bluuebunny/crossref_metadata_2025 huggingface dataset:
Back to basics: likelihood ratios for olive and grass pollen specific IgE in seasonal allergic rhinitis
Authors: Manzanares Bárbara , González Rafael , Serrano Pilar , Navas Ana , Alonso Corona , Fernandez Lourdes , Jurado Aurora , Moreno-Aguilar Carmen
Published: October 2023

Introduction

Specific IgE (sIgE) is merely a sensitization marker that cannot be used for allergy diagnosis if there are no associated clinical symptoms. As of 2023, there is still no evidence regarding the quantity of sIgE necessary to confirm or exclude clinical disease. Therefore, this study aimed to calculate cut-offs for sIgE, allowing us to effectively diagnose olive or grass pollen allergy and select allergenic immunotherapy (AIT) candidate patients in a region under high olive and grass allergenic pressure.

Methods

An observational retrospective study consisting of the review of electronic medical records from 1,172 patients diagnosed with seasonal rhino-conjunctivitis and suspected allergy to olive or grass pollen. Symptoms correlated with sIgE to Poaceae and Oleaceae whole extracts and sIgE to genuine allergenic components were evaluated. Optimal cut-off values were calculated using receiver operating characteristic curves. Relevant clinical symptoms and AIT indications were taken into consideration when determining the clinical allergy diagnosis.

Results

sIgE to Lolium showed the best area under the curve (AUC) for both diagnosis (0.957) and an indication of AIT (0.872). The optimal cut-off values for grass diagnosis and AIT indication were 1.79 kUA/L and 8.83 kUA/L, respectively. A value of 5.62 kUA/L was associated with a positive likelihood ratio (LR) of 10.08 set for grass allergy. Olea sIgE showed the best AUC for the diagnosis (0.950). The optimal cut-off for diagnosis was 2.41 kUA/L. A value of 6.49 kUA/L was associated with a positive LR of 9.98 to confirm olive pollen allergy. In regard to immunotherapy, Ole e 1 sIgE showed the best AUC (0.860). The optimal cut-off was 14.05 kUA/L. Ole e 1 sIgE value of 4.8 kUA/L was associated with a 0.09 negative LR to exclude olive AIT indication.

Conclusions

The sIgE cut-offs found in this population under high olive and grass allergenic pressure reduce the gap between sensitization and clinical allergy, providing a new tool for the diagnosis of seasonal allergic rhinitis/asthma and helping to discriminate patients who will benefit from AIT.
Injury risk functions for the four primary knee ligaments
Authors: Nusia Jiota , Xu Jia-Cheng , Knälmann Johan , Sjöblom Reimert , Kleiven Svein
Published: October 2023

The purpose of this study was to develop injury risk functions (IRFs) for the anterior and posterior cruciate ligaments (ACL and PCL, respectively) and the medial and lateral collateral ligaments (MCL and LCL, respectively) in the knee joint. The IRFs were based on post-mortem human subjects (PMHSs). Available specimen-specific failure strains were supplemented with statistically generated failure strains (virtual values) to accommodate for unprovided detailed experimental data in the literature. The virtual values were derived from the reported mean and standard deviation in the experimental studies. All virtual and specimen-specific values were thereafter categorized into groups of static and dynamic rates, respectively, and tested for the best fitting theoretical distribution to derive a ligament-specific IRF. A total of 10 IRFs were derived (three for ACL, two for PCL, two for MCL, and three for LCL). ACL, MCL, and LCL received IRFs in both dynamic and static tensile rates, while a sufficient dataset was achieved only for dynamic rates of the PCL. The log-logistic and Weibull distributions had the best fit (p-values: >0.9, RMSE: 2.3%–4.7%) to the empirical datasets for all the ligaments. These IRFs are, to the best of the authors’ knowledge, the first attempt to generate injury prediction tools based on PMHS data for the four knee ligaments. The study has summarized all the relevant literature on PHMS experimental tensile tests on the knee ligaments and utilized the available empirical data to create the IRFs. Future improvements require upcoming experiments to provide comparable testing and strain measurements. Furthermore, emphasis on a clear definition of failure and transparent reporting of each specimen-specific result is necessary.
Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity
Authors: Brisset Morgan , Mehlen Patrick , Meurette Olivier , Hollande Frédéric
Published: October 2023

Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and recurrence seems to be an attractive approach to improve treatment outcome in cancer patients. However, this remains challenging due to the complexity and incomplete characterization of tumor cell subpopulations. The heterogeneity of cells exhibiting stemness-related features, such as self-renewal and chemoresistance, fuels this complexity. Notch signaling is a known regulator of cancer stem cell (CSC) features in colorectal cancer (CRC), though the effects of its heterogenous signaling on CRC cell stemness are only just emerging. In this review, we discuss how Notch ligand-receptor specificity contributes to regulating stemness, self-renewal, chemoresistance and cancer stem cells heterogeneity in CRC.
The development of a Modular Accessible Musical Instrument Technology Toolkit using action research
Authors: Ward Asha
Published: October 2023

