bluuebunny/crossref_metadata_2025 huggingface dataset:
A cross-sectional observational study for ethno-geographical disparities in sleep quality, brain morphometry and cognition (a SOLACE study) in Indians residing in India, and South Asians and Europeans residing in the UK – a study protocol
Authors: Soni Rishabh , Dale Caroline , Garfield Victoria , Akhtar Nasreen
Published: February 2024

Introduction

As individuals age, their sleep patterns change, and sleep disturbances can increase the risk of dementia. Poor sleep quality can be a risk factor for mild cognitive impairment (MCI) and dementia. Epidemiological studies show a connection between sleep quality and cognitive changes, with brain imaging revealing grey matter volume reduction and amyloid beta accumulation in Alzheimer’s disease. However, most research has focused on Europeans, with little attention to other ethnic groups.

Methods

This is a cross sectional study comparing effects across countries and ethnicities. Group 1 (n = 193) will be Indians residing in India (new participant recruitment), Group 2 will be South Asians residing in UK and group 3 will be Europeans residing in the UK. For group 2 and 3 (n = 193), data already collected by UK-based Southall and Brent REvisited (SABRE) tri-ethnic study will be used. For group 1, Pittsburgh Sleep Quality Index questionnaire (PSQI) will be used for assessment of sleep quality, Indian Council of Medical Research (Neurocognitive ToolBox) (ICMR-NCTB) for cognition testing and a 3 T MRI cerebral scan for brain morphometry. The data will be compared to sleep, cognitive function and brain MRI parameters from SABRE.

Discussion

Racial and ethnic differences can impact the relationships of cognitive function, sleep quality and brain structure in older adults. Earlier studies have highlighted higher prevalence of poor sleep among black individuals compared to white individuals. Genetic or epigenetic mechanisms may contribute to these variations. Socio-cultural and environmental factors, such as neighbourhood, migration, lifestyle, stress and perceived discrimination may influence sleep patterns. The aim of the study is to examine the ethnogeographic variations in sleep quality, cognitive performance and brain morphometry among Indians living in India, and South Asians and Europeans residing in the UK.
tRNS boosts visual perceptual learning in participants with bilateral macular degeneration
Authors: Contemori Giulio , Maniglia Marcello , Guénot Jade , Soler Vincent , Cherubini Marta , Cottereau Benoit R. , Trotter Yves
Published: February 2024

Perceptual learning (PL) has shown promise in enhancing residual visual functions in patients with age-related macular degeneration (MD), however it requires prolonged training and evidence of generalization to untrained visual functions is limited. Recent studies suggest that combining transcranial random noise stimulation (tRNS) with perceptual learning produces faster and larger visual improvements in participants with normal vision. Thus, this approach might hold the key to improve PL effects in MD. To test this, we trained two groups of MD participants on a contrast detection task with (n = 5) or without (n = 7) concomitant occipital tRNS. The training consisted of a lateral masking paradigm in which the participant had to detect a central low contrast Gabor target. Transfer tasks, including contrast sensitivity, near and far visual acuity, and visual crowding, were measured at pre-, mid and post-tests. Combining tRNS and perceptual learning led to greater improvements in the trained task, evidenced by a larger increment in contrast sensitivity and reduced inhibition at the shortest target to flankers’ distance. The overall amount of transfer was similar between the two groups. These results suggest that coupling tRNS and perceptual learning has promising potential applications as a clinical rehabilitation strategy to improve vision in MD patients.
Revised Temperament and Character Inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years
Authors: Ronat Lucas , Rönnlund Michael , Adolfsson Rolf , Hanganu Alexandru , Pudas Sara
Published: February 2024

Introduction

Personality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer’s disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study.

Methods

Mixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD.

Results

Two personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors.

