bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of genetic markers for drug resistance after the introduction of dihydroartemisinin–piperaquine as first-line anti-malarial treatment for uncomplicated falciparum malaria in Indonesia
Authors: Rahmasari Farindira Vesti , Asih Puji Budi Setia , Rozi Ismail Ekoprayitno , Wangsamuda Suradi , Risandi Rifqi , Dewayanti Farahana Kresno , Permana Dendi Hadi , Syahrani Lepa , Prameswari Helen Dewi , Basri Herdiana H. , Bustos Maria Dorina G. , Charunwatthana Prakaykaew , Dondorp Arjen M. , Imwong Mallika , Syafruddin Din
Published: August 2023

Background

Dihydroartemisinin–piperaquine has been Indonesia’s first-line anti-malarial treatment since 2008. Annual therapeutic efficacy studies (TES) done in the last 12 years showed continued high treatment efficacy in uncomplicated Plasmodium falciparum malaria. Although these studies did not show evidence for artemisinin resistance, a slight increase in Late Treatment Failure was observed over time. It is highlight to explore the evolution of genetic markers for ACT partner drug resistance since adopting DHA–PPQ.

Methods

Dry blood spots were identified from a mass blood survey of uncomplicated falciparum malaria patients (N = 50) in Sumba from 2010 to 2018. Analysis of genotypic profile (N = 51) and a Therapeutic Efficacy Study (TES) from Papua (N = 142) from 2020 to 2021, 42-day follow-up. PCR correction using msp1, msp2, and glurp was used to distinguish recrudescence and reinfection. Parasite DNA from DBSs was used for genotyping molecular markers for antimalaria drug resistance, including in Pfk13, pfcrt, and pfmdr1, as well as gene copy number variation in pfpm2/3 and pfmdr1.

Results

The study revealed the absence of SNPs associated with ART resistance and several novel SNPs such as L396F, I526V, M579I and N537S (4.25%). In Sumba, the mutant haplotype SDD of pfmdr1 was found in one-third of the isolates, while only 8.9% in Papua. None of the pfcrt mutations linked to piperaquine resistance were observed, but 71% of isolates had pfcrt I356L. Amplification of the pfpm2/3 genes was in Sumba (17.02%) and Papua (13.7%), while pfmdr1 copy number prevalence was low (3.8%) in both areas. For the TES study, ten recurrences of infection were observed on days 28, 35, and 42. Late parasitological failure (LPF) was observed in 10/117 (8.5%) subjects by microscopy. PCR correction revealed that all nine cases were re-infections and one was confirmed as recrudescence.

Conclusion

This study revealed that DHA–PPQ is still highly effective against P. falciparum. The genetic architecture of the parasite P. falciparum isolates during 2010–2021 revealed single copy of Pfpm2 and pfmdr1 were highly prevalent. The slight increase in DHA–PPQ LTF alerts researchers to start testing other ACTs as alternatives to DHA–PPQ for baseline data in order to get a chance of achieving malaria elimination wants by 2030.

Graphical Abstract
Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits
Authors: Xu Jia , Li Haocheng , Jin Gui , Zhuang Wei , Bai Zelin , Sun Jian , Chen Mingsheng , Wang Feng , Yang Xu , Qin Mingxin
Published: August 2023

Background

Cerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia.

Methods

The adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments.

Results

There was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = − 0.642, p = 0.002) after 40 min after ischemia. The Bland–Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084).

Conclusion

The animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.
REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial
Authors: Martin-Broto Javier , Valverde Claudia , Hindi Nadia , Vincenzi Bruno , Martinez-Trufero Javier , Grignani Giovanni , Italiano Antoine , Lavernia Javier , Vallejo Ana , Tos Paolo Dei , Le Loarer Francois , Gonzalez-Campora Ricardo , Ramos Rafael , Hernández-Jover Diana , Gutierrez Antonio , Serrano Cesar , Monteagudo Maria , Letón Rocio , Robledo Mercedes , Moura David S. , Martin-Ruiz Marta , López-Guerrero Jose A. , Cruz Julia , Fernandez-Serra Antonio , Blay Jean-Yves , Fumagalli Elena , Martinez-Marin Virginia
Published: August 2023

Background

Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST.

Methods

Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment.

Results

From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST.

Conclusions

Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST.

