bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of hub genes based on integrated analysis of single-cell and microarray transcriptome in patients with pulmonary arterial hypertension
Authors: Qin Yuhan , Yan Gaoliang , Qiao Yong , Wang Dong , Tang Chengchun
Published: December 2023

Background

Pulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution.

Methods

Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram.

Results

Nineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439.

Conclusion

WDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH.
Exploring quantitative traits-associated copy number deletions through reanalysis of UK10K consortium whole genome sequencing cohorts
Authors: Lee Sejoon , Kim Jinho , Ohn Jung Hun
Published: December 2023

Objectives

We performed comprehensive association analyses of common high-confidence gnomAD-reported copy number deletions (CNDs) with 60 quantitative traits from UK10K consortium WGS data.

Methods

The study made use of data generated by the UK10K Consortium. UK10K consortium WGS data consist of TwinsUK (n = 1754, middle-aged females) and ALSPAC (n = 1867, birth to adolescence) cohorts. UK10K consortium called 18,739 CNDs (hg19) with GenomeSTRiP software. After filtering out variants with minor allele frequency < 0.05 or HWE P < 1.0 × 10− 6, 1222 (TwinsUK) and 1211 (ALSPAC) CNDs remained for association analyses with 60 normalized quantitative traits.

Results

We identified 23 genome-wide significant associations at 13 loci, among which 2 associations reached experiment-wide significance. We found that two common deletions in chromosome 4, located between WDR1 and ZNF518B (23.3 kb, dbVar ID:nssv15888957, 4:10211262–10,234,569 and 9.8 kb, dbVar ID:nssv15888975, 4:10392422–10,402,191), were associated with uric acid levels (P = 5.23 × 10− 11 and 2.29 × 10− 8, respectively). We also discovered a novel deletion spanning chromosome 18 (823 bp, dbVar ID: nssv15841628, 8:74347187–74,348,010) associated with low HDL cholesterol levels (P = 4.15 × 10− 7). Additionally, we observed two red blood cell traits-associated loci with genome-wide significance, a 13.2 kb deletion in 7q22.1 (nssv15922542) and a 3.7 kb deletion in 12q24.12 (nssv15813226), both of which were located in regions previously reported to be associated with red blood cell traits. Two deletions in 11q11 (nssv15803200 and nssv15802240), where clusters of multiple olfactory receptor genes exist, and a deletion (nssv15929560) upstream to DOCK5 were associated with childhood obesity. Finally, when defining Trait-Associated copy number Deletions (TADs) as CNDs with phenotype associations at sub-threshold significance (P < 10− 3), we identified 157 (97.5%) out of 161 TADs in non-coding regions, with a mean size of 4 kb (range: 209 − 47,942 bp).

Conclusion

We conducted a reanalysis of the UK10K Whole Genome Sequencing cohort, which led to the identification of multiple high confidence copy number deletions associated with quantitative traits. These deletions have standard dbVar IDs and replicate previous findings, as well as reveal novel loci that require further replication studies.
Establishment and validation of a prediction nomogram for heart failure risk in patients with acute myocardial infarction during hospitalization
Authors: Chen Shengyue , Pan Xinling , Mo Jiahang , Wang Bin
Published: December 2023

Background

Acute myocardial infarction (AMI) with consequent heart failure is one of the leading causes of death in humans. The aim of this study was to develop a prediction model to identify heart failure risk in patients with AMI during hospitalization.

Methods

The data on hospitalized patients with AMI were retrospectively collected and divided randomly into modeling and validation groups at a ratio of 7:3. In the modeling group, the independent risk factors for heart failure during hospitalization were obtained to establish a logistic prediction model, and a nomogram was constructed. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical value. Machine learning models with stacking method were also constructed and compared to logistic model.

Results

A total of 1875 patients with AMI were enrolled in this study, with a heart failure rate of 5.1% during hospitalization. The independent risk factors for heart failure were age, heart rate, systolic blood pressure, troponin T, left ventricular ejection fraction and pro-brain natriuretic peptide levels. The area under the curve (AUC) of the model in modeling group and validation group were 0.829 and 0.846, respectively. The calibration curve showed high prediction accuracy and the DCA curve showed good clinical value. The AUC value of the ensemble model by the stacking method in the validation group were 0.821, comparable to logistic prediction model.

