bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract
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.