bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary involvement of gallbladder by acute lymphoblastic leukemia presenting clinically as cholecystitis in a young patient: a case report
Authors: Rahim Shabina , Ahmad Zubair , Chundriger Qurratulain , Ahmed Arsalan , Ali Natasha , Abdul-Ghafar Jamshid
Published: February 2023

Background

Primary lymphoma of the liver, gallbladder, and extrahepatic bile ducts or secondary involvement of these organs by leukemia is exceedingly rare. Patients with primary lymphoma or leukemic involvement of the biliary tract and liver often present with symptoms and signs of biliary tract obstruction or inflammation.

Case presentation

We present a case of a 24-year-old male with biliary tract symptoms who underwent laparoscopic cholecystectomy. His precholecystectomy complete blood count performed on the same morning showed 72% lymphocytes while peripheral blood smears showed approximately 15% blasts. Surgeon went ahead with the procedure. Imaging done prior to surgery showed thickened gallbladder, while the liver, biliary tract, and pancreas did not show any thickening or mass lesion. However, the liver was enlarged. Grossly, the gallbladder wall did not show any stones or discrete mass involving the wall. Instead, there was subtle thickening of the gallbladder wall due to diffuse infiltration by the leukemic infiltrate. This lymphoid population reacted with PAX-5 and TdT immunohistochemical antibodies in a diffuse manner confirming precursor B-cell origin. This patient was found to have B-lymphoblastic leukemia involving his bone marrow on further clinical and diagnostic workup. Patient responded well to chemotherapy and is currently on maintenance treatment. He is well 1.5 years after his diagnosis.

Conclusion

This case highlights a unique and rare scenario where a previously undiagnosed and unsuspected hematologic malignancy initially presented with clinical features of a chronic inflammatory condition involving an abdominal organ owing to secondary involvement by the malignant infiltrate.
Barriers and facilitators to physical activity for young adult women: a systematic review and thematic synthesis of qualitative literature
Authors: Peng Bo , Ng Johan Y. Y. , Ha Amy S.
Published: February 2023

Background

Physical activity (PA) has many benefits in preventing diseases and maintaining physical and mental health. Women, in particular, can benefit from regular PA. However, women’s PA did not increase over the past decade globally, and the situations faced by women are often gender-specific. Healthy young adult women's PA does not receive as much attention as older women and adolescent girls, yet, they face the same situation of low level of PA. This review aims to explore and synthesise the self-identified barriers and facilitators to young adult women's participation in PA from qualitative research studies and offer suggestions for future studies and programs designed for this population.

Methods

A systematic search was conducted in Pubmed, Web of Science, Scopus, Medline, and SPORTDiscus for studies published between January 2000 to February 2022 to identify qualitative studies on the barriers and facilitators of young adult women’s PA between ages 18 to 40. The search yielded 694 studies initially, of which 23 were included. The research quality of included studies was appraised using the Critical Appraisal Skills Programme (CASP) tool. Data were extracted and thematically analysed based on the tenets of the social-ecological model (SEM).

Results

Identified barriers and facilitators were grouped into different levels of the SEM, with the most frequently cited factors being time, body image and societal beauty standards, family duty and social support, religious and cultural norms, organisation and community facilities and environment, safety issues and physical environment. Descriptive data were thematically analysed and synthesised in line with the five levels: body image, health and beauty; multiple roles, support, and PA; religious identity, cultural identity, and PA; safety issues and women’s fears.

Conclusions

This qualitative synthesis revealed in-depth information on barriers and facilitators influencing young adult women’s PA. It highlighted that the factors young adult women face are diverse at different levels yet holistic and intertwined. Future studies on young adult women’s PA should address the social-cultural influence and would benefit from applying multilevel strategies employing the SEM model. It is critical to create an open and inclusive environment and offer more opportunities for women.

Trial registration

PROSPERO CRD42021290519.
Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial
Authors: Hsu Shih-Pin , Lu Chia-Feng , Lin Bing-Fong , Tang Chih-Wei , Kuo I-Ju , Tsai Yun-An , Guo Chao-Yu , Lee Po-Lei , Shyu Kuo-Kai , Niddam David M. , Lee I-Hui
Published: February 2023

Background

Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients.

Methods

We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2–56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke.

Results

Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect sizeη2 = 0.211; responder rate: 77% vs. 36%,p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01).

Conclusions

Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation.

