bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of different risk scores for Parkinson disease in a population‐based 10‐year study
Authors: Marini Kathrin , Seppi Klaus , Kiechl Stefan , Stockner Heike , Willeit Peter , Willeit Johann , Djamshidian Atbin , Rungger Gregorio , Poewe Werner , Mahlknecht Philipp
Published: July 2023

Background and purpose

Different algorithms aiming to identify individuals at risk of Parkinson disease (PD) have been proposed. Comparative studies of these scores and their recent updates in the general elder population are needed.

Methods

We have previously applied the “basic” PREDICT‐PD algorithm, designed for remote screening, and the original and updated Movement Disorder Society (MDS) criteria for prodromal PD to the longitudinal population‐based Bruneck study cohort. We have now additionally employed the “enhanced” PREDICT‐PD algorithm (which includes motor assessment, olfaction, probable rapid eye movement sleep behaviour disorder status, pesticide exposure, and diabetes as additional factors). Risk scores were calculated based on comprehensive baseline assessments (2005) in 574 subjects aged 55–94 years (290 females), and cases of incident PD were identified at 5‐year (n = 11) and 10‐year follow‐up (n = 9). We analysed the association of the different log‐transformed risk scores with incident PD at follow‐up (calculated per 1‐SD unit change).

Results

The enhanced PREDICT‐PD algorithm was associated with incident PD over 10‐years of follow‐up, yielding higher odds for incident PD (odds ratio [OR] = 4.61, 95% confidence interval [CI] = 2.68–7.93, p < 0.001) compared with the basic PREDICT‐PD score (OR = 2.38, 95% CI = 1.49–3.79, p < 0.001). The updated MDS prodromal criteria yielded a numerically higher OR of 7.13 (95% CI = 3.49–14.54, p < 0.001) in comparison with the original criteria as well as the enhanced PREDICT‐PD algorithm, with overlapping 95% CIs.

Conclusions

The enhanced PREDICT‐PD algorithm was significantly associated with incident PD. The consistent performance of both the enhanced PREDICT‐PD algorithm and the updated MDS prodromal criteria compared to their original versions supports their use in PD risk screening.
Blood neurofilament light chain as a surrogate marker for dystonia
Authors: Wu Meng‐Chen , Chang Yung‐Yee , Lan Min‐Yu , Chen Ying‐Fa , Tai Chun‐Hwei , Chen Szu‐Ju , Lin Chin‐Hsien
Published: July 2023

Background and purpose

Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia.

Method

We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single‐molecule array.

Results

Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole‐exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores.

Conclusion

Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.
TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features
Authors: Zhao Bi , Jiang Qirui , Lin Junyu , Wei Qianqian , Li Chunyu , Hou Yanbing , Cao Bei , Zhang Lingyu , Ou Ruwei , Liu Kuncheng , Yang Tianmi , Xiao Yi , Shang Huifang
Published: July 2023

Background and purpose

Haploinsufficiency of TANK‐binding kinase 1 (TBK1) loss‐of‐function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians.

Methods

Genetic analysis was performed on 2011 Chinese ALS patients. Software was used to predict the deleteriousness of missense variants in TBK1. In addition, PubMed, Embase and Web of Science were searched for related literature.

Results

Twenty‐six TBK1 variants were identified in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants, 12 of which were predicted to be deleterious (0.6%). In addition to TBK1 variants, 11 patients had other ALS‐related gene variants. Forty‐two previous studies found that the frequency of TBK1 variants was 1.81% in ALS/FTD patients. The frequency of TBK1 LoF variants in ALS was 0.5% (Asians 0.4%; Caucasian 0.6%) and that of missense variants was 0.8% (Asians 1.0%; Caucasian 0.8%). ALS patients with TBK1 LoF variants affecting the kinase domain had a significantly younger age of onset than patients carrying LoF variants affecting the coiled coil domains CCD1 and CCD2. FTD has a frequency of 10% in Caucasian ALS patients with TBK1 LoF variants, which was not found in our cohort.

