bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventricular Pacing in Pacemaker Bigeminy to Rule in/out Truncated Pacemaker-mediated Tachycardia
Authors: Mondal Sudipta , P Raja Dinesh , Vijay Jyothi
Published: February 2024

Pacemaker bigeminy is not an uncommon electrocardiographic finding in device clinics. However, such a pattern mandates the differentiation of important possible diagnostic considerations such as premature atrial contractions, oversensing the T wave or the QRS complex, dual AV nodal physiology, and retrograde atrial depolarization. We present a case of pacemaker bigeminy where ventricular pacing was used to exclude the truncated form of pacemaker-mediated tachycardia and reach a diagnosis of atrial bigeminy, which was crucial from the management’s perspective.
Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia
Authors: Tam Constantine S. , Opat Stephen , D'Sa Shirley , Jurczak Wojciech , Lee Hui-Peng , Cull Gavin , Owen Roger G. , Marlton Paula , Wahlin Björn E. , García-Sanz Ramón , McCarthy Helen , Mulligan Stephen , Tedeschi Alessandra , Castillo Jorge J. , Czyż Jarosław , Fernández De Larrea Carlos , Belada David , Libby Edward , Matous Jeffrey , Motta Marina , Siddiqi Tanya , Tani Monica , Trněný Marek , Minnema Monique C. , Buske Christian , Leblond Véronique , Treon Steven P. , Trotman Judith , Wu Binghao , Yu Yiling , Shen Zhirong , Chan Wai Y. , Schneider Jingjing , Allewelt Heather , Cohen Aileen , Dimopoulos Meletios A.
Published: February 2024

The phase 3 ASPEN trial (NCT03053440) compared Bruton tyrosine kinase inhibitors (BTKis), zanubrutinib and ibrutinib, in patients with Waldenström macroglobulinemia (WM). Post-hoc biomarker analysis was performed using next-generation sequencing on pretreatment bone marrow samples from 98 patients treated with zanubrutinib and 92 patients treated with ibrutinib with mutated (MUT) MYD88 and 20 patients with wild-type (WT) MYD88 treated with zanubrutinib. Of 329 mutations in 52 genes, mutations in CXCR4 (25.7%), TP53 (24.8%), ARID1A (15.7%), and TERT (9.0%) were most common. TP53MUT, ARID1AMUT, and TERTMUT were associated with higher rates of CXCR4MUT (P < .05). Patients with CXCR4MUT (frameshift or nonsense [NS] mutations) had lower very good partial response (VGPR) and complete response rates (CR; 17.0% vs 37.2%, P = .020) and longer time to response (11.1 vs 8.4 months) than patients with CXCR4WT treated with BTKis. CXCR4NS was associated with inferior progression-free survival (PFS; hazard ratio [HR], 3.39; P = .017) in patients treated with ibrutinib but not in those treated with zanubrutinib (HR, 0.67; P = .598), but VGPR + CR rates were similar between treatment groups (14.3% vs 15.4%). Compared with ibrutinib, patients with CXCR4NS treated with zanubrutinib had a favorable major response rate (MRR; 85.7% vs 53.8%; P = .09) and PFS (HR, 0.30; P = .093). In patients with TP53MUT, significantly lower MRRs were observed for patients treated with ibrutinib (63.6% vs 85.7%; P = .04) but not for those treated with zanubrutinib (80.8% vs 81.9%; P = .978). In TP53MUT, compared with ibrutinib, patients treated with zanubrutinib had higher VGPR and CR (34.6% vs 13.6%; P < .05), numerically improved MRR (80.8% vs 63.6%; P = .11), and longer PFS (not reached vs 44.2 months; HR, 0.66; P = .37). Collectively, patients with WM with CXCR4MUT or TP53MUT had worse prognosis compared with patients with WT alleles, and zanubrutinib led to better clinical outcomes.
Type 2M/2A von Willebrand disease: a shared phenotype between type 2M and 2A
Authors: Seidizadeh Omid , Mollica Luca , Zambarbieri Serena , Baronciani Luciano , Cairo Andrea , Colpani Paola , Cozzi Giovanna , Pagliari Maria Teresa , Ciavarella Alessandro , Siboni Simona M. , Peyvandi Flora
Published: February 2024

