bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective assessment of the association between telomere length, a biomarker of aging, and health screening indicators: A cross-sectional study
Authors: Fu Yiting , Lou Huiling , Chen Qiaocong , Wu Shu , Chen Hansen , Liang Kaixin , Ge Yuanlong , Zhao Chunzhen
Published: June 2024

Physical examination data are used to indicate individual health status and organ health, and understanding which physical examination data are indicative of physiological aging is critical for health management and early intervention. There is a lack of research on physical examination data and telomere length. Therefore, the present study analyzed the association between blood telomere length and physical examination indices in healthy people of different ages to investigate the role and association of various organs/systems with physiological aging in the human body. The present study was a cross-sectional study. Sixteen physical examination indicators of different tissue and organ health status were selected and analyzed for trends in relation to actual age and telomere length (TL). The study included 632 individuals with a total of 11,766 data for 16 physical examination indicators. Age was linearly correlated with 11 indicators. Interestingly, telomere length was strongly correlated only with the renal indicators eGFR (P < .001), CYS-C (P < .001), and SCR (P < .001). The study established that renal aging or injury is a risk factor for Physical aging of the human body. Early identification and management are essential to healthcare.
Study on the mechanism of inhibition of Escherichia coli by Polygonum capitatum based on network pharmacology and molecular docking technology: A review
Authors: Chen Shunhuan , Zhai Dongyan , Li Yuan , Tan Yong , Tang Xiaoke , Pu Xiang , Chai Yihui , Li Lailai
Published: June 2024

This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.
Chronic inflammatory demyelinating polyneuropathy with pulmonary nocardiosis: A case report
Authors: Yan Cheng , Liu Ting-Ting , Gao Li-Tao
Published: June 2024

Rationale:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated motor sensory peripheral neuropathy that is rare in clinical practice. This treatment method aims to suppress potential immunopathology. Nocardiosis is a rare, destructive, opportunistic disease. We report a case of failed treatment of CIDP combined with pulmonary nocardiosis, and for the first time, we link these 2 diseases together.

Patient concerns:

A 65-year-old man developed symmetrical limb weakness. Four months later, he was diagnosed with CIDP and started receiving glucocorticoid (GC) treatment. The disease progressed slowly and was treated with mycophenolate mofetil (MMF) in combination. He did not follow the doctor requirements for monthly follow-up visits, and the preventive medication for sulfamethoxazole/trimethoprim was not strictly implemented. Two months after the combination therapy, the patient developed fever, coughing and sputum production, as well as fatigue and poor appetite. Based on imaging and etiological results, he was diagnosed with pulmonary nocardiosis.

Diagnoses:

Chronic inflammatory demyelinating polyneuropathy, pulmonary nocardiosis.

Interventions:

After treatment with antibiotics, the patient lung infection temporarily improved. However, the patient CIDP condition progressed, limb weakness worsened, respiratory muscle involvement occurred, and intravenous immunoglobulin (IVIG) was administered. However, there was no significant improvement in the condition, and the patient died.

Outcomes:

In this report, we present a case of a patient with CIDP and pulmonary nocardiosis. It is worth noting that in order to avoid the progression and recurrence of CIDP, we did not stop using related therapeutic drugs during the treatment process, the patient had repeatedly refused to use IVIG. Despite this, the patient condition worsened when lung inflammation improved, leading to persistent respiratory failure and ultimately death. Treatment contradictions, medication issues, and patient compliance issues reflected in this case are worth considering.

Lessons:

For patients with CIDP receiving immunosuppressive therapy, attention should be paid to the occurrence and severity of Nocardia infection. Therefore, early detection and treatment are necessary. We need to pay attention to the compliance of patients with prophylactic use of antibiotics, strengthen the follow-up, and urge them to return to their appointments on time.
Argon gas poisoning leading to persistent memory impairment: A 2-year case report
Authors: Gao Weiwei , She Jingjing , Wang Mingyang , Li Shuixian , Chen Xingyu , Zhu Renjing
Published: June 2024

Rationale:

Argon gas poisoning is an often overlooked yet critical public health concern with the potential for severe and persistent neurological consequences. Current treatment protocols primarily focus on acute-phase management, but a comprehensive understanding of the long-term neurological effects remains incomplete.

Patient concerns:

A 22-year-old male worker was found unconscious in the furnace room of an argon production facility. After regaining consciousness, he presented with symptoms of dizziness, headache, fatigue, and irritability. Neurological examination revealed impairments in both recent and remote memory, notably pronounced short-term memory deficits and reduced arithmetic skills.

