bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-decadal observations in the Alps reveal less and wetter snow, with increasing variability
Authors: Marty Christoph , Rohrer Mario B. , Huss Matthias , Stähli Manfred
Published: June 2023

Snowpack is an important temporal water storage for downstream areas, a potential source of natural hazards (avalanches or floods) and a prerequisite for winter tourism. Here, we use thousands of manual measurements of the water equivalent of the snow cover (SWE) from almost 30 stations between 1,200 and 2,900 m a.s.l. from four long-term monitoring programs (earliest start in 1937) in the center of the European Alps to derive daily SWE based on snow depth data for each station. The inferred long-term daily SWE time series were analyzed regarding spatial differences, as well as potential temporal changes in variability and seasonal averages during the last 7 decades (1957–2022). The investigation based on important hydro-climatological SWE indicators demonstrates significant decreasing trends for mean SWE (Nov-Apr) and for maximum SWE, as well as a significantly earlier occurrence of the maximum SWE and earlier disappearance of the continuous snow cover. The anomalies of mean SWE revealed that the series of low-snow winters since the 1990s is unprecedented since the beginning of measurements. Increased melting during the accumulation period below 2000 m a.s.l is also observed–especially in the most recent years–as well as slower melt rates in spring, and higher day-to-day variability. For these trends no regional differences were found despite the climatological variability of the investigated stations. This indicates that the results are transferable to other regions of the Alps.
Maximal parathyroid gland diameter as a predictive factor for autograft-dependent recurrent secondary hyperparathyroidism after total parathyroidectomy
Authors: Hiramitsu Takahisa , Hasegawa Yuki , Futamura Kenta , Okada Manabu , Goto Norihiko , Narumi Shunji , Watarai Yoshihiko , Tominaga Yoshihiro , Ichimori Toshihiro
Published: June 2023

Introduction

Following total parathyroidectomy (PTx), transcervical thymectomy, and forearm autograft for secondary hyperparathyroidism (SHPT), recurrent SHPT can occur in the autografted forearm. However, few studies have investigated the factors contributing to re-PTx due to autograft-dependent recurrent SHPT before the completion of the initial PTx.

Methods

A total of 770 patients who had autografted parathyroid fragments derived from only one of the resected parathyroid glands (PTGs) and who had undergone successful initial total PTx and transcervical thymectomy—defined by serum intact parathyroid hormone level < 60 pg/mL on postoperative day 1—between January 2001 and December 2022 were included in this retrospective cohort study. Factors contributing to re-PTx due to graft-dependent recurrent SHPT before the completion of the initial PTx were investigated using multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to obtain the optimal maximum diameter of PTG for autograft.

Results

Univariate analysis showed that dialysis vintage and maximum diameter and weight of the PTG for autograft were significant factors contributing to graft-dependent recurrent SHPT. However, multivariate analysis revealed that dialysis vintage (P=0.010; hazard ratio [HR], 0.995; 95% confidence interval [CI], 0.992–0.999) and the maximum diameter of the PTG for autograft (P=0.046; HR, 1.107; 95% CI, 1.002–1.224) significantly contributed to graft-dependent recurrent SHPT. ROC curve analysis showed that < 14 mm was the optimal maximum diameter of PTG for autograft (area under the curve, 0.628; 95% CI, 0.551–0.705).

Conclusions

The dialysis vintage and maximum diameter of PTG for autograft may contribute to re-PTx due to autograft-dependent recurrent SHPT, which can be prevented by using PTGs with a maximum diameter of < 14 mm for autograft.
Particle-based nutrients and metal contaminants in the habitat of Unionidae mussels in the Tisza River (Hungary)
Authors: Dobosy Péter , Almeshal Wael , Illés Ádám , Tserendorj Davaakhuu , Sandil Sirat , Kovács Zsófia , Endrédi Anett , Záray Gyula
Published: June 2023

Introduction:Unioniade is a species-rich family of freshwater mussels with an almost worldwide distribution. In Central European rivers Unio crassus, Unio tumidus and Unio pictorum have relatively high populations. In order to characterize the habitats of these suspension feeders, their nutrient supply and potential metal contaminants were investigated in near-bottom suspended (NBS) sediments and bottom sediments (BS) collected at four sampling locations along the Tisza River.

Methods: The grain size distribution of sediments was determined by laser-diffraction technique. The total organic carbon (TOC) and the total Kjeldahl nitrogen (TN) were measured by a TOC analyzer and automated colorimetry, respectively. The phosphorous and metal concentrations were determined by inductively coupled plasma mass spectrometry following a microwave assisted acidic extraction of sediments with aqua regia.