Four variants have been continuously subjected to debate and received different von Willebrand disease (VWD) classifications: p.R1315L, p.R1315C, p.R1374H, and p.R1374C. We chose to comprehensively investigate these variants with full set of VWD tests, protein-modeling predictions and applying structural biology. Patients with p.R1315L, p.R1315C, p.R1374H, and p.R1374C were included. A group with type 2A and 2M was included to better understand similarities and differences. Patients were investigated for phenotypic assays and underlying disease mechanisms. We applied deep protein modeling predictions and structural biology to elucidate the causative effects of variants. Forty-three patients with these variants and 70 with 2A (n = 35) or 2M (n = 35) were studied. Patients with p.R1315L, p.R1374H, or p.R1374C showed a common phenotype between 2M and 2A using von Willebrand factor (VWF):GPIbR/VWF:Ag and VWF:CB/VWF:Ag ratios and VWF multimeric profile, whereas p.R1315C represented a type 2M phenotype. There was an overall reduced VWF synthesis or secretion in 2M and cases with p.R1315L, p.R1374H, and p.R1374C, but not in 2A. Reduced VWF survival was observed in most 2A (77%), 2M (80%), and all 40 cases with p.R1315L, p.R1374H, and p.R1374C. These were the only variants that fall at the interface between the A1-A2 domains. p.R1315L/C mutants induce more compactness and internal mobility, whereas p.R1374H/C display a more extended overall geometry. We propose a new classification of type 2M/2A for p.R1315L, p.R1374H, and p.R1374C because they share a common phenotype with 2M and 2A. Our structural analysis shows the unique location of these variants on the A1-A2 domains and their distinctive effect on VWF.
Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes
Authors: Zou Yuan , Zhang Jing , Sun Fei , Xu Qianqian , Chen Longmin , Luo Xi , Wang Ting , Zhou Qing , Zhang Shu , Xiong Fei , Kong Wen , Yang Ping , Yu Qilin , Liu Shiwei , Wang Cong-Yi
Published: February 2024

Background

Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.

Method

Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes.

Result

Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines.

Conclusion

Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.
A novel homozygous TSGA10 missense variant causes acephalic spermatozoa syndrome in a Pakistani family
Authors: Khan Khalid , Zhang Xiangjun , Dil Sobia , Khan Ihsan , Unar Ahsanullah , Ye Jingwei , Zeb Aurang , Zubair Muhammad , Shah Wasim , Zhang Huan , Khan Muzammil Ahmad , Wu Limin , Xu Bo , Ma Hui , Wen Zina , Shi Qinghua
Published: February 2024

Background

Acephalic spermatozoa syndrome is a rare type of teratozoospermia causing male infertility due to detachment of the sperm head and flagellum, which precludes fertilization potential. Although loss-of-function variations in several genes, including TSGA10, have been associated with acephalic spermatozoa syndrome, the genetic cause of many cases remains unclear.

Results

We recruited a Pakistani family with two infertile brothers who suffered from acephalic spermatozoa syndrome. Through whole-exome sequencing (WES) followed by Sanger sequencing, we identified a novel missense variant in TSGA10 (c.1112T > C, p. Leu371Pro), which recessively co-segregated with the acephalic spermatozoa syndrome within this family. Ultrastructural analyses of spermatozoa from the patient revealed that 98% of flagellar cross-sections displayed abnormal axonemal ultrastructure, in addition to the head-flagellum detachment. Real-time quantitative PCR analysis revealed almost no detectable TSAG10 mRNA and western blot analysis also failed to detect TSAG10 protein in patient's sperm samples while TSGA10 expression was clearly detected in control samples. Consistently, immunofluorescence analysis demonstrated the presence of TSGA10 signal in the midpiece of sperm from the control but a complete absence of TSGA10 signal in sperm from the patient.

Conclusion

Altogether, our study identifies a novel TSGA10 pathogenic variant as a cause of acephalic spermatozoa syndrome in this family and provides information regarding the clinical manifestations associated with TSGA10 variants in human.
A new approach to describe the taxonomic structure of microbiome and its application to assess the relationship between microbial niches
Authors: Pappalardo Vincent Y. , Azarang Leyla , Zaura Egija , Brandt Bernd W. , de Menezes Renée X.
Published: February 2024

Background

Data from microbiomes from multiple niches is often collected, but methods to analyse these often ignore associations between niches. One interesting case is that of the oral microbiome. Its composition is receiving increasing attention due to reports on its associations with general health. While the oral cavity includes different niches, multi-niche microbiome data analysis is conducted using a single niche at a time and, therefore, ignores other niches that could act as confounding variables. Understanding the interaction between niches would assist interpretation of the results, and help improve our understanding of multi-niche microbiomes.

Methods

In this study, we used a machine learning technique called latent Dirichlet allocation (LDA) on two microbiome datasets consisting of several niches. LDA was used on both individual niches and all niches simultaneously. On individual niches, LDA was used to decompose each niche into bacterial sub-communities unveiling their taxonomic structure. These sub-communities were then used to assess the relationship between microbial niches using the global test. On all niches simultaneously, LDA allowed us to extract meaningful microbial patterns. Sets of co-occurring operational taxonomic units (OTUs) comprising those patterns were then used to predict the original location of each sample.

