bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factor screening and prediction modeling of gastrointestinal adverse reactions caused by GLP-1RAs
Authors: Gao Rui , Li Yue , Li Anan , Zhou Penglin , Zong Huiying , Li Yan
Published: December 2024

Objective

This study aimed to explore the risk factors for gastrointestinal side effects (GISEs) in patients with type 2 diabetes mellitus (T2DM) during treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) based on real-world data and to develop a prediction model for GLP-1RA-related GISEs.

Methods

A total of 855 patients who attended the First Affiliated Hospital of Shandong First Medical University from January 2020 to May 2023 were selected as the study participants, who were divided into the training set (598 cases) and the validation set (297 cases) using a simple random sampling method at a ratio of 7:3. The general information and biochemical indicators of the participants were collected to assess the risk factors for GLP-1RA-related GISEs, and multifactorial logistic regression analysis was used to obtain the best predictors. A nomogram prediction model was constructed. The Hosmer–Lemeshow test was used to assess the differentiation and calibration of the nomogram model, and decision curve analysis (DCA) was used to evaluate the clinical utility of the model.

Results

Age, gender, history of gastrointestinal disorders, and number of combined oral medications were found as risk factors for the occurrence of GISEs in patients with T2DM using GLP-1RAs (p < 0.05). The nomogram prediction model based on these four factors had good discriminability (AUC values of the training and validation sets of 0.855 and 0.836, respectively) and accuracy (Hosmer–Lemeshow test: p > 0.05 for the validation set). DCA showed that the prediction model curve had clinical utility in the threshold probability interval of >5%.

Conclusions

The established nomogram model has an excellent predictive effect on GISEs induced by GLP-1RAs in patients with T2DM.
Heat wave: a new characterization in terms of energy
Authors: Barrios-Barocio Alejandra , Peralta Oscar , Ochoa-Moya Carlos A. , Luyando Elda , Espinosa-Fuentes María de la Luz
Published: December 2024

Heat waves (HW) are prolonged periods of excessively hot weather that can cause severe socioeconomic and environmental impacts. This study aims to evaluate the differences in stored heat and turbulent flux partitioning during a heat wave event in Mexico City, using observations from an eddy covariance tower during the period from 14 June to 21 June 2023. During this period, net radiation (Rn) and sensible heat flux (H) increased significantly, particularly from noon to evening, reflecting stable atmospheric conditions. The air temperature showed a noticeable increase in the afternoon and evening, whereas absolute humidity decreased. We found that during the heat wave, the Bowen ratio (β) increased by 80% during daylight hours and 65% over a full 24-hour period compared to the pre-heat wave period. This heat release at night prolonged warm conditions, intensifying heat stress. The partitioning of net radiation for latent heat (LE), sensible heat (H), and heat storage (ΔQs) showed significant changes; during the heat wave, 51% of Rn was allocated to H and 34% to ΔQs, compared to pre-heat wave values of 49% and 27%, respectively. This study introduces a new characterization of heat waves in terms of energy, emphasizing the significant shifts in energy flux partitioning and storage. The new characterization highlights the critical role of urban heat storage and its release in exacerbating heat stress during and after heat wave events. This approach provides a comprehensive understanding of the energy dynamics during heat waves, which is essential for developing effective mitigation strategies to combat the adverse effects of extreme heat in urban environments.
Using triaxial accelerometry to detect hunts and kills by African wild dogs
Authors: Redcliffe James , Creel Scott , Goodheart Ben , Reyes de Merkle Johnathan , Matsushima Stephani S. , Mungolo Michelo , Kabwe Ruth , Kaseketi Emmanuel , Donald Will , Kaluka Adrian , Chifunte Clive , Becker Matthew S. , Wilson Rory
Published: December 2024

Most large carnivores feed on prey infrequently and may expend large amounts of energy to locate, capture and kill their prey. This makes them probabilistically vulnerable to fluctuating rates of energy acquisition over time, especially within the increasingly human-altered landscapes that dominate their remaining range. Consequently, quantifying their hunting behaviors and success rates is critical, yet direct observation of these events is rarely feasible. We theorized that we could determine prey pursuit and capture in African wild dogs (Lycaon pictus) using a mechanistic approach by constructing Boolean algorithms applied to accelerometer data derived from collar-mounted tags. Here, we used this method and then iteratively improved algorithms by testing them on observed hunts and kills of collared packs. Using this approach on 47 days of acceleration from three wild dogs in three packs, we identified 29 hunts with 10 kills, all of which were confirmed by direct observation except for a single kill. Our results demonstrate that hunting effort and success can largely be determined from acceleration data using a mechanistic approach. This is particularly valuable when such behaviors are rarely quantified and offers a template for research on foraging in canid species, while also contributing to the expanding body of literature that employs similar methods to quantify hunting in large carnivores.
The win-stay, lose-switch renesting strategy of a territorial bird endemic to subtropical salt marshes
Authors: Sandretti-Silva Giovanna , Corrêa Leandro , Amirati Mariana , Laurino Ivan Rodrigo Abrão , Passos Fernando Camargo , Pie Marcio R. , Bornschein Marcos R.
Published: December 2024