Results: The NBS sediments contained smaller grains than the BS samples, with roughly 85%–90% of the particles being less than 60 μm, allowing these mussels to catch them. Contrarily, only 2.47%–51.8% of BS samples were less than 60 μm. The NBS sediments contained 30, 23, and 15% more organic carbon, nitrogen, and phosphorous, respectively, than the BS samples. The rounded C:N:P molar ratios in the NBS sediments were 60:4:1, whereas they were 45:3:1 in the bottom sediments. The concentration of metals was also greater in the NBS sediments with the exception of Zn at Tokaj and Fe, Al, Mn, and Cr at Szeged, where prior contaminations transported by the tributaries Bodrog and Maros are stored in the top 10 cm of BS.

Discussion: On basis of the measured C:N:P molar ratios it can be stated that soil-derived organic materials are the main sources of the nutrient elements in the habitats of suspension feeders in the Tisza River. The finer NBS sediments have higher specific surface area than the BS and thereby contain more biofilms on the grains resulting in higher proportion of organic nutrients and metal ions bounded as complexes or chelates. Comparing the measured metal concentrations of sediments with the concentration limits summarized in the Consensus-Based Sediment Quality Guidelines developed for evaluation of potential risk of metal contaminants in sediments for the benthic-dwelling organisms, it can be established that only the Hg concentration exceeded the probable effect concentration.
Elevated levels of interleukin-9 in the serum of bullous pemphigoid: possible association with the pathogenicity of bullous pemphigoid
Authors: Koga Hiroshi , Teye Kwesi , Sugawara Arisa , Tsutsumi Masahiro , Ishii Norito , Nakama Takekuni
Published: June 2023

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease (sAIBD). In addition to disease causing autoantibodies, several leukocyte subsets, including mast cells and eosinophils, play key roles in mediating skin inflammation. Detailed immunophenotyping and, more recently, the therapeutic effects of interleukin-4 (IL-4) receptor alpha inhibition in BP pointed to a prominent role of T helper 2 (Th2) cells. Among other cell types, IL-9 is expressed by Th2 and mast cells and potentially drives allergic, Th2-dominated inflammation. Although cytokines in BP have been relatively well investigated, the role of IL-9 has remained enigmatic. This study aimed to evaluate the effect of IL-9 in BP. Serum IL-9 levels were significantly elevated in patients with BP and decreased upon induction of remission. Serum IL-9 levels were not elevated in epidermolysis bullosa acquisita, another sAIBD. The time-course analysis using serum sets from four patients with BP revealed that serum IL-9 was a sensitive biomarker of BP. IL-9–positive cells infiltrated dominantly in BP lesions, especially in the blister fluid, and Th9 cells were abundant. Therefore, IL-9 was elevated in the serum and lesions of BP, which could be a biomarker of BP.
Oxytocin administration is a potential tool for behavioral management in felids
Authors: Burkhart Jessica C. , Heilbronner Sarah R. , Packer Craig
Published: June 2023

Living in a group setting is essential for the health and wellbeing of social carnivores; however, the managed formation of captive groups of territorial animals can be challenging because of the risk of aggression, injury, and even death. Numerous laboratory and clinical studies have implicated oxytocin in the formation of social bonds. Previously, we have shown that oxytocin (OT) administration reduced social vigilance in African lions. Here, we describe a series of case reports in which OT administration was used to facilitate social bonding in both familiar and unfamiliar conspecific pairs and groups of African lions and tigers, and we provide qualitative descriptions of the study animals’ behaviors before and after treatment. We hypothesized that the repeated intranasal administration of oxytocin over a period of 6–8 weeks would facilitate (1) the bonding process during introductions of unfamiliar individuals and (2) reconciliation between paired individuals that had developed ongoing negative social relationships. Following OT treatment, positive social interactions were either observed for the first time or were restored in all seven study groups.
Tonic down-rolling and eccentric down-positioning of eyes under sevoflurane anesthesia without non-depolarizing muscle relaxant and its relationship with depth of anesthesia
Authors: Chaurasia Shweta , Soni Shiv Lal , Ganesh Venkata , Ram Jagat , Sukhija Jaspreet , Chaurasia Swati , Takkar Aastha
Published: June 2023

Purpose

To analyze the relationship between eccentric downward eye movement/eccentric downward eye-positioning (EDEM/EDEP) encountered in patients undergoing ophthalmic surgeries and its return to a centralized position under general anesthesia (GA) with the depth of anesthesia (DOA).

Methods

Patients undergoing ophthalmic surgeries (6 months-12 years) under sevoflurane anesthesia without non-depolarizing muscle relaxant (NDMR) who witnessed a sudden tonic EDEM/EDEP were both retrospectively (R-group) and prospectively (P-group) enrolled (ambispective study). R-group included data-points after induction (AI) till the time surgery lasted while P-group compiled data both during induction (DI) and AI. DOA in terms of MAC (minimum alveolar concentration) at the time of EDEM/EDEP and centralization of eyeball and their timings were noted and compared for both AI and DI data-points. Also, vertical eccentric eye positions were scored and correlated with MAC.