Diagnosis:

Argon gas poisoning, hypoxic encephalopathy, and mild hepatic and renal dysfunction.

Interventions:

Upon admission, symptomatic supportive measures included oxygen therapy via nasal cannula (3 L/min), daily hyperbaric oxygen therapy (1.5 ATA, 60 minutes), oral neurotrophic methylcobalamin (0.5 mg, 3 times daily), and intravenous vitamin C infusion (2 g daily) to scavenge oxygen free radicals.

Outcome:

A 2-year telephone follow-up indicated persistent short-term memory impairment, particularly with memorizing numbers. In a memory test, he achieved a digit span forward of 5 but a digit span backward of 2, indicating impairment. Despite these challenges, his daily life and work performance remained largely unaffected.

Lesson:

This case offers valuable insights into the biological mechanisms underlying prolonged neurological sequelae following asphyxiating gas exposure, specifically the persistent impairment of hippocampal function.
Frontiers and hotspots in hand, foot, and mouth disease research during 2006 to 2023: A bibliometric and visual analysis
Authors: Li Yunzhi , Ruan Ying , Zhai Xiangjie , Ye Junjie , Xiao Yujie , Liang Jiawei , Zhu Ni
Published: June 2024

Background:

Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD.

Methods:

Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package “Bibiometrix,” SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data.

Results:

A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research.

Conclusion:

By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.
Prognosis and recurrence of spontaneously ruptured hepatocellular carcinoma treated after hepatectomy: A single institution experience
Authors: Xu KangHe , Ryu DongHee , Choi Hanlim , Choi Jae-Woon , Lee Jiho
Published: June 2024

Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11–32) and 23 (17–38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8–37, P = .099) and 33 (12–51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.
NGS panel enhance precise diagnosis of myeloid neoplasms under WHO-HAEM5 and International Consensus Classification: An observational study
Authors: Ye Xiangjun , Zheng Zhikang , Wu Yuwei , Zhang Zhihui , Xu Zhiping , Liu Yameng , Jiang Lei , Wu Jianguo
Published: June 2024

This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) and the International Consensus Classification (ICC) of Myeloid Tumors. A cohort of 112 patients diagnosed with MN according to the revised fourth edition of the WHO classification (WHO-HAEM4R) underwent testing with a 141-gene NGS panel for hematological diseases. Ancillary studies were also conducted, including bone marrow cytomorphology and routine cytogenetics. The cases were then reclassified according to WHO-HAEM5 and ICC to assess the practical impact of these 2 classifications. The mutation detection rates were 93% for acute myeloid leukemia (AML), 89% for myelodysplastic syndrome (MDS), 94% for myeloproliferative neoplasm (MPN), and 100% for myelodysplasia/myeloproliferative neoplasm (MDS/MPN) (WHO-HAEM4R). NGS provided subclassified information for 26 and 29 patients with WHO-HAEM5 and ICC, respectively. In MPN, NGS confirmed diagnoses in 16 cases by detecting JAK2, MPL, or CALR mutations, whereas 13 “triple-negative” MPN cases revealed at least 1 mutation. NGS panel testing for hematological diseases improves the diagnosis and classification of MN. When diagnosed with ICC, NGS produces more classification subtype information than WHO-HAEM5.
Gut microbiota, inflammatory factors, and scoliosis: A Mendelian randomization study
Authors: Zhao Xiaojiang , Liu Jingjing , Zhang Lei , Ma Chao , Liu Yanan , Wen Hebao , Li Chang qing
Published: June 2024

Several studies have reported a potential association between the gut microbiota (GM) and scoliosis. However, the causal relationship between GM and scoliosis and the role of inflammatory factors (IFs) as mediators remain unclear. This study aimed to analyze the relationship between GM, IFs, and scoliosis. We investigated whether IFs act as mediators in pathways from the GM to scoliosis. Additionally, using reverse Mendelian randomization (MR) analysis, we further investigated the potential impact of genetic predisposition to scoliosis on the GM and IFs. In this study, we searched for publicly available genome-wide association study aggregate data and utilized the MR method to establish bidirectional causal relationships among 211 GM taxa, 91 IFs, and scoliosis. To ensure the reliability of our research findings, we employed 5 MR methods, with the inverse variance weighting approach serving as the primary statistical method, and assessed the robustness of the results through various sensitivity analyses. Additionally, we investigated whether IFs mediate pathways from GM to scoliosis. Three negative causal correlations were observed between the genetic predisposition to GM and scoliosis. Additionally, both positive and negative correlations were found between IFs and scoliosis, with 3 positive and 3 negative correlations observed. IFs do not appear to act as mediators in the pathway from GM to scoliosis. In conclusion, this study demonstrated a causal association between the GM, IFs, and scoliosis, indicating that IFs are not mediators in the pathway from the GM to scoliosis. These findings offer new insights into prevention and treatment strategies for scoliosis.
Prevalence and molecular detection of Staphylococcus aureus resistance to antibiotics
Authors: Dendi Fatima Zahra , Allem Rachida , Sebaihia Mohammed , Bensefia Sidahmed , Cheurfa Mohammed , Alamir Hannan , Obeagu Emmanuel Ifeanyi
Published: June 2024

