bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic EBV variants confound disease-specific variant interpretation and predict variable immune therapy responses
Authors: Briercheck Edward L. , Ravishankar Shashidhar , Ahmed Elshafa Hassan , Carías Alvarado César Camilo , Barrios Menéndez Juan Carlos , Silva Oscar , Solórzano-Ortiz Elizabeth , Siliézar Tala Marcos Mauricio , Stevenson Philip , Xu Yuexin , Wohns Anthony Wilder , Enriquez-Vera Daniel , Barrionuevo Carlos , Yu Shan-Chi , Freud Aharon G. , Oakes Christopher , Weigel Christoph , Weinstock David M. , Klimaszewski Haley L. , Ngankeu Apollinaire , Mutalima Nora , Samayoa-Reyes Gabriela , Newton Robert , Rochford Rosemary , Valvert Fabiola , Natkunam Yasodha , Shustov Andrei , Baiocchi Robert A. , Warren Edus H.
Published: May 2024

Epstein-Barr virus (EBV) is a potent carcinogen linked to hematologic and solid malignancies and causes significant global morbidity and mortality. Therapy using allogeneic EBV-specific lymphocytes shows promise in certain populations, but the impact of EBV genome variation on these strategies remains unexplored. To address this, we sequenced 217 EBV genomes, including hematologic malignancies from Guatemala, Peru, Malawi, and Taiwan, and analyzed them alongside 1307 publicly available EBV genomes from cancer, nonmalignant diseases, and healthy individuals across Africa, Asia, Europe, North America, and South America. These included, to our knowledge, the first natural killer (NK)/T-cell lymphoma (NKTCL) EBV genomes reported outside of East Asia. Our findings indicate that previously proposed EBV genome variants specific to certain cancer types are more closely tied to geographic origin than to cancer histology. This included variants previously reported to be specific to NKTCL but were prevalent in EBV genomes from other cancer types and healthy individuals in East Asia. After controlling for geographic region, we did identify multiple NKTCL-specific variants associated with a 7.8-fold to 21.9-fold increased risk. We also observed frequent variations in EBV genomes that affected peptide sequences previously reported to bind common major histocompatibility complex alleles. Finally, we found several nonsynonymous variants spanning the coding sequences of current vaccine targets BALF4, BKRF2, BLLF1, BXLF2, BZLF1, and BZLF2. These results highlight the need to consider geographic variation in EBV genomes when devising strategies for exploiting adaptive immune responses against EBV-related cancers, ensuring greater global effectiveness and equity in prevention and treatment.
Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death
Authors: Zheng Li-yu , Duan Yu , He Peng-yi , Wu Meng-yao , Wei Shu-ting , Du Xiao-hui , Yao Ren-qi , Yao Yong-ming
Published: May 2024

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC’s RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.

Graphical Abstract
Arrhythmogenic right ventricular cardiomyopathy with sustained ventricular tachycardia: a case report
Authors: Ban Ying , Yao Feng-juan , Li Wei
Published: May 2024

Introduction

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC.

Case presentation

A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement.

Conclusion

Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.
Non-linear relationship between serum cholesterol levels and cognitive change among older people in the preclinical and prodromal stages of dementia: a retrospective longitudinal study in Taiwan
Authors: Chang Hsin-Te , Chan Po-Chi , Chiu Pai-Yi
Published: May 2024

Background

Adverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia.

Methods

Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments.

Results

Most associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R2 = 0.003–0.006, p < 0.016, Šidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R2 = 0.02–0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266–0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05).

Conclusion

These findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia.
Relative frequencies and clinical features of Guillain-Barré Syndrome before and during the COVID-19 pandemic in North China
Authors: Li Yaqian , Zhao Rongjuan , Li Ling , Xue Huiru , Meng Huaxing , Li Guanxi , Liang Feng , Zhang Huiqiu , Ma Jing , Pang Xiaomin , Wang Juan , Chang Xueli , Guo Junhong , Zhang Wei
Published: May 2024

Objective

Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China.

Methods

GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively.

Results

The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001).

