bluuebunny/crossref_metadata_2025 huggingface dataset:
ImReLnc: Identifying Immune-Related LncRNA Characteristics in Human Cancers Based on Heuristic Correlation Optimization
Authors: Gao Meihong , Liu Shuhui , Qi Yang , Guo Xinpeng , Shang Xuequn
Published: January 2022

Long non-coding RNAs (lncRNAs) play critical roles in cancer through gene expression and immune regulation. Identifying immune-related lncRNA (irlncRNA) characteristics would contribute to dissecting the mechanism of cancer pathogenesis. Some computational methods have been proposed to identify irlncRNA characteristics in human cancers, but most of them are aimed at identifying irlncRNA characteristics in specific cancer. Here, we proposed a new method, ImReLnc, to recognize irlncRNA characteristics for 33 human cancers and predict the pathogenicity levels of these irlncRNAs across cancer types. We first calculated the heuristic correlation coefficient between lncRNAs and mRNAs for immune-related enrichment analysis. Especially, we analyzed the relationship between lncRNAs and 17 immune-related pathways in 33 cancers to recognize the irlncRNA characteristics of each cancer. Then, we calculated the Pscore of the irlncRNA characteristics to evaluate their pathogenicity levels. The results showed that highly pathogenic irlncRNAs appeared in a higher proportion of known disease databases and had a significant prognostic effect on cancer. In addition, it was found that the expression of irlncRNAs in immune cells was higher than that of non-irlncRNAs, and the proportion of irlncRNAs related to the levels of immune infiltration was much higher than that of non-irlncRNAs. Overall, ImReLnc accurately identified the irlncRNA characteristics in multiple cancers based on the heuristic correlation coefficient. More importantly, ImReLnc effectively evaluated the pathogenicity levels of irlncRNAs across cancer types. ImReLnc is freely available at https://github.com/meihonggao/ImReLnc.
Dissecting Cellular Heterogeneity Based on Network Denoising of scRNA-seq Using Local Scaling Self-Diffusion
Authors: Duan Xin , Wang Wei , Tang Minghui , Gao Feng , Lin Xudong
Published: January 2022

Identifying the phenotypes and interactions of various cells is the primary objective in cellular heterogeneity dissection. A key step of this methodology is to perform unsupervised clustering, which, however, often suffers challenges of the high level of noise, as well as redundant information. To overcome the limitations, we proposed self-diffusion on local scaling affinity (LSSD) to enhance cell similarities’ metric learning for dissecting cellular heterogeneity. Local scaling infers the self-tuning of cell-to-cell distances that are used to construct cell affinity. Our approach implements the self-diffusion process by propagating the affinity matrices to further improve the cell similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness, we applied LSSD on two simulated and four real scRNA-seq datasets. Comparing with other single-cell clustering methods, our approach demonstrates much better clustering performance, and cell types identified on colorectal tumors reveal strongly biological interpretability.
Strengthening Visceral Leishmaniasis Diagnosis Capacity to Improve Access to Care in Kenya: The Example of Marsabit County
Authors: de Souza Dziedzom K. , Picado Albert , Bessell Paul R. , Liban Abduba , Wachira Davis , Mwiti Daniel , Matendechero Sultani H. , Bosch Mercedes , Ndung’u Joseph M. , Cruz Israel
Published: January 2022

Background

Visceral leishmaniasis (VL), also known as kala-azar, is a neglected tropical disease (NTD) that is fatal if not treated early. The WHO targets the elimination of VL as a public health problem in its 2030 NTD road map. However, improving access to VL diagnosis and treatment remains a major challenge in many VL-endemic countries. Kenya is endemic for VL and is among the top 6 high-disease burden countries in the world.

Methods

FIND, through its activities in improving the diagnosis of VL and supporting the elimination of the disease in Kenya, has worked with various county ministries of health (MOH) and central MOH over the last couple of years. FIND’s activities in Marsabit county started in 2018. In this work, we present the implementation of activities and the impacts in Marsabit county. We reviewed the data for 2017 and 2019 outbreaks (before and after the implementation of FIND’s activities) and assessed the importance of improving access and community sensitization to VL diagnosis. We assessed the contribution of each facility to the total distance traveled from a perspective of location optimization.