Conclusion

The results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.
Metabolic energy decline coupled dysregulation of catecholamine metabolism in physiologically highly active neurons: implications for selective neuronal death in Parkinson’s disease
Authors: Wimalasena Kandatege , Adetuyi Oluwatosin , Eldani Maya
Published: February 2024

Parkinson’s disease (PD) is an age-related irreversible neurodegenerative disease which is characterized as a progressively worsening involuntary movement disorder caused by the loss of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc). Two main pathophysiological features of PD are the accumulation of inclusion bodies in the affected neurons and the predominant loss of neuromelanin-containing DA neurons in substantia nigra pars compacta (SNpc) and noradrenergic (NE) neurons in locus coeruleus (LC). The inclusion bodies contain misfolded and aggregated α-synuclein (α-Syn) fibrils known as Lewy bodies. The etiology and pathogenic mechanisms of PD are complex, multi-dimensional and associated with a combination of environmental, genetic, and other age-related factors. Although individual factors associated with the pathogenic mechanisms of PD have been widely investigated, an integration of the findings to a unified causative mechanism has not been envisioned. Here we propose an integrated mechanism for the degeneration of DA neurons in SNpc and NE neurons in LC in PD, based on their unique high metabolic activity coupled elevated energy demand, using currently available experimental data. The proposed hypothetical mechanism is primarily based on the unique high metabolic activity coupled elevated energy demand of these neurons. We reason that the high vulnerability of a selective group of DA neurons in SNpc and NE neurons in LC in PD could be due to the cellular energy modulations. Such cellular energy modulations could induce dysregulation of DA and NE metabolism and perturbation of the redox active metal homeostasis (especially copper and iron) in these neurons.
Association between serum estradiol levels and cognitive function in older women: a cross-sectional analysis
Authors: Xu Qian , Ji Meng , Huang Shicai , Guo Weifeng
Published: February 2024

Introduction

Estradiol is a sex steroid hormone, which has been implicated in the pathogenesis of Alzheimer’s disease and cognitive impairment. This cross-sectional study aimed to examine the relationship between serum estradiol levels and cognitive performance in older American women.

Methods

Data were obtained from the National Health and Nutrition Examination Survey 2013–2014. A total of 731 women aged ≥60 years who met the inclusion criteria were included in this study. Serum estradiol levels were measured using the isotope dilution liquid chromatography tandem mass spectrometry (ID-LC–MS/MS) method developed by the Centers for Disease Control and Prevention for routine analysis. All measured serum levels were further divided into three parts: T1, <3.68 pg./mL; T2, 3.68–7.49 pg./mL; T3, >7.49 pg./mL, and analyzed. Participants’ cognitive abilities were tested using the Vocabulary Learning Subtest (CERAD), Animal Fluency Test (AFS), and digital symbol substitution test (DSST). Scores for each test were calculated based on the sample mean and standard deviation (SD). To examine the relationship between serum estradiol level tertiles and cognitive scores, multiple linear regression models were developed, controlling for race/ethnicity, education level, hypertension, diabetes, and insomnia.

Results

The mean age of the participants was 69.57 ± 6.68 years. The non-Hispanic whites were 78.95%, and those who had completed at least some college-level education were 60.62%. The mean BMI of the participants was 29.30 ± 6.79, and 10.85% had a history of smoking. Further, 73.41% did not have a history of alcohol consumption, and 63.03% had hypertension (63.03%). In addition, 81.81 and 88.3% did not have a history of diabetes mellitus and did not have sleep disorders, respectively. The mean serum estradiol level was 8.48 ± 0.77 pg./mL. Multivariate linear regression of the reference group consisting of participants in tertiles of serum estradiol levels revealed that one unit increase in serum estradiol levels increased DSST scores by 0.61 (0.87, 6.34) in the T3 group. However, no significant correlation was found in the CERAD and AFS tests.

Conclusion

Participants with higher estradiol levels had higher DSST scores and better processing speed, sustained attention, and working memory, suggesting that serum estradiol may serve as a biomarker for cognitive decline in older women.
Effect of tuina on sleep quality, psychological state and neurotransmitter level in patients with insomnia: a systematic review and meta-analysis
Authors: Wang Zhen , Xu Hui , Wang Zheng , Zhou Hang , Zhang Lijuan , Wang Yu , Li Miaoxiu , Zhou Yunfeng
Published: February 2024

Background

Abnormal psychological state and neurotransmitter levels are important factors affecting sleep quality. Numerous studies have shown that tuina can improve the symptoms of sleep disorders in patients with insomnia while relieving anxiety and depression and regulating neurotransmitter levels. However, there have been no meta-analyses on the effect of tuina on psychological states and neurotransmitter levels.

Objectives

A meta-analysis was performed to systematically evaluate the effects of massage on sleep quality, psychological state, and neurotransmitter levels in patients with insomnia.

