , Giordano Lisa
Published: September 2024

Transient abnormal myelopoiesis is a syndrome that causes excess proliferation of immature myeloid cells and occurs in 10% to 15% of neonates with trisomy 21. Transient abnormal myelopoiesis usually resolves spontaneously but occasionally requires treatment with chemotherapy. The disorder is not typically associated with eosinophilia. We report on a neonate with trisomy 21 and transient abnormal myelopoiesis characterized by leukocytosis with marked eosinophilia. The patient required 2 cycles of cytarabine for adequate myeloproliferative control. Furthermore, this patient was subsequently also diagnosed with neurofibromatosis type 1, which has no known association with trisomy 21 or transient abnormal myelopoiesis.
A case report of labyrinthine infarction: a ‘central’ cause of vertigo with ‘peripheral’ presentation
Authors: El Bouhmadi Khadija , Darouich Safa , Youbi Myriam , Anajar Said , Essaadi Mustapha , Snoussi Khalid , Hajjij Amal
Published: September 2024

Introduction and Importance:

The inner ear is considered an ‘end organ’ since its vascular supply comes from one terminal artery, making the labyrinth especially vulnerable to ischemia, causing loss of auditory and vestibular function with variable clinical patterns according to the different arterial distribution in the inner ear and which vascular branches are concerned by the embolism.

Case Presentation:

We report a misleading case of central vascular vertigo caused by a labyrinthine infarction resulting from an embolic vertebral artery, which manifested in a typical peripheral clinical presentation mimicking a vestibular neuritis.

Clinical Discussion:

Vertigo is the result of asymmetrical responses from the vestibules of both ears resulting from any disruption along the complex vestibular pathways, whether peripheral or central. The recognition of the origin of an acute isolated vertigo is fundamental since the therapeutic strategy and prognosis differ, but it can be challenging in the absence of neurological signs, especially when the clinical pattern involves only the vestibular part of the labyrinth.

Conclusion:

The diagnosis strategy should consider the patient vascular risk factors and the clinical bedside tests with diffusion-weighted magnetic resonance imaging (MRI). Then, the management of these patients requires pluridisciplinary cooperation with early vestibular rehabilitation.
Epigenetics of Dietary Phytochemicals in Cancer Prevention
Authors: Chou PoChung Jordan , Peter Rebecca Mary , Shannar Ahmad , Pan Yuxin , Dave Parv Dushyant , Xu Jiawei , Sarwar Md Shahid , Kong Ah-Ng
Published: September 2024

Cancer development takes 10 to 50 years, and epigenetics plays an important role. Recent evidence suggests that ~80% of human cancers are linked to environmental factors impinging upon genetics/epigenetics. Because advanced metastasized cancers are resistant to radiation/chemotherapeutic drugs, cancer prevention by relatively nontoxic “epigenetic modifiers” will be logical. Many dietary phytochemicals possess powerful antioxidant and anti-inflammatory properties that are hallmarks of cancer prevention. Dietary phytochemicals can regulate gene expression of the cellular genome via epigenetic mechanisms. In this review, we will summarize preclinical studies that demonstrate epigenetic mechanisms of dietary phytochemicals in skin, colorectal, and prostate cancer prevention. Key examples of the importance of epigenetic regulation in carcinogenesis include hypermethylation of the NRF2 promoter region in cancer cells, resulting in inhibition of NRF2-ARE signaling. Many dietary phytochemicals demethylate NRF2 promoter region and restore NRF2 signaling. Phytochemicals can also inhibit inflammatory responses via hypermethylation of inflammation-relevant genes to block gene expression. Altogether, dietary phytochemicals are excellent candidates for cancer prevention due to their low toxicity, potent antioxidant and anti-inflammatory properties, and powerful epigenetic effects in reversing procarcinogenic events.
Advancements in Understanding and Preventing Obesity-Related Colon Cancer
Authors: Shieh Christine , Thompson Henry J. , McLaughlin Eric , Chiang Chien-Wei , Hussan Hisham
Published: September 2024

