bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Plane 3-Dimensional Isotropic Spin-Echo Magnetic Resonance Imaging Reconstructions of Shoulder Exhibit Superior Correlation to Surgical Findings Than 2-Dimensional Dixon Multiplanar Magnetic Resonance Imaging
Authors: Haider Shamrez , Cabrera Alison , Thakur Uma , Xi Yin , Chhabra Avneesh
Published: November 2023

Objective

The aim of the study is to evaluate concordance of multiplanar 2-dimensional magnetic resonance imaging (2D-MRI) versus 3D isotropic MRI for rotator cuff and labral tears with the reference standard of arthroscopic surgical findings.

Methods

It was an institutional review board–approved retrospective single-center study of consecutive preoperative patients with isotropic 3D-MRI on 3-Tesla scanners, multiplanar 2D-MRI, and shoulder arthroscopy. Scapular plane-oriented contiguous multiplanar reconstructions of 3D-images were evaluated by 2 experienced fellowship-trained musculoskeletal radiologists. Variables included the following: labral tear presence and rotator-cuff tear Ellman grade, thickness, and width. Sensitivities (Sen) and specificities (Spe) were calculated for binary variables. Mean squared errors (MSE) were calculated for ordinal variables. Lower MSE indicated higher concordance.

Results

Seventy-two patients (43 female) with a mean age of 50.75 ± 9.76 years were evaluated. For infraspinatus-tear presence, 3D-MRI showed higher sensitivity (0.96) and specificity (0.68) than 2D-MRI (Sen = 0.85, Spe = 0.32) (Psen= 0.005,Pspe= 0.002). For subscapularis-tear presence, 3D-MRI showed higher sensitivity (0.94) and specificity (0.73) compared with 2D-MRI (Sen = 0.83, Spe = 0.56) (Psen= 0.02,Pspe= 0.04). For supraspinatus-tear presence, there was no significant difference between 3D-MRI (Sen =0.96, Spe = 0.67) compared with 2D-MRI (Sen = 0.98, Spe = 0.83) (Psen= 0.43,Pspe= 0.63). For infraspinatus-tear thickness, 3D-MRI showed lower MSE (0.35) compared with 2D-MRI MSE (0.82) (P= 0.01). For subscapularis-tear thickness, 3D-MRI had lower MSE (0.31) compared with 2D-MRI MSE (0.51) (P= 0.007). However, no difference noted for supraspinatus-tear thickness when comparing 3D-MRI MSE (0.39) and 2D-MRI MSE (0.51) (P= 0.49). For labral-tear presence, 3D-MRI had a lower MSE (0.20) compared with 2D-MRI MSE (0.57) (P< 0.001).

Conclusions

Three-dimensional MRI of the shoulder is time efficient with a shorter acquisition time and exhibits comparable with superior correlation to surgical findings than 2D-MRI for detection of labral tears and some rotator cuff tears. Three-dimensional MRI may be used in place of traditional 2D-MRI in detection of soft-tissue shoulder injury in centers equipped to do so.
Effects of the Training Data Condition on Arterial Spin Labeling Parameter Estimation Using a Simulation-Based Supervised Deep Neural Network
Authors: Ishida Shota , Isozaki Makoto , Fujiwara Yasuhiro , Takei Naoyuki , Kanamoto Masayuki , Kimura Hirohiko , Tsujikawa Tetsuya
Published: November 2023

Objective

A simulation-based supervised deep neural network (DNN) can accurately estimate cerebral blood flow (CBF) and arterial transit time (ATT) from multidelay arterial spin labeling signals. However, the performance of deep learning depends on the characteristics of the training data set. We aimed to investigate the effects of the ground truth (GT) ranges of CBF and ATT on the performance of the DNN when training data were prepared using arterial spin labeling signal simulation.

Methods

Deep neural networks were individually trained using 36 patterns of the training data sets. Simulation test data (1,000,000 points), 17 healthy volunteers, and 1 patient with moyamoya disease were included. The simulation test data were used to evaluate accuracy, precision, and noise immunity of the DNN. The best-performing DNN was determined by the normalized mean absolute error (NMAE), normalized root mean squared error (NRMSE), and normalized coefficient of variation over repeated training (CVNet). Cerebral blood flow and ATT values and their histograms were compared between the GT and predicted values. For the in vivo data, the dependency of the predicted values on the GT ranges was visually evaluated by comparing CBF and ATT maps between the best-performing DNN and the other DNNs. Moreover, using the synthesized noisy images, noise immunity was compared between the best-performing DNN based on the simulation study and a conventional method.

