bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC class I inhibitor domatinostat sensitizes pancreatic cancer to chemotherapy by targeting cancer stem cell compartment via FOXM1 modulation
Authors: Roca Maria Serena , Moccia Tania , Iannelli Federica , Testa Cristina , Vitagliano Carlo , Minopoli Michele , Camerlingo Rosa , De Riso Giulia , De Cecio Rossella , Bruzzese Francesca , Conte Mariarosaria , Altucci Lucia , Di Gennaro Elena , Avallone Antonio , Leone Alessandra , Budillon Alfredo
Published: March 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet clinical need due to the very poor prognosis and the lack of effective therapy. Here we investigated the potential of domatinostat (4SC-202), a new class I histone deacetylase (HDAC) inhibitor, currently in clinical development, to sensitize PDAC to first line standard gemcitabine (G)/taxol (T) doublet chemotherapy treatment.

Methods

Synergistic anti-tumor effect of the combined treatment was assessed in PANC1, ASPC1 and PANC28 PDAC cell lines in vitro as well as on tumor spheroids and microtissues, by evaluating combination index (CI), apoptosis, clonogenic capability. The data were confirmed in vivo xenograft models of PANC28 and PANC1 cells in athymic mice. Cancer stem cells (CSC) targeting was studied by mRNA and protein expression of CSC markers, by limiting dilution assay, and by flow cytometric and immunofluorescent evaluation of CSC mitochondrial and cellular oxidative stress. Mechanistic role of forkhead box M1 (FOXM1) and downstream targets was evaluated in FOXM1-overexpressing PDAC cells.

Results

We showed that domatinostat sensitized in vitro and in vivo models of PDAC to chemotherapeutics commonly used in PDAC patients management and particularly to GT doublet, by targeting CSC compartment through the induction of mitochondrial and cellular oxidative stress. Mechanistically, we showed that domatinostat hampers the expression and function of FOXM1, a transcription factor playing a crucial role in stemness, oxidative stress modulation and DNA repair. Domatinostat reduced FOXM1 protein levels by downregulating mRNA expression and inducing proteasome-mediated protein degradation thus preventing nuclear translocation correlated with a reduction of FOXM1 target genes. Furthermore, by overexpressing FOXM1 in PDAC cells we significantly reduced domatinostat-inducing oxidative mitochondrial and cellular stress and abolished GT sensitization, both in adherent and spheroid cells, confirming FOXM1 crucial role in the mechanisms described. Finally, we found a correlation of FOXM1 expression with poor progression free survival in PDAC chemotherapy-treated patients.

Conclusions

Overall, we suggest a novel therapeutic strategy based on domatinostat to improve efficacy and to overcome resistance of commonly used chemotherapeutics in PDAC that warrant further clinical evaluation.
Meiosis-specific cohesin complexes display essential and distinct roles in mitotic embryonic stem cell chromosomes
Authors: Choi Eui-Hwan , Yoon Seobin , Koh Young Eun , Hong Tae Kyung , Do Jeong Tae , Lee Bum-Kyu , Hahn Yoonsoo , Kim Keun P.
Published: March 2022

Background

Cohesin is a chromosome-associated SMC–kleisin complex that mediates sister chromatid cohesion, recombination, and most chromosomal processes during mitosis and meiosis. However, it remains unclear whether meiosis-specific cohesin complexes are functionally active in mitotic chromosomes.

Results

Through high-resolution 3D-structured illumination microscopy (3D-SIM) and functional analyses, we report multiple biological processes associated with the meiosis-specific cohesin components, α-kleisin REC8 and STAG3, and the distinct loss of function of meiotic cohesin during the cell cycle of embryonic stem cells (ESCs). First, we show that STAG3 is required for the efficient localization of REC8 to the nucleus by interacting with REC8. REC8-STAG3-containing cohesin regulates topological properties of chromosomes and maintains sister chromatid cohesion. Second, REC8-cohesin has additional sister chromatid cohesion roles in concert with mitotic RAD21-cohesin on ESC chromosomes. SIM imaging of REC8 and RAD21 co-staining revealed that the two types of α-kleisin subunits exhibited distinct loading patterns along ESC chromosomes. Third, knockdown of REC8 or RAD21-cohesin not only leads to higher rates of premature sister chromatid separation and delayed replication fork progression, which can cause proliferation and developmental defects, but also enhances chromosome compaction by hyperloading of retinoblastoma protein–condensin complexes from the prophase onward.

Conclusions

Our findings indicate that the delicate balance between mitotic and meiotic cohesins may regulate ESC-specific chromosomal organization and the mitotic program.
Foot tapping and unilateral vertical jump performance in athletes after knee surgery: an explorative cross-sectional study
Authors: Kurz Eduard , Schwesig René , Pröger Stefan , Delank Karl-Stefan , Bartels Thomas
Published: March 2022

Background

Guiding athletes through the rehabilitation process and judging the time at which return to sports can be enabled after anterior cruciate ligament (ACL) injuries are still challenging processes. The purpose of this explorative cross-sectional study was to retrospectively compare unilateral vertical jump as well as vertical foot tapping outcomes in athletes returned to sports after ACL reconstruction (ACLR) with uninjured athletes.