Methods

A comprehensive literature search was conducted from inception to July 2023 using eight electronic databases to identify randomized controlled trials (RCTs) on tuina therapy for insomnia. Gray literature was also searched. The methodological quality of the included studies was assessed using the Cochrane Handbook. Reviewer Manager 5.4 and Stata 16.0 were employed for statistical analysis.

Results

A total of 23 studies were included, including 1780 patients with insomnia, of whom 892 and 888 were in the experimental and control groups, respectively. Meta-analysis indicated that tuina therapy was superior to other therapies for the treatment of insomnia in increasing the total effective rate [OR = 4.12, 95%CI (2.80, 6.06), p < 0.00001] and 5-hydroxytryptamine (5-HT) level [MD = 16.03, 95% CI (13.40, 18.65), p < 0.00001], while reducing the Pittsburgh Sleep Quality Index score [MD = −2.34, 95% CI (−2.94, −1.74), p < 0.00001], Athens Insomnia Scale score [MD = −2.10, 95% CI (−2.67, −1.52), p < 0.00001], self-rating anxiety scale score [MD = −6.77, 95% CI (−8.34, −5.20), p < 0.00001] and self-rating depression scale score [MD = −6.60, 95% CI (−8.82, −4.37), p < 0.00001]. Subgroup analysis showed that tuina alone or in combination with other therapies was superior to drugs or acupuncture alone in improving all outcomes (p < 0.05). Only two studies reported minor adverse events.

Conclusion

Tuina for insomnia has certain therapeutic advantages and can significantly improve sleep quality, relieve anxiety-depressive states, and increase 5-HT levels with high safety. Due to the limitations of the quality of the included studies, additional high-quality clinical trials are required for further verification.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=447839, identifier CRD42023447839.
The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke—a pilot study
Authors: Tseng Shih-Chiao , Cherry Dana , Ko Mansoo , Fisher Steven R. , Furtado Michael , Chang Shuo-Hsiu
Published: February 2024

Purpose

Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS.

Methods

A total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT.

Results

a-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training.

Clinical implications

The preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251).
Postural impairments in unilateral and bilateral vestibulopathy
Authors: Corre Julie , Cugnot Jean-François , Boutabla Anissa , Cavuscens Samuel , Ranieri Maurizio , van de Berg Raymond , Peterka Robert J. , Guinand Nils , Fornos Angélica Pérez
Published: February 2024

Chronic imbalance is a major complaint of patients suffering from bilateral vestibulopathy (BV) and is often reported by patients with chronic unilateral vestibulopathy (UV), leading to increased risk of falling. We used the Central SensoriMotor Integration (CSMI) test, which evaluates sensory integration, time delay, and motor activation contributions to standing balance control, to determine whether CSMI measures could distinguish between healthy control (HC), UV, and BV subjects and to characterize vestibular, proprioceptive, and visual contributions expressed as sensory weights. We also hypothesized that sensory weight values would be associated with the results of vestibular assessments (vestibulo ocular reflex tests and Dizziness Handicap Inventory scores). Twenty HCs, 15 UVs and 17 BVs performed three CSMI conditions evoking sway in response to pseudorandom (1) surface tilts with eyes open or, (2) surface tilts with eyes closed, and (3) visual surround tilts. Proprioceptive weights were identified in surface tilt conditions and visual weights were identified in the visual tilt condition. BVs relied significantly more on proprioception. There was no overlap in proprioceptive weights between BV and HC subjects and minimal overlap between UV and BV subjects in the eyes-closed surface-tilt condition. Additionally, visual sensory weights were greater in BVs and were similarly able to distinguish BV from HC and UV subjects. We found no significant correlations between sensory weights and the results of vestibular assessments. Sensory weights from CSMI testing could provide a useful measure for diagnosing and for objectively evaluating the effectiveness of rehabilitation efforts and future treatments designed to restore vestibular function such as hair cell regeneration and vestibular implants.
Atypical neurological manifestations in anti-IgLON5 disease: a case report
Authors: Chen Yun , Chen Jingyao , Pei Zhaohua , Qian Wei
Published: February 2024