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.
Doxycycline Sclerotherapy of Mandibular Aneurysmal Bone Cysts: A Brief Clinical Study
Authors: Wong Megan N. , Murakami James W.
Published: September 2024

Aneurysmal bone cysts (ABCs) are benign bone tumors typically affecting children. Mandibular ABCs can be difficult to treat surgically, given their sensitive anatomic location and functional and cosmetic impacts. This report presents 3 pediatric patients with mandibular ABCs successfully treated with image-guided percutaneous doxycycline sclerotherapy. The first 2 patients presented with pain and swelling, whereas the third was diagnosed incidentally. Sclerotherapy was the sole treatment for cases 1 and 2, whereas case 3 had sclerotherapy after recurrence following prior surgeries. In all 3 patients, clinical symptoms resolved, and stable bone healing was documented on long-term follow-up. There were no functional or cosmetic complications. Doxycycline sclerotherapy is a safe and viable treatment for primary and recurrent mandibular ABCs.
Trends and antibiotic susceptibility patterns of diarrhoeal pathogens – experience over 14 years in southern India
Authors: Mohanty Ankita , Lakra Nayannika , Mandal Jharna
Published: September 2024

Introduction. Enteric pathogens contribute significantly to morbidity in a developing country such as India. Early and prompt diagnosis of diarrhoeal diseases can reduce the mortality rate, particularly in children. The pattern of sensitivity to antimicrobials for the common pathogens can vary from time to time. The present study was conducted to study the pathogen distribution and antimicrobial susceptibility pattern during the study period (January 2010 to December 2023).

Hypothesis/gap statement. Studying the changing trend in the antimicrobial sensitivity pattern of diarrhoeal pathogens over a decade can help to plan future treatment options.

Aim. This study was undertaken to provide insights into the changing pattern of pathogen distribution and antimicrobial susceptibility for enteric pathogens over 14 years.

Methods. A retrospective observational cohort analysis was conducted on all the stool pathogens isolated from the samples received in the microbiology department of a tertiary care hospital from 2010 to 2023. The demographic details, stool microscopy, culture reports, and antimicrobial susceptibility patterns were noted.

Results. A total of 18 336 stool specimens were received in the microbiology laboratory between January 2010 and December 2023, of which 1354 specimens had diarrhoeal pathogens grown in culture. Out of these 1354 specimens, 591 (44%) had Salmonella, 471 (35%) Shigella, 181 (13%) Vibrio cholerae, and 80 (6%) Aeromonas species. Among these pathogens, susceptibility to ceftriaxone was seen in 93% (552 isolates) of Salmonella species, 89% (420 isolates) of Shigella species, and 95% (171 isolates) of Vibrio cholerae; 91% (73 isolates) of Aeromonas species were susceptible to chloramphenicol. Some major parasites were also observed on microscopy.

Conclusion. Timely diagnosis of diarrhoeal pathogens can be life-saving for patients at the extremes of age, i.e. in children and the elderly. Pathogens can exhibit a changing susceptibility pattern to antibiotics, which should be regularly observed to plan future therapy.
Tree diversity reduces pathogen damage in temperate forests: a systematic review and meta-analysis
Authors: Field Elsa , Hector Andrew , Barsoum Nadia , Koricheva Julia
Published: September 2024

