bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging negative myelopathy in Leber’s hereditary optic neuropathy: a case report
Authors: Martikainen Mika H. , Suomela Miika , Majamaa Kari
Published: December 2022

Background

Leber’s hereditary optic neuropathy (LHON) is a common form of mitochondrial disease. The typical clinical presentation of LHON is subacute, painless loss of vision resulting from bilateral optic nerve atrophy. Moreover, extra-ocular manifestations such as cardiac conduction abnormalities and neurological manifestations such as multiple sclerosis (MS) like disease or parkinsonism are encountered in some patients. Abnormal findings in spinal cord MR imaging or in the cerebrospinal fluid (CSF) have been observed in previous cases of LHON-associated myelopathy.

Case presentation

We report a male patient with LHON who developed symptoms of myelopathy including gait unsteadiness, enhanced deep tendon reflexes and sensory loss of the lower extremities. Imaging of the brain and spinal cord, CSF analysis, as well as neurography and electromyography did not disclose any abnormalities. The somatosensory evoked potential (SEP) findings were suggestive of dorsal column dysfunction.

Conclusions

The patient case demonstrates that myelopathy associated with LHON can present without abnormal findings in central nervous system MR imaging or in the CSF, and without evidence suggestive of multiple sclerosis or MS-like disease. The dorsal column seems to be particularly vulnerable to myelopathy changes in LHON. Evoked potential investigations may assist in confirming the diagnosis, when clinical features are in line with myelopathy but findings in CSF analysis and central nervous system imaging are normal.
Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID)
Authors: Mao Chenhui , Zhou Liangrui , Li Jie , Pang Junyi , Chu Shanshan , Jin Wei , Huang Xinying , Wang Jie , Liu Caiyan , Liu Qing , Hao Honglin , Zhou Yan , Hou Bo , Feng Feng , Shen Lu , Tang Beisha , Peng Bin , Cui Liying , Gao Jing
Published: December 2022

Background

Neuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort.

Methods

Patients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed.

Results

Thirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aβ42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a “kite-like” specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia.

Conclusions

Specific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.
Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort
Authors: Vella Katia , Vella Sandro , Savona-Ventura C. , Vassallo J.
Published: December 2022

Background

Thyroid dysfunction is known to adversely affect pregnancy. This study evaluates the prevalence of thyroid disorders and explores their association with pregnancy complications/comorbidities and modes of delivery in the Maltese pregnant population over a ten year period.

Design

A population based observational study.

Method

We analysed data from the National Obstetrics Information Service of the Department of Health Informations and Research (NOIS) for all births delivered in Malta between 2006 and 2016. Cases identified and recorded by NOIS to have had some form of thyroid dysfunction during pregnancy were confirmed by cross-referencing  with laboratory results found in patients’ medical records and/or iSOFT® database system. Using the Statistical Package for the Social sciences (SPSS®)  demographic data, past obstetric and medical history and obstetric outcomes were analysed for pregnancies with thyroid dysfunction and compared to data pertaining to pregnancies in euthyroid patients, that is those with no recorded thyroid dysfunction on NOIS. Chi square/Fisher's exact test were used to compare categorical variables while ANOVA/Mann-Whitney U test was used to compare continuous variables. Statistical significance was defined by a two-sidedpvalue <0.05.

Results

Data was available for 46,283 women (mean [SD] age = 29.2 [5.4] years). 587 pregnancies (1.3%) suffered from thyroid dysfunction. Of these, 67.3% were hypothyroid, 3.2% had hyperthyroidism, 28.3% had isolated hypothyroxinaemia (IHT) while 1.2% had a history of thyroid carcinoma. Patients with IHT and hypothyroidism were older than euthyroid patients (p< 0.001).  IHT and hypothyroid patients had a statistically significant higher body mass index (BMI) than euthyroid women (p=0.001 for hypothyroid women,p= 0.035 for IHT). Hypothyroid  and IHT women were more likely to have had a previous lower segment caesarean section  (p=0.043,  and 0.006 respectively). Type 1 diabetes and gestational diabetes p= 0.012) were more common associated comorbidities in hypothyroid pregnancies. Offspring of patients with IHT had a higher birth weight than those born to euthyroid patients (p=0.009). Patients with hyperthyroidism were found to have a significantly increased risk of early preterm delivery before 34 weeks of gestation and were also more likely to have suspected intrauterine growth restriction and low mean birth weight. We report no significant differences in past history of obstetric loss, antenatal complications, mode of delivery, gestational age at delivery and postpartum haemorrhage rates across thyroid categories.

