bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of drought, precipitation and fossorial mammal reintroduction on the density of fossorial arthropods and their burrows in arid Australia
Authors: Coulter Brianna , West Rebecca S. , Kingsford Richard T. , Moseby Katherine E. 
Published: May 2023

AbstractThe density and abundance of arid‐dwelling taxa often change significantly in response to precipitation fluctuations and the abundance of their predators. The survival and density of burrowing arthropods and their burrows in arid environments following prolonged dry periods and subsequent rains is poorly understood, as is the potential influence of reintroductions of their predators, such as fossorial mammals. The persistence of these arthropods and their burrows may be important for other species that rely on them for food or use their burrows for shelter. In this study, we examined the density of burrowing and ground‐nesting arthropods and their burrows in Australia's Strzelecki Desert over two years between 2019 and 2021. This period spanned the tail‐end of the worst drought on record and subsequent drought‐breaking rains. We employed a Before‐After Control‐Impact (BACI) study design to examine the short‐term effects of a fossorial mammal reintroduction of the greater bilby (Macrotis lagotis) into predator‐free fenced exclosures and used an inspection camera to detect the presence of spiders and other taxa within individually marked burrows. We observed the largest changes in arthropod abundance and burrow density between a period that encompassed a third consecutive summer in drought and the commencement of drought‐breaking rains, with some taxa declining by as much as 77% (p < 0.001). While the density of harvester ant middens erupted over this time, the density of tarantulas, trapdoor spiders and scorpions declined significantly. The greater bilby reintroduction had no short‐term effect on the densities of the arthropods or their burrows, but their arrival may have implications on their post‐drought recovery. Further studies are needed to determine if the significant declines in arthropod populations and burrows are reflective of normal boom‐bust population dynamics due to the poor natural history knowledge of the arthropods we examined.
Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy
Authors: Ma Yingjie , Yu Junxian , Ma Xiaoting , Li Qin , Su Qiang , Cao Bangwei 
Published: May 2023

AbstractEsophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC.
Implementation of the combined use of non‐invasive fetal electrocardiography and electrohysterography during labor: A prospective clinical study
Authors: Frenken Maria W. E. , Van Der Woude Daisy A. A. , Vullings Rik , Oei Swan G. , Van Laar Judith O. E. H. 
Published: May 2023

AbstractIntroductionFetal electrocardiography (NI‐fECG) and electrohysterography (EHG) have been proven more accurate and reliable than conventional non‐invasive methods (doppler ultrasound and tocodynamometry) and are less affected by maternal obesity. It is still unknown whether NI‐fECG and EHG will eliminate the need for invasive methods, such as the intrauterine pressure catheter and fetal scalp electrode. We studied whether NI‐fECG and EHG can be successfully used during labor.Material and MethodsA prospective clinical pilot study was performed in a tertiary care teaching hospital. A total of 50 women were included with a singleton pregnancy with a gestational age between 36+0 and 42+0 weeks and had an indication for continuous intrapartum monitoring. The primary study outcome was the percentage of women with NI‐fECG and EHG monitoring throughout the whole delivery. Secondary study outcomes were reason and timing of a switch to conventional monitoring methods (i.e., tocodynamometry and fetal scalp electrode or doppler ultrasound), repositioning of the abdominal electrode patch, success rates (i.e., the percentage of time with signal output), and obstetric and neonatal outcomes. Clinical trial registration: Dutch trial register (NL8024).ResultsIn 45 women (90%), NI‐fECG and EHG monitoring was used throughout the whole delivery. In the other five women (10%), there was a switch to conventional methods: in two women because of insufficient registration quality of uterine contractions and in three women because of insufficient registration quality of the fetal heart rate. In three out of five cases, the switch was after full dilation was reached. Repositioning of the abdominal electrode patch occurred in two women. The overall success rate was 94.5%. In 16% (n = 8) of women, a cesarean delivery was performed due to non‐progressing dilation (n = 7) and due to suspicion of fetal distress (n = 1). Neonatal metabolic acidosis did not occur. Two neonates (4%) were admitted to the neonatal intensive care unit for complications not related to intrapartum monitoring.ConclusionsNI‐fECG and EHG can be successfully used during labor in 90% of women. Future research is needed to conclude whether implementation of electrophysiological monitoring can improve obstetric and neonatal outcomes.
Visual function in adults born preterm with very low birth weight—A two‐country birth cohort study
Authors: Kulmala Maarit , Jørgensen Anna Perregaard Munch , Aakvik Kristina Anna Djupvik , Jussinniemi Laura , Benum Silje Dahl , Ingvaldsen Sigrid Hegna , Austeng Dordi , Kajantie Eero , Evensen Kari Anne I. , Majander Anna , Morken Tora Sund 
Published: May 2023