Conclusion

Our study expanded the genotypic spectrum of ALS patients with TBK1 variants and found that the clinical manifestations of TBK1 carriers are diverse.
Sham‐controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness
Authors: Thibaut Aurore , Fregni Felipe , Estraneo Anna , Fiorenza Salvatore , Noe Enrique , Llorens Roberto , Ferri Joan , Formisano Rita , Morone Giovanni , Bender Andreas , Rosenfelder Martin , Lamberti Gianfranco , Kodratyeva Ekaterina , Kondratyev Sergey , Legostaeva Liudmila , Suponeva Natalia , Krewer Carmen , Müller Friedemann , Dardenne Nadia , Jedidi Haroun , Laureys Steven , Gosseries Olivia , Lejeune Nicolas , Martens Géraldine ,   the IBIA DOC‐SIG
Published: July 2023

Background and purpose

Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double‐blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS.

Methods

Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months’ follow‐up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non‐traumatic). Interim analyses were planned to continue or stop the trial.

Results

The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post‐injury, 18 women, 32 MCS, 39 non‐traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months’ follow‐up revealed a significant improvement for patients in MCS and with traumatic aetiology.

Conclusions

Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.
Everolimus precision therapy for the GATOR1‐related epilepsies: A case series
Authors: Moloney Patrick B. , Kearney Hugh , Benson Katherine A. , Costello Daniel J. , Cavalleri Gianpiero L. , Gorman Kathleen M. , Lynch Bryan J. , Delanty Norman
Published: July 2023

Background

Pathogenic variants in the GAP activity towards RAGs 1 (GATOR1) complex genes (DEPDC5, NPRL2, NPRL3) cause focal epilepsy through hyperactivation of the mechanistic target of rapamycin pathway. We report our experience using everolimus in patients with refractory GATOR1‐related epilepsy.

Methods

We performed an open‐label observational study of everolimus for drug‐resistant epilepsy caused by variants in DEPDC5, NPRL2 and NPRL3. Everolimus was titrated to a target serum concentration (5–15 ng/mL). The primary outcome measure was change in mean monthly seizure frequency compared with baseline.

Results

Five patients were treated with everolimus. All had highly active (median baseline seizure frequency, 18/month) and refractory focal epilepsy (failed 5–16 prior anti‐seizure medications). Four had DEPDC5 variants (three loss‐of‐function, one missense) and one had a NPRL3 splice‐site variant. All patients with DEPDC5 loss‐of‐function variants had significantly reduced seizures (74.3%–86.1%), although one stopped everolimus after 12 months due to psychiatric symptoms. Everolimus was less effective in the patient with a DEPDC5 missense variant (43.9% seizure frequency reduction). The patient with NPRL3‐related epilepsy had seizure worsening. The most common adverse event was stomatitis.

Conclusions

Our study provides the first human data on the potential benefit of everolimus precision therapy for epilepsy caused by DEPDC5 loss‐of‐function variants. Further studies are needed to support our findings.
Trends in the neurological emergency room, focusing on persons with seizures
Authors: Welte Tamara M. , Ernst Sebastian , Stritzelberger Jenny , Gollwitzer Stephanie , Lang Johannes D. , Reindl Caroline , Sprügel Maximilian I. , Olmes David , Schwab Stefan , Blinzler Christian , Hamer Hajo M.
Published: July 2023

Background and purpose

Previous studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS.

Methods

We retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER.

Results

A total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS.

Conclusion

After 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment.
Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications
Authors: Bethamcharla Raviteja , Abou‐Al‐Shaar Hussam , Maarbjerg Stine , Chang Yue‐Fang , Gacka Caroline N. , Sekula Raymond F.
Published: July 2023

Background and purpose

Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG).

Methods

We performed a retrospective single‐center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale.

Results

Forty‐five patients underwent a total of 66 PGRs of the TG. At short‐term follow‐up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow‐up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb‐V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications.

Conclusion

In patients with these anatomical subtypes of TN there was a high rate of short‐term pain relief for the first 1–2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.
Machine learning using multimodal clinical, electroencephalographic, and magnetic resonance imaging data can predict incident depression in adults with epilepsy: A pilot study
Authors: Delgado‐García Guillermo , Engbers Jordan D. T. , Wiebe Samuel , Mouches Pauline , Amador Kimberly , Forkert Nils D. , White James , Sajobi Tolulope , Klein Karl Martin , Josephson Colin B. ,   the Calgary Comprehensive Epilepsy Program Collaborators
Published: July 2023

Objective

This study was undertaken to develop a multimodal machine learning (ML) approach for predicting incident depression in adults with epilepsy.