Conclusions

COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis.
Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation
Authors: Awwad Aya , Rhee Eugene P. , Grams Morgan , Choles Hernan Rincon , Sondheimer James , He Jiang , Chen Jing , Hsu Chi-yuan , Vasan Ramachandran S , Kimmel Paul L. , Wulczyn Kendra , Berg Anders , Lash Jim , Tang Mengyao , Kalim Sahir ,   the CRIC Study Investigators, Anderson Amanda H , Appel Lawrence J. , Cohen Debbie L , Dember Laura M , Go Alan S. , Nelson Robert G. , Rahman Mahboob , Rao Panduranga S. , Shah Vallabh O , Unruh Mark L.
Published: May 2024

Background

Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.

Methods

Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.

Results

Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.

Conclusions

C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Relationship between sleep disturbance and developmental status in preschool-aged children with developmental disorder
Authors: Kim Sung Hyun , Kim Chung Reen , Park Donghwi , Cho Kang Hee , Nam Je Shik
Published: May 2024

Background

Sleep has been known to affect childhood development. Sleep disturbance is likely more common in children with developmental delay (DD) than in typical development. There are few studies on the correlation between sleep disturbance and developmental features in children with DD. Therefore, this study aimed to evaluate the associations between the two in children with DD.

Methods

A total of 45 children (age range 27.0 ± 11.1) with DD were recruited and evaluated using the Sleep Disturbance Scale for Children (SDSC) and Bayley Scales of Infant and Toddler Development (BSID-III). The outcomes are expressed as means and standard deviations. The correlation between SDSC and BSID-III was assessed using Spearman’s rank correlation test. Multiple regression analysis was performed to investigate the relationship between BSID-III domains and SDSC questionnaire subscales. Statistical significance was set at p < 0.05.

Results

Based on the correlation analysis and subsequent hierarchical regression analysis, cognition and socio-emotional domains of BSID-III were significantly associated with the DOES subscale of the SDSC questionnaire. In addition, the expressive language domain of the BSID-III was found to be associated with the DA subscale of the SDSC questionnaire. It seems that excessive daytime sleepiness might negatively affect emotional and behavioral problems and cognitive function. Also, arousal disorders seem to be related to memory consolidation process, which is thought to affect language expression.

Conclusion

This study demonstrated that DA and DOES subscales of the SDSC questionnaire were correlated with developmental aspects in preschool-aged children with DD. Sleep problems in children with DD can negatively affect their development, thereby interfering with the effectiveness of rehabilitation. Identifying and properly managing the modifiable factors of sleep problems is also crucial as a part of comprehensive rehabilitation treatment. Therefore, we should pay more attention to sleep problems, even in preschool-aged children with DD.
Gender disparities in all-cause mortality among individuals with early-onset cardiovascular diseases
Authors: Yang Jing , Wu Shouling , Liu Yang , Jiang Jinguo , Chen Shuohua , Zhang Boheng , Li Wei , Zhang Qi
Published: May 2024

Background and objective

Gender disparities in mortality among individuals with early-onset cardiovascular disease (CVD) remain uncertain. This study aimed to investigate gender differences in all-cause mortality and identify influencing factors.

Methods

Data extracted from the Kailuan Study, a prospective cohort study initiated in 2006, were analyzed. A total of 2,829 participants with early-onset CVD were included. Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CI) for gender disparities in all-cause mortality, adjusting for various factors.

Results

Males experienced a median follow-up duration of 7.54 years with 276 recorded deaths, and females had a median follow-up of 6.45 years with 105 recorded deaths. Gender disparities in all-cause mortality were observed, with men experiencing a higher all-cause mortality risk compared to women (HR: 1.42, 95% CI: 1.04, 1.92) in the fully adjusted model. Both in men and women with early-onset CVD, elevated hs-CRP levels and an eGFR < 60 mL/min/1.73m2 notably escalated the risk of all-cause mortality. Furthermore, the utilization of antiplatelet agents and successful blood glucose control might mitigate the risk of all-cause mortality. Smoking and eGFR decline modified the association between gender and all-cause death, women were more vulnerable to tobacco consumption and kidney misfunctioning than men (P-interaction = 0.019).

Conclusion

The study highlights gender disparities in all-cause mortality among individuals with early-onset CVD, with men experiencing a higher risk of mortality compared to women. Addressing these disparities is important for improving outcomes in this population. Further research is needed to develop sex-specific interventions and strategies to reduce gender-related mortality disparities in early-onset CVD.
Impact of COVID-19 pandemic responses on tuberculosis incidence: insights from Shantou, China
Authors: Su Yaqian , Chang Qiaocheng , Chen Ruiming , Chen Zhuanghao , Lin Jianxiong , Fu Hui , Cao Zicheng , Li Liping , Liu Suyang
Published: May 2024

Background

Various measures taken against the COVID-19 pandemic are not only effective in reducing the spread of the disease, but also lead to some unexpected results. This article regarded these measures as an intervention and explored their impact on the incidence of tuberculosis in Shantou, China.