In Algeria, the issue of antibiotic resistance is on the rise, being the Staphylococcus aureus infection as a significant concern of hospital-acquired infections. The emergence of antibiotic resistance in this bacterium poses a worldwide challenge. The aim of this study aims to establish the incidence of S aureus strains in Algeria as well as identify phenotypic and genotypic resistance based on the “mecA” and “nuc” genes. From 2014 to 2017, a total of 185 S aureus strains were isolated from patients at a hospital in the city of Rouïba, Algiers the number of isolates was slightly higher in males at 58.06% compared to females at 41.94%, resulting in a sex ratio of 1.38. the Oxacillin and Cefoxitin DD test (1 μg oxacillin disk and 30 μg cefoxitin disk) identified 42 strains as resistant. The results indicated high resistance to lactam antibiotics, with penicillin having a 100% resistance rate. There was also significant resistance to oxacillin (51.25%) and cefoxitin (50%). This resistance was frequently associated with resistance to other antibiotic classes, such as aminoglycosides (50%) and Macrolides (28.29%). To confirm methicillin-resistant characteristics, a polymerase chain reaction (PCR) multiplex was conducted on 10 isolates (6 SARM; 4 MSSA) on a phenotypic level. Three isolates tested positive for “mecA,” while 7 were negative. All strains carry the nuc gene, which is specific to S aureus. In Algeria, the incidence of S aureus resistance is slightly lower compared to other countries, but it is increasing over time. It is now more crucial than ever to restrict the proliferation of multidrug-resistant strains and reduce undue antibiotic prescriptions. To achieve this, it is vital to keep updated on the epidemiology of this bacterium and its antibiotic susceptibility. This will enable the formulation of appropriate preventive control measures to manage its progression.
Pattern and causes of missed appointments in a Nigerian Psychiatric Hospital: A cross-sectional study
Authors: Edet Bassey Eyo , Essien Emmanuel Aniekan , Omamurhomu Olose Emmanuel , Okafor Chidi John , Ogbodum Molly Unoh , Daniel Faithful Miebaka
Published: June 2024

Psychiatric patients exhibit a higher rate of missed appointments compared to other medical specialities, leading to provider frustration, increased relapse, and suboptimal outcomes. This study investigates the patterns and correlates of missed appointments among outpatients at the Federal Neuropsychiatric Hospital in Calabar, Nigeria. A cross-sectional study involving 403 consecutive outpatient clinic attendees was conducted. The study questionnaire inquired about sociodemographic characteristics and hospital utilization. The Oslo Social Support Scale, the Internalized Stigma of Mental Illness Scale, the Perceived Devaluation and Discrimination Scale, and the Treatment Perception Questionnaire were administered. The mean participant age was 36.19 years (SD = 11.25), with females constituting 52.6%. Missed appointments occurred in 16.6%. The primary reasons for missed appointments included financial difficulties, forgetfulness, and distance to the hospital. Factors significantly associated with missed appointments were marital status (married), having children, believing appointments were too frequent, medication nonadherence, and concerns about medication cost (P < .05). Additionally, individuals who received unorthodox or delayed traditional care during their first mental health episode were more likely to miss appointments (P < .05). Missed appointments are prevalent among psychiatric patients, often attributed to financial challenges, forgetfulness, and geographical barriers to the hospital. Some of these factors are modifiable, suggesting targeted interventions in adherence improvement programs are needed.
CDCA gene family promotes progression and prognosis in lung adenocarcinoma
Authors: Liu XiangSen , Zhu Xudong , Zhao Yi , Shan Yuchen , Gao ZhaoJia , Yuan Kai
Published: June 2024

Background:

The cell division cycle-associated (CDCA) family participates in the cell cycle, and the dysregulation of its expression is associated with the development of several types of cancers. However, the roles of CDCAs in lung adenocarcinomas (LUAD) have not been investigated in systematic research.