Methods

We randomly selected 200 patients from the Calgary Comprehensive Epilepsy Program registry and linked their registry‐based clinical data to their first‐available clinical electroencephalogram (EEG) and magnetic resonance imaging (MRI) study. We excluded patients with a clinical or Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E)‐based diagnosis of major depression at baseline. The NDDI‐E was used to detect incident depression over a median of 2.4 years of follow‐up (interquartile range [IQR] = 1.5–3.3 years). A ReliefF algorithm was applied to clinical as well as quantitative EEG and MRI parameters for feature selection. Six ML algorithms were trained and tested using stratified threefold cross‐validation. Multiple metrics were used to assess model performances.

Results

Of 200 patients, 150 had EEG and MRI data of sufficient quality for ML, of whom 59 were excluded due to prevalent depression. Therefore, 91 patients (41 women) were included, with a median age of 29 (IQR = 22–44) years. A total of 42 features were selected by ReliefF, none of which was a quantitative MRI or EEG variable. All models had a sensitivity > 80%, and five of six had an F1 score ≥ .72. A multilayer perceptron model had the highest F1 score (median = .74, IQR = .71–.78) and sensitivity (84.3%). Median area under the receiver operating characteristic curve and normalized Matthews correlation coefficient were .70 (IQR = .64–.78) and .57 (IQR = .50–.65), respectively.

Significance

Multimodal ML using baseline features can predict incident depression in this population. Our pilot models demonstrated high accuracy for depression prediction. However, overall performance and calibration can be improved. This model has promise for identifying those at risk for incident depression during follow‐up, although efforts to refine it in larger populations along with external validation are required.
Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population‐based cohort study
Authors: Larsson David , Mroué Deala , Andrén Kerstin , Zelano Johan
Published: July 2023

Objective

Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real‐world data. Third‐generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden.

Methods

A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy.

Results

A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52–77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow‐up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty‐nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p = .010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16–3.51).

Significance

Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow‐up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.
First seizure from sleep: Clinical features and prognosis
Authors: Lawn Nicholas D. , Pang Elaine W. , Lee Judy , Dunne John W.
Published: July 2023

Objectives

Patients with a first‐ever unprovoked seizure commonly have subsequent seizures and identifying predictors of recurrence has important management implications. Both prior brain insult and epileptiform abnormalities on electroencephalography (EEG) are established predictors of seizure recurrence. Some studies suggest that a first‐ever seizure from sleep has a higher likelihood of recurrence. However, with relatively small numbers and inconsistent definitions, more data are required.

Methods

Prospective cohort study of adults with first‐ever unprovoked seizure seen by a hospital‐based first seizure service between 2000 and 2015. Clinical features and outcomes of first‐ever seizure from sleep and while awake were compared.

Results

First‐ever unprovoked seizure occurred during sleep in 298 of 1312 patients (23%), in whom the 1‐year cumulative risk of recurrence was 56.9% (95% confidence interval [CI] 51.3–62.6) compared to 44.2% (95% CI 41.1–47.3, p < .0001) for patients with first‐ever seizure while awake. First‐ever seizure from sleep was an independent predictor of seizure recurrence, with a hazard ratio [HR] of 1.44 (95% CI 1.23–1.69), similar to epileptiform abnormalities on EEG (HR 1.48, 95% CI 1.24–1.76) and remote symptomatic etiology (HR 1.47, 95% CI 1.27–1.71). HR for recurrence in patients without either epileptiform abnormalities or remote symptomatic etiology was 1.97 (95% CI 1.60–2.44) for a sleep seizure compared to an awake seizure. For first seizure from sleep, 76% of second seizures also arose from sleep (p < .0001), with 65% of third seizures (p < .0001) also from sleep. Seizures from sleep were less likely to be associated with injury other than orolingual trauma, both with the presenting seizure (9.4% vs 30.6%, p < .0001) and first recurrence (7.5% vs 16.3%, p = .001).