Methods

The incidence rate and the surveillance data of tuberculosis from January 1st, 2018 to December 31st, 2021 were provided by the Shantou Tuberculosis Prevention and Control Institute. Data were divided into pre-pandemic period (January 1st, 2018 - December 31st, 2019) and pandemic periods (January 1st, 2020 - December 31st, 2021). The Interrupted Time Series (ITS) was used to analyze the trend of tuberculosis incidence prior to and during the COVID-19 epidemic.

Results

The results showed that the incidence of tuberculosis cases in Shantou decreased significantly (p < 0.05) during the pandemic as compared to that prior to the pandemic. Among them, the 45–64 age group and the 65 + age group have statistically significant declines. When patients were stratified by occupation, the unemployed and those working in agriculture reduced the most.

Conclusions

In response to the pandemic, measures like lockdowns and quarantines seem to have reduced tuberculosis incidence. However, this does not imply a true decrease. Underlying causes for the reduced true incidence need further scrutiny. Findings offer a preliminary exploration of interventions designed for one disease but functioning as unexpected results for another.
Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease – the PROSA study: rationale and study design
Authors: Böger Rainer , Hannemann Juliane
Published: May 2024

Background

Chronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers.

Methods

148 COPD patients (GOLD stage 2–3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation.

Discussion

The PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028.

Trial registration

The PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).
Health workers’ adherence to malaria case management protocols in Northern Sudan: a qualitative study
Authors: Khalid Mohamed Sahar , Khalid Mohamed Duha , Ahmed Khansaa , Saad Fadwa , Zurovac Dejan
Published: May 2024

Background

Nonadherence to national standards for malaria diagnosis and treatment has been reported in Sudan. In this study, qualitative research examined the clinical domains of nonadherence, factors influencing nonadherent practices and health workers’ views on how to improve adherence.

Methods

In September 2023, five Focus Group Discussions (FGDs) were undertaken with 104 health workers from 42 health facilities in Sudan’s Northern State. The participants included medical assistants, doctors, nurses, laboratory personnel, pharmacists and public health officers. The FGDs followed a semi-structured guide reflecting the national malaria case management protocol. Qualitative thematic analysis was performed.

Results

Nonadherent practices included disregarding parasitological test results, suboptimal paediatric artemether–lumefantrine (AL) dosing, lack of counselling, use of prohibited artemether injections for uncomplicated and severe malaria, artesunate dose approximations and suboptimal preparations, lack of AL follow on treatment for severe malaria; and rare use of primaquine for radical Plasmodium vivax treatment and dihydroartemisinin-piperaquine as the second-line treatment for uncomplicated malaria. Factors influencing nonadherence included stock-outs of anti-malarials and RDTs; staff shortages; lack of training, job aids and supervision; malpractice by specialists; distrust of malaria microscopy and RDTs; and patient pressure for diagnosis and treatment. Health workers recommended strengthening the supply chain; hiring personnel; providing in-service protocol training including specialists; establishing external quality assurance for malaria diagnosis; and providing onsite supportive supervision and public health campaigns.

Conclusions

This study revealed a broad spectrum of behavioural and systemic challenges in malaria management among frontline health workers in Northern Sudan, including nonadherence to protocols due to resource shortages, training gaps, a lack of supportive supervision and patient pressure. These insights, including health workers’ views about improvements, will inform evidence-based interventions by Sudan’s National Malaria Control Programme to improve health systems readiness and the quality of malaria case management.
Hyperbaric oxygen therapy ameliorates intestinal and systematic inflammation by modulating dysbiosis of the gut microbiota in Crohn’s disease
Authors: Li Yong , Sun Ruizheng , Lai Chen , Liu Kezhen , Yang Huixiang , Peng Ziheng , Xu Duo , Huang Fangling , Tang Keke , Peng Yu , Liu Xiaowei
Published: May 2024

Background

Dysbiosis of the gut microbiota is pivotal in Crohn’s disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown.