Results

AI data included 22 (14R+8P) events and their mean MAC of EDEM/EDEP and centralization were 1.60 ± 0.25 and 1.18 ± 0.17 respectively (p = 0.000). DI data included 62 (P) cases and its mean MAC of EDEM/EDEP and centralization was 2.19 ± 0.43 and 1.39 ± 0.26 respectively (p = 0.000). Median (IQR) eye positions during down-positioning in 84 events was −3 (−3.9 to −2.5). It was preceded by an eccentric upward drift of eyes in 10/22 (6R+4P) AI cases. A strong negative correlation was seen between DOA and eccentric eye positions (r = −0.77, p = 0.000).

Conclusions

Tonic down-rolling of eyes is not uncommon in children seen without NDMR with higher depths of sevoflurane anesthesia compared to point of centralization and fluctuations in DOA should be avoided to circumvent inadvertent complications during ocular surgery.
Soil bacterial community structure and functioning in a long-term conservation agriculture experiment under semi-arid rainfed production system
Authors: Pratibha G. , Manjunath M. , Raju B. M. K. , Srinivas I. , Rao K. V. , Shanker Arun K. , Prasad J. V. N. S. , Rao M. Srinivasa , Kundu Sumanta , Indoria A. K. , Kumar Upendra , Rao K. Srinivasa , Anna Shivakumar , Rao Ch. Srinivasa , Singh V. K. , Biswas A. K. , Chaudhari S. K.
Published: June 2023

Soil microbial communities are important drivers of biogeochemical cycling of nutrients, organic matter decomposition, soil organic carbon, and Greenhouse gas emissions (GHGs: CO2, N2O, and CH4) and are influenced by crop and soil management practices. The knowledge on the impact of conservation agriculture (CA) on soil bacterial diversity, nutrient availability, and GHG emissions in semi-arid regions under rainfed conditions is vital to develop sustainable agricultural practices, but such information has not been systemically documented. Hence, studies were conducted for 10 years in rainfed pigeonpea (Cajanus cajanL.)—castor bean (Ricinus communisL.) cropping system under semi-arid conditions to assess the effects of tillage and crop residue levels on the soil bacterial diversity, enzyme activity (Dehydrogenase, urease, acid phosphatase, and alkaline phosphatase), GHG emissions, and soil available nutrients (Nitrogen, phosphorus, and potassium). Sequencing of soil DNA through Illumina HiSeq-based 16S rRNA amplicon sequencing technology has revealed that bacterial community responded to both tillage and residue levels. The relative abundance of Actinobacteria in terms of Operational Taxonomic Unit (OTUs) at phyla, class as well as genera level was higher in CA (NTR1: No Tillage + 10 cm anchored residue and NTR2 NT + 30 cm anchored residue) over CT (conventional tillage without crop residues). CA resulted in higher enzyme activities (dehydrogenase, urease, acid phosphatase, and alkaline phosphatase) and reduction in GHG emissions over CT. CA recorded 34% higher and 3% lower OC, as compared to CT, and CTR1, respectively. CA recorded 10, 34, and 26% higher available nitrogen, phosphorus, and potassium over CT and CTR1, respectively. NTR1 recorded 25 and 38% lower N2O emissions as compared to CTR1 and CTR2, respectively. Whereas only NT recorded 12% higher N2O emissions as compared to CT. Overall, the results of the study indicate that CA improves the relative abundance of soil bacterial communities, nutrient availability, and enzyme activities, and may help to contribute to the mitigation of climate change, and sustainability in rainfed areas.
Contribution of microbial activity and vegetation cover to the spatial distribution of soil respiration in mountains
Authors: Sushko Sofia , Ovsepyan Lilit , Gavrichkova Olga , Yevdokimov Ilya , Komarova Alexandra , Zhuravleva Anna , Blagodatsky Sergey , Kadulin Maxim , Ivashchenko Kristina
Published: June 2023

