bluuebunny/crossref_metadata_2025 huggingface dataset:
Public health impact of the spread of Anopheles stephensi in the WHO Eastern Mediterranean Region countries in Horn of Africa and Yemen: need for integrated vector surveillance and control
Authors: Al-Eryani Samira M. , Irish Seth R. , Carter Tamar E. , Lenhart Audrey , Aljasari Adel , Montoya Lucia Fernández , Awash Abdullah A. , Mohammed Elmonshawe , Ali Said , Esmail Mohammed A. , Hussain Abdulhafid , Amran Jamal G. , Kayad Samatar , Nouredayem Mujahid , Adam Mariam A. , Azkoul Lina , Assada Methaq , Baheshm Yasser A. , Eltahir Walid , Hutin Yvan J.
Published: June 2023

Background

Anopheles stephensi is an efficient vector of both Plasmodium falciparum and Plasmodium vivax in South Asia and the Middle East. The spread of An. stephensi to countries within the Horn of Africa threatens progress in malaria control in this region as well as the rest of sub-Saharan Africa.

Methods

The available malaria data and the timeline for the detection of An. stephensi was reviewed to analyse the role of An. stephensi in malaria transmission in Horn of Africa of the Eastern Mediterranean Region (EMR) in Djibouti, Somalia, Sudan and Yemen.

Results

Malaria incidence in Horn of Africa of EMR and Yemen, increased from 41.6 in 2015 to 61.5 cases per 1000 in 2020. The four countries from this region, Djibouti, Somalia, Sudan and Yemen had reported the detection of An. stephensi as of 2021. In Djibouti City, following its detection in 2012, the estimated incidence increased from 2.5 cases per 1000 in 2013 to 97.6 cases per 1000 in 2020. However, its contribution to malaria transmission in other major cities and in other countries, is unclear because of other factors, quality of the urban malaria data, human mobility, uncertainty about the actual arrival time of An. stephensi and poor entomological surveillance.

Conclusions

While An. stephensi may explain a resurgence of malaria in Djibouti, further investigations are needed to understand its interpretation trends in urban malaria across the greater region. More investment for multisectoral approach and integrated surveillance and control should target all vectors particularly malaria and dengue vectors to guide interventions in urban areas.
The clinicopathological and immunohistochemical features of breast carcinomas with signet-ring-cell differentiation
Authors: Zheng Jie , Liu Junlin , Yang Wan , Yao Jia , Guo Jiao , Liu Changqing
Published: June 2023

Background

This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin.

Methods

A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People’s Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis.

Results

Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic.

Conclusion

We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.
TRPM2-mediated Ca2+ signaling as a potential therapeutic target in cancer treatment: an updated review of its role in survival and proliferation of cancer cells
Authors: Ali Eunus S. , Chakrabarty Brototi , Ramproshad Sarker , Mondal Banani , Kundu Neloy , Sarkar Chandan , Sharifi-Rad Javad , Calina Daniela , Cho William C.
Published: June 2023

The transient receptor potential melastatin subfamily member 2 (TRPM2), a thermo and reactive oxygen species (ROS) sensitive Ca2+-permeable cation channel has a vital role in surviving the cell as well as defending the adaptability of various cell groups during and after oxidative stress. It shows higher expression in several cancers involving breast, pancreatic, prostate, melanoma, leukemia, and neuroblastoma, indicating it raises the survivability of cancerous cells. In various cancers including gastric cancers, and neuroblastoma, TRPM2 is known to conserve viability, and several underlying mechanisms of action have been proposed. Transcription factors are thought to activate TRPM2 channels, which is essential for cell proliferation and survival. In normal physiological conditions with an optimal expression of TRPM2, mitochondrial ROS is produced in optimal amounts while regulation of antioxidant expression is carried on. Depletion of TRPM2 overexpression or activity has been shown to improve ischemia–reperfusion injury in organ levels, reduce tumor growth and/or viability of various malignant cancers like breast, gastric, pancreatic, prostate, head and neck cancers, melanoma, neuroblastoma, T-cell and acute myelogenous leukemia. This updated and comprehensive review also analyzes the mechanisms by which TRPM2-mediated Ca2+ signaling can regulate the growth and survival of different types of cancer cells. Based on the discussion of the available data, it can be concluded that TRPM2 may be a unique therapeutic target in the treatment of several types of cancer.
Local GHR roles in regulation of mitochondrial function through mitochondrial biogenesis during myoblast differentiation
Authors: Hu Bowen , Zhao Changbin , Pan Xiangchun , Wei Haohui , Mo Guodong , Xian Mingjian , Luo Wen , Nie Qinghua , Li Hongmei , Zhang Xiquan
Published: June 2023