Conclusions

Available evidence suggests that thyroid dysfunction is more likely in the setting of older age, and higher body mass index. Moreover, it impacts on neonatal birth weight, rates of early preterm delivery and intrauterine growth restriction.
Physical self-concept and ability to swim in patients born with anorectal malformation and Hirschsprung’s disease: a case control study
Authors: König Tatjana Tamara , Krude Mattis , Muensterer Oliver J.
Published: December 2022

Background

Children with anorectal malformation (ARM) and Hirschsprung’s Disease (HD) live with permanent urinary and bowel symptoms, possibly impairing motor development in early childhood. Not being able to swim adds an unnecessary health risk. The aim of this study was to determine the ability to swim and physical self-concept in patients with ARM and HD.

Methods

We performed an anonymous survey among the members of the national patient organization SoMA e.V. (6 through 25 years). A control group was recruited from our department. Ability to swim, symptom load according to Rintala Score and physical self-concept were recorded using validated questionnaires. Patients were matched with controls according to gender and age. Mean scores and 95%-confidence intervals (95%-CI) were calculated, χ2-test and multiple linear regression models were used as appropriate.

Results

Totally, 83 match-control-pairs were included. Patients learned to swim at a similar age and rate (6.5 years, 95%-CI: 6.1–6.9, 74.7% swimmers) compared to controls (6.4 years, 95%-CI: 6.1–6.8, 79.5% swimmers, p = 0.46). VACTERL patients had a significantly lower swimmer rate (59.1%, p = 0.048). Swimmers had a significantly higher mean Rintala Score (12.5, 95%-CI: 11.6–13.2) compared to non-swimmers (10.4, 95%-CI: 8.1–12.1, p = 0,049). In prepubertal children (6 through 12 years), no difference in physical self-concept was shown compared to controls. Adolescents and young adults with ARM/HD, especially females, had a significantly lower mean score for the subscales of flexibility, speed, endurance and sports competence, independent of bowel symptom load according to Rintala Score.

Conclusions

Patients with ARM/HD have normal swimming skills and a normal physical self-concept in childhood that decreases with age compared to peers. In adolescence, parents and health care professionals should actively promote physical activity in ARM/HD patients.
Factors associated with recent and regular non-use of dental services by students from a university in southeastern Brazil: a cross-sectional study
Authors: de Oliveira Cunha Rafaela , Leite Isabel Cristina Gonçalves
Published: December 2022

Background

Lack of use of dental services can be a risk factor for oral health. In addition to recent visits to dental services, it is important to assess the regularity of use of these services, as well as the motivations for visiting the dentist. There is a gap in literature studies on the patterns of use of oral health services by the young university students. The goal of this study was to assess the factors associated with recent and regular non-use of dental services by young university students, using the Andersen model as a reference.

Methods

This was a cross-sectional study with 477 university students between 18 and 24 years old, carried out as a web survey, through which predisposing, enabling and need variables were collected, according to the model proposed by Andersen, to test the factors associated with recent and regular non-use of dental services. Bivariate analyses and robust Poisson regression were performed, with estimation of crude and adjusted prevalence ratios, using confidence intervals of 95%. The variables with p < 0.05 remained in the final model.

Results

The prevalence of recent non-use was of 19.5% (95% CI 16.0–23.3%), and of regular non-use, of 53.5% (95% CI 48.9–58.0%). After the adjusted analysis, the following were found to be associated with the outcome of recent non-use: type of service used (PR = 0.91; 95% CI 0.85–0.98) and perceived need for dental treatment (PR = 0.98; 95% CI 0.97–0.99); and the following variables were associated with regular non-use: father’s level of education (PR = 0.86; 95% CI 0.78–0.96), area of study (PR = 1.08; 95% CI 1.02–1.15), reason for last dental appointment (PR = 0.81; 95% CI 0.75–0.88), use of dental services throughout childhood (PR = 0.92; 95% CI 0.86–0.97), self-perceived oral health (PR = 0.86; 95% CI 0.76–0.88), and toothaches over the last 2 years (PR = 0.93; 95% CI 0.87–0.99).

Conclusion

The motivation for young university students to use dental services are curative treatment needs, not prevention. The results point to the need to implement health prevention and promotion policies in higher education institutions and to expand access to dental services for this young population.
Antifungal activity, mechanical properties, and accuracy of three-dimensionally printed denture base with microencapsulated phytochemicals on varying post-polymerization time
Authors: Jo Ye-Hyeon , Lee Won-Jun , Lee Ji-Hyun , Yoon Hyung-In
Published: December 2022

Background

Studies on the antifungal activity, flexural strength, Vickers hardness, and intaglio surface trueness of three-dimensionally printed (3DP) denture bases with microencapsulated phytochemicals with respect to changes in post-polymerization time (PPT) are lacking.

Methods

Specimens of various shapes and dimensions were fabricated with a 3DP denture base resin mixed with 5 wt% phytoncide-filled microcapsules. Each specimen was subjected to different PPT protocols of 5, 10, 20, and 30 min. Specimens without microcapsules with 5-min PPT were used as the negative control group. Cell colonies were counted to evaluate antifungal activity. Three-point bending and Vickers hardness tests were performed to measure the flexural strengths and hardness of the specimens. Fourier-transform infrared spectrometry was used to inspect the degree of conversion (DC). The intaglio surface trueness was measured using root-mean-square estimates calculated by superimposition analysis. A non-parametric Kruskal–Wallis test or one-way analysis of variance was performed (α = 0.05).

