bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial
Authors: Zelicha Hila , Kloting Nora , Kaplan Alon , Yaskolka Meir Anat , Rinott Ehud , Tsaban Gal , Chassidim Yoash , Bluher Matthias , Ceglarek Uta , Isermann Berend , Stumvoll Michael , Quayson Rita Nana , von Bergen Martin , Engelmann Beatrice , Rolle-Kampczyk Ulrike E. , Haange Sven-Bastiaan , Tuohy Kieran M. , Diotallevi Camilla , Shelef Ilan , Hu Frank B. , Stampfer Meir J. , Shai Iris
Published: September 2022

Background

Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT).

Methods

In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) andWolffia globosa(duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues.

Results

Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%;p< 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, andWolffia globosa; lower red meat intake; higher total plasma polyphenols (mainlyhippuric acid), and elevated urineurolithin Apolyphenol were significantly related to greater VAT loss (p< 0.05, multivariate models).

Conclusions

A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.

Trial registration

ClinicalTrials.gov, NCT03020186
Risk factors and a nomogram model for postoperative delirium in elderly gastric cancer patients after laparoscopic gastrectomy
Authors: Chen Jie , Ji Xiaoli , Xing Hailin
Published: September 2022

Background

To evaluate the risk factors of postoperative delirium (POD) in elderly gastric cancer (GC) patients after laparoscopic gastrectomy and construct a predictive model.

Methods

Elderly GC patients undergoing laparoscopic gastrectomy were enrolled and grouped based on the status of POD development within postoperative 7 days. Independent risk factors were selected out by univariate and multivariate logistic regression analyses and then enrolled in the nomogram prediction model.

Results

A total of 270 elderly GC patients were enrolled, and POD occurred in 74 (27.4%) patients within postoperative 7 days. The results of multivariate regression analysis indicated that age (OR: 3.30, 95% CI: 1.41–6.85, P < 0.001), sleeping pills (OR: 1.87, 95% CI: 1.12–3.09, P = 0.012), duration of ICU stay (OR: 1.55, 95% CI: 1.02–2.37, P = 0.029), albumin/fibrinogen ratio (AFR) (OR: 1.74, 95% CI: 1.03–2.76, P = 0.019), and neutrophils/lymphocytes ratio (NLR) (OR: 2.12, 95% CI: 1.11–4.01, P = 0.016) were five independent risk factors for POD in elderly GC patients. The AUC of the constructed nomogram model based on these five factors was 0.807.

Conclusions

This study highlighted that age, AFR, NLR, sleeping pills taking, and duration of ICU stay were independent risk factors for POD, and the nomogram model based on these factors could effectively predict POD in elderly GC patients.
Assessing the causal association between human blood metabolites and the risk of epilepsy
Authors: Cai Jiahao , Li Xiaoyu , Wu Shangbin , Tian Yang , Zhang Yani , Wei Zixin , Jin Zixiang , Li Xiaojing , Chen Xiong , Chen Wen-Xiong
Published: September 2022

Background

Metabolic disturbance has been reported in patients with epilepsy. Still, the evidence about the causal role of metabolites in facilitating or preventing epilepsy is lacking. Systematically investigating the causality between blood metabolites and epilepsy would help provide novel targets for epilepsy screening and prevention.

Methods

We conducted two-sample Mendelian randomization (MR) analysis. Data for 486 human blood metabolites came from a genome-wide association study (GWAS) comprising 7824 participants. GWAS data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium for primary analysis and the FinnGen consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.

Results

482 out of 486 metabolites were included for MR analysis following rigorous genetic variants selection. After IVW and sensitivity analysis filtration, six metabolites with causal effects on epilepsy were identified from the ILAE consortium. Only four metabolites remained significant associations with epilepsy when combined with the FinnGen consortium [uridine: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.48–3.71, P = 0.0003; 2-hydroxystearate: OR = 1.61, 95% CI = 1.19–2.18, P = 0.002; decanoylcarnitine: OR = 0.82, 95% CI = 0.72–0.94, P = 0.004; myo-inositol: OR = 0.77, 95% CI = 0.62–0.96, P = 0.02].