Diversifying planted forests to reduce the risks associated with large scale disturbances, such as pathogens, is a major aim of sustainable forest management. Previous meta-analyses have shown that insect pest damage is lower in mixed forest stands compared to monocultures, but the same has not been shown for pathogens. Here, we provide the first systematic review and meta-analysis specifically testing the effects of tree species diversity on pathogen damage. Relevant studies were retrieved using bibliographic databases and internet searches, as well as previously unpublished data sets contributed by stakeholders. We found that more diverse forest stands overall had significantly lower pathogen damage, and that this result was most pronounced in temperate forests for which the most studies were available. Although in some cases tree diversity had a strong effect, this was not universal and was influenced neither by pathogen specialism, nor by the presence of alternative hosts in stands. Instead, we found that tree neighbour identity rather than species richness emerged as a crucial variable impacting pathogen damage in mixed stands. Neighbour identity effects reported in studies were far-ranging, including impacts on the microclimate of stands. Future work should focus on mechanistic explanations that could underpin neighbour identity effects in mixed forests. We suggest the use of the disease triangle as a tool for considering the multiple factors that can influence pathogen damage in mixed forest stands.
Fungus-infectedMeiogyneflowers offer a brood site for beetle pollinators in a tripartite nursery pollination system
Authors: Liu Ming-Fai , Chen Junhao , Xue Bine , Wang Rui-Jiang , Saunders Richard M. K.
Published: September 2024

Fungi are widely known for their pathological impact on flowers, but some play a beneficial role in pollination. We report a case of tripartite pollination system in the flowering plantMeiogyne hainanensis(Annonaceae) in Hainan, China. The flowers emit a fruity scent composed of a mixture of mostly sesquiterpenes and aliphatic esters, attracting the primary beetle pollinatorsParaphloeostibasp. (Staphylinidae) andMimemodessp. (Monotomidae). The pollinators utilise the floral chamber as a mating ground and oviposit onto the adaxial corrugations of the inner petals. After the end of anthesis, extensive growth of filamentous fungi was observed to be restricted on these corrugated tissues. Upon hatching, theParaphloeostibaandMimemodeslarvae consumed the fungal mycelia. ITS2 metabarcoding analysis reveals that the diet of the larvae consists of similar fungal taxa as those found on the inner petals. Both were primarily composed of ascomycete fungi such asFusarium,PenicilliumandCladosporiumspecies. The flower has an unusually long post-anthetic phase that lasts at least 21 days and up to 2 months, during which the fungus-infested petals remain arboreal, offering suitable microclimate and shelter for the broods. This is the second reported angiosperm genus that exhibits tripartite brood-site pollination in which filamentous fungi are an essential mutualistic partner.
Genetic liability to insomnia and substance use disorders in patients with bipolar disorder
Authors: Melhuish Beaupre Lindsay M. , Coombes Brandon , Batzler Anthony , Sanchez-Ruiz Jorge A. , Kolla Bhanu Prakash , Romo-Nava Francisco , Pazdernik Vanessa , Jenkins Gregory , Waller T. Cameron , Skime Michelle , McElroy Susan , Frye Mark , Biernacka Joanna M.
Published: September 2024

Background

Insomnia and substance use disorders (SUD) are common comorbidities of bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered shared genetic contributions to insomnia and BD as well as SUDs and BD. Using electronic health record (EHR) derived phenotypes (phecodes) and questionnaire data, the authors examined the relationship between insomnia genetic liability and SUDs in BD.

Methods

40,839 participants from the Mayo Clinic Bipolar Disorder Biobank (BD Biobank; n=774) and Mayo Clinic Biobank (n=485 BD cases, n=39,580 controls) were included in the phecode analyses [insomnia, SUD, alcohol use disorder (AUD) and tobacco use disorder (TUD)]. 1789 cases were included in analyses of the BD Biobank questionnaire data, which included information on BD subtype and various SUDs. Logistic regression was used to test for associations between insomnia polygenic risk scores (PRS) and insomnia and SUD phenotypes in BD cases and controls.

Results

Insomnia PRS was associated with the insomnia phecode in controls (OR=1.19, p=9.64e-33) but not in BD cases (OR=1, p=0.95). Associations between insomnia PRS and SUD phecodes were significant in BD cases and controls with the effect of the association between insomnia PRS and SUD being stronger in BD cases (interaction p=0.024). In the BD Biobank, the insomnia PRS was associated with increased odds of AUD (OR=1.19, p=4.26e-04), TUD (OR=1.21, p=1.25e-05) and cannabis use disorder (OR=1.16, p=4.19e-03).

