bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of two anti-tumor drugs, pazopanib, and axitinib, on the development and thyroid-axis of zebrafish (Danio rerio) embryos/larvae
Authors: Yang Liu , Tu Ping-hui , Zhang Cao-xu , Xie Rong-rong , Dong Mei , Jing Yu , Chen Xia , Wei Gang , Song Huai-dong 
Published: July 2023

IntroductionIn recent years, the potential toxicities of different pharmaceuticals toward the thyroid system have received increasing attention. In this study, we aim to evaluate the toxic effects of pazopanib and axitinib, two anti-tumor drugs with widespread clinical use, on thyroid function in the zebrafish model.MethodsWe measured levels of thyroid-related hormones using the commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Whole-mount in situ hybridization (WISH) analysis was employed to detect target gene expression changes. Morphology of the thyroid were evaluated by using transgenic Tg (tg: EGFP) fish line under a confocal microscope. The relative mRNA expression of key genes was verified through quantitative real-time polymerase chain reaction (RT‒qPCR). The size and number of the follicles was quantified whereby Hematoxylin–Eosin (H &amp; E) staining under a light microscope.ResultsThe results revealed that fertilized zebrafish embryos were incubated in pazopanib or axitinib for 96 hours, development and survival were significantly affected, which was accompanied by significant disturbances in thyroid endocrine system (e.g., increased thyroid-stimulating hormone (TSH) content and decreased triiodothyronine (T3) and thyroxine (T4) content, as well as transcription changes of genes associated with the hypothalamus-pituitary-thyroid (HPT) axis. Moreover, based on whole-mount in situ hybridization staining of tg and histopathological examination of zebrafish embryos treated with pazopanib and axitinib, we observed a significantly abnormal development of thyroid follicles in the Tg (tg: EGFP) zebrafish transgenic line.ConclusionCollectively, these findings indicate that pazopanib and axitinib may have toxic effects on thyroid development and function, at least partially, by influencing the regulation of the HPT axis. Thus, we believe that the potential thyroid toxicities of pazopanib and axitinib in their clinical applications should receive greater attention.
Immune checkpoint inhibitor-induced hypothyroidism predicts treatment response in Japanese subjects
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Dan Kazunori , Ohnishi Mana , Takenouchi Haruka , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Shimoda Masashi , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki 
Published: July 2023

BackgroundImmune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response or survival with ICIs.MethodThis is a single-center, retrospective, observational study. The study included 466 patients who received ICI at Kawasaki Medical School Hospital from September 1, 2014, to May 31, 2022 and evaluated the degree of abnormal thyroid function and survival and remission rates after treatment with ICIs. Primary hypothyroidism of less than 10 μIU/mL TSH was classified as grade 1, and primary hypothyroidism requiring more than 10 μIU/mL TSH or levothyroxine as grade 2-4.ResultThe mean age of the study participants was 68.2 ± 10.3 years, and the percentage of male participants was 72.6%. The frequency of ICI-induced thyroid dysfunction in the study participants was 28.2%. TSH levels were significantly higher in Grade 1 and Grades 2-4 when treated with ICI compared to NTF (p&lt;0.0001). The survival rate at 1 year after ICI administration was significantly higher with 64.9% for grade 1 and 88.9% for grades 2-4 compared to 52.1% for NTF (p&lt;0.0001). Cancer stage at the time of ICI administration did not differ among the groups (p=0.68). Nevertheless, the remission rate assessed by RECIST criteria was significantly higher in grades 2-4 compared to NTF (p&lt;0.0001).ConclusionICI-induced thyroid dysfunction was significantly correlated with survival, mean observation time, and treatment remission rate. It is important to monitor thyroid hormone levels regularly in patients receiving ICIs.
Vaccination with an in vitro culture attenuated Babesia bovis strain safely protects highly susceptible adult cattle against acute bovine babesiosis
Authors: Bastos Reginaldo G. , Capelli-Peixoto Janaina , Laughery Jacob M. , Suarez Carlos E. , Ueti Massaro W. 
Published: July 2023