Methods:

Using data retrieved from The Cancer Genome Atlas (TCGA), the expression of CDCAs in LUAD and normal tissues was compared, and survival analysis was performed using the data. Also, the correlation between clinical characteristics and the expression of CDCAs was assessed. Using data from cBioPortal, we investigated genetic alterations in CDCAs and their prognostic implications. Immunohistochemical analyses were performed to validate our findings from TCGA data. Following this, we created a risk score model to develop a nomogram. We also performed gene set enrichment analyses (GSEA), gene ontology, and KEGG pathway analysis. We used Timer to analyze the correlation between immune cell infiltration, tumor purity, and expression data.

Results:

Our results indicated that all CDCAs were expressed at high levels in LUAD; this could be associated with poor overall survival, as indicated in TCGA data. Univariate and multivariate Cox analyses revealed that CDCA4/5 could serve as independent risk factors. The results of immunohistochemical analyses confirmed our results. Based on the estimation of expression levels, clinical characteristics, alterations, and immune infiltration, the low-risk group of CDCA4/5 had a better prognosis than the high-risk group. Immune therapy is also a potential treatment option.

Conclusion:

In conclusion, our findings indicate that CDCAs play important roles in LUAD, and CDCA4/5 can serve as diagnostic and prognostic biomarkers and therapeutic targets in LUAD.
Personalized prediction of survival rate with combination of penalized Cox models in patients with colorectal cancer
Authors: Lee Seon Hwa , Cha Jae Myung , Shin Seung Jun
Published: June 2024

The investigation into individual survival rates within the patient population was typically conducted using the Cox proportional hazards model. This study was aimed to evaluate the performance of machine learning algorithm in predicting survival rates more than 5 years for individual patients with colorectal cancer. A total of 475 patients with colorectal cancer (CRC) and complete data who had underwent surgery for CRC were analyze to measure individual’s survival rate more than 5 years using a machine learning based on penalized Cox regression. We conducted thorough calculations to measure the individual’s survival rate more than 5 years for performance evaluation. The receiver operating characteristic curves for the LASSO penalized model, the SCAD penalized model, the unpenalized model, and the RSF model were analyzed. The least absolute shrinkage and selection operator penalized model displayed a mean AUC of 0.67 ± 0.06, the smoothly clipped absolute deviation penalized model exhibited a mean AUC of 0.65 ± 0.07, the unpenalized model showed a mean AUC of 0.64 ± 0.09. Notably, the random survival forests model outperformed the others, demonstrating the most favorable performance evaluation with a mean AUC of 0.71 ± 0.05. Compared to the conventional unpenalized Cox model, recent machine learning techniques (LASSO, SCAD, RSF) showed advantages for data interpretation.
Kidney disease knowledge among patients visiting the nephrology clinic in the Kingdom of Saudi Arabia
Authors: Alobaidi Sami
Published: June 2024

This study aimed to explore chronic kidney disease (CKD)-related knowledge and its predictors among non-dialysis patients with CKD in the Kingdom of Saudi Arabia (KSA). It was a cross-sectional survey conducted at 2 nephrology centers in KSA. Data were gathered using a survey questionnaire that included sociodemographic information and enquiries about CKD. The questionnaire used to explore CKD knowledge consisted of 24 questions with 3 multiple-choice answers for each question: “True,” “False,” and “I don’t know.” Data were obtained from 185 patients who visited a nephrology clinic. The major study population was drawn from the western region of the Kingdom of Saudi Arabia. The participants’ mean (SD) total renal disease knowledge scores was 12.56 (3.55) out of a maximum of 24 points on the renal disease knowledge assessment. This suggests that the participants, on average, exhibited a moderate level of knowledge regarding renal disease. Most respondents correctly answered questions related to blood and urine tests (90.3% and 89.7%, respectively), living with a single kidney (88.1%), kidney function in blood cleansing (83.8%), risk factors like diabetes (82.7%), and hypertension (80%). Additionally, they recognized symptoms such as water retention (85.9%) and fatigue (61.6%) and the potential of certain medications to slow chronic kidney disease progression (72.4%). However, fewer respondents correctly identified nausea/vomiting (31.4%) and loss of appetite (31.4%) as signs of kidney disease, the role of kidneys in maintaining blood pressure (58.9%) and bone health (16.2%), and obesity as a risk factor (54.1%). Furthermore, there were notable differences in knowledge scores between genders, with men scoring significantly higher than women (2.05, P = .041). In general, the understanding of CKD within the CKD patient community in the KSA was at a moderate level. However, male respondents had a greater understanding of CKD than did female respondents. The findings of this study indicate an urgent need to conduct educational activities to improve CKD knowledge among patients with CKD in the KSA.
A rare case of infected urachal cyst leading to intestinal obstruction in a 3-month-old boy with febrile urinary tract infection: Case report
Authors: Song Ji Yeon , Kim Soo-Hong
Published: June 2024