Results

The specimens with microcapsules and 10-min PPT showed the highest antifungal activity among the tested groups. Compared with the positive control group (5-min PPT), the specimens with PPTs of 10 min or longer showed significantly higher mean flexural strength, higher DC, greater hardness, and better trueness (all,P < 0.05). Except for the difference in antifungal activity, no statistically significant differences were detected between the specimens subjected to 10-, 20-, and 30-min PPT.

Conclusion

The 3DP denture base filled with microencapsulated phytoncide showed different antifungal activity and physical properties on changing PPT. The 3DP denture base containing phytoncide-filled microcapsules at 5 wt% concentration and subjected to 10-min PPT exhibited sufficient antifungal activity as well as mechanical properties and accuracy within clinical acceptance.
Periodontal maintenance: individual patient responses and discontinuations
Authors: Graetz Christian , Ehrenthal Johannes C. , Kowalski Rebecca , Cyris Miriam , Geiken Antje , Dörfer Christoph E.
Published: December 2022

Aim

There is a lack of data on long-term impact of different psychological variables on periodontitis. Aim of the current study was to investigate the impact of psychological factors in patients with chronic periodontitis (CP; according to the 1999 Classification of Periodontal Diseases) to explain adherence to or discontinuation of supportive periodontal therapy (SPT) in a university setting.

Methods

A sample of n = 119 patients were examined in a questionnaire-based, cross-sectional survey. All patients had received active periodontal treatment (APT) and were reevaluated in a university setting (Kiel) before 2016 [T1: start SPT]. Patients who showed sufficient adherence to SPT of ≥ 2 years (maximum ± 6 months of deviation between SPT intervals, last visit and questionnaire at T2) were assigned to the adherence group (AG: n = 58), or, if they interrupted SPT or stopped treatment altogether, to the non-adherence group (NAG: n = 61). In addition to dental parameters, we assessed socio-demographic, treatment-related (critical attitudes/complaints), dental as well as psychological variables (especially psychological attachment, but also dental fear, patient participation style, personality functioning) and examined between-group differences as well as possible mediating factors of non-adherence to treatment continuation.

Results

For both groups we found similar average observation time (NAG/AG: 15.9(8.9)/14.9(10.6)years). There were significant differences in age, critical attitudes, dental fear, and patient participation style between the groups. With the help of exploratory sequential mediation models, we found a significant indirect pathway of the impact of attachment anxiety on discontinuation of treatment mediated through dental fear and number of critical attitudes/complaints.

Conclusion

Considering the limitations, dentists should be aware of personality-related risk-factors such as attachment anxiety as well as their interplay with levels of dental fear and critical attitudes which may influence adherence to SPT.

Trial registration: The clinical trial was retrospectively registered in the DRKS—German Clinical Trials Register (https://www.drks.de) with registration DRKS00030092 (26/08/2022).
Long-term outcome of ultrasound-guided focused ultrasound ablation for gestational trophoblastic neoplasia in the cesarean scar: a case report
Authors: Qu Dacheng , Chen Yan , Jiang Jing , Shi Qiuling , Zhou Honggui , Wang Zhibiao
Published: December 2022

Background

The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility.

Case presentation

A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up.

Conclusion

Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding.
Conformational alteration in glycan induces phospholipase Cβ1 activation and angiogenesis
Authors: Wang Sheng-Hung , Cheng Jing-Yan , Tsai Hsiu-Hui , Lo Tzu-Chi , Hung Jung-Tung , Lin Chun-Cheng , Lee Chien-Wei , Ho Yi-Hsuan , Kuo Huan-Hsien , Yu Alice L. , Yu John
Published: December 2022

Background

In endothelial cells, phospholipase C (PLC) β1-activated Ca2+ is a crucial second messenger for the signaling pathways governing angiogenesis. PLCβ1 is inactivated by complexing with an intracellular protein called translin-associated factor X (TRAX). This study demonstrates specific interactions between Globo H ceramide (GHCer) and TRAX, which highlight a new angiogenic control through PLCβ1 activation.

Methods

Globo-series glycosphingolipids (GSLs), including GHCer and stage-specific embryonic antigen-3 ceramide (SSEA3Cer), were analyzed using enzyme-linked immunosorbent assay (ELISA) and Biacore for their binding with TRAX. Angiogenic activities of GSLs in human umbilical vein endothelial cells (HUVECs) were evaluated. Molecular dynamics (MD) simulation was used to study conformations of GSLs and their molecular interactions with TRAX. Fluorescence resonance energy transfer (FRET) analysis of HUVECs by confocal microscopy was used to validate the release of PLCβ1 from TRAX. Furthermore, the in vivo angiogenic activity of extracellular vesicles (EVs) containing GHCer was confirmed using subcutaneous Matrigel plug assay in mice.