Conclusions

This model, combining laboratory and clinical factors, has good efficacy in predicting heart failure during hospitalization in AMI patients.
Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study
Authors: Lim Hyun , Park Jong Kyu , Chung Hyunsoo , Lee Si Hyung , Park Jae Myung , Park Jung Ho , Kim Gwang Ha , Shin Sung Kwan , Hong Su Jin , Lee Kwang Jae , Park Moo In , Jung Hye-Kyung , Kim Hyun-Soo , Sung Jae Kyu , Jeon Seong Woo , Choi Suck Chei , Moon Jeong Seop , Kim Nayoung , Park Jong-Jae , Hong Sung Hee , Kim Na Young , Jung Hwoon-Yong
Published: December 2023

Background

Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE).

Methods

We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups.

Results

By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups.

Conclusions

The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD.

Trial registration

NCT04080726 (https://classic.clinicaltrials.gov/ct2/show/NCT04080726), registration date: 25/10/2018.
Preoperative assessment of retroperitoneal Liposarcoma using volume-based 18F-FDG PET/CT: implications for surgical strategy and prognosis
Authors: Liu Dao-Ning , Wu Jian-Hui , Li Zhong-Wu , Wang Hai-Yue , Tian Xiu-Yun , Hao Chun-Yi
Published: December 2023

Purpose

Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue.

Methods

We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors.

Results

MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS).

Conclusions

Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.
Application of the ‘online assessment + FOBT at home’ to improve participation and the efficacy of opportunistic screening for colorectal cancer: a retrospective cohort study
Authors: Peng Xudong , Tang Gang , Wang Yonghong , Zeng Fanling , Chen Yuedong , Zhang Weidan , Mo Chunmei , Yang Yana , Li Shuang , Bai Lian , Xiao Dachun , Zheng Guolian , Ran Wenhua , Chen Cheng , Yang Yonghong , Gao Yuanze , Zhu Shuangwei , Huang Zheng , Zhao Dongqing , Wu Chaofeng , Xu Li , Wei Zhengqiang
Published: December 2023

Background

Colorectal cancer (CRC) screening faces two major challenges: insufficient screening coverage and poor adherence. A smartphone applet named “Early Screening Assistant (ESA)” was developed to create an online risk-assessment and fecal occult blood test (FOBT) at home. This retrospective study was designed to evaluate whether the new CRC screening strategy can improve the colonoscopy participation rate (PR) and lesion detection rate (DR).

Methods

In total, 6194 individuals who accepted normal health examinations and CRC screening based on the ESA from June 2020 to May 2022 were assigned to the ESA group. Accordingly, 7923 inhabitants who only accepted normal health examinations were assigned to the control group. The colonoscopy PR and neoplastic lesion DR were then compared between the two groups.

Results

Overall, a higher proportion of subjects in the ESA group (285 of 6194 [4.6%]) completed colonoscopy than in the control group (126 of 7923, [1.6%]), p < 0.01). The neoplastic lesion DR also significantly increased in the ESA group (76 of 6194 [1.22%]) compared with the control group (15 of 7923 [0.19%]) (p < 0.01). The adjusted diagnostic sensitivity and specificity of the “Online assessment + FOBT at home” were 41.5% and 62.6% for neoplastic lesions, respectively.

Conclusions

This retrospective cohort study confirmed that the new CRC screening strategy based on the “Online assessment + FOBT at home” can improve colonoscopy participation and the neoplastic lesion detection rate and may represent a promising screening strategy for CRC.

Trial registration

This study was registered in China Clinical Trial Registry (https://www.chictr.org.cn) on 29/09/2022. Registration number: ChiCTR2200064186.
Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study
Authors: Li Xiaocong , Dehghan Mahshid , Tse Lap Ah , Lang Xinyue , Rangarajan Sumathy , Liu Weida , Hu Bo , Yusuf Salim , Wang Chuangshi , Li Wei
Published: December 2023

Background

Previous in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults.

Methods

Our study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35–70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite.

Results

A total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses.

