bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights Into the Regulation of Offspring Growth by Maternally Derived Ghrelin
Authors: Sato Takahiro , Ida Takanori , Shiimura Yuki , Matsui Kazuma , Oishi Kanae , Kojima Masayasu
Published: February 2022

The regulation of fetal development by bioactive substances such as hormones and neuropeptides derived from the gestational mother is considered to be essential for the development of the fetus. On the other hand, it has been suggested that changes in the physiological state of the pregnant mother due to various factors may alter the secretion of these bioactive substances and induce metabolic changes in the offspring, such as obesity, overeating, and inflammation, thereby affecting postnatal growth and health. However, our knowledge of how gestational maternal bioactive substances modulate offspring physiology remains fragmented and lacks a systematic understanding. In this mini-review, we focus on ghrelin, which regulates growth and energy metabolism, to advance our understanding of the mechanisms by which maternally derived ghrelin regulates the growth and health of the offspring. Understanding the regulation of offspring growth by maternally-derived ghrelin is expected to clarify the fetal onset of metabolic abnormalities and lead to a better understanding of lifelong health in the next generation of offspring.
Integration of Count Difference and Curve Similarity in Negative Regulatory Element Detection
Authors: He Na , Wang Wenjing , Fang Chao , Tan Yongjian , Li Li , Hou Chunhui
Published: February 2022

Negative regulatory elements (NREs) down-regulate gene expression by inhibiting the activities of promoters or enhancers. The repressing activity of NREs can be measured globally by massively parallel reporter assays (MPRAs). However, most existing algorithms are designed for the statistical detection of positively enriched signals in MPRA datasets. To identify reduced signals in MPRA experiments, we designed a NRE identification program, fast-NR, by integrating the count and graphic features of sequenced reads to detect NREs using datasets generated by experiments of self-transcribing active regulatory region sequencing (STARR-seq). Fast-NR identified hundreds of silencers in human K562 cells that can be validated by independent methods.
Risk Factors and Nomogram for Predicting Relapse Risk in Pediatric Neuromyelitis Optica Spectrum Disorders
Authors: Zhang Shanchao , Qiao Shan , Li Haiyun , Zhang Ranran , Wang Meiling , Han Tao , Liu Xuewu , Wang Yunshan
Published: February 2022

Background

Neuromyelitis optica spectrum disorders (NMOSDs) are attack-relapsing autoimmune inflammatory diseases of the central nervous system, which are characterized by the presence of serological aquaporin-4 (AQP4) antibody. However, this disorder is uncommon in children, and AQP4 antibody was often found to be seronegative. However, some pediatric patients diagnosed with NMOSDs were tested to be positive for myelin oligodendrocyte glycoprotein (MOG) antibody. The previous investigations of pediatric NMOSDs were usually focused on the clinical presentation, treatment responses, and long-term prognoses, but little is known about the risk factors predicting NMOSD relapse attacks in a shorter time, especially, for Chinese children.

Methods

We retrospectively identified 64 Chinese pediatric patients, including 39 positive for AQP4 antibody, 12 positive for MOG antibody, and the rest negative for AQP4 and MOG antibodies. Independent risk factors predicting relapse in 1-year follow-up were extracted by multivariate regression analysis to establish a risk score model, its performance evaluation was analyzed using receiver operating characteristic (ROC) curve, and the independent risk factors related to relapse manifestation were also explored through multivariate logistic analysis. A nomogram was generated to assess relapse attacks in 1-year follow-up. Thirty-five patients from 3 other centers formed an external cohort to validate this nomogram.

Results

Four independent relapsed factors included discharge Expanded Disability Status Scale (EDSS) (p = 0.017), mixed-lesion onset (p = 0.010), counts (≧1) of concomitant autoantibodies (p = 0.015), and maintenance therapy (tapering steroid with mycophenolate mofetil (MMF), p = 0.009; tapering steroid with acetazolamide (AZA), p = 0.045; and tapering steroid only, p = 0.025). The risk score modeled with these four factors was correlated with the likelihood of relapse in the primary cohort (AUC of 0.912) and the validation cohort (AUC of 0.846). Also, our nomogram exhibited accurate relapse estimate in the primary cohort, the validation cohort, and the whole cohort, but also in the cohorts with positive/negative AQP4 antibody, and noticeably, it performed predictive risk improvement better than other factors in the concordance index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Conclusions

The risk score and nomogram could facilitate accurate prognosis of relapse risk in 1-year follow-up for pediatric NMOSDs and help clinicians provide personalized treatment to decrease the chance of relapse.
High PIRCHE Scores May Allow Risk Stratification of Borderline Rejection in Kidney Transplant Recipients
Authors: Lezoeva Ekaterina , Nilsson Jakob , Wüthrich Rudolf , Mueller Thomas F. , Schachtner Thomas
Published: February 2022

Background

The diagnosis of borderline rejection (BLR) ranges from mild inflammation to clinically significant TCMR and is associated with an increased risk of allograft dysfunction. Currently, there is no consensus regarding its treatment due in part to a lack of biomarkers to identify cases with increased risk for immune-mediated injury.