Methods

Seven-teen ACLR athletes (male/female: 12/5) were examined 11 (6–23) months after their ACL injury and after return to sport clearance together with 67 uninjured athletes (male/female: 51/16). Seventeen age and stature matched controls were selected from the sample of uninjured athletes. Participants unilaterally performed acyclic (squat jump, SJ; drop jump, DJ) and cyclic (foot tapping, FT) tests. SJ peak power, DJ take-off efficiency (TOE) and FT coefficients (FTC) were compared between ACLR and matched as well as unmatched control groups. Limb symmetry index (LSI) as well as performance score were calculated.

Results

Analyses of the SJ peak power revealed moderate effects of group (right:P < 0.09, ηp2 = 0.06; left:P < 0.05, ηp2 = 0.08). The TOE was largely affected by group (right:P < 0.01, ηp2 = 0.12; left:P < 0.01, ηp2 = 0.13). No effect of group was found on the FTC (P > 0.8, ηp2 < 0.01). The SJ peak power LSI (r = 0.46,P < 0.07) and TOE LSI (r = 0.38,P = 0.13) were positively associated with the performance score of the ACLR group.

Conclusion

Although already returned to sports, the ACLR group underperformed the matched and unmatched control groups significantly. Unilaterally performed vertical jumps may provide additional information on athletes’ rehabilitation progress and help to manage the rehabilitation process and decisions on potential readiness after ACLR. More attention should be paid to the direction of the LSI results.
Regression-based beam training for UAV mmWave communications
Authors: Zhang Junjie , Zhong Weizhi , Gu Yong , Zhu Qiuming , Zhang Lulu
Published: March 2022

For unmanned aerial vehicle (UAV) millimeter-wave (mmWave) communication systems, efficient and accurate beam training is urgently required to overcome beam misalignment. By taking into account the mmWave propagation environment, a three-dimensional (3D) intelligent beam training strategy that leverages the polynomial regression (PR) model and optimized beam patterns is proposed in this paper. We treat mmWave beam selection as a PR problem. By using machine learning (ML), the regression function is determined. The training dataset applied in the ML method consists of measured power and estimated angles and is obtained by carefully designed beam patterns. Furthermore, a noise suppression method involving the use of a denoising autoencoder (DAE) is developed to overcome the noise sensitivity of the proposed regression model. The numerical simulation results demonstrate that our proposed beam training strategy is capable of obtaining the same precision as an exhaustive search with a shorter time.
Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling
Authors: Hu Jingjuan , Deng Fan , Zhao Bingcheng , Lin Zebin , Sun Qishun , Yang Xiao , Wu Mei , Qiu Shida , Chen Yu , Yan Zhengzheng , Luo Sidan , Zhao Jin , Liu Weifeng , Li Cai , Liu Ke Xuan
Published: March 2022

Background

Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury.

Results

Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury.

Conclusion

The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice.
Benefits of mindfulness in academic settings: trait mindfulness has incremental validity over motivational factors in predicting academic affect, cognition, and behavior
Authors: Kuroda Yuji , Yamakawa Osamu , Ito Masayuki
Published: March 2022

Background

Achievement motivation research has established that motivational factors predict academic affect, cognition, and behavior. Recent studies have shown that trait mindfulness might also predict these academic outcomes. However, it remains unclear whether trait mindfulness has incremental validity over motivational factors. We hypothesized that trait mindfulness would explain unique variance in academic outcomes beyond motivational factors, because mindfulness that is characterized by the being mode of mind (i.e., a present-focused, non-striving, and accepting mind mode) would contribute to academic outcomes through unique and effective self-regulatory processes (i.e., bottom-up self-regulation of learning and present-focused, acceptance-based self-regulation of academic stress), which differ from those (i.e., top-down self-regulation of learning and future-focused, change-oriented self-regulation of academic stress) promoted by motivational factors that are characterized by the doing mode of mind (i.e., a goal-oriented, striving, and change-seeking mind mode). We tested the hypothesis by examining four established motivational factors (competence perception, implicit theory of intelligence, achievement goals, and autonomous and controlled academic reasons) and five outcome variables (test anxiety, enjoyment of learning, study strategy, mind-wandering, and help-seeking avoidance) that had been investigated in both the trait mindfulness and achievement motivation literatures.

Methods

One hundred and seventy-five students (104 females) were recruited from undergraduate psychology and cultural studies classes at two universities in Japan. Trait mindfulness was assessed using the Five Facet Mindfulness Questionnaire. The other study variables were assessed using established measures as well. We conducted hierarchical multiple regression analyses to test the hypothesis.

Results

Trait mindfulness predicted four of the five outcome variables (i.e., test anxiety, enjoyment of learning, mind-wandering, and help-seeking avoidance) after controlling for the motivational factors. The acting-with-awareness facet predicted three outcome variables, whereas the other facets predicted one outcome each.