Within the field of digital musical instruments, there have been a growing number of technological developments aimed at addressing the issue of accessibility to music-making for disabled people. This study summarizes the development of one such technological system—The Modular Accessible Musical Instrument Technology Toolkit (MAMI Tech Toolkit). The four tools in the toolkit and accompanying software were developed over 5 years using an action research methodology. A range of stakeholders across four research sites were involved in the development. This study outlines the methodological process, the stakeholder involvement, and how the data were used to inform the design of the toolkit. The accessibility of the toolkit is also discussed alongside findings that have emerged from the process. This study adds to the established canon of research around accessible digital musical instruments by documenting the creation of an accessible toolkit grounded in both theory and practical application of third-wave human–computer interaction methods. This study contributes to the discourse around the use of participatory and iterative methods to explore issues with, and barriers to, active music-making with music technology. Outlined is the development of each of the novel tools in the toolkit, the functionality they offer, as well as the accessibility issues they address. The study advances knowledge around active music-making using music technology, as well as in working with diverse users to create these new types of systems.
Tricuspid regurgitation, right ventricular function, and renal congestion: a cardiorenal triangle
Authors: Forado-Benatar Ilana , Caravaca-Pérez Pedro , Rodriguez-Espinosa Diana , Guzman-Bofarull Joan , Cuadrado-Payán Elena , Moayedi Yasbanoo , Broseta José Jesús , Farrero Marta
Published: October 2023

There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the “forgotten” defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.
Supraglacial geomorphology of Companion Glacier, central Himalaya: evolution, controls and consequences
Authors: Garg Purushottam Kumar , Mehta Manish , Shukla Aparna , Chauhan Pankaj , Kesarwani Kapil , Mukherjee Sandipan
Published: October 2023

Supraglacial debris cover greatly influences glacier dynamics. The present study combines field and remote sensing observations acquired between 2000 and 2020 to understand debris characteristics, area and terminus changes, surface velocity, and mass balance of the Companion Glacier, Central Himalaya, along with a systematic investigation of its supraglacial morphology. According to field observations, the glacier’s lower ablation zone has very coarse and thick debris (1–3 m). Owing to thick debris and consequent protected margins, the glacier could maintain its geometry during the study (2000–2020) showing much less area loss (0.07% ±0.1% a−1) and terminus retreat (1.2 ±1.9 m a−1) than other glaciers in the study region. The average mass balance (−0.12 ±0.1 m w. e. a−1; 2000–2020) was also less negative than the regional trend. Interestingly, in contrast to widespread regional velocity reduction, Companion’s average velocity increased (by 21%) from 6.97 ±3.4 (2000/01) to 8.45 ±2.1 m a−1 (2019/20). Further, to investigate supraglacial morphology, the glacier ablation zone is divided into five zones (Zone-I to V; snout-to-up glacier) based on 100 m altitude bins. Analysis reveals that stagnation prevails over Zone-I to Zone-III, where despite slight acceleration, the velocity remains <∼8 m a−1. Zone-V is quite active (12.87 ±2.1 m a−1) and has accelerated during the study. Thus, Zone-IV with stable velocity, is sandwiched between fast-moving Zone-V and slow-moving Zone-III, which led to bulging and development of mounds. Debris slides down these mounds exposing the top portion for direct melting and the meltwater accumulates behind the mounds forming small ponds. Thus, as a consequence of changing morphology, a new ablation mechanism in the form of spot-melting has dominated Zone-IV, leading to the highest negative mass balance here (−0.5 ±0.1 m w. e. a−1). The changing snout and supraglacial morphology, active mound-top’s melting and formation of ponds likely promote relatively higher glacier wastage in the future.
The relationship between sarcopenia and mortality in Chinese community-dwelling adults: a 7-year cohort study with propensity score matching and Mendelian randomization
Authors: Xiong Lijiao , Liao Tingfeng , Guo Tianting , Zeng Zhaohao , Wang Shuojia , Yang Guangyan , Wang Xiaohao , Wang Xinyu , Zhu Jing , Zhao Pengfei , Li Yanchun , Li Lixing , Kang Lin , Yang Shu , Liang Zhen
Published: October 2023

Background

Sarcopenia has been linked to adverse health outcomes, including an increased risk of mortality. This study aimed to assess the 7-year mortality risk of sarcopenia in a community-based population in China and explore the causal relationship between components of sarcopenia and any death.

Methods

Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) conducted between 2011 and 2018. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Logistic regression, Kaplan–Meier (KM) survival analysis, and propensity score matching with inverse probability of treatment weighting were used. Mendelian randomization (MR) analyses, conducted using European population data, were utilized to assess causality between sarcopenia and any death.