Results

The simulation study showed that a network trained by the GT of CBF and ATT in the ranges of 0 to 120 mL/100 g/min and 0 to 4500 milliseconds, respectively, had the highest performance (NMAECBF, 0.150; NRMSECBF, 0.231; CVNET CBF, 0.028; NMAEATT, 0.158; NRMSEATT, 0.257; and CVNET ATT, 0.028). Although the predicted CBF and ATT varied with the GT range of the training data sets, the appropriate settings preserved the accuracy, precision, and noise immunity of the DNN. In addition, the same results were observed in in vivo studies.

Conclusions

The GT ranges to prepare the training data affected the performance of the simulation-based supervised DNNs. The predicted CBF and ATT values depended on the GT range; inappropriate settings degraded the accuracy, whereas appropriate settings of the GT range provided accurate and precise estimates.
Proteomic Analysis Reveals Potential Exosomal Biomarkers in Patients With Sporadic Alzheimer Disease
Authors: Plaschke Konstanze , Kopitz Jürgen , Gebert Johannes , Wolf Nadine D. , Wolf Robert Christian
Published: November 2023

Background:

Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD.

Materials and Methods:

In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics.

Results:

Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins.

Conclusions:

These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.
Novel APOE Mutation in a Moroccan Subject Suffering from Alzheimer Disease
Authors: Razouqi Youssef , El Bouchikhi Ihssane , El-Abid Hassan , Baammi Soukayna , Nedbour Ayoub , Touhami Ahami Ahmed Omar , El Allali Achraf , Bouguenouch Laila
Published: November 2023

Alzheimer disease (AD) is a major public health concern worldwide. It is a severe neurodegenerative disease that primarily affects the elderly and causes significant brain cell death. According to the most complete scientific research, the APOE gene, which encodes the APOE protein, maybe the key to identifying the likely cause of delayed AD. The development of plaques and tangles, as well as increased amyloid (amyloid-β) levels and deposition, have been linked to APOE4. Pathogenic mutations in this gene can impact how beta-amyloid deposits and how they are cleared from the body. In this study, we report a novel pathogenic mutation, Arg160Leu, in APOE that was identified in a Moroccan patient. The magnetic resonance imaging of this 67-year-old woman revealed hippocampal shrinkage, and the results of her cognition testing revealed that she is suffering from severe AD. The current study may increase awareness of the genetic risk factors for AD caused by APOE4 mutations.
Characterization of Multidrug Resistant serogroup 19 Streptococcus pneumoniae isolated from the healthy children below five years of age in Indonesia
Authors: Salsabila Korrie , Winarti Yayah , Paramaiswari Wisiva Tofriska , Tafroji Wisnu , Putri Hanifah Fajri Maharani , Daningrat Wa Ode Dwi , Wulandari I Gusti Ayu Inten , Soebandrio Amin , Safari Dodi
Published: November 2023

We investigated the resistance genes, pilus islet, biofilm formation ability, and sequence types of multidrug-resistant Streptococcus pneumoniae (MDRSP) isolated from the healthy children below 5 years of age in Indonesia. In all, 104 archived MDRSP isolates from previous carriage study in Indonesia in 2016-2019 were screened for the presence of antibiotic resistance genes and the rrgC (pilus islet 1) and pitB (pilus islet 2) genes. Multilocus sequence typing and biofilm formation was determined by PCR-Sequencing and the ability of cells to adhere to the walls, respectively. Results have shown that the mefA, ermB, and tetM genes were found in 93%, 52%, and 100% of MDRSP isolates respectively. The insertion of arginine, proline, and Ile-100-Leu were the most common mutations in the folA and folP genes. Pilus islet 1 and type 2 were discovered in 93% and 82% of MDRSP isolates respectively. The MDRSP isolates showed no biofilm formation ability (64%), and five out of ten strains of MDRSP strains were ST1464. This finding can be used to provide further considerations in implementing and monitoring pneumococcal vaccination in Indonesia.
Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains
Authors: Bouzidi Hawa Sophia , Driouich Jean-Sélim , Klitting Raphaëlle , Bernadin Ornéllie , Piorkowski Géraldine , Amaral Rayane , Fraisse Laurent , Mowbray Charles E. , Scandale Ivan , Escudié Fanny , Chatelain Eric , Lamballerie Xavier de , Nougairède Antoine , Touret Franck
Published: November 2023

Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid®) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova®), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvirin vitrofollowing repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutantsin vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation, in the multi-passage strain, confers a high level ofin vivoresistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova® in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness.
Severe acute myositis and myocarditis upon initiation of six-weekly Pembrolizumab post-COVID-19 mRNA vaccination
Authors: Watson Robert A. , Ye Weiyu , Taylor Chelsea A. , Jungkurth Elsita , Cooper Rosalin , Tong Orion , James Tim , Shine Brian , Hofer Monika , Jenkins Damian , Pell Robert , Ieremia Eleni , Jones Stephanie , Maldonado-Perez David , Roberts Ian S.D. , Coupe Nicholas , Middleton Mark R. , Payne Miranda J. , Fairfax Benjamin P.
Published: November 2023

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within one month of receiving the initial cycle of the anti-PD-1 drug Pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognising viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.
Risk Factor Profile in Different Subtypes of Acute Ischemic Stroke: A Prospective Observational Study
Authors: Chaudhari Rajkamal , Parikh Amrita , Dalal Yagnya , Desai Dev , Parikh Ami
Published: November 2023

Introduction

Acute ischemic stroke is a major subtype of acute stroke. More than 65% of stroke-related deaths occur in developing countries. Various modifiable and non-modifiable risk factors are associated with the stroke. TOAST classification categorizes ischemic stroke into five etiologic subgroups.

Aims

To identify subtypes of acute ischemic stroke and compare the influence of various risk factors on them.

Methodology

A prospective observational study was conducted in a tertiary care teaching hospital. 200 consecutive patients diagnosed as having acute ischemic stroke were randomly enrolled. Patients were categorized into 3 groups-Group A: 18-39 years (17%); Group B: 40-60 years (20%) and Group C: >60 years (63%). Stroke subtypes were ascertained using TOAST classification. Data analysis was done. For categorical variables, data values were represented as numbers and percentages. A chi-square test was applied to find the level of significance. p value<0.05 was considered significant.

Results

The study included 136 men and 64 women. Overall male dominance (Male: Female = 2.125:1), while in Group A, strong female dominance (Male: Female = 1:4.67) was observed. The commonest subtype was embolism (29.4%) in Group A, and small vessel disease in Group B, and C ((30% & 46.03% respectively). Hypertension was the commonest risk factor (62%). A higher incidence of hypertension was found in Group A (73.02%, p = 0.002), dyslipidemia in Group B (45%, p = 0.004), valvular heart disease (29.4%, p = 0.00001), and atrial fibrillation (29.4%, p = 0.005) in Group-C. Smoking and diabetes mellitus were strongly related to the male gender (p = 0.000001, p=0.002 respectively) and valvular heart disease to the female gender (p= 0.0002).

Conclusions

Awareness of risk factors and lifestyle modifications may have a bearing on stroke prevention. Cardiovascular risk factors in young patients mandate the need for robust prevention and screening.
Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections
Authors: Lee Sung-Gwon , Furth Priscilla A. , Hennighausen Lothar , Lee Hye Kyung
Published: November 2023

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, and its subsequent variants has underscored the importance of understanding the host-viral molecular interactions to devise effective therapeutic strategies. A significant aspect of these interactions is the role of alternative splicing in modulating host responses and viral replication mechanisms. Our study sought to delineate the patterns of alternative splicing of RNAs from immune cells across different SARS-CoV-2 variants and vaccination statuses, utilizing a robust dataset of 190 RNA-seq samples from our previous studies, encompassing an average of 212 million reads per sample. We identified a dynamic alteration in alternative splicing and genes related to RNA splicing were highly deactivated in COVID-19 patients and showed variant- and vaccination-specific expression profiles. Overall, Omicron-infected patients exhibited a gene expression profile akin to healthy controls, unlike the Alpha or Beta variants. However, significantly, we found identified a subset of infected individuals, most pronounced in vaccinated patients infected with Omicron variant, that exhibited a specific dynamic in their alternative splicing patterns that was not widely shared amongst the other groups. Our findings underscore the complex interplay between SARS-CoV-2 variants, vaccination-induced immune responses, and alternative splicing, emphasizing the necessity for further investigations into these molecular cross-talks to foster deeper understanding and guide strategic therapeutic development.
Using e-vouchers to promote use of a family planning call center: A comparative interruptive time series analysis
Authors: Meekers Dominique , Turk Lynn Abu , Olutola Olaniyi
Published: November 2023

Introduction

This study examines the effectiveness of an e-voucher campaign to promote the use of a toll-free family planning call center (Honey&Banana), which is measured by the number of calls received by the call center.

Methods

A comparative interrupted time series design is used to measure the effect of the e-voucher campaign on the call volume. The study design presumes that without the e-voucher campaign, the intervention and control groups would have parallel trends in terms of the number of calls received. The difference between the actual and anticipated number of calls received is used to estimate the effect of the campaign.