Results

Our approach showed that the per-niche sub-communities displayed a strong association between supragingival plaque and saliva, as well as between the anterior and posterior tongue. In addition, the LDA-derived microbial signatures were able to predict the original sample niche illustrating the meaningfulness of our sub-communities. For the multi-niche oral microbiome dataset we had an overall accuracy of 76%, and per-niche sensitivity of up to 83%. Finally, for a second multi-niche microbiome dataset from the entire body, microbial niches from the oral cavity displayed stronger associations to each other than with those from other parts of the body, such as niches within the vagina and the skin.

Conclusion

Our LDA-based approach produces sets of co-occurring taxa that can describe niche composition. LDA-derived microbial signatures can also be instrumental in summarizing microbiome data, for both descriptions as well as prediction.
Genome-wide characterization of the CPA gene family in potato and a preliminary functional analysis of its role in NaCl tolerance
Authors: Liu Jintao , Li Dianjue , Wang Jing , Wang Qian , Guo Xiao , Fu Qi , Kear Philip , Zhu Guangtao , Yang Xiaohui
Published: February 2024

Background

The cation/proton antiporter (CPA) superfamily plays a crucial role in regulating ion homeostasis and pH in plant cells, contributing to stress resistance. However, in potato (Solanum tuberosum L.), systematic identification and analysis of CPA genes are lacking.

Results

A total of 33 StCPA members were identified and classified into StNHX (n = 7), StKEA (n = 6), and StCHX (n = 20) subfamilies. StCHX owned the highest number of conserved motifs, followed by StKEA and StNHX. The StNHX and StKEA subfamilies owned more exons than StCHX. NaCl stress induced the differentially expression of 19 genes in roots or leaves, among which StCHX14 and StCHX16 were specifically induced in leaves, while StCHX2 and StCHX19 were specifically expressed in the roots. A total of 11 strongly responded genes were further verified by qPCR. Six CPA family members, StNHX1, StNHX2, StNHX3, StNHX5, StNHX6 and StCHX19, were proved to transport Na+ through yeast complementation experiments.

Conclusions

This study provides comprehensive insights into StCPAs and their response to NaCl stress, facilitating further functional characterization.
The impact of selective HDAC inhibitors on the transcriptome of early mouse embryos
Authors: Shao Ruiqi , Suzuki Takayoshi , Suyama Mikita , Tsukada Yuichi
Published: February 2024

Background

Histone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a crucial role in the control of gene expression. HDAC inhibitors (HDACi) have shown potential in cancer therapy; however, the specific roles of HDACs in early embryos remain unclear. Moreover, although some pan-HDACi have been used to maintain cellular undifferentiated states in early embryos, the specific mechanisms underlying their effects remain unknown. Thus, there remains a significant knowledge gap regarding the application of selective HDACi in early embryos.

Results

To address this gap, we treated early embryos with two selective HDACi (MGCD0103 and T247). Subsequently, we collected and analyzed their transcriptome data at different developmental stages. Our findings unveiled a significant effect of HDACi treatment during the crucial 2-cell stage of zygotes, leading to a delay in embryonic development after T247 and an arrest at 2-cell stage after MGCD0103 administration. Furthermore, we elucidated the regulatory targets underlying this arrested embryonic development, which pinpointed the G2/M phase as the potential period of embryonic development arrest caused by MGCD0103. Moreover, our investigation provided a comprehensive profile of the biological processes that are affected by HDACi, with their main effects being predominantly localized in four aspects of zygotic gene activation (ZGA): RNA splicing, cell cycle regulation, autophagy, and transcription factor regulation. By exploring the transcriptional regulation and epigenetic features of the genes affected by HDACi, we made inferences regarding the potential main pathways via which HDACs affect gene expression in early embryos. Notably, Hdac7 exhibited a distinct response, highlighting its potential as a key player in early embryonic development.

Conclusions

Our study conducted a comprehensive analysis of the effects of HDACi on early embryonic development at the transcriptional level. The results demonstrated that HDACi significantly affected ZGA in embryos, elucidated the distinct actions of various selective HDACi, and identified specific biological pathways and mechanisms via which these inhibitors modulated early embryonic development.
Comparison of the analgesic effect of dezocine and esketamine in combination with sufentanil respectively after laparoscopic cholecystectomy: a prospective randomized controlled study
Authors: Deng Boran , Wang Dingding , Xie Zifeng , Wang Yongqin , Huang Li , Jiang Manlin , Shen Tu
Published: February 2024

Background

Sufentanil in combination with dezocine or esketamine is often used for postoperative analgesia. However, there is a lack of clinical evidence of efficacy. This study compares the analgesic effects of esketamine and dezocine combined with sufentanil for relieving pain after laparoscopic cholecystectomy(LC).

Methods

A total of 58 patients were randomly assigned to the esketamine group (ES group) and dezocine group (DE group). In the ES group, 1.5 mg/kg esketamine was used. In the DE group, 0.3 mg/kg dezocine was used. Primary outcome measures were Visual Analog Scale (VAS) score at 4 h, 8 h, 24 h and 48 h after surgery. The second outcome measures were Interleukin-6 (IL-6) and C-reactive protein (CRP) levels in the serum 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery.