Conclusion

The effect of genetic predisposition to insomnia on SUD may be stronger in BD cases than controls. This could have clinical treatment implications for individuals with BD and comorbid SUD.
Clonal Hematopoiesis and the Risk for Rheumatoid Arthritis
Authors: Corty Robert , Heimlich J. Brett , Pershad Yash , Sharber Brian , Vlasschaert Caitlyn , Ormseth Michelle , Stein C. Michael , Bick Alexander
Published: September 2024

Objective

Rheumatoid arthritis (RA) is a systemic autoimmune disease with complex pathogenesis involving the innate and adaptive immune system. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by clonal proliferation of one hematopoietic stem cell and is typically asymptomatic. Both are common among older adults. CHIP is associated with multiple autoimmune diseases, but has not been thoroughly evaluated for its relationship with RA.

Methods

We examined three large biobanks where CHIP status of participants has been determined from whole genome sequencing data. We ascertained cases of RA, seropositive RA (SPRA), and seronegative RA (SNRA) using established methods and used survival analysis to test whether CHIP status was predictive of incident disease. We combined the results of the three biobank studies using random effects meta-analysis. For validation, we performed deep, targeted sequencing of CHIP-causing genes in an established clinical cohort of 132 RA cases, 56 controls, and 544 external controls. We compared the rates of CHIP between cases and controls using logistic linear regression.

Results

In the UKBiobank and in meta-analysis, the presence of a large CHIP clone was associated with an increased risk for SPRA (HR = 2.57 with CI [1.46, 4.52] and p = 0.001) and RA (HR = 1.43 with CI [1.16, 1.75] and p = 7 × 10−4). Medium CHIP clones were associated with smaller increases in risk for SPRA and RA, and small CHIP clones carried no increased risk of any outcome. There were no associations detected between SNRA and CHIP of any size. In the clinical RA cohort, cases were more likely to have CHIP than controls after correcting for age, age2, and sex (OR: 2.08, HR [1.09, 3.83], p = 0.02).

Conclusion

In a meta-analysis combing data from three large biobanks, large CHIP clones were associated with an increased risk for incident SPRA and, to a lesser extent, increased risk for RA. Validating this biobank-based finding, in a well-phenotyped clinical cohort, cases had higher rates of CHIP than age-matched controls. The mechanism by which CHIP drives the increased risk for SPRA is not known, but if it were discovered, could inform early intervention for patients with CHIP to prevent RA or personalized therapy for patients with RA based on CHIP status.
A one-step protocol to generate impermeable fluorescent HaloTag substrates forin situlive cell application and super-resolution imaging
Authors: Roßmann Kilian , Sun Siqi , Olesen Christina Holmboe , Kowald Maria , Tapp Eleni , Pabst Ulrich , Bieck Marie , Birke Ramona , Shields Brenda C. , Jeong PyeongHwa , Hong Jiyong , Tadross Michael R. , Levitz Joshua , Lehmann Martin , Lipstein Noa , Broichhagen Johannes
Published: September 2024