Conclusion

The evidence that the four metabolites mentioned above are associated with epilepsy in a causal way provides a novel insight into the underlying mechanisms of epilepsy by integrating genomics with metabolism, and has an implication for epilepsy screening and prevention.
A genetic map of the chromatin regulators to drug response in cancer cells
Authors: Chen Bo , Li Pengfei , Liu Mingyue , Liu Kaidong , Zou Min , Geng Yiding , Zhuang Shuping , Xu Huanhuan , Wang Linzhu , Chen Tingting , Li Yawei , Zhao Zhangxiang , Qi Lishuang , Gu Yunyan
Published: September 2022

Background

Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging.

Methods

In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets.

Results

Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment.

Conclusions

The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy.
Determinants of mother to child HIV transmission (HIV MTCT); a case control study in governmental health centers of East Gojjam Zone, Northwest Ethiopia, 2019
Authors: Tariku Mengistie Kassahun
Published: September 2022

Background

Mother to child human immune virus (HIV) transmission is the passage of HIV from mother to her child during pregnancy, labor, delivery or breast-feeding. The objective of this study was to identify determinants of mother to child HIV transmission among HIV exposed infants who were born from HIV positive mothers at Governmental health centers of East Gojjam Zone, Northwestern Ethiopia, 2019.

Methods

A case–control study was conducted on 210(42 cases and 168 controls) from April 1 to 30/ 2019. All cases were included in the study. Controls were selected by simple random sampling. Secondary data were extracted by using checklists from the document of 8 health centers ART register book, antenatal care (ANC) follow up register book, PMTCT service registration log book charts and infant dried blood sample (DBS) tally sheets. After Bivariable logistic regression analysis, all variables with p-value $$\le$$
≤
0.25 were entered into multivariable logistic regression and p value < 0.05 considered as significantly associated with the outcome variable.

Results

HIV exposed infants who were being rural dweller versus (vs) those infants who were being urban dweller [adjusted odds ratio (AOR) = 3.73; 95% CI; 1.27–10.69], have no history of antenatal care follow up of HIV exposed infants’ HIV positive mothers versus (vs) those mothers who have been having history of ANC follow up [ AOR = 5.0;95%CI; 2.02–12.16] and initial CD4 count of HIV infants’ mothers $$\le 350$$

≤
350

vs those mothers whose CD4 > 350 [AOR = 2.7;95%CI;1.35–5.52] were significantly associated with HIV infection.

Conclusion

Mother to child HIV transmission was significantly associated with history of ANC follow up of exposed infants’ mothers and initial CD4 counts of mothers. Strong effort should be made to further increase the ANC service utilization of HIV positive pregnant women.
Cardiovascular disease, self-care and emotional regulation processes in adult patients: balancing unmet needs and quality of life
Authors: Cilli Eleonora , Ranieri Jessica , Guerra Federica , Ferri Claudio , Di Giacomo Dina
Published: September 2022

Background

Cardiovascular disease is a chronic non-communicable illness that causes more than half of all deaths across Europe. Unhealthy lifestyle, inadequate adherence to medical prescriptions, themselves associated with psycho-emotional disorders are considered risk factors for reduced quality of life as well physical condition.

Objective

Aim of our study was to understand predictive factors for disease management by evaluating psychological aspects, self-care processes and emotional regilati0on in CVD outpatients.

Methods

An observational study was conducted. Sixty-one patients, age 18–75 years (M 56.4 ± sd 12.0), diagnosed with CVD participated in the study. The psychological battery was administered during clinical follow-up oriented to detect emotional and psychological dimensions as well adaptive behavioral and quality of life by standardized questionnaire/scales.

Results

Finding showed that emotional dysregulation might influence QoL, particularly significant effect of awareness (β= 0.022; SE = 1.826; p < 0.002), goals (β = - 0.54; SE = 1.48; p < 0.001) and clarity (β = - 0.211; SE = 2.087; p < 0.003). The results also suggest that the mediated effect accounted for awareness index was 18.7% (R2 = 0.187) of the variance; goals index 62.8% (R2 = 0.628) of the variance and, then significant mediated effect of clarity was 58.8% (R2 = 0.588) of the variance. This evidence suggests that the relationship between triggers and QoL is mediated by emotional dysregulation indexes.

Conclusion

In clinical practice psychological screening can be an effective tool for detecting predictive factors in the management of the CVD patient's health and adherence to medical treatment: the screening of predictive psychological factors for allowing a good clinical condition management and a self-care empowerment aimed at increasing psychological well-being and the Quality of Life by planning adequate integrated and multidisciplinary support.
SOULMATE: the Swedish study of liver transplantation for isolated colorectal cancer liver metastases not suitable for operation or ablation, compared to best established treatment—a randomized controlled multicenter trial
Authors: Reivell Veronica , Hagman Helga , Haux Johan , Jorns Carl , Lindnér Per , Taflin Helena
Published: September 2022

Background

Around one fourth of patients with colorectal cancer present themselves with distant metastases at the time of diagnosis, and one additional one fifth of the patients will develop distant metastases during the disease, most commonly in the liver.