Conclusions

This study supports the incremental validity of trait mindfulness relative to motivational factors, suggesting that not only the doing mode of mind but also the being mode is beneficial for academic learning.
Mental health and self-determination profiles of the diverse population of medical students in Malaysia during the COVID-19 pandemic
Authors: Cockburn Jessica Grace , Tan Chee Yang , Poh Dawn Celine Siaw Chern , Tan Ding Jun , Foong Chan Choong , Hong Wei-Han
Published: March 2022

Introduction

Medical schools throughout the world were forced to modify their programming during the COVID-19 pandemic. In Malaysia, virtual learning plans were implemented for non-clinical programming, while clinical posting modifications were designed to meet local SOPs. The prolonged enforcement of these modifications to undergraduate medical education will have affected student experiences, including well-being. Since these feelings can relate to perceived relatedness, autonomy, and competence, it is important to identify any potential factors that may lead to reduced intrinsic motivation in students. It is also important to consider how demographic features may contribute to student perspectives, which can be studied using the unique diversity represented by Malaysian students.

Methods

A quantitative survey was distributed to Malaysian medical students to assess their overall wellbeing, autonomy in educational decision making, student experiences, and position on changes to graduation timing. Intrinsic components were identified using Principal Component Analysis and were aligned with the three needs for self-determination, namely relatedness, autonomy, and competence. Finally, trends in responses for participants from various sub-populations were assessed using ANOVA testing.

Results

Responses were collected from 442 students representing 23 accredited Malaysian medical schools. Upon validation and reliability testing, eight components were identified with themes relating to: mental health, social concerns, communication, timing of modifications, depth of learning, and student-centred learning. Of these, gender was related to mental health, student-centred learning, and delayed graduation, while stage was related to student-centred learning and delayed graduation in addition to concerns about depth of learning and timing of modifications. Interestingly, ethnicity was related to differences in opinions about delayed graduation and income was related to social concerns.

Conclusion

The results of this study indicate that, while students were satisfied in general with the content and delivery of their programmes given the circumstances, there is evidence to suggest negative effects on emotional wellbeing and expression of student voice, due to the modifications that were made. Additionally, these feelings related to the three motivational needs, suggesting that students were experiencing a dampened motivational profile during the pandemic. Further, motivational profiles were distinct between student sub-groups, providing insight for developing appropriate and inclusive accommodations moving forward.
Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation
Authors: Liu Andy J. , Lusk Jay B. , Ervin John , Burke James , O’Brien Richard , Wang Shih-Hsiu J.
Published: March 2022

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 and TSC2 genes and autosomal dominantly inherited. These mutations cause hyperactivation of the mammalian Target of Rapamycin (mTOR) pathway, leading to the development of nonmalignant masses involving various organ systems. Patients with TSC also experience neuropsychiatric symptoms collectively termed Tuberous Sclerosis Complex Associated Neuropsychiatric Disorder (TAND). Due to research advancements in TSC, patients now live well beyond the age of 50. Many experience objective impairment of memory and executive function, supported by formal neuropsychological testing, beginning in their late 40s. Biomarker analysis has described elevated levels of phosphorylated tau-181 in the cerebrospinal fluid of patients with TAND. Tau-PET imaging has also shown focal accumulation of the radiotracer flortaucipir (AV1451), suggesting that TSC may be a neurodegenerative disorder arising from accumulation of phosphorylated tau. However, the flortaucipir tracer has been reported to have significant off-target binding, preventing definitive conclusions from being drawn about the molecular etiology of neurodegeneration in TSC. Therefore, we initiated the Colocalization of AV1451 and Phosphorylated Tau in Adult brain tissue (CAPA) study. This study aimed to determine if flortaucipir is bound to phosphorylated tau in brains of patients with TSC and further sought to determine the specific tau isoform seen in TSC. Our results show that flortaucipir labels the 3R/4R isoform of phosphorylated tau, commonly seen in Alzheimer’s disease. However, amyloid staining was negative in brains of adult patients with TSC. Therefore, we conclude that TAND symptoms are due to the accumulation of the phosphorylated tau isoform seen in Alzheimer’s disease. This study suggests that hyperactivation of the mammalian Target of Rapamycin pathway may play a role in the amyloid-independent development of 3R/4R tau aggregation. Our findings could lead to a new era of anti-tau therapies used to treat both disorders.
A canonical model for seasonal climate prediction using Big Data
Authors: Ramos M. P. , Tasinaffo P. M. , Cunha A. M. , Silva D. A. , Gonçalves G. S. , Dias L. A. V.
Published: March 2022