Introduction

The “win-stay, lose-switch” (WSLS) strategy used by birds involves decisions to maintain or alter the characteristics of the subsequent nest according to the outcome of the previous one. In salt marshes, nest failure occurs due to flooding, predation, or tipping, creating a trade-off for nest placement: it should be low enough to avoid predators from above and tipping by the wind, and high enough to avoid flooding. In salt marshes of Southern Brazil, predation from above is carried out by rails that also prey on nests from below, promoting nondirectional pressure capable of neutralizing bird responses. We aim to test the WSLS strategy and to assess its adaptive significance for Formicivora acutirostris, the only thamnophilid endemic to salt marshes. Our general premise is that the adoption of the WSLS strategy would vary in response to the fate of the previous nest, considering also the environment type.

Methods

We evaluated the fate, environment type, height, altitude, and thickness of nests of F. acutirostris in southern Brazil, between 2006 and 2023. We assessed the effects of the nest attributes, tested the adoption of the WSLS strategy, and explored its adaptive significance using generalized linear mixed models. We also examined the influence of factors such as nest environment, nesting timing, and pair age on nest fate and parental behavior.

Results

We studied 98 renesting cases. Flooded nests were at a lower height than predated, tipped, and successful nests, and tipped nests were thicker than flooded and successful nests. Nest heights differed among environment types. The species adopted the WSLS strategy by increasing nest height after flooding, but we do not support its adaptive significance. No additional factors influenced the behavior of the species.

Discussion

Although the adoption of the WSLS strategy by F. acutirostris was confirmed regarding the increase in nest height after flooding, it did not result in a significant increase in reproductive success, suggesting that other pressures, such as predation and tipping, are limiting the adaptive potential of this strategy. We emphasize the threat of the high reproductive failure for the conservation of F. acutirostris and proposes reducing predation pressure as an important conservation strategy.
Seeing through the gray box: an integrated approach to physiological modeling of phytoplankton stoichiometry
Authors: Jones Catriona L. C. , Camps-Castella Judith , Smykala Mike , Sobol Morgan S. , Inomura Keisuke
Published: December 2024

The ‘black boxes’ of ecological stoichiometry, planktonic microbes, have long been recognized to have considerable effects on global biogeochemical cycles. Significant progress has been made in studying these effects and expanding our understanding of microbial stoichiometry. However, the ‘black box’ has not been completely cracked open; there remain gaps in our knowledge of the fate of elements within the phytoplankton cell, and the effect of external processes on nutrient fluxes through their metabolism and into macromolecules and biomass - the eponymous ‘gray box’. In this review paper, we describe the development of an integrative modeling approach that involves a stoichiometrically explicit model of Macromolecular Allocation and Genome-scale Metabolic Analysis (MAGMA) to gain insights into the intra- and extracellular fluxes of nutrients using the cyanobacterium Parasynechococcus marenigrum WH8102 as a target model organism. We then describe an example of the genome-scale resources for P. marenigrum that can be used to build such an integrated modeling tool to see through the gray box of phytoplankton stoichiometry and improve our understanding of the effects of resource supplies and other environmental drivers, especially temperature, on C:N:P demand, acquisition, and allocation at the cellular level.
UDP-glucuronosyltransferases 2A3 as a biomarker for ulcerative colitis and colon cancer
Authors: Chen Hao
Published: December 2024

Background

Ulcerative colitis has a serious impact on the quality of life of patients and is more likely to progress to colon cancer. Therefore, early diagnosis and timely intervention are of considerable importance.

Methods

Gene expression data of active ulcerative colitis were downloaded from the Gene Expression Omnibus (GEO) database, and genes with significant differential expression were identified. Biochemical markers with diagnostic significance were selected through machine learning methods. The expression differences of the selected markers between colon adenocarcinoma (COAD) and healthy control groups in The Cancer Genome Atlas (TCGA) database were analyzed to evaluate their diagnostic value. In addition, the correlation between the selected markers and clinical indicators, as well as their predictive efficacy for the survival of COAD patients, was explored.

Results

Through machine learning and LASSO regression analysis, UGT2A3 was finally determined as a diagnostic marker for ulcerative colitis. It demonstrated high diagnostic accuracy in both the training set and the external validation set. Furthermore, UGT2A3 was significantly downregulated in COAD tissues compared to normal control tissues. The ROC curve suggested that UGT2A3 could serve as a diagnostic marker for COAD with excellent performance, achieving an AUC of 0.969. Immune infiltration analysis indicated a significant negative correlation between the expression of UGT2A3 and neutrophils. Correlation analysis suggested a link between UGT2A3 and the pathological classification of colon cancer. Survival analysis showed that UGT2A3 is negatively correlated with OS, PPS, and RFS in colon cancer.

