bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Geriatric Assessment: Application and correlations in a real-life cross-sectional study
Authors: Salis Francesco , Loddo Simona , Zanda Francesca , Peralta Maria Monica , Serchisu Luca , Mandas Antonella
Published: September 2022

Background

The assessment process of elderly people considers all aspects of an individual’s life, including physical, mental, and social aspects. Frailty refers to a decline in physiological functions or strengths leading to increased vulnerability to stressors and decreased ability to cope with them. Comprehensive Geriatric Assessment (CGA) is a validated and useful tool in this context to holistically study elderly people. The primary aim of this study was to determine the prevalence of impaired health status in a large geriatric population turning to outpatient service, based on the components of the CGA, and thus to describe its usefulness in real-life clinical practice. The secondary aim of this study was the evaluation of the association between nutritional status, assessed with Mini Nutritional Assessment (MNA)—within the CGA—and cognitive-affective and functional capacities, and multimorbidity.

Materials and methods

This real-life, retrospective cross-sectional study included subjects consecutively evaluated from January 2009 to December 2020 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy. A sum of 3,260 patients were subjected to CGA.

Results

Only a small proportion of the sample (2.24%) showed an absence of impairment in cognitive-affective, functional, and nutritional domains. Moderate correlations were found between MNA and several other CGA variables, namely, Geriatric Depression Scale (GDS; ϱ = −0.41, p < 0.0001), Barthel Index of Independence in Activities of Daily Living (ADL) (ϱ = 0.51, p < 0.0001), Instrumental Activities of Daily Living (IADL) (ϱ = 0.43, p < 0.0001), and Performance-Oriented Mobility Assessment (ϱ = 0.44, p < 0.0001). A multiple regression also highlighted these variables as significant regressors of MNA. Finally, malnutrition showed a significant association with depression (odds ratio [OR]: 4.97), dependence on ADL (OR: 19.8) and IADL (OR: 7.04), and falling risk (OR: 5.16).

Conclusion

This study has figured out the complex situation in which geriatric care finds itself the complexity and severe impairment of elderly people. The possibilities of intervention are often limited, but the literature confirms the benefits of good nutritional status on the general health status. The data that emerged from our study fit into this assumption, highlighting the close association between the nutritional domain and the other CGA domains.
Gut microbe metabolism of small molecules supports human development across the early stages of life
Authors: Tarracchini Chiara , Fontana Federico , Mancabelli Leonardo , Lugli Gabriele Andrea , Alessandri Giulia , Turroni Francesca , Ventura Marco , Milani Christian
Published: September 2022

From birth to adulthood, the human gut-associated microbial communities experience profound changes in their structure. However, while the taxonomical composition has been extensively explored, temporal shifts in the microbial metabolic functionalities related to the metabolism of bioactive small molecules are still largely unexplored. Here, we collected a total of 6,617 publicly available human fecal shotgun metagenomes and 42 metatranscriptomes from infants and adults to explore the dynamic changes of the microbial-derived small molecule metabolisms according to the age-related development of the human gut microbiome. Moreover, by selecting metagenomic data from 250 breastfed and 217 formula-fed infants, we also investigated how feeding types can shape the metabolic functionality of the incipient gut microbiome. From the small molecule metabolism perspective, our findings suggested that the human gut microbial communities are genetically equipped and prepared to metabolically evolve toward the adult state as early as 1 month after birth, although at the age of 4 years, it still appeared functionally underdeveloped compared to adults. Furthermore, in respect of formula-fed newborns, breastfed infants showed enrichment in microbial metabolic functions related to specific amino acids present at low concentrations in human milk, highlighting that the infant gut microbiome has specifically evolved to synthesize bioactive molecules that can complement the human breast milk composition contributing to complete nutritional supply of infant.
Genome mining to unravel potential metabolic pathways linked to gallium bioleaching ability of bacterial mine isolates
Authors: Chung Ana Paula , Francisco Romeu , Morais Paula V. , Branco Rita
Published: September 2022

Gallium (Ga) is considered a high-tech Critical Metal, used in the manufacture of several microelectronic components containing either gallium arsenide (GaAs) or gallium nitride (GaN). The current high demand for this critical metal urges the development of effective recovery processes from secondary resources such as mine tailings or electronic recycling material. The importance of bioleaching as a biotechnological process to recover metals prompted this study, where an integrative approach combining experimental and genomic analysis was undertaken to identify potential mechanisms involved in bioleaching ability and strategies to cope with high metal(loid)s concentrations in five mine isolates. The Clusters of Orthologous Group (COG) annotation showed that the “amino acid transport and metabolism” [E] was the most predominant functional category in all genomes. In addition, the KEEG pathways analysis also showed predicted genes for the biosynthetic pathways of most amino acids, indicating that amino acids could have an important role in the Ga leaching mechanism. The presence of effective resistance mechanisms to Ga and arsenic (As) was particularly important in GaAs bioleaching batch assays, and might explain the divergence in bioleaching efficiency among the bacterial strains. Rhodanobacter sp. B2A1Ga4 and Sphingomonas sp. A2-49 with higher resistance, mainly to As, were the most efficient bioleaching strains under these conditions. In bioleaching assays using cell-free spent medium Arthrobacter silviterrae A2-55 with lower As resistance outperformed all the other stains. Overall, higher efficiency in Ga leaching was obtained in bioleaching assays using GaAs when compared to GaN.
Structural and functional alterations of intestinal flora in mice induced by halonitromethanes exposure
Authors: Yin Jinbao , Li Dingxin , Zheng Tianming , Wang Xun , Hu Bin , Wang Peifang
Published: September 2022

Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts (DBPs) have been widely found in drinking water and are receiving more and more attentions because of their high cytotoxicity, genotoxicity, and developmental toxicity. However, the effects of HNMs exposure on the intestinal tract and intestinal flora remain unknown. This study comprehensively determined the effects of trichloronitromethane, bromonitromethane, and bromochloronitromethane exposure on the intestinal tract and intestinal flora. Results showed that the three HNMs induced intestinal oxidative stress and inflammatory response. Further, HNMs exposure could change the diversities and community structure of intestinal flora, thereby triggering intestinal flora dysbiosis, which might be associated with the intestinal damage such as oxidative stress and inflammation. The intestinal flora dysbiosis was accompanied with mark alterations in function of intestinal flora, such as carbohydrate, lipid, and amino acid metabolisms. This research provides a new insight into studying the toxicity of HNMs exposure based on intestinal flora, which will further improve the health risk assessment of DBPs in drinking water.
Inhibition of Plasmodium falciparum Hsp70-Hop partnership by 2-phenylthynesulfonamide
Authors: Muthelo Tshifhiwa , Mulaudzi Vhahangwele , Netshishivhe Munei , Dongola Tendamudzimu Harmfree , Kok Michelle , Makumire Stanley , de Villiers Marianne , Burger Adélle , Zininga Tawanda , Shonhai Addmore
Published: September 2022

Plasmodium falciparum Hsp70-1 (PfHsp70-1; PF3D7_0818900) and PfHsp90 (PF3D7_0708400) are essential cytosol localized chaperones of the malaria parasite. The two chaperones form a functional complex via the adaptor protein, Hsp90-Hsp70 organizing protein (PfHop [PF3D7_1434300]), which modulates the interaction of PfHsp70-1 and PfHsp90 through its tetracopeptide repeat (TPR) domains in a nucleotide-dependent fashion. On the other hand, PfHsp70-1 and PfHsp90 possess C-terminal EEVD and MEEVD motifs, respectively, which are crucial for their interaction with PfHop. By coordinating the cooperation of these two chaperones, PfHop plays an important role in the survival of the malaria parasite. 2-Phenylthynesulfonamide (PES) is a known anti-cancer agent whose mode of action is to inhibit Hsp70 function. In the current study, we explored the antiplasmodial activity of PES and investigated its capability to target the functions of PfHsp70-1 and its co-chaperone, PfHop. PES exhibited modest antiplasmodial activity (IC50 of 38.7 ± 0.7 µM). Furthermore, using surface plasmon resonance (SPR) analysis, we demonstrated that PES was capable of binding recombinant forms of both PfHsp70-1 and PfHop. Using limited proteolysis and intrinsic fluorescence-based analysis, we showed that PES induces conformational changes in PfHsp70-1 and PfHop. In addition, we demonstrated that PES inhibits the chaperone function of PfHsp70-1. Consequently, PES abrogated the association of the two proteins in vitro. Our study findings contribute to the growing efforts to expand the arsenal of potential antimalarial compounds in the wake of growing parasite resistance against currently used drugs.
The effect of neurologic music therapy in patients with cerebral palsy: A systematic narrative review
Authors: Yang Seoyon , Suh Jee Hyun , Kwon SuYeon , Chang Min Cheol
Published: September 2022

Background

Cerebral palsy (CP) is one of the most common causes of disability in children. It is characterized by impairment in motor function and coordination and difficulties in performing daily life activities. Previous research supports that neurologic music therapy (NMT) was effective in improving motor function, cognition, and emotional wellbeing in patients with various neurologic disorders. However, the benefit of NMT in patients with CP have not yet been thoroughly investigated. The aim of this review was to investigate the potential effect of NMT motor rehabilitation techniques for patients.

Materials and methods

We searched articles published up to May 24, 2022 in PubMed, Embase, Scopus, Cochrane library, Web of science, and Ovid MEDLINEdatabases. We included studies that investigated the effect of NMT in patients with CP.

Results

After search, 4,117 articles were identified using the search terms. After reading the titles and abstracts, 4,089 articles that did not meet our inclusion criteria were excluded. The remaining 28 articles which were assessed for eligibility. Finally, 15 studies were included in this systematic review. Among 15 studies that investigated the effect of NMT on patients with CP, 7 studies were on rhythmic auditory stimulation (RAS), 6 studies were on therapeutic instrumental music performance (TIMP), and 2 studies were on patterned sensory enhancement (PSE).