Conclusions

Our findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose–response relationships and to refine global dietary recommendations.
Acceptability and use of the electronic community health information system and its determinants among health extension workers in Ethiopia: a retrospective cross-sectional observational study
Authors: Bogale Tariku Nigatu , Willems Herman , Bongassie Loko Abraham , Eyob Yemariam , Mengesha Chaluma Kumela , Yihun Bantalem Yeshanew , Mohammed Mesud , Wendrad Naod , Melkamu Gemechis , Daka Dawit Wolde , Meressa Selamawit , Bekele Tadesse Alemu
Published: December 2023

Background

The electronic community health information system has been increasingly developed and deployed to quantify and support quality health service delivery by community health workers in Ethiopia. However, the success and failure of the electronic community health information system depend on the acceptability and use by its users. This study assessed the acceptability and use of the electronic community health information system and its determinants among health extension workers in Ethiopia.

Methods

A retrospective cross-sectional observational study was conducted among 587 randomly selected health extension workers from six regions of Ethiopia. The Revised Technology Acceptance Model was used as a theoretical framework for the study. Descriptive statistics, structural equation modeling, and principal component analysis techniques were used to analyze the data. For all significance tests, multiple comparison adjustments were made using the Bonferroni Correction Method.

Results

There was near universal acceptance of the electronic community health information system, ranging from 94.4 to 97.4% among health extension workers. However, actual use of the system was considerably lower, at 50%. Perceived usefulness of the electronic community health information system had a direct and positive effect on acceptability (β3 = 0.415, p < 0.001). Perceived ease of use had both direct and indirect positive effects on electronic community health information system acceptability (β2 = 0.340, p < 0.001 and β1*β3 = 0.289, p < 0.001, respectively), while acceptability had a direct and positive effect on the use of the electronic community health information system (β3 = 0.297, p < 0.001).

Conclusions

Despite the very high acceptability of the electronic community health information system among health extension workers, actual use of the system is considerably lower. Hence, an integrated and coordinated approach is required to close the acceptance-use gap.
Compassion fatigue and stress related to cardiopulmonary resuscitation: a study of critical care nurses’ experiences
Authors: El-Ashry Ayman Mohamed , Elsayed Shimmaa Mohamed , Ghoneam Mohamed Adel , Atta Mohamed Hussein Ramadan
Published: December 2023

Background

Cardiopulmonary resuscitation (CPR) is considered one of the most stressful experiences in critical care nursing; it directly and indirectly leads to compassion fatigue and burnout.

Aim

Determine the levels of and relationship between postcode stress and compassion fatigue.

Design and methods

A descriptive-correlational study using 300 critical care nurses from five intensive care units in two hospitals was conducted.

Tools

Demographic and work-related data, the Postcode Stress Scale, and the Professional Quality of Life Scale: Compassion Fatigue subscale.

Results

Nurses had moderate to high postcode stress and compassion fatigue (67.98 ± 16.39 and 65.40±14.34, respectively). Moreover, there was a significant positive correlation between postcode stress, burnout (r=0.350, p=<0.001), secondary traumatic stress (r=0.518, p=<0.001), and subsequently, compassion fatigue (r=0.449, p=<0.001). In addition, higher levels of postcode stress were associated with higher levels of compassion fatigue with its subscales: burnout and secondary traumatic stress, with a coefficient of determination for compassion fatigue (0.199), burnout subscale (0.121), and secondary traumatic stress (0.266).

Conclusion

Critical care nurses involved in resuscitation experiences are susceptible to postcode stress, burnout, secondary traumatic stress, and compassion fatigue. There is a significant relationship between these factors, with higher levels of postcode stress contributing to higher levels of compassion fatigue and its subscales: burnout and secondary traumatic stress. These results highlight the importance of addressing and managing the psychological well-being of nurses in resuscitation settings to mitigate the adverse effects of stress and promote their overall resilience and well-being.
De novo identification of expressed cancer somatic mutations from single-cell RNA sequencing data
Authors: Zhang Tianyun , Jia Hanying , Song Tairan , Lv Lin , Gulhan Doga C. , Wang Haishuai , Guo Wei , Xi Ruibin , Guo Hongshan , Shen Ning
Published: December 2023

Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA – Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA.
Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
Authors: Morishita Masahiro , Higo Shimpei , Iwata Kinuyo , Ishii Hirotaka
Published: December 2023

Background

ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506).

Methods

To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch’s t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey–Kramer test were used for comparisons among multiple groups with different estrogen treatments.

Results

ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers.