This article addresses the elaboration of a canonical model, involving methods, techniques, metrics, tools, and Big Data, applied to the knowledge of seasonal climate prediction, aiming at greater dynamics, speed, conciseness, and scalability. The proposed model was hosted in an environment capable of integrating different types of meteorological data and centralizing data stores. The seasonal climate prediction method called M-PRECLIS was designed and developed for practical application. The usability and efficiency of the proposed model was tested through a case study that made use of operational data generated by an atmospheric numerical model of the climate area found in the supercomputing environment of the Center for Weather Forecasting and Climate Studies linked to the Brazilian Institute for Space Research. The seasonal climate prediction uses ensemble members method to work and the main Big Data technologies used for data processing were: Python language, Apache Hadoop, Apache Hive, and the Optimized Row Columnar (ORC) file format. The main contributions of this research are the canonical model, its modules and internal components, the proposed method M-PRECLIS, and its use in a case study. After applying the model to a practical and real experiment, it was possible to analyze the results obtained and verify: the consistency of the model by the output images, the code complexity, the performance, and also to perform the comparison with related works. Thus, it was found that the proposed canonical model, based on the best practices of Big Data, is a viable alternative that can guide new paths to be followed.
Aβ promotes CD38 expression in senescent microglia in Alzheimer’s disease
Authors: Hu Yiran , Huang Yan , Xing Sanli , Chen Chuan , Shen Dingzhu , Chen Jiulin
Published: March 2022

Background

In Alzheimer’s disease (AD), the neuroinflammatory response mediated by the activation of senescent microglia is closely related to energy dysmetabolism. However, the mechanism underlying the interaction between the energy metabolism of aging microglia and neuroinflammation remains unclear.

Methods

We used biochemical methods, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blot to determine the effects and mechanism of CD38 knockdown on energy metabolism and neuroinflammation in Aβ1-40 injured BV2 cells. Using AD model mice, we detected CD38 enzyme activity, energy metabolism factors (ATP, NAD +, and NAD + /NADH), and neuroinflammatory factors (IL-1β, IL-6, and TNF-α) following the addition of CD38 inhibitor. Using a combination of biochemical analysis and behavioral testing, we analyzed the effects of the CD38 inhibitor on energy metabolism disorder, the neuroinflammatory response, and the cognition of AD mice.

Results

Following Aβ1-40 injury, SA-β-Gal positive cells and senescence-related proteins P16 and P21 increased in BV2 cells, while energy-related molecules (ATP, NAD +, and NAD + /NADH) and mitochondrial function (mitochondrial ROS and MMP) decreased. Further studies showed that CD38 knockdown could improve Aβ1-40-induced BV2 cells energy dysmetabolism and reduce the levels of IL-1β, IL-6, and TNF-α. In vivo results showed an increase in senile plaque deposition and microglial activation in the hippocampus and cortex of 34-week-old APP/PS1 mice. Following treatment with the CD38 inhibitor, senile plaque deposition decreased, the number of Iba1 + BV2 cells increased, the energy metabolism disorder was improved, the proinflammatory cytokines were reduced, and the spatial learning ability was improved.

Conclusions

Our results confirm that senescent microglia appeared in the brain of 34-week-old APP/PS1 mice, and that Aβ1-40 can induce senescence of BV2 cells. The expression of CD38 increases in senescent BV2 cells, resulting in energy metabolism disorder. Therefore, reducing CD38 expression can effectively improve energy metabolism disorder and reduce proinflammatory cytokines. Following intervention with the CD38 inhibitor in APP/PS1 mice, the energy metabolism disorder was improved in the hippocampus and cortex, the level of proinflammatory cytokines was reduced, and cognitive impairment was improved.
Treatment Considerations for Compulsive Exercise in High-Performance Athletes with an Eating Disorder
Authors: Martenstyn Jordan A. , Jeacocke Nikki A. , Pittman Jana , Touyz Stephen , Maguire Sarah
Published: March 2022

Compulsive exercise is linked with poorer treatment outcomes in people with eating disorder (EDs). High-performance athletes represent a growing and complex subcomponent of the broader ED population, and emergent evidence indicates that different conceptualisations of compulsive exercise are needed in this population. Existing randomised controlled trials in ED populations have demonstrated small treatment effects on compulsive exercise compared with control groups; however, athletes were sparsely sampled across these studies. Thus, the extent to which current treatments for compulsive exercise in EDs are also effective in high-performance athletes is unknown. For this opinion paper, we sought representation from high-performance sports leadership, someone with lived experience of both an ED and high-performance athletics, and ED clinical experts. We discuss the utility of recommending exercise abstinence in ED treatment with athletes, as well as a number of other treatment strategies with some evidence in other contexts for further consideration and research in this population. These include using mindfulness-based interventions as an adjunct to cognitive-behavioural therapies, using wearable technologies and self-reported fatigue to inform training decisions, and incorporating greater exercise variation into training programs. We also offer practical considerations for clinicians seeking to apply foundational elements of cognitive-behavioural interventions (e.g., exposure and response prevention, cognitive restructuring, behavioural experiments) into an ED treatment program for a high-performance athlete. Future research is needed to examine characteristics of pathological compulsive exercise in athletes and whether available treatments are both feasible and effective in the treatment of compulsive exercise in athletes with an ED.
Can YouTube be used as an educational tool in lymphedema rehabilitation?
Authors: Küçükakkaş Okan , İnce Buğra
Published: March 2022

Background

Lymphedema is defined as the abnormal accumulation of interstitial fluid and fibro-adipose tissues resulting from injury, infection, or congenital abnormalities of the lymphatic system. The gold standard approach in the treatment of lymphedema is Complete Decongestive Therapy and it has many components that require practical knowledge and skills. YouTube can be a useful tool to provide these skills to healthcare professionals and patients. The aim of this study was to examine the videos about lymphedema rehabilitation on YouTube and analyze their technical features, sources, contents, educational value and reliability.