Results

Before the e-voucher campaign, the monthly trend in the number of calls for family planning information in the intervention and control groups followed a similar pattern. As soon as the campaign was launched, the call center experienced a seven-fold increase in the number of family planning requests that were received from callers in the intervention zone, from under 400 calls per month to about 3,000 calls per month. No comparable increase occurred for the control zone. We estimate that the e-voucher campaign resulted in a net gain of over 12,000 requests for family planning information. When the campaign ended, the number of calls from the intervention zone decreases, but at least temporarily remained above the pre-intervention levels.

Discussion

Earlier studies demonstrated that e-voucher campaigns can be effective for increasing use of smoking cessation hotlines. This study expands the evidence base by demonstrating the effectiveness of e-vouchers for increasing demand for family planning information hotlines. Additional research is needed to assess the long-term effects of such e-voucher campaigns, and to determine the extent to which increased use of family planning hotlines translates into improved family planning outcomes.
An Exploration of the Mental Health impact among Menopausal Women: The MARIE Project Protocol (International Arm)
Authors: Delanerolle Gayathri , Cavalini Heitor , Taylor Julie , Hinchliff Sharron , Talaulikar Vikram , Zingela Zukiswa , Toh Teck-Hock , Wong Xiu-Sing , Lee Kim-Yen , Lee Jeffrey Soon-Yit , Pati Sanghamitra , Rathnayake Nirmala , Sundarappeuma Thamudi , Mudalige Tharanga , Dasanayake Lanka , Dasanayake Damayanthi , Pathiraja Vindya , Herath Prasanna , Kurmi Om , Shetty Ashish , Irfan Muhammed , Kareem Rabia , Kemp Helen , Palo Subrata Kumar , Eleje George Uchenna , Vwalika Bellington , Zhao Wenjing , Shi Jian Qing , Phiri Peter
Published: November 2023

Introduction

Menopause is characterised by the ending of the menstrual cycle as part of a natural process. However, menopause can also be caused by other health conditions, such as premature ovarian failure or cancers that may have led to an oophorectomy or a radical hysterectomy. The physiological and psychological mechanisms linked to menopause across all age groups, races and ethnicities are not well understood. The paucity of data could reduce the advancement of optimal clinical practice, leading to reduced quality of life for women. To better explore and assess menopause, we have designed theMenopAuse mental hEalth Rating (MARiE)tool.

Methods

We will conduct a prospective mixed methods study using two workstreams of WP2a and WP2b among in women and trans-men ≥18 years old that are experiencing perimenopause, menopause or post-menopause among an array of ethnicities and races. WP2a will involve a number of validated clinical assessments of Hospital Anxiety and Depression Scale, Insomnia Severity Index Scale, Menopause Rating Scale, Greene Climacteric Scale, Health Related Quality of Life, Quebec Pain Disability Scale, and Burnout Assessment Tool will be administered digitally using the Qualtrex platform. WP2b will assess the feasibility of using a novel tool called MARiE to report face validity and efficacy.

Ethics approval

Research Ethics approval reference for this study in the UK is 22/EE/0159. As required, country-specific approvals have been obtained and continue to be secured.

Dissemination

The study findings will be made available using a peer-review publication journal, workshops and conferences.
Participant perceptions of disability training for health workers: a qualitative study in Ghana
Authors: Rotenberg Sara , Ryan Sara , Ziebland Sue , Ganle John
Published: November 2023

Introduction

Disabled people often report poor treatment by health workers, and health workers often report wanting more training about how to care for disabled people. However, existing disability training for health workers is usually delivered in one-off interventions, with little follow-up, evaluation, and focus on long-term learning. This insufficiency makes it important to understand how disability training for health workers can be more effective. Therefore, we interviewed stakeholders involved in an existing disability training intervention in Ghana to understand how disability training for health workers could be improved.

Methods

In-depth, qualitative interviews were conducted with 33 people involved in disability training (either as trainers or trainees) in Ghana. Data were analysed using thematic analysis.

Results

Participants spoke about the challenges with existing training, namely how the current approach was insufficient, the consequences of informality in running training and the need for more sign language instruction. Several participants suggested improvements for training, including having external motivation (i.e., professional development credits, monetary benefits, etc.), more collaborative initiatives across institutions and government, and curriculum integration. We developed a theory of change model to show how different components of disability training support learning.