Surgical treatment such as liver resection or ablation, often combined with chemotherapy and targeted therapy, is the only treatment option with curative potential, but only about 20% of the patients with liver metastases are candidates for surgical intervention. Standard treatment for unresectable patients is palliative oncological therapy; however, less than 10% of these patients will achieve a 5-year survival.

Non-randomized studies indicate that liver transplantation could be an option for selected patients with colorectal liver metastases (CRLM), which are not suitable for operation or ablation due to surgical technical reasons such as massive tumor burden and small future liver remnant, or oncological reasons, for example, early relapse after liver surgery. Since there is a shortage of donated liver grafts, it is important to select the patient group that benefit most from the treatment. Although some studies present positive results from liver transplantation of CRLM, the results must be validated in a randomized controlled trial before this new indication for liver transplantation can be introduced as a clinical routine.

Methods

The SOULMATE study is a randomized study evaluating if liver transplantation with liver grafts, primarily from extended criteria donors, increases overall survival in patients with CRLM, not suitable for resection or ablation, in comparison with best established treatment.

Patients will be randomized to liver transplantation (LT)+ best established treatment (BET) or to best established treatment only.

In the SOULMATE trial, we will evaluate the use of livers from extended criteria donors to decrease the risk of prolonging waiting time for patients on the waiting list for LT.

Discussion

The SOULMATE study has the possibility to confirm the positive results of previous studies in a randomized setting. The use of extended criteria donors will make the results transferable globally, as most countries are struggling with organ shortage.

Trial registration

Clinical Trial number: NCT04161092 registered 13 November 2019.
Construction and yield optimization of a cinnamylamine biosynthesis route in Escherichia coli
Authors: Wang Qi , Ma Linlin , Wang Zhiguo , Chen Quan , Wang Qian , Qi Qingsheng
Published: September 2022

Background

With the development of metabolic engineering and synthetic biology, the biosynthesis of aromatic compounds has attracted much attention. Cinnamylamine is an aromatic compound derived from l-phenylalanine, which is used in the synthesis of biologically active molecules, including drugs, and energetic materials. Cinnamylamine has been mainly synthesized by chemical methods to date, and few reports have focused on the biosynthesis of cinnamylamine. Therefore, it is desirable to establish an efficient biosynthesis method for cinnamylamine.

Results

The ω-aminotransferase Cv-ωTA from Chromobacterium violaceum has been demonstrated to have high enzyme activity in the conversion of cinnamaldehyde to cinnamylamine. To prevent the preferable conversion of cinnamaldehyde to cinnamyl alcohol in wild-type Escherichia coli, the E. coli MG1655 strain with reduced aromatic aldehyde reduction (RARE) in which six aldehyde ketone reductase and alcohol dehydrogenase genes have been knocked out was employed. Then, the carboxylic acid reductase from Neurospora crassa (NcCAR) and phosphopantetheinyl transferase (PPTase) from E. coli were screened for a high conversion rate of cinnamic acid to cinnamaldehyde. To shift the equilibrium of the reaction toward cinnamylamine, saturation mutagenesis of Cv-ωTA at key amino acid residues was performed, and Cv-ωTA Y168G had the highest conversion rate with 88.56 mg/L cinnamylamine obtained after 4 h of fermentation. Finally, by optimizing the substrates and the supply of the cofactors, PLP and NADPH, in the fermentation, the yield of cinnamylamine in engineered E. coli reached 523.15 mg/L.

Conclusion

We achieved the first biosynthesis of cinnamylamine using cinnamic acid as the precursor in E. coli using a combinatorial metabolic engineering strategy. This study provides a reference for the biosynthesis of other amine compounds and lays a foundation for the de novo synthesis of cinnamylamine.
Medullary sponge kidney: unusual finding in kidney transplant recipient
Authors: Righini M. , Felicani C. , Lopez A. , Mazzotta E. , De Molo C. , Mancini E. , Capelli I. , Serra C. , La Manna G.
Published: September 2022

Background

Medullary sponge kidney is generally considered a benign condition, gold standard for the diagnosis is urography but it has almost been replaced by UroCT that did not present the same sensibility. Although it is really rare, our sonography’s findings were consistent with medullary sponge kidney in the transplanted kidneys.