Methods

The YouTube database was searched using the “lymphedema rehabilitation”, “lymphedema treatment”, “complete decongestive therapy”, “lymphedema massage”, and “lymphedema exercises” keywords. Two reviewers (Physical medicine and rehabilitation specialist) assessed videos for educational quality using a Global Quality Scale (GQS). To evaluate the reliability the 5-point Discern scale was used.

Results

A total of 90 videos, which met the inclusion criteria were included in the analysis. The mean duration of the videos was 8.9 ± 10.5 min. The mean number of daily views was 22.7 ± 47.1 for a day. The majority of the videos were created to inform patients (57.8%).The uploaders were mostly private healthcare institutions or healthcare professionals (65.6%). Information providers were lymphedema therapists mostly (63.3%). Manual lymphatic drainage was observed to stand out as the most mentioned lymphedema rehabilitation component on YouTube. The mean of reliability and GQS scores of the videos were 2.2 ± 1.0 and 2.7 ± 1.0, respectively.

Conclusions

The biggest obstacle for YouTube to be an excellent source of information is that it hosts large volumes of uncontrolled and low-quality data. When Youtube content related to lymphedema rehabilitation was examined, it was observed that many videos were quite insufficient and incomplete even though there were useful videos. If careful controlling measures are implemented and if medical videos aim to meet reliability and GQS criteria, YouTube can become an effective and useful source of information for lymphedema rehabilitation.
The effects of repeated brain MRI on chromosomal damage
Authors: Herate Cecile , Brochard Patricia , De Vathaire Florent , Ricoul Michelle , Martins Bernadette , Laurier Laurence , Deverre Jean-Robert , Thirion Bertrand , Hertz-Pannier Lucie , Sabatier Laure
Published: March 2022

Background

Magnetic resonance imaging (MRI) is currently considered a safe imaging technique because, unlike computed tomography, MRI does not expose patients to ionising radiation. However, conflicting literature reports possible genotoxic effects of MRI. We herein examine the chromosomal effects of repeated MRI scans by performing a longitudinal follow-up of chromosomal integrity in volunteers.

Methods

This ethically approved study was performed on 13 healthy volunteers (mean age 33 years) exposed to up to 26 3-T MRI sessions. The characterisation of chromosome damage in peripheral blood lymphocytes was performed using the gold-standard biodosimetry technique augmented with telomere and centromere staining.

Results

Cytogenetic analysis showed no detectable effect after a single MRI scan. However, repeated MRI sessions (from 10 to 20 scans) were associated with a small but significant increase in chromosomal breaks with the accumulation of cells with chromosomal terminal deletions with a coefficient of 9.5% (95% confidence interval 6.5–12.5%) per MRI (p < 0.001). Additional exposure did not result in any further increase. This plateauing of damage suggests lymphocyte turnover. Additionally, there was no significant induction of dicentric chromosomes, in contrast to what is observed following exposure to ionising radiation.

Conclusions

Our study showed that MRI can affect chromosomal integrity. However, the amount of damage per cell might be so low that no chromosomal rearrangement by fusion of two deoxyribonucleic breaks is induced, unlike that seen after exposure to computed tomography. This study confirms that MRI is a safe imaging technique.
Potential pharmacological properties of methanol leaves extract of Culcasia Angolensis (Araceae): antinociceptive, antiinflammatory and antipyretic activities in laboratory animals
Authors: Nock Doshu Daniel , Abraham Idagu Godwin , Ahmad Mubarak Hussaini
Published: March 2022

Background

Pain, inflammation and fever are serious conditions that are associated with various disease conditions. In modern medicine, non-steroidal anti-inflammatory drugs (NSAIDs), opioids together with corticosteroids have been considered to manage algesia and inflammation-related conditions. However, these conventional drugs are not affordable, not readily available, particularly to people living in rural areas in developing nations. Besides, they are associated with undesirable pharmacological actions. Generally, medicinal plants have been employed to manage various ailments. In Northern-Nigeria, the leaves of Culcasia angolensis (Araceae) are used traditionally to manage pain, fever and inflammation. However, scientific data validating its folkloric claim in treating pain and inflammatory-related abnormalities are not available. Hence, the current study aims to validate the antinociceptive, anti-inflammatory and antipyretic potentials of the methanol leaf extract of Culcasia angolensis (MECA). Phytochemical and acute toxicity effects of the MECA were conducted as per standard experimental procedures. The analgesic potential of the MECA was determined using abdominal writhing elicited by acetic acid and hot plate tests in mice. The actions of the MECA on acute inflammation were conducted using formalin-induced hind paw oedema and carrageenan-induced paw oedema. The Brewer's yeast-induced pyrexia was employed to check its antipyretic effect.