Trial registration: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).
ADSC-derived exosomes attenuate myocardial infarction injury by promoting miR-205-mediated cardiac angiogenesis
Authors: Wang Tingting , Li Tao , Niu Xiaolin , Hu Lang , Cheng Jin , Guo Dong , Ren He , Zhao Ran , Ji Zhaole , Liu Pengyun , Li Yan , Guo Yanjie
Published: February 2023

Background

Acute myocardial infarction is a major health problem and is the leading cause of death worldwide. Myocardial apoptosis induced by myocardial infarction injury is involved in the pathophysiology of heart failure. Therapeutic stem cell therapy has the potential to be an effective and favorable treatment for ischemic heart disease. Exosomes derived from stem cells have been shown to effectively repair MI injury-induced cardiomyocyte damage. However, the cardioprotective benefits of adipose tissue-derived mesenchymal stem cell (ADSC)-Exos remain unknown. This study aimed to investigate the protective effects of exosomes from ADSC on the hearts of MI-treated mice and to explore the underlying mechanisms.

Methods

Cellular and molecular mechanisms were investigated using cultured ADSCs. On C57BL/6J mice, we performed myocardial MI or sham operations and assessed cardiac function, fibrosis, and angiogenesis 4 weeks later. Mice were intramyocardially injected with ADSC-Exos or vehicle-treated ADSCs after 25 min following the MI operation.

Results

Echocardiographic experiments showed that ADSC-Exos could significantly improve left ventricular ejection fraction, whereas ADSC-Exos administration could significantly alleviate MI-induced cardiac fibrosis. Additionally, ADSC-Exos treatment has been shown to reduce cardiomyocyte apoptosis while increasing angiogenesis. Molecular experiments found that exosomes extracted from ADSCs can promote the proliferation and migration of microvascular endothelial cells, facilitate angiogenesis, and inhibit cardiomyocytes apoptosis through miRNA-205. We then transferred isolated exosomes from ADSCs into MI-induced mice and observed decreased cardiac fibrosis, increased angiogenesis, and improved cardiac function. We also observed increased apoptosis and decreased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in HMEC-1 transfected with a miRNA-205 inhibitor.

Conclusion

In summary, these findings show that ADSC-Exos can alleviate cardiac injury and promote cardiac function recovery in MI-treated mice via the miRNA-205 signaling pathway. ADSC-Exos containing miRNA205 have a promising therapeutic potential in MI-induced cardiac injury.
Interaction between Wolbachia pipientis and Leishmania infantum in heartworm infected dogs
Authors: Latrofa Maria Stefania , Varotto-Boccazzi Ilaria , Louzada-Flores Viviane Noll , Iatta Roberta , Mendoza-Roldan Jairo Alfonso , Roura Xavier , Zatelli Andrea , Epis Sara , Bandi Claudio , Otranto Domenico
Published: February 2023

Background

Wolbachia is a Gram-negative endosymbiont associated with several species of arthropods and filarioid nematodes, including Dirofilaria immitis. This endosymbiont may elicit a Th1 response, which is a component of the immunity against Leishmania infantum.

Methods

To investigate the interactions between Wolbachia of D. immitis and L. infantum in naturally infected dogs and cytokine circulation, dogs without clinical signs (n = 187) were selected. Dogs were tested for microfilariae (mfs) by Knott, for female antigens of D. immitis by SNAP, and for anti-L. infantum antibodies by IFAT and assigned to four groups. Dogs of group 1 (G1) and 2 (G2) were positive for D. immitis and positive or negative to L. infantum, respectively. Dogs of group 3 (G3) and 4 (G4) were negative to D. immitis and positive or negative to L. infantum, respectively. Wolbachia and L. infantum DNA was quantified by real-time PCR (qPCR) in dog blood samples. A subset of dogs (n = 65) was examined to assess pro- and anti-inflammatory cytokine production using an ELISA test.

Results

Of 93 dogs positive to D. immitis with circulating mfs, 85% were positive to Wolbachia, with the highest amount of DNA detected in G1 and the lowest in dogs with low mfs load in G1 and G2. Among dogs positive to L. infantum, 66% from G1 showed low antibody titer, while 48.9% from G3 had the highest antibody titer. Of 37 dogs positive to Wolbachia from G1, 26 (70.3%) had low antibody titers to L. infantum (1:160). Among cytokines, TNFα showed the highest mean concentration in G1 (246.5 pg/ml), IFNγ being the one most represented (64.3%). IL-10 (1809.5 pg/ml) and IL-6 (123.5 pg/ml) showed the highest mean concentration in dogs from G1. A lower percentage of dogs producing IL-4 was observed in all groups examined, with the highest mean concentration (2794 pg/ml) recorded in G2.

