bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of optical coherence tomography angiography results in patients with internal carotid artery stenosis who underwent carotid artery stenting and carotid endarterectomy
Authors: Ozdogru Derya , Kurumoglu Incekalan Tugba , Simdivar Goksu Hande Naz , Ozturk Ilker , Simsek Yeliz , Okten Candan Cudi , Avci Akkan
Published: August 2024

It is important to examine the ocular hemodynamic changes after carotid artery stenting (CAS) and carotid endarterectomy (CEA) in patients with internal carotid artery stenosis (ICAS). We aimed to compare the differences in retinal and optic nerve head blood flow after 2 surgical methods. The ipsilateral eyes of 34 patients who had over 50% ICAS with no ocular findings and 30 healthy controls were included in the study. Foveal avascular zone vessel density in the superficial retinal capillary plexus, deep retinal capillary plexus (DCP), and radial peripapillary capillary plexus (RPCP) were measured with an optical coherence tomography angiography device. These measurements were repeated 1 month after CAS or CEA in patients with ICAS. The preoperative and postoperative values of the patients were compared both within themselves and with the control group. When patients with ICAS were compared with the control group, lower vessel density values were found in the DCP parafovea, RPCP whole image, and peripapillary regions both before and after the procedure. There was no significant difference in terms of other parameters. Furthermore, there was no significant difference in any parameter examined between the pre- and postprocedural values of the patients who underwent CAS and CEA. DCP and RPCP are mostly affected in patients with ICAS. We observed that after application of the CAS and CEA methods, the effects on ocular blood flow were similar.
Bibliometric analysis of scientific outputs on psychobiotics: Strengthening the food and mood connection
Authors: Kaya Muhammed , Erdoğan Kaya Ayşe , Eskin Fatih
Published: August 2024

The role of human microbiota in mental health and the underlying mechanisms of psychobiotics, which can modulate mood and behavior through the microbiota–gut–brain axis, has been a focus of scientific scrutiny. This work presents a bibliometric analysis to uncover research trends and insights in psychobiotics literature. The Clarivate Analytics Web of Science database served as the source for articles and reviews on psychobiotics spanning the years 2012 to 2023. Bibliometric network visualization and graphing were conducted using VOSviewer, Microsoft Excel for Windows 10, and Datawrapper software. A total of 348 publications were included, and it has been determined that the number of publications and citations shows an increasing trend from 2012 to 2023. The most active authors on psychobiotics, in order, were Dinan TG, Cryan JF, and Tsai YC. The most active organizations have been identified as University College Cork, National Yang Ming Chiao Tung University, and Bened Biomedical Co. Ltd. The most active countries in psychobiotic research were China, Ireland, and United States of America, while the most active journals were Nutrients, International Journal of Molecular Sciences, and Probiotics and Antimicrobial Proteins. The most commonly used keywords were “psychobiotics,” “probiotics,” and “gut–brain axis.” This bibliometric analysis has revealed the growing academic interest in psychobiotics, indicating that the relationship between gut microbiota and mental health will increasingly be supported by scientific evidence in the years ahead.
Impact of the COVID-19 pandemic on risk of sarcopenia: From lockdown and infection perspectives: A systematic review and meta-analysis
Authors: Wang Xiang , Guo Qiaofeng , Huang Kai , Ma Gouping , Zhai Lifeng , Lin Bingyuan , Ren Haiyong , Yang Ze
Published: August 2024

Background:

During the new coronavirus disease 2019 (COVID-19) pandemic, there are numerous symptoms in the skeletal muscular system, such as decreased skeletal muscle mass, strength, and muscle function, which are the main manifestations of sarcopenia. To investigate the impact of the COVID-19 pandemic on sarcopenia from the perspectives of COVID-19 pandemic lockdown and COVID-19 infection, we conducted this study.

Methods:

We searched for literature related to COVID-19 and sarcopenia published in PubMed, Embase, Cochrane Library, and Web of Science. Two researchers independently searched and screened the articles, extracted data, and assessed the quality of the final included literature. RevMan 5.4 was used for meta-analysis.

Results:

A total of 8 articles with a total of 1145 patients were included. There was a significant difference in SARC-F scores (MD = 0.67, 95%CI = [0.41, 0.93], Z = 5.00, P < .00001), handgrip (MD = ‐1.57, 95%CI = [‐2.41, ‐0.73], Z = 3.66, P = .0002), body weight (MD = ‐1.87, 95%CI = [‐3.69, ‐0.05], Z = 2.01, P = .04), and skeletal muscle mass index (MD = ‐0.28, 95%CI = [‐0.54, ‐0.02], Z = 2.13, P = .03) between the time before the COVID-19 pandemic and during the COVID-19 pandemic. However, the results showed that there was no significant difference in muscle mass between the 2 groups (MD = ‐1.72, 95%CI = [‐4.39, 0.94], Z = 1.27, P = .21).