Conclusions

Various techniques of NMT brings beneficial effects for gross and fine motor improvements in patients with CP. NMT techniques, such as RAS, TIMP, and PSE, may be a potential alternative rehabilitation strategy to enhance gross and fine motor skills for patients with CP.
Association between neutrophil percentage-to-albumin ratio and 3-month functional outcome in acute ischemic stroke patients with reperfusion therapy
Authors: Cui Ting , Wang Changyi , Zhu Qiange , Li Shucheng , Yang Yuan , Wang Anmo , Zhang Xuening , Shang Wenzuo , Wu Bo
Published: September 2022

Background

Neutrophils and albumin are associated with outcomes in patients with acute ischemic stroke (AIS). We aimed to explore the association between the neutrophil percentage-to-albumin ratio (NPAR), a novel marker of inflammation and oxidative stress, and the 3-month functional outcome in AIS patients with reperfusion therapy.

Methods

This single-center, retrospective cohort study consecutively enrolled AIS patients with reperfusion therapy. Neutrophils and albumin were collected on admission. The primary outcome was a poor functional outcome, which was defined as a modified Rankin scale score of 3–6 at 3 months.

Results

A total of 647 patients with AIS who received reperfusion therapy were analyzed. The mean age was 68.9 ± 13.9 years, and 358 (55.3%) of the patients were men. The median NPAR was 1.89 (interquartile range [IQR] 1.64–2.09). The percentage of patients with a 3-month poor functional outcome was 57.0% (369/647). NPAR was positively associated with a poor functional outcome (odds ratio [OR] 2.76, 95% CI: 1.52–5.03, p = 0.001). When patients were classified into tertiles, patients in the upper tertile (2.03–7.59) had a higher risk of poor outcome than patients in the lower tertile after adjusting for potential confounders (0.78–1.73) (OR 2.10, 95% CI: 1.28–3.42, p = 0.003). The risk of poor outcome increased with NPAR tertiles (p-trend = 0.003). The optimal cut-off value of the NPAR for predicting a poor outcome was 1.72, with a sensitivity of 0.75, and a specificity of 0.43.

Conclusion

Neutrophil percentage-to-albumin ratio was significantly associated with 3-month poor functional outcomes in patients with AIS who received reperfusion therapy.
Comparative effectiveness of electroacupuncture VS neuromuscular electrical stimulation in the treatment of chronic low back pain in active-duty personals: A single-center, randomized control study
Authors: Meng Xiao-yan , Bu Lan , Chen Jia-ying , Liu Qiu-jia , Sun Li , Li Xiao-long , Wu Fei-xiang
Published: September 2022

Introduction

Low back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.

Methods

The study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit.

Results

Eighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.

Conclusion

Both the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.

Trial registration

ChiCTR, (ChiCTR2100043726); registered February 27, 2021.
Effect of therapeutic exercise on the balance of patients with progressive supranuclear palsy: A pilot study
Authors: Matsuda Naomi , Takamatsu Yasuyuki , Aiba Ikuko
Published: September 2022

Background

Progressive supranuclear palsy (PSP) is a parkinsonian-like progressive neurodegenerative syndrome. Key clinical features include ocular motor dysfunction, postural instability, and cognitive dysfunction. Maintaining and improving balance function and gait function are very important for patients with PSP with severe postural dysfunction and repeated falls. In addition, patients with PSP have a poor response to pharmacological treatment; hence, rehabilitation is a key approach in dealing with this syndrome. However, no conclusion on the beneficial effects of rehabilitation for patients with PSP have been established in the literature.

Objectives

The effectiveness of multiple therapeutic exercise program with probable or possible PSP according to the Movement Disorder Society criteria for the clinical diagnosis of PSP was validated.

Methods

Participants underwent multiple therapeutic exercise program customized for each participant, including resistance training, balance training, and walking exercises that were performed for 60–80 minutes a day, 5 days a week for 4 weeks. The outcomes measured were as follows: pull test, Berg Balance Scale (BBS), timed up and go test (TUG), and gait speed test.

Results

A total of 117 patients with PSP were enrolled and the analysis was performed on 20 patients with probable PSP. Four-week rehabilitation significantly improved pull test (p = 0.034) and BBS scores (p = 0.001). There were no significant differences both TUG (p = 0.502) and gait speed (p = 0.813).

Conclusion

The multiple therapeutic exercise program had beneficial effects on balance performance in patients with PSP in 4 weeks and could be an essential element in their rehabilitation. Although this pilot study was conducted without a control group, it provided valuable information for future prospective randomized controlled trials.
Social determinants of participant recruitment and retention in a prospective cohort study of pediatric mild traumatic brain injury
Authors: Wells Jordee M. , Galarneau Jean-Michel , Minich Nori M. , Cohen Daniel M. , Clinton Kameron , Taylor H. Gerry , Bigler Erin D. , Bacevice Ann , Mihalov Leslie K. , Bangert Barbara A. , Zumberge Nicholas A. , Yeates Keith Owen
Published: September 2022

Background

Prior studies have shown poor recruitment and retention of minoritized groups in clinical trials.