Conclusion

Results show the association of D. immitis and Wolbachia with the lower antibody titers of L. infantum in co-infected dogs, suggesting the hypothesis that the endosymbiont may affect the development of the patent leishmaniosis. However, due to the limitations associated with the heterogeneity of naturally infected dogs in field conditions, results should be validated by investigation on experimental models.

Graphical Abstract
Regulatory networks driving expression of genes critical for glioblastoma are controlled by the transcription factor c-Jun and the pre-existing epigenetic modifications
Authors: Roura Adria-Jaume , Szadkowska Paulina , Poleszak Katarzyna , Dabrowski Michal J. , Ellert-Miklaszewska Aleksandra , Wojnicki Kamil , Ciechomska Iwona A. , Stepniak Karolina , Kaminska Bozena , Wojtas Bartosz
Published: February 2023

Background

Glioblastoma (GBM, WHO grade IV) is an aggressive, primary brain tumor. Despite extensive tumor resection followed by radio- and chemotherapy, life expectancy of GBM patients did not improve over decades. Several studies reported transcription deregulation in GBMs, but regulatory mechanisms driving overexpression of GBM-specific genes remain largely unknown. Transcription in open chromatin regions is directed by transcription factors (TFs) that bind to specific motifs, recruit co-activators/repressors and the transcriptional machinery. Identification of GBM-related TFs-gene regulatory networks may reveal new and targetable mechanisms of gliomagenesis.

Results

We predicted TFs-regulated networks in GBMs in silico and intersected them with putative TF binding sites identified in the accessible chromatin in human glioma cells and GBM patient samples. The Cancer Genome Atlas and Glioma Atlas datasets (DNA methylation, H3K27 acetylation, transcriptomic profiles) were explored to elucidate TFs-gene regulatory networks and effects of the epigenetic background. In contrast to the majority of tumors, c-Jun expression was higher in GBMs than in normal brain and c-Jun binding sites were found in multiple genes overexpressed in GBMs, including VIM, FOSL2 or UPP1. Binding of c-Jun to the VIM gene promoter was stronger in GBM-derived cells than in cells derived from benign glioma as evidenced by gel shift and supershift assays. Regulatory regions of the majority of c-Jun targets have distinct DNA methylation patterns in GBMs as compared to benign gliomas, suggesting the contribution of DNA methylation to the c-Jun-dependent gene expression.

Conclusions

GBM-specific TFs-gene networks identified in GBMs differ from regulatory pathways attributed to benign brain tumors and imply a decisive role of c-Jun in controlling genes that drive glioma growth and invasion as well as a modulatory role of DNA methylation.
Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization
Authors: Albon Dana , Zhang Lijia , Patrie James , Jones Marieke , Li Z. Galvin , Noonan Emily , Borish Larry
Published: February 2023

Background

The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients.

Research question

This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data.

Study design and methods

We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL.

Results

Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization.

Interpretation

This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.
Implementing organized colorectal cancer screening programs in Europe—protocol for a systematic review of determinants and strategies
Authors: Albers Bianca , Auer Reto , Caci Laura , Nyantakyi Emanuela , Plys Ekaterina , Podmore Clara , Riegel Franziska , Selby Kevin , Walder Joel , Clack Lauren
Published: February 2023

Background

With a high mortality of 12.6% of all cancer cases, colorectal cancer (CRC) accounts for substantial burden of disease in Europe. In the past decade, more and more countries have introduced organized colorectal cancer screening programs, making systematic screening available to entire segments of a population, typically based on routine stool tests and/or colonoscopy. While the effectiveness of organized screening in reducing CRC incidence and mortality has been confirmed, studies continuously report persistent program implementation challenges. This systematic review will synthesize the literature on organized CRC screening programs. Its aim is to understand what is currently known about the barriers and facilitators that influence the implementation of these programs and about the implementation strategies used to navigate these determinants.

Methods

A systematic review of primary studies of any research design will be conducted. CENTRAL, CINAHL, EMBASE, International Clinical Trials Registry Platform, MEDLINE, PsycINFO, and Scopus will be searched. Websites of (non-)government health care organizations and websites of organizations affiliated with authors of included studies will be screened for unpublished evaluation reports. Existing organized CRC screening programs will be contacted with a request to share program-specific grey literature. Two researchers will independently screen each publication in two rounds for eligibility. Included studies will focus on adult populations involved in the implementation of organized CRC screening programs and contain information about implementation determinants/ strategies. Publications will be assessed for their risk of bias. Data extraction will include study aim, design, location, setting, sample, methods, and measures; program characteristics; implementation stage, framework, determinants, strategies, and outcomes; and service and other outcome information. Findings will be synthesized narratively using the three stages of thematic synthesis.