Results

There was a sharp increase in the number of people tested in the 2017 outbreak compared to the 2019 outbreak. In 2017, 437 people were tested compared to 2,338 in 2019. The county reported 234 and 688 VL cases in 2017 and 2019, respectively. The data revealed a shift in the demographic structures of cases toward the younger population (mean age in 2017 was 17.6 years and 15.3 years in 2019), with more female cases reported in 2019 compared to 2017. In 2017, 44.4% were 10 years of age or under. In 2019, the proportion 10 years or below was 52.2%. The addition of two new diagnosis facilities in 2018 resulted in a decrease in the distance traveled by confirmed VL cases from 28.1 km in 2017 to 10.8 km in 2019. Assessing the impact of facility placement indicated the most optimal facilities to provide VL diagnostic services and minimize the distance traveled by patients. Adding new facilities reduces the travel distance until a point where the addition of a new facility provides no additional impact.

Conclusion

The results from this study indicate the need to carefully consider the placement of health facilities in improving access to VL diagnosis and treatment and could serve as an investment case in deciding when to stop adding new facilities in a particular setting. Extending the activities in Kenya to other VL-endemic countries in East Africa will contribute significantly toward the elimination of the disease, addressing the needs of marginalized populations and leaving no one behind.
Integrated Marine Management in the United Kingdom Overseas Territories
Authors: Hardman Emily , Thomas Hannah L. , Baum Diane , Clingham Elizabeth , Hobbs Rhys , Stamford Tammy , Whomersley Paul , Smith Ness
Published: January 2022

Like many small island communities, the United Kingdom Overseas Territories (UKOTs) are directly dependent on their marine resources for a range of ecosystem services, such as income generation, subsistence, leisure, recreation and wellbeing. Healthy marine ecosystems also play a broader role in climate regulation, coastal resilience and habitat provision. With Blue Belt Programme assistance, the UKOTs are developing enhanced protection and sustainable management strategies for their marine environments, using an Integrated Marine Management (IMM) approach. This coordinates cross-sectoral planning and management to carefully balance marine conservation and sustainable use of resources in order to minimize socio-cultural and economic impacts to the local community. We describe the IMM approach taken in two UKOT case studies. In Ascension Island, a conservation planning and resource management process was initiated with an objective to protect at least 50% of Ascension’s waters from commercial fishing, resulting in the designation of one of the largest Marine Protected Areas (MPAs) in the Southern Atlantic. In St Helena, a new licensing framework for marine developments was developed within an existing sustainable use MPA. From these two approaches, we highlight aspects of the process, lessons learned and recommendations that may be useful for other small islands planning to implement IMM, particularly regarding the importance of effective stakeholder engagement, coordination across different governance scales, and long-term financial resources.
Correlation Between Previous Caesarean Section and Adverse Maternal Outcomes Accordingly With Robson Classification: Systematic Review and Meta-Analysis
Authors: Jamshed Shazia , Chien Shuo-Chen , Tanweer Afifa , Asdary Rahma-Novita , Hardhantyo Muhammad , Greenfield David , Chien Chia-Hui , Weng Shuen-Fu , Jian Wen-Shan , Iqbal Usman
Published: January 2022

Background: The increasing rates of Caesarean section (CS) beyond the WHO standards (10–15%) pose a significant global health concern.

Objective: Systematic review and meta-analysis to identify an association between CS history and maternal adverse outcomes for the subsequent pregnancy and delivery among women classified in Robson classification (RC).

Search Strategy: PubMed/Medline, EbscoHost, ProQuest, Embase, Web of Science, BIOSIS, MEDLINE, and Russian Science Citation Index databases were searched from 2008 to 2018.

Selection Criteria: Based on Robson classification, studies reporting one or more of the 14 adverse maternal outcomes were considered eligible for this review.

Data Collection: Study design data, interventions used, CS history, and adverse maternal outcomes were extracted.

Main Results: From 4,084 studies, 28 (n = 1,524,695 women) met the inclusion criteria. RC group 5 showed the highest proportion among deliveries followed by RC10, RC7, and RC8 (67.71, 32.27, 0.02, and 0.001%). Among adverse maternal outcomes, hysterectomy had the highest association after preterm delivery OR = 3.39 (95% CI 1.56–7.36), followed by Severe Maternal Outcomes OR = 2.95 (95% CI 1.00–8.67). We identified over one and a half million pregnant women, of whom the majority were found to belong to RC group 5.

