bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of CD47 and Its Association With Tumor Immune Microenvironment Heterogeneity in Ovarian Cancer
Authors: Yu Lan , Ding Yi , Wan Ting , Deng Ting , Huang He , Liu Jihong
Published: December 2021

Background

It was reported that tumor heterogeneity and the surrounding tumor microenvironment (TME) in ovarian cancer affects immunotherapy efficacy and patient outcomes. And the TME of ovarian cancer is intrinsically heterogeneous. CD47 plays vital roles in cell functional behavior and immune homeostasis relating to cancer prognosis. But how it affects TME and its contribution to heterogeneity in ovarian cancer has not been fully illustrated. Therefore, we aimed to identify a prognostic biomarker which may help explain tumor immune microenvironment heterogeneity of ovarian cancer.

Methods

Cancer single-cell state atlas (CancerSEA) was used to evaluate functional role of CD47. Several bioinformatics database including Oncomine, Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), The Human Protein Atlas (HPA), Ualcan and Kaplan-Meier plotter (KM plotter) were applied to illustrate correlation of CD47 with ovarian cancer prognosis and immune infiltration. Tumor Immune Single-cell Hub (TISCH) single cell database was employed to evaluate correlation of CD47 with tumor microenvironment. GeneMANIA was implemented to identify regulation networks of CD47. Differentially expressed genes (DEGs) between CD47 high and low expression groups were analyzed with R package DESeq2. Kyoto encyclopedia of genes and genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were utilized to explore how CD47 affect the immune related cell signaling pathway.

Results

CD47 expression was upregulated and connected to worse OS and PFS in ovarian cancer. Close relation was found between CD47 expression level and immune infiltration in ovarian cancer, especially with Treg cells, Monocytes, Macrophages and T cell exhaustion (P<0.05). The CD47 expression level was relatively low in plasma cells, dendritic cells and Mono/Macro cells of OV_GSE115007, in myofibroblasts, fibroblasts and endothelial cells of OV_GSE118828, compared to malignant cells of OV_GSE118828 dataset. The cell components and distribution in primary and metastatic ovarian cancer are quite distinct, which may lead to TME heterogeneity of ovarian cancer.

Conclusion

Our results indicated that CD47 is closely correlated to ovarian cancer immune microenvironment and might induce ovarian cancer heterogeneity. Therefore, CD47 may be used as a candidate prognostic biomarker and provide us with new insights into potential immunotherapy in ovarian cancer patients.
Siglec Signaling in the Tumor Microenvironment
Authors: van Houtum Eline J. H. , Büll Christian , Cornelissen Lenneke A. M. , Adema Gosse J.
Published: December 2021

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that recognize sialoglycans – sialic acid containing glycans that are abundantly present on cell membranes. Siglecs are expressed on most immune cells and can modulate their activity and function. The majority of Siglecs contains immune inhibitory motifs comparable to the immune checkpoint receptor PD-1. In the tumor microenvironment (TME), signaling through the Siglec-sialoglycan axis appears to be enhanced through multiple mechanisms favoring tumor immune evasion similar to the PD-1/PD-L1 signaling pathway. Siglec expression on tumor-infiltrating immune cells appears increased in the immune suppressive microenvironment. At the same time, enhanced Siglec ligand expression has been reported for several tumor types as a result of aberrant glycosylation, glycan modifications, and the increased expression of sialoglycans on proteins and lipids. Siglec signaling has been identified as important regulator of anti-tumor immunity in the TME, but the key factors contributing to Siglec activation by tumor-associated sialoglycans are diverse and poorly defined. Among others, Siglec activation and signaling are co-determined by their expression levels, cell surface distribution, and their binding preferences forcis-andtrans-ligands in the TME. Siglec binding preference are co-determined by the nature of the proteins/lipids to which the sialoglycans are attached and the multivalency of the interaction. Here, we review the current understanding and emerging conditions and factors involved in Siglec signaling in the TME and identify current knowledge gaps that exist in the field.
Assessing and Minimizing the Effect of Malaria on SARS-CoV-2 Serodiagnostics
Authors: Woodford John , Sagara Issaka , Kwan Jennifer , Zaidi Irfan , Dicko Alassane , Duffy Patrick E.
Published: December 2021

Malaria may affect the reliability of SARS-CoV-2 seroassay performance and limit understanding of SARS-CoV-2 epidemiology in malaria-endemic regions. We present our experience conducting SARS-CoV-2 serosurveillance in seasonal malaria-affected communities in Mali and discuss relevant literature regarding the effect of malaria on the performance of SARS-CoV-2 serodiagnostics, including approaches to minimize the effect of malaria-associated assay interference.
Influence of High Temperature Thermal Radiation on the Transition Characteristics of Coal Oxidation and Spontaneous Combustion
Authors: Wang Liancong , Hu Weizhao , Hu Yuan
Published: December 2021