Methods

We identified 60 of 924 kidney transplant recipients (KTRs) with isolated and untreated BLR. We analyzed the impact of predicted indirectly recognizable HLA epitopes (PIRCHE) score on future rejection, de novo DSA development, and recovery to baseline allograft function. Additionally, we compared the outcomes of different Banff rejection phenotypes.

Results

Total PIRCHE scores were significantly higher in KTRs with BLR compared to the entire study population (p=0.016). Among KTRs with BLR total PIRCHE scores were significantly higher in KTRs who developed TCMR/ABMR in follow-up biopsies (p=0.029). Notably, the most significant difference was found in PIRCHE scores for the HLA-A locus (p=0.010). PIRCHE scores were not associated with the development of de novo DSA or recovery to baseline allograft function among KTRs with BLR (p>0.05). However, KTRs under cyclosporine-based immunosuppression were more likely to develop de novo DSA (p=0.033) than those with tacrolimus, whereas KTRs undergoing retransplantation were less likely to recover to baseline allograft function (p=0.003).

Conclusions

High PIRCHE scores put KTRs with BLR at an increased risk for future TCMR/ABMR and contribute to improved immunological risk stratification. The benefit of anti-rejection treatment, however, needs to be evaluated in future studies.
Reactivity of NK Cells Against Ovarian Cancer Cells Is Maintained in the Presence of Calcium Phosphate Nanoparticles
Authors: Hrvat Antonio , Schmidt Mathias , Obholzer Martin , Benders Sonja , Kollenda Sebastian , Horn Peter A. , Epple Matthias , Brandau Sven , Mallmann-Gottschalk Nina
Published: February 2022

Calcium phosphate nanoparticles (CaP-NPs) are biodegradable carriers that can be functionalized with biologically active molecules. As such, they are potential candidates for delivery of therapeutic molecules in cancer therapies. In this context, it is important to explore whether CaP-NPs impair the natural or therapy-induced immune cell activity against cancer cells. Therefore, in this study, we have investigated the effects of different CaP-NPs on the anti-tumor activity of natural killer (NK) cells using different ovarian cancer (OC) cell line models. We explored these interactions in coculture systems consisting of NK cells, OC cells, CaP-NPs, and therapeutic Cetuximab antibodies (anti-EGFR, ADCC-inducing antibody). Our experiments revealed that aggregated CaP-NPs can serve as artificial targets, which activate NK cell degranulation and impair ADCC directed against tumor targets. However, when CaP-NPs were properly dissolved by sonication, they did not cause substantial activation. CaP-NPs with SiO2-SH-shell induced some activation of NK cells that was not observed with polyethyleneimine-coated CaP-NPs. Addition of CaP-NPs to NK killing assays did not impair conjugation of NK with OC and subsequent tumor cytolytic NK degranulation. Therapeutic antibody coupled to functionalized CaP-NPs maintained substantial levels of antibody-dependent cellular cytotoxic activity. Our study provides a cell biological basis for the application of functionalized CaP-NPs in immunologic anti-cancer therapies.
A Paradise for Rare Species: Tanaidacean Fauna of the West African Continental Margin
Authors: Jóźwiak Piotr , Pabis Krzysztof , Sobczyk Robert , Serigstad Bjorn
Published: February 2022

The benthic ecology of the Gulf of Guinea is critically understudied, and knowledge about the composition and biodiversity of the tanaidacean communities remains lacking. Our analysis of tanaidacean collection from 270 quantitative samples collected using 0.1 m2van Veen grab along the Ghanaian coast (nine transects, six stations at each transect, 25–1,000 m depth range) reveals a high species richness and very low abundance. The mean density of Tanaidacea across all the samples equals only 0.03 ± 0.55 ind./0.1 m2. A total of 87 tanaidacean species were recorded, of which only three were known for science (3.4%), emphasizing the need for intensified taxonomic effort in this region.Circa40% of the species were singletons, 98% of the species had a total abundance lower than 10 individuals, and approximately half of the species were found only in one sample. The highest species richness was recorded in the slope (500–1,000 m), despite the elevated levels of barium and hydrocarbons at those depths. This area was also characterized by the most unique species composition. Species accumulation curves did not reach an asymptote, suggesting an undersampling of the area and a great rarity of the species. Results of the canonical correspondence analysis (CCA) and cluster analysis demonstrated a positive influence of oxygen concentration and fluorescence, particularly in the shallow shelf sites (25–50 m), which were characterized by a higher abundance of Tanaidacea. Depth zonation of tanaidacean communities with a division between shallow-water taxa (Leptocheliidae Lang, 1973 and Kalliapseudidae Lang, 1956) through families with wide bathymetric range (Pseudotanaidae Sieg, 1976, Apseudidae Leach, 1814) to the true deep-sea forms (Paranarthrurellidae Błażewicz, Jóźwiak and Frutos, 2019) is also evident. We further discuss the problems associated with multivariate analysis of highly speciose but less abundant taxa.
Management of Obstructive Sleep Apnea in Patients With Heart Failure
Authors: Wang Youmeng , Schöbel Christoph , Penzel Thomas
Published: February 2022