Case presentation

A 45-year-old woman with a long history of double-kidney transplantation complained of frequent urinary tract infections, a history of vague loin pain and came to our attention for sonography follow-up. Her kidney function was normal, we did not find signs of infections in the transplanted kidneys and urinary findings were normal. Curiously, the transplanted kidneys came from a newborn and the patient received a double-kidney transplantation in order to guarantee a satisfactory renal function.

Conclusions

Despite a long history of kidney transplantation, genetic disease should not be forgotten when symptoms and images recall to specific inherited alterations. Sonography has to be considered in diagnostic path of kidney cystic disease.
A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events
Authors: Cappozzo Andrea , McCrory Cathal , Robinson Oliver , Freni Sterrantino Anna , Sacerdote Carlotta , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Iacoviello Licia , Ricceri Fulvio , Sieri Sabina , Chiodini Paolo , McKay Gareth J. , McKnight Amy Jayne , Kee Frank , Young Ian S. , McGuinness Bernadette , Crimmins Eileen M. , Arpawong Thalida Em , Kenny Rose Anne , O’Halloran Aisling , Polidoro Silvia , Solinas Giuliana , Vineis Paolo , Ieva Francesca , Fiorito Giovanni
Published: September 2022

Background

Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.

Results

Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived aDNAmCVDscorepredictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show thatDNAmCVDscoreoutperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge andDNAmCVDscorewas comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).

Conclusions

We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker,DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.
miR-146a-5p-modified hUCMSC-derived exosomes facilitate spinal cord function recovery by targeting neurotoxic astrocytes
Authors: Lai Xunwei , Wang Yang , wang Xiaokang , Liu Bin , Rong Limin
Published: September 2022

Background

Acute spinal cord injury (SCI) is a devastating result of neurological trauma with subsequent microenvironment dyshomeostasis that induces neurotoxic phenotype acquisition by astrocytes, exacerbating neurological function impairment. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have demonstrated essential therapeutic effects after central nervous system trauma. However, whether hUCMSC-derived exosomes exert therapeutic effects on neurotoxic astrocytes to facilitate SCI function recovery remains unclear. Additionally, the limited efficiency of single exosomes may restrict the optimization of exosomal biological functions.

Methods

We first determined that exosomes reduce the deleterious effects of neurotoxic astrocytes in vitro and in vivo. Then, we identified critical functional microRNAs (miRNAs). miR-146a-5p was overexpressed in exosomes, and then, miR-146a-5p-modified exosomes were used to investigate the ability of exosomes to reduce neurotoxic astrocyte effects, preserve neurons and promote neurological function recovery in rats with SCI.

Results

Cell counting kit-8 and neurite length analyses revealed that exosomes partially reduced the negative effects of neurotoxic astrocytes on PC12 cell viability and neurites in vitro. The exosomes also attenuated inflammatory responses, reduced the number of neurotoxic astrocytes and preserved neural tissue in rats with SCI. Immunofluorescence assays suggested that the number of neurotoxic astrocytes was rapidly increased by injury, reaching a peak 5 days post-injury (dpi) and returning to the normal level 14dpi. Exosomal miR-146a-5p was identified as the critical functional miRNA. Overexpression of miR-146a-5p in exosomes strengthened the biological function of the exosomes. Therefore, the modified exosomes exerted more powerful therapeutic effects than the unmodified exosomes, reducing the deleterious effects of neurotoxic astrocytes both in vitro and in vivo and promoting locomotor function of the hindlimbs in the rats with SCI. Through a series of gain- and loss-of-function experiments, Traf6 and Irak1 were identified as targets of exosomal miR-146a-5p. Ultimately, we found that miR-146a-5p-modified exosomes exerted their function by targeting Traf6/Irak1/NFκB pathway in neurotoxic astrocytes.

