bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypocretin/orexin influences chronic sleep disruption injury in the hippocampus
Authors: Nick Henry , Fenik Polina , Zhu Yan , Veasey Sigrid 
Published: October 2022

Chronic sleep disruption is a risk factor for Alzheimer’s disease (AD), yet mechanisms by which sleep disturbances might promote or exacerbate AD are not understood. Short-term sleep loss acutely increases hippocampal amyloid β (Aβ) in wild type (WT) mice and long-term sleep loss increases amyloid plaque in AD transgenic mouse models. Both effects can be influenced by the wake-promoting neuropeptide, hypocretin (HCRT), but whether HCRT influences amyloid accumulation independent of sleep and wake timing modulation remains unclear. Here, we induced chronic fragmentation of sleep (CFS) in WT and HCRT-deficient mice to elicit similar arousal indices, sleep bout lengths and sleep bout numbers in both genotypes. We then examined the roles of HCRT in CFS-induced hippocampal Aβ accumulation and injury. CFS in WT mice resulted in increased Aβ42 in the hippocampus along with loss of cholinergic projections and loss of locus coeruleus neurons. Mice with HCRT deficiency conferred resistance to CFS Aβ42 accumulation and loss of cholinergic projections in the hippocampus yet evidenced similar CFS-induced loss of locus coeruleus neurons. Collectively, the findings demonstrate specific roles for orexin in sleep disruption hippocampal injury.Significance statementChronic fragmentation of sleep (CFS) occurs in common conditions, including sleep apnea syndromes and chronic pain disorders, yet CFS can induce neural injury. Our results demonstrate that under conditions of sleep fragmentation, hypocretin/orexin is essential for the accumulation of amyloid-β and loss of cholinergic projections in the hippocampus observed in response to CFS yet does not influence locus coeruleus neuron response to CFS.
Effect of acupuncture for non-motor symptoms in patients with Parkinson’s disease: A systematic review and meta-analysis
Authors: Li Qinglian , Wu Chunxiao , Wang Xiaoling , Li Zhen , Hao Xiaoqian , Zhao Lijun , Li Mengzhu , Zhu Meiling 
Published: October 2022

BackgroundAlthough non-motor symptoms of Parkinson’s disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD.MethodsRandomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242–0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181–0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = −0.353; 95% CI = −0.669 to −0.037; p = 0.029) within 2 months (SMD = −0.671; 95% CI = −1.332 to −0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson’s Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046–1.711, p = 0.039; SMD = −0.690, 95% CI = −1.226 to −0.155, p = 0.011; weighted mean difference (WMD) = −1.536, 95% CI = −2.201 to −0.871, p = 0.000; WMD = −2.071, 95% CI = −3.792 to −0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue.ConclusionThe results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.
Case report: Bitter vertigo
Authors: Goldschagg Nicolina , Brem Christian , Strupp Michael 
Published: October 2022

BackgroundThere are many causes of episodes of vertigo and very few causes of episodes of changes in taste, and the combination of the two is very rare. Here, we describe a patient with recurrent short episodes of vertigo in combination with simultaneous episodes of recurrent paroxysmal dysgeusia and altered feeling on the left side of face. The symptoms were caused by compression of the vestibulocochlear nerve and the facial nerve due to dolichoectasia of the basilar artery.MethodsThe patient was diagnosed in our routine clinical practice and underwent a complete neurological and neuro-otological examination, including video head impulse test, caloric irrigation, ocular and cervical vestibular evoked myogenic potentials, acoustic-evoked potentials, neuro-orthoptic examination, cranial MRI, and MR angiography. The patient was seen twice for follow-up.CaseA 71-year-old patient primarily presented with a 2-year history of recurrent short episodes of spinning vertigo. Each of the episodes began with an altered feeling on the left side of the face, followed by a bitter taste on the left half of the tongue, and subsequently vertigo lasting for up to 15 s. The frequency of the attacks was high: up to 80 times per day. Laboratory tests revealed signs of a peripheral vestibular deficit on the left side. There were no signs of sensory or motor deficits or of altered taste between the episodes. An MRI of the brain showed an elongated basilar artery leading to an indentation of the facial and vestibulocochlear nerves on the left side.ConclusionWe propose a neurovascular compression in the proximal part of two cranial nerves because of pulsatile compression by the elongated basilar artery with ephatic discharges as the cause of the recurrent episodes. Consistent with the theory of ephatic discharges, treatment with the sodium channel blocker lacosamide for over six months with a final dosage of 200 mg per day p.o. led to a significant reduction of the attack frequency and intensity. This treatment option with a sodium channel blocker should therefore not only be considered in vestibular paroxysmia but also in cases of paroxysmal dysgeusia.
Case report: Visual snow as the presenting symptom in multiple evanescent white dot syndrome. Two case reports and literature review
Authors: Hang Chenyue , Yan Yan 
Published: October 2022