Trial registration

ClinicalTrials.gov Identifier: NCT02638766.
The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis
Authors: Tang Jianing , Long Guo , Li Xuanxuan , Zhou Ledu , Zhou Yangying , Wu Zheyu
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal human malignancies, and with quite limited treatment alternatives. The proteasome is responsible for most of the protein degradation in eukaryotic cells and required for the maintenance of intracellular homeostasis. However, its potential role in HCC is largely unknown. In the current study, we identified eukaryotic translation initiation factor 3 subunit H (EIF3H), belonging to the JAB1/MPN/MOV34 (JAMM) superfamily, as a bona fide deubiquitylase of O-GlcNAc transferase (OGT) in HCC. We explored that EIF3H was positively associated with OGT in HCC and was related to the unfavorable prognosis. EIF3H could interact with, deubiquitylate, and stabilize OGT in a deubiquitylase-dependent manner. Specifically, EIF3H was associated with the GT domain of ERα via its JAB/MP domain, thus inhibiting the K48-linked ubiquitin chain on OGT. Besides, we demonstrated that the knockdown of EIF3H significantly reduced OGT protein expression, cell proliferation and invasion, and caused G1/S arrest of HCC. We also found that the deletion of EIF3H prompted ferroptosis in HCC cells. Finally, the effects of EIF3H depletion could be reversed by further OGT overexpression, implying that the OGT status is indispensable for EIF3H function in HCC carcinogenesis. In summary, our study described the oncogenic function of EIF3H and revealed an interesting post-translational mechanism between EIF3H, OGT, and ferroptosis in HCC. Targeting the EIF3H may be a promising approach in HCC.
Expression of stem cell markers SALL4, LIN28A, and KLF4 in ameloblastoma
Authors: de Albuquerque Dias Rafaela , Balbinot Karolyny Martins , da Silva Kataoka Maria Sueli , de Melo Alves Júnior Sérgio , de Jesus Viana Pinheiro João
Published: August 2023

Background

Ameloblastoma (AME) is a benign odontogenic tumour of epithelial origin characterised by slow but aggressive growth, infiltration, and recurrence; it is capable of reaching large dimensions and invading adjacent structures. Stem cell research has proven to be significant in the sphere of tumour biology through these cells’ possible involvement in the aetiopathogenesis of this tumour.

Methods

Immunohistochemistry was performed on AME, dentigerous cyst (DC), and dental follicle (DF) samples, and indirect immunofluorescence was performed on the AME-hTERT cell line to determine the expression of SALL4, LIN28A, and KLF4.

Results

Expression of proteins related to cellular pluripotency was higher in AME cells than in DC and DF cells. The analysis revealed that the proteins in question were mainly expressed in the parenchyma of AME tissue samples and were detected in the nuclei of AME-hTERT cells.

Conclusions

Stem cells may be related to the origin and progression of AME.
The roles of METTL3 on autophagy and proliferation of vascular smooth muscle cells are mediated by mTOR rather than by CDK1
Authors: Luo Hanshen , Wu Xingliang , Huo Bo , Liu Liyuan , Jiang Ding-Sheng , Yi Xin
Published: August 2023

Background

Aberrant proliferation of vascular smooth muscle cells (VSMCs) is the cause of neointima formation followed by vascular injury. Autophagy is involved in this pathological process, but its function is controversial. Recently, we found that methyltransferase like 3 (METTL3) inhibited VSMC proliferation by activating autophagosome formation. Moreover, we also demonstrated that METTL3 reduced the levels of phosphorylated mammalian target of rapamycin (p-mTOR) and cyclin dependent kinase 1 (p-CDK1/CDC2), which were critical for autophagy and proliferation regulation. However, whether mTOR and CDK1 mediated the function of METTL3 on autophagy and proliferation in VSMCs remains unknown.

Results

We showed that the activator of mTOR, MHY1485 largely reversed the effects of METTL3 overexpression on VSMC autophagy and proliferation. Rapamycin, the inhibitor of mTOR, obviously nullified the pro-proliferation effects of METTL3 knockdown by activating autophagy in VSMCs. Unexpectedly, mTOR did not contribute to the impacts of METTL3 on migration and phenotypic switching of VSMCs. On the other hand, by knockdown of CDK1 in VSMC with METTL3 deficiency, we demonstrated that CDK1 was involved in METTL3-regulated proliferation of VSMCs, but this effect was not mediated by autophagy.

Conclusions

We concluded that mTOR but not CDK1 mediated the role of METTL3 on VSMC proliferation and autophagy.
Postoperative complications analysis of circular stapled versus linear stapled anastomosis for patients undergoing esophagectomy: a systematic review and meta-analysis
Authors: Gu Hao-Yu , Luo Jing , Qiang Yong
Published: August 2023

Background

The choice of anastomosis technique after esophagectomy is closely associated with the postoperative complications. Whether circular stapled or linear stapled anastomosis is the optimal technique has not been established. Therefore, we conducted this meta-analysis to show the latest and most comprehensive published assessment of circular stapled anastomosis in comparison with linear stapled anastomosis in postoperative complications.