IntroductionLive in vivo attenuated Babesia bovis vaccines produced by sequential passages in splenectomized calves have historically been used to control acute bovine babesiosis in endemic areas worldwide. However, several constraints prevent the widespread use of these vaccines, including the need for several splenectomized calves to produce vaccine batches, and potential inconsistent parasite attenuation, which contraindicates their use for highly Babesia-susceptible adult cattle. Thus, the use of vaccines based on well-defined in vitro culture attenuated B. bovis strains emerges as a more sustainable and efficient alternative. Previous work demonstrated that the culture attenuated strain Att-S74-T3Bo is non-tick transmissible and able to safely protect calves against needle challenge with a B. bovis virulent strain.Methods and resultsHerein we evaluated safety and efficacy of Att-S74-T3Bo in preventing acute babesiosis in adult (&gt;1.5 year of age) cattle. Results demonstrated that Att-S74-T3Bo vaccination of adult animals (n=5) induced self-limiting signs of acute infection and protected the vaccinated animals against challenge with the homologous virulent B. bovis strain Vir-S74-T3Bo. Att-S74-T3Bo-vaccinated adult cattle developed significant (P&lt;0.05) monocytosis, with concomitant neutropenia and CD4+ leukopenia, in peripheral blood early after vaccination. Also, vaccinated animals developed a specific signature of pro- and anti-inflammatory cytokine expression in peripheral blood and significant levels of IgM, total IgG, IgG1, and IgG2 against the B. bovis immunodominant antigen RAP-1 CT. Strikingly, none of the vaccinated animals showed any signs of acute babesiosis after challenge with Vir-S74-T3Bo. In contrast, control adult cattle (n=5) showed pathognomonic symptoms of acute babesiosis, and significant decrease (P&lt;0.05) in lymphocytes, monocytes, and neutrophils, starting on day 7 post-challenge. All control animals developed severe acute disease and were euthanized on days 10 through 12 days post-challenge.Discussion and conclusionEvidence from this study indicates that Att-S74-T3Bo safely protects highly susceptible adult cattle against challenge with a homologous virulent strain of B. bovis. In conclusion, Att-S74-T3Bo may be considered as a potential efficient and sustainable attenuated candidate vaccine strain to control acute bovine babesiosis in highly susceptible adult cattle. Future studies should focus on increasing the number of animals vaccinated, duration of immunity, and efficacy of this attenuated strain against heterologous virulent parasite strains.
Genomic analysis of Plasmodium falciparum isolates across different altitudinal zones along the slope of Mount Cameroon
Authors: Apinjoh Tobias O. , Ajonina Marcelus U. , Abera Deriba , Chi Hanesh F. , Tata Roland B. , Mugri Regina N. , Golassa Lemu , Achidi Eric A. , Amambua-Ngwa Alfred 
Published: July 2023

BackgroundMalaria elimination is threatened by the emergence and rapid spread of drug resistance. Understanding the demographic history of Plasmodium falciparum and the genetic basis of adaptation to antimalarial treatment and host immunity is critical to elimination efforts. This study sought to characterize the diversity of P. falciparum isolates across different altitudes along the slope of Mount Cameroon.MethodologyUsing the Illumina next-generation sequencing platform P. falciparum isolates from low, intermediate and high altitudes along the slope of Mount Cameroon were studied to determine their genetic diversity, population structures, and signatures of selection in known drug resistance alleles.ResultsA total of 77,253 single-nucleotide polymorphisms were identified from 220 quality P. falciparum clinical isolates from high (24,214), intermediate (24,426), and low (28,613) altitude. About 49%, 48.2% and 30% of the parasite isolates from high, intermediate, and low altitudes, respectively had FWS values &gt; 0.95 indicative of dominant mixed genotype infections and low population sub-structure with high potential for out-crossing. No significant difference was observed in within-host diversity while population structure analysis did not separate the isolates in the three major altitudinal groups by PCA, FST and admixtures, suggesting bidirectional gene flow among the populations. A total of 94 antigenic genes under balancing selection were detected in the area including vaccine candidate gene ama1, eba175, msp1, trap, dblmsp, and clag2. Moreover, 17 of these genes were identified to be under both recent positive directional and positive balancing selection including the prominent host immune target genes surfin 8.2, trap, and ama1. Recent directional selection analysis using integrated standardized haplotype score (iHS) did not detect any selection signatures in the Pfdhfr, Pfdhps, Pfmdr1, and PfK13 genes. Furthermore, no PfKelch13 validated mutation associated with artemisinin resistance was identified in this study and no structural divergence was noticed among the P. falciparum parasite populations across different altitudes around the Mount Cameroon region.DiscussionFindings revealed high genetic diversity and low population structure suggesting that malaria transmission remain high in the study area and parasite populations circulating around the slope of Mount Cameroon are homogenous.
Filling parameters and process optimization of mining–filling synergistic coal-based solid waste paste in Renjiazhuang mine
Authors: Li Chao , Chen Denghong , Yang Ke 
Published: July 2023