Discussion

With its sole focus on the implementation of organized CRC screening programs, this review will help to fill a central knowledge gap in the literature on colorectal cancer screening. Its findings can inform the decision-making in policy and practice needed to prioritize resources for establishing new and maintaining existing programs in the future.

Systematic review registration

PROSPERO (CRD42022306580).
Stabilization of hybrid stochastic systems with time-varying delay by discrete-time state feedback control
Authors: Mao Wei , Xiao Xiao , Miao Liangliang , Hu Liangjian
Published: February 2023

In this paper, we are concerned with the stabilization of hybrid stochastic systems with variable delay by discrete-time state feedback control. By using Lyapunov functionals, we obtain an upper bound $\tau ^{*}$

τ
∗

on the duration τ between two consecutive state observations. Meantime, we show that hybrid stochastic systems with variable delay can be stabilized by discrete-time state feedback control as long as $\tau <\tau ^{*}$
τ
<

τ
∗

. Finally, two examples are given to demonstrate the applicability of our work.
Ecological niche modelling of a critically endangered species Commiphora wightii (Arn.) Bhandari using bioclimatic and non-bioclimatic variables
Authors: Mathur Manish , Mathur Preet , Purohit Harshit
Published: February 2023

Background

The aim of this study is to examine the effects of four different bioclimatic predictors (current, 2050, 2070, and 2090 under Shared Socioeconomic Pathways SSP2-4.5) and non-bioclimatic variables (soil, habitat heterogeneity index, land use, slope, and aspect) on the habitat suitability and niche dimensions of the critically endangered plant speciesCommiphora wightiiin India. We also evaluate how niche modelling affects its extent of occurrence (EOO) and area of occupancy (AOO).

Results

The area under the receiver operating curve (AUC) values produced by the maximum entropy (Maxent) under various bioclimatic time frames were more than 0.94, indicating excellent model accuracy. Non-bioclimatic characteristics, with the exception of terrain slope and aspect, decreased the accuracy of our model. Additionally, Maxent accuracy was the lowest across all combinations of bioclimatic and non-bioclimatic variables (AUC = 0.75 to 0.78). With current, 2050, and 2070 bioclimatic projections, our modelling revealed the significance of water availability parameters (BC-12 to BC-19, i.e. annual and seasonal precipitation as well as precipitation of wettest, driest, and coldest months and quarters) on habitat suitability for this species. However, with 2090 projection, energy variables such as mean temperature of wettest quarter (BC-8) and isothermality (BC-3) were identified as governing factors. Excessive salt, rooting conditions, land use type (grassland), characteristics of the plant community, and slope were also noticed to have an impact on this species. Through distribution modelling of this species in both its native (western India) and exotic (North-east, Central Part of India, as well as northern and eastern Ghat) habitats, we were also able to simulate both its fundamental niche and its realized niche. Our EOO and AOO analysis reflects the possibility of many new areas in India where this species can be planted and grown.

Conclusion

According to the calculated area under the various suitability classes, we can conclude thatC. wightii's potentially suitable bioclimatic distribution under the optimum and moderate classes would increase under all future bioclimatic scenarios (2090 > 2050 ≈ current), with the exception of 2070, demonstrating that there are more suitable habitats available forC. wightiiartificial cultivation and will be available for future bioclimatic projections of 2050 and 2090. Predictive sites indicated that this species also favours various types of landforms outside rocky environments, such as sand dunes, sandy plains, young alluvial plains, saline areas, and so on. Our research also revealed crucial information regarding the community dispersion variable, notably the coefficient of variation that, when bioclimatic + non-bioclimatic variables were coupled, disguised the effects of bioclimatic factors across all time frames.
Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction
Authors: Lu Yi , Bu Fa-Qian , Wang Fang , Liu Li , Zhang Shuai , Wang Guan , Hu Xiu-Ying
Published: February 2023

Physical exercise is of great significance for maintaining human health. Exercise can provide varying degrees of benefits to cognitive function at all stages of life cycle. Currently, with the aging of the world’s population and increase of life expectancy, cognitive dysfunction has gradually become a disease of high incidence, which is accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia and weakening of orientation once diagnosed, and are unable to have a normal life. Cognitive dysfunction largely affects the physical and mental health, reduces the quality of life, and causes a great economic burden to the society. At present, most of the interventions are aimed to maintain the current cognitive level and delay deterioration of cognition. In contrast, exercise as a nonpharmacological therapy has great advantages in its nontoxicity, low cost and universal application. The molecular mechanisms underlying the effect of exercise on cognition are complex, and studies have been extensively centered on neural plasticity, the direct target of exercise in the brain. In addition, mitochondrial stability and energy metabolism are essential for brain status. Meanwhile, the organ-brain axis responds to exercise and induces release of cytokines related to cognition. In this review, we summarize the latest evidence on the molecular mechanisms underlying the effects of exercise on cognition, and point out directions for future research.
Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia
Authors: Gu Siyu , Hou Yue , Dovat Katarina , Dovat Sinisa , Song Chunhua , Ge Zheng
Published: February 2023