Methods

Databases (PubMed, Embase, Web of science, Cochrane Library) were searched for all randomized controlled trials and comparative studies comparing circular stapled anastomosis with linear stapled anastomosis after esophagectomy. The odd ratio and mean difference with 95% confidence interval were calculated. We used the Higgins I² statistics to assess the statistical heterogeneity between studies. Review manager (version 5.4) software was used in this analysis.

Results

Sixteen studies with 2322 patients were included in our study. The study demonstrated that the use of linear stapled technique after esophagectomy could reduce the risk of both anastomotic leakage (P = 0.0003) and stricture (P < 0.00001) compared with circular stapled technique. Stratification by anastomotic site showed that no matter what kind of anastomotic site (cervical or thoracic anastomosis) was used, linear stapled anastomosis could effectively reduce the anastomotic stricture in comparison with circular stapled anastomosis. Moreover, linear stapled anastomosis could decrease the risk of thoracic anastomotic leakage. There were no significant differences between circle stapled anastomosis and linear stapled anastomosis in reflux esophagitis (P = 0.17), pneumonia (P = 0.91), operation time (P = 0.41) and hospital stay (P = 0.38).

Conclusions

The study suggested that linear stapled anastomosis could be considered to be an optimal treatment associated with a reduced risk of anastomotic leakage and stricture in comparison with circular stapled anastomosis.
The association of feeding difficulties and generic health-related quality of life among children born with esophageal atresia
Authors: Örnö Ax Sofie , Dellenmark-Blom Michaela , Abrahamsson Kate , Jönsson Linus , Gatzinsky Vladimir
Published: August 2023

Background

Children born with esophageal atresia experience feeding difficulties. This study investigates the association of feeding difficulties and generic health-related quality of life among children aged 2–7 and 8–17 years, born with esophageal atresia.

Methods

108 families (n = 36 aged 2–7 years; n = 72 aged 8–17) answered a survey regarding difficulties in their child’s mealtimes and a validated generic health-related quality of life instrument(PedsQL 4.0). Clinical data was collected from hospital records. The association of feeding difficulties and health-related quality of life was analysed trough Mann-Whitney U-test. Linear regression determined whether the number of concurrent feeding difficulties in the child decreased the health-related quality of life scores. P < 0.05 was considered significant.

Results

In children aged 2–7 and 8–17 years, to have a gastrostomy, to use a food infusion pump, need for energy-enriched food and eating small portions were respectively significantly associated with lower total health-related quality of life scores in the parent-reports (p < 0.05). Most of the feeding difficulties had a negative significant relationship with the domains of physical and social functioning. Additionally, in the older age group, long mealtimes and adult mealtime supervision were associated with lower scores in both child and parent reports. In both age groups, an increased number of feeding difficulties in the child decreased the total generic health-related quality of life scores (p < 0.01).

Conclusion

Specific feeding difficulties are associated with low health-related quality of life among children with esophageal atresia. An increasing number of feeding difficulties is associated to decreasing health-related quality of life-scores. Further research is needed to understand these associations.
Epidemiological research on rare diseases using large-scale online search queries and reported case data
Authors: Zhang Lei , Jin Ye , Li Jiayu , He Zhiyu , Zhang Dingding , Zhang Min , Zhang Shuyang
Published: August 2023

Background

Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China’s national database of rare diseases during the same period.

Results

A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories.

Conclusion

Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies.
Trends in the effect of COVID-19 on consultations for persons with clinical and subclinical eating disorders
Authors: Kawai Keisuke , Tachimori Hisateru , Yamamoto Yurie , Nakatani Yuki , Iwasaki Shinmi , Sekiguchi Atsushi , Kim Yoshiharu , Tamura Naho
Published: August 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of individuals developing eating disorders and has exacerbated existing eating disorders. This observational study investigated the impact of the COVID-19 pandemic on patients with clinical and subclinical eating disorders.

Methods

This study was conducted over a period of four years: two years before and after the onset of the COVID-19 pandemic in Japan. We recorded the number and types of consultations provided by the Eating Disorder Treatment and Support Center coordinator. For subgroup analysis, data were classified by age, body mass index, and source of consultation, including patients, families, and personnel. The Seasonal Decomposition of Time Series by Loess was used for time series analysis.