Conclusions

Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain.
Meningitis in critically ill patients admitted to intensive care unit for severe community-acquired pneumococcal pneumonia
Authors: Jaubert Paul , Charpentier Julien , Benghanem Sarah , Cariou Alain , Pène Frédéric , Mira Jean-Paul , Jozwiak Mathieu
Published: December 2023

Background

Although it has been reported that patients with pneumococcal pneumonia may develop meningitis, lumbar puncture is not systematically recommended in these patients, even in patients with associated bacteremia or invasive pneumococcal disease. The aim of this study was to determine the characteristics and outcomes of patients admitted to intensive care unit (ICU) for pneumococcal community-acquired pneumonia who developed meningitis.

Methods

We retrospectively included all consecutive patients admitted to our ICU from January 2006 to December 2020 for severe pneumococcal community-acquired pneumonia according to American Thoracic Society criteria. Meningitis was defined as pleocytosis > 5 cells/mm3 or a positive culture of cerebrospinal fluid for Streptococcus pneumoniae in lumbar puncture. The primary endpoint was the proportion of patients with meningitis during their ICU stay.

Results

Overall, 262 patients [64(52–75) years old] were included: 154(59%) were male, 80(30%) had chronic respiratory disease, 105(39%) were immunocompromised and 6(2%) were vaccinated against S. pneumoniae. A lumbar puncture was performed in 88(34%) patients with a delay from ICU admission to puncture lumbar of 10.5 (2.8–24.1) h and after the initiation of pneumococcal antibiotherapy in 81(92%) patients. Meningitis was diagnosed in 14 patients: 16% of patients with lumbar puncture and 5% of patients in the whole population. Patients with meningitis had more frequently human immunodeficiency virus positive status (29 vs. 5%, p = 0.02), neurological deficits on ICU admission (43 vs. 16%, p = 0.03) and pneumococcal bacteremia (71 vs. 30%, p < 0.01) than those without. The ICU mortality rate (14 vs. 13%, p = 0.73) and the mortality rate at Day-90 (21 vs. 15%, p = 0.83) did not differ between patients with and without meningitis. The proportion of patients with neurological disorders at ICU discharge was higher in patients with meningitis (64 vs. 23%, p < 0.001) than in those without. The other outcomes did not differ at ICU discharge, Day-30 and Day-90 between the two groups of patients.

Conclusion

Meningitis was diagnosed in 16% of patients with severe pneumococcal community-acquired pneumonia in whom a lumbar puncture was performed, was more frequent in patients with pneumococcal bacteremia and was associated with more frequent neurological disorders at ICU discharge. Further studies are needed to confirm these results.
Online distributed waveform-synchronization for acoustic sensor networks with dynamic topology
Authors: Chinaev Aleksej , Knaepper Niklas , Enzner Gerald
Published: December 2023

Acoustic sensing by multiple devices connected in a wireless acoustic sensor network (WASN) creates new opportunities for multichannel signal processing. However, the autonomy of agents in such a network still necessitates the alignment of sensor signals to a common sampling rate. It has been demonstrated that waveform-based estimation of sampling rate offset (SRO) between any node pair can be retrieved from asynchronous signals already exchanged in the network, but connected online operation for network-wide distributed sampling-time synchronization still presents an open research task. This is especially true if the WASN experiences topology changes due to failure or appearance of nodes or connections. In this work, we rely on an online waveform-based closed-loop SRO estimation and compensation unit for nodes pairs. For WASNs hierarchically organized as a directed minimum spanning tree (MST), it is then shown how local synchronization propagates network-wide from the root node to the leaves. Moreover, we propose a network protocol for sustaining an existing network-wide synchronization in case of local topology changes. In doing so, the dynamic WASN maintains the MST topology after reorganization to support continued operation with minimum node distances. Experimental evaluation in a simulated apartment with several rooms proves the ability of our methods to reach and sustain accurate SRO estimation and compensation in dynamic WASNs.
The efficacy of entrepreneurial networking and innovation in fostering the performance of small businesses in Uganda
Authors: Sendawula Kasimu , Kisubi Moses Kisame , Najjinda Shamirah , Nantale Hanifah , Kabbera Samuel
Published: December 2023