The patterns of change in bioclimatic conditions determine the vegetation cover and soil properties along the altitudinal gradient. Together, these factors control the spatial variability of soil respiration (RS) in mountainous areas. The underlying mechanisms, which are poorly understood, shape the resulting surface CO2 flux in these ecosystems. We aimed to investigate the spatial variability of RS and its drivers on the northeastern slope of the Northwest Caucasus Mountains, Russia (1,260–2,480 m a.s.l.), in mixed, fir, and deciduous forests, as well as subalpine and alpine meadows. RS was measured simultaneously in each ecosystem at 12 randomly distributed points using the closed static chamber technique. After the measurements, topsoil samples (0–10 cm) were collected under each chamber (n = 60). Several soil physicochemical, microbial, and vegetation indices were assessed as potential drivers of RS. We tested two hypotheses: (i) the spatial variability of RS is higher in forests than in grasslands; and (ii) the spatial variability of RS in forests is mainly due to soil microbial activity, whereas in grasslands, it is mainly due to vegetation characteristics. Unexpectedly, RS variability was lower in forests than in grasslands, ranging from 1.3–6.5 versus 3.4–12.7 μmol CO2 m−1 s−1, respectively. Spatial variability of RS in forests was related to microbial functioning through chitinase activity (50% explained variance), whereas in grasslands it was related to vegetation structure, namely graminoid abundance (27% explained variance). Apparently, the chitinase dependence of RS variability in forests may be related to soil N limitation. This was confirmed by low N content and high C:N ratio compared to grassland soils. The greater sensitivity of grassland RS to vegetation structure may be related to the essential root C allocation for some grasses. Thus, the first hypothesis concerning the higher spatial variability of RS in forests than in grasslands was not confirmed, whereas the second hypothesis concerning the crucial role of soil microorganisms in forests and vegetation in grasslands as drivers of RS spatial variability was confirmed.
Two-way communication between cell cycle and metabolism in budding yeast: what do we know?
Authors: Zhang Yanfei , van der Zee Lucas , Barberis Matteo
Published: June 2023

Coordination of cell cycle and metabolism exists in all cells. The building of a new cell is a process that requires metabolic commitment to the provision of both Gibbs energy and building blocks for proteins, nucleic acids, and membranes. On the other hand, the cell cycle machinery will assess and regulate its metabolic environment before it makes decisions on when to enter the next cell cycle phase. Furthermore, more and more evidence demonstrate that the metabolism can be regulated by cell cycle progression, as different biosynthesis pathways are preferentially active in different cell cycle phases. Here, we review the available literature providing a critical overview on how cell cycle and metabolism may be coupled with one other, bidirectionally, in the budding yeast Saccharomyces cerevisiae.
Permutation entropy is not an age-independent parameter for EEG-based anesthesia monitoring
Authors: Hight Darren , Obert David P. , Kratzer Stephan , Schneider Gerhard , Sepulveda Pablo , Sleigh Jamie , García Paul S. , Kreuzer Matthias
Published: June 2023

Background

An optimized anesthesia monitoring using electroencephalographic (EEG) information in the elderly could help to reduce the incidence of postoperative complications. Processed EEG information that is available to the anesthesiologist is affected by the age-induced changes of the raw EEG. While most of these methods indicate a “more awake” patient with age, the permutation entropy (PeEn) has been proposed as an age-independent measure. In this article, we show that PeEn is also influenced by age, independent of parameter settings.

Methods

We retrospectively analyzed the EEG of more than 300 patients, recorded during steady state anesthesia without stimulation, and calculated the PeEn for different embedding dimensions m that was applied to the EEG filtered to a wide variety of frequency ranges. We constructed linear models to evaluate the relationship between age and PeEn. To compare our results to published studies, we also performed a stepwise dichotomization and used non-parametric tests and effect sizes for pairwise comparisons.

Results

We found a significant influence of age on PeEn for all settings except for narrow band EEG activity. The analysis of the dichotomized data also revealed significant differences between old and young patients for the PeEn settings used in published studies.

Conclusion

Based on our findings, we could show the influence of age on PeEn. This result was independent of parameter, sample rate, and filter settings. Hence, age should be taken into consideration when using PeEn to monitor patient EEG.
Keeping up with the kids: the value of co-production in the study of irritability in youth depression and its underlying neural circuitry
Authors: MacSweeney Niamh , Louvet Perrine , Zafar Simal , Chan Stella W. Y. , Kwong Alex S. F. , Lawrie Stephen M. , Romaniuk Liana , Whalley Heather C.
Published: June 2023

Irritability is a core symptom of adolescent depression, characterized by an increased proneness to anger or frustration. Irritability in youth is associated with future mental health problems and impaired social functioning, suggesting that it may be an early indicator of emotion regulation difficulties. Adolescence is a period during which behavior is significantly impacted by one’s environment. However, existing research on the neural basis of irritability typically use experimental paradigms that overlook the social context in which irritability occurs. Here, we bring together current findings on irritability in adolescent depression and the associated neurobiology and highlight directions for future research. Specifically, we emphasize the importance of co-produced research with young people as a means to improve the construct and ecological validity of research within the field. Ensuring that our research design and methodology accurately reflect to lives of young people today lays a strong foundation upon which to better understand adolescent depression and identify tractable targets for intervention.
A fabric-based soft hand exoskeleton for assistance: the ExHand Exoskeleton
Authors: Maldonado-Mejía Juan C. , Múnera Marcela , Diaz Camilo A. R. , Wurdemann Helge , Moazen Mehran , Pontes Maria José , Vieira Segatto Marcelo Eduardo , Monteiro Maxwell E. , Cifuentes Carlos A.
Published: June 2023

Introduction

The rise of soft robotics has driven the development of devices for assistance in activities of daily living (ADL). Likewise, different types of actuation have been developed for safer human interaction. Recently, textile-based pneumatic actuation has been introduced in hand exoskeletons for features such as biocompatibility, flexibility, and durability. These devices have demonstrated their potential use in assisting ADLs, such as the degrees of freedom assisted, the force exerted, or the inclusion of sensors. However, performing ADLs requires the use of different objects, so exoskeletons must provide the ability to grasp and maintain stable contact with a variety of objects to lead to the successful development of ADLs. Although textile-based exoskeletons have demonstrated significant advancements, the ability of these devices to maintain stable contact with a variety of objects commonly used in ADLs has yet to be fully evaluated.