Rationale:

Urachal anomalies are rare and can present with various clinical manifestations. Urachal remnants, in particular, can be difficult to diagnose because of atypical symptoms at presentation. This study reports a case of intestinal obstruction in an infant secondary to an infected urachal cyst.

Patients concerns:

A 3-month-old boy with a known febrile urinary tract infection developed acute abdominal distension

Diagnoses:

Abdominal ultrasound (US) and computed tomography (CT) revealed a nonspecific, ill-defined soft tissue density at the mid-abdomen, associated with intestinal obstruction.

Interventions:

Emergency exploratory laparotomy was performed. The site of the obstruction was found to be at the mid-small bowel; the proximal small bowel was markedly distended, and the small bowel and sigmoid colon were adherent to urachal remnant. The urachal remnant was excised, and the peritoneal adhesions were lysed.

Outcomes:

The day after surgery, the patient was discharged without any complications.

Lessons:

Intestinal obstruction is an exceedingly rare presentation of urachal remnants. This case highlights that urachal anomalies should be considered in the differential diagnosis in patients with intestinal obstruction and a concurrent febrile urinary tract infection.
Analysis of risk factors for fatty liver disease in children with Wilson’s disease
Authors: Jia Shu-Pei , Wang Mei-Xia , Tao Zhuang , Gao Yan-Nan , Yu Gu-Ran , Yang Wen-Ming
Published: June 2024

Background and aims

Many children with Wilson’s disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver disease (FLD) in children with Wilson’s disease.

Methods

We evaluated sex, age, weight, the disease course, treatment course, clinical classification, alanine transaminase (ALT), aspartate transaminase, γ-glutamyl transpeptidase, total biliary acid, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, uric acid, fibrinogen (FBG), creatinine, procollagen III N-terminal propeptide, laminin, hyaluronic acid, type IV collagen, and performed receiver operating characteristic curve analysis to investigate the forecast value of individual biochemical predictors and combined predictive indicators to evaluate FLD in Wilson’s disease.

Results

The multivariate logistic regression analysis revealed that ALT [odds ratio (OR), 1.011; 95% confidence interval (CI), 1.004–1.02; P = 0.006], uric acid (OR, 1.01; 95% CI, 1.002–1.018; P = 0.017), FBG (OR, 3.668; 95% CI, 1.145–13.71; P = 0.037), creatinine (OR, 0.872; 95% CI, 0.81–0.925; P < 0.001), and laminin (OR, 1.01; 95% CI, 1.002–1.018; P = 0.017) acted as independent risk factors in Wilson’s disease complicated with FLD. The receiver operating characteristic curves for combined predictive indicators demonstrated an area under the curve values of 0.872, which was found to be a significant predictors for FLD in Wilson’s disease.

Conclusions

We screened out the most important risk factors, namely ALT, uric acid, creatinine, FBG, and laminin for Wilson’s disease complicated with FLD. The joint prediction achieved is crucial for identifying children with Wilson’s disease complicated with FLD.
Cardiovascular complications during delivery hospitalizations in patients with nonalcoholic fatty liver disease in pregnancy
Authors: Niu Chengu , Zhang Jing , Khalid Nida , Zhu Kaiwen , Syed Tausif , Liu Hongli , Okolo Patrick I.
Published: June 2024

Objective

While the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and long-term cardiovascular risks has been studied, the impact of MASLD on cardiovascular events during delivery hospitalizations remains relatively unexplored. This study aims to examine the prevalence of cardiovascular diseases (CVDs) and cardiac arrhythmias in pregnant patients with MASLD and identify potential risk factors.

Methods

A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted to assess maternal cardiovascular outcomes. Multivariable logistic regression models were employed, and adjusted odds ratios (AOR) were calculated to evaluate the association between MASLD and cardiovascular outcomes during pregnancy.