Conclusions: Previous CS was observed to be associated with adverse maternal outcomes for the subsequent pregnancies. CS rates need to be monitored given the prospective risks which may occur for maternal and child health in subsequent births.
The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study
Authors: Sharifi Kia Danial , Shen Yuanjun , Bachman Timothy N. , Goncharova Elena A. , Kim Kang , Simon Marc A.
Published: January 2022

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.
Spatiotemporal Trends of Colorectal Cancer Mortality Due to Low Physical Activity and High Body Mass Index From 1990 to 2019: A Global, Regional and National Analysis
Authors: Man Jinyu , Zhang Tongchao , Yin Xiaolin , Chen Hui , Zhang Yuan , Zhang Xuening , Chen Jiaqi , Yang Xiaorong , Lu Ming
Published: January 2022

Background: Understanding the spatiotemporal trends of colorectal cancer (CRC) deaths caused by low physical activity (LPA) and high body mass index (BMI) is essential for the prevention and control of CRC. We assessed patterns of LPA and high BMI-induced CRC deaths from 1990 to 2019 at global, regional, and national levels.

Methods: Data on CRC deaths due to LPA and high BMI was downloaded from the Global Burden of Disease 2019 Study. We calculated estimated annual percentage change (EAPC) to quantify spatiotemporal trends in the CRC age-standardized mortality rate (ASMR) due to LPA and high BMI.

Results: In 2019, CRC deaths due to LPA and high BMI were estimated as 58.66 thousand and 85.88 thousand, and the corresponding ASMRs were 0.77/100,000 and 1.07/100,000, with EAPCs of−0.39 [95% confidence interval (CI):−0.49,−0.29] and 0.64[95% CI: 0.57, 0.71] from 1990 to 2019 respectively. Since 1990, the ASMR of CRC attributable to LPA and high BMI has been on the rise in many geographic regions, especially in low middle and middle sociodemographic index (SDI) regions. Thirteen countries had a significant downward trend in CRC ASMR attributed to LPA, with EAPCs < −1. And, only 4 countries had a significant downward trend in CRC ASMR attributable to high BMI, with EAPCs < −1. Countries with a higher baseline burden in 1990 and a higher SDI in 2019 had a faster decline in ASMR due to high BMI and LPA.

Conclusions: The burden of CRC caused by LPA and high BMI is on the rise in many countries. Countries should adopt a series of measures to control the local prevalence of obesity and LPA in order to reduce disease burden, including CRC.
Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV–HCV Coinfected Patients
Authors: Tripathi Gaurav , Rooge Sheetalnath , Yadav Manisha , Mathew Babu , Sharma Nupur , Bindal Vasundhra , Hemati Hamed , Singh Maras Jaswinder , Gupta Ekta
Published: January 2022

Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV–HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV–HCV patients.

Methods: Non-cirrhotic HIV–HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders).

Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = −0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = −0.713) significantly differentiated between nonresponders from responders in HIV–HCV coinfected patients and was able to predict the failure of treatment response.

Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV–HCV coinfected patients.
Matrin3: Disorder and ALS Pathogenesis
Authors: Salem Ahmed , Wilson Carter J. , Rutledge Benjamin S. , Dilliott Allison , Farhan Sali , Choy Wing-Yiu , Duennwald Martin L.
Published: January 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons in the brain and spinal cord. ALS is associated with protein misfolding and inclusion formation involving RNA-binding proteins, including TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS). The 125-kDa Matrin3 is a highly conserved nuclear DNA/RNA-binding protein that is implicated in many cellular processes, including binding and stabilizing mRNA, regulating mRNA nuclear export, modulating alternative splicing, and managing chromosomal distribution. Mutations in MATR3, the gene encoding Matrin3, have been identified as causal in familial ALS (fALS). Matrin3 lacks a prion-like domain that characterizes many other ALS-associated RNA-binding proteins, including TDP-43 and FUS, however, our bioinformatics analyses and preliminary studies document that Matrin3 contains long intrinsically disordered regions that may facilitate promiscuous interactions with many proteins and may contribute to its misfolding. In addition, these disordered regions in Matrin3 undergo numerous post-translational modifications, including phosphorylation, ubiquitination and acetylation that modulate the function and misfolding of the protein. Here we discuss the disordered nature of Matrin3 and review the factors that may promote its misfolding and aggregation, two elements that might explain its role in ALS pathogenesis.
Case Report: Progressive Asymmetric Parkinsonism Secondary to CADASIL Without Dementia
Authors: Guo Weihang , Xu Baolei , Sun Hong , Ma Jinghong , Mei ShanShan , Zeng Jingrong , Sun Junyan , Xu Erhe
Published: January 2022

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.
Left Atrial Appendage Closure Yields Favorable Cardio- and Cerebrovascular Outcomes in Patients With Non-valvular Atrial Fibrillation and Prior Stroke
Authors: Zhao Mingzhong , Zhao Mengxi , Hou Cody R. , Post Felix , Herold Nora , Walsleben Jens , Meng Zhaohui , Yu Jiangtao
Published: January 2022

Introduction: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke are at significantly higher risk of stroke recurrence. Data on the efficacy of left atrial appendage closure (LAAC) on these patients is limited. The aim of this study was to investigate the differences of LAAC efficacy on long-term cardio- and cerebrovascular outcomes in NVAF patients with vs. without prior stroke.