Discussion

These results show that disability training for health workers is important and that there is scope to refine and standardize training. In particular, the findings demonstrate how future initiatives to train health workers can be developed and implemented. They also emphasize the need to solicit perspectives from individuals who have experienced training in order to improve future iterations.
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants
Authors: Wang Qian , Guo Yicheng , Bowen Anthony , Mellis Ian A. , Valdez Riccardo , Gherasim Carmen , Gordon Aubree , Liu Lihong , Ho David D.
Published: November 2023

COVID-19 vaccines have recently been updated with the spike protein of SARS-CoV-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,504-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.
Planning for the End at the Beginning: A Lesson in Sharing Research Findings of a Community-based COVID-19 Seroprevalence Survey
Authors: Trolard Anne M. , Hickner Emily , Anwuri Victoria V. , Johnson Kimberly J. , Goss Charles W. , Cohen Rachel E. , Donaldson Kate , Geng Elvin , Maricque Brett B.
Published: November 2023

Introduction

Sharing research findings with participants is important but challenging. We evaluated a plan to share findings with participants of a COVID-19 seroprevalence project.

Methods

An electronic survey was distributed to participants after completion of the project to determine reach of planned coverage of the findings.

Results

Most respondents (80% n=428) had not seen the coverage; but nearly all (90%, n=388) wanted to see the findings. Participants identified a brief visual report as their preferred avenue. A second follow-up survey found that 99% of those who read the report approved.

Discussion

When researchers alone create a plan to share project findings, efforts may not reach nor be in the format desired by participants.

Conclusions

This work can serve as a model for collaborating with community to disseminate public health data.
Sociodemographic and clinical risk factors for suicidal ideation and suicide attempt in functional/dissociative seizures and epilepsy: a large cohort study
Authors: Faiman Irene , Hodsoll John , Jasani Iman , Young Allan H. , Shotbolt Paul
Published: November 2023

Objective

To identify risk factors for first episodes of suicidal ideation and suicide attempt in people with functional/dissociative seizures (FDS) or epilepsy.

Methods

Retrospective cohort study from the UK’s largest tertiary mental health care provider, with linked national admission data from the Hospital Episode Statistics (HES). Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01/01/2007 and 18/06/2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (ICD-10 X60-X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models.

Results

In both groups, ethnic minorities had significantly reduced odds of hospitalisations following a suicide attempt (OR: 0.45 – 0.49). Disorder-specific risk factors were gender, age, and comorbidity profile. In FDS, both genders had similar risk of suicidality; younger age was a risk factor for both outcomes (OR: 0.16 – 1.91) and a diagnosis of Depression or Personality Disorders was associated with higher odds of reporting suicidal ideation (OR: 1.91 and 3.01 respectively). In epilepsy, females had higher odds of being hospitalised following suicide attempt (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88 – 1.06). A Substance Abuse Disorder was associated to higher suicidal ideation (OR: 2.67) whilst Developmental Disorders lowered the risk (OR: 0.16 – 0.24).

Conclusions

This is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.

KEY MESSAGE BOX

What is already known on this topic

People with epilepsy and people with functional/dissociative seizures (FDS) are at elevated risk of suicide

Identification of risk factors for suicidal ideation and suicide attempt in high-risk groups is essential to inform risk prevention strategies

What this study adds

Several factors are associated with suicidality in FDS, including age, ethnicity, comorbid Depression and Personality Disorders.

In epilepsy, suicidality is associated with age, gender, ethnicity, comorbid Substance Misuse Disorder and Developmental Disorders.

How this study might affect research, practice or policy

Whilst disorder-specific factors will be useful to identify groups at higher risk in clinical settings, general risk factors can be target of population-based preventive strategies.
A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer’s Disease: a serum and CSF-based metabolic analysis
Authors: Schweickart Annalise , Batra Richa , Neth Bryan J. , Martino Cameron , Shenhav Liat , Zhang Anru R. , Shi Pixu , Karu Naama , Huynh Kevin , Meikle Peter J. , Schimmel Leyla , Dilmore Amanda Hazel , Blennow Kaj , Zetterberg Henrik , Blach Colette , Dorrestein Pieter C , Knight Rob ,   Alzheimer’s Gut Microbiome Project Consortium, Craft Suzanne , Kaddurah-Daouk Rima , Krumsiek Jan
Published: November 2023

Alzheimer’s disease (AD) is influenced by a variety of modifiable risk factors, including a person’s dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD’s metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean-ketogenic diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.
Housing insecurity and health: a marginal structural model analysis of the impact of housing payment problems and forced moves on mental health, sleep and hypertension in UK adults, 2009-2019
Authors: Mason Kate , Alexiou Alexandros , Li Ang , Taylor-Robinson David
Published: November 2023

Background

Housing insecurity is an escalating problem in the UK. Limited empirical evidence exists from which to draw reliable causal inferences about the impact of insecure housing on health. Using nationally representative panel data and causally focussed methods, we examined the effect of insecure housing on mental health, sleep disturbance and cardiovascular health, during a period of government austerity.