Background

More effective targeted therapy and new combination regimens are needed for Acute myeloid leukemia (AML), owing to the unsatisfactory long-term prognosis of the disease. Here, we investigated the synergistic effect and the mechanism of a histone deacetylase inhibitor, Chidamide in combination with Cladribine, a purine nucleoside antimetabolite analog in the disease.

Methods

Cell counting kit-8 assays and Chou-Talalay’s combination index were used to examine the synergistic effect of Chidamide and Cladribine on AML cell lines (U937, THP-1, and MV4-11) and primary AML cells. PI and Annexin-V/PI assays were used to detect the cell cycle effect and apoptosis effect, respectively. Global transcriptome analysis, RT-qPCR, c-MYC Knockdown, western blotting, co-immunoprecipitation, and chromatin immunoprecipitation assays were employed to explore the molecule mechanisms.

Results

The combination of Chidamide with Cladribine showed a significant increase in cell proliferation arrest, the G0/G1 phase arrest, and apoptosis compared to the single drug control in AML cell lines along with upregulated p21Waf1/Cip1 expression and downregulated CDK2/Cyclin E2 complex, and elevated cleaved caspase-9, caspase-3, and PARP. The combination significantly suppresses the c-MYC expression in AML cells, and c-MYC knockdown significantly increased the sensitivity of U937 cells to the combination compared to single drug control. Moreover, we observed HDAC2 interacts with c-Myc in AML cells, and we further identified that c-Myc binds to the promoter region of RCC1 that also could be suppressed by the combination through c-Myc-dependent. Consistently, a positive correlation of RCC1 with c-MYC was observed in the AML patient cohort. Also, RCC1 and HDAC2 high expression are associated with poor survival in AML patients. Finally, we also observed the combination significantly suppresses cell growth and induces the apoptosis of primary cells in AML patients with AML1-ETO fusion, c-KIT mutation, MLL-AF6 fusion, FLT3-ITD mutation, and in a CMML-BP patient with complex karyotype.

Conclusions

Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.
Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
Authors: Raggio Víctor , Graña Martín , Winiarski Erik , Mansilla Santiago , Simoes Camila , Rodríguez Soledad , Brandes Mariana , Tapié Alejandra , Rodríguez Laura , Cibils Lucía , Alonso Martina , Martínez Jennyfer , Fernández-Calero Tamara , Domínguez Fernanda , Mezquida Melania Rosas , Castro Laura , Cerisola Alfredo , Naya Hugo , Cassina Adriana , Quijano Celia , Spangenberg Lucía
Published: February 2023

The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients' mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype.
Collaborative dietetic and psychological care in Interprofessional Enhanced Cognitive Behaviour Therapy for adults with Anorexia Nervosa: a novel treatment approach
Authors: Bray Megan , Heruc Gabriella , Byrne Susan , Wright Olivia R. L.
Published: February 2023

Clinical practice guidelines for anorexia nervosa (AN) and atypical anorexia nervosa recommend treatment from a team including a mental health professional and a dietitian. To date, however, AN treatment models such as Enhanced Cognitive Behaviour Therapy (CBT-E) seldom include dietitians and have low to moderate treatment efficacy. Given interprofessional approaches to healthcare have been shown to improve treatment outcomes and enhance patient and clinician satisfaction, formalising collaborative dietetic and psychological treatment may be a feasible strategy to improve treatment outcomes and the patient and clinician experience of treatment. Moreover, malnutrition is a serious consequence of AN, and dietitians are considered experts in its diagnosis and treatment. This paper proposes a novel treatment approach, Interprofessional Enhanced Cognitive Behaviour Therapy (CBT-IE), an adaptation of CBT-E where dietitians deliver content related to malnutrition and dietary restraint and mental health professionals deliver content related to cognitive and behavioural change. The rationale for developing CBT-IE, treatment structure, and future research directions is discussed.
Protective effects of pentoxifylline against chlorine-induced acute lung injury in rats
Authors: Liu Meng-meng , Liu Jiang-zheng , Zhao Chen-qian , Guo Peng , Wang Zhao , Wu Hao , Yu Weihua , Liu Rui , Hai Chun-xu , Zhang Xiao-di
Published: February 2023

Objective

Chlorine is a chemical threat agent that can be harmful to humans. Inhalation of high levels of chlorine can lead to acute lung injury (ALI). Currently, there is no satisfactory treatment, and effective antidote is urgently needed. Pentoxifylline (PTX), a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, is widely used for the treatment of vascular disorders. The present study was aimed to investigate the inhibitory effects of PTX on chlorine-induced ALI in rats.