Results

The VAS scores at 4 h, 8 h, 24 h and 48 h after the surgery in the ES group vs DE group were 2.70 vs 3.50(P=0.013),2.35 vs 3.15(P=0.004),1.69 vs 2.58(P=0.002), and 1.50 vs 2.26(P=0.002), respectively. The serum IL-6 concentrations 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery in the ES group and DE group were 34.39 and 34.12(P=0.901),112.33 and 129.60(P=0.014), and 89.69 and 108.46(P<0.001), respectively. The CRP levels in serum 10 minutes before anesthesia induction, and at 24 h and 48 h after the surgery in the ES group and DE group were 5.99 and 5.86(P=0.639), 28.80 and 35.37(P<0.001), and 23.17 and 30.11(P<0.001), respectively.

Conclusion

For postoperative pain after LC, 1.5mg/kg esketamine provided better analgesia and reduced inflammation levels than 0.3mg/kg dezocine.

Trial registration

This trial was registered in the China Clinical Research Information Center in 31/05/2023 : https://www.chictr.org.cn/bin/home (Registration number: ChiCTR2300072011).
An inflammation-based model for identifying severe acute pancreatitis: a single-center retrospective study
Authors: Li Xiaotong , Zhang Yiyan , Wang Weiwei , Meng Yao , Chen Huimin , Chu Guiyang , Li Hongyu , Qi Xingshun
Published: February 2024

Background and aims

Severe acute pancreatitis (SAP) is potentially lethal. Considering the role of inflammation in the progression of acute pancreatitis (AP), this study aims to develop a model based on inflammatory indexes for identifying the presence of SAP.

Methods

Overall, 253 patients with AP who were consecutively admitted between July 2018 and November 2020 were screened, of whom 60 had SAP. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-platelet ratio (NPR), systemic inflammation response index (SIRI), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), C-reactive protein-to-lymphocyte ratio (CLR), and triglyceride glucose (TyG) index were calculated. Multivariate logistic regression analyses were performed to identify independent risk factors of SAP. Then, inflammation-based models were established. Receiver operating characteristics (ROC) curve analyses were performed. Area under ROC curve (AUROC) was calculated.

Results

Diabetes mellitus, fatty liver, high white blood cell count (WBC), C-reactive protein (CRP), red blood cell distribution width (RDW), procalcitonin (PCT), SII, NLR, NPR, CAR, CLR, and TyG index, and a low LMR were significantly associated with SAP. Considering the collinearity among these variables, 10 multivariate logistic regression analyses were separately performed. Finally, four independent inflammation-based models were established. Of them, the best one, which was calculated as follows: 1.204*fatty liver (yes = 1; no = 0) + 0.419*PCT + 0.005*CLR - 2.629, had an AUROC of 0.795 with a specificity of 73.4% and a sensitivity of 71.7%.

Conclusion

The inflammation-based model consisting of fatty liver, PCT, and CLR has a good diagnostic performance for SAP.
Colistin monotherapy or combination for the treatment of bloodstream infection caused by Klebsiella pneumoniae: a systematic review and meta-analysis
Authors: Wang Tao , Liu Hongcheng , Huang Huiqing , Weng Yuesong , Wang Xiaojun
Published: February 2024

Background

Bloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP.

Methods

Electronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis.

Results

Following the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62–2.97, P = 0.45, Tau2 = 0.00, I2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27–2.45, P = 0.71, Tau2 = 0.00, I2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34–7.04, P = 0.008, Tau2 = 0.00, I2 = 0%) and 0.98 (95%CI = 0.29–3.31, P = 0.98, Tau2 = 0.00, I2 = 0% ), respectively.

Conclusions

Colistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects.

Trial registration

retrospectively registered.
Machine learning-based MRI radiomics for assessing the level of tumor infiltrating lymphocytes in oral tongue squamous cell carcinoma: a pilot study
Authors: Ren Jiliang , Yang Gongxin , Song Yang , Zhang Chunye , Yuan Ying
Published: February 2024

Background

To investigate the value of machine learning (ML)-based magnetic resonance imaging (MRI) radiomics in assessing tumor-infiltrating lymphocyte (TIL) levels in patients with oral tongue squamous cell carcinoma (OTSCC).

Methods

The study included 68 patients with pathologically diagnosed OTSCC (30 with high TILs and 38 with low TILs) who underwent pretreatment MRI. Based on the regions of interest encompassing the entire tumor, a total of 750 radiomics features were extracted from T2-weighted (T2WI) and contrast-enhanced T1-weighted (ceT1WI) imaging. To reduce dimensionality, reproducibility analysis by two radiologists and collinearity analysis were performed. The top six features were selected from each sequence alone, as well as their combination, using the minimum-redundancy maximum-relevance algorithm. Random forest, logistic regression, and support vector machine models were used to predict TIL levels in OTSCC, and 10-fold cross-validation was employed to assess the performance of the classifiers.