Objective

To examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8–16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI).

Methods

Children and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8–16 with either mild TBI or OI.

Results

A total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%).

Conclusions

Racial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.
Characteristics of clinical details and endolymphatic hydrops in unilateral and bilateral Ménière's disease in a single Asian group
Authors: Shi Suming , Li Wenquan , Wang Dan , Ren Tongli , Wang Wuqing
Published: September 2022

Objectives

To elucidate the characteristics of the clinical details and endolymphatic hydrops (EH) in bilateral Ménière's disease (BMD).

Methods

A total of 545 patients with definite MD were enrolled. Demographic variables; the age of onset; disease course; inner ear function; the coexistence of related disorders such as migraine, delayed MD, drop attacks, and autoimmune diseases; familial history; and characteristics of EH were analyzed.

Results

In the study population, the prevalence of BMD was 15.4%. The disease duration of BMD (84.0 ± 89.6 months) was significantly longer than that of unilateral MD (UMD, 60.1 ± 94.0 months) (P = 0.001). As evaluated by hearing thresholds and cervical and ocular vestibular evoked myogenic potentials, inner ear functions were more deteriorated in BMD (P < 0.05) than in UMD. The proportions of delayed MD and a family history of vertigo were significantly larger in BMD (P < 0.05). EH was observed in 100% of cases on the clinically affected side and 6.1% of cases on the unaffected side.

Conclusion

A low prevalence of BMD, longer disease duration, higher frequencies of delayed MD, and family history of vertigo in patients with BMD were significant findings observed in the present study. All affected ears presented with EH, and a low percentage of unaffected sides presented with EH.
Quantifying the amount of greater brain ischemia protection time with pre-hospital vs. in-hospital neuroprotective agent start
Authors: Matossian Vartan , Starkman Sidney , Sanossian Nerses , Stratton Samuel , Eckstein Marc , Conwit Robin , Liebeskind David S. , Sharma Latisha , Tenser May-Kim , Saver Jeffrey L.
Published: September 2022

The objective of this study is to quantify the increase in brain-under-protection time that may be achieved with pre-hospital compared with the post-arrival start of neuroprotective therapy among patients undergoing endovascular thrombectomy. In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Field administration of stroke therapy-magnesium (FAST–MAG) Trial; (2) in-hospital strategy: Efficacy and safety of nerinetide for the treatment of acute ischemic stroke (ESCAPE-NA1) Trial. In the FAST-MAG trial, among 1,041 acute ischemic stroke patients, 44 were treated with endovascular reperfusion therapy (ERT), including 32 treated with both intravenous thrombolysis and ERT and 12 treated with ERT alone. In the ESCAPE-NA1 trial, among 1,105 acute ischemic stroke patients, 659 were treated with both intravenous thrombolysis and ERT, and 446 were treated with ERT alone. The start of the neuroprotective agent was sooner after onset with pre-hospital vs. in-hospital start: 45 m (IQR 38–56) vs. 122 m. The neuroprotective agent in FAST–MAG was started 8 min prior to ED arrival compared with 64 min after arrival in ESCAPE–NA1. Projecting modern endovascular workflows to FAST–MAG, the total time of “brain under protection” (neuroprotective agent start to reperfusion) was greater with pre-hospital than in-hospital start: 94 m (IQR 90–98) vs. 22 m. Initiating a neuroprotective agent in the pre-hospital setting enables a faster treatment start, yielding 72 min additional brain protection time for patients with acute ischemic stroke. These findings provide support for the increased performance of ambulance-based, pre-hospital treatment trials in the development of neuroprotective stroke therapies.
Respiratory sinus arrhythmia during biofeedback is linked to persistent improvements in attention, short-term memory, and positive self-referential episodic memory
Authors: Bögge Lukas , Colás-Blanco Itsaso , Piolino Pascale
Published: September 2022

Background

Heart rate variability (HRV) biofeedback, an intervention based on the voluntary self-regulation of autonomic parameters, has been shown to affect prefrontal brain functioning and improve executive functions. The interest in using HRV biofeedback as cognitive training is typically ascribed to parasympathetic activation and optimized physiological functioning deriving from increased cardiac vagal control. However, the persistence of cognitive effects is poorly studied and their association with biofeedback-evoked autonomic changes has not yet been explored. In addition, no study has so far investigated the influence of HRV biofeedback in adults on long-term episodic memory, which is particularly concerned with self-referential encoding processing.

Methods

In the present study, a novel training system was developed integrating HRV and respiratory biofeedback into an immersive virtual reality environment to enhance training efficacy. Twenty-two young healthy adults were subjected to a blinded randomized placebo-controlled experiment, including six self-regulation training sessions, to evaluate the effect of biofeedback on autonomic and cognitive changes. Cardiac vagal control was assessed before, during, and 5 min after each training session. Executive functions, episodic memory, and the self-referential encoding effect were evaluated 1 week before and after the training program using a set of validated tasks.