In the goaf of the coal mine, there will be some high-temperature points before or during the fire. Under certain conditions, these high-temperature points will radiate heat to the surrounding coal in the form of thermal radiation, which, in turn, may also ignite the coal. Taking this situation into consideration, this study aims to investigate the influence of high-temperature thermal radiation on the transformation characteristics of coal oxidation and spontaneous combustion using the high-temperature thermal radiation method. The results show that an increase in thermal radiation value reduces the ignition time of coal gradually. The peak heat release rate, total heat release, peak smoke release rate, and total smoke release gradually increase. Additionally, the total carbon monoxide release reduces gradually, and the peak carbon dioxide production rate increases gradually. It is worth noting that as the heat radiation value increases, the peak value of CO production rate of lignite and bituminous coal is noted to decrease gradually, whereas that of anthracite increases gradually. The total carbon dioxide emissions of bituminous coal and anthracite increased gradually, whereas the total carbon dioxide emissions of lignite increased firstly and then decreased. This work proposes a novel method to study the coal oxidation and spontaneous combustion by a widely-recognized combustion apparatus.
Sulfated Polysaccharide From Undaria Pinnatifida Induces Apoptosis and Inhibits Proliferation, Migration, and Invasion in Ovarian Cancer via Suppressing the Hedgehog Signaling Pathway
Authors: Yang Yi , Zhang Qin , Xu Yongping , Chen Gang , Qiu Yukuan
Published: December 2021

Objective: To investigate the effects of sulfured polysaccharide from Undaria pinnatifida (SPUP) on the biological behaviors of ovarian cancer (OC) cells and its potential mechanism.

Methods: Sulfated polysaccharide from Undaria pinnatifida (SPUP) was extracted and characterized through a combination of chemical analysis, IR spectra, UV-Vis, gas chromatography, and high-performance gel permeation chromatography. OC and human ovarian surface epithelial cells were used as working model in vitro for evaluation of SPUP’s therapeutic effects. A combination of CCK-8, Transwell, and flow cytometry assay was used to measure the proliferation, migration, invasion, and apoptosis of OC cells, respectively. In addition, the protein expression levels of cells were also measured by Western blot.

Results: SPUP suppressed OC development from three different perspectives: 1) SPUP treatment significantly inhibited the proliferation of OC in a dosage-dependent manner (p < 0.05); 2) SPUP inhibited the migration and invasion of OC cells confirmed by scratch and Transwell experiments (p < 0.05); 3) SPUP induced apoptosis in OC cells and thus further inhibited the growth of OC cells evaluated using flow cytometry (p < 0.05). The underlying mechanism of the suppressing effects of SPUP might be related to the inhibition of the hedgehog (Hh) signaling pathway in OC cells after SPUP treatment. With additional suppression of the Hh signaling pathway, the anticancer effects of SPUP were enhanced (p < 0.05).

Conclusion: Taken together, SPUP could inhibit the proliferation, migration, and invasion and induce apoptosis of OC cells by inhibiting the activation of the Hh signaling pathway, which proposes SPUP as a novel drug to treat OC clinically.
Empowering Patients in the Therapeutic Decision-Making Process: A Glance Into Behçet's Syndrome
Authors: Marinello Diana , Di Cianni Federica , Del Bianco Alessandra , Mattioli Irene , Sota Jurgen , Cantarini Luca , Emmi Giacomo , Leccese Pietro , Lopalco Giuseppe , Mosca Marta , Padula Angela , Piga Matteo , Salvarani Carlo , Taruscio Domenica , Talarico Rosaria
Published: December 2021

Behçet's syndrome (BS) represents a challenging condition, characterized by a variable spectrum of disease profile and associated with a significant limitation of the daily activities as well as a potential negative impact on relationships and psychological status. Considering also the complexity of the therapeutic management of BS, that often includes biological off-label treatments, the participation in the therapeutic decision-making process of the BS patients is essential to ensure the integration of the care process into the life of the patient. For this reason, the empowerment of BS patients represents a crucial need and the present work is aimed at fully exploring all the potential variables implicated in the BS patient empowerment, also highlighting major points to consider and concrete actions to be planned in the immediate future in order to implement a pragmatic facilitation of the patients' empowerment.
Effects of Dexmedetomidine on Postoperative Nausea and Vomiting in Adult Patients Undergoing Ambulatory Thyroidectomy: A Randomized Clinical Trial
Authors: Xie Cuiyu , Zhang Caihui , Sun Hao , Lu Yao
Published: December 2021

Background: Postoperative nausea and vomiting (PONV) is a common and disturbing problem in patients undergoing ambulatory thyroidectomy. This prospective trial aimed to explore whether dexmedetomidine (DEX) combined with azasetron (AZA) can further drop the incidence of PONV in patients undergoing ambulatory thyroidectomy compared with AZA.

Methods: This single-center, randomized, double-blind trial involved 172 adult patients undergoing ambulatory thyroidectomy. The individuals were randomized to DEX + AZA group and AZA group. In the DEX + AZA group, patients received dexmedetomidine 0.5 μg kg−1 for 10 min and then the infusion rate was held at 0.1 μg kg−1 h−1 until the completion of the operation, while the same amount of 0.9% saline in the AZA group. At the completion of the surgery, 10 mg azasetron was administered to every patient in both groups. The primary outcome was the incidence of 24 h PONV after ambulatory thyroidectomy. The secondary outcomes included residence time in recovery room, pain scores, severity of nausea, and adverse events.

Results: No significant difference was found in the incidence of 24-h PONV between the DEX + AZA group and the AZA group [36% (30 of 84) vs. 38% (32 of 84); relative risk, 0.94; 95% confidence interval (CI), 0.63–1.40; P = 0.749]. The incidence of severe nausea was similar between the DEX + AZA group and the AZA group [57% (12 of 21) vs. 43% (9 of 21); relative risk, 1.33; 95% CI, 0.72–2.50; P = 0.355].