Methods

We used longitudinal survey data (2009-2019) from the UK Household Longitudinal Study. Health outcomes included probable common mental disorder; sleep disturbance due to worry; and new diagnoses of hypertension. The primary exposure was housing payment problems in the past 12 months. Using doubly robust marginal structural models) with inverse probability of treatment weights, we estimated absolute and relative health effects of housing payment problems, and population attributable fractions. We performed stratified analyses to assess potentially heterogeneous impacts across the population, and the potential modifying effects of austerity measures in the UK.

Findings

The average absolute effect of housing payment problems was a 2.5 percentage point increased risk of experiencing a common mental disorder (95% CI 1.1%, 3.8%) and 2.0% increased risk of sleep disturbance (95% CI 0.7%, 3.3%). Effects were larger among renters, younger people, less educated, and households with children. Effects were also larger among people living in areas most affected by austerity-related cuts to housing support services. Evidence for a cardiovascular health impact was weak (95% CI -0.1%, 1.2%).

Interpretation

Housing payment problems were associated with worse mental health and sleep disturbance in a large UK sample. Households at risk of falling into rent or mortgage arrears need more support, especially in areas where housing services have been diminished. Rapid and substantial investment is needed to improve supply of social and affordable housing.
Sex differences in health-related quality of life and poverty risk among older people living with HIV in Spain: a cross-sectional study
Authors: Nuño Néstor , Martínez Alberto , Martínez Susana , Cobos Marta , Hernández Juan Sebastián , Polo Rosa
Published: November 2023

Background

Current antiretroviral therapies have increased the life expectancy of people living with HIV (PLHIV). There is, however, limited evidence regarding the health-related quality of life (HRQoL) and living conditions of older people living with HIV (OPLHIV) in Spain.

Methods

We implemented a self-administered online questionnaire to identify sex differences in HRQoL and poverty risk among Spanish OPLHIV (PLHIV ≥50 years). Participants were contacted through non-governmental organisations. We used the standardised WHOQoL-HIV BREF questionnaire and the Europe 2020 guidelines to estimate HRQoL and poverty risk respectively. The statistical analysis included multivariable generalised linear models with potential confounding variables and robust estimates.

Results

The study included 247 OPLHIV (192 men and 55 women). On the WHOQoL-HIV BREF questionnaire, men scored higher on 84% of items and in all six domains. Women had significantly lower HRQoL in five domains: physical health (β: −1.5; 95% CI: −2.5, −0.5;p: 0.002), psychological health (β: −1.0; 95% CI: −1.9, −0.1;p: 0.036), level of independence (β: −1.1; 95% CI: −1.9, −0.2;p: 0.019), environmental health (β: −1.1; 95% CI: −1.8, −0.3;p: 0.008), and spirituality/personal beliefs (β: −1.4; 95% CI: −2.5, −0.3;p: 0.012). No statistical differences were found in the domain of social relations. Poverty risk was considerable for both men (30%) and women (53%), but women were significantly more likely to experience it (OR: 2.9; 95% CI: 1.3, 6.5;p: 0.009).

Conclusion

The aging of PLHIV is a public health concern. Our findings indicate that HRQoL and poverty risk among Spanish OPLHIV differ significantly by sex. Spain should, therefore, implement specific policies and interventions to address OPLHIV needs. The strategies must place a high priority on the reduction of sex inequalities in HRQoL and the enhancement of the structural conditions in which OPLHIV live.
Investigating Dopaminergic Abnormalities in Psychosis with Normative Modelling and Multisite Molecular Neuroimaging
Authors: Giacomel A. , Martins D. , Nordio G. , Easmin R. , Howes O. , Selvaggi Pierluigi , Williams S.C.R. , Turkheimer F. , De Groot M. , Dipasquale O. , Veronese M. ,   the FDOPA PET imaging working group
Published: November 2023