Sleep apnea is traditionally classified as obstructive sleep apnea (OSA), which occurs when the upper airway collapses due to the relaxation of oropharyngeal musculature, and central sleep apnea occurs when the brainstem cannot stimulate breathing. Most sleep apnea in patients with heart failure (HF) results from coexisting OSA and central sleep apnea (CSA), or complex sleep apnea syndrome. OSA and CSA are common in HF and can be involved in its progression by exposure to the heart to intermittent hypoxia, increased preload and afterload, activating sympathetic, and decreased vascular endothelial function. A majority of treatments have been investigated in patients with CSA and HF; however, less or short-term randomized trials demonstrated whether treating OSA in patients with HF could improve morbidity and mortality. OSA could directly influence the patient's recovery. This review will focus on past and present studies on the various therapies for OSA in patients with HF and summarize CSA treatment options for reasons of reference and completeness. More specifically, the treatment covered include surgical and non-surgical treatments and reported the positive and negative consequences for these treatment options, highlighting possible implications for clinical practice and future research directions.
Role of a Urinary Biomarker in the Common Mechanism of Physical Performance and Cognitive Function
Authors: Jiang Shan , Cui Ju , Zhang Li-Qun , Liu Zhen , Zhang Yan , Shi Yuan , Cai Jian-Ping
Published: February 2022

Introduction

Healthy aging is described as a process of developing and maintaining intrinsic abilities, including physical and cognitive functions. Although oxidative stress is a common mechanism shared by loss of muscle strength and dementia, its relationship with decreased physical performance and cognitive impairment remains unclear. We aimed to investigate the role of urinary 8-oxo-7, 8-dihydroguanosine (8-oxoGsn), a biomarker of oxidative damage to RNA, in physical and cognitive decline.

Methods

The study followed a cross-sectional design and recruited 40–94-year-old inhabitants of Beijing, China (471 men and 881 women). The physical performance of the participants was assessed using handgrip strength, walking speed, and the repeated chair stand test. The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) 5-min protocol. Urinary 8-oxoGsn levels were measured for all participants.

Results

Participants with high urinary 8-oxoGsn levels were more likely to have low grip strength, slow walking speed, poor performance in the repeated chair stand test, and low scores on the MoCA 5-min protocol (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.52–7.76; OR 1.71, 95% CI: 1.16–2.53; OR 2.06, 95% CI: 0.92–4.63; OR 1.75, 95% CI: 1.18–2.58), after adjusting for age, sex, smoking habits, alcohol consumption, hypertension, diabetes, cerebro-cardiovascular disease, and chronic kidney disease.

Conclusion

Elevated levels of oxidative stress are independently associated with cognitive and physical impairment. Thus, these results can help in the early identification and development of strategies for the prevention and treatment of intrinsic capacity decline.
Prognostic Value of Radiotherapy and Chemotherapy in Stage I–III Merkel Cell Carcinoma
Authors: Bi Aihong , Yang Sifu , Ding Yang , Yu Yong , Zhan Wenming , Song Tao
Published: February 2022

Purpose

Merkel cell carcinoma (MCC) is a highly malignant cancer associated with dismal survival outcomes. Surgery is the cornerstone for the management of MCC, but the benefit of radiotherapy (RT) and chemotherapy (CT) is still controversial. We aimed to investigate the prognostic value of RT and CT in the management of stage I-III MCC patients using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

Patients with a histopathological diagnosis of MCC between 2010 and 2016 were included. The primary endpoint of this study was overall survival (OS). The prognostic significance for OS was analyzed by Cox proportional hazard regression model.

Results

A total of 1,691 patients were identified in the SEER database. Over half of the patients had received RT (56.7%), and 9.8% of the patients were documented to have received CT. The median OS for the entire cohort was 66.0 months, and the 5-year OS rate was 53.8%. In the multivariate analysis, receiving RT was associated with significantly improved OS (P < 0.001), while receiving CT significantly negatively impacted OS (P = 0.010). In stage III patients who underwent treatment based on surgical resection, RT was still demonstrated to be a positive factor (P = 0.002), while CT had no significant association with OS in the univariate analysis (P = 0.295).