The purpose of this study was to investigate the efficacy of entrepreneurial networking and innovation in fostering the performance of small businesses using evidence from Uganda. The study was cross-sectional and correlational. Data were collected through a self-administered questionnaire survey of 368 small businesses and analyzed through correlation, hierarchical regression, and mediation analysis using the Statistical Package for Social Sciences (SPSS). Study findings indicate that entrepreneurial networking and innovation are significant predictors of small business performance. Results also indicate that innovation partially mediates the relationship between entrepreneurial networking and the performance of small businesses. As such, this study contributes to the extant literature on the performance of small businesses as it provides initial empirical evidence on the efficacy of entrepreneurial networking and innovation in fostering the performance of small businesses. It further contributes to the recent literature on the mediation effect of innovation using evidence from Uganda.
What is the functional reach of wastewater surveillance for respiratory viruses, pathogenic viruses of concern, and bacterial antibiotic resistance genes of interest?
Authors: Sokoloski Kevin J. , Holm Rochelle H. , Smith Melissa , Ford Easton E. , Rouchka Eric C. , Smith Ted
Published: December 2023

Background

Despite a clear appreciation of the impact of human pathogens on community health, efforts to understand pathogen dynamics within populations often follow a narrow-targeted approach and rely on the deployment of specific molecular probes for quantitative detection or rely on clinical detection and reporting.

Main text

Genomic analysis of wastewater samples for the broad detection of viruses, bacteria, fungi, and antibiotic resistance genes of interest/concern is inherently difficult, and while deep sequencing of wastewater provides a wealth of information, a robust and cooperative foundation is needed to support healthier communities. In addition to furthering the capacity of high-throughput sequencing wastewater-based epidemiology to detect human pathogens in an unbiased and agnostic manner, it is critical that collaborative networks among public health agencies, researchers, and community stakeholders be fostered to prepare communities for future public health emergencies or for the next pandemic. A more inclusive public health infrastructure must be built for better data reporting where there is a global human health risk burden.

Conclusions

As wastewater platforms continue to be developed and refined, high-throughput sequencing of human pathogens in wastewater samples will emerge as a gold standard for understanding community health.
Impact of 1,7-malaria reactive community-based testing and response (1,7-mRCTR) approach on malaria prevalence in Tanzania
Authors: Chang Wei , Cohen Jessica , Wang Duo-Quan , Abdulla Salim , Mahende Muhidin Kassim , Gavana Tegemeo , Scott Valerie , Msuya Hajirani M. , Mwanyika-Sando Mary , Njau Ritha John A. , Lu Shen-Ning , Temu Silas , Masanja Honorati , Anthony Wilbald , Aregawi W. Maru , Sunder Naveen , Kun Tang , Bruxvoort Katia , Kitau Jovin , Kihwele Fadhila , Chila Godlove , Michael Mihayo , Castro Marcia , Menzies Nicolas A. , Kim Sein , Ning Xiao , Zhou Xiao-Nong , Chaki Prosper , Mlacha Yeromin P.
Published: December 2023

Background

Progress in malaria control has stalled in recent years and innovative surveillance and response approaches are needed to accelerate malaria control and elimination efforts in endemic areas of Africa. Building on a previous China-UK-Tanzania pilot study on malaria control, this study aimed to assess the impact of the 1,7-malaria Reactive Community-Based Testing and Response (1,7-mRCTR) approach implemented over two years in three districts of Tanzania.

Methods

The 1,7-mRCTR approach provides community-based malaria testing via rapid diagnostic tests and treatment in villages with the highest burden of malaria incidence based on surveillance data from health facilities. We used a difference-in-differences quasi-experimental design with linear probability models and two waves of cross-sectional household surveys to assess the impact of 1,7-mRCTR on malaria prevalence. We conducted sensitivity analyses to assess the robustness of our results, examined how intervention effects varied in subgroups, and explored alternative explanations for the observed results.

Results

Between October 2019 and September 2021, 244,771 community-based malaria rapid tests were completed in intervention areas, and each intervention village received an average of 3.85 rounds of 1-7mRCTR. Malaria prevalence declined from 27.4% at baseline to 11.7% at endline in the intervention areas and from 26.0% to 16.0% in the control areas. 1,7-mRCTR was associated with a 4.5-percentage-point decrease in malaria prevalence (95% confidence interval: − 0.067, − 0.023), equivalent to a 17% reduction from the baseline. In Rufiji, a district characterized by lower prevalence and where larviciding was additionally provided, 1,7-mRCTR was associated with a 63.9% decline in malaria prevalence.