Significance

First‐ever unprovoked seizures from sleep are more likely to recur, independent of other risk factors, with recurrences also usually from sleep, and with a lower risk of seizure‐related injury. These findings may inform treatment decisions and counseling after first‐ever seizure.
A design logic for sequential segmentation across organisms
Authors: Simsek M. Fethullah , Özbudak Ertuğrul M.
Published: July 2023

Multitudes of organisms display metameric compartmentalization of their body plan. Segmentation of these compartments happens sequentially in diverse phyla. In several sequentially segmenting species, periodically active molecular clocks and signaling gradients have been found. The clocks are proposed to control the timing of segmentation, while the gradients are proposed to instruct the positions of segment boundaries. However, the identity of the clock and gradient molecules differs across species. Furthermore, sequential segmentation of a basal chordate, Amphioxus, continues at late stages when the small tail bud cell population cannot establish long‐range signaling gradients. Thus, it remains to be explained how a conserved morphological trait (i.e., sequential segmentation) is achieved by using different molecules or molecules with different spatial profiles. Here, we first focus on sequential segmentation of somites in vertebrate embryos and then draw parallels with other species. Thereafter, we propose a candidate design principle that has the potential to answer this puzzling question.
The effect of sealing process on the textural and sensory properties and protein profile of cooked meat
Authors: Kilic Sare , Oz Emel , Turhan Sadettin , Amarowickz Ryszard , Toldra Fidel , Brennan Charles , Oz Fatih
Published: July 2023

This work aimed to determine the effect of sealing process at different internal temperatures on the cooking loss, lipid oxidation, textural, and sensory properties, as well as the protein profile of cooked meat. For this aim, four different groups were formed. The control group was not sealed, while the other three groups were sealed until their internal temperature reached 20, 30, and 40 °C. Then, all samples were baked until their internal endpoint temperature reached 71 °C to ensure food safety. The lowest cooking loss (11.57%) was detected in the control group, and increased sealing core temperature resulted in an increase in cooking loss. The sealing did not show a significant effect (P > 0.05) on the TBARS value. On the other hand, myofibrillar and sarcoplasmic protein profile were influenced by sealing. Myofibrillar protein profile showed that protein denaturation rate was higher in groups sealed at the internal temperature of 30 and 40 °C. The sealing process affected only the hardness value among the textural properties examined. With the sealing process, the hardness value of the meat significantly (P < 0.05) reduced and the lowest hardness value was determined in the sample sealed at the internal temperature of 20 °C. Sealing positively affected the overall acceptability score of the samples, and the samples sealed until their internal temperatures reached 30 and 40 °C had higher overall acceptability scores.
Histology‐based classifier to distinguish early mycosis fungoides from atopic dermatitis
Authors: Roenneberg Sophie , Braun Stephan Alexander , Garzorz‐Stark Natalie , Stark Sebastian Paul , Muresan Ana‐Maria , Schmidle Paul , Biedermann Tilo , Guenova Emmanuella , Eyerich Kilian
Published: July 2023

Background

Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters.

Objective

To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD).

Methods

In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis‐free prediction model was developed and validated on an independent patient's cohort.

Results

A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter‐individual investigator differences.

Limitations.

The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria.

Conclusion

Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.
The role of in vivo reflectance confocal microscopy for the management of acne: A systematic review
Authors: Cretu S. , Papachatzopoulou E. , Dascalu M. , Salavastru C. M.
Published: July 2023

Acne diagnosis, severity assessment and treatment follow‐up rely primarily on clinical examination. In vivo reflectance confocal microscopy (RCM) provides non‐invasively, real‐time images of skin lesions with a level of detail close to histopathology. This systematic literature review aims to provide an overview of RCM utility in acne and a summary of specific features with clinical application that may increase objectivity in evaluating this condition. We used the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines for reporting our results. We systematically searched three databases: PubMed, Clarivate and Google Scholar (January 2022). All included studies used RCM to investigate acne in human patients and reported the investigated skin area and type (acne lesions or clinically uninvolved skin), the substance used in the case of treatment. Our search identified 2184 records in the three databases investigated. After duplicate removal, 1608 records were screened, 35 were selected for full‐text assessment, and 14 were included in this review. We used the QUADAS‐2 tool to evaluate the risk of bias and applicability concerns. RCM was selected as the index test and clinical examination as the reference standard. The total number of patients from all studies was 291, with 216 acne patients and 60 healthy participants aged between 13 and 45 years. The 14 considered studies analysed 456 follicles from healthy participants, 1445 follicles from uninvolved skin in acne patients and 1472 acne lesions. Consistent RCM findings concerning follicles of acne patients reported across studies were increased follicular infundibulum size, thick, bright border, intrafollicular content and inflammation. Our analysis indicates that RCM is a promising tool for acne evaluation. Nevertheless, standardization, a unified terminology, consistent research methods and unitary reporting of RCM findings are necessary. PROSPERO registration number CRD42021266547.
A pharmacokinetic study of extended‐release buprenorphine in cynomolgus monkeys (Macaca fasicularis)
Authors: Klein Hilton , Levinson Barry L. , Leary Steven L. , Dobson Glenn
Published: July 2023