Communication between cells is largely orchestrated by proteins on the cell surface, which allow information transfer across the cell membrane. Super-resolution and single-molecule visualization of these proteins can be achieved by genetically grafting HTP (HaloTag Protein) into the protein of interest followed by brief incubation of cells with a dye-HTL (dye-linked HaloTag Ligand). This approach allows for use of cutting-edge fluorophores optimized for specific optical techniques or a cell-impermeable dye-HTL to selectively label surface proteins without labeling intracellular copies. However, these two goals often conflict, as many high-performing dyes exhibit membrane permeability. Traditional methods to eliminate cell permeability face synthetic bottlenecks and risk altering photophysical properties. Here we report that dye-HTL reagents can be made cell-impermeable by inserting a charged sulfonate directly into the HTL, leaving the dye moiety unperturbed. This simple, one-step method requires no purification and is compatible with both the original HTL and second-generation HTL.2, the latter offering accelerated labeling. We validate such compounds, termed dye-SHTL (‘dye shuttle’) conjugates, in live cells via widefield microscopy, demonstrating exclusive membrane staining of extracellular HTP fusion proteins. In transduced primary hippocampal neurons, we label mGluR2, a neuromodulatory G protein-coupled receptor (GPCR), with dyes optimized for stimulated emission by depletion (STED) super-resolution microscopy, allowing unprecedented accuracy in distinguishing surface and receptors from those in internal compartments of the presynaptic terminal, important in neural communication. This approach offers broad utility for surface-specific protein labelling.
Unraveling the GM1specificity of Galectin-1 binding to lipid membranes
Authors: Scollo Federica , Kulig Waldemar , Nicita Gabriele , Ludwig Anna-K. , Ricardo Joana C. , Zito Valeria , Kapusta Peter , Vattulainen Ilpo , Cebecauer Marek , Gabius Hans-Joachim , Kaltner Herbert , Maccarrone Giuseppe , Hof Martin
Published: September 2024

Galectin-1 (Gal-1) is a galactose-binding protein involved in various cellular functions. Gal-1’s activity has been suggested to be connected to two molecular concepts, which are however lacking experimental proof: a) enhanced binding affinity of Gal-1 towards membranes containing monosialotetrahexosylganglioside (GM1) over disialoganglioside GD1a and b) cross-linking of GM1’s by homodimers of Gal-1. We provide evidence about the specificity and the nature of Gal-1 interaction with model membranes containing GM1or GD1a, employing a broad panel of fluorescence-based and label-free experimental techniques, complemented by atomistic biomolecular simulations. Our study demonstrates that Gal-1 binds indeed specifically to GM1, and not to GD1a, when embedded in membranes over a wide range of concentrations (i.e., 30 nM to 10 μM). The apparent binding constant is about tens of micromoles. On the other hand, no evidence of Gal-1/GM1cross-linking was observed. Our findings suggest that cross-linking does not result from sole interactions between GM1and Gal-1, indicating that in a physiological context, additional triggers are needed, which shift the GM1/Gal-1 equilibria towards the membrane-bound homodimeric Gal-1.

Abstract Figure
The health, wellbeing and health service use of women attempting or planning pregnancy: a nationwide cross-sectional survey of Australian women
Authors: Steel Amie , Schoenaker Danielle , Harnett Joanna , Adams Jon
Published: September 2024

Background

Health and wellbeing during the preconception period influence maternal and child health outcomes. We describe the sociodemographic and health characteristics of Australian women currently attempting pregnancy or planning to conceive in the next 12 months, compared with other women of reproductive age, to identify opportunities for preconception care.

Methods

A sub-analysis of survey data obtained in 2022 that included 874 responses from females aged 18-49 years was conducted. Socio-demographic characteristics, health and wellbeing status, and health service utilization data were described according to pregnancy intention.

Results

Of 874 women, 64 (7.4%) reported currently attempting pregnancy and 45 (5.2%) reported planning to become pregnant in the next 12 months. Both groups of women were commonly married or in a de facto relationship. Women who were planning to become pregnant were more commonly aged 25-34 years (71.1%) compared to 18 to 24 years (20.0%) or aged 35 years or older (8.9%). They were also more likely to consult a chiropractor (OR 1.5). Women currently attempting pregnancy were less likely to not be in the paid workforce (OR 0.34) compared to working full time. They were also less likely to be using prescription-only pharmaceuticals (OR 0.30) and more likely to be consulting a Traditional Chinese medicine practitioner (OR 2.66) or a dietician (OR 2.11).