Results

The results of ELISA and Biacore analysis showed a stable complex between recombinant TRAX and synthetic GHCer with Kd of 40.9 nM. In contrast, SSEA3Cer lacking a fucose residue of GHCer at the terminal showed ~ 1000-fold decrease in the binding affinity. These results were consistent with their angiogenic activities in HUVECs. The MD simulation indicated that TRAX interacted with the glycan moiety of GHCer at amino acid Q223, Q219, L142, S141, and E216. At equilibrium the stable complex maintained 4.6 ± 1.3 H-bonds. TRAX containing double mutations with Q223A and Q219A lost its ability to interact with GHCer in both MD simulation and Biacore assays. Removal of the terminal fucose from GHCer to become SSEA3Cer resulted in decreased H-bonding to 1.2 ± 1.0 by the MD simulation. Such specific H-bonding was due to the conformational alteration in the whole glycan which was affected by the presence or absence of the fucose moiety. In addition, ELISA, Biacore, and in-cell FRET assays confirmed the competition between GHCer and PLCβ1 for binding to TRAX. Furthermore, the Matrigel plug assay showed robust vessel formation in the plug containing tumor-secreted EVs or synthetic GHCer, but not in the plug with SSEA3Cer. The FRET analysis also indicated the disruption of colocalization of TRAX and PLCβ1 in cells by GHCer derived from EVs.

Conclusions

Overall, the fucose residue in GHCer dictated the glycan conformation for its complexing with TRAX to release TRAX-sequestered PLCβ1, leading to Ca2+ mobilization in endothelial cells and enhancing angiogenesis in tumor microenvironments.
Neutralizing monoclonal antibody in patients with coronavirus disease 2019: an observational study
Authors: Liao Xuejiao , Li Dapeng , Liu Jie , Liu Zhi , Ma Zhenghua , Dong Jingke , Yang Xiangyi , Shu Dan , Yuan Jing , Liu Lei , Zhang Zheng
Published: December 2022

Background

Clinical data on patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant are limited, especially on clinical status after the application of antibody therapy.

Methods

We evaluated clinical status in patients with the SARS-CoV-2 delta variant after BRII-196 and BRII-198 treatment in an infectious disease hospital in China. We collected data on clinical symptoms, laboratory tests, radiological characteristics, viral load, anti-SARS-CoV-2 antibodies, treatment, and outcome.

Results

In mid-June 2021, 36 patients with delta variant infection were identified in Shenzhen. The most common symptoms at illness onset were cough (30.6%), fever (22.2%), myalgia (16.7%), and fatigue (16.7%). A small number of patients in this study had underlying diseases, including diabetes (5.6%) and hypertension (8.3%). The application of BRII-196 and BRII-198 can rapidly increase anti-SARS-CoV-2 IgG. The median peak IgG levels in the antibody treatment group were 32 times higher than those in the control group (P < 0.001). The time from admission to peak IgG levels in the antibody treatment group (mean: 10.2 days) was significantly shorter than that in the control group (mean: 17.7 days). Chest CT score dropped rapidly after antibody therapy, with a mean duration of 5.74 days from admission to peak levels.

Conclusion

The results of this study suggest that the application of BRII-196 and BRII-198 antibody therapy improved clinical status in patients with SARS-CoV-2 delta variant infection.
An unusual occurrence of penetrating aortic arch injury by a ball-point pen: a case report and review of the literature
Authors: Ariaka Herbert , Magala John Paul , Kebba Naomi , Kabuye Ronald , Namirembe Stella Magara , Mwambu Tom Philip , Ahabwe Kenneth , Nalule Miriam
Published: December 2022

Background

Aortic arch injuries account for about 8% of thoracic aortic injuries. Penetrating zone I neck injuries account for 18% of vascular injuries in the neck and have great potential to traverse to involve thoracic vascular structures as well. The hard and soft signs of vascular injury facilitate triage of patients on an individual basis. We present a case of a ball-point pen traversing through zone I of the neck and causing penetrating aortic arch injury with minimal mediastinal haemorrhage.

Case presentation

We present a polytrauma patient who was admitted with traumatic brain injury and a ball-point pen lodged above the sternal notch in zone I of the neck following a road traffic accident. He underwent mediastinal exploration via a median sternotomy. The ball-point pen was found penetrating the anterior wall of the aortic arch and resting in its lumen. The ball-point pen was successfully explanted and primary repair of the penetrating aortic arch injury was done. He had an uneventful recovery without any added secondary neurological complications.