Conclusion:

The COVID-19 pandemic has had an impact on sarcopenia. Both infection with COVID-19 and lockdown during the COVID-19 pandemic increase the risk of sarcopenia. Research should pay more attention to this disease during the COVID-19 pandemic and adopt effective interventions to minimize adverse outcomes.
Efficacy and safety of navigation robot-assisted versus conventional oblique lateral lumbar interbody fusion with internal fixation in the treatment of lumbar degenerative diseases: A retrospective study
Authors: Tong Min , Zhang Siping , Zhang Wenhao , Mou Limin , Dong Zhenyu , Wang Rong , Li Shida , Huang Yifei
Published: August 2024

Effective internal fixation with pedicle screw is a key factor in the success of lumbar fusion with internal fixation. Whether navigation robots can improve the efficacy and safety of screw placement is controversial. Thirty-eight patients who underwent oblique lateral lumbar interbody fusion internal fixation from March 2022 to May 2023 were retrospectively analyzed, 16 cases in the navigational robot group and 22 cases in the fluoroscopy group. Using visual analog score (VAS) for the low back and lower limbs, Oswestry Disability Index to compare the clinical efficacy of the 2 groups; using perioperative indexes such as the duration of surgery, intraoperative blood loss, intraoperative fluoroscopy times, and postoperative hospital stay to compare the safety of the 2 groups; and using accuracy of pedicle screws (APS) and the facet joint violation (FJV) to compare the accuracy of the 2 groups. Postoperative follow-up at least 6 months, there was no statistically significant difference between the 2 groups in the baseline data (P > .05). The navigational robot group’s VAS-back was significantly lower than the fluoroscopy group at 3 days postoperatively (P < .05). However, the differences between the 2 groups in VAS-back at 3 and 6 months postoperatively, and in VAS-leg and Oswestry Disability Index at 3 days, 3 months, and 6 months postoperatively were not significant (P > .05). Although duration of surgery in the navigational robot group was significantly longer than in the fluoroscopy group (P > .05), the intraoperative blood loss and the intraoperative fluoroscopy times were significantly lower than in the fluoroscopy group (P < .05). The difference in the PHS between the 2 groups was not significant (P > .05). The APS in the navigation robot group was significantly higher than in the fluoroscopy group, and the rate of FJV was significantly lower than in the fluoroscopy group (P < .05). Compared with the traditional fluoroscopic technique, navigation robot-assisted lumbar interbody fusion with internal fixation provides less postoperative low back pain in the short term, with less trauma, less bleeding, and lower radiation exposure, as well as better APS and lower FJV, resulting in better clinical efficacy and safety.
A giant solitary fibrous tumor of the abdominal pelvic cavity: A case report and literature review
Authors: Li Cao , Yang Jianyang , Chen Hongli , Yang Lie
Published: August 2024

Rationale:

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor, especially the giant one from the abdominal pelvic cavity. We report on a rare case of a giant SFT of the abdominal pelvic cavity to review the existing literature in detail to improve the diagnosis and treatment of SFT.

Patient concerns:

The patient is a 52-year-old female who presented with 2 weeks of abdominal distension. Abdominal magnetic resonance imaging showed a giant mass (>20 cm) in the abdominal pelvic cavity, considered a mesenchymal tumor. She denies a history of tumor disease.

Diagnoses:

A whole abdomen bulge and a mass of about 18 cm × 10 cm on the right side and middle side were found in the physical examination after admission. Abdominal enhanced computed tomography revealed a giant cystic-solid mass located on the middle and right side of the abdominal pelvic cavity, measuring approximately 20.4 cm × 11.7 cm, with multiple cystic changes and necrosis and compression of adjacent organs and tissues, and marked inhomogeneous enhancement.

Interventions:

The patient underwent an open abdominal pelvic cavity giant tumor operation to achieve a radical resection, and did not undergo chemotherapy or radiotherapy.

Outcomes:

The patient underwent open complete resection of a giant abdominal pelvic tumor with no complications and was diagnosed as SFT according to the pathology, immunohistochemistry showed that the tumor tested positive for CD34(+), STAT-6(+), and Ki-67 (10%). Abdominal computed tomography scans were performed 6 months after resection, and no signs of recurrence or metastasis were found.

Lessons:

The clinical symptoms and imaging features of giant abdominal pelvic cavity SFT are not typical. Preoperative diagnosis is difficult and has the potential for malignancy. Based on the results of the current study, there is no standard treatment strategy around the world and the therapeutic effect of radiation therapy and chemotherapy is relatively limited. Thus, complete surgical resection and close clinical follow-up are advocated.
Critical illness-associated cerebral microbleeds involving the corpus callosum following cardiac arrest: A case report
Authors: Srichawla Bahadar S. , Fang Ton , Kipkorir Vincent , Lalla Rakhee
Published: August 2024

Rationale:

Critical illness-associated cerebral microbleeds (CI-aCMBs) are emerging as significant radiographic findings in patients with hypoxic ischemic injuries. Their occurrence, particularly in the corpus callosum, warrants a closer examination due to the potential implications for neurological outcomes in critically ill patients. We aim to describe a rare case of CI-aCMBs within the corpus callosum following cardiac arrest with the goal of bolstering the scientific literature on this topic.