In this paper, the authors address the issue of large solid waste output and surface subsidence in the western coal base. They focus on the 110904 filling working face of Renjiazhuang Mine and employ a combination of theoretical analysis, numerical simulation, and field practice to analyze the limit caving step and cycle pressure step of the working face. The authors propose a mining-filling coordination scheme called “three mining and one charging”. Through numerical simulation, they demonstrate that this scheme ensures the time-space continuity of the mining-filling cycle and is theoretically feasible. Additionally, the authors conduct nine groups of orthogonal simulation tests to identify the main factors affecting the filling effect. They conclude that the filling rate is the primary controlling factor, and there is a positive correlation between the filling rate and 1-day strength. The authors implement hanging pipe filling in the return air roadway of the 110904 working face, achieving a filling material 1-day strength of 2 MPa and a filling ratio of 80%. The mining-filling synergy scheme proves effective and feasible. However, the issue of pipe plugging during the filling process requires further optimization of the particle gradation in the subsequent filling material ratio scheme. Overall, the proposed mining-filling collaborative process serves as a theoretical reference for similar filling faces.
Tutorial: using NEURON for neuromechanical simulations
Authors: Fietkiewicz Chris , McDougal Robert A. , Corrales Marco David , Chiel Hillel J. , Thomas Peter J. 
Published: July 2023

The dynamical properties of the brain and the dynamics of the body strongly influence one another. Their interaction generates complex adaptive behavior. While a wide variety of simulation tools exist for neural dynamics or biomechanics separately, there are few options for integrated brain-body modeling. Here, we provide a tutorial to demonstrate how the widely-used NEURON simulation platform can support integrated neuromechanical modeling. As a first step toward incorporating biomechanics into a NEURON simulation, we provide a framework for integrating inputs from a “periphery” and outputs to that periphery. In other words, “body” dynamics are driven in part by “brain” variables, such as voltages or firing rates, and “brain” dynamics are influenced by “body” variables through sensory feedback. To couple the “brain” and “body” components, we use NEURON'spointerconstruct to share information between “brain” and “body” modules. This approach allows separate specification of brain and body dynamics and code reuse. Though simple in concept, the use of pointers can be challenging due to a complicated syntax and several different programming options. In this paper, we present five different computational models, with increasing levels of complexity, to demonstrate the concepts of code modularity using pointers and the integration of neural and biomechanical modeling within NEURON. The models include: (1) a neuromuscular model of calcium dynamics and muscle force, (2) a neuromechanical, closed-loop model of a half-center oscillator coupled to a rudimentary motor system, (3) a closed-loop model of neural control for respiration, (4) a pedagogical model of a non-smooth “brain/body” system, and (5) a closed-loop model of feeding behavior in the sea hareAplysia californicathat incorporates biologically-motivated non-smooth dynamics. This tutorial illustrates how NEURON can be integrated with a broad range of neuromechanical models.Code available athttps://github.com/fietkiewicz/PointerBuilder.
The onset of cerebral infarction may be affected by differences in atmospheric pressure distribution patterns
Authors: Fukunaga Atsushi , Koyama Hideki , Fuse Takahisa , Haraguchi Asami 
Published: July 2023