Methods: Three hundred and seventy consecutive NVAF patients who underwent LAAC were enrolled and divided into stroke and non-stroke groups based on history of previous stroke. Endpoints, such as thromboembolism, major bleeding, and mortality post-LAAC, were followed up among groups.

Results: Patients in the stroke group had higher mean CHA2DS2-VASc and HAS-BLED scores compared to the non-stroke group (5.1 vs. 3.6 and 4.1 vs. 3.4, both P < 0.001, respectively). Over a median follow-up of 2.2 years, there were no significant differences in incidence rates of thromboembolism, device-related thrombus (DRT), major bleeding, and combined efficacy endpoints between the two groups. In both stroke and non-stroke groups, LAAC decreased the risk of thromboembolism [relative risk reduction (RRR) 87.5%, P = 0.034, and 74.6%, P = 0.004, respectively] and major bleeding (RRR 68.8%, P = 0.034, and 68.6%, P = 0.007, respectively) compared with predicted risk. The RRR in thromboembolism was greater in patients with vs. without prior stroke (OR 2.45, 95% CI: 1.20–5.12, P = 0.016). The incidence rates of all-cause mortality and non-cardiovascular death were similar between the two groups, but the risks of cardiovascular death post-LAAC both before (1.4% vs. 8.1%, respectively, P = 0.038) and after adjustment for confounding factors (P = 0.048) were significantly decreased in the stroke group.

Conclusions: Patients with vs. without prior stroke did not exhibit a worse clinical prognosis after LAAC. LAAC may provide an increased benefit in cardio-cerebrovascular outcomes in patients with previous stroke compared to those without previous stroke. Further research is necessary to evaluate the efficacy of LAAC in this field.
Benign Intracranial Hypertension Due to Hypoparathyroidism: A Case Report
Authors: Sforza Giorgia , Deodati Annalisa , Moavero Romina , Papetti Laura , Frattale Ilaria , Vigevano Federico , Cianfarani Stefano , Valeriani Massimiliano
Published: January 2022

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism.

Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH2O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations.

Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture.

Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H2O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually.

Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems.
Engineering Organoids for in vitro Modeling of Phenylketonuria
Authors: Borges Alice C. , Broersen Kerensa , Leandro Paula , Fernandes Tiago G.
Published: January 2022

Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.
Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues
Authors: Marinucci Mattia , Ercan Caner , Taha-Mehlitz Stephanie , Fourie Lana , Panebianco Federica , Bianco Gaia , Gallon John , Staubli Sebastian , Soysal Savas D. , Zettl Andreas , Rauthe Stephan , Vosbeck Jürg , Droeser Raoul A. , Bolli Martin , Peterli Ralph , von Flüe Markus , Ng Charlotte K. Y. , Kollmar Otto , Coto-Llerena Mairene , Piscuoglio Salvatore
Published: January 2022

The use of patient-derived organoids (PDO) as a valuable alternative to in vivo models significantly increased over the last years in cancer research. The ability of PDOs to genetically resemble tumor heterogeneity makes them a powerful tool for personalized drug screening. Despite the extensive optimization of protocols for the generation of PDOs from colorectal tissue, there is still a lack of standardization of tissue handling prior to processing, leading to microbial contamination of the organoid culture. Here, using a cohort of 16 patients diagnosed with colorectal carcinoma (CRC), we aimed to test the efficacy of phosphate-buffered saline (PBS), penicillin/streptomycin (P/S), and Primocin, alone or in combination, in preventing organoid cultures contamination when used in washing steps prior to tissue processing. Each CRC tissue was divided into 5 tissue pieces, and treated with each different washing solution, or none. After the washing steps, all samples were processed for organoid generation following the same standard protocol. We detected contamination in 62.5% of the non-washed samples, while the use of PBS or P/S-containing PBS reduced the contamination rate to 50% and 25%, respectively. Notably, none of the organoid cultures washed with PBS/Primocin-containing solution were contaminated. Interestingly, addition of P/S to the washing solution reduced the percentage of living cells compared to Primocin. Taken together, our results demonstrate that, prior to tissue processing, adding Primocin to the tissue washing solution is able to eliminate the risk of microbial contamination in PDO cultures, and that the use of P/S negatively impacts organoids growth. We believe that our easy-to-apply protocol might help increase the success rate of organoid generation from CRC patients.
Case Report: First Case of Consolidation Immunotherapy After Definitive Chemoradiotherapy in Mediastinal Lymph Node Metastatic Sarcomatoid Carcinoma
Authors: Wang Yu , Yang Lin , Wang Jianyang , Gui Lin , Li Wei , Liu Zhiqiang , Ma Xiangyu , Yang Yin , Wang Luhua , Bi Nan
Published: January 2022