Results

The total number of consultations increased after the start of the pandemic and peaked around the beginning of 2022, before subsequently falling despite the increase in the number of COVID-19 infections. A similar trend was observed in patients aged 10–29 years. The study period coincided with social isolation and school/college/university closures.

Conclusions

The number of eating disorder consultations increased after the start of the pandemic. Although COVID-19 infections persisted, the pandemic’s impact was transient.
An amino acid transporter subunit as an antibody–drug conjugate target in colorectal cancer
Authors: Montero Juan Carlos , del Carmen Sofía , Abad Mar , Sayagués José M. , Barbáchano Antonio , Fernández-Barral Asunción , Muñoz Alberto , Pandiella Atanasio
Published: August 2023

Background

Advanced colorectal cancer (CRC) is difficult to treat. For that reason, the development of novel therapeutics is necessary. Here we describe a potentially actionable plasma membrane target, the amino acid transporter protein subunit CD98hc.

Methods

Western blot and immunohistochemical analyses of CD98hc protein expression were carried out on paired normal and tumoral tissues from patients with CRC. Immunofluorescence and western studies were used to characterize the action of a DM1-based CD98hc-directed antibody–drug conjugate (ADC). MTT and Annexin V studies were performed to evaluate the effect of the anti-CD98hc-ADC on cell proliferation and apoptosis. CRISPR/Cas9 and shRNA were used to explore the specificity of the ADC. In vitro analyses of the antitumoral activity of the anti-CD98hc-ADC on 3D patient-derived normal as well as tumoral organoids were also carried out. Xenografted CRC cells and a PDX were used to analyze the antitumoral properties of the anti-CD98hc-ADC.

Results

Genomic as well proteomic analyses of paired normal and tumoral samples showed that CD98hc expression was significantly higher in tumoral tissues as compared to levels of CD98hc present in the normal colonic tissue. In human CRC cell lines, an ADC that recognized the CD98hc ectodomain, reached the lysosomes and exerted potent antitumoral activity. The specificity of the CD98hc-directed ADC was demonstrated using CRC cells in which CD98hc was decreased by shRNA or deleted using CRISPR/Cas9. Studies in patient-derived organoids verified the antitumoral action of the anti-CD98hc-ADC, which largely spared normal tissue-derived colon organoids. In vivo studies using xenografted CRC cells or patient-derived xenografts confirmed the antitumoral activity of the anti-CD98hc-ADC.

Conclusions

The studies herewith reported indicate that CD98hc may represent a novel ADC target that, upon well-designed clinical trials, could be used to increase the therapeutic armamentarium against CRC.
Extracranial anticoagulant related bleedings admitted to intensive care units: a French multicenter retrospective study
Authors: Botrel Thomas , Cunat Sibylle , Helms Julie , Lemarié Jérémie , Gaillon Jeanne , Préau Sébastien , Favory Raphael , Thille Arnaud W. , Boissier Florence , Maury Eric , Joffre Jérémie , Ait-Oufella Hafid
Published: August 2023

Background

Anticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding.

Methods

A retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included.

Results

486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2.

Conclusion

Anticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs.
A Culex quinquefasciatus strain resistant to the binary toxin from Lysinibacillus sphaericus displays altered enzyme activities and energy reserves
Authors: Menezes Heverly Suzany G. , Costa-Latgé Samara G. , Genta Fernando A. , Napoleão Thiago H. , Paiva Patrícia M. G. , Romão Tatiany P. , Silva-Filha Maria Helena N. L.
Published: August 2023

Background

The resistance of a Culex quinquefasciatus strain to the binary (Bin) larvicidal toxin from Lysinibacillus sphaericus is due to the lack of expression of the toxin’s receptors, the membrane-bound Cqm1 α-glucosidases. A previous transcriptomic profile of the resistant larvae showed differentially expressed genes coding Cqm1, lipases, proteases and other genes involved in lipid and carbohydrate metabolism. This study aimed to investigate the metabolic features of Bin-resistant individuals by comparing the activity of some enzymes, energy reserves, fertility and fecundity to a susceptible strain.

Methods

The activity of specific enzymes was recorded in midgut samples from resistant and susceptible larvae. The amount of lipids and reducing sugars was determined for larvae and adults from both strains. Additionally, the fecundity and fertility parameters of these strains under control and stress conditions were examined.