Conclusions: Intraoperative dexmedetomidine combined with azasetron failed to drop the incidence of 24-h PONV compared with azasetron alone in patients undergoing ambulatory thyroidectomy.
Definitions and Risk Factors for Drug-Resistant Epilepsy in an Adult Cohort
Authors: Denton Alyssa , Thorpe Lilian , Carter Alexandra , Angarita-Fonseca Adriana , Waterhouse Karen , Hernandez Ronquillo Lizbeth
Published: December 2021

Background: Less than one-third of people with epilepsy will develop drug-resistant epilepsy (DRE). Establishing the prognosis of each unique epilepsy case is an important part of evaluation and treatment.Most studies on DRE prognosis have been based on a pooled, heterogeneous group, including children, adults, and older adults, in the absence of clear recognition and control of important confounders, such as age group. Furthermore, previous studies were done before the 2010 definition of DRE by the International League Against Epilepsy (ILAE), so data based on the current definitions have not been entirely elucidated. This study aimed to explore the difference between 3 definitions of DRE and clinical predictors of DRE in adults and older adults.

Methods: Patients with a new diagnosis of epilepsy ascertained at a Single Seizure Clinic (SSC) in Saskatchewan, Canada were included if they had at least 1 year of follow-up. The first study outcome was the diagnosis of DRE epilepsy at follow-up using the 2010 ILAE definition. This was compared with 2 alternative definitions of DRE by Kwan and Brodie and Camfield and Camfield. Finally, risk factors were analyzed using the ILAE definition.

Results: In total, 95 patients with a new diagnosis of epilepsy and a median follow-up of 24 months were included. The median age of patients at the diagnosis of epilepsy was 33 years, and 51% were men. In the cohort, 32% of patients were diagnosed with DRE by the Kwan and Brodie definition, 10% by Camfield and Camfield definition, and 15% by the ILAE definition by the end of follow-up. The only statistically significant risk factor for DRE development was the failure to respond to the first anti-seizure medication (ASM).

Conclusion: There were important differences in the percentage of patients diagnosed with DRE when using 3 concurrent definitions. However, the use of the ILAE definition appeared to be the most consistent through an extended follow-up. Finally, failure to respond to the first ASM was the sole significant risk factor for DRE in the cohort after considering the age group.
Optic Nerve Drusen Is Highly Prevalent Among Children With Pseudotumor Cerebri Syndrome
Authors: Genizi Jacob , Meiselles Doron , Arnowitz Elisheva , Segal Idan , Cohen Rony , Goldenberg-Cohen Nitza
Published: December 2021

Introduction: The clinical presentation of pseudotumor cerebri syndrome (PTCS) usually includes headache, nausea, and vomiting with normal physical examination apart from papilledema and diplopia. However, pseudopapilledema, which can be caused by optic nerve drusen, may lead to misdiagnosis. The prevalence of optic nerve drusen in the general population is 0.5–2%. The purpose of our study was to evaluate the prevalence and risk factors of optic nerve drusen among patients with PTCS.

Materials and Methods: Medical records of children evaluated in the pediatric department at Bnai Zion Medical Center due to PTCS between 2008 and 2020 were assessed. Inclusion criteria were children age under 18 years with a PTCS diagnosis and ophthalmic B-mode ultrasonography (US). Exclusion criteria were secondary intracranial hypertension.

Results: Thirty-four children were included with a mean age 10.1 years which included 50% boys. A majority of the patients, 24 (72.4%), complained of headaches, while 15 (45.5%) complained of transient visual obscuration, and 9 (26.5%) of vomiting. Visual acuity on presentation was normal (20/20–20/30) in 23 of the children (67%), moderately diminished (20/40–20/80) in 9 (26%), and showing profound loss (20/200) in 2 (7%). Five patients (14.7%) were diagnosed with optic nerve drusen via B-mode ophthalmic ultrasonography (US). However, they still fulfilled the diagnostic criteria for PTCS, and disc swelling improved after treatment. There were no statistically significant differences between the group with optic nerve drusen and the rest of the patients.

Conclusions: Optic nerve drusen are common among pediatric patients with PTCS. Diagnosis of optic nerve drusen should not rule out the presence of increased intracranial pressure.
Behavioral Account of Attended Stream Enhances Neural Tracking
Authors: Huet Moïra-Phoebé , Micheyl Christophe , Parizet Etienne , Gaudrain Etienne
Published: December 2021

During the past decade, several studies have identified electroencephalographic (EEG) correlates of selective auditory attention to speech. In these studies, typically, listeners are instructed to focus on one of two concurrent speech streams (the “target”), while ignoring the other (the “masker”). EEG signals are recorded while participants are performing this task, and subsequently analyzed to recover the attended stream. An assumption often made in these studies is that the participant’s attention can remain focused on the target throughout the test. To check this assumption, and assess when a participant’s attention in a concurrent speech listening task was directed toward the target, the masker, or neither, we designed a behavioral listen-then-recall task (the Long-SWoRD test). After listening to two simultaneous short stories, participants had to identify keywords from the target story, randomly interspersed among words from the masker story and words from neither story, on a computer screen. To modulate task difficulty, and hence, the likelihood of attentional switches, masker stories were originally uttered by the same talker as the target stories. The masker voice parameters were then manipulated to parametrically control the similarity of the two streams, from clearly dissimilar to almost identical. While participants listened to the stories, EEG signals were measured and subsequently, analyzed using a temporal response function (TRF) model to reconstruct the speech stimuli. Responses in the behavioral recall task were used to infer, retrospectively, when attention was directed toward the target, the masker, or neither. During the model-training phase, the results of these behavioral-data-driven inferences were used as inputs to the model in addition to the EEG signals, to determine if this additional information would improve stimulus reconstruction accuracy, relative to performance of models trained under the assumption that the listener’s attention was unwaveringly focused on the target. Results from 21 participants show that information regarding the actual – as opposed to, assumed – attentional focus can be used advantageously during model training, to enhance subsequent (test phase) accuracy of auditory stimulus-reconstruction based on EEG signals. This is the case, especially, in challenging listening situations, where the participants’ attention is less likely to remain focused entirely on the target talker. In situations where the two competing voices are clearly distinct and easily separated perceptually, the assumption that listeners are able to stay focused on the target is reasonable. The behavioral recall protocol introduced here provides experimenters with a means to behaviorally track fluctuations in auditory selective attention, including, in combined behavioral/neurophysiological studies.
When You Do Not Get the Whole Picture: Scene Perception After Occipital Cortex Lesions
Authors: Geuzebroek Anna C. , Woutersen Karlijn , van den Berg Albert V.
Published: December 2021