Background

Myoblast differentiation requires metabolic reprogramming driven by increased mitochondrial biogenesis and oxidative phosphorylation. The canonical GH-GHR-IGFs axis in liver exhibits a great complexity in response to somatic growth. However, the underlying mechanism of whether local GHR acts as a control valve to regulate mitochondrial function through mitochondrial biogenesis during myoblast differentiation remains unknown.

Methods

We manipulated the GHR expression in chicken primary myoblast to investigate its roles in mitochondrial biogenesis and function during myoblast differentiation.

Results

We reported that GHR is induced during myoblast differentiation. Local GHR promoted mitochondrial biogenesis during myoblast differentiation, as determined by the fluorescence intensity of Mito-Tracker Green staining and MitoTimer reporter system, the expression of mitochondrial biogenesis markers (PGC1α, NRF1, TFAM) and mtDNA encoded gene (ND1, CYTB, COX1, ATP6), as well as mtDNA content. Consistently, local GHR enhanced mitochondrial function during myoblast differentiation, as determined by the oxygen consumption rate, mitochondrial membrane potential, ATP level and ROS production. We next revealed that the regulation of mitochondrial biogenesis and function by GHR depends on IGF1. In terms of the underlying mechanism, we demonstrated that IGF1 regulates mitochondrial biogenesis via PI3K/AKT/CREB pathway. Additionally, GHR knockdown repressed myoblast differentiation.

Conclusions

In conclusion, our data corroborate that local GHR acts as a control valve to enhance mitochondrial function by promoting mitochondrial biogenesis via IGF1-PI3K/AKT/CREB pathway during myoblast differentiation.
Health system evaluation in conflict-affected countries: a scoping review of approaches and methods
Authors: Marzouk Manar , Durrance-Bagale Anna , Lam Sze Tung , Nagashima-Hayashi Michiko , Ung Mengieng , Aribou Zeenathnisa Mougammadou , Zaseela Ayshath , Ibrahim Nafeesah Mohamed , Agarwal Sunanda , Omar Maryam , Newaz Sanjida , Mkhallalati Hala , Howard Natasha
Published: June 2023

Introduction

Strengthening health systems in conflict-affected settings has become increasingly professionalised. However, evaluation remains challenging and often insufficiently documented in the literature. Many, particularly small-scale health system evaluations, are conducted by government bodies or non-governmental organisations (NGO) with limited capacity to publish their experiences. It is essential to identify the existing literature and main findings as a baseline for future efforts to evaluate the capacity and resilience of conflict-affected health systems. We thus aimed to synthesise the scope of methodological approaches and methods used in the peer-reviewed literature on health system evaluation in conflict-affected settings.

Methods

We conducted a scoping review using Arksey and O’Malley’s method and synthesised findings using the WHO health system ‘building blocks’ framework.

Results

We included 58 eligible sources of 2,355 screened, which included examination of health systems or components in 26 conflict-affected countries, primarily South Sudan and Afghanistan (7 sources each), Democratic Republic of the Congo (6), and Palestine (5). Most sources (86%) were led by foreign academic institutes and international donors and focused on health services delivery (78%), with qualitative designs predominating (53%). Theoretical or conceptual grounding was extremely limited and study designs were not generally complex, as many sources (43%) were NGO project evaluations for international donors and relied on simple and lower-cost methods. Sources were also limited in terms of geography (e.g., limited coverage of the Americas region), by component (e.g., preferences for specific components such as service delivery), gendered (e.g., limited participation of women), and colonised (e.g., limited authorship and research leadership from affected countries).

Conclusion

The evaluation literature in conflict-affected settings remains limited in scope and content, favouring simplified study designs and methods, and including those components and projects implemented or funded internationally. Many identified challenges and limitations (e.g., limited innovation/contextualisation, poor engagement with local actors, gender and language biases) could be mitigated with more rigorous and systematic evaluation approaches.
The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients
Authors: van Gassel Rob J. J. , Bels Julia L. M. , Tartaglia Katrien , van Bussel Bas C. T. , van Kuijk Sander M. J. , Deane Adam M. , Puthucheary Zudin , Weijs Peter J. M. , Vloet Lilian , Beishuizen Bert , De Bie Dekker Ashley , Fraipont Vincent , Lamote Stoffel , Ledoux Didier , Scheeren Clarissa , De Waele Elisabeth , van Zanten Arthur R. H. , Mesotten Dieter , van de Poll Marcel C. G.
Published: June 2023

Background

Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets.