Background

A novel buprenorphine (BUP) extended‐release formulation (BUP‐XR) produced as a lipid‐encapsulated, low viscosity BUP suspension for subcutaneous (SC) injection to control pain was evaluated for pharmacokinetics and safety in four adult male cynomolgus monkeys.

Methods

Each animal was given 0.2 mg/kg reformulated BUP‐XR SC. Clinical observations were made during the course of the study. Blood samples were obtained from each animal before BUP‐XR administration, 6, 24, 48, 72, and 96 h post‐BUP‐XR injection. Plasma levels of buprenorphine were analyzed using HPLC‐MS/MS. The PK values calculated included peak plasma concentration of the BUP analyte, time to peak plasma concentration, plasma half‐life, area under the plasma concentration–time curve, clearance, apparent volume of distribution, and elimination rate constant (Cmax, Tmax, T½, AUC0‐t, CL, Vd, and Ke, respectively).

Results

Observable adverse clinical signs were not detected. BUP concentration peaked from 6 to 48 h, then declined in a linear fashion. Quantifiable plasma BUP was measured in all monkeys at all time points. Results indicate that a single BUP‐XR dose at 0.2 mg/kg can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 96 h.

Conclusions

Because of the lack of any clinical observations or adverse effects at the injection site or absence of observable abnormal behaviors, it may be concluded that the use of BUP‐XR is safe and efficacious in this species of non‐human primate at the dose regimen described in this study for up to 96 h post‐administration.
JAG‐1/Notch signaling axis in the spinal cord contributes to bone cancer pain in rats
Authors: Fu Jie , Zhao Baoxia , Luo Ge , Ni Huadong , Xu Longsheng , He Qiuli , Xu Miao , Xu Chengfei , Wang Yahui , Ni Chaobo , Yao Ming
Published: July 2023

Notch signal plays an important role in regulating cell–cell interactions with the adjacent cells. However, it remains unknown whether Jagged1 (JAG‐1) mediated Notch signaling regulates bone cancer pain (BCP) via the spinal cell interactions mechanism. Here, we showed that intramedullary injection of Walker 256 breast cancer cells increased the expression of JAG‐1 in spinal astrocytes and knockdown of JAG‐1 reduced BCP. The supplementation of exogenous JAG‐1 to the spinal cord induced BCP‐like behavior and promoted expression of c‐Fos and hairy and enhancer of split homolog‐1 (Hes‐1) in the spinal cord of the naïve rats. These effects were reversed when the rats were administered intrathecal injections of N‐[N‐(3,5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester (DAPT). The intrathecal injection of DAPT reduced BCP and inhibited Hes‐1 and c‐Fos expression in the spinal cord. Furthermore, our results showed that JAG‐1 up‐regulated Hes‐1 expression by inducing the recruitment of Notch intracellular domain (NICD) to the RBP‐J/CSL‐binding site located within the Hes‐1 promoter sequence. Finally, the intrathecal injection of c‐Fos‐antisense oligonucleotides (c‐Fos‐ASO) and administration of sh‐Hes‐1 to the spinal dorsal horn also alleviated BCP. The study indicates that inhibition of the JAG‐1/Notch signaling axis may be a potential strategy for the treatment of BCP.