PurposeMultiple evanescent white dot syndrome (MEWDS) usually manifests as photopsia, enlarged blind spots, scotomas, and blurred vision, which can be classified into positive and negative visual phenomena. Visual snow and chromatopsia were rarely reported in these patients. Herein, we described two Chinese female patients with MEWDS who initially presented with visual snow, and one of them also had yellow-tinged vision.MethodsFirst, we performed the chart review of two patients. Second, we reviewed the English literature for all cases of MEWDS through PubMed until December 2021, using the terms “MEWDS” or “multiple evanescent white dot syndrome.” We concluded on all the reported patients' demographic features and symptoms. The visual acuity of patients with/without positive or negative visual phenomena was compared through one-way ANOVA.ResultsPatient 1: A 27-year-old Chinese woman experienced continuous visual snow and yellow-tinged vision in the right eye for a week. She noticed tiny white and black dots involving the entire visual field and shimmering light inferiorly. Patient 2: A 22-year-old Chinese woman complained of a gray area with continuous visual snow in the temporal visual field of the left eye for 5 days. The ocular examinations, including fundus autofluorescence (FAF), optical coherence tomography (OCT), and indocyanine green angiography (ICGA), confirmed the diagnosis of MEWDS. Their symptoms resolved spontaneously without treatment. We found 60 MEWDS case reports (147 cases) in PubMed. The mean age was 31.2 years old. The mean LogMAR best-corrected visual acuity was 0.35 ± 0.39 at the first visit and 0.01 ± 0.16 at the last visit. The most common symptoms included blurred vision (72.8%), enlarged blind spot (42.2%), photopsia (37.4%), and scotoma (33.3%). We found the patients with only positive visual phenomena had significantly worse visual acuity at the first and last visit than patients with only negative visual phenomena (p = 0.008) or the patients with both positive and negative visual phenomena (p = 0.026). Four cases similar to visual snow were discovered. Compared to the MEWDS patients without visual snow, the patients with visual snow tend to have a larger proportion of females (p = 0.005) and a better visual acuity at the first visit (p = 0.007).ConclusionHerein, we expand upon the clinical manifestations of MEWDS with visual snow, and the symptoms attributable to visual snow could precede the onset of MEWDS. Neurologists and ophthalmologists should carefully rule out occult chorioretinopathy before diagnosing visual snow syndrome.
CT-guided radiofrequency ablation of the extracranial cranial nerve for the treatment of Meige’s syndrome
Authors: Huang Bing , Du Xin-dan , Yao Ming , Lin Hui-dan , Yu Wen-hua , Zhou Qing-he 
Published: October 2022

BackgroundMeige’ s syndrome, a rare form of dystonia, lacks effective treatment. The purpose of this study was to determine the effects of CT-guided percutaneous extracranial radiofrequency ablation of the facial and/or trigeminal nerves in the treatment of Meige’s syndrome.MethodsA total of 10 patients were enrolled in this study, with the numbers of blepharospasm dystonia syndrome (BDS), oromandibular dystonia syndrome (ODS), and blepharospasm combined with oromandibular dystonia syndrome (B-ODS) being 7, 1, and 2, respectively. BDS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve; ODS patients underwent radiofrequency ablation of the bilateral foramen oval trigeminal mandibular branch, and B-ODS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve and foramen oval trigeminal mandibular branch. The therapeutic effects and complications were observed.ResultsAll 10 patients in this series experienced improved Meige’s syndrome-related symptoms after extracranial radiofrequency ablation of the cranial and/or mandibular branches of the extracranial trigeminal nerve. Adverse events included class II–III facial paralysis and/or mandibular skin numbness. Two patients had recurrences at the 18th and 22nd months postoperatively, respectively; the other patients were being followed up.ConclusionThese results shown that CT-guided radiofrequency ablation of bilateral stylomastoid foramen facial nerve and/or oval foramen trigeminal mandibular branch can effectively treat the corresponding types of Meige’s syndrome. According to preliminary observations, the therapeutic effect may last more than 18 months.
Comparison of waist-height ratio and other obesity indices in the prediction of diabetic peripheral neuropathy
Authors: Lawal Yakubu , Mshelia-Reng Rifkatu , Omonua Special O. , Odumodu Kenechukwu , Shuaibu Ramatu , Itanyi Ukamaka D. , Abubakar Amina I. , Kolade-Yunusa Hadijat O. , Songden Zumnan D. , Ehusani Caleb O. , Adediran Olufemi , Anumah Felicia E. 
Published: October 2022