Conclusion

The findings of this study can be used for informing health service planning and policy that takes a whole-of-health-system approach when designing preconception health primary care interventions.
Impact of 10-valent pneumococcal conjugate vaccine on the epidemiology of otitis media with otorrhea among Bangladeshi children
Authors: Naziat Hakka , Rahman Md Hafizur , Das Rajib C , Islam Maksuda , Saha Shampa , Hussain Md. Manzoor , Sattar Asif , Uddin Mohammad J , Alam Md. Jahangir , Whitney Cynthia G. , Saha Senjuti , Hooda Yogesh , Saha Samir K
Published: September 2024

In 2015, Bangladesh introduced the ten-valent pneumococcal conjugate vaccine (PCV10). This study evaluates the impact of PCV10 on pneumococcal otitis media (OM), a prevalent middle ear infection amongst children in low-and-middle income countries, including Bangladesh. We analyzed ear swabs from OM cases with otorrhea collected at the largest pediatric hospital in Dhaka, Bangladesh from April 2014 to March 2019. The study involved identifying pathogens and conducting pneumococcal serotyping using the Quellung reaction.

Four years post PCV10 introduction, the rate of detection of pneumococcus among otorrhea cases decreased from 18.4% (164/892) in 2014-15 to 15.6% (581/3735) in 2018-19, reflecting a 15.4% reduction. Notably, vaccine serotypes (VTs) demonstrated a significant decline throughout the post-PCV years, with a 44.1% reduction compared to the pre-PCV period. Specific VTs like 14, 6B and 19F exhibited significant reductions of 60.2%, 57.5% and 42.9% respectively. Conversely, non-vaccine serotypes (NVTs) showed non-significant increase of 8.6%; specifically serotype 35B showed a 70.1% increase. Administration of two or three doses of PCV10 provided 84.4% protection against OM cases caused by serotypes covered by PCV10.

This is the first report from South Asia assessing PCV’s impact on pneumococcal OM. It demonstrates a 15.4% reduction in pneumococcal isolation over four years and over 80% efficacy of PCV10 in preventing vaccine type pneumococcal OM cases. While some vaccine serotypes decreased significantly, the impact of PCV10 on overall pneumococcal OM cases was dampened by increasing isolation of non-vaccine serotypes.
BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability
Authors: Longo Michael A. , Ahmed Syed Moiz , Chen Yue , Tsai Chi-Lin , Namjoshi Sarita , Wang Xiaoyan , Perera Rajika L. , Arvai Andy , Lee Miyoung , Kong Li Ren , Engl Wilfried , Shyuan Woei , Zhao Ziqing Winston , Venkitaraman Ashok R. , Tainer John A. , Schlacher Katharina
Published: September 2024

Tumor suppressor protein BRCA2 acts with RAD51 in replication-fork protection (FP) and homology-directed DNA break repair (HDR). Critical for cancer etiology and therapy resistance, BRCA2 C-terminus was thought to stabilize RAD51-filaments after they assemble on single-stranded (ss)DNA. Here we determined the detailed crystal structure for BRCA2 C-terminal interaction-domain (TR2i) with ATP-bound RAD51 prior to DNA binding. In contrast to recombinogenic RAD51-filaments comprising extended ATP-bound RAD51 dimers, TR2i unexpectedly reshapes ATP-RAD51 into a unique dimer conformation accommodating double-stranded B-DNA binding unsuited for HDR initiation. Structural, biochemical, and molecular results with interface-guided mutations uncover TR2i’s FP mechanism. Proline-driven secondary-structure stabilizes residue triads and spans the RAD51 dimer engaging pivotal interactions of RAD51 M210 and BRCA2 S3291/P3292, the cyclin-dependent kinase (CDK) phosphorylation site that toggles between FP during S-phase and HDR in G2. TR2i evidently acts as an allosteric clamp switching RAD51 from ssDNA to double-stranded and B-DNA binding enforcing FP over HDR.