Conclusions

The 1,7-mRCTR approach reduced malaria prevalence. Despite implementation interruptions due to the COVID-19 pandemic and supply chain challenges, the study provided novel evidence on the effectiveness of community-based reactive approaches in moderate- to high-endemicity areas and demonstrated the potential of South-South cooperation in tackling global health challenges.

Graphical Abstract
Discrete space vector modulation and optimized switching sequence model predictive control for three-level voltage source inverters
Authors: Zhou Sheng , Zhu Minlong , Lin Jiaqi , Ipoum-Ngome Paul Gistain , Mon-Nzongo Daniel Legrand , Jin Tao
Published: December 2023

This paper proposes a discrete space vector modulation and optimized switching sequence model predictive controller for three-level neutral-point-clamped inverters in grid-connected applications. The proposed strategy is based on cascaded model predictive control (MPC) for controlling the grid current while maintaining the capacitor voltage balanced without weighting factor. To enhance the closed-loop performance, the external MPC evaluates 19 basic and 138 virtual vectors (VV) of the proposed space vector method. The optimal control voltage is then selected using an extended deadbeat method to reduce the execution time of the proposed control algorithm. By using the discrete space vector modulation principle, the VV are synthesized based on switching sequence (SS) and are divided into negative and positive SSs considering their impact on the neutral point (NP) potential. The inner MPC evaluates both types of SSs and selects the one that keeps the capacitor voltage balanced. Various controllers are evaluated and compared against the proposed control strategy. The results show that the proposed strategy improves performance without weighting factor, while maintaining a total harmonic distortion of current to be less than 2%. Compared to the modulated MPC which provides the same fixed switching frequency, the proposed controller reduces the computational burden by over 50% while also providing better NP voltage balance accuracy.
Penetrating two stab to the throat, survival time and physical mobility: a suicide case and literature review
Authors: Çelik Cemil , Çetinkaya Tuba Akkuş , Ata Uğur , Kamalak Murat , Saka Naile Esra
Published: December 2023

Background

It is difficult to pinpoint the manner of death in cases of death due to sharp force injuries where injury patterns resemble one another. Other issues that might arise include physical mobility and survival time after injury. Within the scope of this case, a 53-year-old male suicide with findings suggestive of homicide is presented, along with research on the nature of sharp neck injuries, survival time, and movement after injury.

Case presentation

Thanks to the surveillance camera video that captured a significant portion of the occurrence, it was determined that the incident in the case that was presented, which had two perforations of the larynx, was suicide. At first appearance, this case could be assumed to be homicidal. Due to the injury, the victim could only walk around 300–350 m. The victim had a 4-h average survival time.

Conclusions

In general terms, the survival time according to the injury sites in the neck can be listed for a person (if the wound sizes are close to each other) as follows: injury causing vagal stimulation < arterial injury with severe blood loss < venous injury with blood loss < airway injury causing aspiration and respiratory failure.
Assessment of mitigation alternatives for differential shortening in high-rise reinforced concrete buildings
Authors: Elansary Ahmed , Metwally Mohamed I. , El-Attar Adel
Published: December 2023

Selecting appropriate structural system for reinforced concrete (RC) buildings is essential in the design process to satisfy serviceability and strength requirements. Using ordinary analysis (OA) may result in inaccurate estimation of differential shortenings (DS) between vertical supporting elements which might lead to structural and architectural problems. Efficiency of staged analysis including time-dependent effects (SAT) has been recently recognized for the analysis of these buildings due to considering the sequential nature of construction. In this research, eight RC buildings with heights ranging between 35 and 175 m and various structural systems, namely rigid frames (RF), shear walls (SW), wall frames (WF), and tube in tube (TT), are analyzed. An assessment is conducted for the adequacy of three mitigation alternatives to decrease changes between DS estimated using OA and SAT. In Alternative 1, cross sections of all vertical elements (columns and shear walls) are increased by 50%. Alternative 2 is performed by iteratively proportioning the dimensions of internal columns without changing the cross sections of edge and corner vertical elements. One outrigger system is introduced along the height of buildings with WF and TT systems in Alternative 3. Analysis of the eight buildings is implemented by developing a numerical model considering the construction stages and time-dependent effects. The alternatives assessment is conducted by comparing differential displacements (DD), bending moments, and shearing forces before and after mitigation obtained from OA and SAT. The numerical results showed that Alternative 1 is not efficient in mitigating the differences between the OA and SAT for all the studied buildings. However, an optimum solution can be achieved using the Alternative 2 for all investigated systems. Also, Alternative 3 was found adequate in partially mitigating the differences between the two analyses for the buildings with WF and TT systems.
Probability of Regulatory Approval Over Time: A Cohort Study of Cancer Therapies
Authors: Hutchinson Nora , Bicer Selin , Feldhake Emma , Carlisle Benjamin G. , Gonen Mithat , Del Paggio Joseph , Kimmelman Jonathan
Published: December 2023