BackgroundSome papers have highlighted a possible causal relationship between the onset of ischemic stroke and weather conditions. This study aimed to elucidate the onset mechanism of cerebral infarction from a meteorological approach. We focused on the atmospheric pressure distribution patterns (APDPs).MethodsThe subjects are 221 cases diagnosed as cardiogenic cerebral embolism (Group A) and 612 cases diagnosed as atherosclerotic cerebral thrombosis (Group B). We investigated the APDP on the date closest to the date and time of onset of cerebral infarction in each patient on the website and chose the most similar one from the reported 11 APDPs. Groups A and B were compared for clinical characteristics and the appearance rate of each APDP in each group.ResultsThe clinical characteristics of Groups A and B were consistent with some previously reported clinical characteristics of cerebral embolism and cerebral thrombosis except for smoking. The appearance rate of the other high-pressure type, which cannot be classified as either the anticyclone belt type or the migratory anticyclone type, in Group B was statistically significantly higher than that in Group A, and the appearance rate of the anticyclone belt type in Group A was statistically significantly higher than that in Group B (p &lt; 0.05, Fisher's exact probability method, respectively).ConclusionsCerebral embolism and cerebral thrombosis exhibited significant differences in APDPs on the day of onset. Dehydration particularly in the other high-pressure type or in the anticyclone belt type should be prevented. Further investigation should focus on the other meteorological factors.
The challenge of measuring physiological parameters during motor imagery engagement in patients after a stroke
Authors: Gäumann Szabina , Aksöz Efe Anil , Behrendt Frank , Wandel Jasmin , Cappelletti Letizia , Krug Annika , Mörder Daniel , Bill Annika , Parmar Katrin , Gerth Hans Ulrich , Bonati Leo H. , Schuster-Amft Corina 
Published: July 2023

IntroductionIt is suggested that eye movement recordings could be used as an objective evaluation method of motor imagery (MI) engagement. Our investigation aimed to evaluate MI engagement in patients after stroke (PaS) compared with physical execution (PE) of a clinically relevant unilateral upper limb movement task of the patients' affected body side.MethodsIn total, 21 PaS fulfilled the MI ability evaluation [Kinaesthetic and Visual Imagery Questionnaire (KVIQ-10), body rotation task (BRT), and mental chronometry task (MC)]. During the experiment, PaS moved a cup to distinct fields while wearing smart eyeglasses (SE) with electrooculography electrodes integrated into the nose pads and electrodes for conventional electrooculography (EOG). To verify MI engagement, heart rate (HR) and oxygen saturation (SpO2) were recorded, simultaneously with electroencephalography (EEG). Eye movements were recorded during MI, PE, and rest in two measurement sessions to compare the SE performance between conditions and SE's psychometric properties.ResultsMI and PE correlation of SE signals varied between r = 0.12 and r = 0.76. Validity (cross-correlation with EOG signals) was calculated for MI (r = 0.53) and PE (r = 0.57). The SE showed moderate test–retest reliability (intraclass correlation coefficient) with r = 0.51 (95% CI 0.26–0.80) for MI and with r = 0.53 (95% CI 0.29 – 0.76) for PE. Event-related desynchronization and event-related synchronization changes of EEG showed a large variability. HR and SpO2 recordings showed similar values during MI and PE. The linear mixed model to examine HR and SpO2 between conditions (MI, PE, rest) revealed a significant difference in HR between rest and MI, and between rest and PE but not for SpO2. A Pearson correlation between MI ability assessments (KVIQ, BRT, MC) and physiological parameters showed no association between MI ability and HR and SpO2.ConclusionThe objective assessment of MI engagement in PaS remains challenging in clinical settings. However, HR was confirmed as a reliable parameter to assess MI engagement in PaS. Eye movements measured with the SE during MI did not resemble those during PE, which is presumably due to the demanding task. A re-evaluation with task adaptation is suggested.
Transatmospheric ileal stoma manometry can be applied for the early detection of stoma outlet obstruction
Authors: Wang Xiaowei , Wang Yizhi , Lin Beibei , Liu Yue , Gu Jin , Ling Limian , Xu Dong , Ding Kefeng 
Published: July 2023