Results

Enzyme assays showed that the esterase activities in the midgut of resistant larvae were significantly lower than susceptible ones using acetyl-, butyryl- and heptanoyl-methylumbelliferyl esthers as substrates. The α-glucosidase activity was also reduced in resistant larvae using sucrose and a synthetic substrate. No difference in protease activities as trypsins, chymotrypsins and aminopeptidases was detected between resistant and susceptible larvae. In larval and adult stages, the resistant strain showed an altered profile of energy reserves characterized by significantly reduced levels of lipids and a greater amount of reducing sugars. The fertility and fecundity of females were similar for both strains, indicating that those changes in energy reserves did not affect these reproductive parameters.

Conclusions

Our dataset showed that Bin-resistant insects display differential metabolic features co-selected with the phenotype of resistance that can potentially have effects on mosquito fitness, in particular, due to the reduced lipid accumulation.

Graphical Abstract
Adherence to rehabilitation and home exercise after myocardial infarction: a qualitative study of expectations, barriers and drivers
Authors: Serves Nina , Pazart Lionel , Gabriel Damien , Mourot Laurent , Ecarnot Fiona
Published: August 2023

Background

Cardiac rehabilitation is a key component of secondary prevention, but uptake is often low, and motivation to pursue exercise and lifestyle changes may be lacking in patients who have suffered from acute myocardial infarction (AMI). We explored the intentions of patients hospitalized for AMI regarding attendance at cardiac rehabilitation and the future pursuit of regular physical exercise at home.

Methods

We performed a qualitative study using semi-structured interviews. Eligible patients were those hospitalized for AMI in the cardiology unit of a large university hospital in Eastern France between 10/11/2021 and 7/3/2022, and who were deemed eligible for rehabilitation by the treating physician. Patients were interviewed before discharge. Interviews were transcribed and analysed by thematic analysis. We administered the Global Physical Activity Questionnaire (GPAQ) questionnaire to all participants.

Results

Of 17 eligible patients, 15 were interviewed, at which point saturation was reached. The majority were males (n = 13, 86%), median age 54 years (41–61). Three key themes emerged: Firstly, there is a mismatch between patients’ perceptions of their physical activity and actual level of activity as assessed by objective tools. Second, cardiac rehabilitation is seen as a vector for information about the return to home after AMI. Third, regarding the intention to change lifestyle, there are persisting obstacles, drivers, fears and expectations.

Conclusion

Patients with AMI often overestimate how physically active they are. Even close to discharge, patients have persisting informational needs, and many see cardiac rehabilitation as a means to obtain this information, rather than as a therapeutic intervention.
The specific DNA methylation landscape in focal cortical dysplasia ILAE type 3D
Authors: Wang Dan-Dan , Katoch Mitali , Jabari Samir , Blumcke Ingmar , Blumenthal David B. , Lu De-Hong , Coras Roland , Wang Yu-Jiao , Shi Jie , Zhou Wen-Jing , Kobow Katja , Piao Yue-Shan
Published: August 2023

Focal Cortical Dysplasia (FCD) is a frequent cause of drug-resistant focal epilepsy in children and young adults. The international FCD classifications of 2011 and 2022 have identified several clinico-pathological subtypes, either occurring isolated, i.e., FCD ILAE Type 1 or 2, or in association with a principal cortical lesion, i.e., FCD Type 3. Here, we addressed the DNA methylation signature of a previously described new subtype of FCD 3D occurring in the occipital lobe of very young children and microscopically defined by neuronal cell loss in cortical layer 4. We studied the DNA methylation profile using 850 K BeadChip arrays in a retrospective cohort of 104 patients with FCD 1 A, 2 A, 2B, 3D, TLE without FCD, and 16 postmortem specimens without neurological disorders as controls, operated in China or Germany. DNA was extracted from formalin-fixed paraffin-embedded tissue blocks with microscopically confirmed lesions, and DNA methylation profiles were bioinformatically analyzed with a recently developed deep learning algorithm. Our results revealed a distinct position of FCD 3D in the DNA methylation map of common FCD subtypes, also different from non-FCD epilepsy surgery controls or non-epileptic postmortem controls. Within the FCD 3D cohort, the DNA methylation signature separated three histopathology subtypes, i.e., glial scarring around porencephalic cysts, loss of layer 4, and Rasmussen encephalitis. Differential methylation in FCD 3D with loss of layer 4 mapped explicitly to biological pathways related to neurodegeneration, biogenesis of the extracellular matrix (ECM) components, axon guidance, and regulation of the actin cytoskeleton. Our data suggest that DNA methylation signatures in cortical malformations are not only of diagnostic value but also phenotypically relevant, providing the molecular underpinnings of structural and histopathological features associated with epilepsy. Further studies will be necessary to confirm these results and clarify their functional relevance and epileptogenic potential in these difficult-to-treat children.
Harnessing education and lifestyle change to support transitional health for returning citizens: a feasibility study protocol
Authors: Sneed Rodlescia S. , El-Alamin Leon , Thrower Marsha , Nadrowski Jessica , Habermehl Kayla
Published: August 2023