Results

The study included 9,006 participants: 3,892 had no sarcopenia, 3,570 had possible sarcopenia, 1,125 had sarcopenia, and 419 had severe sarcopenia. Over 7 years of follow-up, there were 871 deaths, including 196 with sarcopenia and 133 with severe sarcopenia. The KM curves showed that sarcopenia had a higher risk of mortality. Compared to those of no sarcopenia, the odds ratios (ORs) of sarcopenia for 7-year mortality were 1.41 (95% CI, 1.06–1.87) after adjusting for confounding variables (p < 0.05). The ORs of severe sarcopenia were 2.11 (95% CI, 1.51–2.95). Propensity score matching analysis and inverse probability of treatment weighting analysis confirmed these findings. The adjusted ORs of sarcopenia and 7-year mortality were 2.94 (95% CI, 1.6–5.39) in the 45–60 age group, 1.72 (95% CI, 1.11–2.68) in the 60–80 age group, and 5.03 (95% CI, 0.48–52.65) in the ≥80 age group. The ORs of severe sarcopenia and 7-year mortality were 6.92 (95% CI, 1.95–24.5) in the 45–60 age group, 2.59 (95% CI, 1.61–4.17) in the 60–80 age group, and 12.52 (95% CI, 1.18–133.18) in the ≥80 age group. The MR analyses, leveraging the inverse variance weighted (IVW) method, unveiled substantial causal links between low hand grip strength in individuals aged 60 and older, the usual walking pace, and mortality risk.

Conclusion

This study underscores the significant impact of sarcopenia and its components on mortality risk within the Chinese population. Particularly, low hand grip strength and usual walking pace emerged as noteworthy contributors to mortality risk.
Skeletal muscle mass, muscle strength, and physical performance in children and adolescents with obesity
Authors: Zembura Marcela , Czepczor-Bernat Kamila , Dolibog Patrycja , Dolibog Paweł T. , Matusik Paweł
Published: October 2023

Introduction

Sarcopenic obesity (SO) is defined as obesity with low skeletal muscle function and mass. This study aimed to evaluate the presence of sarcopenic obesity according to different diagnostic criteria and assess the elements of sarcopenia in children and adolescents with obesity.

Methods

A total of 95 children and adolescents with obesity (diagnosed with the use of International Obesity Task Force (IOTF) criteria) with a mean age of 12.7( ± 3) years participated in the study. Body composition was assessed with the use of bioelectrical impedance—BIA (Tanita BC480MA) and dual-energy X-ray absorptiometry—DXA (Hologic). Fat mass (FM) and appendicular skeletal muscle mass (SMMa) were expressed as kilograms (kg) and percentage (%). Muscle-to-fat ratio (MFR) was defined as SMMa divided by FM. A dynamometer was used in order to measure grip strength. Six-minute walk test (6MWT) and a timed up-and-go test (TUG) were used to assess physical performance.

Results

The presence of SO ranged from 6.32% to 97.89%, depending on the criteria used to define sarcopenia. Children with sarcopenia, defined as a co- occurrence of low skeletal muscle mass % (SMM%) measured by DXA (≤9th centile) according to McCarthy et al. and weak handgrip strength (≤10th centile) according to Dodds et al., had significantly lower SMMa measured by both DXA and BIA, lower maximal handgrip strength, and lower physical performance. Maximal handgrip was positively correlated with SMMa (kg) and SMMa% derived from both DXA and BIA and BIA-MFR. Maximal handgrip was negatively correlated with waist-to-height ratio (WHtR). The distance of 6MWT correlated positively with BIA-measured SMMa% and BIA-MFR. 6MWT distance correlated negatively with BIA-FM% and body mass index (BMI) z-score. TUG was positively correlated with BIA-FM%, BMI z-score, WHtR, and IOTF categories and negatively correlated with BIA-SMMa% and BIA-MFR.

Discussion

The presence of sarcopenia in our study varied depending on the diagnostic criteria used. This is one of the first studies evaluating muscle mass, muscle strength, and physical performance in children and adolescents with obesity. The study highlighted the need for the implementation of a consensus statement regarding SO diagnostic criteria in children and adolescents.
Characterization of a novel species-specific 51-amino acid peptide, PEP51, as a caspase-3/7 activator in ovarian follicles of the ascidian, Ciona intestinalis Type A
Authors: Sakai Tsubasa , Yamamoto Tatsuya , Watanabe Takehiro , Hozumi Akiko , Shiraishi Akira , Osugi Tomohiro , Matsubara Shin , Kawada Tsuyoshi , Sasakura Yasunori , Takahashi Toshio , Satake Honoo
Published: October 2023