Anti-IgLON5 disease is a recently discovered autoimmune encephalopathy with sleep disorder as a hallmark in the majority of reported cases. Additional neurological manifestations include bulbar dysfunction, gait problems, movement disorders, oculomotor abnormalities, and hyperexcitability of the nervous system. At present, an increasing number of publications have dealt with the course and possible treatment options for anti-IgLON5 disease, and its clinical spectrum has expanded wider and more heterogeneous. Here, we report a case of a 66-year-old female with cognitive impairment accompanied by slow reaction, impaired memory, and decreased orientation. A positive cerebral MRI change and serum and cerebrospinal fluid (CSF) antibodies against IgLON5 were found during the diagnostic course. Subsequently the patient received immunotherapy and was generally in good health with no new symptoms during follow-up. Early testing for IgLON5 antibodies should be considered in patients with atypical neurological symptoms such as cognitive impairment, slow reaction, or decreased orientation. In clinical practice, immunotherapy should be considered in all cases of anti-IgLON5 encephalopathies.
Effects of speech rate modifications on phonatory acoustic outcomes in Parkinson’s disease
Authors: Knowles Thea , Adams Scott G. , Jog Mandar
Published: February 2024

Speech rate reduction is a global speech therapy approach for speech deficits in Parkinson’s disease (PD) that has the potential to result in changes across multiple speech subsystems. While the overall goal of rate reduction is usually improvements in speech intelligibility, not all people with PD benefit from this approach. Speech rate is often targeted as a means of improving articulatory precision, though less is known about rate-induced changes in other speech subsystems that could help or hinder communication. The purpose of this study was to quantify phonatory changes associated with speech rate modification across a broad range of speech rates from very slow to very fast in talkers with and without PD. Four speaker groups participated: younger and older healthy controls, and people with PD with and without deep brain stimulation of the subthalamic nucleus (STN-DBS). Talkers read aloud standardized sentences at 7 speech rates elicited using magnitude production: habitual, three slower rates, and three faster rates. Acoustic measures of speech intensity, cepstral peak prominence, and fundamental frequency were measured as a function of speech rate and group. Overall, slower rates of speech were associated with differential effects on phonation across the four groups. While all talkers spoke at a lower pitch in slow speech, younger talkers showed increases in speech intensity and cepstral peak prominence, while talkers with PD and STN-DBS showed the reverse pattern. Talkers with PD without STN-DBS and older healthy controls behaved in between these two extremes. At faster rates, all groups uniformly demonstrated increases in cepstral peak prominence. While speech rate reductions are intended to promote positive changes in articulation to compensate for speech deficits in dysarthria, the present results highlight that undesirable changes may be invoked across other subsystems, such as at the laryngeal level. In particular, talkers with STN-DBS, who often demonstrate speech deterioration following DBS surgery, demonstrated more phonatory detriments at slowed speech rates. Findings have implications for speech rate candidacy considerations and speech motor control processes in PD.
Human brain activity and functional connectivity associated with verbal long-term memory consolidation across 1 month
Authors: Tallman Catherine W. , Luo Zhishang , Smith Christine N.
Published: February 2024

Introduction

Declarative memories are initially dependent on the hippocampus and become stabilized through the neural reorganization of connections between the medial temporal lobe and neocortex. The exact time-course of these neural changes is not well established, although time-dependent changes in retrieval-related brain function can be detected across relatively short time periods in humans (e.g., hours to months).

Methods

In a study involving older adults with normal cognition (N = 24), we investigated changes in brain activity and functional connectivity associated with the long-term memory consolidation of verbal material over one month. Participants studied fact-like, three-word sentences at 1-month, 1-week, 1-day, and 1-hour intervals before a recognition memory test inside an MRI scanner. Old/new recognition with confidence ratings and response times were recorded. We examined whole-brain changes in retrieval-related brain activity, as well as functional connectivity of the hippocampus and ventromedial prefrontal cortex (vmPFC), as memories aged from 1 hour to 1 month. Secondary analyses minimized the effect of confounding factors affected by memory age (i.e., changes in confidence and response time or re-encoding of targets).

Results

Memory accuracy, confidence ratings, and response times changed with memory age. A memory age network was identified where retrieval-related brain activity in cortical regions increased or decreased as a function of memory age. Hippocampal brain activity in an anatomical region of interest decreased with memory age. Importantly, these changes in retrieval-related activity were not confounded with changes in activity related to concomitant changes in behavior or encoding. Exploratory analyses of vmPFC functional connectivity as a function of memory age revealed increased connectivity with the posterior parietal cortex, as well as with the vmPFC itself. In contrast, hippocampal functional connectivity with the vmPFC and orbitofrontal cortex decreased with memory age.