Conclusion

The author identified UGT2A3 as a diagnostic marker for ulcerative colitis through bioinformatics methods, and verified its significant downregulation in colon cancer, as well as its predictive role in the survival of COAD patients. These findings suggest that UGT2A3 may serve not only as a diagnostic marker for ulcerative colitis and colon cancer but also as a potential prognostic indicator for colon cancer.
AnchorFCI: harnessing genetic anchors for enhanced causal discovery of cardiometabolic disease pathways
Authors: Ribeiro Adèle H. , Crnkovic Milena , Pereira Jaqueline Lopes , Fisberg Regina Mara , Sarti Flavia Mori , Rogero Marcelo Macedo , Heider Dominik , Cerqueira Andressa
Published: December 2024

Introduction

Cardiometabolic diseases, a major global health concern, stem from complex interactions of lifestyle, genetics, and biochemical markers. While extensive research has revealed strong associations between various risk factors and these diseases, latent confounding and limited causal discovery methods hinder understanding of their causal relationships, essential for mechanistic insights and developing effective prevention and intervention strategies.

Methods

We introduce anchorFCI, a novel adaptation of the conservative Really Fast Causal Inference (RFCI) algorithm, designed to enhance robustness and discovery power in causal learning by strategically selecting and integrating reliable anchor variables from a set of variables known not to be caused by the variables of interest. This approach is well-suited for studies of phenotypic, clinical, and sociodemographic data, using genetic variables that are recognized to be unaffected by these factors. We demonstrate the method’s effectiveness through simulation studies and a comprehensive causal analysis of the 2015 ISA-Nutrition dataset, featuring both anchorFCI for causal discovery and state-of-the-art effect size identification tools from Judea Pearl’s framework, showcasing a robust, fully data-driven causal inference pipeline.

Results

Our simulation studies reveal that anchorFCI effectively enhances robustness and discovery power while handles latent confounding by integrating reliable anchor variables and their non-ancestral relationships. The 2015 ISA-Nutrition dataset analysis not only supports many established causal relationships but also elucidates their interconnections, providing a clearer understanding of the complex dynamics and multifaceted nature of cardiometabolic risk.

Discussion

AnchorFCI holds significant potential for reliable causal discovery in complex, multidimensional datasets. By effectively integrating non-ancestral knowledge and addressing latent confounding, it is well-suited for various applications requiring robust causal inference from observational studies, providing valuable insights in epidemiology, genetics, and public health.
Integration of single-cell and bulk analysis reveals TBXAS1 as a key platelet-related gene causing poor prognosis in osteosarcoma
Authors: Liu Han , Da Wacili , Mu Jianhua , He Xuanhong , Li Zhuangzhuang , Gong Taojun , Wang Jingjing , Min Li , Lu Minxun , Tu Chongqi
Published: December 2024

Background

Platelets are associated with poor prognosis in most tumors, but their specific pathogenic mechanism in osteosarcoma is not yet clear. The objective of this study is to conduct an in-depth analysis of how genes closely related to platelet function impact the prognosis of osteosarcoma patients. We hope that through this research, we can uncover the potential mechanisms of these genes in the development and progression of osteosarcoma, thereby providing new therapeutic strategies and theoretical foundations for improving the prognosis of osteosarcoma patients.

Method

We collected the blood routine test data of patients who were initially diagnosed with osteosarcoma at the Department of Bone Tumors, West China Hospital, from January 2012 to January 2022. By applying the LASSO-COX regression analysis, a statistical method, we found that the platelet count is associated with the prognosis of osteosarcoma patients. To further explore this relationship, we obtained single-cell data and bulk RNA data of osteosarcoma patients from the TARGET database and GEO database, respectively. By analyzing these data, we revealed at the transcriptomic level how platelets contribute to the poor prognosis in osteosarcoma patients.

Result

Platelets are associated with the prognosis of osteosarcoma patients (HR = 3.9, 95% CI = 1.9–8.1, P < 0.001). Through the analysis of transcriptomic data from the TARGET database and GEO database, we found significant heterogeneity in tumor-specific pathways and immune infiltration under different platelet-related gene expression patterns. Among these, TBXAS1 was identified as a key gene that affects the prognosis of osteosarcoma patients. In addition, single-cell data analysis showed that the platelet-related gene TBXAS1 is mainly enriched in macrophages, and markers of macrophages are significantly associated with poor prognosis in osteosarcoma patients.

Conclusion

TBXAS1 is a key platelet-related gene that leads to poor prognosis in osteosarcoma, and this gene may affect the prognosis of osteosarcoma patients by interacting with macrophages.
Family planning utilization among postpartum women in the Bule Hora District, southern Ethiopia
Authors: Sirage Nurye , Desalegn Zewuditu , Wako Wako Golicha , Yimer Ali , Bizuneh Fassikaw Kebede , Feleke Sefineh Fenta , Yesuf Adem , Beyene Belda Negesa
Published: December 2024

Background

Contraception use remains low in Ethiopia, particularly within the first year after childbirth. While some women might have medical conditions that limit their contraceptive options, the primary obstacle to wider family planning adoption is not a specific health problem. Instead, it is the lack of equitable access to high-quality family planning services. This barrier significantly hinders women's ability to make informed decisions about their reproductive health. This study examines postpartum family planning utilization and its associated factors among postpartum mothers in the Bule Hora District.