Results

Linear mixed-effects models showed that HRV biofeedback greatly stimulated respiratory sinus arrhythmia during and after training. Moreover, it improved the attentional capabilities required for the identification and discrimination of stimuli (ηp2 = 0.17), auditory short-term memory (ηp2 = 0.23), and self-referential episodic memory recollection of positive stimuli (ηp2 = 0.23). Episodic memory outcomes indicated that HRV biofeedback reinforced positive self-reference encoding processing. Cognitive changes were strongly dependent on the level of respiratory sinus arrhythmia evoked during self-regulation training.

Conclusion

The present study provides evidence that biofeedback moderates respiration-related cardiac vagal control, which in turn mediates improvements in several cognitive processes crucial for everyday functioning including episodic memory, that are maintained beyond the training period. The results highlight the interest in HRV biofeedback as an innovative research tool and medication-free therapeutic approach to affect autonomic and neurocognitive functioning. Finally, a neurocognitive model of biofeedback-supported autonomic self-regulation as a scaffolding for episodic memory is proposed.
Astrocyte development in the cerebral cortex: Complexity of their origin, genesis, and maturation
Authors: Clavreul Solène , Dumas Laura , Loulier Karine
Published: September 2022

In the mammalian brain, astrocytes form a heterogeneous population at the morphological, molecular, functional, intra-, and inter-region levels. In the past, a few types of astrocytes have been first described based on their morphology and, thereafter, according to limited key molecular markers. With the advent of bulk and single-cell transcriptomics, the diversity of astrocytes is now progressively deciphered and its extent better appreciated. However, the origin of this diversity remains unresolved, even though many recent studies unraveled the specificities of astroglial development at both population and individual cell levels, particularly in the cerebral cortex. Despite the lack of specific markers for each astrocyte subtype, a better understanding of the cellular and molecular events underlying cortical astrocyte diversity is nevertheless within our reach thanks to the development of intersectional lineage tracing, microdissection, spatial mapping, and single-cell transcriptomic tools. Here we present a brief overview describing recent findings on the genesis and maturation of astrocytes and their key regulators during cerebral cortex development. All these studies have considerably advanced our knowledge of cortical astrogliogenesis, which relies on a more complex mode of development than their neuronal counterparts, that undeniably impact astrocyte diversity in the cerebral cortex.
The melanin-concentrating hormone system as a target for the treatment of sleep disorders
Authors: Potter Liam E. , Burgess Christian R.
Published: September 2022

Given the widespread prevalence of sleep disorders and their impacts on health, it is critical that researchers continue to identify and evaluate novel avenues of treatment. Recently the melanin-concentrating hormone (MCH) system has attracted commercial and scientific interest as a potential target of pharmacotherapy for sleep disorders. This interest emerges from basic scientific research demonstrating a role for MCH in regulating sleep, and particularly REM sleep. In addition to this role in sleep regulation, the MCH system and the MCH receptor 1 (MCHR1) have been implicated in a wide variety of other physiological functions and behaviors, including feeding/metabolism, reward, anxiety, depression, and learning. The basic research literature on sleep and the MCH system, and the history of MCH drug development, provide cause for both skepticism and cautious optimism about the prospects of MCH-targeting drugs in sleep disorders. Extensive efforts have focused on developing MCHR1 antagonists for use in obesity, however, few of these drugs have advanced to clinical trials, and none have gained regulatory approval. Additional basic research will be needed to fully characterize the MCH system’s role in sleep regulation, for example, to fully differentiate between MCH-neuron and peptide/receptor-mediated functions. Additionally, a number of issues relating to drug design will continue to pose a practical challenge for novel pharmacotherapies targeting the MCH system.
Altered static functional network connectivity predicts the efficacy of non-steroidal anti-inflammatory drugs in migraineurs without aura
Authors: Wei Heng-Le , Yang Wen-Juan , Zhou Gang-Ping , Chen Yu-Chen , Yu Yu-Sheng , Yin Xindao , Li Junrong , Zhang Hong
Published: September 2022

Brain networks have significant implications for the understanding of migraine pathophysiology and prognosis. This study aimed to investigate whether large-scale network dysfunction in patients with migraine without aura (MwoA) could predict the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs). Seventy patients with episodic MwoA and 33 healthy controls (HCs) were recruited. Patients were divided into MwoA with effective NSAIDs (M-eNSAIDs) and with ineffective NSAIDs (M-ieNSAIDs). Group-level independent component analysis and functional network connectivity (FNC) analysis were used to extract intrinsic networks and detect dysfunction among these networks. The clinical characteristics and FNC abnormalities were considered as features, and a support vector machine (SVM) model with fivefold cross-validation was applied to distinguish the subjects at an individual level. Dysfunctional connections within seven networks were observed, including default mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), dorsal attention network (DAN), visual network (VN), and auditory network (AN). Compared with M-ieNSAIDs and HCs, patients with M-eNSAIDs displayed reduced DMN-VN and SMN-VN, and enhanced VN-AN connections. Moreover, patients with M-eNSAIDs showed increased FNC patterns within ECN, DAN, and SN, relative to HCs. Higher ECN-SN connections than HCs were revealed in patients with M-ieNSAIDs. The SVM model demonstrated that the area under the curve, sensitivity, and specificity were 0.93, 0.88, and 0.89, respectively. The widespread FNC impairment existing in the modulation of medical treatment suggested FNC disruption as a biomarker for advancing the understanding of neurophysiological mechanisms and improving the decision-making of therapeutic strategy.
Molecular mechanisms of synaptogenesis
Authors: Qi Cai , Luo Li-Da , Feng Irena , Ma Shaojie
Published: September 2022