Conclusion

Penetrating aortic arch injuries are rare compared to injuries of the ascending aorta and descending aorta. They require a high index of suspicion, rapid investigation and urgent intervention in view of their high associated fatality. The ball-point pen in this case assumed the shape of a plug which acted as a seal at the site of injury preventing catastrophic exsanguination.
Leishmania infantum infection does not affect the main composition of the intestinal microbiome of the Syrian hamster
Authors: Olías-Molero Ana Isabel , Botías Pedro , Cuquerella Montserrat , García-Cantalejo Jesús , Barcia Emilia , Torrado Susana , Torrado Juan José , Alunda José María
Published: December 2022

Background

Visceral leishmaniasis (VL) is the most severe form of all leishmanial infections and is caused by infection with protozoa of Leishmania donovani and Leishmania infantum. This parasitic disease occurs in over 80 countries and its geographic distribution is on the rise. Although the interaction between the intestinal microbiome and the immune response has been established in several pathologies, it has not been widely studied in leishmaniasis. The Syrian hamster is the most advanced laboratory model for developing vaccines and new drugs against VL. In the study reported here, we explored the relationship between the intestinal microbiome and infection with L. infantum in this surrogate host.

Methods

Male Syrian hamsters (120–140 g) were inoculated with 108 promastigotes of a canine-derived L. infantum strain or left as uninfected control animals. Infection was maintained for 19 weeks (endpoint) and monitored by an immunoglobulin G (IgG) enyzme-linked immunosorbent assay throughout the experiment. Individual faecal samples, obtained at weeks 16, 18 and 19 post-inoculation, were analysed to determine the 16S metagenomic composition (the operational taxonomic units [OTUs] of the intestinal microbiome and the comparison between groups were FDR (false discovery rate)-adjusted).

Results

Leishmania infantum infection elicited moderate clinical signs and lesions and a steady increase in specific anti-Leishmania serum IgG. The predominant phyla (Firmicutes + Bacteriodetes: > 90%), families (Muribaculaceae + Lachnospiraceae + Ruminococcaceae: 70–80%) and genera found in the uninfected hamsters showed no significant variations throughout the experiment. Leishmania infantum infection provoked a slightly higher—albeit non-significant—value for the Firmicutes/Bacteriodetes ratio but no notable differences were found in the relative abundance or diversity of phyla and families. The microbiome of the infected hamsters was enriched in CAG-352, whereas Lachnospiraceae UCG-004, the [Eubacterium] ventriosum group and Allobaculum were less abundant.

Conclusions

The lack of extensive significant differences between hamsters infected and uninfected with L. infantum in the higher taxa (phyla, families) and the scarce variation found, which was restricted to genera with a low relative abundance, suggest that there is no clear VL infection-intestinal microbiome axis in hamsters. Further studies are needed (chronic infections, co-abundance analyses, intestinal sampling, functional analysis) to confirm these findings and to determine more precisely the possible relationship between microbiome composition and VL infection.

Graphical Abstract
Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages
Authors: Zhang Ze , Butler Rondi , Koestler Devin C. , Bell-Glenn Shelby , Warrier Gayathri , Molinaro Annette M. , Christensen Brock C. , Wiencke John K. , Kelsey Karl T. , Salas Lucas A.
Published: December 2022

Background

There is considerable evidence that epigenetic mechanisms and DNA methylation are critical drivers of immune cell lineage differentiation and activation. However, there has been limited coordinated investigation of common epigenetic pathways among cell lineages. Further, it remains unclear if long-lived memory cell subtypes differentiate distinctly by cell lineages.

Results

We used the Illumina EPIC array to investigate the consistency of DNA methylation in B cell, CD4 T, and CD8 T naïve and memory cells states. In the process of naïve to memory activation across the three lineages, we identify considerable shared epigenetic regulation at the DNA level for immune memory generation. Further, in central to effector memory differentiation, our analyses revealed specific CpG dinucleotides and genes in CD4 T and CD8 T cells with DNA methylation changes. Finally, we identified unique DNA methylation patterns in terminally differentiated effector memory (TEMRA) CD8 T cells compared to other CD8 T memory cell subtypes.

Conclusions

Our data suggest that epigenetic alterations are widespread and essential in generating human lymphocyte memory. Unique profiles are involved in methylation changes that accompany memory genesis in the three subtypes of lymphocytes.
On generalizations of some integral inequalities for preinvex functions via $(p,q)$-calculus
Authors: Luangboon Waewta , Nonlaopon Kamsing , Tariboon Jessada , Ntouyas Sotiris K. , Budak Hüseyin
Published: December 2022

In this paper, we establish some new $(p,q)$
(
p
,
q
)
-integral inequalities of Simpson’s second type for preinvex functions. Many results given in this paper provide generalizations and extensions of the results given in previous research. Moreover, some examples are given to illustrate the investigated results.
A new feature popularity framework for detecting cyberattacks using popular features
Authors: Zuech Richard , Hancock John , Khoshgoftaar Taghi M.
Published: December 2022