Results

The study sample included 17 593 pregnancies with MASLD and 41 171 211 pregnancies without this condition. Women with MASLD exhibited an increased risk of congestive heart failure [AOR 3.45, 95% confidence interval (CI) 1.04–11.43], cardiac arrhythmia (AOR 2.60, 95% CI 1.94–3.49), and gestational hypertensive complications (AOR 3.30, 95% CI 2.93–3.72). Pregnancies with MASLD were also associated with a higher rate of pulmonary edema (AOR 3.30, 95% CI 1.60–6.81).

Conclusion

MASLD is an independent risk factor for cardiovascular complications during delivery hospitalizations, emphasizing the necessity for prepregnancy screening and targeted prevention strategies to manage CVD risks in expectant patients with MASLD.
Expression and Clinical Significance of Ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients
Authors: Sadeghipour Alireza , Taha Seyed Reza , Shariat Zadeh Mahdieh , Kosari Farid , Babaheidarian Pegah , Fattahi Fahimeh , Abdi Navid , Tajik Fatemeh
Published: June 2024

Introduction:

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated.

Methods:

The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed.

Results:

The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype (P<0.001 and P=0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type (P<0.005) as well as a positive association between c-MYC and recurrence (P=0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not.

Conclusion:

Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.
Identification and characterization of early human photoreceptor states and cell-state-specific retinoblastoma-related features
Authors: Shayler Dominic W.H. , Stachelek Kevin , Cambier Linda , Lee Sunhye , Bai Jinlun , Reid Mark W. , Weisenberger Daniel J. , Bhat Bhavana , Aparicio Jennifer G. , Kim Yeha , Singh Mitali , Bay Maxwell , Thornton Matthew E. , Doyle Eamon K. , Fouladian Zachary , Erberich Stephan G. , Grubbs Brendan H. , Bonaguidi Michael A. , Craft Cheryl Mae , Singh Hardeep P. , Cobrinik David
Published: June 2024

Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin, yet the developmental basis for their distinct behaviors is poorly understood. Here, we used deep full-length single-cell RNA-sequencing to distinguish post-mitotic cone and rod developmental states and identify cone-specific features that contribute to retinoblastomagenesis. The analyses revealed early post-mitotic cone- and rod-directed populations characterized by higher THRB or NRL regulon activities, an immature photoreceptor precursor population with concurrent cone and rod gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Unexpectedly, both L/M cone and rod precursors co-expressedNRLandTHRBRNAs, yet they differentially expressed functionally antagonisticNRLandTHRBisoforms and prematurely terminatedTHRBtranscripts. Early L/M cone precursors exhibited successive expression of several lncRNAs along withMYCN, which composed the seventh most L/M-cone-specific regulon, andSYK, which contributed to the early cone precursors’ proliferative response toRB1loss. These findings reveal previously unrecognized photoreceptor precursor states and a role for early cone-precursor-intrinsicSYKexpression in retinoblastoma initiation.

Impact Statement

Features acquired by early post-mitotic retinal cells underlie the distinct behaviors of rods and the cone cells of origin of retinoblastoma tumors.
Rethinking asexuality: the enigmatic case of functional sexual genes inLepraria(Stereocaulaceae)
Authors: Doellman Meredith M. , Sun Yukun , Barcenas-Peña Alejandrina , Thorsten Lumbsch H. , Grewe Felix
Published: June 2024

Background

The ubiquity of sex across eukaryotes, given its high costs, strongly suggests it is evolutionarily advantageous. Asexual lineages can avoid, for example, the risks and energetic costs of recombination, but suffer short-term reductions in adaptive potential and long-term damage to genome integrity. Despite these costs, lichenized fungi have frequently evolved asexual reproduction, likely because it allows the retention of symbiotic algae across generations. The relatively speciose lichenized fungal genusLeprariais thought to be exclusively asexual, while its sister genusStereocauloncompletes a sexual reproductive cycle. A comparison of sister sexual and asexual clades should shed light on the evolution of asexuality in lichens in general, as well as the apparent long-term maintenance of asexuality inLepraria, specifically.

Results

In this study, we assembled and annotated representative long-read genomes from the putatively asexualLeprariagenus and its sexual sister genusStereocaulon, and added short-read assemblies from an additional 22 individuals across both genera. Comparative genomic analyses revealed that both genera were heterothallic, with intact mating-type loci of both idiomorphs present across each genus. Additionally, we identified and assessed 29 genes involved in meiosis and mitosis and 45 genes that contribute to formation of fungal sexual reproductive structures (ascomata). All genes were present and appeared functional in nearly allLepraria, and we failed to identify a general pattern of relaxation of selection on these genes across theLeprarialineage. Together, these results suggest thatLeprariamay be capable of sexual reproduction, including mate recognition, meiosis, and production of ascomata.