PURPOSE

New cancer therapies are frequently evaluated in multiple disease indications. We evaluated whether the probability of achieving US Food and Drug Administration (FDA) approval for a new cancer therapy changes with time.

METHODS

We identified a cohort of anticancer drugs with a first registered efficacy trial from 2007 to 2011 on ClinicalTrials.gov. We downloaded all clinical trials for each included drug from the initiation of efficacy testing to January 11, 2021. Each trial was categorized by cancer indication and assigned to investigational trajectories on the basis of unique drug-indication pairings. We performed a univariate Cox’s proportional hazards regression to assess the probability of a trajectory leading to regulatory approval over time since initiation of the first efficacy trial for a given drug.

RESULTS

We included 213 drugs in our cohort, of which 37 (17.4%) received FDA approval in at least one oncology indication. In our primary analysis, we found a 15% decrease in the probability of approval for every year since initiation of the first efficacy trial (hazard ratio [HR], 0.85 [95% CI, 0.73 to 0.99]; P = .032). We found a 45% increase in the probability of approval for the first trajectory launched for a given drug in comparison with all others (HR, 0.55 [95% CI, 0.33 to 0.91]; P = .021).

CONCLUSION

Drug-indication pairings pursued years after initial testing for efficacy have lowered probability of affecting care. Clinical trial investigators, sponsors, and regulatory bodies may benefit from awareness of this trend when considering both early and late trajectory trials in a drug's development.
Where Did AIDS Come from?
Authors: Jain Lochlann
Published: December 2023

This chapter analyzes the genealogy of Edward Hooper’s hypothesis that a vaccine trial in the African Belgian colonies caused the species-jump resulting in HIV. The confusing intentions, unclear lines of analysis, and powerful interests inflected in the subsequent discussions opens space for challenging the belief that the vaccine contamination question has been resolved. The reduction of Hooper’s oral polio vaccine (OPV) hypothesis to a “conspiracy theory” rather than a plausible counterfactual results in a missed opportunity to read his book The River as one of the few detailed accounts written of the immense social, political, technological, and interspecies infrastructure constituted by Cold War vaccine production. The chapter interrogates the relationship between historiography and the making of scientific facts, suggesting that historians have been too credulous of scientists’ testimony.
On Uncertainty and the Question of Judgment
Authors: Wedeen Lisa
Published: December 2023

According to established notions of authoritarianism, the withholding of information enables domination. By contrast, in the context of Syria’s uprising and autocratic retrenchment, it is information excess that gets exploited for political gain. The Syrian example also invites renewed exploration of the fragile relationship between truth and politics, a condition that applies not only to authoritarian circumstances but to the proliferation of “fake news” and “alternative truths” in the United States as well. Far from helping to establish “what really happened,” emerging information technologies—from the multiplication of distribution sites, to the ease with which digital photos can be doctored, to the speed with which “news” gets circulated and then superseded by the next catastrophe—have generated novel forms of uncertainty, even as competition among rival discourses leads to polarization. Both developments have consequences for the ability of revolutionary oppositions to sustain their movements and for the ability of citizens to make political judgments.
Adrian Piper and Alien Conspiracies of Bullying and Whistleblowing
Authors: Dumit Joseph
Published: December 2023