Invertebrates lack hypothalamic-pituitary-gonadal axis, and have acquired species-specific regulatory systems for ovarian follicle development. Ascidians are marine invertebrates that are the phylogenetically closest living relatives to vertebrates, and we have thus far substantiated the molecular mechanisms underlying neuropeptidergic follicle development of the cosmopolitan species, Ciona intestinalis Type A. However, no ovarian factor has so far been identified in Ciona. In the present study, we identified a novel Ciona-specific peptide, termed PEP51, in the ovary. Immunohistochemical analysis demonstrated the specific expression of PEP51 in oocyte-associated accessory cells, test cells, of post-vitellogenic (stage III) follicles. Immunoelectron microscopy revealed that PEP51 was localized in the cytosol of test cells in early stage III follicles, which lack secretory granules. These results indicate that PEP51 acts as an intracellular factor within test cells rather than as a secretory peptide. Confocal laser microscopy verified that activation of caspase-3/7, the canonical apoptosis marker, was detected in most PEP51-positive test cells of early stage III. This colocalization of PEP51 and the apoptosis marker was consistent with immunoelectron microscopy observations demonstrating that a few normal (PEP51-negative) test cells reside in the aggregates of PEP51-positive apoptotic test cells of early stage III follicles. Furthermore, transfection of the PEP51 gene into COS-7 cells and HEK293MSR cells resulted in activation of caspase-3/7, providing evidence that PEP51 induces apoptotic signaling. Collectively, these results showed the existence of species-specific ovarian peptide-driven cell metabolism in Ciona follicle development. Consistent with the phylogenetic position of Ciona as the closest sister group of vertebrates, the present study sheds new light on the molecular and functional diversity of the regulatory systems of follicle development in the Chordata.
Study on the effect of waveform film holes on film cooling efficiency
Authors: Qian Cheng , Wang Mingwei , Yang Weihua , Liu Yuang , Zhang Beixuan
Published: October 2023

In order to improve the film cooling efficiency of the cooling gas on the hot side wall of the plate, the flow field, temperature field and the average film cooling efficiency of the cylindrical hole, rectangular hole and waveform hole near the wall were compared and analyzed by numerical calculation method. Compared with cylindrical holes, the average spanwise film cooling efficiency of rectangular hole is improved by 100%, and the average spanwise film cooling efficiency of waveform hole is improved by 130%. In addition, the effects of the amplitude A of the waveform hole and the initial phase ϕ on the cooling efficiency are compared and analyzed. The results show that: Within the scope of this study, when the blowing ratio M = 1, lifting the initial phase ϕ of the waveform hole can effectively improve the film cooling efficiency of the cooling gas on the wall. When the amplitude A of the waveform hole is raised, the film cooling efficiency of the cooling gas on the wall will first increase and then decrease, reaching the maximum at the amplitude A = 0.4D. At low blowing ratio, the geometric structure of waveform hole has little influence on the cooling effect of wall surface. Under high blowing ratio, when the geometric structure of waveform hole is changed, the influence of secondary flow on the average spanwise cooling efficiency of wall surface is great.
Identifying potential DNA methylation markers for the detection of esophageal cancer in plasma
Authors: Pei Bing , Zhao Guodong , Geng Zhixin , Wang Yue , Wang Menglin , Wang Xiaomei , Xiong Shangmin , Zheng Minxue
Published: October 2023

Background: Esophageal cancer (EC) is a leading cause of cancer-related deaths in China, with the 5-year survival rate reaching less than 30%, because most cases were diagnosed and treated at the advanced stage. However, there is still a lack of low-cost, efficient, and accurate non-invasive methods for the early detection of EC at present.

Methods: A total of 48 EC plasma and 101 control plasma samples were collected in a training cohort from 1 January 2021 to 31 December 2021, and seven cancer-related DNA methylation markers (ELMO1, ZNF582, FAM19A4, PAX1, C13orf18, JAM3 and TERT) were tested in these samples to select potential markers. In total, 20 EC, 10 gastric cancer (GC), 10 colorectal cancer (CRC), and 20 control plasma samples were collected in a validation cohort to evaluate the two-gene panel.

Results:ZNF582, FAM19A4, JAM3, or TERT methylation in plasma was shown to significantly distinguish EC and control subjects (p < 0.05), and the combination of ZNF582 and FAM19A4 methylation was the two-gene panel that exhibited the best performance for the detection of EC with 60.4% sensitivity (95% CI: 45.3%–73.9%) and 83.2% specificity (95% CI: 74.1%–89.6%) in the training cohort. The performance of this two-gene panel showed no significant difference between different age and gender groups. When the two-gene panel was combined with CEA, the sensitivity for EC detection was further improved to 71.1%. In the validation cohort, the sensitivity of the two-gene panel for detecting EC, GC, and CRC was 60.0%, 30.0%, and 30.0%, respectively, with a specificity of 90.0%.