Methods

Adult male Sprague-Dawley rats were exposed to 400 ppm Cl2 for 5 min. The histopathological examination was carried out and intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. Subsequently, to evaluate the effect of PTX, a dose of 100 mg/kg was administered. The activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were determined by using commercial kits according to the manufacturer’s instructions. Western blot assay was used to detect the protein expressions of SOD1, SOD2, catalase (CAT), hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), occludin, E-cadherin, bcl-xl, LC 3, Beclin 1, PTEN-induced putative kinase 1 (PINK 1) and Parkin.

Results

The histopathological examination demonstrated that chlorine could destroy the lung structure with hemorrhage, alveolar collapse, and inflammatory infiltration. ROS accumulation was significantly higher in the lungs of rats suffering from inhaling chlorine (P<0.05). PTX markedly reduced concentrations of MAD and GSSG, while increased GSH (P<0.05). The protein expression levels of SOD1 and CAT also decreased (P<0.05). Furthermore, the activity of LDH in rats treated with PTX was significantly decreased compared to those of non-treated group (P<0.05). Additionally, the results also showed that PTX exerted an inhibition effect on protein expressions of HIF-1α, VEGF and occludin, and increased the level of E-cadherin (P<0.05). While the up-regulation of Beclin 1, LC 3II/I, Bcl-xl, and Parkin both in the lung tissues and mitochondria, were found in PTX treated rats (P<0.05). The other protein levels were decreased when treated with PTX (P<0.05).

Conclusion

PTX could ameliorate chlorine-induced lung injury via inhibition effects on oxidative stress, hypoxia and autophagy, thus suggesting that PTX could serve as a potential therapeutic approach for ALI.
Egyptian pediatric clinical practice adapted guidelines: evidence-based [2] steroid-resistant nephrotic syndrome (SRNS) 2022
Authors: Moustafa Bahia , Moselhy Sawsan , Rabie Moftah , Hammad Ayman , Youssef Doaa , Shouman Mohamed , Makar Samuel , Badr Ahmed , Mansour Sameh , Ebrahim Dina , Nabhan Marwa , Ateia Fatma , Abdel-Nabi Hend , Hussein Ahmed , Salman Manal , Korkor Mai S. , Elbahkiry Esraa A. , Dagher Marwa , Selim Abeer , Amer Yasser S. , Omar Tarek , Baky Ashraf Abdel ,   on behalf of the Egyptian Pediatric Clinical Practice Guidelines (EPG) Committee (Chairman Ashraf Abdel Baky), SRNS Clinical & Methodology work group, Badr Ahmed , Attia Fatma , Bahkiry Isra El , Youssef Doaa , Shouman Mohamad , Amer Yasser S. , Sarhan Amr , Soliman Neveen A. , Hakim Ihab El , Zotta Federica
Published: February 2023

Background

Nephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type (SSNS) constitutes about 85–90%, whereas steroid-resistant type (SRNS) only 15–20% (Mickinney et al. Pediatr Nephrol 16:1040-1044, 2001). While MCD is the most common histopathology in SS type, children with SRNS have MCD, mesangial proliferative glomerulonephritis, or focal and segmental glomerulosclerosis (FSGS) (International Study Kidney Disease in children, Kidney Int 20;765-771, 1981). SRNS is defined as those who do not show remission after 6 weeks and standard dose of oral steroids ± 3 IV MPD doses (Trautmann et al. Pediatr Nephrol 35:1529-1561, 2020).

Objectives

These national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from the IPNA 2020, KDIGO 2021, and Japanese 2014 de novo guidelines for diagnosis and management of nephrotic children to be presented in two manuscripts: (1) steroid sensitive (SSNS) and (2) steroid-resistant nephrotic syndrome (SRNS).

Methodology

Formulation of key questions was followed with a review of literature guided by our appraised guidelines using AGREE plus appraisal tool. Virtual monthly meetings all through the year 2021 were activated  for reviewing and validation of final adaptation evidence-based draft, considering all comments of external reviewers including KDIGO assigned reviewer.