Sarcomatoid carcinoma (SC) is a rare lung cancer subtype with poor prognosis and lack of effective treatment regimens. Studies concerning SC indicated common programmed death ligand-1 (PD-L1) overexpression and higher tumor mutational burden, leading to potential benefits from immunotherapy. The present case is the first report employing PD-L1 inhibitor durvalumab following definitive concurrent chemoradiotherapy (cCRT) in a patient with mediastinal lymph node metastatic SC, which was considered as a high probability of pulmonary origin but unclear primary lesion. After the 19-month follow-up, there was neither local recurrence nor distant metastasis. The patient was in a good condition, with the thoracic lesion controlled at Partial response-Response Evaluation Criteria in Solid Tumors (PR-RECIST). Except for grade 2 esophagitis, none of the other adverse events was observed. Our first attempt to adopt the consolidation immunotherapy after cCRT in unresectable locally advanced mediastinal SC exhibited improved local control, manageable safety, and potential survival benefits, representing a novel and promising therapeutic option for SC and encouraging further research exploration of this regimen in the future.
Diagnostic Accuracy of Contemporary Selection Criteria in Prostate Cancer Patients Eligible for Active Surveillance: A Bayesian Network Meta-Analysis
Authors: Fan Yu , Mulati Yelin , Zhai Lingyun , Chen Yuke , Wang Yu , Feng Juefei , Yu Wei , Zhang Qian
Published: January 2022

Background

Several active surveillance (AS) criteria have been established to screen insignificant prostate cancer (insigPCa, defined as organ confined, low grade and small volume tumors confirmed by postoperative pathology). However, their comparative diagnostic performance varies. The aim of this study was to compare the diagnostic accuracy of contemporary AS criteria and validate the absolute diagnostic odds ratio (DOR) of optimal AS criteria.

Methods

First, we searched Pubmed and performed a Bayesian network meta-analysis (NMA) to compare the diagnostic accuracy of contemporary AS criteria and obtained a relative ranking. Then, we searched Pubmed again to perform another meta-analysis to validate the absolute DOR of the top-ranked AS criteria derived from the NMA with two endpoints: insigPCa and favorable disease (defined as organ confined, low grade tumors). Subgroup and meta-regression analyses were conducted to identify any potential heterogeneity in the results. Publication bias was evaluated.

Results

Seven eligible retrospective studies with 3,336 participants were identified for the NMA. The diagnostic accuracy of AS criteria ranked from best to worst, was as follows: Epstein Criteria (EC), Yonsei criteria, Prostate Cancer Research International: Active Surveillance (PRIAS), University of Miami (UM), University of California-San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSKCC), and University of Toronto (UT). I2 = 50.5%, and sensitivity analysis with different insigPCa definitions supported the robustness of the results. In the subsequent meta-analysis of DOR of EC, insigPCa and favorable disease were identified as endpoints in ten and twenty-two studies, respectively. The pooled DOR for insigPCa and favorable disease were 0.44 (95%CI, 0.31–0.58) and 0.66 (95%CI, 0.61–0.71), respectively. According to a subgroup analysis, the DOR for favorable disease was significantly higher in US institutions than that in other regions. No significant heterogeneity or evidence of publication bias was identified.

Conclusions

Among the seven AS criteria evaluated in this study, EC was optimal for positively identifying insigPCa patients. The pooled diagnostic accuracy of EC was 0.44 for insigPCa and 0.66 when a more liberal endpoint, favorable disease, was used.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/], PROSPERO [CRD42020157048].
Risk Factors for Acute Respiratory Infections in Children Between 0 and 23 Months of Age in a Peri-Urban District in Pakistan: A Matched Case–Control Study
Authors: Mir Fatima , Ariff Shabina , Bhura Maria , Chanar Suhail , Nathwani Apsara Ali , Jawwad Muhammad , Hussain Amjad , Rizvi Arjumand , Umer Muhammad , Memon Zahid , Habib Atif , Soofi Sajid Bashir , Bhutta Zulfiqar A.
Published: January 2022

Background: Acute respiratory infection (ARI) accounts for nearly 15% of all childhood mortality in South Asia, with children from rural areas at higher risk due to inaccessibility to healthcare facilities. We therefore aimed to identify risk factors associated with ARI in children under 2 years of age in rural Pakistan.