Methods

The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models.

Discussion

The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes.

Trial registration

ClinicalTrials.gov Identifier: NCT04633421. Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.
Tick communities of cattle in smallholder rural livestock production systems in sub-Saharan Africa
Authors: Heylen Dieter J. A. , Kumsa Bersissa , Kimbita Elikira , Frank Mwiine Nobert , Muhanguzi Dennis , Jongejan Frans , Adehan Safiou Bienvenu , Toure Alassane , Aboagye-Antwi Fred , Ogo Ndudim Isaac , Juleff Nick , Fourie Josephus , Evans Alec , Byaruhanga Joseph , Madder Maxime
Published: June 2023

Background

The majority of the African population lives in rural areas and depends on agriculture for their livelihoods. To increase the productivity and sustainability of their farms, they need access to affordable yield-enhancing inputs of which parasite control is of paramount importance. We therefore determined the status of current tick species with the highest economic impact on cattle by sampling representative numbers of animals in each of seven sub-Saharan countries.

Methods

Data included tick species’ half-body counts from approximately 120 cattle at each of two districts per country, collected four times in approximately 1 year (to include seasonality). Study sites were chosen in each country to include high cattle density and tick burden.

Results

East Africa (Ethiopia, Uganda and Tanzania) showed overall a higher diversity and prevalence in tick infestations compared to West African countries (Benin, Burkina Faso, Ghana and Nigeria). In East Africa, Amblyomma variegatum (vector of Ehrlichia ruminantium), Rhipicephalus microplus (Babesia bovis, B. bigemina, Anaplasma marginale), R. evertsi evertsi (A. marginale) and R. appendiculatus (Theileria parva) were the most prevalent tick species of economic importance. While the latter species was absent in West Africa, here both A. variegatum and R. microplus occurred in high numbers. Rhipicephalus microplus had spread to Uganda, infesting half of the cattle sampled. Rhipicephalus microplus is known for its invasive behaviour and displacement of other blue tick species, as observed in other East and West African countries. Individual cattle with higher body weights, as well as males, were more likely to be infested. For six tick species, we found reduced infestation levels when hosts were treated with anti-parasiticides.

Conclusions

These baseline data allow the determination of possible changes in presence and prevalence of ticks in each of the countries targeted, which is of importance in the light of human-caused climate and habitat alterations or anthropogenic activities. As many of the ticks in this study are vectors of important pathogens, but also, as cattle may act as end hosts for ticks of importance to human health, our study will help a wide range of stakeholders to provide recommendations for tick infestation surveillance and prevention.

Graphical abstract
Anatomically guided self-adapting deep neural network for clinically significant prostate cancer detection on bi-parametric MRI: a multi-center study
Authors: Karagoz Ahmet , Alis Deniz , Seker Mustafa Ege , Zeybel Gokberk , Yergin Mert , Oksuz Ilkay , Karaarslan Ercan
Published: June 2023

Objective

To evaluate the effectiveness of a self-adapting deep network, trained on large-scale bi-parametric MRI data, in detecting clinically significant prostate cancer (csPCa) in external multi-center data from men of diverse demographics; to investigate the advantages of transfer learning.

Methods

We used two samples: (i) Publicly available multi-center and multi-vendor Prostate Imaging: Cancer AI (PI-CAI) training data, consisting of 1500 bi-parametric MRI scans, along with its unseen validation and testing samples; (ii) In-house multi-center testing and transfer learning data, comprising 1036 and 200 bi-parametric MRI scans. We trained a self-adapting 3D nnU-Net model using probabilistic prostate masks on the PI-CAI data and evaluated its performance on the hidden validation and testing samples and the in-house data with and without transfer learning. We used the area under the receiver operating characteristic (AUROC) curve to evaluate patient-level performance in detecting csPCa.

Results

The PI-CAI training data had 425 scans with csPCa, while the in-house testing and fine-tuning data had 288 and 50 scans with csPCa, respectively. The nnU-Net model achieved an AUROC of 0.888 and 0.889 on the hidden validation and testing data. The model performed with an AUROC of 0.886 on the in-house testing data, with a slight decrease in performance to 0.870 using transfer learning.