Discussion

Rationale behind the selection of adopted statements and tailoring of others to suit our local facilities, expertise, and our local disease profile was discussed in the text with reasons.

Conclusion

The provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations.
Egyptian evidence -based pediatric clinical practice adapted guidelines for management of [1] steroid sensitive nephrotic syndrome (EPG/SSNS 2022)
Authors: Moustafa Bahia , El-Kersh Mahmoud M. , Shalaby Sherin , Salam Nancy Abdel , Moselhy Sawsan , Soliman Gamal Taha , Selim Abeer , Amer Yasser S , Baky Ashraf Abdel ,   On Behalf of the Egyptian Pediatric Clinical Practice Guidelines (EPG) Committee
Published: February 2023

Background

Nephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type constitutes about 90% and steroid resistant 10% of total cases. 

Objectives

These national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from IPNA 2020, KDIGO 2021, and Japanese 2014 for diagnosis, evaluation, management and follow-up of nephrotic children for Steroid sensitive nephrotic syndrome (SSNS) as paper one to be followed with SRNS as paper two.

Methodology

Formulation of key questions was followed with review of literature, guided by our retrieved and appraised guidelines using Agree plus appraisal tool. After virtual monthly meetings through the year 2021, the final draft was validated considering the comments of external local reviewers and KDIGO-assigned reviewers. 

Discussion

Rationale behind the selection of adopted statements and tailoring of others to suit our local facilities’ expertise and disease profile was discussed in the text with reasons.

Conclusion

The provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations.
Imaging distributed acoustic sensing-to-geophone conversion data: A field application to CO2 sequestration data
Authors: Ma Yong , Fu Lei , Li Weichang
Published: February 2023

Compared with conventional geophone data, distributed fiber-optic sensing, including distributed acoustic sensing (DAS), can provide better spatial coverage for imaging the subsurface with finer spatial sampling. Because DAS measures subsurface seismic responses differently than the geophone, imaging technologies (e.g., reverse time migration and full-waveform inversion) that are developed for conventional geophone data cannot be readily applied to original DAS data without causing uncertainties in phase or depth, especially when one compares the DAS imaging results against the usual geophone imaging results. Based on vertical seismic profile field data from a CO2 sequestration site, we have compared the imaging results of the CO2 storage reservoir associated with the DAS and the geophone data, respectively, and we illustrate the differences between the imaging results of the DAS and geophone data. The difference between the DAS and geophone imaging results could be critical in obtaining time-lapse signals for monitoring reservoir changes, e.g., in subsurface CO2 sequestration. We propose to convert DAS to geophone data so that we can reduce the discrepancies between DAS and geophone imaging results and we therefore can reuse existing seismic imaging technologies. Two conversion methods, one physics-based and one deep-learning (DL)-based, are used for the DAS-to-geophone transformation. Field data results demonstrate that the DL-based approach can better successfully improve the alignment between the DAS and geophone images, whereas the physics-based solution is constrained by its assumption.
Optimized Detection of Unknown
MET
Exon 14 Skipping Mutations in Routine Testing for Patients With Non–Small-Cell Lung Cancer
Authors: Sun Rui , Wang Zhizhong , Zhao Jiuzhou , Ren Pengfei , Ma Jie , Guo Yongjun
Published: February 2023

PURPOSE

MET
exon 14 (
MET
ex14) skipping is an actionable biomarker in non–small-cell lung cancer. However,
MET
variants are highly complex and diverse, and not all variants lead to exon 14 skipping. Assessing the skipping effect of unknown variants is still a key issue in molecular diagnosis.

MATERIALS AND METHODS

We retrospectively collected
MET
variants around exon 14 from 4,233 patients with non–small-cell lung cancer who underwent next-generation sequencing testing using DNA, as well as two published data sets.

RESULTS

Among the 4,233 patients, 44 unique variants including 29 novel variants (65.9%) were discovered from 53 patients. Notably, 31 samples (58.5%) failed RNA verification. Using RNA verification, nine novel skipping variants and five nonskipping variants were confirmed. We further used SpliceAI with the delta score cutoff of 0.315 to aid the classification of novel variants (sensitivity = 98.88% and specificity = 100%). When applied to the reported variants, we also found three wrongly classified nonskipping variants. Finally, an optimized knowledge-based interpretation procedure for clinical routine was built according to the mutation type and location, and five more skipping mutations from the 13 unknown variants were determined, which improved the population determination rate to 0.92%.