Methods: A retrospective 1:2 matched case–control study was conducted between October and December 2018 in Taluka Kotri, Jamshoro District of Pakistan. Cases were identified as children between 0 and 23 months of age with a history of fever, cough, sore throat, fast breathing, difficulty breathing, or chest indrawing in the 2 weeks prior to the survey. Controls were participants without symptoms of ARI, matched based on age in months. Data analysis was conducted using STATA version 15. Univariate and multivariable conditional logistic regression analyses were used to identify factors associated with ARI, and p < 0.05 was considered statistically significant.

Results: We identified 1,071 cases of ARI who were matched with 2,142 controls. Multivariable analysis revealed that female gender [odds ratio (OR) 0.78, 95% confidence interval (CI): 0.67–0.91], exclusive breastfeeding (OR 0.81, 95% CI: 0.69–0.97), and comorbidity with diarrhea (OR: 1.64, 95% CI: 1.40–1.91) were significantly associated with ARI.

Conclusion: Pakistan continues to progress toward reducing childhood mortality, particularly ARI-related deaths, for which it bears a great burden. This study identifies risk factors such as the male gender, breastfeeding, and comorbidities with diarrhea, which could open grounds for further programmatic implications in targeting a multifaceted approach to reducing incidences of ARI in rural areas of the country.
Nonreversible Markov Chain Monte Carlo Algorithm for Efficient Generation of Self-Avoiding Walks
Authors: Zhao Hanqing , Vucelja Marija
Published: January 2022

We introduce an efficient nonreversible Markov chain Monte Carlo algorithm to generate self-avoiding walks with a variable endpoint. In two dimensions, the new algorithm slightly outperforms the two-move nonreversible Berretti-Sokal algorithm introduced by H. Hu, X. Chen, and Y. Deng, while for three-dimensional walks, it is 3–5 times faster. The new algorithm introduces nonreversible Markov chains that obey global balance and allow for three types of elementary moves on the existing self-avoiding walk: shorten, extend or alter conformation without changing the length of the walk.
Self-Doping and the Mott-Kondo Scenario for Infinite-Layer Nickelate Superconductors
Authors: Yang Yi-feng , Zhang Guang-Ming
Published: January 2022

We give a brief review of the Mott-Kondo scenario and its consequence in the recently-discovered infinite-layer nickelate superconductors. We argue that the parent state is a self-doped Mott insulator and propose an effective t- J-K model to account for its low-energy properties. At small doping, the model describes a low carrier density Kondo system with incoherent Kondo scattering at finite temperatures, in good agreement with experimental observation of the logarithmic temperature dependence of electric resistivity. Upon increasing Sr doping, the model predicts a breakdown of the Kondo effect, which provides a potential explanation of the non-Fermi liquid behavior of the electric resistivity with a power law scaling over a wide range of the temperature. Unconventional superconductivity is shown to undergo a transition from nodeless (d+is)-wave to nodal d-wave near the critical doping due to competition of the Kondo and Heisenberg superexchange interactions. The presence of different pairing symmetry may be supported by recent tunneling measurements.
Secure Communication Scheme for Brain-Computer Interface Systems Based on High-Dimensional Hyperbolic Sine Chaotic System
Authors: Zhang Xiangzi , Ding Xiaobin , Tong Dandan , Chang Pengbin , Liu Jizhao
Published: January 2022

Brain-Computer Interface (BCI) is a direct communication pathway between the brain and the external environment without using peripheral nerves and muscles. This emerging topic is suffering from serious issues such as malicious tampering and privacy leakage. To address this issue, we propose a novel communication scheme for BCI Systems. In particular, this scheme first utilizes high-dimensional chaotic systems with hyperbolic sine nonlinearity as the random number generator, then decorrelation operation is used to remove the physical characteristics of the output sequences. Finally, each of the sequences is applied in differential chaos shift keying (DCSK). Since each output sequence corresponds to a unique electrode, the communication data of different electrodes will not interfere with each other. Compared with popular multi-user DSCK schemes using Walsh code sequences, this scheme does not require the channel data of all electrodes while decoding. Therefore, this scheme has higher efficiency. Experimental results on communication data indicate that the proposed scheme can provide a high level of security.
Time to Move Beyond a “One-Size Fits All” Approach to Inspiratory Muscle Training
Authors: Shei Ren-Jay , Paris Hunter L. , Sogard Abigail S. , Mickleborough Timothy D.
Published: January 2022