Background: Occipital cortex lesions (OCLs) typically result in visual field defects (VFDs) contralateral to the damage. VFDs are usually mapped with perimetry involving the detection of point targets. This, however, ignores the important role of integration of visual information across locations in many tasks of everyday life. Here, we ask whether standard perimetry can fully characterize the consequences of OCLs. We compare performance on a rapid scene discrimination task of OCL participants and healthy observers with simulated VFDs. While the healthy observers will only suffer the loss of part of the visual scene, the damage in the OCL participants may further compromise global visual processing.

Methods: VFDs were mapped with Humphrey perimetry, and participants performed two rapid scene discrimination tasks. In healthy participants, the VFDs were simulated with hemi- and quadrant occlusions. Additionally, the GIST model, a computational model of scene recognition, was used to make individual predictions based on the VFDs.

Results: The GIST model was able to predict the performance of controls regarding the effects of the local occlusion. Using the individual predictions of the GIST model, we can determine that the variability between the OCL participants is much larger than the extent of the VFD could account for. The OCL participants can further be categorized as performing worse, the same, or better as their VFD would predict.

Conclusions: While in healthy observers the extent of the simulated occlusion accounts for their performance loss, the OCL participants’ performance is not fully determined by the extent or shape of their VFD as measured with Humphrey perimetry. While some OCL participants are indeed only limited by the local occlusion of the scene, for others, the lesions compromised the visual network in a more global and disruptive way. Yet one outperformed a healthy observer, suggesting a possible adaptation to the VFD. Preliminary analysis of neuroimaging data suggests that damage to the lateral geniculate nucleus and corpus callosum might be associated with the larger disruption of rapid scene discrimination. We believe our approach offers a useful behavioral tool for investigating why similar VFDs can produce widely differing limitations in everyday life.
Effects of Non-invasive Brain Stimulation on Multiple System Atrophy: A Systematic Review
Authors: Zhang Mengjie , He Ting , Wang Quan
Published: December 2021

Background/Objective: Multiple system atrophy (MSA) refers to a progressive neurodegenerative disease characterized by autonomic dysfunction, parkinsonism, cerebellar ataxia, as well as cognitive deficits. Non-invasive brain stimulation (NIBS) has recently served as a therapeutic technique for MSA by personalized stimulation. The primary aim of this systematic review is to assess the effects of NIBS on two subtypes of MSA: parkinsonian-type MSA (MSA-P) and cerebellar-type MSA (MSA-C).

Methods: A literature search for English articles was conducted from PubMed, Embase, Web of Science, Cochrane Library, CENTRAL, CINAHL, and PsycINFO up to August 2021. Original articles investigating the therapeutics application of NIBS in MSA were screened and analyzed by two independent reviewers. Moreover, a customized form was adopted to extract data, and the quality of articles was assessed based on the PEDro scale for clinical articles.

Results: On the whole, nine articles were included, i.e., five for repetitive transcranial magnetic stimulation (rTMS), two for transcranial direct current stimulation (tDCS), one for paired associative stimulation, with 123 patients recruited. The mentioned articles comprised three randomized controlled trials, two controlled trials, two non-controlled trials, and two case reports which assessed NIBS effects on motor function, cognitive function, and brain modulatory effects. The majority of articles demonstrated significant motor symptoms improvement and increased cerebellar activation in the short term after active rTMS. Furthermore, short-term and long-term effects on improvement of motor performance were significant for tDCS. As opposed to the mentioned, no significant change of motor cortical excitability was reported after paired associative stimulation.

Conclusion: NIBS can serve as a useful neurorehabilitation strategy to improve motor and cognitive function in MSA-P and MSA-C patients. However, further high-quality articles are required to examine the underlying mechanisms and standardized protocol of rTMS as well as its long-term effect. Furthermore, the effects of other NIBS subtypes on MSA still need further investigation.
The Role of microRNA in Pathogenesis, Diagnosis, Different Variants, Treatment and Prognosis of Mycosis Fungoides
Authors: Wen Pengfei , Xie Yao , Wang Lin
Published: December 2021