Results

Based on the features selected from each sequence alone, the ceT1WI models outperformed the T2WI models, with a maximum area under the curve (AUC) of 0.820 versus 0.754. When combining the two sequences, the optimal features consisted of one T2WI and five ceT1WI features, all of which exhibited significant differences between patients with low and high TILs (all P < 0.05). The logistic regression model constructed using these features demonstrated the best predictive performance, with an AUC of 0.846 and an accuracy of 80.9%.

Conclusions

ML-based T2WI and ceT1WI radiomics can serve as valuable tools for determining the level of TILs in patients with OTSCC.
Impact of C-reactive protein on the effect of Roxadustat for the treatment of anemia in chronic kidney disease: a systematic review of randomized controlled trials
Authors: Luo Xiaoyu , Li Guoli , Yang Hongyu , Chen Lang , Gao Yinyan , Cong Jing , Luo Hui , Zhang Weiru
Published: February 2024

Background

Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD.

Methods

We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA).

Results

A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP.

Conclusions

Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation.

Trial registration

CRD42023396704.
Genome-wide quantification of copy-number aberration impact on gene expression in ovarian high-grade serous carcinoma
Authors: Jamalzadeh Sanaz , Dai Jun , Lavikka Kari , Li Yilin , Jiang Jing , Huhtinen Kaisa , Virtanen Anni , Oikkonen Jaana , Hietanen Sakari , Hynninen Johanna , Vähärautio Anna , Häkkinen Antti , Hautaniemi Sampsa
Published: February 2024

Copy-number alterations (CNAs) are a hallmark of cancer and can regulate cancer cell states via altered gene expression values. Herein, we have developed a copy-number impact (CNI) analysis method that quantifies the degree to which a gene expression value is impacted by CNAs and leveraged this analysis at the pathway level. Our results show that a high CNA is not necessarily reflected at the gene expression level, and our method is capable of detecting genes and pathways whose activity is strongly influenced by CNAs. Furthermore, the CNI analysis enables unbiased categorization of CNA categories, such as deletions and amplifications. We identified six CNI-driven pathways associated with poor treatment response in ovarian high-grade serous carcinoma (HGSC), which we found to be the most CNA-driven cancer across 14 cancer types. The key driver in most of these pathways was amplified wild-type KRAS, which we validated functionally using CRISPR modulation. Our results suggest that wild-type KRAS amplification is a driver of chemotherapy resistance in HGSC and may serve as a potential treatment target.
Microbiological isolates and associated complications of dacryocystitis and canaliculitis in a prominent tertiary ophthalmic teaching hospital in northern China
Authors: Tian Xiaobo , Sun Hua , Huang Yanfei , Sui Wenjun , Zhang Dan , Sun Yufeng , Jin Jing , He Yueqing , Lu Xinxin
Published: February 2024

Background

To report the microbiological isolates, aetiology, complications, antibiotic susceptibilities, and clinical remission of dacryocystitis and canaliculitis in a prominent tertiary ophthalmic teaching and referral hospital located in northern China and to offer appropriate recommendations for preventing and formulating drug treatment strategies.

Methods

This prospective study recruited a total of 477 participants who had been diagnosed with either dacryocystitis or canaliculitis. The cohort comprised 307 patients with chronic dacryocystitis, 111 patients with acute dacryocystitis, and 59 patients with canaliculitis. Purulent discharge from the lacrimal duct was collected using a sterile swab and immediately subjected to microbial culture. Antimicrobial susceptibility testing was conducted following established protocols. All participants were scheduled for follow-up visits within 14 days after receiving antibiotic therapy.

Results

The present findings indicated that women exhibited a higher susceptibility to the condition, as evidenced by the occurrence of 367 cases in comparison to 110 cases among men. Among the 477 patients, definitive causes were established in 59 individuals, accounting for 12.4% of the patients. Additionally, ocular complications were reported by 132 patients, representing 27.7% of the total. Monocular involvement was observed in the majority of cases, with 402 out of 477 patients (84.3%) affected, while binocular involvement was present in 75 patients (15.7%). In total, 506 microbiological strains were recovered from 552 eyes, withStaphylococcus epidermidis(16.4%) being the most prevalent microorganism. Other predominant isolates includedCorynebacterium macginleyi(9.1%),Staphylococcus aureus(5.1%),Streptococcus pneumoniae(4.9%), Haemophilus (4.4%),Propionibacterium acnes(3.5%), andEikenella corrodens(3.1%). Among the 12 isolated fungi,Candida parapsilosisaccounted for 66.7%. The susceptibility to antimicrobial agents tested in gram-negative bacilli (79.5%) was observed to be higher than that of anaerobic bacteria (76.7%) and gram-positive cocci (55.4%). With pharmacological therapy, the remission rate of acute dacryocystitis (72.7%) was found to be higher than that of canaliculitis (53.3%) and chronic dacryocystitis (42.3%).