Methods

CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed.

Results

HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn’s Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4.

Conclusions

HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605.
Boosting antitumor efficacy using docetaxel-loaded nanoplatforms: from cancer therapy to regenerative medicine approaches
Authors: Beheshtizadeh Nima , Amiri Zahra , Tabatabaei Seyedeh Zoha , Seraji Amir Abbas , Gharibshahian Maliheh , Nadi Akram , Saeinasab Morvarid , Sefat Farshid , Kolahi Azar Hanieh
Published: May 2024

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel’s therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects.

Graphical Abstract
Comparison between one-stage and two-stage CT-guided localization of lung nodules with surgical resection: a single medical center experience
Authors: Hsueh Kai-Yun , Tang En-Kuei , Wu Fu-Zong , Tsai Ping-Chung , Shu Chih-Wen , Tseng Yen-Chiang , Goan Yih-Gang
Published: May 2024

Background

This retrospective study aimed to compare the efficacy and safety of one-stage computed tomography (OSCT)- to that of two-stage computed tomography (TSCT)-guided localization for the surgical removal of small lung nodules.

Methods

We collected data from patients with ipsilateral pulmonary nodules who underwent localization before surgical removal at Veteran General Hospital Kaohsiung between October 2017 and January 2022. The patients were divided into the OSCT and TSCT groups.

Results

We found that OSCT significantly reduced the localization time and risky time compared to TSCT, and the success rate of localization and incidence of pneumothorax were similar in both groups. However, the time spent under general anesthesia was longer in the OSCT group than in the TSCT group.

Conclusions

The OSCT-guided approach to localize pulmonary nodules in hybrid operation room is a safe and effective technique for the surgical removal of small lung nodules.
Unveiling the role of HP1α-HDAC1-STAT1 axis as a therapeutic target for HP1α-positive intrahepatic cholangiocarcinoma
Authors: Xiong Fei , Wang Da , Xiong Wei , Wang Xin , Huang Wen-hua , Wu Guan-hua , Liu Wen-zheng , Wang Qi , Chen Jun-sheng , Kuai Yi-yang , Wang Bing , Chen Yong-jun
Published: May 2024

Background

Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear.

Methods

The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP).

Results

HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents.

Conclusions

HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.
The association of arterial partial oxygen pressure with mortality in critically ill sepsis patients: a nationwide observational cohort study
Authors: Hyun Dong-gon , Ahn Jee Hwan , Huh Jin Won , Hong Sang-Bum , Koh Younsuck , Oh Dong Kyu , Lee Su Yeon , Park Mi Hyeon , Lim Chae-Man ,   The Korean Sepsis Alliance (KSA) Investigators
Published: May 2024

Background

Although several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension.

Methods

From the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality.

Results

The median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0–134.0) and 84.4 (71.2–112.0) in day 1110.0 (93.4–132.0) and 80.0 (71.0–100.0) in day 2, and 106.0 (91.9–127.4) and 78.0 (69.0–94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65–0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67–0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73–0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg.

Conclusions

In critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.
Correlation among post-surgery recurrence of CRSwNP and TCM syndromes and tissue inflammatory cell infiltration type: a study protocol
Authors: Xie Yan , Liang Fangqi , Zhou Li , Chen Qing , Chen Feifei , Fu Qinwei , Wu Shiqi , Zeng Dandi , Cui Wanling , Liao Linzhi , Jiang Luyun
Published: May 2024

Background

Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types.

Methods and analysis

This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People’s Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients’ pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches.

Discussion

This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP.

Systematic review registration

PROSPERO ChiCTR2100041646.
Prevalence of iodine deficiency and associated factors among school-age children in Ethiopia: a systematic review and meta-analysis
Authors: Baffa Lemlem Daniel , Angaw Dessie Abebaw , Abriham Zufan Yiheyis , Gashaw Moges , Agimas Muluken Chanie , Sisay Mekonnen , Muhammad Esmael Ali , Mengistu Berhanu , Belew Aysheshim Kassahun
Published: May 2024

Background

Currently, iodine deficiency has become a significant burden globally; where 2 billion people and 29.8% of school-age children are iodine deficient. It is a leading cause of preventable brain damage among children, resulting in impaired cognitive and motor development. Even though salt iodization was started to be implemented to alleviate this burden in Ethiopia, primary studies assessing iodine deficiency in the country show highly variable findings, and no systematic review was conducted to determine the pooled prevalence of the problem which makes it difficult to assess the effect of the intervention as well as to design appropriate and timely measures. Therefore, this systematic review and meta-analysis aimed to determine the pooled prevalence of iodine deficiency and the common factors affecting its occurrence among school-age children in Ethiopia.