Conclusions

The state-of-the-art deep learning method using prostate masks trained on large-scale bi-parametric MRI data provides high performance in detecting csPCa in internal and external testing data with different characteristics, demonstrating the robustness and generalizability of deep learning within and across datasets.

Clinical relevance statement

A self-adapting deep network, utilizing prostate masks and trained on large-scale bi-parametric MRI data, is effective in accurately detecting clinically significant prostate cancer across diverse datasets, highlighting the potential of deep learning methods for improving prostate cancer detection in clinical practice.

Graphical Abstract
Dynamic chest radiography: a state-of-the-art review
Authors: Fyles Fred , FitzMaurice Thomas S. , Robinson Ryan E. , Bedi Ram , Burhan Hassan , Walshaw Martin J.
Published: June 2023

Dynamic chest radiography (DCR) is a real-time sequential high-resolution digital X-ray imaging system of the thorax in motion over the respiratory cycle, utilising pulsed image exposure and a larger field of view than fluoroscopy coupled with a low radiation dose, where post-acquisition image processing by computer algorithm automatically characterises the motion of thoracic structures. We conducted a systematic review of the literature and found 29 relevant publications describing its use in humans including the assessment of diaphragm and chest wall motion, measurement of pulmonary ventilation and perfusion, and the assessment of airway narrowing. Work is ongoing in several other areas including assessment of diaphragmatic paralysis. We assess the findings, methodology and limitations of DCR, and we discuss the current and future roles of this promising medical imaging technology.

Critical relevance statement Dynamic chest radiography provides a wealth of clinical information, but further research is required to identify its clinical niche.

Graphical abstract
Purtscher-like retinopathy in a 19-year-old with maturity-onset diabetes of the young: a case report
Authors: Oh Angela J. , Javaheri Michael , Hosseini Hamid , Prasad Pradeep S.
Published: June 2023

Background

We report the first case of Purtscher-like retinopathy in a patient with 17q12 deletion-associated maturity-onset diabetes of the young.

Case presentation

A 19-year-old diabetic Hispanic male with history of cataracts and toe amputations presented with sudden onset of painless bilateral vision loss for 1 week with no associated trauma. Visual acuity was counting fingers at six feet in both eyes. Dilated retinal examination revealed bilateral peripapillary cotton wool spots and intraretinal hemorrhages, and significant subretinal and intraretinal fluid on optical coherence tomography. Fluorescein angiography revealed arteriolar staining and leakage around the disc with areas of capillary nonperfusion, supporting the diagnosis of Purtscher-like retinopathy. Systemic workup revealed multiple diabetic complications including chronic osteomyelitis of multiple toes, nonhealing diabetic foot ulcers, neurogenic bladder and bowel, and bilateral lower-extremity muscular neuropathies. Genetic evaluation revealed a 17q12 deletion, which is associated with maturity-onset diabetes of the young 5. On follow-up examination, he received a single intravitreal antivascular endothelial growth factor injection in the left eye (off label) for persistent macular edema. Although his retinal edema improved, his visual acuity remained poor.

Conclusions

The presentation of our patient’s multiple diabetic complications along visual symptoms suggests Purtscher-like retinopathy can be a sequela of uncontrolled diabetes. Purtscher-like retinopathy is a rare but possible consideration in diabetic patients who present with acute-onset vision loss.
Long-term follow-up and exploration of the mechanism of stromal vascular fraction gel in chronic wounds
Authors: Cai Yuan , Zhang Fang , Feng Jingwei , Wu Bihua , Li Hai , Xiao Shune , Lu Feng , Wei Zairong , Deng Chengliang
Published: June 2023

Background

Chronic refractory wounds easily relapse and seriously affect the patients’ quality of life. Previous studies have shown that stromal vascular fraction gel (SVF-gel) significantly promotes the early healing of chronic wounds; however, the mechanisms of SVF-gel function per se remain unclear, and a long-term follow-up is lacking. This study aims to explore the mechanisms of SVF-gel promoting the healing of chronic wounds and follow up the long-term efficacy of SVF-gel.