Discussion

The observed changes in retrieval-related brain activity and functional connectivity align with the predictions of standard systems consolidation theory. These results suggest that processes consistent with long-term memory consolidation can be identified over short time periods using fMRI, particularly for verbal material.
Effects of acute and long-term mindfulness on neural activity and the conflict resolution component of attention
Authors: Elcin Dehan , Velasquez Miguel , Colombo Paul J.
Published: February 2024

Mindfulness practices have been linked to enhanced attention and conflict resolution abilities. While much research has focused on the long-term effects of mindfulness, the immediate impact of a single session has been less studied. This study recruited 20 experienced meditators and 20 novices and assigned them to a mindfulness or a control condition. They completed a Stroop Task to measure cognitive conflict resolution before and after the intervention, with brain activity monitored via functional near-infrared spectroscopy (fNIRS). Novices showed an age-related decline in conflict resolution ability, while experienced meditators didn’t. Initially, both groups showed similar Stroop performance, but experienced meditators had greater brain activation in the left dorsolateral prefrontal cortex (DLPFC). Post-intervention, novices in the breath count task became more similar to experienced meditators in their neural activity during conflict resolution. Our findings indicate that long-term mindfulness experience may protect against age-related decline in cognitive conflict resolution speed, and may alter neural processing of cognitive conflict resolution.
The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review
Authors: Wen Xin , Dong Hao , Zou Wei
Published: February 2024

Intracerebral hemorrhagic stroke, characterized by acute hemorrhage in the brain, has a significant clinical prevalence and poses a substantial threat to individuals’ well-being and productivity. Recent research has elucidated the role of gut microorganisms and their metabolites in influencing brain function through the microbiota-gut-brain axis (MGBA). This article provides a comprehensive review of the current literature on the common metabolites, short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), produced by gut microbiota. These metabolites have demonstrated the potential to traverse the blood–brain barrier (BBB) and directly impact brain tissue. Additionally, these compounds have the potential to modulate the parasympathetic nervous system, thereby facilitating the release of pertinent substances, impeding the buildup of inflammatory agents within the brain, and manifesting anti-inflammatory properties. Furthermore, this scholarly analysis delves into the existing dearth of investigations concerning the influence of gut microorganisms and their metabolites on cerebral functions, while also highlighting prospective avenues for future research.
Genomic amplifications identified by circulating tumor DNA analysis guide prognosis in metastatic castration-resistant prostate cancer
Authors: Dincman Toros A. , Karam Joseph A. Q. , Giordano Antonio , Li Hong , Drusbosky Leylah M. , Gourdin Theodore S. , Howe Philip H. , Lilly Michael B.
Published: February 2024

Purpose

Analysis of circulating tumor DNA (ctDNA) in patients with metastatic prostate cancer (mPC) provides an opportunity to identify and monitor genomic alterations during a patient’s treatment course. We evaluated whether the presence of specific gene amplifications (GAs) and plasma copy number (PCN) alterations are associated with disease features.

Methods

This is a single-institution retrospective study of patients with mPC who underwent ctDNA profiling using Guardant360® (Guardant Health Inc.). This test identifies single nucleotide variants (SNVs) and GAs of select genes by next-generation sequencing. A total of 155 men with mPC were studied. Patients were stratified by GA status. The Kaplan-Meier method and multivariate cox regression models were used to estimate overall survival (OS) or failure-free survival (FFS) from either the date of GA detection or the initiation of systemic therapy. The chi-square test was used to evaluate associations between clinical factors and GAs.

Results

The presence of liver and/or lung metastases was associated with GAs of BRAF, CDK6, PI3KCA, and FGFR1. Survival analyses were completed on a subset of 83 patients with metastatic castration-resistant prostate cancer (mCRPC). Median OS was improved in patients with 1 GA compared to patients with ≥2 GAs, whether determined from the date of initial GA(s) detection (14.9 mo vs. 8.9 mo) or date of therapy initiation nearest to GA detection (16.7 mo vs. 9.0 mo). Patients without GAs had not reached median OS. Patients with androgen receptor (AR) GA only were also found to have better median OS compared to patients with AR GA plus at least one other additional GA (19.3 mo vs. 8.9 mo). Patients with PIK3CA GA had significantly lower median OS compared to patients with GAs that did not have a PIK3CA GA (5.9 mo vs. 16.0 mo). In patients with AR and/or MYC GA(s), median OS improved in those with reduced AR or MYC PCN during therapy compared to those without such a reduction (25.1 mo vs. 15.9 mo).