Conclusions

The current data in the SEER database are consistent with earlier studies supporting the benefit of adjuvant RT for stage I-III MCC patients, but caution should be taken regarding the routine use of CT. For stage III MCC patients, the value of adjuvant CT needs to be confirmed in future studies.
Role of Environment and Experimenter in Reproducibility of Behavioral Studies With Laboratory Mice
Authors: Nigri Martina , Åhlgren Johanna , Wolfer David P. , Voikar Vootele
Published: February 2022

Behavioral phenotyping of mice has received a great deal of attention during the past three decades. However, there is still a pressing need to understand the variability caused by environmental and biological factors, human interference, and poorly standardized experimental protocols. The inconsistency of results is often attributed to the inter-individual difference between the experimenters and environmental conditions. The present work aims to dissect the combined influence of the experimenter and the environment on the detection of behavioral traits in two inbred strains most commonly used in behavioral genetics due to their contrasting phenotypes, the C57BL/6J and DBA/2J mice. To this purpose, the elevated O-maze, the open field with object, the accelerating rotarod and the Barnes maze tests were performed by two experimenters in two diverse laboratory environments. Our findings confirm the well-characterized behavioral differences between these strains in exploratory behavior, motor performance, learning and memory. Moreover, the results demonstrate how the experimenter and the environment influence the behavioral tests with a variable-dependent effect, often with mutually exclusive contributions. In this context, our study highlights how both the experimenter and the environment can have an impact on the strain effect size without altering the direction of the conclusions. Importantly, the general agreement on the results is reached by converging evidence from multiple measures addressing the same trait. In conclusion, the present work elucidates the contribution of both the experimenter and the laboratory environment in the intricate field of reproducibility in mouse behavioral phenotyping.
Wearable Power-Assist Locomotor for Gait Reconstruction in Patients With Spinal Cord Injury: A Retrospective Study
Authors: Koyama Soichiro , Tanabe Shigeo , Gotoh Takeshi , Taguchi Yuta , Katoh Masaki , Saitoh Eiichi , Otaka Yohei , Hirano Satoshi
Published: February 2022

Wearable robotic exoskeletons (WREs) have been developed from orthoses as assistive devices for gait reconstruction in patients with spinal cord injury. They can solve some problems encountered with orthoses, such as difficulty in independent walking and standing up and high energy consumption during walking. The Wearable Power-Assist Locomotor (WPAL), a WRE, was developed based on a knee–ankle–foot orthosis with a single medial hip joint. The WPAL has been updated seven times during the period from the beginning of its development, in 2005, to 2020. The latest version, launched as a commercialized model in 2016, is available for medical facilities. In this retrospective study, which included updated results from previous reports, all data were extracted from development research records from July 2007 to December 2020. The records were as follows: patient characteristics [the number of participants, injury level, and the American Spinal Injury Association Impairment Scale (AIS) score], the total number of WPAL trials when aggregating the cases with all the versions or only the latest version of the WPAL, and maximum walking performance (functional ambulation category [FAC], distance, and time of continuous walking). Thirty-one patients participated in the development research. The levels of spinal cord injury were cervical (C5–C8), upper thoracic (T3–T6), lower thoracic (T7–T12), and lumbar (L1) in 10, 5, 15, and 1 of the patients, respectively. The numbers of patients with AIS scores of A, B, C, and D were 20, 7, 4, and 0, respectively. The total number of WPAL trials was 1,785, of which 1,009 were used the latest version of the WPAL. Twenty of the patients achieved an FAC score of 4 after an average of 9 (median 8, range 2–22) WPAL trials. The continuous walking distance and time improved with the WPAL were compared to the orthosis. We confirmed that the WPAL improves walking independence in people with a wide range of spinal cord injuries, such as cervical spinal cord injuries. Further refinement of the WPAL will enable its long-term use at home.
Maternal Cigarette Smoke Exposure Exaggerates the Behavioral Defects and Neuronal Loss Caused by Hypoxic-Ischemic Brain Injury in Female Offspring
Authors: Huang Taida , Huang Xiaomin , Li Hui , Qi Junhua , Wang Nan , Xu Yi , Zeng Yunxin , Xiao Xuewen , Liu Ruide , Chan Yik Lung , Oliver Brian G. , Yi Chenju , Li Dan , Chen Hui
Published: February 2022

Objective

Hypoxic-ischemic encephalopathy affects ∼6 in 1,000 preterm neonates, leading to significant neurological sequela (e.g., cognitive deficits and cerebral palsy). Maternal smoke exposure (SE) is one of the common causes of neurological disorders; however, female offspring seems to be less affected than males in our previous study. We also showed that maternal SE exaggerated neurological disorders caused by neonatal hypoxic-ischemic brain injury in adolescent male offspring. Here, we aimed to examine whether female littermates of these males are protected from such insult.