Methods

Autologous SVF-gel transplantation was performed in 20 patients with chronic wounds (from March 2016 to September 2019), and the size of the wound before and after SVF-gel transplantation was observed. The conditioned medium (CM) was harvested from SVF-gel under serum-free, serum-deprivation and 10% fetal bovine serum (FBS) microenvironment in vitro, respectively. The concentration of the growth factors in the two kinds of gel-CM was tested, and their effects on the proliferation and migration of human dermal fibroblasts (HDFs) were detected.

Results

All patients had 100% wound closure eventually, and the average time to complete closure was 28.3 ± 9.7 days. The time of follow-up ranged from 2 to 6 years, and there was no wound recurrence. Interestingly, the concentrations of epidermal growth factor and transforming growth factor β1 of the CM were higher in serum-free and serum-deprivation condition than in 10% FBS microenvironment (p < 0.05). Correspondingly, the proliferation and migration ability of HDFs treated with gel-CM from serum-free condition were stronger than those treated with gel-CM from serum-deprivation (2% FBS) or 10% FBS microenvironment (p < 0.05).

Conclusion

These results indicate that it is safe, effective, and lasting in effect to treat chronic wounds with SVF-gel and mechanisms of action that include secreting various cytokines and promoting cell proliferation and migration ability.

Trial registration: Chinese Clinical Trail Registry, ChiCTR2000034624. Registered 12 July 2020—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=56058
A neonatal rat model of pulmonary vein stenosis
Authors: Li Debao , Qiu Lisheng , Hong Haifa , Chen Hao , Zhao Peibin , Xiao Yingying , Zhang Hao , Sun Qi , Ye Lincai
Published: June 2023

Objectives

Pulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS.

Methods

PVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, fibrosis staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining, fibrosis staining, and immunofluorescence.

Results

At P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time—indicators of PAH—at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness.

Conclusions

A neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.
WDIG: a wavelet domain image generation framework based on frequency domain optimization
Authors: Zhu Qing , Li Xiumei , Sun Junmei , Bai Huang
Published: June 2023

In the end-to-end image generation task, the spatial domain of pixel space cannot explicitly separate the low-frequency general information such as texture and color from the high-frequency detail information such as structure and identity. The loss function calculated in the spatial domain fails to effectively constrain the maintenance of detail information, and the generated image quality is insufficient. In this paper, a wavelet domain image generation (WDIG) framework is proposed to preserve the frequency information of images, in which the loss functions are constructed in the pixel space and wavelet space. In the pixel space, the low-frequency and high-frequency characteristic information of the signal are obtained by setting the appropriate Gaussian kernel and adopting the Gaussian fuzzy method. The loss function of $$\ell_{1}$$

ℓ
1

norm spatial domain is constructed for the low-frequency and high-frequency characteristic information. In the wavelet space, the corresponding channel sub-band coefficients are obtained by wavelet transform, and the image is explicitly separated into high-frequency information and low-frequency information. The $$\ell_{1}$$

ℓ
1

norm frequency domain loss function is constructed respectively for the sub-band coefficients. The WDIG can constrain model training more accurately and optimize model more precisely, so as to better maintain the details and quality of generated image. The WDIG framework is evaluated in the image generation applications including style transfer, image translation and Generative Adversarial Nets (GAN) Inversion. Experimental results show that the WDIG framework can effectively retain the details of images and generate more realistic images, and improve the image quality of the above applications in image generation.
Effectiveness of Mindfulness-Based Cognitive Therapy in reducing psychological distress and improving sleep in patients with Inflammatory Bowel Disease: study protocol for a multicentre randomised controlled trial (MindIBD).
Authors: ter Avest Milou M , van Velthoven Annelieke S M , Speckens Anne E M , Dijkstra Gerard , Dresler Martin , Horjus Carmen S , Römkens Tessa E H , Witteman Ellen M , van Dop Willemijn A , Bredero Quirine M , Nissen Loes H C , Huijbers Marloes J
Published: June 2023

Background

Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD.

Methods

The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted.

Discussion

This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions.