Conclusion: The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers.
LncRNA MALAT1/microRNA-30b axis regulates macrophage polarization and function
Authors: Ahmad Imran , Naqvi Raza Ali , Valverde Araceli , Naqvi Afsar R.
Published: October 2023

Macrophages (Mφ) are long-lived myeloid cells that can polarize towards the proinflammatory M1 or proresolving M2 phenotype to control diverse biological processes such as inflammation, tissue damage, and regeneration. Noncoding RNA are a class of nonprotein-coding transcriptome with numerous interdependent biological roles; however, their functional interaction in the regulation of Mφ polarization and immune responses remain unclear. Here, we show antagonistic relationship between lncRNA (MALAT1) and microRNA (miR-30b) in shaping macrophage polarization and immune functions. MALAT1 expression displays a time-dependent induction during Mφ differentiation and, upon challenge with TLR4 agonist (E. coli LPS). MALAT1 knockdown promoted the expression of M2Mφ markers without affecting M1Mφ markers, suggesting that MALAT1 favors the M1 phenotype by suppressing M2 differentiation. Compared to the control, MALAT1 knockdown resulted in reduced antigen uptake and processing, bacterial phagocytosis, and bactericidal activity, strongly supporting its critical role in regulating innate immune functions in Mφ. Consistent with this, MALAT1 knockdown showed impaired cytokine secretion upon challenge with LPS. Importantly, MALAT1 exhibit an antagonistic expression pattern with all five members of the miR-30 family during M2 Mφ differentiation. Dual-luciferase assays validated a novel sequence on MALAT1 that interacts with miR-30b, a microRNA that promotes the M2 phenotype. Phagocytosis and antigen processing assays unequivocally demonstrated that MALAT1 and miR-30b are functionally antagonistic. Concurrent MALAT1 knockdown and miR-30b overexpression exhibited the most significant attenuation in both assays. In human subjects with periodontal disease and murine model of ligature-induced periodontitis, we observed higher levels of MALAT1, M1Mφ markers and downregulation of miR-30b expression in gingival tissues suggesting a pro-inflammatory function of MALAT1 in vivo. Overall, we unraveled the role of MALAT1 in Mφ polarization and delineated the underlying mechanism of its regulation by involving MALAT-1-driven miR-30b sequestration.
Von Economo neurons as a specialized neuron class of the human cerebral cortex
Authors: Petanjek Zdravko , Banovac Ivan , Sedmak Dora , Prkačin Matija Vid , Hladnik Ana
Published: October 2023

By studying human cortical cytoarchitecture, von Economo noticed large spindle-shaped-neurons within layer Vb in the anterior-cingulate and fronto-insular cortex. Those neurons had such extremely elongated stick-like or corkscrew-like soma shape that appeared to him as a pathological alteration. Eventually, he realized that this was a specialized-type of neuron which he described as distinct from the main cortical cell populations, including the commonly found spindle cells. Data from recent studies suggest that specialized-stick-corkscrew-neurons may have first developed in the fronto-insular cortex before the division of hominids and Old World monkeys, and that they have become abundant in the anterior-cingulate cortex only in the hominid line. Golgi analysis found that they have distinctive somato-dendritic morphology with a characteristic very distal position of their axon origin. Many additional studies claimed to find cells similar to the specialized cells described by von Economo in other non-primate species, even in functionally unrelated cortical regions and layers. However, these studies did not provide sufficient evidence that the cells they described are indeed distinct from common spindle-shaped-neurons, and that they truly correspond to the specialized-stick-corkscrew-cells described by von Economo. We believe that present evidence primarily supports the presence of specialized-stick-corkscrew-neurons in hominids, with a seeming increase in their number in humans compared to other primates. The functional significance of such neuronal specialization within specific areas of the human cerebral cortex remains to be elucidated.
Chromosome-level genome assembly of Patagonian moray cod (Muraenolepis orangiensis) and immune deficiency of major histocompatibility complex (MHC) class II
Authors: Kim Jinmu , Lee Seung Jae , Jo Euna , Choi Eunkyung , Cho Minjoo , Choi Soyun , Kim Jeong-Hoon , Park Hyun
Published: October 2023

The Patagonian moray cod, Muraenolepis orangiensis, belongs to the family Muraenolepididae and is the sole order of Gadiformes that inhabits the temperate and cold waters of the southern hemisphere. One of the features of the Gadiformes order is that they have a remarkably unique immune gene repertoire that influences innate and adaptive immunity, and they lack major histocompatibility complex (MHC) class II, invariant chains (CD74), and CD4 genes. In this study, a high-quality chromosome-level genome assembly was constructed, resulting in a final assembled genome of 893.75 Mb, with an N50 scaffold length of 30.07 Mb and the longest scaffold being 39.77 Mb. Twenty-five high-quality pseudochromosomes were assembled, and the complete BUSCO rate was 93.4%. A total of 34,553 genes were structurally annotated, and 27,691 genes were functionally annotated. Among the 10 primary genes involved in MHC class II, only two ERAP1 genes and one AIRE gene were identified through the genome study. Although no specific reason for the MHC class II deficiency has been identified, it has been shown that the toll-like receptors (TLRs), which are significant to the innate immune response, are significantly expanded in M. orangiensis. A total of 44 TLRs have been identified, with 32 TLR13 genes distributed evenly on six different pseudochromosomes. This study is the first to reveal the whole genome of a Muraenolepididae family and provides valuable insights into the potential rationale for the MHC class II deficiency in a Gadiformes fish species.
An integrated machine learning predictive scheme for longitudinal laboratory data to evaluate the factors determining renal function changes in patients with different chronic kidney disease stages
Authors: Tsai Ming-Hsien , Jhou Mao-Jhen , Liu Tzu-Chi , Fang Yu-Wei , Lu Chi-Jie
Published: October 2023

Background and objectives

Chronic kidney disease (CKD) is a global health concern. This study aims to identify key factors associated with renal function changes using the proposed machine learning and important variable selection (ML&IVS) scheme on longitudinal laboratory data. The goal is to predict changes in the estimated glomerular filtration rate (eGFR) in a cohort of patients with CKD stages 3–5.