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Prevalence of bruxism in obstructive sleep apnea syndrome (OSAS) patients: A systematic review conducted according to PRISMA guidelines and the cochrane handbook for systematic reviews of interventions
Authors: Alshahrani Ahid Amer , Alshadidi Abdulkhaliq Ali F. , Alamri Mazen Awadh A. , Alamri Abdullah Awadh A. , Alshehri Abdullah Hassan J. , Cicciù Marco , Isola Gaetano , Minervini Giuseppe
Published: July 2023

Background

Sleep bruxism (SB) and obstructive sleep apnea syndrome (OSAS) are two sleep‐related conditions that have been associated with significantly conflicting results in literature. Understanding the prevalence of bruxism among OSA patients is crucial for identifying possible comorbidities and optimising treatment strategies.

Objective

This systematic review aimed at analysing the prevalence of SB in OSAS sufferers and understanding the association between the two.

Methods

Five online databases were searched for relevant articles in accordance with the PRISMA guidelines for conduction of systematic reviews. Studies reporting the prevalence of bruxism in OSAS patients and diagnosed through clinical assessments or polysomnography were included. Data extraction and quality assessment were performed independently by two reviewers. Methodological quality of the included studies was assessed using Risk of Bias In Non‐randomised Studies of Interventions (ROBINS‐I).

Results

A thorough search of literature yielded only two studies were eligible for this review. SB was found to be significantly present in the OSAS group. Despite methodological variations, the majority of studies reported higher rates of bruxism in OSAS patients compared to the general population or control groups.

Conclusion

The results of this systematic review point to a significant association between bruxism and obstructive sleep apnea. Further research is required to determine a more precise prevalence rate and investigate the potential therapeutic implications of the bruxism‐OSAS association that uses a standardised assessment techniques and larger sample sizes.
A technique for iris disk positioning on a custom ocular prosthesis
Authors: Abd‐ELLAH Mervat Elsayed , Khamis Mohamed Moataz , Neena Akram Fathy
Published: July 2023

Various techniques have been described for the rehabilitation of ocular defects with ocular prostheses to restore lost anatomical structures and correct cosmetic defects. This article describes a technique for optimizing the position of an iris disk over a custom‐made ocular prosthesis, by using eyeglasses with customized graph paper pattern lenses. It presents a simplified method that will be useful for people with ocular defects in remote and distant service areas with limited resources.
Long‐term stability of posterior crossbite correction, treated in the mixed or permanent dentition of growing children: A systematic review and meta‐analysis
Authors: Beltrami Fara , Kiliaridis Stavros , Antonarakis Gregory S.
Published: July 2023

When treating posterior crossbite, the primary goal is to achieve long‐term crossbite correction. The majority of studies however focus on relapse of the increase in the transverse dimension, but not relapse of the crossbite itself, which is an essential outcome. The aim of the present study was to determine long‐term stability (2 years minimum post‐treatment) of posterior crossbite correction, treated in mixed or early permanent dentitions of growing children. Following registration in PROSPERO (CRD42022348858), an electronic literature search including PubMed, Embase, Web of Science, the Cochrane Library, and a manual search were conducted up to January 2023, to identify longitudinal studies looking into the long‐term stability of crossbite correction in growing children. Data extraction and risk of bias assessment were carried out, and subsequently, a random‐effects meta‐analyses models were used to calculate estimates for relapse of the crossbite and relapse at the transverse level. Twenty‐two studies were included, of varying designs and quality, representing 1076 treated patients, with different expansion appliances and protocols. Meta‐analysis results showed that 19.5% (95% CI: 15%; 25%) of patients present with relapse of posterior crossbite at long‐term follow‐up. At the transverse level, 19.3% of the total expansion (including overexpansion) relapsed (95% CI: 13%; 27%) regardless of whether there a was relapse of the crossbite itself. Data from existing studies, with a moderate level of evidence, indicate that the long‐term stability of posterior crossbite correction in growing children is unfavourable in roughly 1 in 5 growing children, with crossbite relapse long‐term. On average, 19% of the maxillary expansion performed (including overexpansion) relapses long‐term, which may occur in cases with or without relapse of the crossbite.
Evaluation of quality of care in neonatal anesthesia using a bundle of intraoperative parameters
Authors: Salaün Jean‐Philippe , Beaufils Roxane , Chagnot Audrey , Alexandre Cénéric , Petit Thierry , Hanouz Jean‐Luc , Orliaguet Gilles
Published: July 2023

Background

Maintenance of physiological homeostasis is key in the safe conduct of pediatric anesthesia. Achieving this goal is especially difficult in neonatal surgery.