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), accounting for approximately 50% of all CTCLs. Although various molecular changes in MF have been described in existing studies, no obvious disease-specific changes have been found thus far. microRNAs (miRs) are short, noncoding RNA molecules that play roles in the post-transcriptional regulation of oncogenes and tumor suppressor genes in various diseases. Recently, there has been rapidly expanding experimental evidence for the role of miRs in the progression, early diagnosis, prognosis prediction for MF. Efforts to improve early diagnosis and develop personalized therapy options have become more important in recent years. Here, we provide an overview and update of recent advances regarding miRs associated with MF. Furthermore, we provide insights into future opportunities for miR-based therapies.
Intravitreal Ranibizumab Had Limited Effect on Cystoid Macular Edema Due to Albumin-Bound Paclitaxel: A Case Report and Literature Review
Authors: Ye Suna , Fang Qiqi , Yao Jinyu , Xing Jianqiang , Tang Shibo , Ma Jacey Hongjie
Published: December 2021

Angiographically silent cystoid macular edema (CME) is a rare complication from nab-paclitaxel. Here we report a 45-year-old woman with breast cancer who developed CME after several months of treatment with albumin-bound paclitaxel (nab-paclitaxel). Her visual acuity did not improve significantly with the cessation of nab-paclitaxel and intravitreal ranibizumab treatment. Then, brinzolamide eye drops were prescribed. One month later, her vision improved, with the macular edema significantly subsided. Finally, we reviewed other cases of CME induced by nab-paclitaxel that have been reported in the literature and discussed the underlying pathogenesis of nab-paclitaxel-induced CME.
Comparison of Drainage Methods After Pyeloplasty in Children: A 14-Year Study
Authors: Kong Xiangpan , Li Zhenpeng , Li Mujie , Liu Xing , He Dawei
Published: December 2021

Objective: To summarize our experiences with drainage methods after laparoscopic pyeloplasty with a 14-year study.

Methods: We reviewed the data of the 838 children operated on for hydronephrosis due to congenital ureteropelvic junction obstruction (UPJO) between July 2007 and July 2020. Patients' demographics, perioperative details, postoperative drainage stents [including double-J stent, percutaneous trans-anastomotic (PU) stent, and trans-uretero-cystic external urethral stent (TEUS)], complications, hospital stay, and long-term follow-up outcomes were analyzed. Long-term follow-up was performed by outpatient visits and telephone follow-up. Moreover, we reviewed the details of nine cases of recurrence after laparoscopic pyeloplasty.

Results: Comparison of preoperative general data among the three groups indicated that there was no statistical difference in age, gender, and surgical side of the three groups. Statistical differences were found in the incidence of postoperative complications from the three postoperative drainage method groups, especially the incidence of reoperations (p < 0.01): there were six cases (3.19%) of recurrences in the TEUS group, two cases (0.36%) in the DJ group, and one case (0.93%) in the PU group. In the six recurrent cases from the TEUS group, four cases (44.4%) were found to have stenosis, and two cases (22.2%) have iatrogenic valvular formation.

Conclusion: Not all three types of drainage methods are suitable for drainage after pyeloplasty. Based on our findings, TEUS is not recommended.
Case Report: Compound Heterozygous Variants of SLC13A3 Identified in a Chinese Patient With Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation
Authors: Kang Qingyun , Yang Liming , Liao Hongmei , Yang Sai , Yang Haiyang , Ning Zeshu , Liao Caishi , Wu Liwen
Published: December 2021

Background:SLC13A3 gene encodes the Na+/dicarboxylate cotransporter 3 (NaDC3), which locates on the plasma membrane and is mainly expressed in kidney, astrocytes and the choroid plexus. It imports four to six carbon dicarboxylates together with three Na+ ions into the cytosol. Nowadays, pathogenic variants of SLC13A3 gene were found to cause acute reversible leukoencephalopathy and α-ketoglutarate accumulation (ARLIAK) in patients. Here, we report two novel SLC13A3 variants c.185C>T (p.T62M) and c.331C>T (p.R111*) identified in a Chinese patient with ARLIAK.

Case Presentation: The patient was a Chinese girl aged 13 years and 7 months old, who had acute, recurrent neurological deterioration during two febrile episodes. She presented with reversible leukoencephalopathy and increased urinary excretion of α-ketoglutarate. Genetic studies revealed compound heterozygous variants (c.185C>T, p.T62M, and c.331C>T, p.R111*) in SLC13A3, which had not been reported previously.

Conclusions: These findings expand the variant spectrum of SLC13A3, providing the basis for the further study of this rare disease.
Ketone Bodies Impact on Hypoxic CO2 Retention Protocol During Exercise
Authors: Prins Philip J. , Buxton Jeffrey D. , McClure Tyler S. , D’Agostino Dominic P. , Ault Dana L. , Welton Gary L. , Jones Dalton W. , Atwell Adam D. , Slack Macey A. , Slack Marah L. , Williams Chloe E. , Blanchflower Morgan E. , Kannel Kristia K. , Faulkner Madison N. , Szmaciasz Hannah L. , Croll Stephanie M. , Stanforth Lindsey M. , Harris Tim D. , Gwaltney Holton C. , Koutnik Andrew P.
Published: December 2021