Patient concerns:

A 34-year-old man with a history of polysubstance abuse was found unconscious and experienced a pulseless electrical activity (PEA) cardiac arrest after a suspected drug overdose. Post-resuscitation, the patient exhibited severe respiratory distress, acute kidney injury, and profound neurological deficits.

Diagnoses:

Initial magnetic resonance imaging scans post-cardiac arrest showed no acute brain abnormalities. However, subsequent imaging revealed extensive cerebral microbleeds predominantly in the corpus callosum, diagnosed as CI-aCMBs. These findings were made in the absence of high signal intensity on T2-weighted images, suggesting a unique pathophysiological profile of microhemorrhages.

Interventions:

The patient underwent targeted temperature management (TTM) and supportive care in the intensive care unit after cardiac arrest.

Outcomes:

He was subsequently extubated and had significant recovery without any neurological deficits.

Lessons:

CI-aCMBs is a rare radiographic finding after cardiac arrest. These lesions may be confined to the corpus callosum and the long-term clinical and radiographic sequelae are still largely unknown.
Complementary therapy with Chinese aromatic herbs to promote awakening in a comatose patient: A case report
Authors: Chen Shi-Jia , Qiu Chang-Lin , Zhang Li-Ping , Jiang Ling-Zhi , Zhao Xiao-Yu , Hou Qun , Jiang Yan
Published: August 2024

Rationale:

Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be “resuscitation with aromatics” based on traditional Chinese medicines theory.

Patient concerns:

A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury.

Diagnoses:

Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease.

Interventions:

According to the patient’s condition, we use the Chinese aromatic herbs as a complementary therapy.

Outcomes:

Following a month-long administration, the patient’s consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background.

Lessons:

The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient’s consciousness and EEG background. This could be attributed to the herbs’ inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.
Intrarenal venous flow patterns – Guiding fluid management in sepsis with AKI: A case report
Authors: Zhang Qian , Li Yi , Liu Lixia , Hu Zhenjie , Huo Yan
Published: August 2024

Introduction:

Sepsis often leads to acute kidney injury (AKI), presenting significant challenges in fluid management. This study explores the potential of analyzing intrarenal venous flow (IRVF) patterns to guide tailored fluid therapy, aiming to improve patient outcomes.

Patient concerns:

A patient was admitted to the intensive care unit with symptoms of septic shock, including fever, severe hypotension, and altered mental status, secondary to a perforated ascending colon adenocarcinoma.

Diagnosis:

The patient was diagnosed with perforated ascending colon adenocarcinoma, septic shock, and AKI. Clinical findings included elevated inflammatory markers and impaired renal function.

Interventions:

The primary therapeutic interventions included surgical resection of the perforated colon, administration of broad-spectrum antibiotics, and fluid resuscitation. Fluid management was guided by continuous monitoring of IRVF, which facilitated precise adjustments to optimize fluid balance and renal perfusion.

Outcomes:

By utilizing IRVF patterns to guide fluid therapy, the patient’s circulatory status and renal function significantly improved. The individualized fluid management approach contributed to better stabilization of the patient’s condition.

Lessons:

This case underscores the potential utility of IRVF patterns in guiding fluid management strategies for patients with sepsis and AKI. The main is the benefit of IRVF-guided fluid therapy in improving patient outcomes. Further research is warranted to validate the efficacy and safety of this approach, with the aim of enhancing clinical outcomes in critically ill patients.
An unusual case of an 0.018-inch (0.457 mm) guidewire fracture during primary percutaneous nephrostomy for percutaneous nephrolithotomy treated without removal and followed up for 5 years: A case report and literature review
Authors: Oh Seunghoon , Cho Bum Sang , Kim Yook , Lee Jisun , Yi Kyung Sik , Lee Sang-Cheol
Published: August 2024

Introduction:

Although rare, guidewire fractures can occur during interventional procedures. In most cases, the fractured guidewire segment can be removed.

Patient concerns:

We report the case of a 54-year-old woman who experienced a guidewire fracture during percutaneous nephrostomy (PCN) for percutaneous nephrolithotomy to remove renal stones.

Diagnosis:

Nephrolithiasis.

Interventions:

PCN and percutaneous nephrolithotomy.

Outcomes:

In this case, the remaining segment could not be removed and caused inflammation and infection. However, her symptoms improved with inpatient treatment. Therefore, she was discharged from the hospital and followed up for 5 years.