Methods

BALB/c dams were exposed to cigarette smoke generated from 2 cigarettes twice daily for 6 weeks before mating, during gestation and lactation. To induce hypoxic-ischemic brain injury, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen) at postnatal day (P) 10. Behavioral tests were performed at P40–44, and brain tissues were collected at P45.

Results

Maternal SE worsened the defects in short-term memory and motor function in females with hypoxic-ischemic injury; however, reduced anxiety due to injury was observed in the control offspring, but not the SE offspring. Both hypoxic-ischemic injury and maternal SE caused significant loss of neuronal cells and synaptic proteins, along with increased oxidative stress and inflammatory responses.

Conclusion

Oxidative stress and inflammatory response due to maternal SE may be the mechanism of worsened neurological outcomes by hypoxic-ischemic brain injury in females, which was similar to their male littermates shown in our previous study.
Muscular Function as an Alternative to Identify Cognitive Impairment: A Secondary Analysis From SABE Colombia
Authors: Garcia-Cifuentes Elkin , Botero-Rodríguez Felipe , Ramirez Velandia Felipe , Iragorri Angela , Marquez Isabel , Gelvis-Ortiz Geronimo , Acosta María-Fernanda , Jaramillo-Jimenez Alberto , Lopera Francisco , Cano-Gutiérrez Carlos Alberto
Published: February 2022

Background

Identification of cognitive impairment is based traditionally on the neuropsychological tests and biomarkers that are not available widely. This study aimed to establish the association between motor function (gait speed and handgrip strength) and cognitive performance in the Mini-Mental State Examination, globally and by domains. A secondary goal was calculating a cut-off point for gait speed and handgrip strength to classify older adults as cognitively impaired.

Methods

This is a secondary analysis of SABE Colombia (Salud, Bienestar & Envejecimiento), a survey that was conducted in 2015 on health, wellbeing, and aging in Colombia. This study used linear regression models to search for an association between motor function and cognitive performance. The accuracy of motor function measurements in identifying cognitive impairment was assessed with receiver operating characteristic (ROC) curves. This study also analyzed other clinical and sociodemographical variables.

Results

Gait speed was associated with orientation (r2 = 0.16), language (r2 = 0.15), recall memory (r2 = 0.14), and counting (r2 = 0.08). Similarly, handgrip strength was associated with orientation (r2 = 0.175), language (r2 = 0.164), recall memory (r2 = 0.137), and counting (r2 = 0.08). To differentiate older adults with and without cognitive impairment, a gait speed cut-off point of 0.59 m/s had an area under the curve (AUC) of 0.629 (0.613–0.646), and a weak handgrip (strength below 17.5 kg) had an AUC of 0.653 (0.645-0.661). The cut-off points for handgrip strength and gait speed were significantly higher in male participants.

Conclusions

Gait speed and handgrip strength are similarly associated with the cognitive performance, exhibiting the most extensive association with orientation and language domains of the Mini-Mental State Examination. Gait speed and handgrip strength can easily be measured by any clinician, and they prove to be useful screening tools to detect cognitive impairment.
Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia
Authors: Fung Christian , Z'Graggen Werner J. , Jakob Stephan M. , Gralla Jan , Haenggi Matthias , Rothen Hans-Ulrich , Mordasini Pasquale , Lensch Michael , Söll Nicole , Terpolilli Nicole , Feiler Sergej , Oertel Markus F. , Raabe Andreas , Plesnila Nikolaus , Takala Jukka , Beck Jürgen
Published: February 2022

Background

We demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH.

Methods

SAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS).

Results

Seven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died.

Conclusion

Administration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.
Acute Cerebellitis Associated With Anti-homer 3 Antibodies: A Rare Case Report and Literature Review
Authors: Miao Ailiang , Yu Chuanyong , Sun Yulei , Wang Lingling , Ge Jianqing , Wang Xiaoshan
Published: February 2022

Acute cerebellitis associated with Homer-3 antibodies is very rare. Here we present a 20-year-old woman who suffered from uncontrollable head shaking quickly from side to side and an unsteady gait for 2 days after the cold. Antibodies were screened by cell-based assays. The indirect immunofluorescence technique results revealed anti-Homer-3 antibody titers of 1:3.2 in the CSF and 1:100 in the serum. The woman was obviously improved after antiviral and immunosuppression (immunoglobin, methylprednisolone and mycophenolate mofetil) treatment. Our report indicated immune-mediated causes should be considered in the acute cerebellitis. Immunotherapy can contribute to the improvement of cerebellar syndrome.
Longitudinal Analysis of Self-Reported Symptoms, Behavioral Measures, and Event-Related Potential Components of a Cued Go/NoGo Task in Adults With Attention-Deficit/Hyperactivity Disorder and Controls
Authors: Münger Marionna , Sele Silvano , Candrian Gian , Kasper Johannes , Abdel-Rehim Hossam , Eich-Höchli Dominique , Müller Andreas , Jäncke Lutz
Published: February 2022