Trial registration

ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.
Humanized APOE genotypes influence lifespan independently of tau aggregation in the P301S mouse model of tauopathy
Authors: Williams Tristan , Bathe Tim , Vo Quan , Sacilotto Patricia , McFarland Karen , Ruiz Alejandra Jolie , Hery Gabriela P. , Sullivan Patrick , Borchelt David R. , Prokop Stefan , Chakrabarty Paramita
Published: June 2023

Apolipoprotein (APOE) E4 isoform is a major risk factor of Alzheimer’s disease and contributes to metabolic and neuropathological abnormalities during brain aging. To provide insights into whether APOE4 genotype is related to tau-associated neurodegeneration, we have generated human P301S mutant tau transgenic mice (PS19) that carry humanized APOE alleles (APOE2, APOE3 or APOE4). In aging mice that succumbed to paralysis, PS19 mice homozygous for APOE3 had the longest lifespan when compared to APOE4 and APOE2 homozygous mice (APOE3 > APOE4 ~ APOE2). Heterozygous mice with one human APOE and one mouse Apoe allele did not show any variations in lifespan. At end-stage, PS19 mice homozygous for APOE3 and APOE4 showed equivalent levels of phosphorylated tau burden, inflammation levels and ventricular volumes. Compared to these cohorts, PS19 mice homozygous for APOE2 showed lower induction of phosphorylation on selective epitopes, though the effect sizes were small and variable. In spite of this, the APOE2 cohort showed shorter lifespan relative to APOE3 homozygous mice. None of the cohorts accumulated appreciable levels of phosphorylated tau compartmentalized in the insoluble cell fraction. RNAseq analysis showed that the induction of immune gene expression was comparable across all the APOE genotypes in PS19 mice. Notably, the APOE4 homozygous mice showed additional induction of transcripts corresponding to the Alzheimer’s disease-related plaque-induced gene signature. In human Alzheimer’s disease brain tissues, we found no direct correlation between higher burden of phosphorylated tau and APOE4 genotype. As expected, there was a strong correlation between phosphorylated tau burden with amyloid deposition in APOE4-positive Alzheimer’s disease cases. Overall, our results indicate that APOE3 genotype may confer some resilience to tauopathy, while APOE4 and APOE2 may act through multiple pathways to increase the pathogenicity in the context of tauopathy.
Skin-Net: a novel deep residual network for skin lesions classification using multilevel feature extraction and cross-channel correlation with detection of outlier
Authors: Alsahafi Yousef S. , Kassem Mohamed A. , Hosny Khalid M.
Published: June 2023

Human Skin cancer is commonly detected visually through clinical screening followed by a dermoscopic examination. However, automated skin lesion classification remains challenging due to the visual similarities between benign and melanoma lesions. In this work, the authors proposed a new Artificial Intelligence-Based method to classify skin lesions. In this method, we used Residual Deep Convolution Neural Network. We implemented several convolution filters for multi-layer feature extraction and cross-channel correlation by sliding dot product filters instead of sliding filters along the horizontal axis. The proposed method overcomes the imbalanced dataset problem by converting the dataset from image and label to vector of image and weight. The proposed method is tested and evaluated using the challenging datasets ISIC-2019 & ISIC-2020. It outperformed the existing deep convolutional networks in the multiclass classification of skin lesions.

Graphical Abstract
Mirizzi syndrome type V complicated with triple fistula: a case report
Authors: Lalountas Miltiadis , Smyrlis Nikolaos , Mouratidis Stylianos Vladimiros , Makedos Panagiotis
Published: June 2023

Background

Mirizzi syndrome (MS) is a complicated form of longstanding, symptomatic cholelithiasis. According to Beltran Classification MS Type V has been introduced to describe the cholecystoenteric fistula, with or without gallstone ileus. Mirizzi syndrome Type V with double fistula has been reported in the past; however, the triple fistula is an even rarer case, first described in the international literature so far.

Case presentation

A 77-year-old male was admitted to our surgical department with recurrent episodes of abdominal pain, which initially presented in the last 6 months and was accompanied with jaundice. Computed tomography showed findings of cholelithiasis, pneumobilia and choledocholithiasis. We performed an ERCP, which showed two fistulas of the gallbladder with the pyloric antrum and the duodenum, respectively. Surgical treatment was immediately undergone and during laparotomy, we confirmed these findings. We ligated and dissected these communications. In addition, a third fistula between the gallbladder and the common bile duct was identified. An insertion of a Kehr T-tube into the common bile duct was performed via the gallbladder. After 3 months, the Kehr T-tube was removed and in the subsequent 2 years of follow-up the patient was presented without complications.