We propose a novel feature popularity framework, and introduce this new framework to the cybersecurity domain. Feature popularity has not yet been used in machine learning or data mining, and we implement it with three web attacks from the CSE-CIC-IDS2018 dataset: Brute Force, SQL Injection, and XSS web attacks. Feature popularity is based upon ensemble Feature Selection Techniques (FSTs) and allows us to more easily understand common and important features between different cyberattacks. Three filter-based and four supervised learning-based FSTs are used to generate feature subsets for each of our three different web attack datasets, and then our feature popularity frameworks are applied. Classification performance for feature popularity is mostly similar as compared to when “all features” are evaluated (with feature popularity subsets having better performance in 5 out of 15 experiments). Our feature popularity technique effectively builds an ensemble of ensembles by first building an ensemble of FSTs for each dataset, and then building another ensemble across a dataset agreement dimension. The Jaccard similarity is also employed with our feature popularity framework in order to better identify which attack classes should (or should not) be grouped together when applying feature popularity. The four most popular features across all three web attacks from this experiment are: Flow_Bytes_s, Flow_IAT_Max, Fwd_IAT_Std, and Fwd_IAT_Total. When only using these four features as input to our models, classification performance is not seriously degraded. This feature popularity framework granted us new and previously unseen insights into the web attack detection process with CSE-CIC-IDS2018 big data, even though we had intensely studied it previously. We realized these four particular features cannot properly identify our three web attacks, as they operate mainly from the time dimension and NetFlow features from layers 3 and 4 of the OSI model. Conversely, our three web attacks operate in the application layer (7) of the OSI model and should not leave signatures in these four features. Feature popularity produces easier to explain models which provide domain experts better visibility into the problem, and can also reduce the complexity of implementing models in real-world systems.
Plasmodium vivax: the potential obstacles it presents to malaria elimination and eradication
Authors: Habtamu Kassahun , Petros Beyene , Yan Guiyun
Published: December 2022

Initiatives to eradicate malaria have a good impact on P. falciparum malaria worldwide. P. vivax, however, still presents significant difficulties. This is due to its unique biological traits, which, in comparison to P. falciparum, pose serious challenges for malaria elimination approaches. P. vivax's numerous distinctive characteristics and its ability to live for weeks to years in liver cells in its hypnozoite form, which may elude the human immune system and blood-stage therapy and offer protection during mosquito-free seasons. Many malaria patients are not fully treated because of contraindications to primaquine use in pregnant and nursing women and are still vulnerable to P. vivax relapses, although there are medications that could radical cure P. vivax. Additionally, due to CYP2D6's highly variable genetic polymorphism, the pharmacokinetics of primaquine may be impacted. Due to their inability to metabolize PQ, some CYP2D6 polymorphism alleles can cause patients to not respond to treatment. Tafenoquine offers a radical treatment in a single dose that overcomes the potentially serious problem of poor adherence to daily primaquine. Despite this benefit, hemolysis of the early erythrocytes continues in individuals with G6PD deficiency until all susceptible cells have been eliminated. Field techniques such as microscopy or rapid diagnostic tests (RDTs) miss the large number of submicroscopic and/or asymptomatic infections brought on by reticulocyte tropism and the low parasitemia levels that accompany it. Moreover, P. vivax gametocytes grow more quickly and are much more prevalent in the bloodstream. P. vivax populations also have a great deal of genetic variation throughout their genome, which ensures evolutionary fitness and boosts adaptation potential. Furthermore, P. vivax fully develops in the mosquito faster than P. falciparum. These characteristics contribute to parasite reservoirs in the human population and facilitate faster transmission. Overall, no genuine chance of eradication is predicted in the next few years unless new tools for lowering malaria transmission are developed (i.e., malaria elimination and eradication). The challenging characteristics of P. vivax that impede the elimination and eradication of malaria are thus discussed in this article.
Time to initiate postpartum modern contraceptives among pregnant women in Ambo Town, Central Ethiopia; Cox-proportional hazard regression analysis
Authors: Bekele Gemechu Gelan , Roga Ephrem Yohannes , Gonfa Dajane Negesse , Yami Amare Tesfaye
Published: December 2022

Background

Timing of postpartum family planning is crucial for maternal and child wellbeing by preventing unintended and closely spaced pregnancies. However, studies are limited on the time to use modern contraceptives in Ethiopia. Therefore, this study aimed to fill these gaps by assessing the time to initiate postpartum modern contraceptive and identifying its predictors among pregnant women in Ambo town, central Ethiopia.

Methods

An institution based cross-sectional study was conducted among 356 pregnant women in Ambo town, Central Ethiopia. The data were analysed using STATA-16 software. Kaplan–Meier estimates were performed to explain time-to- modern contraceptive use. A Cox-proportional hazard regression analysis was conducted to identify predictors. The adjusted hazard ratio (AHR) with a 95% confidence interval was considered to declare a statistically significant association.