Methods

We conducted a community-based cross-sectional study. A multistage sampling technique was employed to recruit a total of 630 women who had given birth. To collect the data, structured, standardized, and pretested questionnaires were used, and the collected data were coded and entered into Epi-data version 4.6. The data were analyzed using SPSS version 25. Both bivariable and multivariable logistic regressions were used to identify factors associated with postpartum family planning utilization.

Results

The study found that 71.3% of women utilized postpartum family planning. Significant associations were found between postpartum family planning utilization and various factors, including counseling on family planning during pregnancy [adjusted odds ratio (AOR) = 1.79, 95% confidence interval (CI) 1.61–2.82], delivery (AOR = 2.62, 95% CI 1.56–4.38), and the postpartum period (AOR = 2.71, 95% CI 1.75–4.21). Women who resumed sexual activity after birth (AOR = 1.92, 95% CI 1.25–2.96), and who had at least four antenatal care visits (AOR = 3.09, 95% CI 1.61–5.92) were also more likely to use postpartum family planning. Women with grand multiparity were 69% less likely to use family planning methods than primiparous women (AOR = 0.31, 95% CI 0.13–0.73).

Conclusion

Postpartum family planning use in this study was higher than the national average. Factors such as parity; counseling during the pregnancy, delivery, and postpartum periods; and early resumption of sexual activity were linked to increased contraceptive use. These findings suggest that enhanced counseling during antenatal, delivery, and postnatal care could significantly increase contraceptive use.
Understanding the development of tuberculous granulomas: insights into host protection and pathogenesis, a review in humans and animals
Authors: Lyu Jiwon , Narum Drew E. , Baldwin Susan L. , Larsen Sasha E. , Bai Xiyuan , Griffith David E. , Dartois Véronique , Naidoo Threnesan , Steyn Adrie J. C. , Coler Rhea N. , Chan Edward D.
Published: December 2024

Granulomas, organized aggregates of immune cells which form in response to Mycobacterium tuberculosis (Mtb), are characteristic but not exclusive of tuberculosis (TB). Despite existing investigations on TB granulomas, the determinants that differentiate host-protective granulomas from granulomas that contribute to TB pathogenesis are often disputed. Thus, the goal of this narrative review is to help clarify the existing literature on such determinants. We adopt the a priori view that TB granulomas are host-protective organelles and discuss the molecular and cellular determinants that induce protective granulomas and those that promote their failure. While reports about protective TB granulomas and their failure may initially seem contradictory, it is increasingly recognized that either deficiencies or excesses of the molecular and cellular components in TB granuloma formation may be detrimental to the host. More specifically, insufficient or excessive expression/representation of the following components have been reported to skew granulomas toward the less protective phenotype: (i) epithelioid macrophages; (ii) type 1 adaptive immune response; (iii) type 2 adaptive immune response; (iv) tumor necrosis factor; (v) interleukin-12; (vi) interleukin-17; (vii) matrix metalloproteinases; (viii) hypoxia in the TB granulomas; (ix) hypoxia inducible factor-1 alpha; (x) aerobic glycolysis; (xi) indoleamine 2,3-dioxygenase activity; (xii) heme oxygenase-1 activity; (xiii) immune checkpoint; (xiv) leukotriene A4 hydrolase activity; (xv) nuclear-factor-kappa B; and (xvi) transforming growth factor-beta. Rather, more precise and timely coordinated immune responses appear essential for eradication or containment of Mtb infection. Since there are several animal models of infection with Mtb, other species within the Mtb complex, and the surrogate Mycobacterium marinum – whether natural (cattle, elephants) or experimental (zebrafish, mouse, guinea pig, rabbit, mini pig, goat, non-human primate) infections – we also compared the TB granulomatous response and other pathologic lung lesions in various animals infected with one of these mycobacteria with that of human pulmonary TB. Identifying components that dictate the formation of host-protective granulomas and the circumstances that result in their failure can enhance our understanding of the macrocosm of human TB and facilitate the development of novel remedies – whether they be direct therapeutics or indirect interventions – to efficiently eliminate Mtb infection and prevent its pathologic sequelae.
Generation of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation
Authors: Matsumoto Yusuke , Honda Tomoko , Yasui Fumihiko , Endo Akinori , Sanada Takahiro , Toyama Sakiko , Takagi Asako , Munakata Tsubasa , Kono Risa , Yamaji Kenzaburo , Yamamoto Naoki , Saeki Yasushi , Kohara Michinori
Published: December 2024

Introduction

To analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.