Conclusion:

When performing PCN to remove renal stones, the possibility of a guidewire fracture must be considered. If resistance or scraping is felt while handling the guidewire, then it should be replaced.
Global hotspots and trends in diabetic peripheral neuropathy research from 2011 to 2023
Authors: Tang Fei , Zhao Fukun , Jiang Yong , Zhang Tao , Wang Bangfeng
Published: August 2024

Diabetic peripheral neuropathy (DPN) is a prevalent disease, and the relevant literature has been increasingly investigated over the past years. Consequently, it is imperative to conduct a scientific and comprehensive DPN research field bibliometric analysis. This study aims to summarize and visualize the literature distribution laws, the research hotspots, and the development trends in DPN using bibliometric methods. We searched all relevant documents published from 2011 to 2023 in the Web of Science Core Collection. Bibliometric analysis and network visualization were performed using VOSviewer, R-bibliometrix, and CiteSpace tools, focusing on countries, institutions, authors, journals, highly cited papers, references, and keywords. This study included a total of 2708 documents. The annual number of publications in the field has notably increased. China, the USA, and the UK take on critical significance in DPN research. The University of Manchester in the UK has the highest number of publications (109). Malik has the most publications (86). Tesfaye literature has been most frequently cited by scholars of DPN research. The Journal of Diabetes and its Complications and Frontiers in Endocrinology have the most publications (45 each). Diabetes Care stands out with the highest impact factor (16.200), number of citations (2516), and H-index (27) among the number of publications top 10 journals. The paper “Colloca, L. et al Neuropathic pain. Nature Reviews Disease Primers. 2017, 3 (1):1–19” has the highest number of citations (1224 times). The most critical co-cited reference is “Tesfaye S, 2010, DIABETES CARE, V33, P2285” (cited 408 times). Keywords like “type 2 diabetes,” “diagnosis,” “association,” “retinopathy,” “risk factors,” “progression,” “corneal confocal microscopy,” “nephropathy,” “balance,” “microvascular complications,” “inflammation,” “disease,” and “insulin resistance” represent the recent research hotspots. The development, research hotspots, and future trends of the global DPN domain from 2011 to 2023 were summarized and visualized in this study. This study can present more insights into the general situation of DPN research and provide a useful reference for clinical decision-making and directions of subsequent research.
Development and implementation of a core genome multilocus sequence typing scheme for Haemophilus influenzae
Authors: Krisna Made Ananda , Jolley Keith A. , Monteith William , Boubour Alexandra , Hamers Raph L. , Brueggemann Angela B. , Harrison Odile B. , Maiden Martin C. J.
Published: August 2024

Haemophilus influenzae is part of the human nasopharyngeal microbiota and a pathogen causing invasive disease. The extensive genetic diversity observed in H. influenzae necessitates discriminatory analytical approaches to evaluate its population structure. This study developed a core genome multilocus sequence typing (cgMLST) scheme for H. influenzae using pangenome analysis tools and validated the cgMLST scheme using datasets consisting of complete reference genomes (N = 14) and high-quality draft H. influenzae genomes (N = 2297). The draft genome dataset was divided into a development dataset (N = 921) and a validation dataset (N = 1376). The development dataset was used to identify potential core genes, and the validation dataset was used to refine the final core gene list to ensure the reliability of the proposed cgMLST scheme. Functional classifications were made for all the resulting core genes. Phylogenetic analyses were performed using both allelic profiles and nucleotide sequence alignments of the core genome to test congruence, as assessed by Spearman’s correlation and ordinary least square linear regression tests. Preliminary analyses using the development dataset identified 1067 core genes, which were refined to 1037 with the validation dataset. More than 70% of core genes were predicted to encode proteins essential for metabolism or genetic information processing. Phylogenetic and statistical analyses indicated that the core genome allelic profile accurately represented phylogenetic relatedness among the isolates (R
2 = 0.945). We used this cgMLST scheme to define a high-resolution population structure for H. influenzae, which enhances the genomic analysis of this clinically relevant human pathogen.
Prevalence and associated risk factors assessment of bovine fasciolosis in and around Bahir Dar, Ethiopia
Authors: Temesgen Abraham Belete , Mesfin Tesfaye
Published: August 2024