Exogenous ketone esters have demonstrated the capacity to increase oxygen availability during acute hypoxic exposure leading to the potential application of their use to mitigate performance declines at high altitudes. Voluntary hypoventilation (VH) with exercise reliably reduces oxygen availability and increases carbon dioxide retention without alterations to ambient pressure or gas content. Utilizing a double-blind randomized crossover design, fifteen recreational male distance runners performed submaximal exercise (4 × 5 min; 70% VO2 Max) with VH. An exogenous ketone ester (KME; 573 mg⋅kg–1) or iso-caloric flavor matched placebo (PLA) was consumed prior to exercise. Metabolites, blood gases, expired air, heart rate, oxygen saturation, cognition, and perception metrics were collected throughout. KME rapidly elevated R-β-hydroxybutyrate and reduced blood glucose without altering lactate production. KME lowered pH, bicarbonate, and total carbon dioxide. VH with exercise significantly reduced blood (SpO2) and muscle (SmO2) oxygenation and increased cognitive mean reaction time and respiratory rate regardless of condition. KME administration significantly elevated respiratory exchange ratio (RER) at rest and throughout recovery from VH, compared to PLA. Blood carbon dioxide (PCO2) retention increased in the PLA condition while decreasing in the KME condition, leading to a significantly lower PCO2 value immediately post VH exercise (IPE; p = 0.031) and at recovery (p = 0.001), independent of respiratory rate. The KME’s ability to rapidly alter metabolism, acid/base balance, CO2 retention, and respiratory exchange rate independent of respiratory rate changes at rest, during, and/or following VH exercise protocol illustrates a rapid countermeasure to CO2 retention in concert with systemic metabolic changes.
Only the Rye Derived Part of the 1BL/1RS Hybrid Centromere Incorporates CENH3 of Wheat
Authors: Karimi-Ashtiyani Raheleh , Schubert Veit , Houben Andreas
Published: December 2021

The precise assembly of the kinetochore complex at the centromere is epigenetically determined by substituting histone H3 with the centromere-specific histone H3 variant CENH3 in centromeric nucleosomes. A chromosome 1B reconstructed in wheat by centric misdivision from two wheat-rye centric translocations is known to carry a hybrid wheat-rye centromere. The resulting hybrid (dicentric)centromere is composed of both wheat and rye centromeric repeats. As CENH3 is a marker for centromere activity, we applied Immuno-FISH followed by ultrastructural super-resolution microscopy to address whether both or only parts of the hybrid centromere are active. Our study demonstrates that only the rye-derived centromere part incorporates CENH3 of wheat in the 1BL/1RS hybrid centromere. This finding supports the notion that one centromere part of a translocated chromosome undergoes inactivation, creating functional monocentric chromosomes to maintain chromosome stability.
Interaction Mechanisms Between Major Depressive Disorder and Non-alcoholic Fatty Liver Disease
Authors: Shao Qi , Wu Yiping , Ji Jing , Xu Tian , Yu Qiaoyu , Ma Chongyang , Liao Xuejing , Cheng Fafeng , Wang Xueqian
Published: December 2021

Major depressive disorder (MDD), which is highly associated with non-alcoholic fatty liver disease (NAFLD), has complex pathogenic mechanisms. However, a limited number of studies have evaluated the mutual pathomechanisms involved in MDD and NAFLD development. Chronic stress-mediated elevations in glucocorticoid (GC) levels play an important role in the development of MDD-related NAFLD. Elevated GC levels can induce the release of inflammatory factors and changes in gut permeability. Elevated levels of inflammatory factors activate the hypothalamic–pituitary–adrenal (HPA) axis, which further increases the release of GC. At the same time, changes in gut permeability promote the release of inflammatory factors, which results in a vicious circle among the three, causing disease outbreaks. Even though the specific role of the thyroid hormone (TH) in this pathogenesis has not been fully established, it is highly correlated with MDD and NAFLD. Therefore, changing lifestyles and reducing psychological stress levels are necessary measures for preventing MDD-related NAFLD. Among them, GC inhibitors and receptor antagonists may be key in the alleviation of early and mid-term disease progression. However, combination medications may be important in late-stage diseases, but they are associated with various side effects. Traditional Chinese medicines have been shown to be potential therapeutic alternatives for such complex diseases.
Cost-Utility Analysis of the Integrated Care Models for the Management of Hypertension Patients: A Quasi-Experiment in Southwest Rural China
Authors: Ke Xiatong , Zhang Liang , Tang Wenxi
Published: December 2021

Background: Hypertension has become the second-leading risk factor for death worldwide. However, the fragmented three-level “county–township–village” medical and healthcare system in rural China cannot provide continuous, coordinated, and comprehensive health care for patients with hypertension, as a result of which rural China has a low rate of hypertension control. This study aimed to explore the costs and benefits of an integrated care model using three intervention modes—multidisciplinary teams (MDT), multi-institutional pathway (MIP), and system global budget and performance-based payments (SGB-P4P)—for hypertension management in rural China.

Methods: A Markov model with 1-year per cycle was adopted to simulate the lifetime medical costs and quality-adjusted life-years (QALYs) for patients. The interventions included Option 1 (MDT + MIP), Option 2 (MDT + MIP + SGB–P4P), and the Usual practice (usual care). We used the incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and net health benefit (NHB) to make economic decisions and a 5% discount rate. One-way and probability sensitivity analyses were performed to test model robustness. Data on the blood pressure control rate, transition probability, utility, annual treatment costs, and project costs were from the community intervention trial (CMB-OC) project.

Results: Compared with the Usual practice, Option 1 yielded an additional 0.068 QALYs and an additional cost of $229.99, resulting in an ICER of $3,373.75/QALY, the NMB was –$120.97, and the NHB was −0.076 QALYs. Compared with the Usual practice, Option 2 yielded an additional 0.545 QALYs, and the cost decreased by $2,007.31, yielding an ICER of –$3,680.72/QALY. The NMB was $2,879.42, and the NHB was 1.801 QALYs. Compared with Option 1, Option 2 yielded an additional 0.477 QALYs, and the cost decreased by $2,237.30, so the ICER was –$4,688.50/QALY, the NMB was $3,000.40, and the NHB was 1.876 QALYs. The one-way sensitivity analysis showed that the most sensitive factors in the model were treatment cost of ESRD, human cost, and discount rate. The probability sensitivity analysis showed that when willingness to pay was $1,599.16/QALY, the cost-effectiveness probability of Option 1, Option 2, and the Usual practice was 0.008, 0.813, and 0.179, respectively.