Design

A retrospective cohort study.

Setting and participants

A total of 710 outpatients who presented with stable nondialysis-dependent CKD stages 3–5 at the Shin-Kong Wu Ho-Su Memorial Hospital Medical Center from 2016 to 2021.

Methods

This study analyzed trimonthly laboratory data including 47 indicators. The proposed scheme used stochastic gradient boosting, multivariate adaptive regression splines, random forest, eXtreme gradient boosting, and light gradient boosting machine algorithms to evaluate the important factors for predicting the results of the fourth eGFR examination, especially in patients with CKD stage 3 and those with CKD stages 4–5, with or without diabetes mellitus (DM).

Main outcome measurement

Subsequent eGFR level after three consecutive laboratory data assessments.

Results

Our ML&IVS scheme demonstrated superior predictive capabilities and identified significant factors contributing to renal function changes in various CKD groups. The latest levels of eGFR, blood urea nitrogen (BUN), proteinuria, sodium, and systolic blood pressure as well as mean levels of eGFR, BUN, proteinuria, and triglyceride were the top 10 significantly important factors for predicting the subsequent eGFR level in patients with CKD stages 3–5. In individuals with DM, the latest levels of BUN and proteinuria, mean levels of phosphate and proteinuria, and variations in diastolic blood pressure levels emerged as important factors for predicting the decline of renal function. In individuals without DM, all phosphate patterns and latest albumin levels were found to be key factors in the advanced CKD group. Moreover, proteinuria was identified as an important factor in the CKD stage 3 group without DM and CKD stages 4–5 group with DM.

Conclusion

The proposed scheme highlighted factors associated with renal function changes in different CKD conditions, offering valuable insights to physicians for raising awareness about renal function changes.
Ticks are unlikely to play a role in leprosy transmission in the Comoros (East Africa) as they do not harbour M. leprae DNA
Authors: Krausser Lena , Chauvaux Elien , Van Dyck-Lippens Magalie , Yssouf Amina , Assoumani Younoussa , Tortosa Pablo , de Jong Bouke Catherine , Braet Sofie Marijke
Published: October 2023

Introduction

Leprosy, one of the oldest known human diseases, continues to pose a global challenge for disease control due to an incomplete understanding of its transmission pathways. Ticks have been proposed as a potential contributor in leprosy transmission due to their importance as vectors for other infectious diseases.

Methods

In 2010, a sampling of ticks residing on cattle was conducted on the islands Grande Comore, Anjouan, and Mohéli which constitute the Union of the Comoros where leprosy remains endemic. To investigate the potential role of ticks as a vector in transmission of leprosy disease, molecular analyses were conducted.

Results

Out of the 526 ticks analysed, none were found to harbour Mycobacterium leprae DNA, as determined by a quantitative polymerase chain reaction (qPCR) assay targeting a family of dispersed repeats (RLEP) specific to M. leprae.

Discussion

Therefore, our results suggest that in the Union of the Comoros, ticks are an unlikely vector for M. leprae.
Conserved core microbiota in managed and free-ranging Loxodonta africana elephants
Authors: Thorel Milan , Obregon Dasiel , Mulot Baptiste , Maitre Apolline , Mateos-Hernandez Lourdes , Moalic Pierre-Yves , Wu-Chuang Alejandra , Cabezas-Cruz Alejandro , Leclerc Antoine
Published: October 2023

The gut microbiota plays a crucial role in animal health and homeostasis, particularly in endangered species conservation. This study investigated the fecal microbiota composition of European captive-bred African savanna elephants (Loxodonta africana) housed in French zoos, and compared it with wild African savanna elephants. Fecal samples were collected and processed for DNA extraction and amplicon sequencing of the 16S rRNA gene. The analysis of α and β diversity revealed significant effects of factors such as diet, daily activity, and institution on microbiota composition. Specifically, provision of branches as part of the diet positively impacted microbiota diversity. Comparative analyses demonstrated distinct differences between captive and wild elephant microbiomes, characterized by lower bacterial diversity and altered co-occurrence patterns in the captive population. Notably, specific taxa were differentially abundant in captive and wild elephants, suggesting the influence of the environment on microbiota composition. Furthermore, the study identified a core association network shared by both captive and wild elephants, emphasizing the importance of certain taxa in maintaining microbial interactions. These findings underscore the impact of environment and husbandry factors on elephant gut microbiota, highlighting the benefits of dietary enrichment strategies in zoos to promote microbiome diversity and health. The study contributes to the broader understanding of host-microbiota interactions and provides insights applicable to conservation medicine and captive animal management.
Intracellular traffic and polarity in brain development
Authors: Polenghi Martina , Taverna Elena
Published: October 2023