BackgroundWaist-height ratio (WHtR) is increasingly being studied as a simple and effective measure of central obesity. Reports have shown that WHtR is a better predictor of hypertension, diabetes, and cardiovascular diseases when compared to traditional obesity indices like body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR). This study is therefore aimed at comparing WHtR with other obesity indices in the prediction of peripheral neuropathy in persons with diabetes mellitus (DM).MethodologyOne thousand and forty persons with DM were enrolled following consent. Relevant details of history were obtained, followed by physical examinations. Data were analyzed using IBM-SPSS version 23. Logistic regression was used to compare the odds ratio of obesity indices in the prediction of peripheral neuropathy. The level of significance used was p = 0.05.ResultsLogistic regression showed that WHtR had the highest odds ratio (OR) for the prediction of “probable” diabetic peripheral neuropathy (OR 9.11, 95% CI 3.07–47.97, p = 0.002), followed by WC (OR 2.01, 95% CI 1.09–4.05, p = 0.004), and BMI (OR 1.26, 95% CI 1.00–3.99, p = 0.019) after correction for age; systemic hypertension; duration of DM; control of SBP, DBP, HbA1c, FPG, and 2HrPP.ConclusionWHtR has the highest odds ratio in the prediction of “probable” diabetic peripheral neuropathy in both genders, followed by WC in the males and BMI in the females.
Erythritol synthesis is elevated in response to oxidative stress and regulated by the non-oxidative pentose phosphate pathway in A549 cells
Authors: Ortiz Semira R. , Heinz Alexander , Hiller Karsten , Field Martha S. 
Published: October 2022

BackgroundErythritol is a predictive biomarker of cardiometabolic diseases and is produced from glucose metabolism through the pentose phosphate pathway (PPP). Little is known regarding the regulation of endogenous erythritol synthesis in humans.ObjectiveIn the present study, we investigated the stimuli that promote erythritol synthesis in human lung carcinoma cells and characterized potential points of regulation along the PPP.MethodsHuman A549 lung carcinoma cells were chosen for their known ability to synthesize erythritol. A549 cells were treated with potential substrates for erythritol production, including glucose, fructose, and glycerol. Using siRNA knockdown, we assessed the necessity of enzymes G6PD, TKT, TALDO, and SORD for erythritol synthesis. We also used position-specific13C-glucose tracers to determine whether the carbons for erythritol synthesis are derived directly from glycolysis or through the oxidative PPP. Finally, we assessed if erythritol synthesis responds to oxidative stress using chemical and genetic models.ResultsIntracellular erythritol was directly associated with media glucose concentration. In addition, siRNA knockdown of TKT or SORD inhibited erythritol synthesis, whereas siG6PD did not. Both chemically induced oxidative stress and constitutive activation of the antioxidant response transcription factor NRF2 elevated intracellular erythritol.ConclusionOur findings indicate that in A549 cells, erythritol synthesis is proportional to flux through the PPP and is regulated by non-oxidative PPP enzymes.
Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: A systematic review and meta-analysis
Authors: Mushtaq Muhammad Umair , Shahzad Moazzam , Tariq Ezza , Iqbal Qamar , Chaudhary Sibgha Gull , Zafar Muhammad U. , Anwar Iqra , Ahmed Nausheen , Bansal Rajat , Singh Anurag K. , Abhyankar Sunil H. , Callander Natalie S. , Hematti Peiman , McGuirk Joseph P. 
Published: October 2022