Aims

The first aim was to document the absolute number of seven intraoperative parameters monitored during anesthesia in neonates undergoing gastroschisis surgery. The second aims were to determine the frequency of monitoring of each of these intraoperative parameters as well as the proportion of cases in which each parameter was both monitored and maintained within a pre‐defined range.

Methods

This retrospective observational analysis includes data from 53 gastroschisis surgeries performed at Caen University Hospital (2009–2020). Seven intraoperative parameters were analyzed. First, we assessed if the intraoperative parameters were monitored or not. Second, when monitored, we assessed if these parameters were maintained within a pre‐defined range, based on the current literature and on local agreement.

Results

The median [first–third Q], range (min–max) number of intraoperative parameters monitored during the 53 gastroschisis surgeries was 6 [5–6], range (4–7). There were no missing data for the automatically recorded ones such as arterial blood pressure, heart rate, end‐tidal CO2, and oxygen saturation. Temperature was monitored in 38% of the patients, glycemia in 66%, and natremia in 68% of the cases. Oxygen saturation and heart rate were maintained within the pre‐defined range in 96% and 81% of the cases respectively. The blood pressure (28%) and temperature (30%) were instead the least often maintained within the pre‐defined range.

Conclusion

Although a median of six out of the seven selected intraoperative parameters were monitored during gastroschisis repair, only two of them (oxygen saturation and heart rate) were maintained within the pre‐defined range more than 80% of the time. It might be of interest to extend physiologic age‐ and procedure‐based approach to the development of specific preoperative anesthetic planning.
Calcium (Ca2+) sensors and MYC2 are crucial players during jasmonates‐mediated abiotic stress tolerance in plants
Authors: Khan F. S. , Goher F. , Paulsmeyer M. N. , Hu C.‐G. , Zhang J.‐Z.
Published: July 2023

Plants evolve stress‐specific responses that sense changes in their external environmental conditions and develop various mechanisms for acclimatization and survival. Calcium (Ca2+) is an essential stress‐sensing secondary messenger in plants. Ca2+ sensors, including calcium‐dependent protein kinases (CDPKs), calmodulins (CaMs), CaM‐like proteins (CMLs), and calcineurin B‐like proteins (CBLs), are involved in jasmonates (JAs) signalling and biosynthesis. Moreover, JAs are phospholipid‐derived phytohormones that control plant response to abiotic stresses. The JAs signalling pathway affects hormone–receptor gene transcription by binding to the basic helix–loop–helix (bHLH) transcription factor. MYC2 acts as a master regulator of JAs signalling module assimilated through various genes. The Ca2+ sensor CML regulates MYC2 and is involved in a distinct mechanism mediating JAs signalling during abiotic stresses. This review highlights the pivotal role of the Ca2+ sensors in JAs biosynthesis and MYC2‐mediated JAs signalling during abiotic stresses in plants.
Deep soil dissolved C and N stocks and stratification affected by afforestation along a restoration chronosequence of Robinia pseudoacacia plantations on the Loess Plateau, China
Authors: Li Changzhen , Li Changjiang , Han Xinhui , Zhao Luhong , Yang Gaihe
Published: July 2023