Methods

We conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.

Results

In this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication. An early circulating strain of SARS-CoV-2 caused the most severe weight loss when compared to SARS-CoV-2 variants such as Alpha, Beta and Gamma, although histopathological findings, viral replication, and cytokine expression characteristics were comparable

Discussion

We found that a distinct proteome of an early circulating strain infected lung characterized by elevated complement activation and blood coagulation, which were mild in other variants, can contribute to disease severity. Unraveling the specificity of early circulating SARS-CoV-2 strains is important in elucidating the origin of the pandemic.
Chemo-free salvage treatment outperforms traditional chemotherapy in advanced lines of relapsed/refractory subcutaneous panniculitis-like T-cell lymphoma
Authors: Chen Chao , Yin Jingjing , Duan Minghui , Wang Wei , Zhao Danqing , Wei Chong , Jia Congwei , Zhang Wei , Zhou Daobin , Zhang Yan
Published: December 2024

Introduction

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma with a good prognosis, but the optimal treatment for relapsed/refractory (R/R) SPTCL has been rarely discussed.

Methods

This study aims to compare the efficacy of conventional chemotherapy and chemo-free immunomodulatory regimen for R/R SPTCL. We retrospectively reviewed the patients with first relapse or primary refractory SPTCL between September 1997 and October 2020.

Results

A total of 19 patients with R/R SPTCL with a median age of 34 were included. All patient received the first-line chemotherapy-based treatment with a median PFS of 1.8 months. In these patients, 16 received salvage second-line treatment with an ORR of 31.3% and a median TTNT of 3.0 months. 13 of these 16 patients received chemotherapy-based treatment, resulting in a median TTNT of 2.4 months. 2 of these 16 patients received allogeneic hematopoietic stem cell transplantation and achieved long term complete remission (CR). In third-line treatment, 7 patients received chemotherapy-based regimen and 6 received chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. The median TTNT of chemotherapy and chemo-free group were 3.2 months and not reached, respectively.

Discussion

Chemo-free group had a better TTNT than chemotherapy group (p=0.007). The use of chemotherapy-free regimens for R/R SPTCL appears promising and warrants further validation.
Emerging influence of RNA post-transcriptional modifications in the synovial homeostasis of rheumatoid arthritis
Authors: Fatima Madiha , Huang Fengmei , Fu Xiaohong
Published: December 2024

Rheumatoid arthritis (RA) is an important autoimmune disease that affects synovial tissues, accompanied by redness, pain, and swelling as main symptoms, which will limit the quality of daily life and even cause disability. Multiple coupling effects among the various cells in the synovial micro-environment modulate the poor progression and development of diseases. Respectively, synovium is the primary target tissue of inflammatory articular pathologies; synovial hyperplasia, and excessive accumulation of immune cells lead to joint remodelling and destroyed function. In general, epigenetic modification is an effective strategy to regulate dynamic balance of synovial homeostasis. Several typical post-transcriptional changes in cellular RNA can control the post-transcriptional modification of RNA structure. It can inhibit important processes, including degradation of RNA and nuclear translocation. Recent studies have found that RNA modification regulates the homeostasis of the synovial micro-environment and forms an intricate network in the “bone-cartilage-synovium” feedback loop. Aberrant regulation of RNA methylation triggers the pathological development of RA. Collectively, this review summarises recent advanced research about RNA modification in modulating synovial homeostasis by making close interaction among resident synovial macrophages, fibroblasts, T cells, and B cells, which could display the dramatic role of RNA modifications in RA pathophysiological process and perform the promising therapeutic target for treating RA.
Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial
Authors: Xu Guolin , Paglialunga Sabina , Qian Xuchen , Ding Ru , Webster Kenneth , van Haarst Aernout , Engel Caroline , Hui Chin Wai , Lam Lik Hang , Li Weimin , Wu Wai Chung , Rasmussen Scott , Hunt Allen , Leung Shui-on
Published: December 2024

Background

Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.

Methods

Wild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17’s pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.

Results

Animal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.

Conclusion

In the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT05332834.
Case report: A novel third-generation anti-CD19/CD22 CAR T-cells combined with auto-HSCT for relapsed Burkitt lymphoma
Authors: Luo Xiaodan , Chen Ao , Qin Le , Weinkove Robert , Zhao Rong , Ye Ting , Chen Sihui , Tang Jianli , Liu Jianbo , Huang Jiayu , Shi Boyun , Yuan Danyun , Tan Huo , Qin Dajiang , Tang Zhaoyang , Li Peng , Zheng Runhui
Published: December 2024

This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications. This case suggests that combining myeloablative ASCT with tandem anti-CD19/CD22 CAR T cell therapy could be an effective approach for R/R BL, warranting further clinical validation.
Evidence of horizontal transmission of Wolbachia wCcep in rice moths parasitized by Trichogramma chilonis and its persistence across generations
Authors: Lai C. T. , Hsiao Y. T. , Wu Li-Hsin
Published: December 2024

