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Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma

by Levi Matthies, Hendrik Amir-Kabirian, Medhanie T. Gebrekidan, Andreas S. Braeuer, Ulrike S. Speth, Ralf Smeets, Christian Hagel, Martin Gosau, Christian Knipfer, Reinhard E. Friedrich

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins–complete tumor removal while attempting to preserve viable tissue–remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Associations between intravaginal practices and incidence of sexually transmitted infections and bacterial vaginosis among women enrolled in the dapivirine vaginal ring trial (The Ring Study) in southwestern Uganda: a retrospective secondary analysis

Por: Kusemererwa · S. · Ruzagira · E. · Onyango · M. · Kabarambi · A. · Abaasa · A.
Objectives

We assessed associations between intravaginal practices (IVPs) and the incidence of sexually transmitted infections (STIs) and bacterial vaginosis (BV) among women using the dapivirine vaginal ring (DVR) or placebo vaginal ring in southwestern Uganda.

Methods

This was a retrospective secondary analysis of data collected from women at risk of HIV infection recruited into the Ring Study. The latter evaluated the safety and efficacy of the DVR between 2013 and 2016. At baseline, a behavioural questionnaire was administered to obtain information on sexual activity and IVP (exposure) defined as; insertion inside the vagina of any items aimed at cleaning the vagina for any reason before, during or after sex other than practices to manage menses. Each participant self-inserted the DVR/placebo and replaced it every 4 weeks for 2 years. Outcomes were diagnosis of STIs, that is, Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis (TV), HIV and BV. The incidence rate of STI/BV was estimated, overall, by IVP and trial arm in single-event-per-participant and multiple-event-per-participant analyses.

Results

Of the 197 women enrolled, 66 (33.5%) were

Conclusions

IVP was not associated with risk of STIs/BV in the Ring Study.

Trial registration number

NCT01539226.

Prevalence and risk factors of work-related musculoskeletal disorders among shopkeepers in Ethiopia: Evidence from a workplace cross-sectional study

by Amensisa Hailu Tesfaye, Gebisa Guyasa Kabito, Fantu Mamo Aragaw, Tesfaye Hambisa Mekonnen

Introduction

Work-related musculoskeletal disorders (WRMSDs) are the leading cause of disability worldwide. Shopkeepers are prone to developing work-related musculoskeletal disorders, but they are largely overlooked in research and policy actions, particularly in developing countries. So far, there is a lack of data on the magnitude and factors influencing work-related musculoskeletal disorders among shopkeepers in Ethiopia. Therefore, the current study aimed to explore the prevalence and risk factors of work-related musculoskeletal disorders among shopkeepers in Gondar City, Ethiopia.

Methods

A workplace-based cross-sectional study was conducted from July to August 2022, in Gondar city, Northwest Ethiopia. A multistage sampling technique was used to select 625 shopkeepers. The data were collected using an interviewer-administered standardized Nordic Musculoskeletal Questionnaire. Analysis was made using Stata version 14. Factors associated with the prevalence of work-related musculoskeletal disorders were identified using the multivariable Poisson regression model. The adjusted prevalence ratio with 95% confidence intervals (CIs) and p-value Results

The overall prevalence of work-related musculoskeletal disorders among shopkeepers in the past 12 months was found to be 81.1% (N = 507). The most frequently affected body part was the lower back (46.6%), followed by the upper back (43.8%) and shoulder (35.4%). Being female (p = 0.043), being in the age group of ≥40 years (p = 0.028), being overweight (p = 0.035), experiencing job stress (p = 0.006) and prolonged sitting (p = 0.045) were significant factors for the prevalence of work-related musculoskeletal disorders among shopkeepers.

Conclusion

This study revealed that shopkeepers face an alarmingly high prevalence of work-related musculoskeletal disorders. Female, older, overweight, stressed and shopkeepers who sit in the same position for long periods of time were identified as particularly vulnerable groups. These findings call for the urgent development and implementation of preventive measures, including ergonomic adjustments, education and training programs, stress management techniques and the promotion of physical activity, to protect this vulnerable workforce from the debilitating effects of work-related musculoskeletal disorders and to ensure their long-term health and well-being.

Multimodality radiomics for tumor prognosis in nasopharyngeal carcinoma

by Sararas Khongwirotphan, Sornjarod Oonsiri, Sarin Kitpanit, Anussara Prayongrat, Danita Kannarunimit, Chakkapong Chakkabat, Chawalit Lertbutsayanukul, Sira Sriswasdi, Yothin Rakvongthai

Background

The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment.

Purpose

To investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC.

Materials and methods

A retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme.

Results

Integrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (pp Conclusions

The combination of multimodality radiomic features from CT and MR images could offer superior predictive performance for OS, PFS, and DMFS compared to relying on conventional clinical data alone.