AbstractPurposeThe purpose of the study was to investigate visual function and vision‐related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s–40s.MethodsWe recruited 137 adults born preterm with VLBW and 158 term‐born controls aged 31–43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best‐corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self‐reported vision‐targeted health status with the National Eye Institute Visual Function Questionnaire‐25.ResultsVLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self‐reported vision‐targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity.ConclusionWe suggest that lower visual function and vision‐related health represent life‐long consequences of prematurity and VLBW in the studied 31‐ to 43‐year‐old cohort. The underlying mechanisms remain to be determined.
Post‐marketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System
Authors: Zhuang Wei , Xu Jiabing , Wu Ye , Yang Jianhui , Lin Xiuxian , Liao Yufang , Wan Jun , Weng Lizhu , Lin Wanlong 
Published: May 2023

AimsNirmatrelvir is an antiviral drug with a novel mechanism of action, targeting the 3‐CL protease, and is used in the treatment of COVID‐19. However, the potential side effects have not yet been fully studied. The aim of this study was to identify potential safety signals of nirmatrelvir by analysing post‐marketing safety data based on the largest publicly available worldwide pharmacovigilance database.MethodsWe analysed nirmatrelvir adverse events to identify and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. The case/non‐case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered 4 or more.ResultsA total of 26 846 cases were included. Disease recurrence (ROR [95% CI] = 413.2 [395.6–431.59]), dysgeusia (ROR [95% CI] = 110.84 [106.04–115.85]), anosmia (ROR [95% CI] = 15.21 [12.76–18.11]), ageusia (ROR [95% CI] = 9.80 [8.50–11.3]) and urticaria (ROR [95% CI] = 1.91 [1.69–2.17]) were the main safety signals. In addition, abdominal pain upper and skin toxicity were two specific safety signals of nirmatrelvir. In the pregnant population, there was a significant increased ROR for life‐threatening conditions (ROR [95% CI] = 8.00 [1.77–36.20]).ConclusionsOur study identified that the main and specific safety signals of nirmatrelvir were disease recurrence, dysgeusia, abdominal pain upper and skin toxicity. Clinicians and pharmacists should be vigilant of these AEs, although differentiating between COVID‐19 symptoms and AEs can be challenging. Notably, a potential safety concern of nirmatrelvir should be a warning based on a small number of events in the pregnant population. However, the available data are insufficient, and further continued pharmacovigilance and surveillance is needed to fully understand this issue.
Dissecting calvarial bones and sutures at single‐cell resolution
Authors: Li Bo , Li Jingya , Fan Yi , Zhao Zhihe , Li Longjiang , Okano Hideyuki , Ouchi Takehito 
Published: May 2023

ABSTRACTCranial bones constitute a protective shield for the vulnerable brain tissue, bound together as a rigid entity by unique immovable joints known as sutures. Cranial sutures serve as major growth centres for calvarial morphogenesis and have been identified as a niche for mesenchymal stem cells (MSCs) and/or skeletal stem cells (SSCs) in the craniofacial skeleton. Despite the established dogma of cranial bone and suture biology, technological advancements now allow us to investigate these tissues and structures at unprecedented resolution and embrace multiple novel biological insights. For instance, a decrease or imbalance of representation of SSCs within sutures might underlie craniosynostosis; dural sinuses enable neuroimmune crosstalk and are newly defined as immune hubs; skull bone marrow acts as a myeloid cell reservoir for the meninges and central nervous system (CNS) parenchyma in mediating immune surveillance, etc. In this review, we revisit a growing body of recent studies that explored cranial bone and suture biology using cutting‐edge techniques and have expanded our current understanding of this research field, especially from the perspective of development, homeostasis, injury repair, resident MSCs/SSCs, immunosurveillance at the brain's border, and beyond.
Discovery of [5,5′‐bibenzo[d][1,3]dioxol]‐6‐substituted amine derivatives as potent proprotein convertase subtilisin/kexin type 9 inhibitors
Authors: Zhu Dongqi , Qin Hongyu , Wang Xiaojing , Jia Yuping , Wang Xuejian , Zhang Lei 
Published: May 2023

AbstractProprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hyperlipidemia. In discovery of novel small molecules that interfere PCSK9/LDLR protein–protein interaction (PPI), structural modification was performed based on our previously derived compounds. A series of [5,5′‐bibenzo[d][1,3]dioxol]‐6‐amine analogs were designed and synthesized for the activity evaluation. In the PCSK9/LDLR PPI impairing test, molecules D28 and D29, exhibited remarkable inhibitory potency with IC50 values of 8.30 and 6.70 μM compared with SBC‐115337 (17.89 μM), respectively. Molecular docking predicted the binding pattern of compounds D28 and D29 in the LDLR binding site of PCSK9. Hydrophobic interactions play an important role in the binding of aromatic molecular fragments to the pockets in the PCSK9/LDLR binding interface. Further LDLR expression and LDL uptake studies revealed that both D28 and D29 restored LDLR expression on the surface of hepatic HepG2 cells and improved extracellular LDL uptake in the presence of PCSK9. It is significant that molecules D28 and D29 exhibited potential for the treatment of hyperlipidemia in current in vitro investigations. Generally, lead compounds with novel structures were developed in the present study for further design of lipid‐lowering molecules by targeting PCSK9/LDLR PPI.
Arctigenin improves neuropathy via ameliorating apoptosis and modulating autophagy in streptozotocin‐induced diabetic mice
Authors: Medras Zekrayat J. H. , Mostafa Yasser M. , Ahmed Amal A. M. , El‐Sayed Norhan M. 
Published: May 2023

AbstractBackgroundOxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property. The present study aimed to explore the mechanistic neuroprotective effect of ARC on animal model for DN.MethodsDN was induced using streptozotocin (STZ) at a dose of 45 mg/kg, i.p, for five consecutive days and ARC was administered orally (25 or 50 mg) for 3 weeks. The mechanical sensitivity and thermal latency were determined using von Frey and hotplate, respectively. Beclin, p62, and LC3 were detected as markers for autophagy by western blot. Levels of reduced glutathione, lipid peroxides, and activities of catalase and superoxide dismutase were detected as readout for oxidative stress. Apoptotic parameters and histopathological changes were revealed in all experimental groups.ResultsThe present study showed deterioration of the function and structure of neurons as a result of hyperglycemia. Oxidative stress and impaired autophagy were observed in diabetic neurons as well as the activation of apoptotic pathway. ARC improved the behavioral and histopathological changes of diabetic mice. ARC combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis. ARC augmented the expression of Beclin and LC3 while it lessened the expression of p62 indicating the activation of autophagy. These findings suggest that ARC can ameliorate DN by combating apoptosis and oxidative stress and improving autophagy.
Endothelial TREM‐1 receptor regulates the blood–brain barrier integrity after intracerebral hemorrhage in mice via SYK/β‐catenin signaling
Authors: Xie Yonglin , He Wei , Ma Li , Ren Reng , Yang Shuxu , Lu Qin 
Published: May 2023