Background

Exercise and healthy eating are known to reduce chronic disease risk; however, formerly incarcerated individuals (i.e., returning citizens) face significant social barriers when attempting to engage with existing community-based physical activity and nutrition programs. Given the high disease burden and unique educational needs of returning citizens, this proposed work fills an important gap in the support services currently offered to this population.

Methods

This article describes a process for evaluating the feasibility and acceptability of a physical activity and nutrition intervention tailored to the needs of returning citizens via a partnership between an academic research organization and a community-based reentry program for returning citizens. Staff from the community-based reentry program will train four returning citizens as group fitness instructors and work with a nutritionist to design a 16-week nutrition education curriculum. Reentry program staff will enroll up to 15 formerly incarcerated adults (aged 18 +) in the exercise and nutrition program. Participants will take part in weekly nutrition classes led by the nutritionist and weekly group exercise classes led by a peer instructor. Research staff will evaluate program success in four domains: reach, preliminary effectiveness, implementation, and maintenance.

Results

This feasibility study will allow us to design and test a program that can eventually be evaluated in a large, randomized trial. It also addresses the multitude of social determinants that impact the health of returning citizens and builds a framework for program sustainability. Individuals recruited as fitness trainers will acquire skills and certifications that may be used to sustain physical fitness activities within the reentry program.

Conclusions

This feasibility study will test our ability to address social determinants that impact the health of returning citizens through a peer-led physical activity and nutrition programming. In the long term, study results may inform development and implementation of reentry programming and policy on a wider scale.
Private banking development in China under two organizational structures: Economic analysis from an organizational innovation perspective
Authors: Liu He , Bai Yun , Huang Zhiguang , Qiao Han , Wang Shouyang
Published: August 2023

This paper investigates optimal decisions for private banking development in China under two innovative organizational structures—the big retail mode (BRM) and the independent development mode (IDM). Under the BRM, the retail and private banking divisions form a cooperative relationship wherein the former transfers high-net-worth customers to the latter. In addition, retail banking receives a share of private banking revenues. We investigate the optimal revenue-sharing ratio between the two divisions and the optimal effort by private banking to serve transferred customers within the cooperative relationship. The analytical results show that as the private banking division becomes more developed, the optimal revenue-sharing ratio decreases, and the private banking division’s optimal effort to serve transferred customers decreases because it puts more effort into acquiring new customers. Under the IDM, the two divisions form a competitive relationship since they compete to acquire customers independently. We investigate customer acquisition efforts in this interdivisional competition. Optimal customer acquisition efforts by both divisions increase in potential assets and rates of return. This paper contributes to the literature by (1) analyzing financial innovation by private banks from an organizational perspective; (2) providing an economic analysis for private banking development in China.
A novel tuberculosis model incorporating a Caputo fractional derivative and treatment effect via the homotopy perturbation method
Authors: Olayiwola Morufu Oyedunsi , Adedokun Kamilu Adewale
Published: August 2023

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a contagious infectious disease that primarily targets the lungs but can also impact other critical systems such as the bones, joints, and neurological system. Despite significant efforts to combat TB, it remains a major global health concern. To address this challenge, this study aims to explore and evaluate various tuberculosis control approaches using a mathematical modeling framework.

Results

The study utilized a novel SEITR mathematical model to investigate the impact of treatment on physical limitations in tuberculosis. The model underwent qualitative analysis to validate key aspects, including positivity, existence, uniqueness, and boundedness. Disease-free and endemic equilibria were identified, and both local and global stability of the model was thoroughly examined using the derived reproduction number. To estimate the impact of each parameter on each compartment, sensitivity analysis was conducted, and numerical simulations were performed using Maple 18 software with the homotopy perturbation method. The obtained results are promising and highlight the potential of the proposed interventions to significantly reduce tuberculosis virus prevalence. The findings emphasize the significance of fractional-order analysis in understanding the effectiveness of treatment strategies for mitigating tuberculosis prevalence. The study suggests that the time fractional dynamics of TB treatment correspond to the treatment’s efficacy, as the conceptual results showed that non-local interactions between the disease and the treatment may lead to more accurate ways of eradicating tuberculosis in real-world scenarios. These insights contribute to a better understanding of effective treatment strategies and their potential impact on tuberculosis control and public health.