Inspiratory muscle training (IMT) has been studied as a rehabilitation tool and ergogenic aid in clinical, athletic, and healthy populations. This technique aims to improve respiratory muscle strength and endurance, which has been seen to enhance respiratory pressure generation, respiratory muscle weakness, exercise capacity, and quality of life. However, the effects of IMT have been discrepant between populations, with some studies showing improvements with IMT and others not. This may be due to the use of standardized IMT protocols which are uniformly applied to all study participants without considering individual characteristics and training needs. As such, we suggest that research on IMT veer away from a standardized, one-size-fits-all intervention, and instead utilize specific IMT training protocols. In particular, a more personalized approach to an individual’s training prescription based upon goals, needs, and desired outcomes of the patient or athlete. In order for the coach or practitioner to adjust and personalize a given IMT prescription for an individual, factors, such as frequency, duration, and modality will be influenced, thus inevitably affecting overall training load and adaptations for a projected outcome. Therefore, by integrating specific methods based on optimization, periodization, and personalization, further studies may overcome previous discrepancies within IMT research.
Modeling of the Potential Geographical Distribution of Three Fritillaria Species Under Climate Change
Authors: Jiang Ruiping , Zou Meng , Qin Yu , Tan Guodong , Huang Sipei , Quan Huige , Zhou Jiayu , Liao Hai
Published: January 2022

Fritillaria species, a well-known Chinese traditional medicine for more than 2,000 years, have become rare resources due to excessive harvesting. In order to balance the economical requirement and ecological protection of Fritillaria species, it is necessary to determine (1) the important environmental variables that were responsible for the spatial distribution, (2) distribution change in response to climate change in the future, (3) ecological niche overlap between various Fritillaria species, and (4) the correlation between spatial distribution and phylogenies as well. In this study, the areas with potential ecological suitability for Fritillaria cirrhosa, Fritillaria unibracteata, and Fritillaria przewalskii were predicted using MaxEnt based on the current occurrence records and bioclimatic variables. The result indicated that precipitation and elevation were the most important environmental variables for the three species. Moreover, the current suitable habitats of F. cirrhosa, F. unibracteata, and F. przewalskii encompassed 681,951, 481,607, and 349,199 km2, respectively. Under the scenario of the highest concentration of greenhouse gas emission (SSP585), the whole suitable habitats of F. cirrhosa and F. przewalskii reach the maximum from 2021 to 2100, while those of F. unibracteata reach the maximum from 2021 to 2100 under the scenario of moderate emission (SSP370) from 2021 to 2100. The MaxEnt data were also used to predict the ecological niche overlap, and thus high overlap occurring among three Fritillaria species was observed. The niche overlap of three Fritillaria species was related to the phylogenetic analysis despite the non-significance (P > 0.05), indicating that spatial distribution was one of the factors that contributed to the speciation diversification. Additionally, we predicted species-specific habitats to decrease habitat competition. Overall, the information obtained in this study provided new insight into the potential distribution and ecological niche of three species for the conservation and management in the future.
Aggressiveness in Judokas and Team Athletes: Predictive Value of Personality Traits, Emotional Intelligence and Self-Efficacy
Authors: Stanković Nemanja , Todorović Dušan , Milošević Nikola , Mitrović Milica , Stojiljković Nenad
Published: January 2022

Combat sports and martial arts are often associated with aggressiveness among the general public, although data on judo and/or martial arts and aggressiveness seem to be unclear. This research aims to compare athletes who have trained judo for a prolonged time (minimum 5 years) and athletes from various team sports, primarily regarding the manifestation of aggression, but also regarding personality traits, emotional intelligence, and self-efficacy. Also, the potential predictive value of personality traits, emotional intelligence, and self-efficacy for aggression within subsamples of judokas and team athletes was tested. The research findings showed that professional judo athletes are characterized by a low degree of aggression, especially low indirect and physical manifestations of aggression. In addition, the personality traits Honesty-Humility and Openness to experience are well expressed, contrary to Emotionality and Extraversion, which are less pronounced. They are also characterized by moderate general self-efficacy. On the other hand, members of team sports produced the opposite results, as they are characterized by increased aggression, pronounced traits of Emotionality and Extraversion, somewhat less pronounced traits of Honesty-Humility, Openness to new experience, and less pronounced general self-efficacy. The percentage of explained variability of aggression is slightly higher in the subsample of team sports and constitutes 49.9% of the variability, while in the subsample of judokas it constitutes 47.8% of the variability of the criteria. Practical implications, limitations, and future research directions were discussed.
Implications of COVID-19 Vaccine Hesitancy: Results of Online Bulletin Board Interviews
Authors: Gorman Jack M. , Gorman Sara E. , Sandy William , Gregorian Nellie , Scales David A.
Published: January 2022