Conclusions: The integrated care model with performance-based prepaid payments was the most beneficial intervention, whereas the general integrated care model (MDT + MIP) was not cost-effective. The integrated care model (MDT + MIP + SGB-P4P) was suggested for use in the community management of hypertension in rural China as a continuous, patient-centered care system to improve the efficiency of hypertension management.
Insufficient Lycopene Intake Is Associated With High Risk of Prostate Cancer: A Cross-Sectional Study From the National Health and Nutrition Examination Survey (2003–2010)
Authors: Lu You , Edwards Andrea , Chen Zhong , Tseng Tung-Sung , Li Mirandy , Gonzalez Gabrielle V. , Zhang Kun
Published: December 2021

Although lycopene intake and risk of prostate cancer have been explored for decades, recent studies show that Non-Hispanic Black Prostate Cancer (PCa) patients benefit less than Non-Hispanic White patients from a lycopene intake intervention program. This study examined whether a lycopene intake-related racial disparity exists in reducing the risk of PCa in healthy adults. Data on healthy, cancer-free Non-Hispanic Black (NHB) men (n = 159) and Non-Hispanic White (NHW) men (n = 478) from the 2003 to 2010 NHANES dataset were analyzed. Total lycopene intake from daily diet, age, living status, race/ethnicity, education level, poverty income ratio, body mass index, and smoking status were studied as independent variables. The combination of total Prostate-Specific Antigen (PSA) level and the ratio of free PSA was set as criteria for evaluating the risk of PCa. Multivariable logistic regression was used in race-stratified analyses to compute odds ratios (OR) and 95% confidence intervals (95% CI) comparing high PCa risk with low PCa risk. We found, in the whole population, race/ethnicity was the only factor that influenced lycopene intake from the daily diet. NHB men consumed less lycopene than NHW men (3,716 vs. 6,487 (mcg), p = 0.01). Sufficient lycopene intake could reduce the risk of PCa (OR: 0.40, 95% CI: 0.18–0.85, p = 0.02). Men aged between 66 and 70 had high PCa risk (OR: 3.32, 95% CI: 1.12–9.85, p = 0.03). Obesity served as a protective factor against the high risk of PCa (OR: 0.25, 95% CI: 0.12–0.54, p = 0.001). NHW men aged between 66 and 70 had a high risk of PCa (OR: 4.01, 95% CI: 1.02–15.73, p = 0.05). Obese NHW men also had lower risk of PCa (OR: 0.18, 95% CI: 0.07–0.47 p = 0.001). NHB men had a high risk of PCa compared to NHW men (OR: 2.27, 95% CI: 1.35–3.81 p = 0.004). NHB men who were living without partners experienced an even higher risk of PCa (OR: 3.35, 95% CI: 1.01–11.19 p = 0.07). Sufficient lycopene intake from daily food could serve as a protector against PCa. Such an association was only observed in NHW men. Further studies are needed to explore the dose-response relationship between lycopene intake and the association of PCa risk in NHB men.
Optimizing Evaluation of Older Adults With Vision and/or Hearing Loss Using the interRAI Community Health Assessment and Deafblind Supplement
Authors: Urqueta Alfaro Andrea , McGraw Cathy , Guthrie Dawn M. , Wittich Walter
Published: December 2021

Purpose: Service providers must identify and assess older adults who have concurrent vision and hearing loss, or dual sensory impairment (DSI). An assessment tool suitable for this purpose is the interRAI Community Health Assessment (CHA) and its Deafblind Supplement. This study's goal was to explore this assessment's administration process and to generate suggestions for assessors to help them optimize data collection.

Methods: A social worker with experience working with adults who have sensory loss, who was also naïve to the interRAI CHA, administered the assessment with 200 older adults (65+) who had visual and/or hearing loss. The assessor evaluated the utility of the instrument for clinical purposes, focusing on sections relevant to identifying/characterizing adults with DSI.

Results: Suggestions include the recommendation to ask additional questions regarding the person's functional abilities. This will help assessors deepen their understanding of the person's sensory status. Recommendations are also provided regarding sensory impairments and rehabilitation, in a general sense, to help assessors administer the interRAI CHA.

Conclusions: Suggestions will help assessors to deepen their knowledge about sensory loss and comprehensively understand the assessment's questions, thereby allowing them to optimize the assessment process and increase their awareness of sensory loss in older adults.
Great Lakes Basin Heat Waves: An Analysis of Their Increasing Probability of Occurrence Under Global Warming
Authors: Xie Fengyi , Erler Andre R. , Chandan Deepak , Peltier W. Richard
Published: December 2021