Bovine fasciolosis is a parasitic disease of cattle caused by ingesting metacercariae of liver flukes from the genus Fasciola. A cross-sectional study was conducted from November 2021 to April 2022, encompassing a total of 384 cattle randomly selected from diverse locations. The study included cattle of various ages and genders, aiming to to determine the prevalence of bovine fasciolosis and its associated risk factors in and around Bahir Dar, Ethiopia. Fecal examinations were performed to detect fluke eggs, and data were analyzed using descriptive statistics in STATA Version 20.0 to summarize bovine fasciolosis prevalence. Chi-square tests assessed relationships with infection rates and risk factors, with significance set at P < 0.05. Out of 384 fecal samples analyzed, 49.21% tested positive for Fasciola eggs. The prevalence of the condition varied significantly by origin, with rates of 50% in Tikurit, 61.84% in Sebatamit, 27.65% in Latammba, and 59.37% in Kebele 11. In terms of body condition, prevalence was notably higher in cattle classified as poor (64%) compared to those in medium condition (50%) and fat cattle (26.96%), with these differences being statistically significant. Age also influenced prevalence, with young cattle having a rate of 50.38%, adults 47.33%, and old cattle 50.47%; however, these differences were not statistically significant. Sex did not significantly impact prevalence, with males at 49.73% and females at 48.73%. Additionally, local cattle exhibited a prevalence of 51.62%, whereas crossbreeds had a prevalence of 46.15%, with no significant differences observed between these groups (p < 0.05). The persistently high rates of bovine fasciolosis highlight the urgent need for comprehensive control measures. Implementing enhanced management practices to minimize cattle exposure to contaminated pastures and water sources is essential for effective prevention and control of this parasitic infection.
Targeted Time-Varying Functional Connectivity
Authors: Alonso Sonsoles , Cocchi Luca , Hearne Luke J , Shine James M , Vidaurre Diego
Published: August 2024

To elucidate the neurobiological basis of cognition, which is dynamic and evolving, various methods have emerged to characterise time-varying functional connectivity (FC) and track the temporal evolution of functional networks. However, given a selection of regions, many of these methods are based on modelling all possible pairwise connections, diluting a potential focus of interest on individual connections. This is the case with the hidden Markov model (HMM), which relies on region-by-region covariance matrices across all pairs of selected regions, assuming that fluctuations in FC occur across all investigated connections; that is, that all connections are locked to the same temporal pattern. To address this limitation, we introduce Targeted Time-Varying FC (T-TVFC), a variant of the HMM that explicitly models the temporal fluctuations between two sets of regions in a targeted fashion, rather than across the entire connectivity matrix. In this study, we apply T-TVFC to both simulated and real-world data. Specifically, we investigate thalamocortical connectivity, hypothesizing distinct temporal signatures compared to corticocortical networks. Given the thalamus' role as a critical hub, thalamocortical connections might contain unique information about cognitive processing that could be overlooked in a coarser representation. We tested these hypotheses on high-field functional magnetic resonance data from 60 participants engaged in a reasoning task with varying complexity levels. Our findings demonstrate that the time-varying interactions captured by T-TVFC contain task-related information not detected by more traditional decompositions.
Ectopic cambia in Japanese wisteria (Wisteria floribunda) vines are associated with the expression of conservedKNOXgenes
Authors: Cunha Neto Israel L. , Snead Anthony A. , Landis Jacob B. , Specht Chelsea D. , Onyenedum Joyce G.
Published: August 2024

Secondary growth is a conserved mechanism that gives rise to vascular tissues produced via a single vascular cambium. Molecular mechanisms underlying this process are characterized mostly in model species bearing typical vascular architecture, while the genetics underlying ecologically-important atypical vascular architectures remain unexplored. We use developmental anatomy, comparative transcriptomics, and molecular evolutionary analyses to address this knowledge gap, investigating how multiple ectopic cambia (EC) form in the woody vine Japanese wisteria. Anatomical studies show EC in Japanese wisteria arise from cortical parenchyma, while cambium-specific transcriptome comparisons reveal that genes acting as regulators of typical cambium development in model species are likewise associated with atypical EC development. Gene trees of KNOX proteins indicate duplication events may contribute to EC formation, including a Fabaceae-specific duplication of KNAT6 detected as under positive selection. These findings reveal insights into the genetics of EC formation, advancing our understanding of the development of complex vascular traits.
Focality of sound source placement by higher (9th) order ambisonics and perceptual effects of spectral reproduction errors
Authors: Zargarnezhad Nima , Mesquita Bruno , Macpherson Ewan A , Johnsrude Ingrid
Published: August 2024

Higher-order ambisonic rendering is an increasingly common soundscape reproduction technique that, in theory, enables presentation of virtual sounds at nearly any location in 3D space, relatively unconstrained by the veridical locations of loudspeakers. We evaluated whether 3D sound reproduction through a 9th-order ambisonic loudspeaker array was indeed sufficiently accurate to probe the limits of human spatial perception. We first estimated minimum audible angles for human listeners for a variety of reference points on the horizontal plane. We demonstrated that the system can reproduce sounds with a spatial resolution that is equal or superior to the limits of human acuity, at least on the horizontal plane at the front. Importantly, the resolution of ambisonic reproduction appeared equivalent for regions of the system with high and low loudspeaker density. We also estimated localization cues at the same locations and showed that although localization cues for low-frequency components were well preserved, they were somewhat distorted for components above 4000 Hz. Finally, we provide evidence that these high-frequency distortions can serve elevation cues by human listeners. In summary, we showed that a 9thorder ambisonic system is able to render highly focal sound sources, and that high-frequency reproduction distortions may introduce unwanted localization cues.
Histone variant H3.3 mediates cGAS-STING pathway activation via telomere deprotection
Authors: Huang Chiao-Ming , Chen Liuh-Yow
Published: August 2024