Can an integrated intervention package including peer support increase the proportion of health facility births? A cluster randomised controlled trial in Northern Uganda

Por: Nankabirwa · V. · Mukunya · D. · Ndeezi · G. · Odongkara · B. · Arach · A. A. · Achora · V. · Mugenyi · L. · Sebit · M. B. · Wandabwa · J. N. · Waako · P. · Tylleskär · T. · Tumwine · J. K.
Objective

To assess the effect of an integrated intervention package compared with routine government health services on the frequency of health facility births.

Setting

Three subcounties of Lira district in Northern Uganda.

Design

A cluster randomised controlled trial where a total of 30 clusters were randomised in a ratio of 1:1 to intervention or standard of care.

Participants

Pregnant women at ≥28 weeks of gestation.

Interventions

Participants in the intervention arm received an integrated intervention package of peer support, mobile phone messaging and birthing kits during pregnancy while those in the control arm received routine government health services (‘standard of care’).

Primary and secondary outcome measures

The primary outcome was the proportion of women giving birth at a health facility in the intervention arm compared with the control arm. Secondary outcomes were perinatal and neonatal deaths.

Results

In 2018–2019, 995 pregnant women were included in 15 intervention clusters and 882 in 15 control clusters. The primary outcome was ascertained for all except one participant who died before childbirth. In the intervention arm, 754/994 participants (76%) gave birth at a health facility compared with 500/882 (57%) in the control arm. Participants in the intervention arm were 35% more likely to give birth at a health facility compared with participants in the control arm, (risk ratio 1.35 (95% CI 1.20 to 1.51)) and (risk difference 0.20 (95% CI 0.13 to 0.27)). Adjusting for baseline differences generated similar results. There was no difference in secondary outcomes (perinatal or neonatal mortality or number of postnatal visits) between arms.

Conclusion

The intervention was successful in increasing the proportion of facility-based births but did not reduce perinatal or neonatal mortality.

Trial registration number

NCT02605369

Inter- and intra-rater reproducibility of quantitative T1 measurement using semiautomatic region of interest placement in myometrium

by Sadahiro Nakagawa, Takahiro Uno, Shunta Ishitoya, Eriko Takabayashi, Akiko Oya, Wakako Kubota, Atsutaka Okizaki

Purpose

This study aimed to investigate the inter- and intraobserver reproducibility of quantitative T1 (qT1) measurements using manual and semiautomatic region of interest (ROI) placements. We hypothesized the usefulness of the semiautomatic method, which utilizes a three-dimensional (3D) anatomical relationship between the myometrium and other tissues, for minimizing ROI placement variation, thereby improving qT1 reproducibility compared to the manual approach. The semiautomatic approach, which considered anatomical relationships, was expected to enhance reproducibility by reducing ROI placement variabilities.

Materials and methods

This study recruited 23 healthy female volunteers. Data with variable flip angle (VFA) and inversion recovery were acquired using 3D-spoiled gradient echo and spin echo sequences, respectively. T1 maps were generated with VFA. Manual and semiautomatic ROI placements were independently conducted. Mean qT1 values were calculated from the T1 maps using the corresponding pixel values of the myometrial ROI. Inter- and intraobserver reproducibility of qT1 values was investigated. The inter- and intraobserver reproducibility of qT1 values was evaluated by calculating the coefficient of variation (CoV). Further, reproducibility was evaluated with inter- and intraobserver errors and intraclass correlation coefficients (ICCs). Bland–Altman analysis was utilized to compare the results, estimate bias, and determine the limits of agreement.

Results

The mean inter- and intraobserver CoV of the qT1 values for semiautomatic ROI placement was significantly lower than those for manual ROI placement (p p p p Conclusion

Semiautomatic ROI placement demonstrated high reproducibility of qT1 measurements compared with manual methods. Semiautomatic ROI placement may be useful for evaluating uterine qT1 with high reproducibility.

Impact of multimorbidity and complex multimorbidity on healthcare utilisation in older Australian adults aged 45 years or more: a large population-based cross-sectional data linkage study

Por: Kabir · A. · Conway · D. P. · Ansari · S. · Tran · A. · Rhee · J. J. · Barr · M.
Objectives

As life expectancy increases, older people are living longer with multimorbidity (MM, co-occurrence of ≥2 chronic health conditions) and complex multimorbidity (CMM, ≥3 chronic conditions affecting ≥3 different body systems). We assessed the impacts of MM and CMM on healthcare service use in Australia, as little was known about this.

Design

Population-based cross-sectional data linkage study.

Setting

New South Wales, Australia.

Participants

248 496 people aged ≥45 years who completed the Sax Institute’s 45 and Up Study baseline questionnaire.

Primary outcome

High average annual healthcare service use (≥2 hospital admissions, ≥11 general practice visits and ≥2 emergency department (ED) visits) during the 3-year baseline period (year before, year of and year after recruitment).