Neurons forming the human brain are generated during embryonic development by neural stem and progenitor cells via a process called neurogenesis. A crucial feature contributing to neural stem cell morphological and functional heterogeneity is cell polarity, defined as asymmetric distribution of cellular components. Cell polarity is built and maintained thanks to the interplay between polarity proteins and polarity-generating organelles, such as the endoplasmic reticulum (ER) and the Golgi apparatus (GA). ER and GA affect the distribution of membrane components and work as a hub where glycans are added to nascent proteins and lipids. In the last decades our knowledge on the role of polarity in neural stem and progenitor cells have increased tremendously. However, the role of traffic and associated glycosylation in neural stem and progenitor cells is still relatively underexplored. In this review, we discuss the link between cell polarity, architecture, identity and intracellular traffic, and highlight how studies on neurons have shaped our knowledge and conceptual framework on traffic and polarity. We will then conclude by discussing how a group of rare diseases, called congenital disorders of glycosylation (CDG) offers the unique opportunity to study the contribution of traffic and glycosylation in the context of neurodevelopment.
Distinctive biophysical features of human cell-types: insights from studies of neurosurgically resected brain tissue
Authors: Chameh Homeira Moradi , Falby Madeleine , Movahed Mandana , Arbabi Keon , Rich Scott , Zhang Liang , Lefebvre Jérémie , Tripathy Shreejoy J. , De Pittà Maurizio , Valiante Taufik A.
Published: October 2023

Electrophysiological characterization of live human tissue from epilepsy patients has been performed for many decades. Although initially these studies sought to understand the biophysical and synaptic changes associated with human epilepsy, recently, it has become the mainstay for exploring the distinctive biophysical and synaptic features of human cell-types. Both epochs of these human cellular electrophysiological explorations have faced criticism. Early studies revealed that cortical pyramidal neurons obtained from individuals with epilepsy appeared to function “normally” in comparison to neurons from non-epilepsy controls or neurons from other species and thus there was little to gain from the study of human neurons from epilepsy patients. On the other hand, contemporary studies are often questioned for the “normalcy” of the recorded neurons since they are derived from epilepsy patients. In this review, we discuss our current understanding of the distinct biophysical features of human cortical neurons and glia obtained from tissue removed from patients with epilepsy and tumors. We then explore the concept of within cell-type diversity and its loss (i.e., “neural homogenization”). We introduce neural homogenization to help reconcile the epileptogenicity of seemingly “normal” human cortical cells and circuits. We propose that there should be continued efforts to study cortical tissue from epilepsy patients in the quest to understand what makes human cell-types “human”.
Study protocol of a phase II clinical trial evaluating the efficacy of neoadjuvant intraperitoneal and systemic albumin-bound paclitaxel combined with camrelizumab and S-1 in the treatment of patients with exfoliative cell-positive gastric cancer
Authors: Lv Jingxia , Wu Jiaxiang , Wu Haotian , Ding Ping’an , Guo Honghai , Yang Peigang , Tian Yuan , Liu Yang , Zhao Qun
Published: October 2023

Background

Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients.

Methods/design

This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification.

Discussion

This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner.

Clinical trial registration

http://clinicaltrials.gov/, identifier NCT05410847.
Use and accuracy of decision support systems using artificial intelligence for tumor diseases: a systematic review and meta-analysis
Authors: Oehring Robert , Ramasetti Nikitha , Ng Sharlyn , Roller Roland , Thomas Philippe , Winter Axel , Maurer Max , Moosburner Simon , Raschzok Nathanael , Kamali Can , Pratschke Johann , Benzing Christian , Krenzien Felix
Published: October 2023

Background

For therapy planning in cancer patients multidisciplinary team meetings (MDM) are mandatory. Due to the high number of cases being discussed and significant workload of clinicians, Clinical Decision Support System (CDSS) may improve the clinical workflow.

Methods

This review and meta-analysis aims to provide an overview of the systems utilized and evaluate the correlation between a CDSS and MDM.

Results

A total of 31 studies were identified for final analysis. Analysis of different cancers shows a concordance rate (CR) of 72.7% for stage I-II and 73.4% for III-IV. For breast carcinoma, CR for stage I-II was 72.8% and for III-IV 84.1%, P≤ 0.00001. CR for colorectal carcinoma is 63% for stage I-II and 67% for III-IV, for gastric carcinoma 55% and 45%, and for lung carcinoma 85% and 83% respectively, all P>0.05. Analysis of SCLC and NSCLC yields a CR of 94,3% and 82,7%, P=0.004 and for adenocarcinoma and squamous cell carcinoma in lung cancer a CR of 90% and 86%, P=0.02.