Materials and methods

This paper presents the development and experimental validation in healthy users of a fabric-based soft hand exoskeleton through a grasping performance test using The Anthropomorphic Hand Assessment Protocol (AHAP), which assesses eight types of grasping with 24 objects of different shapes, sizes, textures, weights, and rigidities, and two standardized tests used in the rehabilitation processes of post- stroke patients.

Results and discussion

A total of 10 healthy users (45.50 ± 14.93 years old) participated in this study. The results indicate that the device can assist in developing ADLs by evaluating the eight types of grasps of the AHAP. A score of 95.76 ± 2.90% out of 100% was obtained for the Maintaining Score, indicating that the ExHand Exoskeleton can maintain stable contact with various daily living objects. In addition, the results of the user satisfaction questionnaire indicated a positive mean score of 4.27 ± 0.34 on a Likert scale ranging from 1 to 5.
Case Report: Long segmental lesions of the spinal cord caused by exposure to xylene
Authors: Du Qin , Chen Hongxi , Shi Ziyan , Zhou Hongyu
Published: June 2023

Xylene has the potential to cause nervous system disturbances since it is a lipophilic substance with high affinity for lipid-rich tissue, such as the brain. Involvement in the spinal cord, especially long segmental spinal cord lesions that permeate almost the entire cervical and thoracic spinal cord, is extremely rare. We report two cases of occupational exposure to excessive xylene, both of which presented with severe and rapidly progressive numbness and weakness in the limbs that, more importantly, led to poor outcomes: one died and the other was left severely disabled. In both, spinal magnetic resonance imaging showed long segmental lesions in the cervicothoracic spinal cord. These findings may provide some insights into the effects of xylene as an isolated agent on the spinal cord injury.
Models of traumatic brain injury-highlights and drawbacks
Authors: Zhao Qinghui , Zhang Jianhua , Li Huige , Li Hongru , Xie Fei
Published: June 2023

Traumatic brain injury (TBI) is the leading cause for high morbidity and mortality rates in young adults, survivors may suffer from long-term physical, cognitive, and/or psychological disorders. Establishing better models of TBI would further our understanding of the pathophysiology of TBI and develop new potential treatments. A multitude of animal TBI models have been used to replicate the various aspects of human TBI. Although numerous experimental neuroprotective strategies were identified to be effective in animal models, a majority of strategies have failed in phase II or phase III clinical trials. This failure in clinical translation highlights the necessity of revisiting the current status of animal models of TBI and therapeutic strategies. In this review, we elucidate approaches for the generation of animal models and cell models of TBI and summarize their strengths and limitations with the aim of exploring clinically meaningful neuroprotective strategies.
Examining temporal features of BOLD-based cerebrovascular reactivity in clinical populations
Authors: Marchena-Romero Kayley-Jasmin , Ji Xiang , Sommer Rosa , Centen Andrew , Ramirez Joel , Poulin Joshua M. , Mikulis David , Thrippleton Michael , Wardlaw Joanna , Lim Andrew , Black Sandra E. , MacIntosh Bradley J.
Published: June 2023

Background

Conventional cerebrovascular reactivity (CVR) estimation has demonstrated that many brain diseases and/or conditions are associated with altered CVR. Despite the clinical potential of CVR, characterization of temporal features of a CVR challenge remains uncommon. This work is motivated by the need to develop CVR parameters that characterize individual temporal features of a CVR challenge.

Methods

Data were collected from 54 adults and recruited based on these criteria: (1) Alzheimer’s disease diagnosis or subcortical Vascular Cognitive Impairment, (2) sleep apnea, and (3) subjective cognitive impairment concerns. We investigated signal changes in blood oxygenation level dependent (BOLD) contrast images with respect to hypercapnic and normocapnic CVR transition periods during a gas manipulation paradigm. We developed a model-free, non-parametric CVR metric after considering a range of responses through simulations to characterize BOLD signal changes that occur when transitioning from normocapnia to hypercapnia. The non-parametric CVR measure was used to examine regional differences across the insula, hippocampus, thalamus, and centrum semiovale. We also examined the BOLD signal transition from hypercapnia back to normocapnia.