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.MethodsA literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsA total of 3336 patients from 19 studies were included. The median age was 52.1 years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively. In-vivo T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131/3030) and 41.2% (95% CI 0.35-0.48, n=1337/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888/3196) after a median follow-up of 2.6 (1-5) years.ConclusionMMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.
Clinicopathological features and prognosis of TFE3-positive renal cell carcinoma
Authors: Dong Xiang , Chen Yuxin , Pan Jun , Ma Wenliang , Zhou Peng , Chen Ming , Guo Hongqian , Gan Weidong 
Published: October 2022

BackgroundThis study aimed to investigate the expression profile of TFE3 in renal cell carcinoma (RCC) and the clinicopathological features as well as prognosis of TFE3-positive RCC.MethodsTissue sections from 796 patients with RCC were collected for immunohistochemical staining of TFE3. Molecular TFE3 rearrangement tests were also carried out on the TFE3-positive RCCs using fluorescence in situ hybridization and RNA-sequencing assays. Both clinicopathological features and follow-up information were collected for further analysis.ResultsThe present study showed that 91 patients with RCC (91/796, 11.4%) were TFE3 positive expression but only 31 (31/91, 34.1%) of the patients were diagnosed with Xp11.2 translocation RCC. Further, it was found that the patients with TFE3-positive RCCs were more likely to develop lymph node and distant metastasis at diagnosis as well as presented a significantly higher WHO/ISUP nuclear grade and AJCC stage as compared with patients with TFE3-negative RCCs (p&lt;0.01). Results of univariate and multivariate analyses showed that TFE3 positive expression was an independent prognostic factor associated with poor progression-free survival. Further, the findings of survival analysis showed that patients with positive TFE3 expression showed a shorter progression-free survival as compared with the patients with negative expression of TFE3 (p&lt;0.001). In addition, results of the survival analysis found that there was no significant difference in progression-free survival between the Xp11.2 translocation RCC and TFE3-positive non-Xp11.2 translocation RCC groups (p=0.9607).ConclusionThis study found that nuclear TFE3 expression is not specific to the Xp11.2 translocation RCC. Moreover, the positive TFE3 expression is associated with tumor progression and poor prognosis in patients with RCC irrespective of the presence of TFE3 translocation.
Radiomics features based on internal and marginal areas of the tumor for the preoperative prediction of microsatellite instability status in colorectal cancer
Authors: Ma Yi , Lin Changsong , Liu Song , Wei Ying , Ji Changfeng , Shi Feng , Lin Fan , Zhou Zhengyang 
Published: October 2022

ObjectivesTo explore whether the preoperative CT radiomics can predict the status of microsatellite instability (MSI) in colorectal cancer (CRC) patients and identify the region with the most stable and high-efficiency radiomics features.MethodsThis retrospective study involved 230 CRC patients with preoperative computed tomography scans and available MSI status between December 2019 and October 2021. Image segmentation and radiomic feature extraction were performed as follows. First, slices with the maximum tumor area (region of interest, ROI) were manually contoured. Subsequently, each ROI was shrunk inward by 1, 2, and 3 mm, respectively, where the remaining ROIs were considered as the internal region of the tumor (named as IROI1, IROI2, and IROI3), and the shrunk regions were considered as marginal regions of the tumor (named as MROI1, MROI2, and MROI3). Finally, radiomics features were extracted from each of the ROI. The intraclass correlation coefficient and least absolute shrinkage and selection operator method were used to choose the most reliable and relevant features of MSI status. Clinical, radiomics, and combined clinical radiomics models have been established. Calibration curve and decision curve analyses (DCA) were generated to explore the correction effect and assess the clinical applicability of the above models, respectively.ResultsIn the testing cohort, the radiomics model based on IROI3 yielded the highest average area under the curve (AUC) value of 0.908, compared with the remaining radiomics models. Additionally, hypertension and N stage were considered as clinically independent factors of MSI status. The combined clinical radiomics model achieved excellent diagnostic efficacy (AUC: 0.928; sensitivity: 0.840; specificity: 0.867) in the testing cohort, as well as favorable calibration and clinical utility by calibration curve and DCA analyses.ConclusionsThe IROI3 model, which is based on a 3-mm shrink in the largest areas of the tumor, could noninvasively reflect the heterogeneity and genetic instability within the tumor. This suggests that it is an important biomarker for the preoperative prediction of MSI status. The model can extract more robust and effective radiomics features, which lays a foundation for the radiomics study of hollow organs, such as in CRC.