Molecular neuroimaging techniques, like PET and SPECT, offer invaluable insights into the brain’s in-vivo biology and its dysfunction in neuropsychiatric patients. However, the transition of molecular neuroimaging into diagnostics and precision medicine has been limited to a few clinical applications, hindered by issues like practical feasibility and high costs. In this study, we explore the use of normative modelling (NM) for molecular neuroimaging to identify individual patient deviations from a reference cohort of subjects. NM potentially addresses challenges such as small sample sizes and diverse acquisition protocols that are typical of molecular neuroimaging studies. We applied NM to two PET radiotracers targeting the dopaminergic system ([11C]-(+)-PHNO and [18F]FDOPA) to create a normative model to reference groups of controls. The models were subsequently utilized on various independent cohorts of patients experiencing psychosis. These cohorts were characterized by differing disease stages, treatment responses, and the presence or absence of matched controls. Our results showed that patients exhibited a higher degree of extreme deviations (∼3-fold increase) than controls, although this pattern was heterogeneous, with minimal overlap in extreme deviations topology (max 20%). We also confirmed the value of striatal [18F]FDOPA signal to predict treatment response (striatal AUC ROC: 0.77-0.83). Methodologically, we highlighted the importance of data harmonization before data aggregation. In conclusion, normative modelling can be effectively applied to molecular neuroimaging after proper harmonization, enabling insights into disease mechanisms and advancing precision medicine. The method is valuable in understanding the heterogeneity of patient populations and can contribute to maximising cost efficiency in studies aimed at comparing cases and controls.
Baseline tumor-infiltrating lymphocyte patterns and response to immune checkpoint inhibition in metastatic cutaneous melanoma
Authors: van Duin Isabella A.J. , Schuiveling Mark , ter Maat Laurens S. , van Amsterdam Wouter A.C. , van den Berkmortel Franchette , Boers-Sonderen Marye , de Groot Jan Willem B. , Hospers Geke A.P. , Kapiteijn Ellen , Labots Mariette , Piersma Djura , Schrader Anne M.R. , Vreugdenhil Gerard , Westgeest Hans , Veta Mitko , Blokx Willeke A.M. , van Diest Paul J. , Suijkerbuijk Karijn P.M.
Published: November 2023

Introduction

The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors of response.

Methods

In this multicenter cohort study, patients who received first-line anti-PD1 ± anti-CTLA4 for advanced cutaneous melanoma were identified. TILs were scored as absent, non-brisk or brisk on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases. Scoring systems evaluating the infiltration and intensity patterns (‘MIA-score’) and the percentage of stromal TILs were also evaluated. The primary outcome was objective response rate (ORR), with PFS and OS being secondary outcomes. Univariable and multivariable logistic regression and Cox proportional hazard regression analyses were performed, adjusting.for age, sex, disease stage, ICI type, BRAF mutation, lactate dehydrogenase (LDH) level and WHO performance score.

Results

Metastatic melanoma specimens were available for 650 patients and primary specimens from 565 patients.. No association was found between TILs in primary melanoma specimens and response. In metastatic specimens, patients with non-brisk TILs (aOR 1.56, 95% CI 1.06-2.29) and brisk TILs (aOR 3.28, 95% CI 1.72-6.56) had a higher probability of response, longer median PFS (9.2 and 19.4 vs. 6.5months [p=0.009]) and median OS (49.5 and 40.9 vs 21.3 months [p=0.007]) when compared to absent TILs. Similar results were noted using the MIA- and stromal TIL scores.

Conclusion

In advanced melanoma patients, TIL patterns on H&E slides of pre-treatment metastases are associated with ICI response. This is independent of known clinical predictors. TILs are easily scored on readily available H&Es, which facilitates the use of this biomarker for ICI outcomes in clinical practice.
Home-based transcranial direct current stimulation RCT in major depression
Authors: Woodham Rachel D , Selvaraj Sudhakar , Lajmi Nahed , Hobday Harriet , Sheehan Gabrielle , Ghazi-Noori Ali-Reza , Lagerberg Peter J , Rizvi Maheen , Kwon Sarah S , Orhii Paulette , Maislin David , Hernandez Lucia , Machado-Vieira Rodrigo , Soares Jair C , Young Allan H , Fu Cynthia HY
Published: November 2023

Background Transcranial direct current stimulation (tDCS) has been proposed as a novel treatment in major depressive disorder (MDD). However, efficacy and safety of home-based tDCS treatment have not been investigated. Methods Fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of home-based tDCS treatment in MDD was conducted in UK and USA. Participants were adults 18 years or older, having MDD diagnosis based on DSM-5 criteria, in current depressive episode of at least moderate severity, measured by score >=16 on 17-item Hamilton Depression Rating Scale (HDRS), without treatment resistant depression history. Protocol was 10-week blinded phase: 5 tDCS sessions per week for 3 weeks then 3 sessions per week for 7 weeks; followed by 10-week open label phase. tDCS montage was bifrontal, 30-minute sessions, active tDCS 2 mA, and sham tDCS 0 mA with brief ramp up and down to mimic active device. Primary outcome was HDRS change at week 10 in modified intention-to-treat analysis. Results 174 MDD participants were randomized: active (n=87; mean age 37.1 + 11.1 years) and sham (n=87; mean age 38.3 + 10.9 years) treatment. Significant improvement in HDRS was observed in active (9.4 + 6.25 points) relative to sham treatment (7.1 + 6.10 points) (95% CI 0.5 to 4.0, p = 0.012), with no differences in discontinuation rates between active (n=13) and sham (n=12). Conclusions Home-based tDCS with remote supervision is a potential first line treatment for MDD that is acceptable and safe. Consideration of continuing effective safety monitoring is required. Trial registration numberNCT05202119
Causality between Peripheral Immune Cell Counts and Membranous Nephropathy: A Bidirectional Mendelian Randomization Study
Authors: Su Zhihang , Wen Liu , Feng Xiangning , Wan Qijun
Published: November 2023