Conclusions

Despite apparent maintenance of machinery essential for fungal sex, over 200 years of careful observations by lichenologists have produced no evidence of canonical sexual reproduction inLepraria. We suggest thatLeprariamay have instead evolved a form of parasexual reproduction, perhaps by repurposingMATand meiosis-specific genes. This may, in turn, allow these lichenized fungi to avoid long-term consequences of asexuality, while maintaining the benefit of an unbroken bond with their algal symbionts.
Painting cell-cell interactions by horseradish peroxidase and endogenously generated hydrogen peroxide
Authors: Jeong Inyoung , Kim Kwang-eun , Rhee Hyun-Woo
Published: June 2024

Cell-Cell interactions are fundamental in biology for maintaining physiological conditions, with direct contact being the most straightforward mode of interaction. Recent advancements have led to the development of various chemical tools for detecting or identifying these interactions. However, the use of exogenous cues, such as toxic reagents, bulky probes, and light irradiations, can disrupt normal cell physiology. For example, the toxicity of hydrogen peroxide (H2O2) limits the applications of peroxidases in proximity labeling field. In this study, we aimed to address this limitation by demonstrating that membrane-localized Horseradish Peroxidase (HRP-TM) efficiently utilizes endogenously generated extracellular H2O2. By harnessing endogenous H2O2, we observed that HRP-TM-expressing cells can effectively label contacting cells without the need for exogenous H2O2treatment. Furthermore, we confirmed that HRP-TM labels proximal cells in an interaction-dependent manner. These findings offer a novel approach for studying cell-cell interactions under more physiological conditions, without the confounding effects of exogenous stimuli. Our study contributes to elucidating cell-cell interaction networks in various model organisms, providing valuable insights into the dynamic interplay between cells in their native network.
A genetically encoded sensor for real-time monitoring of poly-ADP-ribosylation dynamics in-vitro and in cells
Authors: Thomas Alix , Upadhyaya Kapil , Bejan Daniel , Adoff Hayden , Cohen Michael , Schultz Carsten
Published: June 2024

ADP-ribosylation, the transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) groups to proteins, is a conserved post-translational modification (PTM) that occurs most prominently in response to DNA damage. ADP-ribosylation is a dynamic PTM regulated by writers (PARPs), erasers (ADPr hydrolases), and readers (ADPR binders). PARP1 is the primary DNA damage-response writer responsible for adding a polymer of ADPR to proteins (PARylation). Real-time monitoring of PARP1-mediated PARylation, especially in live cells, is critical for understanding the spatial and temporal regulation of this unique PTM. Here, we describe a genetically encoded FRET probe (pARS) for semi-quantitative monitoring of PARylation dynamics. pARS feature a PAR-binding WWE domain flanked with turquoise and Venus. With a ratiometric readout and excellent signal-to-noise characteristics, we show that pARS can monitor PARP1-dependent PARylation temporally and spatially in real-time. pARS provided unique insights into PARP1-mediated PARylation kinetics in vitro and high-sensitivity detection of PARylation in live cells, even under mild DNA damage. We also show that pARS can be used to determine the potency of PARP inhibitors in vitro and, for the first time, in live cells in response to DNA damage. The robustness and ease of use of pARS make it an important tool for the PARP field.
COVID-19 advocacy bias in theBMJ: meta-research evaluation
Authors: Kepp Kasper P. , Cristea Ioana Alina , Muka Taulant , Ioannidis John P.A.
Published: June 2024

Objectives

During the COVID-19 pandemic,BMJ, the premier journal on evidence-based medicine worldwide, published many views by advocates of specific COVID-19 policies. We aimed to evaluate the presence and potential bias of this advocacy.

Design and Methods

Scopus was searched for items published until April 13, 2024 on “COVID-19 OR SARS-CoV-2”.BMJpublication numbers and types before (2016−2019) and during (2020−2023) the pandemic were compared for a group of advocates favoring aggressive measures (leaders of both the Independent Scientific Advisory Group for Emergencies (indieSAGE) and the Vaccines-Plus initiative) and four control groups: leading members of the governmental Scientific Advisory Group for Emergencies (SAGE), UK-based key signatories of the Great Barrington Declaration (GBD) (favoring more restricted measures), highly-cited UK scientists, and UK scientists who published the highest number of COVID-19-related papers in the entire scientific literature (n=16 in each group).