Telomeric deposition of histone variant H3.3 is controlled by ATRX, DAXX, HIRA, and ASF1 proteins. Point mutations of H3.3 and defective mutants of ATRX are associated with cancers that utilize the alternative lengthening of telomeres (ALT) pathway to protect and maintain chromosome ends. Here, we identify a cascade of events following the expression of a TRF2 dominant negative mutant, TRF2ΔBΔM, which are regulated by H3.3 expression. H3.3 regulates the formation of damaged foci at telomeres and subsequent telomere-to-telomere fusion events controlled by the DNA repair pathway. Telomere fusion events also contributes to the formation of micronuclei and abnormal segregation. Micronuclei formation triggers activation of the cGAS-STING mediated innate immune response to intracellular DNA and inhibits cell growth. All of these phenotypes are controlled by the expression of H3.3. Additionally, disruption of ATRX, DAXX, HIRA, or ASF1 elicits an impairment phenotype similar to that is caused by H3.3 inhibition. Our results indicate that cGAS-STING-mediated cellular senescence is triggered by deprotected telomeres and is controlled by the expression and deposition of H3.3 on telomeres.
Impaired neurogenesis and synaptogenesis in iPSC-derived Parkinson’s patient cortical neurons with D620N VPS35 mutation
Authors: Scheller Ute , Lee ChoongKu , Seibler Philip , Mitkovski Miso , Rhee JeongSeop , van Riesen Christoph
Published: August 2024

Presynaptic dysfunction is an important early process in the pathophysiology of Parkinson’s disease (PD) that drives disease progression. To gain insight into the intrinsic synapse impairment in PD, we performed comprehensive electrophysiological and morphological analysis of iPSC-derived cortical neurons derived from PD patients with the VPS35-D620N mutation. Our findings reveal significant impairment in neurogenesis and synaptogenesis within individual patient neurons, culminating to synaptic dysfunction even in the absence of neuronal interactions. The neurons exhibited significantly reduced synaptic responsiveness, fewer synapse and decreased dendritic length and complexity. Thus, the VPS35-D620N mutation in human cortical neurons independently can cause pathophysiology via synaptic dysfunction. Our study highlights the urgent need to develop disease-modifying therapies aimed at preserving synaptic function in PD.
Outer hair cells stir cochlear fluids
Authors: Lee Choongheon , Shokrian Mohammad , Henry Kenneth S. , Carney Laurel H. , Holt Joseph C. , Nam Jong-Hoon
Published: August 2024

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid-structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently suggest that active outer hair cells in the tail region of cochlear traveling waves drive cochlear fluid circulation.
The effect of performance contingent reward prospects flexibly adapts to more versus less specific task goals
Authors: Liegel Nathalie , Schneider Daniel , Wascher Edmund , Klatt Laura-Isabelle , Arnau Stefan
Published: August 2024

In some situations, e.g., when we expect to gain a reward in case of good performance, goal-driven top-down attention is particularly strong. Little is known about the task specificity of such increases of top-down attention due to environmental factors. To understand to what extent performance-contingent reward prospects can result in specific and unspecific changes in cognitive processing, we here investigate reward effects under different levels of task specification.

Thirty-two participants performed a visual or an auditory discrimination task cued by two consecutive visual stimuli: First, a reward cue indicated if good performance was rewarded. Second, a task cue announced either which of the two tasks would follow (precise cue) or that both tasks would follow equally likely (imprecise cue).

Reward and task cue preciseness both significantly improved performance. Moreover, the response time difference between precisely and imprecisely cued trials was significantly stronger in rewarded than in unrewarded trials. These effects were reflected in ERP slow wave amplitudes: Reward and preciseness both significantly enhanced the contingent negative variation (CNV) prior to the task stimulus. In an early CNV time interval, both factors also showed an interaction. A negative slow wave prior to the task cue was also significantly enhanced for rewarded trials. This effect correlated with the reward difference in response times.