Reluctance to accept vaccination against COVID-19 poses a significant public health risk and is known to be a multi-determined phenomenon. We conducted online focus groups, or “bulletin boards,” in order to probe the nature of COVID-19 vaccine hesitancy and its implications. Participants were 94 individuals from three distinct U.S. geographical areas and represented a range of demographic and socioeconomic characteristics. Six themes emerged from the 3 day-long bulletin boards: the most trusted source of health information sought is the personal physician; information about health is nevertheless obtained from a wide variety of sources; stories about adverse side effects are especially “sticky”; government health institutions like CDC and FDA are not trusted; most respondents engaged in individualistic reasoning; and there is a wide spectrum of attitudes toward vaccination.
Rhabdophis tigrinus (Yamakagashi) Bites in Japan Over the Last 50 Years: A Retrospective Survey
Authors: Hifumi Toru , Sakai Atsushi , Yamamoto Akihiko , Morokuma Kazunori , Otani Norio , Takahashi Motohide , Ato Manabu
Published: January 2022

Introduction:Rhabdophissnakes, which include 27 species, are rear-fanged venomous snakes that are widely distributed from India to East Asia and Russia. Severe envenomation byR. tigrinus(Yamakagashi snake) in Japan andR. subminiatusin Southeast Asia has been reported. The epidemiology ofR. tigrinusbites, such as geographical features, the incidence, and changes in the number of bites over time have not been comprehensively examined. Hence, we intended to clarify the epidemiological features ofR. tigrinusbites through a careful review of scientific data over the last 50 years in Japan.

Methods:Patient records ofR. tigrinusbites between 1971 and 2020 at the Japan Snake Institute were examined retrospectively. The following were ascertained: patient characteristics, clinical symptoms, laboratory data, treatment-related factors, and hospital mortality. These variables were compared in the antivenom and the without-antivenom groups.

Results:Over the 50-year study period, 43R. tigrinusbites, including five fatal cases, were encountered. Severe cases ofR. tigrinusbites have been treated with antivenom since 1985; however, fatalities occurred in 2006 and 2020.R. tigrinusbite cases have been well-distributed in the western part of Japan since 2000. The mortality rate in the antivenom group was significantly lower in the patient group that was not administered the antivenom (0 vs. 23.8%,p= 0.048).

Conclusion:This study clarified the epidemiology ofR. tigrinusbites in Japan over a 50-year period. Almost all severe cases ofR. tigrinusbites have been treated with the antivenom in the current situation, and fatalities occurred in cases not treated with the antivenom. It is important to diagnoseR. tigrinusbites in the early phase of the clinical course. The antivenom, the definitive treatment forR. tigrinusbites, is an unapproved drug. Hence, approval needs to be obtained for the drug.
Issues Faced by Prosthetists and Physiotherapists During Lower-Limb Prosthetic Rehabilitation: A Thematic Analysis
Authors: Turner Shruti , Belsi Athina , McGregor Alison H.
Published: January 2022

Successful prosthetic rehabilitation is essential to improve the physical and mental outcomes of people with lower-limb amputation. Evaluation of prosthetic services from a prosthesis user perspective have been published and commissioned by the national bodies, however, the perspectives of clinicians working with service users during rehabilitation have not to date been sought. We sought to determine factors impacting lower-limb prosthetic rehabilitation from a clinician's perspective to inform studies focusing on prosthetic and socket design and fitting. Six clinician (2 prosthetists, 4 physiotherapists) interviewees were self-selected from a survey exploring issues and frustrations during lower-limb prosthetic rehabilitation. Semi-structured interviews explored the impactors on and frustrations with rehabilitation and the prosthetic socket. A thematic analysis was subsequently conducted to identify themes in the responses. Five themes were identified: Service Disparity, Body Impactors, Consequences of Ill-Fit, Prosthesis Irritants, and Limitations of Practice. Each theme, though distinct, relates to the others either as a cause or consequence and should be viewed as such. Addressing the themes will have benefits beyond the issues addressed but also expand into the other themes. This study provides an insight into the clinician perspectives on lower-limb prosthetic rehabilitation, which has not been formally documented to date.