Synapses are the basic units for information processing and storage in the nervous system. It is only when the synaptic connection is established, that it becomes meaningful to discuss the structure and function of a circuit. In humans, our unparalleled cognitive abilities are correlated with an increase in the number of synapses. Additionally, genes involved in synaptogenesis are also frequently associated with neurological or psychiatric disorders, suggesting a relationship between synaptogenesis and brain physiology and pathology. Thus, understanding the molecular mechanisms of synaptogenesis is the key to the mystery of circuit assembly and neural computation. Furthermore, it would provide therapeutic insights for the treatment of neurological and psychiatric disorders. Multiple molecular events must be precisely coordinated to generate a synapse. To understand the molecular mechanisms underlying synaptogenesis, we need to know the molecular components of synapses, how these molecular components are held together, and how the molecular networks are refined in response to neural activity to generate new synapses. Thanks to the intensive investigations in this field, our understanding of the process of synaptogenesis has progressed significantly. Here, we will review the molecular mechanisms of synaptogenesis by going over the studies on the identification of molecular components in synapses and their functions in synaptogenesis, how cell adhesion molecules connect these synaptic molecules together, and how neural activity mobilizes these molecules to generate new synapses. Finally, we will summarize the human-specific regulatory mechanisms in synaptogenesis and results from human genetics studies on synaptogenesis and brain disorders.
Prognostic value of micro-RNA 375, 133, 143, 145 in esophageal carcinoma: A systematic review and meta-analysis
Authors: Fang Pinhao , Zhou Jianfeng , Li Xiaokun , Luan Siyuan , Xiao Xin , Shang Qixin , Zhang Hanlu , Yang Yushang , Zeng Xiaoxi , Yuan Yong
Published: September 2022

Many studies have confirmed that micro-RNA (mir) is related to the prognosis of esophageal carcinoma (EC), suggesting the mir could be used to guide the therapeutic strategy of EC. Some of mir molecules are considered as favorable prognostic factors for EC. The purpose of our study is to evaluate the prognostic potential of mir-375, 133, 143, 145 in primary EC, we summarized all the results from available studies, aiming delineating the prognostic role of mir in EC. Relevant studies were identified by searching databases including Medline, Embase, Web of science, Cochrane Library. The studies which explored the prognostic value of mir-375, 133, 143, 145 expressions on survival outcomes in patients with EC were included in this study. The hazard ratios (HR) and their responding 95% confidence interval (CI) were also extracted. A total of 25 studies were collected, including 1260 patients, and the prognostic values of four mirs in EC were analyzed. Survival outcomes including overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were used as the primary endpoint to evaluate the prognostic value of mir. The pooled analysis results showed that up-regulation of mir-375 indicated favorable OS (HR=0.50; 95%CI: 0.37-0.69; P<0.001). In addition, the up-regulation of mir-133 (HR=0.40, 95%CI: 0.24-0.65, P<0.001), 143 (HR=0.40, 95%CI: 0.21-0.76, P < 0.001) and 145 (HR=0.55, 95%CI: 0.34-0.90, P<0.001) are also proved as protected factors in EC. Therefore, our study demonstrated that these mirs may have the potential to be used as prognostic biomarkers for EC in clinical practice.
Neoadjuvant camrelizumab and chemotherapy in patients with resectable stage IIIA squamous non-small-cell lung cancer: Clinical experience of three cases
Authors: Li Xin , Xia Chunqiu , Liu Minghui , Liu Jinghao , Dong Ming , Zhao Honglin , Xu Song , Wang Dan , Wei Sen , Song Zuoqing , Chen Gang , Liu Hongyu , Chen Jun
Published: September 2022