Results

The MECA inhibited abdominal writhes produced by acetic acid administration (p < 0.05) and elevated the pain threshold in the hot plate test. The MECA also reduced the formalin-induced paw oedema. Besides, it produced an effective (p < 0.05) and dose-dependent action against oedema produced by carrageenan and reduced the rectal temperature against the pyrexia caused by Brewer's yeast administration.

Conclusions

The outcome of the study suggests that the MECA could possess pharmacologically active constituents with antinociceptive, anti-inflammatory and antipyretic properties. Therefore, the results justified its ethnomedicinal use to manage pain and inflammatory-associated conditions.
Paroxysmal sympathetic hyperactivity following acute diffuse brain swelling due to traumatic brain injury: a case report with good clinical outcome
Authors: Sakai Kyohei , Kitagawa Takehiro , Suzuki Kohei , Toh Keita , Yamamoto Junkoh
Published: March 2022

Background

Paroxysmal sympathetic hyperactivity (PSH) may occur after acquired brain injury. The clinical presentation of PSH results from increased sympathetic overdrive, including transient paroxysms of tachycardia, hypertension, hyperventilation, hyperthermia, dystonic posturing, and excessive sweating. The exact pathophysiology of PSH, however, remains unclear, and no definitive treatment is available. Herein, the authors report a case of PSH in a male patient who experienced acute brain swelling after acquired head injury, for which a good clinical outcome was achieved due to multimodal treatment. The ensuing discussion also addresses the pathophysiology of PSH.

Case presentation

An 18-year-old man was transported to the authors’ hospital after experiencing a traumatic brain injury. On admission, computed tomography revealed cerebral herniation due to diffuse brain edema in the left parietal lobe. Emergency decompressive craniotomy and internal decompression were performed. After surgery, anti-edema therapy (glycerol and mannitol) was continued. Ten days postoperatively, PSH was diagnosed in accordance with the PSH assessment score (20 points). Vecuronium, fentanyl, morphine, propofol, dexmedetomidine, and a calcium channel blocker were administered; however, the drug effect was insufficient. Thirty-two days postsurgery, the patient gradually recovered from the adrenergic symptoms of PSH, and head computed tomography performed 32 days after surgery revealed improvement in diffuse brain edema. Ultimately, the patient fully recovered and lived independently at home.

Conclusions

Considering the pathophysiology of PSH, cerebral contusion, acute brain swelling, and secondary mechanisms of brain injury may trigger sympathetic nerve-enhancing regions and cause hyperexcitation of the sympathetic nervous system, resulting in PSH. The outcome of the present case demonstrates that PSH can be reversed if it is identified early and before it becomes irreversible, that is, post the development of hypoxic encephalopathy or widespread brain damage. Appropriate management, including decompression craniotomy for brain swelling and multidisciplinary treatment, leads to good clinical outcomes.
Broadening the clinical spectrum of ALGS: an Egyptian cohort with five novel mutations in JAG1 gene
Authors: Khairat Rabab , El-Karaksy Hanaa , El-Bassyouni Hala T. , Saad Ahmed K. , Rabie Eman , Hamed Khaled , Yassin Noha A.
Published: March 2022

Background

Alagille syndrome (ALGS) is a rare autosomal dominant multisystem disorder that affects the liver, heart, eyes, vertebrae, and kidneys and is associated with characteristic facies. This work aimed to study the spectrum of the clinical features of ALGS in an Egyptian cohort of patients in conjunction with partial sequencing of the JAG1 gene.

Methods

This study included 17 pediatric ALGS patients diagnosed on clinical grounds: facial features, cholestatic liver disease, and cardiac, vertebral, and ocular findings. Molecular analysis was conducted in 10 selected exons of the JAG1 gene.

Results

The clinical features of ALGS included cholestatic liver disease (100%), facial dysmorphism (100%), cardiac abnormalities (88.2%), butterfly vertebrae (64.7%), posterior embryotoxon (35.2%), poor growth (41%), xanthomata (11.8%), and hiatus hernia (11.8%). Five novel pathogenic JAG1 mutations were identified in this study, including two nonsense mutations, one splicing mutation, one frameshift insertion, and one frameshift deletion. In two patients, the mutations were confirmed to be de novo, as the mutations could not be detected in both parents.

Conclusion

Five novel JAG1 pathogenic variants were identified in this study. This is the first molecular study to report pathogenic mutations in the JAG1 gene within an Egyptian cohort of children with ALGS.
Myocardiocyte autophagy in the context of myocardiocytes regeneration: a potential novel therapeutic strategy
Authors: Marzoog Basheer Abdullah , Vlasova Tatyana Ivanovna
Published: March 2022

Background

The regeneration strategy involves several aspects, such as reprogramming aspects, targeting pathophysiological processes, and inducing the physiological one. Autophagy targeting is a potential physiological/pathogenetic strategy to enhance myocardiocytes' function. Myocardiocytes' injury-related death remains to be the highest in our era. Unfortunately, myocardiocytes have a limited proliferation capacity to compensate for what was lost by infarction. However, partially injured myocardiocytes can be preserved by improving the autophagy process of myocardiocytes.