Extreme heat events in the Great Lakes Basin (GLB) region of eastern North America are expected to increase in concert with greenhouse gas (GHG) induced global warming. The extent of this regional increase is also influenced by the direct effects of the Great Lakes themselves. This paper describes results from an ensemble of dynamically downscaled global warming projection using the Weather Research and Forecast (WRF) regional climate model coupled to the Freshwater Lake (FLake) model over the Great Lakes region. In our downscaling pipeline, we explore two sets of WRF physics configurations, with the initial and boundary conditions provided by four different fully coupled Global Climate Models (GCMs). Three time periods are investigated, namely an instrumental period (1979–1989) that is employed for validation, and a mid-century (2050–2060) and an end-century (2085–2100) periods that are used to understand the future impacts of global warming. Results from the instrumental period are characterized by large variations in climate states between the ensemble members, which is attributed to differences in both GCM forcing and WRF physics configuration. Results for the future periods, however, are such that the regional model results have good agreement with GCM results insofar as the rise of average temperature with GHG is concerned. Analysis of extreme heat events suggests that the occurrence rate of such events increase steadily with rising temperature, and that the Great Lakes exert strong lake effect influence on extreme heat events in this region.
Muscle Oxygenation, Heart Rate, and Blood Lactate Concentration During Submaximal and Maximal Interval Swimming
Authors: Dalamitros Athanasios A. , Semaltianou Eleni , Toubekis Argyris G. , Kabasakalis Athanasios
Published: December 2021

This study aimed to determine the relationship between three testing procedures during different intensity interval efforts in swimming. Twelve national-level swimmers of both genders executed, on different occasions and after a standardized warm-up, a swimming protocol consisting of either a submaximal (Submax: 8 efforts of 50 m) or a maximal interval (Max: 4 efforts of 15 m), followed by two series of four maximal 25 m efforts. Near-infrared spectroscopy in terms of muscle oxygen saturation (SmO2), heart rate (HR), and blood lactate concentration (BLa) were analyzed at three testing points: after the Submax or the Max protocol (TP1), after the 1st 4 × 25-m (TP2), and after the 2nd maximal 4 × 25-m set (TP3). BLa and HR showed significant changes during all testing points in both protocols (P ≤ 0.01; ES range: 0.45–1.40). SmO2 was different only between TP1 and TP3 in both protocols (P ≤ 0.05–0.01; ES range: 0.36–1.20). A large correlation during the Max protocol between SmO2 and HR (r: 0.931; P ≤ 0.01), and also between SmO2 and BLa was obtained at TP1 (r: 0.722; P ≤ 0.05). A range of moderate-to-large correlations was revealed for SmO2/HR, and BLa/HR for TP2 and TP3 after both protocols (r range: 0.595–0.728; P ≤ 0.05) were executed. SmO2 is a novel parameter that can be used when aiming for a comprehensive evaluation of competitive swimmers' acute responses to sprint interval swimming, in conjunction with HR and BLa.
Management of Acute Traumatic Spinal Cord Injury: A Review of the Literature
Authors: Wang Timothy Y. , Park Christine , Zhang Hanci , Rahimpour Shervin , Murphy Kelly R. , Goodwin C. Rory , Karikari Isaac O. , Than Khoi D. , Shaffrey Christopher I. , Foster Norah , Abd-El-Barr Muhammad M.
Published: December 2021

Traumatic spinal cord injury (TSCI) is a debilitating disease that poses significant functional and economic burden on both the individual and societal levels. Prognosis is dependent on the extent of the spinal injury and the severity of neurological dysfunction. If not treated rapidly, patients with TSCI can suffer further secondary damage and experience escalating disability and complications. It is important to quickly assess the patient to identify the location and severity of injury to make a decision to pursue a surgical and/or conservative management. However, there are many conditions that factor into the management of TSCI patients, ranging from the initial presentation of the patient to long-term care for optimal recovery. Here, we provide a comprehensive review of the etiologies of spinal cord injury and the complications that may arise, and present an algorithm to aid in the management of TSCI.
Exploring Central Vascular Anatomy With Axial Computed Tomography During Surgery for Sigmoid Colon and Rectal Cancer: New Insights Into the Anatomical Relationship Between the Inferior Mesenteric Artery and the Duodenum
Authors: Cheng Zhiqiang , Ren Pengfei , Wang Xiaoyan , Wang Kexin , Yan Zhibo , Bi Dongsong , Wang Yanlei , Dai Yong , Zhang Xiang
Published: December 2021

Background: In some individuals, the inferior mesenteric artery (IMA) originates from the aorta above the lower edge of the duodenum. This anatomical feature has rarely been reported but may be important in guiding central vascular ligation and lymph node dissection in colorectal surgery. This retrospective study aimed to explore the anatomical relationship between the IMA and the duodenum and evaluate its potential impact on the efficacy of D3 lymph node dissection.

Methods: A total of 439 patients undergoing laparoscopic colorectal surgery at the Department of General Surgery, Qilu Hospital of Shandong University, were retrospectively enrolled. Clinical data from axial computed tomography (CT) scans were collected and analysed.

Results: In 27.69% of patients, the IMA originated at or above the lower edge of the duodenum (median distance: −8 mm). These patients were characterised by a shorter superior mesenteric artery to aortic bifurcation distance, a superiorly located IMA origin, and a greater distance between the IMA and both the left colic artery and the inferior mesenteric vein. The number of harvested lymph nodes was not significantly associated with the distance between the IMA and the duodenum (P = 0.858).

Conclusions: Preoperative axial CT scans can provide a great deal of information regarding central vascular anatomy in the context of sigmoid colon and rectal cancer surgery. Nearly one-third of patients have the IMA originating at or above the duodenum. Whether this anatomical feature affects D3 lymph node dissection warrants further investigation.
New Traits of Agriculture/Food Quality Interface 2.0
Authors: Durazzo Alessandra , Lucarini Massimo
Published: December 2021

We announce a second edition of the Special Issue “New Traits of Agriculture/Food Quality Interface” [...]