Results

We found a linear association between isolated temporal features of successive CO2 challenges. Our study concluded that the transition rate from hypercapnia to normocapnia was significantly associated with the second CVR response across all regions of interest (p < 0.001), and this association was highest in the hippocampus (R2 = 0.57, p < 0.0125).

Conclusion

This study demonstrates that it is feasible to examine individual responses associated with normocapnic and hypercapnic transition periods of a BOLD-based CVR experiment. Studying these features can provide insight on between-subject differences in CVR.
A novel tablet-based software for the acquisition and analysis of gaze and eye movement parameters: a preliminary validation study in Parkinson’s disease
Authors: de Villers-Sidani Étienne , Voss Patrice , Guitton Daniel , Cisneros-Franco J. Miguel , Koch Nils A. , Ducharme Simon
Published: June 2023

The idea that eye movements can reflect certain aspects of brain function and inform on the presence of neurodegeneration is not a new one. Indeed, a growing body of research has shown that several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s Disease, present characteristic eye movement anomalies and that specific gaze and eye movement parameters correlate with disease severity. The use of detailed eye movement recordings in research and clinical settings, however, has been limited due to the expensive nature and limited scalability of the required equipment. Here we test a novel technology that can track and measure eye movement parameters using the embedded camera of a mobile tablet. We show that using this technology can replicate several well-known findings regarding oculomotor anomalies in Parkinson’s disease (PD), and furthermore show that several parameters significantly correlate with disease severity as assessed with the MDS-UPDRS motor subscale. A logistic regression classifier was able to accurately distinguish PD patients from healthy controls on the basis of six eye movement parameters with a sensitivity of 0.93 and specificity of 0.86. This tablet-based tool has the potential to accelerate eye movement research via affordable and scalable eye-tracking and aid with the identification of disease status and monitoring of disease progression in clinical settings.
Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure
Authors: Upreti Deepa , Rouzer Siara K. , Bowring Abigail , Labbe Emma , Kumar Rosaline , Miranda Rajesh C. , Mahnke Amanda H.
Published: June 2023

Alcohol exposure in adulthood can result in inflammation, malnutrition, and altered gastroenteric microbiota, which may disrupt efficient nutrient extraction. Clinical and preclinical studies have documented convincingly that prenatal alcohol exposure (PAE) also results in persistent inflammation and nutrition deficiencies, though research on the impact of PAE on the enteric microbiota is in its infancy. Importantly, other neurodevelopmental disorders, including autism spectrum and attention deficit/hyperactivity disorders, have been linked to gut microbiota dysbiosis. The combined evidence from alcohol exposure in adulthood and from other neurodevelopmental disorders supports the hypothesis that gut microbiota dysbiosis is likely an etiological feature that contributes to negative developmental, including neurodevelopmental, consequences of PAE and results in fetal alcohol spectrum disorders. Here, we highlight published data that support a role for gut microbiota in healthy development and explore the implication of these studies for the role of altered microbiota in the lifelong health consequences of PAE.
STNet: shape and texture joint learning through two-stream network for knowledge-guided image recognition
Authors: Wang Xijing , Han Hongcheng , Xu Mengrui , Li Shengpeng , Zhang Dong , Du Shaoyi , Xu Meifeng
Published: June 2023

Introduction

The human brain processes shape and texture information separately through different neurons in the visual system. In intelligent computer-aided imaging diagnosis, pre-trained feature extractors are commonly used in various medical image recognition methods, common pre-training datasets such as ImageNet tend to improve the texture representation of the model but make it ignore many shape features. Weak shape feature representation is disadvantageous for some tasks that focus on shape features in medical image analysis.

Methods

Inspired by the function of neurons in the human brain, in this paper, we proposed a shape-and-texture-biased two-stream network to enhance the shape feature representation in knowledge-guided medical image analysis. First, the two-stream network shape-biased stream and a texture-biased stream are constructed through classification and segmentation multi-task joint learning. Second, we propose pyramid-grouped convolution to enhance the texture feature representation and introduce deformable convolution to enhance the shape feature extraction. Third, we used a channel-attention-based feature selection module in shape and texture feature fusion to focus on the key features and eliminate information redundancy caused by feature fusion. Finally, aiming at the problem of model optimization difficulty caused by the imbalance in the number of benign and malignant samples in medical images, an asymmetric loss function was introduced to improve the robustness of the model.

Results and conclusion

We applied our method to the melanoma recognition task on ISIC-2019 and XJTU-MM datasets, which focus on both the texture and shape of the lesions. The experimental results on dermoscopic image recognition and pathological image recognition datasets show the proposed method outperforms the compared algorithms and prove the effectiveness of our method.
Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of Down syndrome
Authors: Qiu Jia-jun , Liu Yan-na , Wei Hao , Zeng Fanyi , Yan Jing-bin
Published: June 2023

Introduction

Down syndrome (DS) is the most common genetic condition that causes intellectual disability in humans. The molecular mechanisms behind the DS phenotype remain unclear. Therefore, in this study, we present new findings on its molecular mechanisms through single-cell RNA sequencing.