The horizontal transmission of endosymbionts between hosts and parasitoids plays a crucial role in biological control, yet its mechanisms remain poorly understood. This study investigates the dynamics of horizontal transfer of Wolbachia (wCcep) from the rice moth, Corcyra cephalonica, to its parasitoid, Trichogramma chilonis. Through PCR detection and phylogenetic analysis, we demonstrated the presence of identical wCcep strains in both host and parasitoid populations, providing evidence for natural horizontal transmission. To investigate thoroughly, Wolbachia-free colonies were acquired through tetracycline treatment, and the initial density of wCcep in host eggs significantly influences transmission efficiency. High-density wCcep infections led to rapid transmission, with F1 parasitoid titers increasing by as much as 100-fold, while low-density infections exhibited more gradual increases. Additionally, without continuous exposure to infected hosts, wCcep density in T. chilonis diminished over generations. These findings enhance our understanding of Wolbachia’s transfer dynamics and have important implications for developing effective and sustainable biological control strategies using parasitoid wasps, particularly in managing Wolbachia-related pest populations in agricultural systems.
Phytoplankton community composition links to environmental drivers across a fjord to shelf gradient on the central coast of British Columbia
Authors: Del Bel Belluz Justin , Jackson Jennifer M. , Kellogg Colleen T. E. , Peña M. Angelica , Giesbrecht Ian J. W. , Hobson Louis A.
Published: December 2024

Rapid environmental change is altering coastal phytoplankton dynamics and, thereby the productivity of coastal marine food webs. Unfortunately, a paucity of phytoplankton community data hinders the prediction of future conditions in ecologically productive regions such as the coastal northeast Pacific. To help fill this gap, this study characterized phytoplankton communities from 2018 to 2020 across a fjord, channel and shelf station transect on the central coast of British Columbia, Canada. Monthly samples were collected for microscopy-based taxonomy and pigment-based phytoplankton composition (i.e. CHEMTAX and size-fractionated chlorophyll). Correlation analysis was used to investigate drivers of phytoplankton biomass and hierarchical clustering and redundancy analysis highlighted drivers of compositional trends. Spring blooms formed the peak of annual biomass at each station and earlier blooms at the fjord station suggested a sheltering effect from winter wind conditions. Later spring blooms at the channel station coincided with seasonal wind reductions and increased sunlight. Of the six derived compositional clusters, three represented flagellate dominated conditions at all stations: two represented low biomass winter conditions and the third, moderate biomass spring and autumn blooms occurring under nutrient replete conditions. The remaining three clusters were diatom-dominated and spanned much of the growing season. The first diatom cluster represented Skeletonema marinoi dominated samples, many from 2020, observed under moderate nutrient and high stratification and freshwater discharge conditions. The second represented high diatom richness spring bloom conditions at all stations that were associated with nutrient depletion. Finally, the third included 2018 and 2019 summer shelf samples showing harmful Rhizosolenia setigera and Pseudo-nitzschia seriata blooms under high surface water salinity and temperature. These results highlight high spatial-temporal variability and sensitivity of coastal northeast Pacific phytoplankton communities to altered freshwater, temperature and wind dynamics with potential for profound ecosystem level implications.
Reflections on the interpretation and application of the due diligence obligation in international climate litigation: a comparative study of Daniel Billy et al. v. Australia and the COSIS advisory opinion
Authors: Liang Shiqi
Published: December 2024

This article examines the interpretation and implementation of due diligence obligation in international climate litigation and advisory opinions, specifically by comparing Daniel Billy et al. v. Australia and the COSIS Advisory Opinion. It offers insights into the definition of due diligence obligation, the criteria for breach, and the remedies available under various legal frameworks. The due diligence obligation is not solely a direct duty under a specific treaty; it also imposes a positive obligation of conduct that must be evaluated within a broader legal framework. This method facilitates systemic integration. It facilitates the citation of pertinent regulations and precedents from different domains of international law during treaty interpretation. This approach promotes the harmonization and integration of various legal systems. The essay performs a comparative analysis of two cases. It analyses the implementation of the due diligence obligation in the realms of environmental and human rights protection. The emphasis is on the legal responsibility of States about climate change. The paper ultimately outlines the significance of the two instances for the future of international environmental law and the protection of human rights, highlighting the crucial role of due diligence responsibilities in combating climate change.
Nonspecific cervical spine pain/neck pain/in medical personnel of north-eastern Poland—A cross-sectional study
Authors: Citko Anna , Górski Stanisław , Marcinowicz Ludmiła , Mateusz Cybulski , Matylda Sierakowska
Published: December 2024

Both mechanical and psychological overload are inherent to the work of nurses and paramedics, resulting spondylogenic pain.

Aim of the study

To identify potential risk factors influencing the prevalence of non-specific cervical spine pain in professionally active nurses and paramedics.