Method

To obtain the eligible studies, databases (EMBASE, Scopus, Hinari, and PubMed), websites (Google and Google Scholar), and references of the eligible studies were searched systematically. Data were extracted using an Excel spreadsheet and analyzed using the STATA 17 version. The I2 test was used to assess heterogeneity between the studies. A DerSimonian and Laird random-effects model was used to estimate the pooled prevalence and pooled odds ratio. A funnel plot and Egger’s test were used to detect publication bias.

Result

A total of 15 eligible studies, representing 15,611 school-age children, were included in the systematic review and meta-analysis. The pooled prevalence of iodine deficiency among school-age children in Ethiopia was found to be 58% (95%CI 44.00–77.00), while the highest prevalence was recorded in the Oromia Region, which was 64% (95% CI 49–79). Goitrogenic food consumption (adjusted odds ratio (AOR) 2.93, 95% CI 1.60–5.35) and being female (adjusted odds ratio (AOR) 1.87, 95% CI 1.43–2.44) showed a significant association with the prevalence of iodine deficiency.

Conclusion

Iodine deficiency among school-age children in Ethiopia was noticeably high. Goitrogenic food consumption and the sex of the child were determinant factors for the occurrence of iodine deficiency among the children. Therefore, appropriate advice should be given to households to limit goitrogenic foods in the diet of their children by giving due attention to their female children.
Assessment of nucleic acid extraction protocols for antibiotic resistance genes (ARGs) quantification in aircraft wastewater
Authors: Smith Wendy J. M. , Liu Yawen , Simpson Stuart L. , Bivins Aaron , Ahmed Warish
Published: May 2024

This study evaluated ten nucleic acid extraction protocols (EP1 to EP10) for measuring five endogenous antibiotic resistance genes (ARGs) in four aircraft wastewater samples (AWW1 to AWW4). The targeted ARGs, including blaCTX-M, blaNDM-1, ermB, qnrS, and tetA, encompassed highly and minimally abundant ARGs. TetA and ermB were consistently detected across four aircraft wastewater samples using the DNeasy Blood and Tissue Kit and the AllPrep PowerViral DNA/RNA kit. QnrS displayed high detection rates with specific extraction protocols and aliquot volumes. Concentrations of ARGs varied across aircraft wastewater samples, with differing extraction protocols influencing quantitative results. The concentrations of tetA, ermB, and qnrS in AWW1 were distinct, while AWW2 to AWW4 exhibited a broader range for tetA, ermB, qnrS, blaCTX-M, and blaNDM-1. EP1 consistently produced the highest concentrations for several ARGs. Collective data analysis revealed varying ARG concentrations across the ten extraction protocols, suggesting the importance of careful extraction protocol selection in ARG monitoring in aircraft wastewater samples. Based on the results, we suggest that a small sample volume (as low as 0.2 mL) may be sufficient for ARG characterization in aircraft wastewater samples. The findings also emphasize the need for considering toilet paper removal without compromising nucleic acid extraction efficiency. The study highlights promising prospects for aircraft wastewater monitoring of ARGs, calling for further investigation into the import and spread of unique ARGs through transport hubs.
The war between the immune system and the tumor - using immune biomarkers as tracers
Authors: Yang Kai , Lu Rongrong , Mei Jie , Cao Kai , Zeng Tianyu , Hua Yijia , Huang Xiang , Li Wei , Yin Yongmei
Published: May 2024

Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.
Deep vs shallow: GPS tags reveal a dichotomy in movement patterns of loggerhead turtles foraging in a coastal bay
Authors: Lamont Margaret M. , Slone Daniel , Reid James P. , Butler Susan M. , Alday Joseph
Published: May 2024

Background

Individual variation in movement strategies of foraging loggerhead turtles have been documented on the scale of tens to hundreds of kilometers within single ocean basins. Use of different strategies among individuals may reflect variations in resources, predation pressure or competition. It is less common for individual turtles to use different foraging strategies on the scale of kilometers within a single coastal bay. We used GPS tags capable of back-filling fine-scale locations to document movement patterns of loggerhead turtles in a coastal bay in Northwest Florida, U.S.A.