Conclusions

In summary, miR-146a-5p-modified exosomes exerted a more powerful effect than unmodified exosomes to promote neurological function recovery in rats with SCI by targeting neurotoxic astrocytes. Therefore, miR-146a-5p-modified exosomes are promising therapeutics for SCI.
Gestational hypoxia in late pregnancy differentially programs subcortical brain maturation in male and female rat offspring
Authors: Wilson E. Nicole , Mabry Steve , Bradshaw Jessica L. , Gardner Jennifer J. , Rybalchenko Nataliya , Engelland Rachel , Fadeyibi Oluwadarasimi , Osikoya Oluwatobiloba , Cushen Spencer C. , Goulopoulou Styliani , Cunningham Rebecca L.
Published: September 2022

Background

Hypoxia is associated with pregnancy complications, such as preeclampsia, placental abruption, and gestational sleep apnea. Hypoxic insults during gestation can impact the brain maturation of cortical and subcortical pathways, such as the nigrostriatal pathway. However, the long-term effects of in utero hypoxic stress exposure on brain maturation in offspring are unclear, especially exposure during late gestation. The purpose of this study was to determine the impact of gestational hypoxia in late pregnancy on developmental programming of subcortical brain maturation by focusing on the nigrostriatal pathway.

Methods

Timed pregnant Long–Evans rats were exposed to chronic intermittent hypoxia or room air normoxia from gestational day (GD) 15–19 (term 22–23 days). Male and female offspring were assessed during two critical periods: puberty from postnatal day (PND) 40–45 or young adulthood (PND 60–65). Brain maturation was quantified by examining (1) the structural development of the nigrostriatal pathway via analysis of locomotor behaviors and the substantia nigra dopaminergic neuronal cell bodies and (2) the refinement of the nigrostriatal pathway by quantifying ultrasonic vocalizations (USVs).

Results

The major findings of this study are gestational hypoxia has age- and sex-dependent effects on subcortical brain maturation in offspring by adversely impacting the refinement of the nigrostriatal pathway in the absence of any effects on the structural development of the pathway. During puberty, female offspring were impacted more than male offspring, as evidenced by decreased USV call frequency, chirp USV call duration, and simple call frequency. In contrast, male offspring were impacted more than female offspring during young adulthood, as evidenced by increased latency to first USV, decreased simple USV call intensity, and increased harmonic USV call bandwidth. No effects of gestational hypoxia on the structural development of the nigrostriatal pathway were observed.

Conclusions

These novel findings demonstrate hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Impairment of cortical and subcortical pathways maturation, such as the nigrostriatal pathway, may increase risk for neuropsychiatric disorders (e.g., mood disorders, cognitive dysfunction, brain connectivity dysfunction).
Megaconial congenital muscular dystrophy due to novel CHKB variants: a case report and literature review
Authors: Magri Francesca , Antognozzi Sara , Ripolone Michela , Zanotti Simona , Napoli Laura , Ciscato Patrizia , Velardo Daniele , Scuvera Giulietta , Nicotra Valeria , Giacobbe Antonella , Milani Donatella , Fortunato Francesco , Garbellini Manuela , Sciacco Monica , Corti Stefania , Comi Giacomo Pietro , Ronchi Dario
Published: September 2022

Background

Choline kinase beta (CHKB) catalyzes the first step in the de novo biosynthesis of phosphatidyl choline and phosphatidylethanolamine via the Kennedy pathway. Derangement of this pathway might also influence the homeostasis of mitochondrial membranes.

Autosomal recessive CHKB mutations cause a rare form of congenital muscular dystrophy known as megaconial congenital muscular dystrophy (MCMD).

Case presentation

We describe a novel proband presenting MCMD due to unpublished CHKB mutations. The patient is a 6-year-old boy who came to our attention for cognitive impairment and slowly progressive muscular weakness. He was the first son of non-consanguineous healthy parents from Sri Lanka. Neurological examination showed proximal weakness at four limbs, weak osteotendinous reflexes, Gowers’ maneuver, and waddling gate. Creatine kinase levels were mildly increased. EMG and brain MRI were normal. Left quadriceps skeletal muscle biopsy showed a myopathic pattern with nuclear centralizations and connective tissue increase. Histological and histochemical staining suggested subsarcolemmal localization and dimensional increase of mitochondria. Ultrastructural analysis confirmed the presence of enlarged (“megaconial”) mitochondria. Direct sequencing of CHKB identified two novel defects: the c.1060G > C (p.Gly354Arg) substitution and the c.448-56_29del intronic deletion, segregating from father and mother, respectively. Subcloning of RT-PCR amplicons from patient’s muscle RNA showed that c.448-56_29del results in the partial retention (14 nucleotides) of intron 3, altering physiological splicing and transcript stability. Biochemical studies showed reduced levels of the mitochondrial fission factor DRP1 and the severe impairment of mitochondrial respiratory chain activity in patient’s muscle compared to controls.