Conclusions

This study highlights the microbial spectrum of dacryocystitis and canaliculitis, particularlyC.macginleyi,E.corrodensandC.parapsilosis, which are also more frequently isolated. Vancomycin and imipenem may be more effective treatment options. Most cases have an unknown aetiology, and essential preventive measures involve postoperative cleansing of the lacrimal passage following eye and nasal surgeries, as well as the proactive management of rhinitis.
Depression among psychiatrists and psychiatry trainees and its associated factors regarding work, social support, and loneliness
Authors: Pitanupong Jarurin , Anantapong Kanthee , Aunjitsakul Warut
Published: February 2024

Background

This study aimed to survey the prevalence of depression and its associated factors among psychiatrists and psychiatry trainees (physicians in psychiatric residency training).

Methods

This cross-sectional study surveyed Thai psychiatrists and psychiatry trainees from January to February 2023 using an online questionnaire. The questionnaires consisted of (1) the demographic and work-related information; (2) perceptions towards social support and work; (3) the Patient Health Questionnaire-9 (PHQ-9) Thai version; and (4) the 6-item Revised UCLA Loneliness Scale Thai version. All data were analyzed using descriptive statistics, and the associated factors concerning depression were analyzed via multiple linear regression analyses.

Results

Of the 225 total participants, 52(23.1%) and 173 (76.9%) were psychiatry trainees and psychiatrists, respectively. Most of them were female (64.9%) with overall median age (interquatile) was 34 (30, 42) years. Regarding the PHQ-9 findings, the prevalence of depression among all participants was 12.4% (psychiatrists 13.9% and psychiatry trainees 7.7%). From regression analyses, depression was associated with loneliness and perceived levels of work satisfaction and work stress in psychiatrists, while in psychiatry trainees, depression was associated with loneliness and perceived level of ability to control work schedule.

Conclusions

One-tenth of psychiatrists and psychiatry trainees had depression. Although the prevalence of depression in this study was not extremely high, key contributing factors related to depression, such as loneliness, work satisfaction, work stress, and ability to control the work schedule should be required to action to reduce the depression rate among mental health personnel.
Navigating work and life– a qualitative exploration of managers’ and employees’ views of return-to-work after sick leave due to common mental disorders
Authors: Holmlund Lisa , Ljungberg Helena Tinnerholm , Bültmann Ute , Brämberg Elisabeth Björk
Published: February 2024

Background

Incorporating multiple perspectives and contexts in knowledge mobilisation for return-to-work after sick leave due to common mental disorders can promote interprofessional and organisational strategies for facilitating the return-to-work process. This study aimed to explore the facilitators of and barriers to return-to-work after common mental disorders. This exploration considered the perspectives of employees and managers and the realms of work and private life.

Methods

A qualitative approach was used with data from 27 semi-structured telephone interviews. The strategic sample consisted of employees who returned to work after sick leave due to common mental disorders (n = 17) and managers responsible for their return-to-work process (n = 10). Thematic analysis conducted in a six-step process was used to generate themes in the interview data.

Results

The analysis generated three main themes with subthemes, illustrating experiences of barriers to and facilitators of return-to-work positioned in the employees’ private and work contexts: (1) Getting along: managing personal difficulties in everyday life; (2) Belonging: experiencing social connectedness and support in work and private life; and (3) Organisational support: fostering a supportive work environment. The results contribute to a comprehensive understanding of the return-to-work process, including the challenges individuals face at work and in private life.

Conclusions

The study suggests that return-to-work after sick leave due to CMDs is a dynamic and ongoing process embedded in social, organisational, and societal environments. The results highlight avenues for an interprofessional approach and organisational learning to support employees and managers, including space for the employee to recover during the workday.

Trial registration

This study recruited employees from a two-armed cluster-randomised controlled trial evaluating a problem-solving intervention for reducing sick leave among employees sick-listed due to common mental disorders (reg. NCT3346395).
Symptoms of depression and risk of emergency department visits among people aged 70 years and over
Authors: Dwyer Rosamond , Jachno Kim , Tran Thach , Owen Alice , Layton Natasha , Collyer Taya , Kirkman Maggie , Lowthian Judy , Hammarberg Karin , McNeil John J. , Woods Robyn L. , Berk Michael , Fisher Jane
Published: February 2024

Background

Older people experiencing depression and anxiety have higher rates of health service utilisation than others, but little is known about whether these influence their seeking of emergency care. The aim was to examine the associations between symptoms of depression and the use of emergency health care, in an Australian context, among a population of people aged 70 years and over initially free of cardiovascular disease, dementia or major physical disability.