Results

122 authors published more than 5 COVID-19-related items each inBMJ. Of those, 18 were leading members/signatories of aggressive measures advocacy groups publishing 231 COVID-19 related BMJ documents, 53 were editors/journalists, and 51 scientists were not identified as associated with any advocacy. Of 41 authors with >10 publications inBMJ, 8 were scientists advocating for aggressive measures, 7 were editors, 23 were journalists, and only 3 were non-advocate scientists. Some aggressive measures advocates already had strongBMJpresence pre-pandemic. During pandemic years, the studied indieSAGE/Vaccines-Plus advocates outperformed inBMJpresence leading SAGE members by 16.0-fold, UK-based GBD advocates by 64.2-fold, the most-cited scientists by 16.0-fold, and the authors who published most COVID-19 papers overall by 10.7-fold. The difference was driven mainly by short opinion pieces and analyses.

Conclusions

BMJappears to have favored and massively promoted specific COVID-19 advocacy views during the pandemic, thereby strongly biasing the scientific picture on COVID-19.

Summary box

Section 1: What is already known on this topic

Advocacy is intensely debated for its merits to science and policy.

Many journals increasingly publish pieces by advocates and it is thus important to understand the nature, scale and impact of this phenomenon.

Section 2: What this study adds

This study provides a detailed quantitative assessment of journal-promoted advocacy, focusing on the world’s premier evidence-based medical journal, theBMJ.

We show thatBMJhad massive bias towards specific COVID-19-related advocacy favoring aggressive measures.

Our study reveals a need for editorial guidelines on journal-promoted advocacy.
Comparing lagged impacts of mobility changes and environmental factors on COVID-19 waves in rural and urban India: a Bayesian spatiotemporal modelling study
Authors: Cleary Eimear , Atuhaire Fatumah , Sorcihetta Alessandro , Ruktanonchai Nick , Ruktanonchai Cori , Cunningham Alexander , Pasqui Massimiliano , Schiavina Marcello , Melchiorri Michele , Bondarenko Maksym , Shepherd Harry E R , Padmadas Sabu S , Wesolowski Amy , Cummings Derek A T , Tatem Andrew J , Lai Shengjie
Published: June 2024

Previous research in India has identified urbanisation, human mobility and population demographics as key variables associated with higher district level COVID-19 incidence. However, the spatiotemporal dynamics of mobility patterns in rural and urban areas in India, in conjunction with other drivers of COVID-19 transmission, have not been fully investigated. We explored travel networks within India during two pandemic waves using aggregated and anonymized weekly human movement datasets obtained from Google, and quantified changes in mobility before and during the pandemic compared with the mean baseline mobility for the 8-week time period at the beginning of 2020. We fit Bayesian spatiotemporal hierarchical models coupled with distributed lag non-linear models (DLNM) within the integrated nested Laplace approximate (INLA) package in R to examine the lag-response associations of drivers of COVID-19 transmission in urban, suburban, and rural districts in India during two pandemic waves in 2020-2021. Model results demonstrate that recovery of mobility to 99% that of pre-pandemic levels was associated with an increase in relative risk of COVID-19 transmission during the Delta wave of transmission. This increased mobility, coupled with reduced stringency in public intervention policy and the emergence of the Delta variant, were the main contributors to the high COVID-19 transmission peak in India in April 2021. During both pandemic waves in India, reduction in human mobility, higher stringency of interventions, and climate factors (temperature and precipitation) had 2-week lag-response impacts on theRtof COVID-19 transmission, with variations in drivers of COVID-19 transmission observed across urban, rural and suburban areas. With the increased likelihood of emergent novel infections and disease outbreaks under a changing global climate, providing a framework for understanding the lagged impact of spatiotemporal drivers of infection transmission will be crucial for informing interventions.
Vestibular afferent neurons develop normally in the absence of quantal/glutamatergic input
Authors: Núñez Katherine Regalado , Bronson Daniel , Chang Ryan , Kalluri Radha
Published: June 2024

The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons’ membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons. To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined the maturation of the vestibular epithelium and ganglion neurons inVglut3-komice whose hair cell synapses lack glutamate. Despite lacking glutamatergic input, the knockout mice showed no notable balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of theVglut3-kovestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wildtype animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in theVglut3-komice is comparable to that found in wildtype controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type. Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.