Conclusions

This report expands the molecular findings associated with MCMD and confirms the importance of considering CHKB variants in the differential diagnosis of patients presenting with muscular dystrophy and mental retardation. The clinical outcome of MCMD patients seems to be influenced by CHKB molecular defects. Histological and ultrastructural examination of muscle biopsy directed molecular studies and allowed the identification and characterization of an intronic mutation, usually escaping standard molecular testing.
First-in-human use of 11C-CPPC with positron emission tomography for imaging the macrophage colony-stimulating factor 1 receptor
Authors: Coughlin Jennifer M. , Du Yong , Lesniak Wojciech G. , Harrington Courtney K. , Brosnan Mary Katherine , O’Toole Riley , Zandi Adeline , Sweeney Shannon Eileen , Abdallah Rehab , Wu Yunkou , Holt Daniel P. , Hall Andrew W. , Dannals Robert F. , Solnes Lilja , Horti Andrew G. , Pomper Martin G.
Published: September 2022

Purpose

Study of the contribution of microglia to onset and course of several neuropsychiatric conditions is challenged by the fact that these resident immune cells often take on different phenotypes and functions outside the living brain. Imaging microglia with radiotracers developed for use with positron emission tomography (PET) allows researchers to study these cells in their native tissue microenvironment. However, many relevant microglial imaging targets such as the 18 kDa translocator protein are also expressed on non-microglial cells, which can complicate the interpretation of PET findings. 11C-CPPC was developed to image the macrophage colony-stimulating factor 1 receptor, a target that is expressed largely by microglia relative to other cell types in the brain. Our prior work with 11C-CPPC demonstrated its high, specific uptake in brains of rodents and nonhuman primates with neuroinflammation, which supports the current first-in-human evaluation of its pharmacokinetic behavior in the brains of healthy individuals.

Methods

Eight healthy nonsmoker adults completed a 90-min dynamic PET scan that began with bolus injection of 11C-CPPC. Arterial blood sampling was collected in order to generate a metabolite-corrected arterial input function. Tissue time-activity curves (TACs) were generated using regions of interest identified from co-registered magnetic resonance imaging data. One- and two-tissue compartmental models (1TCM and 2TCM) as well as Logan graphical analysis were compared.

Results

Cortical and subcortical tissue TACs peaked by 37.5 min post-injection of 11C-CPPC and then declined. The 1TCM was preferred. Total distribution volume (VT) values computed from 1TCM aligned well with those from Logan graphical analysis (t* = 30), with VT values relatively high in thalamus, striatum, and most cortical regions, and with relatively lower VT in hippocampus, total white matter, and cerebellar cortex.

Conclusion

Our results extend support for the use of 11C-CPPC with PET to study microglia in the human brain.
Development and validation of 68Ga-PSMA-11 PET/CT-based radiomics model to detect primary prostate cancer
Authors: Zang Shiming , Ai Shuyue , Yang Rui , Zhang Pengjun , Wu Wenyu , Zhao Zhenyu , Ni Yudan , Zhang Qing , Sun Hongbin , Guo Hongqian , Jia Ruipeng , Wang Feng
Published: September 2022

Background

This study aimed to develop a novel analytic approach based on a radiomics model derived from 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT for predicting intraprostatic lesions in patients with prostate cancer (PCa).

Methods

This retrospective study included consecutive patients with or without PCa who underwent surgery or biopsy after 68Ga-PSMA-11 PET/CT. A total of 944 radiomics features were extracted from the images. A radiomics model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm with tenfold cross-validation in the training set. PET/CT images for the test set were reviewed by experienced nuclear medicine radiologists. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for the model and radiologists’ results. The AUCs were compared.

Results

The total of 125 patients (86 PCa, 39 benign prostate disease [BPD]) included 87 (61 PCa, 26 BPD) in the training set and 38 (61 PCa, 26 BPD) in the test set. Nine features were selected to construct the radiomics model. The model score differed between PCa and BPD in the training and test sets (both P < 0.001). In the test set, the radiomics model performed better than the radiologists’ assessment (AUC, 0.85 [95% confidence interval 0.73, 0.97] vs. 0.63 [0.47, 0.79]; P = 0.036) and showed higher sensitivity (model vs radiologists, 0.84 [0.63, 0.95] vs. 0.74 [0.53, 0.88]; P = 0.002).