Methods

We undertook secondary analyses of data from a large cohort of community-dwelling Australians aged $$ \ge $$70 years. Multivariable logistic regression was used to compare the association of symptoms of depression (measured using the Center for Epidemiological Studies Depression Scale 10 question version, CESD at baseline) with subsequent episodes of emergency care, adjusting for physical and social factors of clinical interest. Marginal adjusted odds ratios were calculated from the logistic regression.

Results

Data were available for 10,837 Australian participants aged at least 70 years. In a follow-up assessment three years after the baseline assessment, 17.6% of people self-reported an episode of emergency care (attended an ED of called an emergency ambulance) in the last 12 months. Use of emergency healthcare was similar for men and women (17.8% vs. 17.4% p = 0.61). A score above the cut-off on the CESD at baseline was associated with greater use of emergency health care (OR = 1.35, 95% CI 1.11,1.64). When modelled separately, there was a greater association between a score above the cut-off on the CESD and emergency healthcare for women compared with men.

Conclusions

This study is unique in demonstrating how depressive symptoms among healthy older persons are associated with subsequent increased use of emergency healthcare. Improved understanding and monitoring of mental health in primary care is essential to undertake effective healthcare planning including prevention of needing emergency care.
Resting heart rate is associated with the prevalence of chronic kidney disease in Korean adult: the Korean National Health and Nutrition Survey
Authors: Park Dong-Hyuk , Chung Choon Hee , Lee Dong Hoon , Lee Eun Young , Jeon Justin Y.
Published: February 2024

Background

Chronic kidney disease (CKD) poses a significant health challenge, yet early detection remains difficult. Resting heart rate (RHR) has been shown to be a reliable indicator of type 2 diabetes, prompting interest in its potential as an independent predictor of CKD. This study aimed to investigate the association between RHR and CKD prevalence, as well as explore potential interactions between RHR and other risk factors for CKD in a sample of 25,246 adults.

Methods

Data from the Korean National Health and Nutrition Examination Survey (2011–2014) were utilized for this study, with 19,210 participants included after screening. Logistic regression analysis was employed to examine the relationship between RHR and CKD prevalence. Stratified analyses were conducted based on known risk factors for CKD.

Results

Participants with an RHR ≥ 90 bpm exhibited a 2.07-fold [95% confidence interval (CI): 1.28–3.34] and 2.22-fold (95% CI: 1.42–3.48) higher prevalence of CKD in men and women, respectively, compared to those with an RHR < 60 bpm. The association between RHR and CKD prevalence was particularly pronounced in younger participants (40–59 years vs. ≥ 60 years), individuals with diabetes (yes vs. no), and those with a longer duration of diabetes (≥ 7 years vs. < 7 years).

Conclusion

Elevated RHR was found to be significantly associated with a higher prevalence of CKD in both men and women, independent of demographic, lifestyle, and medical factors. These findings suggest that RHR could serve as a valuable predictor for undiagnosed CKD.
Barriers and facilitators to access sexual and reproductive health services among young migrants in Tarapacá, Chile: a qualitative study
Authors: Obach Alexandra , Blukacz Alice , Sadler Michelle , Carreño Calderón Alejandra , Cabieses Báltica , Díaz Carolina
Published: February 2024

Background

Chile has become a destination country for immigrants from Latin America, including youth. Guaranteeing access and use of sexual and reproductive health services for young migrants is crucial because of their overlapping experiences of transitioning to a new country and to adulthood. However, the existing evidence shows barriers to accessing sexual and reproductive healthcare among young migrant populations. In this context, the main objective of this article is to identify the barriers and facilitators that young migrants experience to access sexual and reproductive healthcare in the Tarapacá region of Chile.

Methods

A qualitative study was conducted in the Tarapacá region of Chile. Semi-structured interviews with 25 young migrants from Venezuela, Colombia, and Ecuador, as well as 10 health workers, were carried out. The interviews were transcribed and thematically analysed. The study was approved by the Ethics Committee of the Universidad del Desarrollo (#2019-22).

Results

Young migrants face barriers linked to structural shortcomings within the healthcare system, which may be similar to those faced by the local population. Barriers are also derived from reductionist sexual and reproductive health approaches, which prioritise the prevention of pregnancy, sexually transmitted infections, and HIV, with a predominantly heteronormative focus. The prevailing narratives from the health system are those of risk and lack of control and self-care among young people, and they are exacerbated in the case of migrants. Young migrants, especially from the Caribbean, are stereotyped as over-sexualised and liberal in comparison to the local population and believed to be engaging in riskier sexual behaviours that should be kept under check. This may translate into experiences of discrimination and mistreatment when receiving care. Facilitators include good-quality information and community-level interventions.