Neoadjuvant immunochemotherapy has attracted much attention as a treatment for locally advanced non-small-cell lung cancer. However, there is scarce evidence of the safety and efficacy of camrelizumab as neoadjuvant in lung cancer. Here, we present three patients who were diagnosed with IIIA squamous non-small-cell lung cancer from September to December in 2020 and received two cycles of neoadjuvant camrelizumab plus nab-paclitaxel and nedaplatin, followed by surgical resection. All three patients had a reduction in the tumor size on CT image and not delayed planned surgery. We did not observe grade 3 or 4 adverse events. Two of the three patients achieved a major pathological response (MPR), including one complete tumor regression of the primary lung tumor. Multiplex fluorescent immunohistochemistry revealed that CD8+ T cells, FoxP3+ regulatory T cells, and PD-L1 expression on immune cells in the surgical specimen were much higher than in the pretreatment biopsy sample in patients with MPR. This was not observed in the patient without MPR. Camrelizumab plus chemotherapy could potentially be a neoadjuvant regimen for resectable IIIA squamous non-small-cell lung cancer, with a high MPR proportion, and did not compromise surgical procedure. Our findings should be validated in a future randomized clinical trial.
Evaluation of a new method of calculating breast tumor volume based on automated breast ultrasound
Authors: Ma Jing-Jing , Meng Shan , Dang Sha-Jie , Wang Jia-Zhong , Yuan Quan , Yang Qi , Song Can-Xu
Published: September 2022

Objective

To evaluate the effectiveness and advantages of a new method for calculating breast tumor volume based on an automated breast ultrasound system (ABUS).

Methods

A total of 42 patients (18–70 years old) with breast lesions were selected for this study. The Ivenia ABUS 2.0 (General Electric Company, USA) was used, with a probe frequency of 6–15 MHz. Adobe Photoshop CS6 software was used to calculate the pixel ratio of each ABUS image, and to draw an outline of the tumor cross-section. The resulting area (in pixels) was multiplied by the pixel ratio to yield the area of the tumor cross-section. The Wilcoxon signed rank test and Bland-Altman plot were used to compare mean differences and mean values, respectively, between the two methods.

Results

There was no significant difference between the tumor volumes calculated by pixel method as compared to the traditional method (P>0.05). Repeated measurements of the same tumor volume were more consistent with the pixel method.

Conclusion

The new pixel method is feasible for measuring breast tumor volume and has good validity and measurement stability.
Diffusion tensor imaging, intra-operative neurophysiological monitoring and small craniotomy: Results in a consecutive series of 103 gliomas
Authors: Carrabba Giorgio , Fiore Giorgio , Di Cristofori Andrea , Bana Cristina , Borellini Linda , Zarino Barbara , Conte Giorgio , Triulzi Fabio , Rocca Alessandra , Giussani Carlo , Caroli Manuela , Locatelli Marco , Bertani Giulio
Published: September 2022

Diffusion tensor imaging (DTI) allows visualization of the main white matter tracts while intraoperative neurophysiological monitoring (IONM) represents the gold standard for surgical resection of gliomas. In recent years, the use of small craniotomies has gained popularity thanks to neuronavigation and to the low morbidity rates associated with shorter surgical procedures. The aim of this study was to review a series of patients operated for glioma using DTI, IONM, and tumor-targeted craniotomies. The retrospective analysis included patients with supratentorial glioma who met the following inclusion criteria: preoperative DTI, intraoperative IONM, tumor-targeted craniotomy, pre- and postoperative MRI, and complete clinical charts. The DTI was performed on a 3T scanner. The IONM included electroencephalography (EEG), transcranial (TC) and/or cortical motor-evoked potentials (MEP), electrocorticography (ECoG), and direct electrical stimulation (DES). Outcomes included postoperative neurological deficits, volumetric extent of resection (EOR), and overall survival (OS). One hundred and three patients (61 men, 42 women; mean age 54 ± 14 years) were included and presented the following WHO histologies: 65 grade IV, 19 grade III, and 19 grade II gliomas. After 3 months, only three patients had new neurological deficits. The median postoperative volume was 0cc (IQR 3). The median OS for grade IV gliomas was 15 months, while for low-grade gliomas it was not reached. In our experience, a small craniotomy and a tumor resection supported by IONM and DTI permitted to achieve satisfactory results in terms of neurological outcomes, EOR, and OS for glioma patients.
Cost-effectiveness analysis of metronomic capecitabine as adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma
Authors: She Longjiang , Tian Kun , Han Jiaqi , Zuo Weihan , Wang Zhu , Zhang Ning
Published: September 2022

Background

Adding metronomic capecitabine to concurrent chemoradiotherapy (CCRT) brings failure-free survival (FFS) benefits to patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study assesses the cost-effectiveness of metronomic capecitabine in locoregionally advanced NPC.

Methods

We created a Markov model to calculate the expense and health outcomes of metronomic capecitabine compared to those observed in locoregionally advanced NPC. Related costs, like life-years (LYs), quality-adjusted life years (QALYs), and incremental cost-effective ratios (ICERs) were measured at a willingness-to-pay (WTP) threshold of $33,585 per QALY. A combination of different sensitivity analyses was used to test for model robustness. Additionally, a subgroup analysis was also performed.

Results

In contrast to what is observed in the locoregionally advanced NPC, adding the metronomic adjuvant capecitabine yielded an additional 1.11 QALYs with an incremental cost of $10,741.59, which obtained an ICER of $9,669.99 per QALY. The result of one-way sensitive analysis indicated that the utility of FFS, progression disease (PD), and the cost of follow-up were the most significant factors. The probability of metronomic capecitabine being cost-effective was 97.1% at a WTP of $33,585 per QALY.