Main text

Autophagy induction involved controlling the cellular and subcellular environment as well as gene expression. Autophagy is well known to prolong the longevity of cell and human life. Inhibition of the mTOR receptor, proapoptotic gene Bnip3, IP3, and lysosome inhibitors, inhibition of microRNA-22 and overexpression of microRNA-99a, modulators of activated protein kinase with adenosine monophosphate, resveratrol, sirtuin activators, Longevinex and calcium lowering agents can promote physiological myocardiocyte autophagy and improve post-myocardial modulation and recovery speed. The paper aimed to assess autophagy role in myocardiocytes regeneration modulation.

Conclusions

The autophagy strategy can be applied to infarcted myocardiocytes, as well as heart failure. However, cell self-eating is not the preferred therapy for preserving injured myocardiocytes or causing regeneration.
A new case of trisomy 5 with complex karyotype abnormalities in B-cell prolymphocytic leukemia: a case study
Authors: Makongoro Musa , Abu Rakhey Mahmoud Matar Mohammad , Yu Yafei , Sun Jianzhi , Li Guosheng , He Na , Abd El-Kaream Samir Ali , Ma Daoxin
Published: March 2022

Background

The B-cell prolymphocytic leukemia (B-PLL) diagnosis is challenging due to the superposition with mature B-cell leukemia and/or lymphoma.

Objective

An insight case study of trisomy 5 with complex karyotype abnormalities in B-cell prolymphocytic leukemia.

Subject and methods

A 72-year-old man was referred to the Hematology Department, Qilu Hospital, Shandong University, because of persistent fever (10 days) and lymphocytosis. A detailed diagnostic methods including complete blood count, bone marrow aspiration, flow cytometry, conventional karyotype analysis, fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (qRT-PCR), next-generation sequencing technology (NGS) used to detect 41 kinds of mutant genes related to hematological malignancies were conducted and reasonable therapeutic regimens including emergent leukapheresis accompanied by basification of urine and hydrotherapy, followed by a regimen of cyclophosphamide and dexamethasone.

Results

Subject white blood cell count was 143.43 × 109/L, and 56% prolymphocytes. He did not show lymphadenopathy but splenomegaly. Immunophenotyping of prolymphocytes was CD5(+low), CD10(−), CD11c(−), CD19(+), CD20(+), cCD22(+), CD23(−), cCD79a(+), CD79b(+), FMC7(±), CD43(−), CD3(−), CD56(−), CD103(−), HLA-DR(+), and Lambda(+). R-banding and FISH revealed that leukemia cells carried extra chromosome 5. Considering the rare occurrence of trisomy 5 found in prolymphocytic leukemia, especially in Asians, with rapid disease progression. We know that median survival of B-PLL is three years after diagnosis, while survival time of this patient was only 1 month.

Conclusion

This study could provide the firsthand materials for precision, medicine and mechanism research in cytogenetics and molecular biology. It inferred that trisomy 5 might be a poor prognosis indicator, providing directions for clinical practice in the foreseeable future.
Long proximal pouch oesophageal atresia with tracheo-oesophageal fistula, a diagnostic dilemma: case report
Authors: Machaea Sello , Nogela Vuyo , Chitnis Milind
Published: March 2022

Background

Oesophageal atresia is a congenital abnormality commonly encountered in neonates. Classification proposed by Gross is the most frequently used. It divides the oesophageal anomalies into five types. Type C—proximal oesophageal atresia and distal tracheo-oesophageal fistula—is the most common. Dafoe and Ross described a rare subtype with a long proximal pouch. Only 11 cases of a long proximal pouch have been reported in the English literature so far. We describe a neonate with long proximal pouch oesophageal atresia with distal tracheo-oesophageal fistula emphasizing the difficulty in arriving at the diagnosis.

Case presentation

A 1-week-old neonate presented with feed intolerance and failure to advance orogastric tube into the stomach. Water soluble upper gastrointestinal tract contrast revealed a blind ending proximal oesophagus at the level of the diaphragm. Gastric volvulus was considered as a diagnosis. Patient underwent a laparotomy where a normal stomach was found. Bubbles were seen coming from the fashioned gastrostomy with each inspiration. This prompted us to consider the possibility of a missed oesophageal atresia with distal tracheo-oesophageal fistula. Diagnosis was confirmed on bronchoscopy and right thoracotomy. The tracheo-oesophageal fistula was ligated and a cervical oesophagostomy and Stamm gastrostomy were performed due to irreparable tear in the long upper pouch.

Conclusion

This rare subtype of long upper pouch oesophageal atresia poses a diagnostic dilemma that can result in delay in the diagnosis and management. This diagnosis should be suspected if the tip of the orogastric/feeding tube is seen to be far below the level of the carina.
Total aplasia of the paranasal sinuses and nasal cavity: the first case report
Authors: Hasan Trefa Salih
Published: March 2022

Background

The paranasal sinuses (PNSs) are small empty spaces around the nasal cavity at the entrance to the respiratory tract, and they have various functions. The development and anatomy of the PNSs are exposed to many variations, often leading to patients’ complaints upon presentation.