Conclusions

Mirizzi syndrome complicated with triple fistula, first described in the international literature, to the best of our knowledge, confirms the long natural history of inflammation.
Developing and implementing a public health co-research program for Special Olympics athletes
Authors: Kirova Anna-Mariya , Jakab Tyler , Bartsch Graham , Corazzini Stephanie , Sokoloff Alexis , Delahunty Erin , Seymour Rachel , Rubenstein Eric
Published: June 2023

Individuals with intellectual and developmental disabilities are often the subject of research while rarely being included in formulating research questions, planning studies, and making decisions related to protocols and analyses. In turn, most research regarding people with intellectual and developmental disabilities is not carried out by researchers with disabilities themselves. We developed a co-research training program where individuals with intellectual and developmental disabilities were taught about research. The program was designed using best practices and existing materials resources. We recruited four participants from Special Olympics Massachusetts and conducted the training in the Fall of 2021. We evaluated the program with surveys, qualitative interviews, and tracking continued involvement of co-researchers in research projects. Participants were partners in the evaluation process. The training program was six sessions and included lessons about why research is important, how to conduct research, and an experiential learning project where co-researchers conducted a study of their coaches. The program was well received by participants, and one year later they were still involved with research projects. A co-researcher training focused on public health for Special Olympics athletes is feasible and beneficial for athletes, researchers, and Special Olympics programs. However, there are still barriers like a lack of funding and time, that need to be addressed to ensure wide program success.
Application of Tinel’s test combed with clinical neurosensory test distinguishes spontaneous healing of lingual nerve neuropathy after mandibular third molar extraction
Authors: Fujita Shigeyuki , Tojyo Itaru , Suzuki Shigeru , Tajima Fumihiro
Published: June 2023

Background

Extraction of the mandibular third molar, the most frequent and important surgical procedure in the clinical practice of oral surgery, is associated with the risk of injury of the lingual nerve. Neuropathy of the lingual nerve poses diagnostic challenges regarding the transient or permanent nature of the injury. No consensus or criteria have been established regarding the diagnosis of lingual nerve neuropathy. We applied both Tinel’s test and clinical neurosensory testing together, which can be easily used at the bedside in the early stages of injury. Therefore, we propose a new method to differentiate between lesions with the ability to heal spontaneously and those that cannot heal without surgery.

Results

Thirty-three patients (29 women,  4 men; mean age, 35.5 years) were included in this study. For all patients, the median interval between nerve injury and initial examination was 1.6 months and that between nerve injury and the second examination before determining the need for surgical management was 4.5 months. The patients were assigned to either group A or B. The spontaneous healing group (group A, n = 10) revealed a tendency for recovery within 6 months after tooth extraction. In this group, although there were individual differences in the degree of recovery, a remarkable tendency for recovery was observed based on clinical neurosensory testing in all cases. None of the patients were diagnosed with allodynia. In seven cases, the Tinel test result was negative at the first inspection, and in three cases, the result changed to negative at the second inspection. Conversely, in group B(n = 23), no recovery trend was observed with regard to clinical neurosensory testing, and nine patients had allodynia. Further, the Tinel test result was positive for all patients in both examinations.

Conclusions

Our findings indicate that in case of transient lingual nerve paralysis, clinical neurosensory testing findings deteriorate immediately after tooth extraction and gradually recover, while Tinel’s test shows a negative result. Using Tinel’s test and clinical neurosensory testing together enabled early and easy identification of the severity of the lingual nerve disorder and of lesions that would heal spontaneously without surgical management.
Childcare in Italy among migrants and natives: who uses which type and why?
Authors: Mussino Eleonora , Ortensi Livia Elisa
Published: June 2023

The Italian welfare state is characterised by a preference for income transfers over transfers in kind and the marginal role of policies aimed directly at supporting the family. Despite the growing participation of women in the labour market, the Italian welfare system still assumes the family, with its unbalanced gender division of housework and its intergenerational solidarity, to be the primary provider of protection and support. As a result, in Italy in 2019 only 26.9% of children under 3 years of age were enrolled in formal childcare, which is below the European average. In this context, births from at least one foreign parent had increased over time, and foreign national children accounted for 14.0% of all children aged 0–3 in 2019. Despite this, migrants are still seen as ‘suppliers’ rather than citizens who, as parents, are potential consumers of childcare services. Aspects related to the use of childcare by migrants and differences compared to natives in Italy are currently understudied. We use the 2012 Birth Sample Survey by the Italian National Institute of Statistics to fill this gap. Mothers were interviewed about 18–21 months after having given birth: information on sociodemographic characteristics of both parents was collected, including their use of childcare services, their reasons for not using them, their unmet need for childcare services, and the lack of access to the job market due to care work. Our study aims to understand childcare patterns among migrants and the differences between them and those of the native-born population. We found that Italian mothers use informal care more than migrants. Unlike the evidence from other international studies, our results show that migrant mothers use daycare for children aged 0–3 more than native-born mothers. However, we found that the migrants who had arrived as children show patterns more similar to natives. This finding might be associated with a better knowledge of the system and a more extensive network (including grandparents) in Italy. Similarly, we found that migrant mothers who co-parent with an Italian father use more informal care and experience lower logistical barriers to accessing daycare. In addition, we observed that obstacles to children’s enrolment resulting in an unmet need for daycare are also related to migrant background.
More of what? Dissociating effects of conceptual and numeric mappings on interpreting colormap data visualizations
Authors: Soto Alexis , Schoenlein Melissa A. , Schloss Karen B.
Published: June 2023