Conclusions

The association of select GAs with survival provides an additional tool for assessing mCRPC prognosis and informing management. Serial monitoring of ctDNA GAs is also useful to guide prognosis and therapeutic response.
Targeted therapy or immunotherapy in BRAF-mutated metastatic melanoma: a Spanish center’s decade of experience
Authors: Sun Chen , España Sofia , Richarz Nina , Solé-Blanch Carme , Boada Aram , Martinez-Cardús Anna , Chu Alan , Liu Zongwen , Manzano Jose Luis
Published: February 2024

Background

Targeted therapies and immunotherapy are currently considered the mainstay first-line treatment for advanced BRAF-mutated melanoma. However, the impact of treatment (targeted therapy and immunotherapy) and the prognostic factors are still not clear.

Material and methods

Medical records of 140 patients diagnosed with advanced melanoma between 2011 and 2021 were retrospectively reviewed to extract demographic, BRAF status, treatment, performance status, and survival data. ORR, PFS, and OS were compared between patients diagnosed with advanced melanoma and treated with first-line IT or BRAF/MEKi. The prognostic factors were assessed using Cox regression models.

Results

In all patients and those treated with immunotherapy, we did not find any effect of BRAF status on ORR, PFS, or OS. In patients with BRAF-mutated melanoma, ORR was 43.8% vs. 70% (P=0.04), PFS was 19.2 vs. 11.5 months (p=0.22), and OS was 33.4 vs. 16.4 months for the immunotherapy and targeted therapy groups, respectively (P=0.04). ECOG, presence of brain metastases, and high LDH level from initiation of first-line treatment were all associated with differences in PFS and OS.

Conclusion

Patients with advanced BRAF-mutated melanoma treated with first-line immunotherapy had a significantly longer PFS and OS than those treated with first-line BRAF/MEKi; however, first-line BRAF/MEKi treatment had a significantly higher ORR than first-line immunotherapy.
Case report: Synchronous tumors of the female reproductive tract in systemic lupus erythematosus: report of two cases and review of the literature
Authors: Wang Ling , Zhang Qin , Shi Nan , Wang Jiaxi , Song Shuang , Yang Huadi , Chen Xingbei
Published: February 2024

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors.

Case presentation

We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer.

Conclusion

The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.
Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study
Authors: Azari Mojtaba , Barkhordar Maryam , Bahri Tanaz , Rad Soroush , Kamranzadeh Fumani Hosein , Mousavi Seied Asadollah , Tavakoli Shiraji Sahar , Azari Morteza , Shafaroudi Parisa , Vaezi Mohammad
Published: February 2024

Introduction

Donor choosing remains to play a pivotal role in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous criteria beyond HLA compatibility impact the selection of a suitable donor.

Methods

We evaluated the effect of donor parity on transplant outcomes in a large homogeneously treated population that received an HLA-matched allo-HSCT between 2010 and 2021 at our center. All patients were transplanted from a peripheral blood stem cell source following a myeloablative Busulfan-based conditioning and an identical protocol for graftversus-host disease (GVHD) prophylaxis regimen.

Results

A total of 1103 allo-HSCT recipients were included. 188 (17%) had transplants from parous female donors, whereas 621 (56.30%) and 294 (26.70%) received transplants from male and nulliparous female donors, respectively. HSCTs from parous female donors compared to male and nulliparous females were associated with a significantly higher incidence of grade III-IV acute (a) GVHD (55.27% vs. 11.34 and 10.84%) and extensive chronic (c) GVHD (64.32% vs. 15.52 and 13.65%), as well as lower relapse incidence (RI).

Discussion

This study finds that while parous female donors are associated with higher incidences of grade III-IV aGVHD and extensive cGVHD post-allo-HSCT, the advantages, such as a lower RI, outweigh the risks. The results of our study provide valuable insights for donor selection.
BioPrev-C – development and validation of a contemporary prostate cancer risk calculator
Authors: Hermanns Thomas , Wettstein Marian S. , Kaufmann Basil , Lautenbach Noémie , Kaufmann Ernest , Saba Karim , Schmid Florian A. , Hötker Andreas M. , Müntener Michael , Umbehr Martin , Poyet Cédric
Published: February 2024

Objectives

To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy.

Materials and methods

Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC).

Results

Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability.