Material and methods

324 nurses (53.2% of the total) and 285 paramedics (46.8%) were included in the study−609 people in total. The study was carried out using an auditorium survey technique supervised by the researchers. The methods used were: Nordic Musculoskeletal Questionnaire, a spinal pain questionnaire validated according to IEA guidelines, a short version of the IPAQ and the author's survey questionnaire, concerning sociodemographic data, chronic diseases including metabolic syndrome (MetS). A univariate logistic regression model was used in the statistical analysis. The level of statistical significance was taken as p < 0.05.

Results

Recurrent NP was significantly more common in paramedics compared to nurses (29.5 % vs. 9.3 %; p < 0.0001). In a univariate logistic regression model, the risk of NP was significantly increased by: length of service > 15 years (p < 0.024), presence of: low back pain (p < 0.0001), type 2 diabetes (p = 0.013), hypertension (p < 0.001), depression (p < 0.01). Of the modifiable factors, the risk of NP was significantly increased by high physical activity and short sleep <7 h (p < 0.001).
Traumatic renal artery thrombosis: a case report and literature review
Authors: Xia Xiaohua , Zhao Guang , Feng Qiupeng , Guo Zhiqiang , Ma Jin , Yuan Hua
Published: December 2024

Traumatic Renal Artery Thrombosis (TRAT) is an uncommon condition characterized by a low clinical incidence and a lack of specific symptoms, making it highly susceptible to being overlooked or misdiagnosed. This retrospective analysis aims to review the diagnostic and therapeutic approaches applied to a TRAT patient who received successful treatment in the Emergency Medicine Department of the First People’s Hospital of Kunshan. The objective is to enhance clinicians’ comprehension of TRAT, promote early diagnosis and intervention, and ultimately improve patient outcomes.
Genomic analysis, culturing optimization, and characterization of Escherichia bacteriophage OSYSP, previously studied as effective pathogen control on fresh produce
Authors: Yesil Mustafa , Huang En , Yang Xu , Yousef Ahmed E.
Published: December 2024

Advances in bacteriophage genome sequencing and regulatory approvals of some bacteriophages in various applications have renewed interest in these antibacterial viruses as a potential solution to persistent food safety challenges. Here, we analyzed in depth the genome of the previously studied Escherichia bacteriophage OSYSP (phage OSYSP), revealed its application-related characteristics, and optimized its enumeration techniques for facilitating industrial implementation. We previously sequenced phage OSYSP genome completely by combining results from Illumina Miseq and Ion Torrent sequencing platforms and completing the remaining sequence gaps using PCR. Based on the genomics analysis completed herein, phage OSYSP was confirmed as an obligate lytic phage of the Caudoviricetes class. The genome encodes 81 proteins of identifiable functions, including two endolysins and 45 proteins that support host-independent DNA replication, transcription, and repair. Despite its similarities to T5-like phages, unique genome arrangements confirm phage OSYSP’s novelty. The genomic analysis also confirmed the absence of DNA sequences encoding virulence or antibiotic resistance factors. For optimizing phage detection and quantification in the conventional plaque assay, it was observed that decreasing the concentration of agar or agarose, when used as a medium gelling agent, increased phage recovery (p < 0.05), but using agarose resulted in smaller plaque diameters (p < 0.05). Phage OSYSP inactivated pathogenic and non-pathogenic strains of E. coli and some Salmonella enterica serovars, with more pronounced effect against E. coli O157:H7. Phage titers remained fairly unchanged throughout a 24-month storage at 4°C. Incubation for 30 min at 4°C−47°C or pH 4–11 had no significant detrimental effect (p > 0.05) on phage infectivity. In vitro application of phage OSYSP against E. coli O157:H7 EDL933 decreased the pathogen’s viable population by >5.7-log CFU/mL within 80 min, at a multiplicity of infection as low as 0.01. The favorable genome characteristics, combined with improved enumeration methodology, and the proven infectivity stability, make phage OSYSP a promising biocontrol agent against pathogenic E. coli for food or therapeutic applications.
Bibliometric and visual analysis of human microbiome—breast cancer interactions: current insights and future directions
Authors: Zhou Yi , Jiang Min , Li Xiaoyu , Shen Ke , Zong Hui , Lv Qing , Shen Bairong
Published: December 2024