In visual communication, people glean insights about patterns of data by observing visual representations of datasets. Colormap data visualizations (“colormaps”) show patterns in datasets by mapping variations in color to variations in magnitude. When people interpret colormaps, they have expectations about how colors map to magnitude, and they are better at interpreting visualizations that align with those expectations. For example, they infer that darker colors map to larger quantities (dark-is-more bias) and colors that are higher on vertically oriented legends map to larger quantities (high-is-more bias). In previous studies, the notion of quantity was straightforward because more of the concept represented (conceptual magnitude) corresponded to larger numeric values (numeric magnitude). However, conceptual and numeric magnitude can conflict, such as using rank order to quantify health—smaller numbers correspond to greater health. Under conflicts, are inferred mappings formed based on the numeric level, the conceptual level, or a combination of both? We addressed this question across five experiments, spanning data domains: alien animals, antibiotic discovery, and public health. Across experiments, the high-is-more bias operated at the conceptual level: colormaps were easier to interpret when larger conceptual magnitude was represented higher on the legend, regardless of numeric magnitude. The dark-is-more bias tended to operate at the conceptual level, but numeric magnitude could interfere, or even dominate, if conceptual magnitude was less salient. These results elucidate factors influencing meanings inferred from visual features and emphasize the need to consider data meaning, not just numbers, when designing visualizations aimed to facilitate visual communication.
miR-155 and miR-92 levels in ALL, post-transplant aGVHD, and CMV: possible new treatment options
Authors: Saadi Mahdiyar Iravani , Nikandish Mohsen , Ghahramani Zahra , Valandani Fatemeh Mardani , Ahmadyan Maryam , Hosseini Fakhroddin , Rahimian Zahra , Jalali Heeva , Tavasolian Fataneh , Abdolyousefi Ehsan Nabi , Kheradmand Nadiya , Ramzi Mani
Published: June 2023

Background

Acute lymphoblastic leukemia (ALL) is a malignancy that leads to altered blast cell proliferation, survival, and maturation and eventually to the lethal accumulation of leukemic cells. Recently, dysregulated expression of various micro-RNAs (miRNAs) has been reported in hematologic malignancies, especially ALL. Cytomegalovirus infection can induce ALL in otherwise healthy individuals, so a more detailed evaluation of its role in ALL-endemic areas like Iran is required.

Methods

In this cross-sectional study, 70 newly diagnosed adults with ALL were recruited. The expression level of microRNA-155(miR-155) and microRNA-92(miR-92) was evaluated by real-time SYBR Green PCR. The correlations between the miRNAs mentioned above and the severity of disease, CMV infection, and acute graft vs. host disease after hematopoietic stem cell transplantation (HSCT) were assessed. B cell and T cell ALL distinction in the level of miRNAs was provided.

Results

After the statistical analysis, our results indicated a marked increase in the expression of miR-155 and miR-92 in ALL patients vs. healthy controls (*P = 0.002–*P = 0.03, respectively). Also, it was shown that the expression of miR-155 and miR-92 was higher in T cell ALL compared to B cell ALL (P = 0.01–P = 0.004, respectively), CMV seropositivity, and aGVHD.

Conclusion

Our study suggests that the plasma signature of microRNA expression may act as a powerful marker for diagnosis and prognosis, providing knowledge outside cytogenetics. Elevation of miR-155 in plasma can be a beneficial therapeutic target for ALL patients, with consideration of higher plasma levels of miR-92 and miR-155 in CMV + and post-HSCT aGVHD patients.