Methods

Baseline questionnaire data were linked with hospital, Medicare claims and ED datasets. Poisson regression models were used to estimate adjusted and unadjusted prevalence ratios for high service use with 95% CIs. Using a count of chronic conditions (disease count) as an alternative morbidity metric was requested during peer review.

Results

Prevalence of MM and CMM was 43.8% and 15.5%, respectively, and prevalence increased with age. Across three healthcare settings, MM was associated with a 2.02-fold to 2.26-fold, and CMM was associated with a 1.83-fold to 2.08-fold, increased risk of high service use. The association was higher in the youngest group (45–59 years) versus the oldest group (≥75 years), which was confirmed when disease count was used as the morbidity metric in sensitivity analysis.

When comparing impact using three categories with no overlap (no MM/CMM, MM with no CMM, and CMM), CMM had greater impact than MM across all settings.

Conclusion

Increased healthcare service use among older adults with MM and CMM impacts on the demand for primary care and hospital services. Which of MM or CMM has greater impact on risk of high healthcare service use depends on the analytic method used. Ageing populations living longer with increasing burdens of MM and CMM will require increased Medicare funding and provision of integrated care across the healthcare system to meet their complex needs.

Childhood and adolescent factors shaping vulnerability to underage entry into sex work: a quantitative hierarchical analysis of female sex workers in Nairobi, Kenya

Por: Shah · P. · Kabuti · R. · Beksinska · A. · Nyariki · E. · Babu · H. · Kungu · M. · Jama · Z. · Ngurukiri · P. · The Maisha Fiti Study Champions · Kaul · R. · Kyegombe · N. · Medley · G. F. · Devries · K. · Seeley · J. · Weiss · H. A. · Beattie · T. S. · Kimani · J. · Gwala · Oside · Kamen
Objective

To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya.

Background

Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation.

Design

Building on previous qualitative research with this cohort, analysis of behavioural–biological cross-sectional data using hierarchical logistic regression.

Participants and measures

FSWs aged 18–45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural–biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling.

Results

Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (

Conclusions

Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences.

Randomised controlled trial of automated VR therapy to improve positive self-beliefs and psychological well-being in young people diagnosed with psychosis: a study protocol for the Phoenix VR self-confidence therapy trial

Por: Freeman · D. · Freeman · J. · Rovira · A. · Miguel · A. L. · Ward · R. · Bousfield · M. · Riffiod · L. · Leal · J. · Kabir · T. · Yu · L.-M. · Beckwith · H. · Waite · F. · Rosebrock · L.
Introduction

The confidence of young people diagnosed with psychosis is often low. Positive self-beliefs may be few and negative self-beliefs many. A sense of defeat and failure is common. Young people often withdraw from many aspects of everyday life. Psychological well-being is lowered. Psychological techniques can improve self-confidence, but a shortage of therapists means that very few patients ever receive such help. Virtual reality (VR) offers a potential route out of this impasse. By including a virtual coach, treatment can be automated. As such, delivery of effective therapy is no longer reliant on the availability of therapists. With young people with lived experience, we have developed a staff-assisted automated VR therapy to improve positive self-beliefs (Phoenix). The treatment is based on established cognitive behavioural therapy and positive psychology techniques. A case series indicates that this approach may lead to large improvements in positive self-beliefs and psychological well-being. We now aim to conduct the first randomised controlled evaluation of Phoenix VR.

Methods and analysis

80 patients with psychosis, aged between 16 and 30 years old and with low levels of positive self-beliefs, will be recruited from National Health Service (NHS) secondary care services. They will be randomised (1:1) to the Phoenix VR self-confidence therapy added to treatment as usual or treatment as usual. Assessments will be conducted at 0, 6 (post-treatment) and 12 weeks by a researcher blind to allocation. The primary outcome is positive self-beliefs at 6 weeks rated with the Oxford Positive Self Scale. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention to treat.

Ethics and dissemination

The trial has received ethical approval from the NHS Health Research Authority (22/LO/0273). A key output will be a high-quality VR treatment for patients to improve self-confidence and psychological well-being.

Trial registration number

ISRCTN10250113.