Results

This study showed that the median survival time to initiate postpartum modern contraceptives was 6 months. In this study, the risk of modern contraceptive use was 2.13 times higher (AHR = 2.13; 95% CI: 1.02–4.45) among younger women, 1.44 times higher (AHR = 1.44; 95% CI: 1.09–2.66) among women with no desire for more children, and 2.25 times higher (AHR = 2.25; 95% CI: 1.02–4.95) among nulliparous women. However, it is 57% times lower (AHR = 0.57; 95% CI: 0.32–0.94) among pregnant women with current unintended pregnancy.

Conclusion and recommendation

The median survival time to initiate postpartum modern contraceptive was 6 months. Age of the women, desire for more children, parity and pregnancy status were found to be the significant predictors of time to initiate postpartum modern contraceptive. Therefore health care providers and concerned stakeholders should consider these factors to increase the uptake of the postpartum contraceptive methods.
Regional differences in the reduction in cerebral FDG uptake induced by the ketogenic diet
Authors: Bennett O. A. , Ramsay S. C. , Malacova E. , Bourgeat P. , Goodman S. J. , Dunn C. J. , Robinson B. M. , Lee K. , Pattison D. A.
Published: December 2022

Background

The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using18F-FDG uptake as a surrogate marker.

Methods

A retrospective audit was conducted of the brain18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels.

Results

The expected negative association between serum glucose levels and whole brain18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain.

Conclusion

In a real-world clinical PET setting, cerebral18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.
Utility of gated SPECT parameters in detection of coronary artery disease in patients with normal perfusion images
Authors: Chantadisai Maythinee , Sirisalipoch Sasitorn , Vachatimanont Sira
Published: December 2022

Background

False negative myocardial perfusion images on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a substantial problem in the interpretation of MPI. To explore possible parameters from gated SPECT that could detected coronary artery disease (CAD) in patients with normal perfusion images, we retrospectively selected patients who underwent a 2-day Tc-99 m MIBI adenosine stress/rest MPI and a subsequent invasive coronary angiography. Gated SPECT parameters, including end systolic volume (ESV), end diastolic volume (EDV), left ventricular ejection fraction (LVEF), and transient ischemic dilation (TID) ratio of patients with and without CAD were compared and assessed for their respective diagnostic performance using receiver operating characteristics (ROC) area under the curve (AUC).

Results

Among 22 patients with normal perfusion images, 7 patients had CAD. Despite the small number of patients, we found significant differences between the ESV, the EDV, and the LVEF between patients with and without CAD. The analysis of ROC curve showed the stress ESV could excellently detect CAD (AUC = 0.900). The rest ESV, the stress EDV, the rest EDV, the stress LVEF and the rest LVEF could likewise perform well in the detection of CAD (AUC = 0.833, 0.819, 0.790, 0.862, and 0.838, respectively). In contrast, the change in LVEF and the TID ratio (AUC = 0.667 and 0.524, respectively) did not seem as reliable as other parameters. Optimal cutoffs for detection of CAD in patients with normal perfusion images from our study were ≥ 20.0 mL for the stress ESV, ≥ 71.0 mL for the stress EDV, ≤ 66.3 EF units for the stress LVEF, ≥ 18.0 mL for the rest ESV, ≥ 67.0 mL for the rest EDV and ≤ 70.0 EF unit for the rest LVEF.

Conclusions

Gated SPECT parameters could facilitate detection of CAD in patient with normal perfusion images on Tc-99m MIBI MPI. These parameters should be carefully interpreted to improve diagnostic accuracy and reduce false negative MPI.
Dynamic Craniotomy With NuCrani Reversibly Expandable Cranial Bone Flap Fixation Plates: A Technical Report
Authors: Khanna Rohit , Munz Michael , Baxter Silvia , Han Patrick
Published: December 2022

BACKGROUND:

Dynamic craniotomy provides cranial decompression without bone flap removal along with avoidance of cranioplasty and reduced risks for complications.

OBJECTIVE:

To report the first clinical cases using a novel dynamic craniotomy bone flap fixation system. The NeuroVention NuCrani reversibly expandable cranial bone flap fixation plates provide dynamic bone flap movement to accommodate changes in intracranial pressure (ICP) after a craniotomy.

METHODS:

The reversibly expandable cranial bone flap fixation plates were used for management of cerebral swelling in a patient with a subdural hemorrhage after severe traumatic brain injury and another patient with a hemorrhagic stroke.

RESULTS:

Both cases had high ICP's which normalized immediately after the dynamic craniotomy. Progressive postoperative cerebral swelling was noted which was compensated by progressive outward bone flap migration thereby maintaining a normal ICP, and with resolution of the cerebral swelling, the plates retracted the bone flaps to an anatomic flush position.

CONCLUSION:

The reversibly expandable plates provide an unhinged cranial bone flap outward migration with an increase in ICP and retract the bone flap after resolution of brain swelling while also preventing the bone flap from sinking inside the skull.
Patient, Disease, and Treatment-Related Factors Affecting Progression-Free and Disease-Specific Survival in Recurrent Chondrosarcomas of the Skull Base
Authors: Snyder Rita , Gadot Ron , Gidley Paul W. , Nader Marc-Elie , Hanna Ehab Y. , Su Shirley Y. , DeMonte Franco , Raza Shaan M.
Published: December 2022

BACKGROUND:

Recurrent skull base chondrosarcomas (CSA) are difficult to treat, and limited data are available to help guide subsequent therapy.