This study characterizes a large sample of adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls regarding their task performance and neurophysiology; cross-sectionally and longitudinally. Self-reported symptoms, behavioral measures, and event-related potentials from a classical cued Go/NoGo task were used to outline the symptom burden, executive function deficits and neurophysiological features, and the associations between these domains. The study participants (N = 210 ADHD, N = 158 controls, age: 18–62 years) were assessed five (ADHD) or three (controls) times over two years. We describe cross-sectional and longitudinal group differences, and associations between symptom burden, and behavioral and event-related potential (ERP) components variables by latent growth curve models, including random slopes and intercepts. The ADHD group showed increased reaction time variability, increased commission and omission errors, and attenuated cueP3, CNV, N2d, and P3d amplitudes. We observed a decrease in self-reported symptoms in the ADHD group over the two years. The behavioral measures (reaction time variability, number of omission, and commission errors) did not change over time, whereas the cueP3, P3d, and N2d amplitude attenuated in both groups. There was no evidence for a robust association between symptom burden and behavioral or ERP measures. The changes in the ERP components with stable task performance, potentially indicate more efficient neuronal processing over the two years. Whether the lack of association between symptom burden and behavioral or ERP measures might be due to the low reliability of the ADHD assessment criteria, or the inappropriateness of the objective measures cannot be inferred.
Neuroimaging Examination of Driving Mode Switching Corresponding to Changes in the Driving Environment
Authors: Ohata Ryu , Ogawa Kenji , Imamizu Hiroshi
Published: February 2022

Car driving is supported by perceptual, cognitive, and motor skills trained through continuous daily practice. One of the skills that characterize experienced drivers is to detect changes in the driving environment and then flexibly switch their driving modes in response to the changes. Previous functional neuroimaging studies on motor control investigated the mechanisms underlying behaviors adaptive to changes in control properties or parameters of experimental devices such as a computer mouse or a joystick. The switching of multiple internal models mainly engages adaptive behaviors and underlies the interplay between the cerebellum and frontoparietal network (FPN) regions as the neural process. However, it remains unclear whether the neural mechanisms identified in previous motor control studies also underlie practical driving behaviors. In the current study, we measure functional magnetic resonance imaging (fMRI) activities while participants control a realistic driving simulator inside the MRI scanner. Here, the accelerator sensitivity of a virtual car is abruptly changed, requiring participants to respond to this change flexibly to maintain stable driving. We first compare brain activities before and after the sensitivity change. As a result, sensorimotor areas, including the left cerebellum, increase their activities after the sensitivity change. Moreover, after the change, activity significantly increases in the inferior parietal lobe (IPL) and dorsolateral prefrontal cortex (DLPFC), parts of the FPN regions. By contrast, the posterior cingulate cortex, a part of the default mode network, deactivates after the sensitivity change. Our results suggest that the neural bases found in previous experimental studies can serve as the foundation of adaptive driving behaviors. At the same time, this study also highlights the unique contribution of non-motor regions to addressing the high cognitive demands of driving.
Conditional Knockout of Bmal1 in Corticotropin-Releasing Factor Neurons Does Not Alter Sleep–Wake Rhythm in Mice
Authors: Hung Chi Jung , Yamanaka Akihiro , Ono Daisuke
Published: February 2022

Sleep and wakefulness are regulated by both the homeostatic mechanism and circadian clock. In mammals, the central circadian clock, the suprachiasmatic nucleus, in the hypothalamus plays a crucial role in the timing of physiology and behavior. Recently, we found that the circadian regulation of wakefulness was transmitted via corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus to orexin neurons in the lateral hypothalamus. However, it is still unclear how the molecular clock in the CRF neurons contributes to the regulation of sleep and wakefulness. In the present study, we established CRF neuron-specific Bmal1-deficient mice and measured locomotor activity or electroencephalography and electromyography. We found that these mice showed normal circadian locomotor activity rhythms in both light–dark cycle and constant darkness. Furthermore, they showed normal daily patterns of sleep and wakefulness. These results suggest that Bmal1 in CRF neurons has no effect on either circadian locomotor activity or sleep and wakefulness.
Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy—Analysis of the Phase 3 XELAVIRI Trial
Authors: Kurreck Annika , Heinemann Volker , Fischer von Weikersthal Ludwig , Decker Thomas , Kaiser Florian , Uhlig Jens , Schenk Michael , Freiberg-Richter Jens , Peuser Bettina , Denzlinger Claudio , Graeven Ullrich , Heinrich Kathrin , Held Swantje , Stahler Arndt , Alig Annabel Helga Sophie , Jelas Ivan , von Einem Jobst C. , Stintzing Sebastian , Giessen-Jung Clemens , Modest Dominik P.
Published: February 2022

Introduction

Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial.