Case presentation

Here, the first case of total aplasia of the paranasal sinuses and nasal cavity and its contents is presented. Several cases of varying degrees of combined aplasia and hypoplasia, even total sinus aplasia, have been reported in the literature, but to the author’s knowledge, no cases of total sinus aplasia and associated nasal aplasia have been described thus far.

Conclusion

This case report describes a rare, and probably the first, case of severe sinonasal developmental defects elegantly identified with bone window computed tomography (CT).
Inactivation of Type 3 Deiodinase Results in Life-long Changes in the Brown Adipose Tissue Transcriptome in the Male Mouse
Authors: Fonseca Tatiana L , Russo Samuel C , Luongo Cristina , Salvatore Domenico , Bianco Antonio C
Published: March 2022

Adaptive thermogenesis in small mammals and infants takes place in brown adipose tissue (BAT). Heat is produced via uncoupling protein 1 (UCP1)-mediated uncoupling between oxidation of energy substrates and adenosine 5′-triphosphate synthesis. Thyroid hormone (TH) signaling plays a role in this process. The deiodinases activate thyroxine (T4) to 3,5,3′-triiodothyronine (T3) (D2) or inactivate T4 and T3 to 3,3,5′-triiodothyronine and T2 (D3), respectively. Using a mouse model with selective inactivation of Dio3 in BAT (flox-Dio3 × UCP1-cre = BAT-D3KO), we now show that knocking out D3 resulted in premature exposure of developing brown adipocytes (embryonic days 16.5-18.5) to T3 signaling, leading to an earlier expression of key BAT genes, including Cidea, Cox8b, Dio2, Ucp1, and Pgc1α. Adult BAT-D3KO mice exhibited increased expression of 1591 genes as assessed by RNA sequencing, including 19 gene sets related to mitochondria, 8 related to fat, and 8 related to glucose homeostasis. The expression of 243 genes was changed by more than 1.5-fold, 36 of which play a role in metabolic/thermogenic processes. BAT-D3KO mice weigh less and exhibit smaller white adipocyte area, but maintain normal energy expenditure at room temperature (22 °C) and in the cold (4 °C). They also defend their core temperature more effectively and do not lose as much body weight when exposed to cold. We conclude that the coordinated actions of Dio3 in the embryonic BAT define the timing and intensity of T3 signaling during brown adipogenesis. Enhanced T3 signaling during BAT embryogenesis (Dio3 inactivation) results in selective life-long modifications in the BAT transcriptome.
Class: A Useful Category of Analysis in the History of Sexual Harassment
Authors: Phelps Christopher
Published: March 2022

Beginning with Leonora Barry of the Knights of Labor, women in the labor movement have envisioned class action as a means of overcoming sexual harassment. Drawing upon Brooke Meredith Beloso's emphasis on the “class constitution of gender and sexuality” and “gendered and sexual constitution of class,” this essay considers four historical phases—the Gilded Age, the Progressive Era, the Great Depression and Second World War, and the present era since the 1970s—to maintain the value of class as an analytic category in understanding sexual harassment and resistance to it in the history of American capitalism. Attentive to gender and race, it contests perspectives that erase or subordinate class while in turn seeking to situate class within a full-spectrum intersectionality. Bringing class back in reveals sexual harassment to be one form of the enactment of class, not merely gender. Although sexual harassment can in no way be reduced to class, class shapes sexual harassment and sexual harassment shapes class.
The Final Cut: Evolution of Cavernous Sinus Decompression Beyond the Dolenc Cut
Authors: Peto Ivo , Matos-Cruz Alejandro , Flores-Milan Gabriel , Heller Robert , van Loveren Harry , Agazzi Siviero
Published: March 2022

BACKGROUND:

Meningiomas involving the cavernous sinus (CS) represent a formidable challenge to neurosurgeons. Because of high morbidity, aggressive tumor resection within the CS has been largely replaced by extracavernous tumor resection and decompression of the CS. The widely used Dolenc method involves blind dural transection over the oculomotor nerve, potentially placing the crossing trochlear nerve at risk.

OBJECTIVE:

To provide a safer way for the decompression of the CS and at the same time, circumferential resection of the temporal lobe dura.

METHODS:

Cadaveric dissection of 8 cadaveric heads (16 sides) was performed. Frontotemporal craniotomy with zygomatic osteotomy was performed. Extradural and intradural dissection of the lateral wall of the CS and free edge of tentorium was performed. Photographic documentation, artistic illustrations, and illustrative video cases are provided.

RESULTS:

Three tether points were released: anterior—the meningo-orbital band, lateral—dura over the V2 and V3, and medial—superficial layer of the free edge of tentorium. Transection of the superficial layer of the free edge of the tentorium along its edge, in conjunction with a lateral cut over the temporal convexity, constitutes the final cut, allowing a resection of the lateral CS wall and the circumferential resection of temporal lobe dura.

CONCLUSION:

Using the “final cut” technique allows for a circumferential resection of the temporal lobe dura and lateral CS wall while avoiding blind cuts that could put cranial nerves at risk. All dural transections are performed in anatomically separated layers under constant visualization.