CONCLUSION

This study discovered more
MET
ex14 skipping variants and optimized an innovative approach that could be adapted for the interpretation of infrequent or novel
MET
ex14 variants timely without experimental validation.
A Case of Lymphocytic Infundibulo-neurohypophysitis Exhibiting Spontaneous Regression
Authors: Hasebe Masashi , Shibue Kimitaka , Honjo Sachiko , Hamasaki Akihiro
Published: February 2023

Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk, typically presenting with central diabetes insipidus (CDI). LINH is considered underdiagnosed because the definitive diagnosis requires invasive pituitary surgery with a high risk of complications. We present a case of CDI resulting from LINH, which was treated with conservative management, eschewing both glucocorticoid treatment and pituitary surgery. At presentation, the hormonal assessment indicated the presence of CDI without anterior pituitary dysfunction. Magnetic resonance imaging revealed stalk thickening without a posterior pituitary bright spot, and anti-rabphilin-3A antibodies were positive in serum. Collectively, we made a diagnosis of LINH. Considering that the patient did not exhibit any symptoms of mass effect, we chose conservative treatment with desmopressin acetate. One year later, the stalk thickening regressed spontaneously without surgical or glucocorticoid treatment, although the posterior pituitary bright spot remained absent, and CDI did not improve. The inflammatory process of LINH is mostly self-limited and recovers spontaneously, whereas life-long desmopressin treatment may be required because of pituitary stalk fibrosis and atrophy. Our case highlights the importance of noninvasive diagnosis and careful follow-up in preventing unnecessary interventions for patients with LINH.
Serum Adiponectin and Leptin Is Not Related to Skeletal Muscle Morphology and Function in Young Women
Authors: Yoshiko Akito , Ohta Megumi , Kuramochi Rieko , Mitsuyama Hirohito
Published: February 2023

Adipokines secreted from adipose tissue, such as adiponectin and leptin, enhance skeletal muscle metabolism. Animal studies have shown that adipokine knockout leads to a reduction in muscle function. Muscle function is determined by muscle size and quality; therefore, it is speculated that lower adipokine levels affect skeletal muscle size and quality, eventually leading to lower muscle function. This study aimed to investigate the relationship between adipokines and skeletal muscle morphology and function in young individuals. A total of 21 young women participated in this study. Adiponectin and leptin levels were analyzed using fasting blood samples from all participants. B-mode ultrasound images of the thigh and calf were obtained, and the muscle thickness and echo intensity were measured in the vastus lateralis (VL) and medial gastrocnemius (MG). The shear modulus was measured from the VL and MG using shear wave elastography. Knee extension and plantar flexion peak torques were measured as muscle functions. Adiponectin and leptin were not related to echo intensity, shear modulus, and muscle thickness in the VL and MG (rs = −0.26−0.37, P > .05). Furthermore, no relationship was observed between adiponectin, leptin, knee extension, and dorsiflexion peak torque (rs = −0.28−0.41, P > .05). These negative results suggest that adiponectin and leptin levels in young women are not associated with muscle size and quality, nor are they related to muscle function.
Environmental Preferences and Technological Choices: Is Market Competition Clean or Dirty?
Authors: Aghion Philippe , Bénabou Roland , Martin Ralf , Roulet Alexandra
Published: February 2023

We investigate the effects of consumers’ environmental concerns and market competition on firms’ decisions to innovate in “clean” technologies. Agents care about their consumption and environmental footprint; firms pursue greener products to soften price competition. Acting as complements, these forces determine R&D, pollution, and welfare. We test the theory using panel data on patents by 7,060 automobile sector firms in 25 countries, environmental willingness to pay, and competition. As predicted, exposure to prosocial attitudes fosters clean innovation, all the more so where competition is strong. Plausible increases in both together can spur it as much as a large fuel price increase. (JEL D22, L62, O31, O34, Q52, Q53, Q54)
Cognitive Decline, Limited Awareness, Imperfect Agency, and Financial Well-Being
Authors: Ameriks John , Caplin Andrew , Lee Minjoon , Shapiro Matthew D. , Tonetti Christopher
Published: February 2023

Cognitive decline may lead older Americans to make poor financial decisions. Preventing poor decisions may require timely transfer of financial control to a reliable agent. Cognitive decline, however, can develop unnoticed, creating the possibility of suboptimal timing of the transfer of control. This paper presents survey-based evidence that older Americans with significant wealth regard suboptimal timing of the transfer of control, in particular delay due to unnoticed cognitive decline, as a substantial risk to financial well-being. This paper provides a theoretical framework to model such a lack of awareness and the resulting welfare loss. (JEL G51, G53, H55, J14, J26, J32)