Background

Membranous nephropathy (MN), an autoimmune disease, has not yet been fully elucidated regarding its relationship with immune cells.

Methods

As a primary method in this Mendelian randomization (MR) analysis, we employed the Inverse Variance Weighted (IVW), Wald Ratio (WR), Steiger filtering, Weighted Median, Weighted mode, MR-Egger, Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) and Leave-one-out sensitivity test. Reverse MR analysis was utilized to investigate whether MN affects immune cells.

Results

After False Discovery Rate multiple correction (threshold was 10%), it was determined that CD45RA+CD8+T cell (IVW OR=1.074, 95%CI: 1.034-1.114, P=0.0001, PFDR=0.036), Effector Memory CD8+T cell (IVW OR=0.929, 95%CI: 0.895-0.964, P=0.0001, PFDR=0.036), HLA DR+CD8+T cell (IVW OR=0.921, 95%CI: 0.884-0.960, P=0.0001, PFDR=0.036) are significantly affected by MN. CD28+CD45RA-CD8+T cell (WR OR=0.513, 95%CI: 0.357-0.793, P=0.0003, PFDR=0.061), CD8 on Terminally Differentiated CD8+T cell (WR OR=0.378, 95%CI: 0.219-0.652, P=0.0005, PFDR=0.061), and HVEM on Effector Memory CD4+T cell (WR OR=0.378, 95%CI: 0.219-0.652, P=0.0005, PFDR=0.065), among others, are considered immune cells that possess protective factors against MN. However, HLA DR on CD33+HLA DR+CD14-(WR OR=1.910, 95%CI: 1.269-2.876, P=0.002, PFDR=0.065), CD80 on granulocyte (WR OR=2.606, 95%CI: 1.417-4.792, P=0.002, PFDR=0.065), and CD62L-plasmacytoid Dendritic Cell (WR OR=1.508, 95%CI: 1.138-1.998, P=0.004, PFDR=0.071) pose a risk to MN. When increased by one standard deviation in peripheral blood, these immune cells positively or negatively impact the risk of MN with an odds ratio (OR).

Conclusions

The MR analysis unveiled the association between immune cells and MN. We have deepened our understanding of the pathogenic mechanisms linking MN and immune cells and also identified new targets for immunotherapy in MN.
Long-term survival, psychiatric, physiological, and functional outcomes of critically ill patients requiring prolonged mechanical ventilation: a systematic review
Authors: Ludski Jarryd , Honeywill Conor
Published: November 2023

Purpose

Invasive mechanical ventilation is utilized in over 50% of Australian Intensive Care Unit patients, with rates increasing world-wide. Prolonged mechanical ventilation is associated with increased length of hospital stay and in-hospital mortality compared with patients ventilated under the time threshold. Previous studies have highlighted mortality rates, but much remains unknown regarding the long-term physiological, functional, and psychiatric effects of prolonged mechanical ventilation. With a greater understanding of these outcomes, models of care can be formulated to reduce long-term morbidity.

Methods

Medline, CINAHL and the Cochrane Library were searched between 1998 and March 2019, for PMV, patients in ICU and long-term outcomes. Included studies had patients, that received greater than or equal to 14 days of IMV. Primary outcome was mortality rates with secondary outcomes clustered into physiological, functional, and psychiatric outcomes.

Results

1057 studies were identified, with 24 included. 73% of PMV patients were discharged from ICU, with mortality rates of 57% and 69% at 12 and 48 months. 30.2% were discharged home, 25% developed new onset ventilator acquired pneumonia and up to 39% experienced psychiatric complications.

Conclusion

Despite a high proportion of patients surviving to hospital discharge, subsequent outcomes are extremely poor for patients that require PMV.
Strength of spatial correlation between structural brain network connectivity and brain-wide patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival
Authors: Kesler Shelli R. , Harrison Rebecca A. , Schultz Alexa De La Torre , Michener Hayley , Bean Paris , Vallone Veronica , Prinsloo Sarah
Published: November 2023

Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.