BackgroundStoma outlet obstruction (SOO) is a common complication of diverting ileostomy and usually detected at the advanced stage when the intestine is obviously obstructed. The objective of this study is to explore the efficacy of transatmospheric ileal stoma manometry (TISM) in early detection of SOO before the manifestation of intestinal obstruction.MethodsA single-center prospective study was performed in patients scheduled to undergo reversal ileostomy and laparoscopic anterior rectal resection and diverting ileostomy in Second Affiliated Hospital of Zhejiang University School of Medicine from 1st July 2022 to 31st December 2022. The stoma pressure was measured by TISM at different time points.ResultsThe mean stoma pressure of the 30 patients before reversal ileostomy was 5.21 cmH2O which was considered as normal standard of stoma pressure, and ranged from 1.2 to 8.56 cmH2O. After excluding two patients with anastomotic leakage, a total of 38 patients who were subjected to laparoscopic anterior rectal resection and diverting ileostomy were further included in this study. The incidence of anastomotic leakage was 5% and that of SOO was 12.5%. The mean postoperative obstruction time was 5.2 (3-7) days and the mean time from elevated stoma pressure to diagnosed as SOO was 2.8 (2-4) days in the five patients who developed SOO. The pressure measured at the third stoma manometry time point (second day after return of gut function) (10.23 vs. 6.04 cmH2O, p&lt;0.001) and the postoperative hospital stay (10 vs. 8.49 days, p=0.028) showed significantly difference between the SOO and non-SOO groups. The pressures measured at the first time point (before return of gut function) (4 vs. 4.49 cmH2O, p=0.585), the second time point (the day of return of gut function) (6.8 vs. 5.62 cmH2O, p=0.123), and the fourth time point (discharge day) (5.88 vs. 5.9 cmH2O, p=0.933) showed no significant difference in both groups.ConclusionTISM can be utilized for early detection of SOO and can be incorporated as a novel diagnostic method together with abdominal CT scan to realize the goal of ERAS.
Oral language skills and mental health in female prisoners: pragmatic skills are essential
Authors: Morken Frøydis , Helland Wenche Andersen , Evanger Elisabeth , Vårvik Aslaug , Jones Lise Øen 
Published: July 2023

IntroductionThere are strong indications of an elevated incidence of both language problems and problems with mental health among prisoners. We also know that women in prison are a particularly vulnerable group who often face conditions that foremost accommodate the needs of men. In order to adapt prison conditions to women’s needs and give better help, we need more information about their characteristics. In this study, we wanted to explore associations between oral language problems and mental health (depression and anxiety) in women in prison.MethodParticipants were 58 women, recruited from high and low security women’s and mixed prisons. They completed a questionnaire covering demographic variables and several self-report measures. In the present study, the language measures were a Language Composite score (comprising articulation, impressive and expressive language, and pragmatics) and the La Trobe Communication Questionnaire (LCQ), measuring pragmatic skills specifically. Hopkins Symptom Checklist-10 (HSCL) was used as a measure of psychological distress. First, we assessed correlations between the language measures and mental health. Second, we performed group comparisons with groups defined as over or under cut-off on the Language Composite, LCQ total, and HSCL total scores.ResultsResults supported a clear connection between overall language and overall mental health. Pragmatic skills were the main driver of this effect. There was no difference in mental health between those scoring above and below cut-off for general language problems but the group with possible pragmatic impairment showed poorer mental health than those without. Conversely, there was no difference in general language skills between the groups scoring within and outside the range of psychological distress, but the first group evaluated their pragmatic skills as significantly poorer than the latter.DiscussionWe conclude that pragmatics seem to be core to the association between oral language skills and mental health among female prisoners. This should have implications for language services in prisons, as attending to these issues could positively affect prognosis and outcome.