Conclusion

BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.
Case report: BCR-ABL-positive acute lymphoblastic leukemia with bone destruction: a treatment dilemma
Authors: Lijun Shi , Zhongrui Ma , Li Wei , Xia Yu , Wei Jiang , Yaning Pan
Published: February 2024

Although bone destruction and hypercalcemia without acute peripheral blast BCR-ABL-positive acute lymphoblastic leukemia (ALL) have been reported in children, they are rare in adults. Herein, we describe a case of BCR-ABL positive ALL with a triploid karyotype, WT1, and CDKN2A mutations with hypercalcemia and bone destruction as the first manifestations. Complete remission (CR) was achieved by induction chemotherapy. BCR-ABL turned negative after treatment with dasatinib. However, computed tomography and whole-body bone scan showed extensive bone destruction. Additionally, bone biopsy showed leukemic infiltration. After treatment with dasatinib and VMCP, leukemia recurred with positive BCR-ABL. The T315I mutation occurred. The patient was surgically diagnosed with calculous cholecystitis and achieved CR2 by postoperative orebatinib and VP regimens. Later, the patient died due to a severe pulmonary infection. BCR-ABL-positive ALL with bone destruction is rare and difficult to control using tyrosine kinase inhibitor chemotherapy alone. Therefore, further exploration of more effective treatments is needed.
Self-medication with antibiotics in Georgian population
Authors: Darakhvelidze Marina , Kalandadze Iagor , Mirzikashvili Nino , Tsereteli David , Zakareishvili Natalia , Ketchakmadze Ivane
Published: February 2024

Background: Self-medication with antibiotics is a global phenomenon and a potential contributor to human pathogen resistance to antibiotics. It involves obtaining medication without a prescription, taking medicines based on the advice of friends and relatives, or previous treatment experience. Self-medication is common in both developed and developing countries; however, the prevalence of self-medication is higher in developing countries. The aim of this study was to determine the characteristics of antimicrobial self-medication in Georgia and its potential to influence the overall situation regarding antimicrobial consumption in the country.

Methods: We conducted a cross-sectional study using a random sampling method and developed a self-administered questionnaire to collect the data. The survey was conducted via the Internet using the Google Forms platform.

Results: The overall number of respondents was 742 adults living in Georgia. The results showed that 23.8% (n = 177) of adults had consumed antibiotics without a doctor’s prescription, and 12.7% (n = 94) confirmed the use of antibiotics by their own decision to treat minor family members. The total prevalence of self-medication was 32.6%. The data analysis revealed a correlation between factor F1 (“personal experience”) and gender (p = 0.042, F = 2.6), and between age and factor F2 (“lack of trust in medical practitioners”) (p = 0.047, F = 2.691). The correlation was stronger among young adults (aged 18–24) and senior adults (aged 60+). The correlation between the level of education and factor F2 was stronger (p = 0.00; F1 = 7.9) than with factor F1 (p = 0.04; F = 2.2).

Conclusion: Self-medication is prevalent in Georgia; pharmacies are the main sources of antimicrobials. No correlation was found between factor F2, pertaining to “lack of trust in medical practitioners” and gender, between age and factor F1, linked to “personal experience.” The study uncovered a lack of knowledge about self-medication with antibiotics and emphasized the importance of public awareness campaigns and implementing effective interventions to regulate the sales of antibiotics without a doctor’s prescription.
Established and emerging GABAA receptor pharmacotherapy for epilepsy
Authors: Richardson Robert J. , Petrou Steven , Bryson Alexander
Published: February 2024

Drugs that modulate the GABAA receptor are widely used in clinical practice for both the long-term management of epilepsy and emergency seizure control. In addition to older medications that have well-defined roles for the treatment of epilepsy, recent discoveries into the structure and function of the GABAA receptor have led to the development of newer compounds designed to maximise therapeutic benefit whilst minimising adverse effects, and whose position within the epilepsy pharmacologic armamentarium is still emerging. Drugs that modulate the GABAA receptor will remain a cornerstone of epilepsy management for the foreseeable future and, in this article, we provide an overview of the mechanisms and clinical efficacy of both established and emerging pharmacotherapies.
Investigation on different materials after pulsed high field conditioning and low-energy H- irradiation
Authors: Serafim C. , Peacock R. , Calatroni S. , Djurabekova F. , Fontenla A. T. Perez , Wuensch W. , Sgobba S. , Grudiev A. , Lombardi A. , Sargsyan E. , Ramberger S. , Bellodi G.
Published: February 2024