The composition of the gut microbiome differs from that of healthy individuals and is closely linked to the progression and development of breast cancer. Recent studies have increasingly examined the relationship between microbial communities and breast cancer. This study analyzed the research landscape of microbiome and breast cancer, focusing on 736 qualified publications from the Web of Science Core Collection (WoSCC). Publications in this field are on the rise, with the United States leading in contributions, followed by China and Italy. Despite this strong output, the centrality value of China in this field is comparatively low at ninth, highlighting a gap between the quantity of research and its global impact. This pattern is repetitively observed in institutional contributions, with a predominance of Western institutes among the top contributors, underscoring a potential research quality gap in China. Keyword analysis reveals that research hotspots are focused on the effect of microbiome on breast cancer pathogenesis and tumor metabolism, with risk factors and metabolic pathways being the most interesting areas. Publications point to a shift toward anti-tumor therapies and personalized medicine, with clusters such as “anti-tumor” and “potential regulatory agent” gaining prominence. Additionally, intratumor bacteria studies have emerged as a new area of significant interest, reflecting a new direction in research. The University of Helsinki and Adlercreutz H are influential institutions and researchers in this field. Current trends in microbiome and breast cancer research indicate a significant shift toward therapeutic applications and personalized medicine. Strengthening international collaborations and focusing on research quality is crucial for advancing microbiome and breast cancer research.
Effects of two Bacillus velezensis strains isolated from different sources on the growth of Capsicum annum
Authors: Wang Bao , Tan Shimeng , Wu Mingde , Feng Yujie , Yan Wanrong , Yun Qian , Ji Xuncong , Lin Runmao , Zhao Zhixiang
Published: December 2024

Microbial inoculants offer an environmentally friendly approach to enhance plant growth and control disease. In this study, two Bacillus velezensis strains, HKSSLJEBR3 (R3) and Ya-1 were isolated from pepper plant roots and tropical rainforest soil, respectively. Both strains exhibited strong antifungal activity against Fusarium oxysporum f. sp. capsici, with inhibition rates of 48.54 ± 0.66% for R3 and 49.35 ± 1.44% for Ya-1. In greenhouse trials, R3 significantly boosted pepper growth, with a 22.12% increase in plant height, 46.44% more leaves, and 56.29% greater fresh weight. These enhancements were likely due to the strong affinity between R3 and pepper plants. Both strains also improved soil quality, with R3 increasing available potassium (AK) by 5.13% and soil organic matter (SOM) by 4.03%, while Ya-1 showed more significant increases. Metagenomic analysis revealed that both strains altered the rhizosphere microbiome, with R3 promoting Pseudomonas and suppressing Fusarium. These results suggest that the R3 strain has strong potential for enhancing pepper growth, improving soil health, and reshaping the rhizosphere microbiome.
Development of anti-cancer drugs for tumor-associated macrophages: a comprehensive review and mechanistic insights
Authors: Bai Bingjun , Xie Shangzhi , Wang Ya , Wu Fei , Chen Yao , Bian Jia , Gao Xing
Published: December 2024

This review provides an in-depth summary of the development of anti-cancer drugs for tumor-associated macrophages (TAMs), with a particular focus on the development and tissue specialization of macrophages, and factors influencing the polarization of M1 and M2 macrophages, and mechanistic insights underlying the targeting therapeutic approaches. TAMs, pivotal in the tumor microenvironment, exhibit notable plasticity and diverse functional roles. Influenced by the complex milieu, TAMs polarize into M1-type, which suppresses tumors, and M2-type, which promotes metastasis. Notably, targeting M2-TAMs is a promising strategy for tumor therapy. By emphasizing the importance of macrophages as a therapeutic target of anti-cancer drugs, this review aims to provide valuable insights and research directions for clinicians and researchers.
Association of plasma homocysteine with cognitive impairment in patients with Parkinson’s disease
Authors: Xiao Yan , Gan Lin-Hua , Liang Xiao-Niu , Xu Zhi-Heng , Hu Tian-Yu , Li Xiu-Yuan , Tang Yi-Lin , Wang Jian , Liu Yi-Qi
Published: December 2024

Background

Elevated plasma homocysteine (Hcy) has been reported as a risk factor for cognitive impairment in the general population. However, there are conflicting results regarding the relationship between Hcy and cognitive impairment across various cognitive domains in Parkinson’s disease (PD).

Objective

This study aims to explore the association between plasma Hcy levels, cognitive impairment, and dysfunction in various cognitive domains among PD patients with and without mild cognitive impairment (MCI).

Methods

A total of 101 PD patients underwent plasma Hcy measurement, comprising 50 PD-MCI patients and 51 patients with normal cognition (PD-NC). A battery of neuropsychological tests was administered to assess different cognitive domains. Adjusted generalized linear models were used to assess the correlations between Hcy levels and cognitive functions.

Results

As anticipated, PD-MCI patients demonstrated a significant decline in cognitive function across all five cognitive domains (memory, executive function, attention/working memory, language, and visuospatial function). Elevated plasma Hcy levels (≥ 10 μmol/L) were associated with a higher odds of PD-MCI, even within the normal range of Hcy levels (< 15 μmol/L). After adjusting for confounding factors, a negative correlation was observed between plasma Hcy levels and the performance on specific cognitive tests evaluating executive functions in PD, such as the Stroop Color-Word Test-C (β = −1.123, 95% CI = −1.845 ∼−0.401, p = 0.0023).

Conclusion

This study underscores a significant link between plasma Hcy levels and PD-MCI, particularly concerning executive dysfunction, even within the normal range of Hcy levels (< 15 μmol/L).