Methods

Iridium-linked GPS tags were deployed on loggerhead turtles at a neritic foraging site in Northwest Florida. After filtering telemetry data, point locations were transformed to movement lines and then merged with the original point file to define travel paths and assess travel speed. Home ranges were determined using kernel density function. Diurnal behavioral shifts were examined by examining turtle movements compared to solar time.

Results

Of the 11 turtles tagged, three tracked turtles remained in deep (~ 6 m) water for almost the entire tracking period, while all other turtles undertook movements from deep water locations, located along edges and channels, to shallow (~ 1–2 m) shoals at regular intervals and primarily at night. Three individuals made short-term movements into the Gulf of Mexico when water temperatures dropped, and movement speeds in the Gulf were greater than those in the bay. Turtles exhibited a novel behavior we termed drifting.

Conclusions

This study highlighted the value provided to fine-scale movement studies for species such as sea turtles that surface infrequently by the ability of these GPS tags to store and re-upload data. Future use of these tags at other loggerhead foraging sites, and concurrent with diving and foraging data, would provide a powerful tool to better understand fine-scale movement patterns of sea turtles.
Enhancing reporting through structure: a before and after study on the effectiveness of SPIRIT-based templates to improve the completeness of reporting of randomized controlled trial protocols
Authors: Blanco David , Donadio Márcio Vinícius Fagundes , Cadellans-Arróniz Aïda
Published: May 2024

Background

Despite the improvements in the completeness of reporting of randomized trial protocols after the publication of the Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) guidelines, many items remain poorly reported. This study aimed to assess the effectiveness of using SPIRIT-tailored templates for trial protocols to improve the completeness of reporting of the protocols that master’s students write as part of their master’s theses.

Methods

Before and after experimental study performed at the University Master’s Degree in Orthopaedic Manual Physiotherapy of the Universitat Internacional de Catalunya (Barcelona, Spain). While students in the post-intervention period were instructed to use a trial protocol template that was tailored to SPIRIT, students in the pre-intervention period did not use the template. Primary outcome: Difference between the pre- and post-intervention periods in the mean number of adequately reported items (0–10 scale). The outcomes were evaluated independently and in duplicate by two blinded assessors. Students and their supervisors were not aware that they were part of a research project. For the statistical analysis, we used a generalized linear regression model (dependent variable: number of adequately reported items in the protocol; independent variables: intervention period, call, language).

Results

Thirty-four trial protocols were included (17, pre-intervention; 17, post-intervention). Protocols produced during the post-intervention period (mean: 8.24; SD: 1.52) were more completely reported than those produced during the pre-intervention period (mean: 6.35; SD: 1.80); adjusted difference: 1.79 (95% CI: 0.58 to 3.00).

Conclusions

SPIRIT-based templates could be used to improve the completeness of reporting of randomized trial protocols.
Organizational aspects of tissue engineering clinical translation: insights from a qualitative case study
Authors: da Silva Renan Gonçalves Leonel , Au Larry , Blasimme Alessandro
Published: May 2024

Background

Tissue engineering is a multidisciplinary field that combines principles from cell biology, bioengineering, material sciences, medicine and surgery to create functional and viable bioproducts that can be used to repair or replace damaged or diseased tissues in the human body. The complexity of tissue engineering can affect the prospects of efficiently translating scientific discoveries in the field into scalable clinical approaches that could benefit patients. Organizational challenges may play a key role in the clinical translation of tissue engineering for the benefit of patients.

Methods

To gain insight into the organizational aspects of tissue engineering that may create impediments to efficient clinical translation, we conducted a retrospective qualitative case study of one tissue engineering multi-site translational project on knee cartilage engineered tissue grafts. We collected qualitative data using a set of different methods: semi-structured interviews, documentary research and audio-visual content analysis.

Results

Our study identified various challenges associated to first-in-human trials in tissue engineering particularly related to: logistics and communication; research participant recruitment; clinician and medical student participation; study management; and regulation.

Conclusions

While not directly generalizable to other types of advanced therapies or to regenerative medicine in general, our results offer valuable insights into organizational barriers that may prevent efficient clinical translation in the field of tissue engineering.