This chapter examines how (1) corporate capitalism in healthcare, pharmaceuticals, fracking, and energy is actively destroying lives and the human ecosystem, and how many of us are standing by as this happens; (2) academic institutions function remarkably similarly in supporting systemic bullying abetted not just by active harassment but also by so-called neutral bystanding. The artistic and philosophical work of Adrian Piper provides one important guide to understand how this is happening at an everyday and infrastructural level, and how we avoid even minor whistleblowing—thus contributing to sustaining worlds we do not want to live in. Thinking with aliens and conspiracies offers a way to "will a supersensible world" into existence. One we might want to live in.
Inhalational Anesthesia Reduced Transient Neurological Events After Revascularization Surgery for Moyamoya Disease
Authors: Kaku Yasuyuki , Ohmori Yuki , Kameno Koki , Uchikawa Hiroki , Takemoto Yushin , Kawano Takayuki , Ishimura Tatsuhiro , Uetani Hiroyuki , Mukasa Akitake
Published: December 2023

BACKGROUND AND OBJECTIVES:

The choice between inhalational and total intravenous anesthesia (TIVA) in revascularization surgery for Moyamoya disease (MMD) remains a topic of debate. Anesthesia methods have changed with the advent of new anesthetics. This study investigated whether modern anesthesia methods affected the development of neurological symptoms after revascularization surgery for MMD.

METHODS:

This single-center retrospective study included 63 adult patients (82 hemispheres) with MMD treated with direct and indirect bypass surgeries at our hospital between 2013 and 2022. Patients were divided into inhalational anesthesia (IA) and TIVA groups based on the anesthesia maintenance method. Baseline patient characteristics; postoperative neurological symptoms, including hyperperfusion syndrome, cerebral infarction, and transient neurological events (TNEs); and cortical hyperintensity belt (CHB) sign scores (5-point scale from 0 to 4) on postoperative magnetic resonance imaging were compared between the two groups. The operation methods, anesthetics, and intraoperative hemodynamic and ventilatory parameters were compared between patients with and without TNEs.

RESULTS:

The IA and TIVA groups comprised 39 and 43 hemispheres, respectively. The frequency of postoperative hyperperfusion syndrome and cerebral infarction did not differ between the groups, but the number of TNEs in the IA group (5/39; 13%) was significantly lower than that in the TIVA group (16/43; 37%). Multivariate logistic regression analysis revealed that TNEs were associated with TIVA (odds ratio, 3.91; 95% CI, 1.24-12.35; P = .02). The median [IQR] postoperative CHB sign score in the IA group (2 [1-3]) was significantly lower than that in the TIVA group (4 [3-4]).

CONCLUSION:

The IA group had fewer postoperative TNEs and lower CHB sign scores than the TIVA group. Although further studies are needed, this study provides insights into the prevention of TNEs with IA and reconsideration of the optimal anesthesia for MMD.
Exercise-Induced Cell-Free DNA Correlates with Energy Expenditure in Multiple Exercise Protocols
Authors: NOGIEC CHRISTOPHER D. , KARLIC ROSA , TABORDA EDDIE , DUNKELBARGER SONIA , FRIDLICH ORI , DOR YUVAL , POLAK PAZ , LI RUI
Published: December 2023

Purpose

Exercise-induced cell-free DNA (ei-cfDNA) has been studied in response to various types of exercise. Its correlation with exercise intensity and duration has been observed consistently. However, comprehensive measurements and exploration of the tissue of origin are lacking. The aim of this study is to establish precise connections between exercise variables and the distribution of tissue of origin, aiming to provide further evidence supporting its use as a biomarker for exercise.

Methods

Twelve self-identified active adults (six men and six women) performed a crossover study starting with either endurance testing or resistance testing under different intensities and protocols. We obtained blood before and after each exercise session and measured the levels of cfDNA and determined its tissue of origin utilizing cell type-specific DNA methylation patterns in plasma.

Results

We found that when duration and intensity are fixed, ei-cfDNA fold change correlates with energy expenditure (P = 0.001) in endurance testing and years trained (P = 0.001) in resistance testing. Most of the ei-cfDNA comes from increases in white blood cells (~95%) where neutrophils make up the majority (~74%) and the distribution is different between exercise modalities and protocols.

Conclusions

This study highlights the potential of exercise-induced cfDNA as a biomarker for exercise, showing correlations with energy expenditure and a consistent pattern of tissue origin. Additional research is needed to investigate potential sex differences in the response of cfDNA to exercise, further exploring its clinical implications.