During operation, the radio-frequency quadrupole (RFQ) of the LINAC4 at CERN is exposed to high electric fields, which can lead to vacuum breakdown. It is also subject to beam loss, which can cause surface modification, including blistering, which can result in reduced electric field holding and an increased breakdown rate. First, experiments to study the high-voltage conditioning process and electrical breakdown statistics have been conducted using pulsed high-voltage DC systems in order to identify materials with high electric field handling capability and robustness to low-energy irradiation. In this paper, we discuss the results obtained for the different materials tested. To complement these, an investigation of their metallurgical properties using advanced microscopic techniques was done to observe and characterize the different materials and to compare results before and after irradiation and breakdown testing.
Deep learning based assessment of hemodynamics in the coarctation of the aorta: comparison of bidirectional recurrent and convolutional neural networks
Authors: Versnjak Jakob , Yevtushenko Pavlo , Kuehne Titus , Bruening Jan , Goubergrits Leonid
Published: February 2024

The utilization of numerical methods, such as computational fluid dynamics (CFD), has been widely established for modeling patient-specific hemodynamics based on medical imaging data. Hemodynamics assessment plays a crucial role in treatment decisions for the coarctation of the aorta (CoA), a congenital heart disease, with the pressure drop (PD) being a crucial biomarker for CoA treatment decisions. However, implementing CFD methods in the clinical environment remains challenging due to their computational cost and the requirement for expert knowledge. This study proposes a deep learning approach to mitigate the computational need and produce fast results. Building upon a previous proof-of-concept study, we compared the effects of two different artificial neural network (ANN) architectures trained on data with different dimensionalities, both capable of predicting hemodynamic parameters in CoA patients: a one-dimensional bidirectional recurrent neural network (1D BRNN) and a three-dimensional convolutional neural network (3D CNN). The performance was evaluated by median point-wise root mean square error (RMSE) for pressures along the centerline in 18 test cases, which were not included in a training cohort. We found that the 3D CNN (median RMSE of 3.23 mmHg) outperforms the 1D BRNN (median RMSE of 4.25 mmHg). In contrast, the 1D BRNN is more precise in PD prediction, with a lower standard deviation of the error (±7.03 mmHg) compared to the 3D CNN (±8.91 mmHg). The differences between both ANNs are not statistically significant, suggesting that compressing the 3D aorta hemodynamics into a 1D centerline representation does not result in the loss of valuable information when training ANN models. Additionally, we evaluated the utility of the synthetic geometries of the aortas with CoA generated by using a statistical shape model (SSM), as well as the impact of aortic arch geometry (gothic arch shape) on the model’s training. The results show that incorporating a synthetic cohort obtained through the SSM of the clinical cohort does not significantly increase the model’s accuracy, indicating that the synthetic cohort generation might be oversimplified. Furthermore, our study reveals that selecting training cases based on aortic arch shape (gothic versus non-gothic) does not improve ANN performance for test cases sharing the same shape.
Differential molecular biomarker expression in corals over a gradient of water quality stressors in Maunalua Bay, Hawaii
Authors: Tisthammer Kaho H. , Martinez Jonathan A. , Downs Craig A. , Richmond Robert H.
Published: February 2024

Coral reefs globally face unprecedented challenges from anthropogenic stressors, necessitating innovative approaches for effective assessment and management. Molecular biomarkers, particularly those related to protein expressions, provide a promising avenue for diagnosing coral health at the cellular level. This study employed enzyme-linked immunosorbent assays to evaluate stress responses in the coral Porites lobata along an environmental gradient in Maunalua Bay, Hawaii. The results revealed distinct protein expression patterns correlating with anthropogenic stressor levels across the bay. Some proteins, such as ubiquitin and Hsp70, emerged as sensitive biomarkers, displaying a linear decrease in response along the environmental gradient, emphasizing their potential as indicators of stress. Our findings highlighted the feasibility of using protein biomarkers for real-time assessment of coral health and the identification of stressors. The identified biomarkers can aid in establishing stress thresholds and evaluating the efficacy of management interventions. Additionally, we assessed sediment and water quality from the inshore areas in the bay and identified organic contaminants, including polycyclic aromatic hydrocarbons and pesticides, in bay sediments and waters.