Conclusions

This study shows a limited approach to the sexual and reproductive health of young migrants in Chile, severely hampering their reproductive and sexual rights. Policies and initiatives must work towards removing structural barriers, changing narratives, and empowering young migrants regarding their sexual and reproductive health.
Clearing the air: evaluating institutions’ social media health messaging on wildfire and smoke risks in the US Pacific Northwest
Authors: Slavik Catherine E. , Chapman Daniel A. , Cohen Alex Segrè , Bendefaa Nahla , Peters Ellen
Published: February 2024

Background

Wildfire smoke contributes substantially to the global disease burden and is a major cause of air pollution in the US states of Oregon and Washington. Climate change is expected to bring more wildfires to this region. Social media is a popular platform for health promotion and a need exists for effective communication about smoke risks and mitigation measures to educate citizens and safeguard public health.

Methods

Using a sample of 1,287 Tweets from 2022, we aimed to analyze temporal Tweeting patterns in relation to potential smoke exposure and evaluate and compare institutions’ use of social media communication best practices which include (i) encouraging adoption of smoke-protective actions; (ii) leveraging numeric, verbal, and Air Quality Index risk information; and (iii) promoting community-building. Tweets were characterized using keyword searches and the Linguistic Inquiry and Word Count (LIWC) software. Descriptive and inferential statistics were carried out.

Results

44% of Tweets in our sample were authored between January-August 2022, prior to peak wildfire smoke levels, whereas 54% of Tweets were authored during the two-month peak in smoke (September-October). Institutional accounts used Twitter (or X) to encourage the adoption of smoke-related protective actions (82% of Tweets), more than they used it to disseminate wildfire smoke risk information (25%) or promote community-building (47%). Only 10% of Tweets discussed populations vulnerable to wildfire smoke health effects, and 14% mentioned smoke mitigation measures. Tweets from Washington-based accounts used significantly more verbal and numeric risk information to discuss wildfire smoke than Oregon-based accounts (p = 0.042 andp = 0.003, respectively); however, Tweets from Oregon-based accounts on average contained a higher percentage of words associated with community-building language (p < 0.001).

Conclusions

This research provides practical recommendations for public health practitioners and researchers communicating wildfire smoke risks on social media. As exposures to wildfire smoke rise due to climate change, reducing the environmental disease burden requires health officials to leverage popular communication platforms, distribute necessary health-related messaging rapidly, and get the message right. Timely, evidence-based, and theory-driven messaging is critical for educating and empowering individuals to make informed decisions about protecting themselves from harmful exposures. Thus, proactive and sustained communications about wildfire smoke should be prioritized even during wildfire “off-seasons.”
The association of psychological distress and economic and health worries with tobacco smoking behavior during the COVID-19 pandemic: a two-year longitudinal cohort study
Authors: Alpers Silvia Eiken , Druckrey-Fiskaaen Karl Trygve , Madebo Tesfaye , Vold Jørn Henrik , Pallesen Ståle , Skogen Jens Christoffer , Lunde Linn-Heidi , Mæland Silje , Fadnes Lars Thore
Published: February 2024

Background

The COVID-19 pandemic and other life events may trigger worries and psychological distress. These impacts may lead to unhealthy behaviors, such as tobacco smoking, but the degree of such associations is unclear. The current three-wave longitudinal study examines changes in tobacco smoking in Norway between 2020 and 2022 and their associations with psychological distress as well as health- and economy-related worries.

Methods

Data were collected in April 2020 (baseline), January 2021, and January 2022 in Bergen, Norway, from an online longitudinal population-based survey. Smoking tobacco (the outcome variable) was dichotomized based on the responses to the question of whether participants smoked cigarettes or not. Tobacco smoking and its associations with psychological distress were assessed among 24,914 participants (response rate 36%) in a mixed model regression presented with coefficients and 95% confidence intervals (CI), adjusting for COVID-19-related worries, home office/study, occupational situation, age, gender, education, having children below 18 years living at home, living alone, and alcohol consumption.

Results

A total of 10% of the study sample were current smokers at baseline. At baseline, smoking tobacco was associated with high levels of psychological distress (absolute difference 13%, 95% CI 10%; 15%), advanced age (50−59 years: 11%, CI 10%; 13%), and hazardous alcohol use (4%, CI 3%; 5%) compared to their counterparts. Higher education (-5%, CI -6%; -4%), working from home (-4%, CI -5%; -4%), and higher physical activity levels (-4%, CI -5%; -3%) were associated with non-smoking. The prevalence of smoking among individuals experiencing severe psychological distress decreased slightly over time (-2% per year, CI -3%; -1%).

Conclusions

Smoking was associated with severe psychological distress, advanced age, and hazardous alcohol use at baseline; non-smoking was associated with high education, working from home, and high physical activity. Nevertheless, the smoking rate among individuals experiencing severe psychological distress slightly decreased over the course of the COVID-19 pandemic.