Methods

DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex.

Results

In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965).

Conclusions

Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.
Case Report: Genetic Analysis of a Small Supernumerary Marker Chromosome in a Unique Case of Mosaic Turner Syndrome
Authors: Li Chao , Luo Weiyao , Xiao Tingting , Yang Xingkun , Ou Miaoling , Zhang Linghua , Huang Xiang , Zhu Xiaodan
Published: February 2022

Background

The aim of this study was to explore the source and morphology of a small supernumerary marker chromosome (sSMC) from karyotype analysis of a patient with a unique case of mosaic Turner syndrome. The study findings will provide technical reference and genetic counseling for similar cases.

Case Presentation

A female patient with 46,X,+mar karyotype was diagnosed by genetic karyotype analysis. Genetic methods including fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq) based on low-depth whole-genome sequencing were used to explore the source and morphology of sSMC. FISH technology showed that 56.5% of the cells were X and 43.5% of the cells were XY. CNV-seq detection found that the sSMC was chrY, implying that the patient's karyotype was mos 45,X[58.6%]/46,XY[41.4%]. Retrospective karyotype analysis indicated that the female patient's sSMC was inherited from her father's small chrY. Customized FISH probe of Yq12 microdeletion was positive, indicating that the sSMC was a del(Y)(q12). Based on the results of genetic diagnosis, the specialist doctor gave a comprehensive genetic consultation and ordered regular follow-up examinations.

Conclusions

The findings of the current study showed that the chromosome description of the unique Turner case was mos 45,X[56.5%]/46,X,del(Y)(q12)[43.5%]. FISH technology played a key role in diagnosis of mosaicism. The terminal deletion of mosaic chrY provided a scientific and an accurate explanation for masculinity failure and abnormal sexual development of the current case.
Human Trafficking ICD-10 Code Utilization in Pediatric Tertiary Care Centers Within the United States
Authors: Garg Anjali , Panda Preeti , Malay Sindhoosha , Slain Katherine N.
Published: February 2022

Background

Human trafficking is a global public health issue that affects pediatric patients widely. The International Labor Organization estimates children comprise approximately 25% of the identified trafficked persons globally, with domestic estimates including over 2000 children a year. Trafficked children experience a broad range of health consequences leading to interface with healthcare systems during their exploitation. In June 2018, International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) released diagnostic codes for human trafficking.

Objective

To use a large, multicenter database of US pediatric hospitalizations to describe the utilization of the ICD-10-CM codes related to child trafficking, as well as the demographic and clinical characteristics of these children.

Methods

This study was descriptive in nature. Encounters using data from the Pediatric Health Information System database (PHIS) with ICD-10-CM codes indicating trafficking from June 1, 2018 to March 1st, 2020 were included in the study cohort, with data collection continuing for 30 days after first hospital encounter, until March 31st, 2020. Patients 19 years old and younger were included. Condition-specific prevalence as well as demographic and clinical characteristics for patient encounters were analyzed. Study subjects were followed for 30 days after first hospital encounter to describe healthcare utilization patterns.

Results

During the study period, 0.005% (n = 293) of patient encounters in the PHIS database were identified as trafficked children. The children of our cohort were mostly female (90%), non-Hispanic Black (38%), and had public insurance (59%). Nearly two-thirds of patients (n = 190) had a documented mental health disorder at the initial encounter, with 32.1% classified as the principal diagnosis. Our cohort had a 30-day hospital inpatient, overnight observation, or emergency department readmission rate of 16% (n = 48).

Discussion

Our study demonstrates a low utilization of human trafficking ICD-10-CM codes in academic children's health centers, with code usage predominantly assigned to Non-Hispanic Black teenage girls. As comparison, in 2019 the National Human Trafficking Hotline identified 2,582 trafficked US children in a single year. These results suggest widespread under-recognition of child trafficking in health care settings, including the intensive care unit, in addition to racial and socioeconomic disparities amongst trafficked children.
Isolated Nocturnal Hypertension in Children
Authors: Awazu Midori
Published: February 2022

Isolated nocturnal hypertension (INH) is attracting attention because it has been shown to correlate with target organ damage as well as cardiovascular events in adults. INH has also been reported in children especially in those with underlying diseases including chronic kidney disease and some studies reported association with markers of early target organ damage. INH occupies the majority of nocturnal hypertension. On the other hand, masked hypertension is largely attributed to INH. INH is usually diagnosed by ambulatory blood pressure monitoring. Recently, it became possible to monitor sleep blood pressure by an automated home blood pressure device feasible also in children. The epidemiology, methodology and reproducibility, pathophysiology, relation to target organ damage, and treatment of INH in children will be reviewed here along with adult data.
Reducing Acneiform Rash Induced by EGFR Inhibitors With Honeysuckle Therapy: A Prospective, Randomized, Controlled Study
Authors: Liu Zhen , Tian Tian , Wang Binbin , Lu Demin , Ruan Jian , Shan Jianzhen
Published: February 2022

Background: Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal cancer or lung cancer. However, most of patients who receive EGFRIs treatment experience cutaneous toxicities, such as acneiform or papulopustular rashes, which affects quality of life and leads to discontinuation of cancer therapies. Honeysuckle is a traditional herb historically used to treat skin rash for thousands of years in Eastern Asia and showed proven safety in human.