These results indicate that reward prospects trigger task-specific changes in preparatory top-down attention which can flexibly adapt over time and across different task requirements. This highlights that a reward-induced increase of cognitive control can occur on different specificity levels.
Predicting the Pathway Involvement of Metabolites in Both Pathway Categories and Individual Pathways
Authors: Huckvale Erik D. , Moseley Hunter N.B.
Published: August 2024

Metabolism is the network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validations iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories were predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite-pathway prediction results published so far in the field.
Retinal thermometry in-vivo using phase-sensitive optical coherence tomography
Authors: Zhuo Yueming , Bhuckory Mohajeet , Li Huakun , Hattori Junya , Pham-Howard Davis , Veysset David , Ling Tong , Palanker Daniel
Published: August 2024

Controlling the tissue temperature rise during retinal laser therapy is essential for predictable outcomes, especially at non-damaging settings. We demonstrate a method for determining the temperature rise in the retina using phase-resolved optical coherence tomography (pOCT) in vivo. Measurements based on the thermally induced optical path length changes (ΔOPL) in the retina during a 10-ms laser pulse allow detection of the temperature rise with a precision less than 1 °C, which is sufficient for calibration of the laser power for patient-specific non-damaging therapy. We observed a significant difference in confinement of the retinal deformations between the normal and the degenerate retina: in wild-type rats, thermal deformations are localized between the retinal pigment epithelium (RPE) and the photoreceptors’ inner segments (IS), as opposed to a deep penetration of the deformations into the inner retinal layers in the degenerate retina. This implies the presence of a structural component within healthy photoreceptors that dampens the tissue expansion induced by the laser heating of the RPE and pigmented choroid. We hypothesize that the thin and soft cilium connecting the inner and outer segments (IS, OS) of photoreceptors may absorb the deformations of the OS and thereby preclude the tissue expansion further inward. Striking difference in the confinement of the retinal deformations induced by a laser pulse in healthy and degenerate retina may be used as a biomechanical diagnostic tool for the characterization of photoreceptor degeneration.
Neuropathology in an α-synuclein preformed fibril mouse model occurs independent of the Parkinson’s disease-linked lysosomal ATP13A2 protein
Authors: Massari Caio M. , Dues Dylan J. , Bergsma Alexis , Sipple Kayla , Moore Darren J.
Published: August 2024

Loss-of-function mutations in theATP13A2(PARK9) gene are implicated in early-onset autosomal recessive Parkinson’s disease (PD) and other neurodegenerative disorders.ATP13A2encodes a lysosomal transmembrane P5B-type ATPase that is highly expressed in brain and specifically within the substantia nigra. Recent studies have revealed its normal role as a lysosomal polyamine transporter, although its contribution to PD-related pathology remains unclear. Cellular studies report that ATP13A2 can regulate α-synuclein (α-syn) secretion via exosomes. However, the relationship between ATP13A2 and α-syn in animal models remains inconclusive.ATP13A2knockout (KO) mice exhibit lysosomal abnormalities and reactive astrogliosis but do not develop PD-related neuropathology. Studies manipulating α-syn levels in mice lacking ATP13A2 indicate minimal effects on pathology. The delivery of α-syn preformed fibrils (PFFs) into the mouse striatum is a well-defined model to study the development and spread of α-syn pathology. In this study, we unilaterally injected wild-type (WT) and homozygousATP13A2KO mice with mouse α-syn PFFs in the striatum and evaluated mice for neuropathology after 6 months. The distribution, extent and spread of α-syn aggregation in multiple regions of the mouse brain was largely independent of ATP13A2 expression. The loss of nigrostriatal pathway dopaminergic neurons and their nerve terminals induced by PFFs were equivalent in WT andATP13A2KO mice. Reactive astrogliosis was induced equivalently by α-syn PFFs in WT and KO mice but was significantly higher inATP13A2KO mice due to pre-existing gliosis. We did not identify asymmetric motor disturbances, microglial activation, or axonal damage induced by α-syn PFFs in WT or KO mice after 6 months. Although α-syn PFFs induce an increase in lysosomal number in the substantia nigra in general, TH-positive dopaminergic neurons did not exhibit either increased lysosomal area or intensity, regardless ofATP13A2genotype. Our study evaluating the spread of α-syn pathology reveals no exacerbation of α-syn pathology, neuronal loss, astrogliosis or motor deficits inATP13A2KO mice, suggesting that selective lysosomal abnormalities resulting from ATP13A2 loss do not play a major role in α-syn clearance or propagationin vivo.
NKX2.2 and KLF4 cooperate to regulate α cell identity
Authors: Brooks Elliott P. , Casey McKenna R. , Wells Kristen L. , Liu Tsung-Yun , Orman Madeline Van , Sussel Lori
Published: August 2024

Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs; yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet α cells by directly activating α cell genes and repressing alternate islet cell fate genes. When compared to the known role of NKX2.2 in islet β cells, we demonstrate that NKX2.2 regulates α cell genes, facilitated in part by α cell specific DNA binding at gene promoters. Furthermore, we have identified the reprogramming factor KLF4 as having enriched expression in α cells, where it co-occupies NKX2.2-bound α cell promoters, is necessary for NKX2.2 promoter occupancy in α cells and co-regulates many NKX2.2 α cell transcriptional targets. Misexpression ofKlf4in β cells is sufficient to manipulate chromatin accessibility, increase binding of NKX2.2 at α cell specific promoter sites, and alter expression of NKX2.2-regulated cell-specific targets. This study identifies KLF4 is a novel α cell factor that cooperates with NKX2.2 to regulate α cell identity.
Wink or blush? Pupil-linked brain arousal signals both change and uncertainty during assessment of changing environmental regularities
Authors: Gesztesi G. , Pajkossy P.
Published: August 2024