Conclusion

CDSS has already been implemented in clinical practice, and while the findings suggest that its use is feasible for some cancers, further research is needed to fully evaluate its effectiveness.
The neutrophil-to-lymphocyte ratio as a new prognostic factor in cancers: a narrative review
Authors: Heshmat-Ghahdarijani Kian , Sarmadi Vida , Heidari Afshin , Falahati Marvasti Alireza , Neshat Sina , Raeisi Sina
Published: October 2023

The increasing incidence of cancer globally has highlighted the significance of early diagnosis and improvement of treatment strategies. In the 19th century, a connection was made between inflammation and cancer, with inflammation recognized as a malignancy hallmark. The neutrophil-to-lymphocyte ratio (NLR), calculated from a complete blood count, is a simple and accessible biomarker of inflammation status. NLR has also been proven to be a prognostic factor for various medical conditions, including mortality classification in cardiac patients, infectious diseases, postoperative complications, and inflammatory states. In this narrative review, we aim to assess the prognostic potential of NLR in cancer. We will review recent studies that have evaluated the association between NLR and various malignancies. The results of this review will help to further understand the role of NLR in cancer prognosis and inform future research directions. With the increasing incidence of cancer, it is important to identify reliable and accessible prognostic markers to improve patient outcomes. The study of NLR in cancer may provide valuable insights into the development and progression of cancer and inform clinical decision-making.
Case Report: Exceptional response to nivolumab plus cabozantinib in a patient with extrarenal clear cell renal cell carcinoma
Authors: Jansen Caroline S. , Choi Yujin , Evans Sean T. , Greenwald Rachel , Behnke Joseph A. , Hartman Caitlin , Kissick Haydn , Harik Lara R. , Bilen Mehmet Asim
Published: October 2023

Extrarenal clear cell renal cell carcinoma (eccRCC) is a rare type of RCC that arises in areas other than the kidney. Given its rarity, consensus guidelines for optimal treatment of eccRCC have not been established, and the literature is lacking any reports of patient response to systemic therapy and any reports of administration of immunotherapy to patients with ecRCC. Here, we present the case of a patient in their 60s with eccRCC arising in the spleen. The patient underwent splenic resection and then received systemic therapy, due to disease recurrence, with a combination of immunotherapy (IO) and tyrosine kinase inhibitor targeted therapy (VEGF-TKI). The patient had an excellent and durable response to this therapeutic regimen with minimal adverse effects, completing 2 years of therapy of nivolumab and cabozantinib. At the time of this report, the disease remains stable. This case demonstrates that combination therapy with IO+VEGF-TKI represents a reasonable and well-tolerated treatment option with activity in eccRCC and reveals interesting correlative data, including nests of stem-like CD8+T-cell infiltration in tumor tissue, which provide important biological context to this patient’s exceptional therapeutic response.
A practical guide to prescribing sublingual immunotherapy tablets in North America for pediatric allergic rhinoconjunctivitis: an injection-free allergy immunotherapy option
Authors: Blaiss Michael , DuBuske Lawrence , Nolte Hendrik , Opstrup Morten , Rance Karen
Published: October 2023

Allergic rhinoconjunctivitis (ARC) is a common disease that affects individuals of all ages. Pediatricians may be the first (and only) point of care for children with ARC. Sublingual immunotherapy (SLIT)-tablets are a convenient at-home, injection-free allergy immunotherapy option that can be used for the treatment of ARC. This paper provides a practical guide for pediatricians to aid in prescribing SLIT-tablets to children with ARC in North America. Topics include a summary of the available SLIT-tablets and their efficacy and safety, guidance on when SLIT-tablets are an appropriate option, and how to diagnose ARC and identify culprit allergens. Practical guidance is also provided through a proposed decision tree, a prescribing checklist and prescribing procedures, and suggested follow-up assessments.
Approach to suspected donor-derived infections
Authors: Bahakel Hannah Kinard , Pellet Madan Rebecca , Danziger-Isakov Lara
Published: October 2023

Prevention of donor-derived disease among pediatric solid organ transplant recipients requires judicious risk-benefit assessment. Comprehensive guidelines outline specific donor risk factors and post-transplant monitoring strategies to prevent and mitigate transmission of HIV, hepatitis B, and hepatitis C. However, elimination of unanticipated donor-derived infections remains challenging. The objectives of this review are to (1) define risk of anticipated vs. unanticipated disease transmission events in pediatric solid organ transplant recipients; (2) discuss donor presentations that confer greater risk of unanticipated disease transmission; (3) develop a matrix for consideration of donor acceptance; and (4) discuss limitations and future directions for donor screening. Although solid organ transplant confers inherent risk of infection transmission, the risk of significant disease transmission events may be mitigated by a comprehensive approach including donor assessment, consideration of recipient need, post-transplant monitoring, and early intervention.