Heart girth best predicts live weights of market-age pigs in Tanzania

by Mwemezi L. Kabululu

The aim of this study was to use linear body measurements to develop and validate a regression-based model for prediction of live weights (LW) of pigs reared under smallholder settings in rural areas in the southern highlands of Tanzania. LW of 400 pigs (range 7 to 91 kg) was measured, along with their heart girths (HG) and body lengths (BL). BL was measured from the midpoint between the ears to the tail base. HG was measured as chest circumference just behind the front legs. LW was determined using a portable hanging scale. An analysis of covariance was performed to test for differences in LW between male and female pigs, including age, HG and BL as covariates. LW was regressed on HG and BL using simple and multiple linear regressions. Models were developed for all pig ages, and separately for market/breeding-age pigs and those below market/breeding age. Model validation was done using a split-samples approach, followed by PRESS-related statistics. Model efficiency and accuracy were assessed using the coefficient of determination, R2, and standard deviation of the random error, respectively. Model stability was determined by assessing ‘shrinkage’ of R2 value. Results showed that HG was the best predictor of LW in market/breeding-age pigs (model equation: LW = 1.22HG—52.384; R2 = 0.94, error = 3.7). BL, age and sex of pigs did not influence LW estimates. It is expected that LW estimation tools will be developed to enable more accurate estimation of LW in the pig value chain in the area.

Associations of serum DNA methylation levels of chemokine signaling pathway genes with mild cognitive impairment (MCI) and Alzheimer’s disease (AD)

by Ting Zou, Xiaohui Zhou, Qinwen Wang, Yongjie Zhao, Meisheng Zhu, Lei Zhang, Wei Chen, Pari Abuliz, Haijun Miao, Keyimu Kabinur, Kader Alimu

Objective

To investigate the associations of serum DNA methylation levels of chemokine signaling pathway genes with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) in elderly people in Xinjiang, China, and to screen out genes whose DNA methylation could distinguish AD and MCI.

Materials and methods

37 AD, 40 MCI and 80 controls were included in the present study. DNA methylation assay was done using quantitative methylation-specific polymerase chain reaction (qMSP). Genotyping was done using Sanger sequencing.

Results

DNA methylation levels of ADCY2, MAP2K1 and AKT1 were significantly different among AD, MCI and controls. In the comparisons of each two groups, AKT1 and MAP2K1’s methylation was both significantly different between AD and MCI (p MAP2K1’s methylation was also significantly different between MCI and controls. Therefore, AKT1’s methylation was considered as the candidate serum marker to distinguish AD from MCI, and its association with AD was independent of APOE ε4 allele (p AKT1 hypermethylation was an independent risk factor for AD and MAP2K1 hypomethylation was an independent risk factor for MCI in logistic regression analysis (p Conclusion

This study found that the serum of AKT1 hypermethylation is related to AD independently of APOE ε4, which was differentially expressed in the Entorhinal Cortex of the brain and was an independent risk factor for AD. It could be used as one of the candidate serum markers to distinguish AD and MCI. Serum of MAP2K1 hypomethylation is an independent risk factor for MCI.

Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach

by Katayi Mwila-Kazimbaya, Samuel Bosomprah, Obvious Nchimunya Chilyabanyama, Caroline Cleopatra Chisenga, Mwelwa Chibuye, Natasha Makabilo Laban, Michelo Simuyandi, Bert Huffer Jr, Miren Iturriza-Gomara, Robert K. M. Choy, Roma Chilengi

Background

Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach.

Methods

Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers.

Results

Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only.

Conclusion

MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.

New factors affecting wound healing and recurrence after pilonidal sinus surgery in adolescents; seborrheic dermatitis and psychiatric co‐occurring conditions

Abstract

Postoperative wound healing problems and recurrence remain common for pilonidal sinus disease (PSD). Our study aimed to examine the effect of comorbidities in addition to the classic known factors that may affect wound complications and recurrence after PSD surgery. We retrospectively analysed 282 adolescent patients operated on in our clinic between 2014 and 2021. We gathered the postoperative wound healing patterns of the patients under four groups. With a mean age of 15.49 ± 1.45, 59.9% (n = 169) were male, 40.1% (n = 113) were female and 23.8% (n = 67) had recurrence. When examined according to the wound healing groups, 53.5% (n = 151) had an uneventful wound, 22.6% (n = 64) had prolonged wound care, 17.7% (n = 50) of the postoperative wounds did not close and had a recurrence and 6% (n = 17) had recurrence after the wound was healed. The number of sinuses, abscess presentation and the incidence of comorbid disease in group 1 were found to be statistically significantly lower than all other groups. Seborrheic dermatitis, obesity and psychiatric diagnoses showed high statistical association with group 3 and acne with group 4. In patients with seborrheic dermatitis or psychiatric diagnosis, a significant correlation was found between wound healing according to the type of surgery (p < 0.05). The wound healing patterns of these patients after total excision and primary closure surgeries were included in Group 3 with a statistically significant high rate. As two new factors, the significance of the presence of seborrheic dermatitis and psychiatric comorbidities should be evaluated in these patients whose wounds remain open postoperatively and do not respond to primary wound care and eventually relapse. Further histologic and pathologic investigations are needed for seborrheic dermatitis and PSD relation. Awareness of these diseases may change the decision of the type of surgery, and their treatment within the same time may support wound healing and ultimately reduce recurrence.

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