AbstractBackgroundIntracerebral hemorrhage (ICH) is a high mortality and disability stroke subtype. Destruction of the blood–brain barrier (BBB) is a crucial contributor to brain edema and neurological deficit after ICH. Triggering receptor expressed on myeloid cells 1 (TREM‐1) has been reported to be expressed in endothelial cells, but its role in ICH remains unclear. This study aims to evaluate the role of TREM‐1 on BBB permeability after ICH in mice.MethodsTwo hundred and forty‐two CD1 mice were used in this study. The ICH model was established by collagenase injection. LP17 was administered intranasally at 2 or 8 h after ICH to inhibit TREM‐1. To explore the underlying mechanism, SYK activation CRISPR was administered intracerebroventricularly with LP17, and Anti‐mouse TREM‐1 rat IgG2a (a specific TREM‐1 agonist) was injected intracerebroventricularly with R406 (a specific SYK inhibitor) intraperitoneally. Neurobehavioral outcome, brain water content, BBB permeability, and protein expression were evaluated.ResultsThe expression level of the TREM‐1 receptor increased rapidly as early as 6 h after ICH, and it was mainly expressed on the endotheliocytes in the neurovascular unit. Early and delayed administration of LP17 significantly decreased brain edema and improved neurobehavioral outcomes at 24 h after ICH. LP17 reduced the BBB permeability by increasing β‐catenin, claudin‐5 and ZO‐1 expression. Furthermore, SYK activation CRISPR abolished the beneficial effect of LP17 on the expression of the above junction molecules. Meanwhile, R406 reversed the impact of the TREM‐1 activator on the downregulation of β‐catenin, claudin‐5 and ZO‐1 expression.ConclusionsThis study demonstrated that TREM‐1 deteriorated BBB permeability via modulating the expression of interendothelial junction molecules after ICH, and this regulation is partly mediated by the SYK/β‐catenin signaling pathway.
Brain functional connectivity‐based prediction of vagus nerve stimulation efficacy in pediatric pharmacoresistant epilepsy
Authors: Chen Hao , Wang Yi , Ji Taoyun , Jiang Yuwu , Zhou Xiao‐Hua 
Published: May 2023

AbstractObjectiveAlthough vagus nerve stimulation (VNS) is a common and widely used therapy for pharmacoresistant epilepsy, the reported efficacy of VNS in pediatric patients varies, so it is unclear which children will respond to VNS therapy. This study aimed to identify functional brain network features associated with VNS action to distinguish VNS responders from nonresponders using scalp electroencephalogram (EEG) data.MethodsTwenty‐three children were included in this study, 16 in the discovery cohort and 7 in the test cohort. Using partial correlation value as a measure of whole‐brain functional connectivity, we identified the differential edges between responders and nonresponders. Results derived from this were used as input to generate a support vector machine‐learning classifier to predict VNS outcomes.ResultsThe postcentral gyrus in the left and right parietal lobe regions was identified as the most significant differential brain region between VNS responders and nonresponders (p < 0.001). The resultant classifier demonstrated a mean AUC value of 0.88, a mean sensitivity rate of 91.4%, and a mean specificity rate of 84.3% on fivefold cross‐validation in the discovery cohort. In the testing cohort, our study demonstrated an AUC value of 0.91, a sensitivity rate of 86.6%, and a specificity rate of 79.3%. Furthermore, for prediction accuracy, our model can achieve 81.4% accuracy at the epoch level and 100% accuracy at the patient level.SignificanceThis study provides the first treatment response prediction model for VNS using scalp EEG data with ictal recordings and offers new insights into its mechanism of action. Our results suggest that brain functional connectivity features can help predict therapeutic response to VNS therapy. With further validation, our model could facilitate the selection of targeted pediatric patients and help avoid risky and costly procedures for patients who are unlikely to benefit from VNS therapy.
Neuropathic pain following spinal cord hemisection induced by the reorganization in primary somatosensory cortex and regulated by neuronal activity of lateral parabrachial nucleus
Authors: Li Jing , Tian Chao , Yuan Shiyang , Yin Zhenyu , Wei Liangpeng , Chen Feng , Dong Xi , Liu Aili , Wang Zhenhuan , Wu Tongrui , Tian Chunxiao , Niu Lin , Wang Lei , Wang Pu , Xie Wanyu , Cao Fujiang , Shen Hui 
Published: May 2023

AbstractAimsNeuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS).MethodsThrough behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two‐photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long‐term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated.ResultsThe calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain.ConclusionThe neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN.
Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study
Authors: Kozuka Kazuhiro , Kobara Hideki , Matsui Takanori , Fujisawa Akihiko , Tatsuta Miwa , Kobayashi Mitsuyoshi , Yasuda Mitsugu , Nakatani Kaho , Tada Naoya , Chiyo Taiga , Kobayashi Nobuya , Yachida Tatsuo , Nishiyama Noriko , Fujihara Shintaro , Kondo Akihiro , Okano Keiichi , Tsuji Akihito , Masaki Tsutomu 
Published: May 2023

ObjectivesNo protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol.MethodsThis was a two‐facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes.ResultsThere were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively.ConclusionsSeven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.