OBJECTIVE:

To further characterize the natural history of CSA and identify treatment modalities that were most effective in prolonging progression-free (PFS) and disease-specific survival (DSS).

METHODS:

We conducted a single-institution retrospective review of patients with recurrent skull base CSA from 1993 to 2021. Kaplan–Meier survival analyses for PFS and DSS were completed. Univariable and multivariable Cox proportional hazards regression models were used to identify patient-related, treatment-related, and disease-related factors that predicted PFS and DSS.

RESULTS:

A total of 28 patients and 84 episodes of recurrence were included. One-year PFS was 70.6%, 5-year PFS was 28.9%, and 10-year DSS was 78.5%. The median time to first progression was 23.9 months (range, 2.8-282 months). In univariable Cox proportional hazards regression, male sex, higher grade histology, fourth or greater progression episode status, distal pattern of recurrence, and treatment of recurrence without surgery or with chemotherapy alone predicted worse PFS. Multivariable regression predicted shortened DSS in male patients (hazard ratio [HR] 0.16; P = .021) and higher-grade tumors (HR 0.22; P = .039). Treatment of recurrence with surgery was associated with, but did not significantly predict, improved DSS (HR 1.78; P = .11).

CONCLUSION:

Several patient and disease-specific factors were associated with shorter PFS and DSS in recurrent skull base chondrosarcoma. For recurrences amenable to resection, surgery is recommended for treatment of recurrent CSA. Local recurrence management without surgery results in shorter PFS and DSS.
Mammalian DNA methylome dynamics: mechanisms, functions and new frontiers
Authors: Wei Alex , Wu Hao
Published: December 2022

DNA methylation is a highly conserved epigenetic modification that plays essential roles in mammalian gene regulation, genome stability and development. Despite being primarily considered a stable and heritable epigenetic silencing mechanism at heterochromatic and repetitive regions, whole genome methylome analysis reveals that DNA methylation can be highly cell-type specific and dynamic within proximal and distal gene regulatory elements during early embryonic development, stem cell differentiation and reprogramming, and tissue maturation. In this Review, we focus on the mechanisms and functions of regulated DNA methylation and demethylation, highlighting how these dynamics, together with crosstalk between DNA methylation and histone modifications at distinct regulatory regions, contribute to mammalian development and tissue maturation. We also discuss how recent technological advances in single-cell and long-read methylome sequencing, along with targeted epigenome-editing, are enabling unprecedented high-resolution and mechanistic dissection of DNA methylome dynamics.
Surface-localized glycoproteins act through class C ARFs to fine-tune gametophore initiation in Physcomitrium patens
Authors: Teh Ooi Kock , Singh Prerna , Ren Junling , Huang Lin Tzu , Ariyarathne Menaka , Salamon Benjamin Prethiviraj , Wang Yu , Kotake Toshihisa , Fujita Tomomichi
Published: December 2022

Arabinogalactan proteins are functionally diverse cell wall structural glycoproteins that have been implicated in cell wall remodeling, although the mechanistic actions remain elusive. Here, we identify and characterize two AGP glycoproteins, SLEEPING BEAUTY (SB) and SB-like (SBL), that negatively regulate the gametophore bud initiation in Physcomitrium patens by dampening cell wall loosening/softening. Disruption of SB and SBL led to accelerated gametophore formation and altered cell wall compositions. The function of SB is glycosylation dependent and genetically connected with the class C auxin response factor (ARF) transcription factors PpARFC1B and PpARFC2. Transcriptomics profiling showed that SB upregulates PpARFC2, which in turn suppresses a range of cell wall-modifying genes that are required for cell wall loosening/softening. We further show that PpARFC2 binds directly to multiple AuxRE motifs on the cis-regulatory sequences of PECTIN METHYLESTERASE to suppress its expression. Hence, our results demonstrate a mechanism by which the SB modulates the strength of intracellular auxin signaling output, which is necessary to fine-tune the timing of gametophore initials formation.
Speech therapy examination of children with impaired violation disorder, rate of speech, stutterinq: еducational methodical manual
Authors: Larina E.
Published: December 2022

Еducational methodical manual guide is intended for full-time and part-time students enrolled in special (defectological) education 44.03.03, training profile Speech therapy. The manual consists of theer sections, they contain a description of the sequence of stages of speech therapy examination of children with violation disorder, rate of speech, stutterinq, the structure of drawing up a speech therapy opinion, a summary on the topic, questions and control tasks for independent work, a list of references and a glossary. The educational-methodical is intended for students of the defectology department of the university, practicing speech therapists, specialists in the field of speech pathology.