Methods

Induced pluripotent stem cells (iPSCs) from the patients with DS and the normal control (NC) patients were differentiated into iPSCs-derived neural stem cells (NSCs). Single-cell RNA sequencing was performed to achieve a comprehensive single-cell level differentiation roadmap for DS-iPSCs. Biological experiments were also performed to validate the findings.

Results and Discussion

The results demonstrated that iPSCs can differentiate into NSCs in both DS and NC samples. Furthermore, 19,422 cells were obtained from iPSC samples (8,500 cells for DS and 10,922 cells for the NC) and 16,506 cells from NSC samples (7,182 cells for DS and 9,324 cells for the NC), which had differentiated from the iPSCs. A cluster of DS-iPSCs, named DS-iPSCs-not differentiated (DSi-PSCs-ND), which had abnormal expression patterns compared with NC-iPSCs, were demonstrated to be unable to differentiate into DS-NSCs. Further analysis of the differentially expressed genes revealed that inhibitor of differentiation family (ID family) members, which exhibited abnormal expression patterns throughout the differentiation process from DS-iPSCs to DS-NSCs, may potentially have contributed to the neural differentiation of DS-iPSCs. Moreover, abnormal differentiation fate was observed in DS-NSCs, which resulted in the increased differentiation of glial cells, such as astrocytes, but decreased differentiation into neuronal cells. Furthermore, functional analysis demonstrated that DS-NSCs and DS-NPCs had disorders in axon and visual system development. The present study provided a new insight into the pathogenesis of DS.
Transcriptomic and proteomic profiling of the anterior cingulate cortex in neuropathic pain model rats
Authors: Qiu Xin-Tong , Guo Chen , Ma Li-Tian , Li Xin-Ning , Zhang Qi-Yan , Huang Fen-Sheng , Zhang Ming-Ming , Bai Yang , Liang Guo-Biao , Li Yun-Qing
Published: June 2023

Background

Neuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing.

Methods

The NP model was established by spared nerve injury (SNI) in Sprague–Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in.

Results

Transcriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels.

Conclusion

The present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.
Leaderless secretory proteins of the neurodegenerative diseases via TNTs: a structure-function perspective
Authors: Padmanabhan Sreedevi , Manjithaya Ravi
Published: June 2023

Neurodegenerative disease-causing proteins such as alpha-synuclein, tau, and huntingtin are known to traverse across cells via exosomes, extracellular vesicles and tunneling nanotubes (TNTs). There seems to be good synergy between exosomes and TNTs in intercellular communication. Interestingly, many of the known major neurodegenerative proteins/proteolytic products are leaderless and are also reported to be secreted out of the cell via unconventional protein secretion. Such classes contain intrinsically disordered proteins and regions (IDRs) within them. The dynamic behavior of these proteins is due to their heterogenic conformations that is exhibited owing to various factors that occur inside the cells. The amino acid sequence along with the chemical modifications has implications on the functional roles of IDRs inside the cells. Proteins that form aggregates resulting in neurodegeneration become resistant to degradation by the processes of autophagy and proteasome system thus leading to Tunneling nanotubes, TNT formation. The proteins that traverse across TNTs may or may not be dependent on the autophagy machinery. It is not yet clear whether the conformation of the protein plays a crucial role in its transport from one cell to another without getting degraded. Although there is some experimental data, there are many grey areas which need to be revisited. This review provides a different perspective on the structural and functional aspects of these leaderless proteins that get secreted outside the cell. In this review, attention has been focused on the characteristic features that lead to aggregation of leaderless secretory proteins (from structural-functional aspect) with special emphasis on TNTs.
Novel blood product transfusion regimen to prevent clotting and citrate accumulation during continuous renal replacement therapy with regional citrate anticoagulation in children
Authors: Sun Yuelin , Li Dong , Bai Ke , Xu Feng , Liu Chengjun , Dang Hongxing
Published: June 2023

Objective

Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children.

Methods

We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT.

Results

Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p < 0.05). Changes in these three indicators were not significant in the PRCTP group.

Conclusion

Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.
Forensic age estimation in living children: how accurate is the Greulich-Pyle method in Sabah, East Malaysia?
Authors: Nang Khin Mya , Ismail Abdul Jabbar , Tangaperumal Anithaa , Wynn Aye Aye , Thein Tin Tin , Hayati Firdaus , Teh Yong Guang
Published: June 2023

Background

The Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist (GP Atlas) is the most widely used method of determining the bone age (BA) of a child. It is also a widely accepted method for forensic age determination. As there is limited local bone age data for forensic age estimation, the purpose of this study was to assess the accuracy of the GP Atlas for forensic age determination in living Sabahan children.