Conclusions

In conclusion, scientists, researchers, and healthcare personnel are urged to take action and utilize the discoveries from this research to facilitate the eradication of the hazardous tuberculosis bacteria.
Role of MRI in diagnosis of pulmonary embolism
Authors: Mohammad Abolhasan Haseib , Mostafa Hossam Mohammed , Megaly Hasan Ibarhim , Mohamed Mohamed Zidan , Taha Mohamad Gaber , Abdelal Sherif M.
Published: August 2023

Background

Pulmonary embolism (PE) is considered a serious condition and has clinical challenges in diagnosis. Computed tomography pulmonary angiography (CTPA) is considered the gold standard in PE diagnosis. Contrast-enhanced MRA also has a strong useful role in the diagnosis. Our study aims to assess the role of non-contrast MRA in diagnosis of acute pulmonary embolism compared to either CT pulmonary angiography or contrast enhanced MRA.

Results

In total, 50 patients with PE confirmed by either CTPA or CE-MRA were included in this study. All patients underwent non-contrast MRPA during the three consecutive days after CTPA or at the same examination setting in CE-MRA. The results were compared and statistically analyzed.

The mean age of our study group was 47.80 ± 14.01 years. Males represented 56% (28/50) and females 44% (22/50). The per-vessel sensitivity, specificity and accuracy of non-contrast MRPA reached about 100% for each parameter at the level of the pulmonary trunk, main pulmonary and lobar arteries. At the segmental level, sensitivity, specificity, and accuracy reached about 88%, 100%, and 94%, while at the subsegmental level, about 35%, 100%, and 66% respectively. The overall sensitivity, specificity, and accuracy of non-contrast MRPA regardless of the site were 84%, 100%, and 90% respectively.

Conclusions

Non-contrast pulmonary MRA has a high sensitivity and specificity in the diagnosis of PE, especially in proximal pulmonary arteries. So, it can be used as an alternative to the CTA and CE-MRA, especially when the CTA and the use of gadolinium are contraindicated.
Utility of Polygenic Scores for Differentiating Diabetes Diagnosis Among Patients With Atypical Phenotypes of Diabetes
Authors: Billings Liana K , Shi Zhuqing , Wei Jun , Rifkin Andrew S , Zheng S Lilly , Helfand Brian T , Ilbawi Nadim , Dunnenberger Henry M , Hulick Peter J , Qamar Arman , Xu Jianfeng
Published: August 2023

Context

Misclassification of diabetes type occurs in people with atypical presentations of type 1 diabetes (T1D) or type 2 diabetes (T2D). Although current clinical guidelines suggest clinical variables and treatment response as ways to help differentiate diabetes type, they remain insufficient for people with atypical presentations.

Objective

This work aimed to assess the clinical utility of 2 polygenic scores (PGSs) in differentiating between T1D and T2D.

Methods

Patients diagnosed with diabetes in the UK Biobank were studied (N = 41 787), including 464 (1%) and 15 923 (38%) who met the criteria for classic T1D and T2D, respectively, and 25 400 (61%) atypical diabetes. The validity of 2 published PGSs for T1D (PGST1D) and T2D (PGST2D) in differentiating classic T1D or T2D was assessed using C statistic. The utility of genetic probability for T1D based on PGSs (GenProb-T1D) was evaluated in atypical diabetes patients.

Results

The joint performance of PGST1D and PGST2D for differentiating classic T1D or T2D was outstanding (C statistic = 0.91), significantly higher than that of PGST1D alone (0.88) and PGST2D alone (0.70), both P less than .001. Using an optimal cutoff of GenProb-T1D, 23% of patients with atypical diabetes had a higher probability of T1D and its validity was independently supported by clinical presentations that are characteristic of T1D.

Conclusion

PGST1D and PGST2D can be used to discriminate classic T1D and T2D and have potential clinical utility for differentiating these 2 types of diseases among patients with atypical diabetes.
Insulin Signaling Is Preserved in Skeletal Muscle During Early Diabetic Ketoacidosis
Authors: Fisker Frederikke A , Voss Thomas S , Svart Mads V , Kampmann Ulla , Vendelbo Mikkel H , Bengtsen Mads B , Lauritzen Esben S , Møller Niels , Jessen Niels
Published: August 2023

Background and aims

During diabetic ketoacidosis (DKA), muscle tissue develops a profound insulin resistance that complicates reversal of this potentially lethal condition. We have investigated mediators of insulin action in human skeletal muscle during total insulin withdrawal in patients with type 1 diabetes, under the hypothesis that initial phases of DKA are associated with impaired postreceptor signaling.