Conclusion

Metronomic capecitabine as adjuvant chemotherapy is a cost-effective strategy for locoregionally advanced NPC patients.
Efficacy and safety of transarterial chemoembolization combining sorafenib with or without immune checkpoint inhibitors in previously treated patients with advanced hepatocellular carcinoma: A propensity score matching analysis
Authors: Yang Xue-Gang , Sun Yan-Yuan , Wang Hai-Qing , Li De-Shan , Xu Guo-Hui , Huang Xiao-Qi
Published: September 2022

Purpose

To compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib and immune checkpoint inhibitors (T+S+ICIs) and TACE plus sorafenib (T+S) when treating patients with advanced hepatocellular carcinoma (HCC) who have previously received locoregional treatment.

Materials and methods

A retrospective analysis was performed on the patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC from May 2019 to December 2020. These patients were treated with locoregional therapy and showed radiographic progression after the treatment. Patients received either T+S+ICIs or T+S. The outcomes, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety, were compared. The propensity score matching (PSM) methodology was used to reduce the influence of confounding factors on the outcomes.

Results

Forty-three patients were included in the T+S group and 33 in the T+S+ICI group. After PSM (n = 29 in each group), patients who received T+S+ICIs had a higher DCR (82.8% vs. 58.6%, p = 0.043), longer median PFS (6.9 vs. 3.8 months, p = 0.003), and longer median OS (12.3 vs. 6.3 months, p = 0.008) than those who underwent T+S. Eastern Cooperative Oncology Group performance status was an independent predictor of PFS, and age was an independent predictor of OS. The incidence of treatment-related adverse events in T+S+ICIs was well controlled.

Conclusions

Compared with TACE combined with sorafenib, TACE combined with sorafenib plus ICIs is a potentially safe and effective treatment regimen for patients with advanced HCC who previously received locoregional treatment.
Pro-metastatic and mesenchymal gene expression signatures characterize circulating tumor cells of neuroblastoma patients with bone marrow metastases and relapse
Authors: Loh Amos H. P. , Angelina Clara , Wong Meng Kang , Tan Sheng Hui , Sukhatme Sarvesh A. , Yeo Trifanny , Lim Su Bin , Lee York Tien , Soh Shui Yen , Leung Wing , Chang Kenneth T. E. , Chua Yong Wei , Alkaff Syed M. F. , Lim Tony K. H. , Lim Chwee Teck , Chen Zhi Xiong
Published: September 2022

Existing marker-based methods of minimal residual disease (MRD) determination in neuroblastoma do not effectively enrich for the circulating disease cell population. Given the relative size differential of neuroblastoma tumor cells over normal hematogenous cells, we hypothesized that cell size-based separation could enrich circulating tumor cells (CTCs) from blood samples and disseminated tumor cells (DTCs) from bone marrow aspirates (BMA) of neuroblastoma patients, and that their gene expression profiles could vary dynamically with various disease states over the course of treatment. Using a spiral microfluidic chip, peripheral blood of 17 neuroblastoma patients at 3 serial treatment timepoints (diagnosis, n=17; post-chemotherapy, n=11; and relapse, n=3), and bone marrow samples at diagnosis were enriched for large intact circulating cells. Profiling the resulting enriched samples with immunohistochemistry and mRNA expression of 1490 cancer-related genes via NanoString, 13 of 17 samples contained CTCs displaying cytologic atypia, TH and PHOX2B expression and/or upregulation of cancer-associated genes. Gene signatures reflecting pro-metastatic processes and the neuroblastoma mesenchymal super-enhancer state were consistently upregulated in 7 of 13 samples, 6 of which also had metastatic high-risk disease. Expression of 8 genes associated with PI3K and GCPR signaling were significantly upregulated in CTCs of patients with bone marrow metastases versus patients without. Correspondingly, in patients with marrow metastases, differentially-expressed gene signatures reflected upregulation of immune regulation in bone marrow DTCs versus paired CTCs samples. In patients who later developed disease relapse, 5 genes involved in immune cell regulation, JAK/STAT signaling and the neuroblastoma mesenchymal super-enhancer state (OLFML2B, STAT1, ARHGDIB, STAB1, TLR2) were upregulated in serial CTC samples over their disease course, despite urinary catecholamines and bone marrow aspirates not indicating the disease recurrences. In summary, using a label-free cell size-based separation method, we enriched and characterized intact circulating cells in peripheral blood indicative of neuroblastoma CTCs, as well as their DTC counterparts in the bone marrow. Expression profiles of pro-metastatic genes in CTCs correlated with the presence of bone marrow metastases at diagnosis, while longitudinal profiling identified persistently elevated expression of genes in CTCs that may serve as novel predictive markers of hematogenous MRD in neuroblastoma patients that subsequently relapse.