One main cornerstone of adaptive behavior is belief updating, whereby new and unexpected observations lead to the updating of learned associations between events, behaviors and outcomes. This process necessitates the detection of changed environmental contingencies which in turn leads to uncertainty about the environmental regularities. Change and uncertainty are thus inherently linked, and both constructs have been linked to pupil size changes, which might reflect activity in neural networks underlying belief updating. Thus, in our study, we aimed to disentangle the effects of change and uncertainty on pupil-linked brain arousal. We used a probabilistic reversal learning task, where participants had to act according to changing preferences of a fictional character, and used specific cues to independently manipulate the level of change and uncertainty (e.g. the fictional character winked for signalizing change, or his face was blushed to indicate uncertainty). We found that when the cues triggered the same amount of uncertainty, larger levels of change in beliefs led to a transient increase in pupil size during cue processing. In contrast, when the cues signalized a similar amount of change, then increased belief uncertainty was associated with a sustained increase in pupil size, extending in time beyond cue processing. Thus, change and uncertainty exerted independent influence on pupil-linked brain arousal, suggesting the activity of different neural networks, and highlighting the need to disentangle the effects of these overlapping but distinct theoretical constructs.
Novel Large Empirical Study of Deep Transfer Learning for COVID-19 Classification Based on CT and X-Ray Images
Authors: Almutaani Mansour , Turki Turki , Taguchi Y-h.
Published: August 2024

The early and highly accurate prediction of COVID-19 based on medical images can speed up the diagnostic process and thereby mitigate disease spread; therefore, developing AI-based models is an inevitable endeavor. The presented work, to our knowledge, is the first to expand the model space and identify a better performing model among 10000 constructed deep transfer learning (DTL) models as follows. First, we downloaded and processed 4481 CT and X-ray images pertaining to COVID-19 and non-COVID-19 patients, obtained from the Kaggle repository. Second, we provide processed images as inputs to four pre-trained deep learning models (ConvNeXt, EfficientNetV2, DenseNet121, and ResNet34) on more than a million images from the ImageNet database, in which we froze the convolutional and pooling layers pertaining to the feature extraction part while unfreezing and training the densely connected classifier with the Adam optimizer. Third, we generate and take a majority vote of two, three, and four combinations from the four DTL models, resulting inmodels. Then, we combine the 11 DTL models, followed by consecutively generating and taking the majority vote ofDTL models. Finally, we select 7953 DTL models from. Experimental results from the whole datasets using five-fold cross-validation demonstrate that the best generated DTL model, named HC, achieving the best AUC of 0.909 when applied to the CT dataset, while ConvNeXt yielded a higher marginal AUC of 0.933 compared to 0.93 for HX when considering the X-ray dataset. These promising results set the foundation for promoting the large generation of models (LGM) in AI.
Dynamics and Evolutionary Conservation of B Complex Protein Recruitment During Spliceosome Activation
Authors: Fu Xingyang , Hoskins Aaron A.
Published: August 2024

Spliceosome assembly and catalytic site formation (called activation) involve dozens of protein and snRNA binding and unbinding events. The B-complex specific proteins Prp38, Snu23, and Spp381 have critical roles in stabilizing the spliceosome during conformational changes essential for activation. While these proteins are conserved, different mechanisms have been proposed for their recruitment to spliceosomes. To visualize recruitment directly, we used Colocalization Single Molecule Spectroscopy (CoSMoS) to study the dynamics of Prp38, Snu23, and Spp381 during splicing in real time. These proteins bind to and release from spliceosomes simultaneously and are likely associated with one another. We designate the complex of Prp38, Snu23, and Spp381 as the B Complex Protein (BCP) subcomplex. Under splicing conditions, the BCP associates with pre-mRNA after tri-snRNP binding. BCP release predominantly occurs after U4 snRNP dissociation and after NineTeen Complex (NTC) association. Under low concentrations of ATP, the BCP pre-associates with the tri-snRNP resulting in their simultaneous binding to pre-mRNA. Together, our results reveal that the BCP recruitment pathway to the spliceosome is conserved betweenS. cerevisiaeand humans. Binding of the BCP to the tri-snRNP when ATP is limiting may result in formation of unproductive complexes that could be used to regulate splicing.

KEY POINTS

Prp38, Snu23, and Spp381 associate together to form the B Complex Proteins (BCP) Complex

During yeast spliceosome assembly, the BCP binds after the tri-snRNP and leaves after NTC arrival

At low ATP, the BCP pre-associates with the tri-snRNP in complexes that are likely unproductive