Method

This study recruited 182 children between the ages of 9 years to 18 years. BA estimation of the left-hand anteroposterior radiographs were performed by two experienced radiologists using the Greulich-Pyle method.

Results

The BA estimates from two radiologists had very high interobserver reliability (ICC 0.937) and a strong positive interobserver correlation (r > 0.90). The GP method, significantly and consistently underestimated chronological age (CA) by 0.7, 0.6 and 0.7 years in overall children, boys and girls respectively with minimal errors. Mean absolute error and root of mean squared error for overall children was 1.5 and 2.2 years respectively, while mean absolute percentage error was 11.6%. This underestimation was consistent across all age groups but was statistically significant only at 13–13.9 and 17–18.9 years old age groups.

Conclusion

Despite high interobserver reliability of BA estimation using the GP Atlas, this method consistently underestimates the age of the child in all children to a significant degree, for both boys and girls across all age groups, with an acceptably low level of error metrics. Our findings suggest that locally validated GP Atlas or other type of assessments (artificial intelligence or machine learning) are needed for assessment of BA to accurately predict CA, since current GP Atlas standards significantly underestimated chronological age with minimal error for children in Sabah. A larger population-based study would be necessary for establishing a validated atlas of a bone age in Malaysia.
In silico analysis of the solute carrier (SLC) family in cancer indicates a link among DNA methylation, metabolic adaptation, drug response, and immune reactivity
Authors: Lavoro Alessandro , Falzone Luca , Tomasello Barbara , Conti Giuseppe Nicolò , Libra Massimo , Candido Saverio
Published: June 2023

Introduction: The oncogenic transformation is driven by genetic and epigenetic alterations influencing cancer cell fate. These alterations also result in metabolic reprogramming by modulating the expression of membrane Solute Carrier (SLC) transporters involved in biomolecules trafficking. SLCs act as tumor suppressors or promoters influencing cancer methylome, tumor growth, immune-escape, and chemoresistance.

Methods: This in silico study aimed to identify the deregulated SLCs in various tumor types compared to normal tissues by analyzing the TCGA Target GTEx dataset. Furthermore, the relationship between SLCs expression and the most relevant tumor features was tackled along with their genetic regulation mediated by DNA methylation.

Results: We identified 62 differentially expressed SLCs, including the downregulated SLC25A27 and SLC17A7, as well as the upregulated SLC27A2 and SLC12A8. Notably, SLC4A4 and SLC7A11 expression was associated with favorable and unfavorable outcome, respectively. Moreover, SLC6A14, SLC34A2, and SLC1A2 were linked to tumor immune responsiveness. Interestingly, SLC24A5 and SLC45A2 positively correlated with anti-MEK and anti-RAF sensitivity. The expression of relevant SLCs was correlated with hypo- and hyper-methylation of promoter and body region, showing an established DNA methylation pattern. Noteworthy, the positive association of cg06690548 (SLC7A11) methylation with cancer outcome suggests the independent predictive role of DNA methylation at a single nucleotide resolution.

Discussion: Although our in silico overview revealed a wide heterogeneity depending on different SLCs functions and tumor types, we identified key SLCs and pointed out the role of DNA methylation as regulatory mechanism of their expression. Overall, these findings deserve further studies to identify novel cancer biomarkers and promising therapeutic targets.
Licraside as novel potent FXR agonist for relieving cholestasis: structure-based drug discovery and biological evaluation studies
Authors: Xi Lili , Shi Axi , Shen Tiantian , Wang Guoxu , Wei Yuhui , Guo Jingjing
Published: June 2023

Cholestasis is a common clinical disease caused by a disorder in bile acids (BAs) homeostasis, which promotes its development. The Farnesoid X receptor (FXR) plays a critical role in regulating BAs homeostasis, making it an essential target for cholestasis treatment. Although several active FXR agonists have been identified, effective drugs for cholestasis are still lacking. To address this, a molecular docking-based virtual screening method was used to identify potential FXR agonists. A hierarchical screening strategy was employed to improve the screening accuracy, and six compounds were selected for further evaluation. Dual-luciferase reporter gene assay was used to demonstrate FXR activation by the screened compounds, and their cytotoxicity was then evaluated. Among the compounds, licraside showed the best performance and was selected for in vivo evaluation using an ANIT-induced cholestasis animal model. Results demonstrated that licraside significantly reduced biliary TBA, serum ALT, AST, GGT, ALP, TBIL, and TBA levels. Liver histopathological analysis showed that licraside also had a therapeutic effect on ANIT-induced liver injury. Overall, these findings suggest that licraside is an FXR agonist with potential therapeutic effects on cholestasis. This study provides valuable insights into the development of novel lead compounds from traditional Chinese medicine for cholestasis treatment.