Soil dissolved carbon (C) and nitrogen (N) are early sensitive indexes to evaluate the changes in C and N pools in terrestrial ecosystems. However, there are few studies on the changes in soil dissolved C and N with revegetation age and their stratification ratios (SRs), especially for deep soil. The changes in soil dissolved C and N and their SRs in one farmland and five Robinia pseudoacacia plantations (RP: 15a, 20a, 25a, 30a and 40a) were studied. The results showed that RP plantations significantly increased the soil organic C (SOC) and total N (TN) stocks with increasing restoration age for 30 years in the shallow and middle soil layers and improved the stocks of dissolved total C (DTC), dissolved organic C (DOC), dissolved total N (DTN), dissolved organic N (DON) and dissolved inorganic N (DIN) in most soil layers, especially in the 20a, 25a and 30a plots. In the 0–200 cm soil layer, the middle and deep soil accounted for 50%–82% of the SOC and soil dissolved C stocks and 63%–84% of the soil TN and dissolved N stocks, respectively. At all soil depths, the SRs of SOC, TN, DTC, DOC and DIN in RP plots were greater than those in farmland plots, and the SRs of SOC and TN in almost all RP plots were >2. These results demonstrated that restoration age and soil depth had significant influences on SOC, TN and soil dissolved C and N, and RP forestation increased the SOC and TN stocks in the shallow and middle soil layers, and the soil dissolved C and N stocks in 20a, 25a and 30a plots were the largest; additionally, the middle and deep soil layers played important roles in estimating the soil C and N pools. In summary, RP afforestation significantly improved soil C and N and their dissolved fractions and the SRs, thus soil quality and nutrient availability consistently improved.
Early differentiation of Casparian strip mediated by nitric oxide is required for efficient K transport under low K conditions in Arabidopsis
Authors: Wu Qi , Feng Zhihang , Tsukagoshi Hironaka , Yang Miaoyan , Ao Yan , Fujiwara Toru , Kamiya Takehiro
Published: July 2023

The Casparian strip (CS) is a cell wall modification made of lignin that functions as an apoplastic barrier in the root endodermis to restrict nutrient and water transport between the soil and stele. CS formation is affected by nutritional conditions, and its physiological roles have been discussed. This study found that low K condition affects CS permeability, lignin deposition, and MYB36 mRNA accumulation. To understand the mechanism underlying these findings, we focused on nitric oxide (NO). NO is known to act as a signaling molecule and participates in cell wall synthesis, especially for lignin composition. However, the mechanism by which NO affects lignin deposition and corrects CS formation in the plant roots remains unclear. Through combining fluorescent observation with histological stains, we demonstrated that the root endodermal cell lignification response to low‐potassium (K) conditions is mediated by NO through the MYB36‐associated lignin‐polymerizing pathway. Furthermore, we discovered the noteworthy ability of NO to maintain nutrient homeostasis for adaptation to low K conditions by affecting the correct apoplastic barrier formation of CS. Collectively, our results suggest that NO is required for the lignification and apoplastic barrier formation in the root endodermis during adaptation to low K conditions, which revealing the novel physiological roles of CS under low nutrient conditions and making a significant contribution to CS biology.
Increasing the collection flow rate to 2 mL/min is effective and reduces the procedure time in off‐line photopheresis
Authors: Mayer Wolfgang , Mayr Jonas , Koch Felix , Rechberger Ulrike , Gasser Werner , Hermann Martin , Kempel Angela , Edlinger Michael , Schennach Harald
Published: July 2023

Background

Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T‐cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off‐line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat.

Study design and methods

In this prospective study, data of routinely performed off‐line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2).

Results

A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 109 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%.

Conclusion

The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate.
Efficacy of stereotactic radiation therapy for the treatment of confirmed or presumed canine glioma
Authors: Trageser Erin , Martin Tiffany , Burdekin Braden , Hart Cullen , Leary Del , LaRue Susan , Boss Mary‐Keara
Published: July 2023

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non‐modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy‐confirmed glioma or a presumptive diagnosis of intra‐cranial glioma based on MRI characteristics that were treated with SRT. Twenty‐three client‐owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty‐one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162–584). Median disease specific survival time was 413 days (95% CI, 217–717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.
Adaptive MIMO fuzzy PID controller based on peak observer
Authors: Uçak Kemal , Arslantürk Beyza Nur
Published: July 2023

In this paper, a novel peak observer based adaptive multi-input multi-output (MIMO) fuzzy proportional-integral-derivative (PID) controller has been introduced for MIMO time delay systems. The adaptation mechanism proposed by Qiao and Mizumoto [1] for single-input single-output (SISO) systems has been enhanced for MIMO system adaptive control. The tracking, stabilization and disturbance rejection performances of the proposed adaptation mechanism have been evaluated for MIMO systems by comparing with non-adaptive fuzzy PID and classical PID controllers. The obtained results indicate that the introduced adjustment mechanism for MIMO fuzzy PID controller can be successfully deployed for MIMO time delay systems.