Methods: To investigate whether honeysuckle therapy could control EGFRIs induced acneiform rashes, a total of 139 colorectal and lung cancer patients with EGFRIs treatments were recruited in a prospective study. Patients were randomized to 3 arms (Arm A: prophylactic treatment with honeysuckle before rash occurred; Arm B: symptomatic treatment with honeysuckle when rash occurred; Arm C: conventional treatment with minocycline and a topical solution when rash occurred). The incidences, severities and recovery time of acneiform rash were observed in each arm.

Results: Honeysuckle treatment reduced incidences of EGFRIs induced acneiform rash, which were 56.5, 68.1 and 71.7% in Arm A, B and C, respectively (p = 0.280). Severities of rash (CTCAE grade 2 and 3) were significantly lower in prophylactic honeysuckle treatment (Arm A) compared to conventional treatment (Arm C) (p = 0.027), which was 10–21%, respectively. Patients with honeysuckle treatment recovered more quickly from pruritus, the median time was 22, 36 and 58 days in Arm A, B and C, respectively (p = 0.016).

Conclusion: Honeysuckle was effective in reducing incidences and severities of EGFRIs induced acneiform rash, especially for prophylactic treatment.
Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung
Authors: Lin Chuyang , Zheng Xiaolan , Lin Sha , Zhang Yue , Wu Jinlin , Li Yifei
Published: February 2022

Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.
What Can Brinley Plots Tell Us About Cognitive Aging? Exploring Simulated Data and Modified Brinley Plots
Authors: Nicosia Jessica , Cohen-Shikora Emily R. , Strube Michael J.
Published: February 2022

Cognitive aging researchers have been challenged with demonstrating age-related effects above and beyond global slowing ever since Cerella raised this issue in 1990. As the literature has made clear, this has indeed proved to be a difficult task and continues to plague the field. One way that researchers have attempted to test for disproportionate age differences across task conditions is by using Brinley plots, or plotting the mean response latencies of older adults against the mean latencies for younger adults. The simplicity and large proportion of variance accounted for by these models has led to the widespread use of Brinley plots over the years. However, as systematically tested here through eight cases of simulated data, it is clear that the Brinley technique is not well suited to either identify or display the underlying structure of datasets examining age-related differences in attentional control. Some of the problems with conventional Brinley plots can be resolved by using a modified Brinley plot that includes study-specific slopes linking trial types and a no-age-difference reference line. Multilevel models find all of the relevant effects, especially if applied to trial-level data, and have the advantage of incorporating study-level moderators that might account for slope heterogeneity. Ultimately, we encourage fellow cognitive aging researchers to access the code and data for this project on OSF (https://osf.io/zxus8/) and employ the use of multilevel models over Brinley plots.
Physical Appearance Perfectionism: Psychometric Properties and Factor Structure of an Assessment Instrument in a Representative Sample of Males
Authors: Rica Robin , Solar María , Moreno-Encinas Alba , Foguet Sara , Compte Emilio Juan , Sepúlveda Ana Rosa
Published: February 2022

Perfectionism is a multidimensional construct with both positive and negative aspects. Recently, the concept of appearance-oriented perfectionism has been introduced, which is associated with body image dissatisfaction and weight and shape control behaviors. The Physical Appearance Perfectionism Scale (PAPS) is a 12-item two-factor instrument developed to assess this new dimension of perfectionism. The aim of the study is to validate the Spanish version of PAPS among a representative sample of 850 male university students in Spain (M = 20 years old; SD = 2.7). Exploratory and confirmatory factorial structure, internal consistency, convergent and concurrent validity, and associated predictor variables analyses have been carried out. Results showed that the Spanish version of the PAPS maintains the original factor structure with all items and proves to be a reliable instrument. Physical appearance-oriented perfectionism is associated with general perfectionism, higher body dissatisfaction, Eating Disorders and Muscle Dysmorphia symptomatology, and compulsive exercise, particularly in the Worry about Imperfection subscale. These variables also act as predictors of physical appearance perfectionism. The use of the PAPS-S and the analysis of its subscales is recommended in the context of body image-related pathologies such as Eating Disorders and Muscle Dysmorphia.