Materials and methods

Muscle biopsies were obtained during a randomized, controlled, crossover trial involving 9 patients with type 1 diabetes. The subjects were investigated during a high-dose insulin clamp preceded by either: (1) insulin-controlled euglycemia (control) or (2) total insulin withdrawal for 14 hours. Insulin action in skeletal muscle and whole-body substrate metabolism were investigated using western blot analysis and indirect calorimetry respectively.

Results

During insulin withdrawal, insulin-stimulated dephosphorylation of glycogen synthase decreased by ∼30% (P < .05) compared with the control situation. This was associated with a decrease in glucose oxidation by ∼30% (P < .05). Despite alterations in glucose metabolism, insulin transduction to glucose transport and protein synthesis (Akt, AS160, mammalian target of rapamycin, and eukaryotic translation initiation factor 4E binding protein) was intact, and glucose transporter (GLUT4) and mitochondrial proteins (succinate dehydrogenase complex, subunit A and prohibitin 1) protein expression were unaffected by the intervention.

Conclusion

DKA impairs insulin-stimulated activation of glycogen synthase, whereas insulin signal transduction to glucose transport and protein synthesis remains intact. Reversal of insulin resistance during treatment of DKA should target postreceptor mediators of glucose uptake.

Clinical Trial Registration number

NCT02077348.
Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis
Authors: Melin Johanna , Forslund Maria , Alesi Simon , Piltonen Terhi , Romualdi Daniela , Spritzer Poli Mara , Tay Chau Thien , Pena Alexia , Witchel Selma Feldman , Mousa Aya , Teede Helena
Published: August 2023

Context

Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.

Objective

As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated.

Data Sources

Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched.

Study Selection

Women with PCOS included in randomized controlled trials (RCTs).

Data Extraction

We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.

Data Synthesis

The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (−118.61 nmol/L; 95% CI −174.46, −62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (−16.61 nmol/L; 95% CI −28.51, −4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (−27.12 pmol/L; 95% CI −40.65, −13.59) and triglycerides (−0.15 mmol/L; 95% CI −0.29, −0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment.

Conclusions

The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).
A HUMAN IN SPACE OF MATERIAL CULTURE
Authors: Mihailova Nadezhda V.
Published: August 2023

Purpose. The article is devoted to analysis of material culture as space of human existence. The subject of the analysis is a system of human relations with space of material culture. The author aims to reveal essence of a man as a biosocial being through analysis of a structure of material culture and its place in a cultural system as a whole.

Methodology. The research is based on a principle of system analysis, culturological and cultural anthropological approaches, as well as on typologization and analysis of written sources methods.

Results. The results of the work are that the author considers material culture as consisting of a number of groups of elements, both external to a human (things, technics, technologies), and a human oneself through one`s physicality and body technologies (physical culture). A position of these elements in a coordinate system “universal – regional (general) – specific” is analysed.

Practical implications. Results of the study can be applied in fields of human socialization and enculturation, analysis of cross-cultural interactions.
THE THEME OF THE HEART IN THE BYZANTINE TRADITION, RUSSIAN ORTHODOX CULTURE AND RUSSIAN PHILOSOPHY
Authors: Makarov Ivan V.
Published: August 2023

The article is devoted to the problem of cardiognosia as the leading one for Russian theological-philosophical and secular religious thought. A special place in Russian (especially in religious) philosophy is occupied by the theme of love and the heart. The main question that we pose in this article is whether the domestic cardiognosy has remained in line with purely Byzantine religious philosophy, or whether our tradition has found an original approach to the study of the heart. This problem is quite relevant due to the fact that modern Russia has often been compared with the Byzantine Empire, such comparative studies have been found for the third decade in various historical, cultural and philosophical studies. The study of the topic of the heart also falls into the piggy bank of spiritual and moral values, to the preservation of which the strategic interests of modern Russian society are addressed.

Russian Orthodox culture reveals the theme of the heart in the ascetic tradition of asceticism, and Russian religious philosophy calls the heart the key to understanding the mentality of the Russian person. Modern researchers focus on the integrative function of the heart. Russian Russian Orthodox culture acts as a bridge between Byzantine traditions and Russian philosophy, and modern Russian philosophy considers the heart to be a place of synthesis of science and art culture.

The results of the article can be applied in the framework of the creation of the concept of spiritual and moral development and education of the personality of a citizen of Russia.