Conclusion

Radiomics analysis based on 68Ga-PSMA-11 PET may non-invasively predict intraprostatic lesions in patients with PCa.
Ethnic differences between South Asians and White Caucasians in cardiovascular disease-related mortality in developed countries: a systematic literature review
Authors: Patel Mubarak , Abatcha Salim , Uthman Olalekan
Published: September 2022

Background

Cardiovascular disease is the leading cause of death worldwide, with significantly worse mortality-related outcomes in ethnic minorities in developed countries. A systematic literature review and meta-analysis of observational studies was conducted to investigate cardiovascular disease-related mortality inequalities between South Asian and White Caucasian ethnic groups.

Methods

Published studies on mortality between South Asians and Whites in developed countries were retrieved from MEDLINE, PubMed, Embase, Web of Science, and grey literature sources (inception—April 2021) and critically appraised using the Quality in Prognosis Studies tool. Bayesian random-effects meta-analyses were performed for both primary and secondary outcomes. Heterogeneity was determined using theI2statistic.

Results

Of the 9879 studies screened originally, 41 were deemed eligible. A further 3 studies were included via the later search. Of these, 15 reported cardiovascular disease-related mortality, 23 reported all-cause mortality, and 6 reported both.

The meta-analysis results showed that South Asians had a significantly increased risk of cardiovascular disease mortality compared to Whites (risk ratio = 1.32; 95% credible interval = 1.14 to 1.54) and a decreased risk of all-cause mortality (risk ratio = 0.95; 95% credible interval = 0.83 to 1.12).

Discussion

South Asians had statistically significantly higher odds of cardiovascular disease-related mortality compared to Whites, but not for all-cause mortality. Risk of bias was a serious concern mainly due to a lack of confounders being reported.

Systematic review registration

PROSPERO: CRD42021240865
Cloud based evaluation of databases for stock market data
Authors: Singh Baldeep , Martyr Randall , Medland Thomas , Astin Jamie , Hunter Gordon , Nebel Jean-Christophe
Published: September 2022

About fifty years ago, the world’s first fully automated system for trading securities was introduced by Instinet in the US. Since then the world of trading has been revolutionised by the introduction of electronic markets and automatic order execution. Nowadays, financial institutions exploit the associated flow of daily data using more and more advanced analytics to gain valuable insight on the markets and inform their investment decisions. In particular, time series of Open High Low Close prices and Volume data are of special interest as they allow identifying trading patterns useful for forecasting both stock prices and volumes. Traditionally, relational databases have been used to store this data; however, the ever-growing volume of this data, the adoption of the hybrid cloud model, and the availability of novel non-relational databases which claim to be more scalable and fault tolerant raise the question whether relational databases are still the most appropriate. In this study, we define a set of criteria to evaluate performance of a variety of databases on a hybrid cloud environment. There, we conduct experiments using standard and custom workloads. Results show that migration to a MongoDB database would be most beneficial in terms of cost, storage space, and throughput. In addition, organisations wishing to take advantage of autoscaling and the maintenance power of the cloud should opt for a cloud native solution.
Long-term skeletal and dentoalveolar effects of hybrid rapid maxillary expansion and facemask treatment in growing skeletal Class III patients: a retrospective follow-up study
Authors: Maino Giuliano B. , Cremonini Francesca , Maino Giovanna , Paoletto Emanuele , De Maio Matteo , Spedicato Giorgio Alfredo , Palone Mario , Lombardo Luca
Published: September 2022

Background

Regardless of the treatment protocol, stability in Class III patients always represents a major concern. The aim of this study was to assess the short and long-term skeletal and dentoalveolar modifications in a group of class III patients treated with hybrid rapid maxillary expander (RME) and facemask (FM). Indeed, no long-term studies have been conducted yet with the objective of evaluating the effects of this kind of approach when applied to patients who have already gone thought their peak of growth.

Material and methods

27 patients with skeletal Class III malocclusion were treated using hybrid RME according to alternating rapid maxillary expansion and constriction (ALT-RAMEC) protocol, followed by 4 months of facemask therapy. After the orthopaedic phase, each patient underwent orthodontic treatment with fixed multibracket appliances. A mean follow-up of 7 years, 10 months was performed. Pre-treatment (TO), post-treatment (T1) and follow up (T2) cephalometric tracing were analysed, comparing dental and skeletal measurements.

Results

Point A advanced by a mean of 3.5 mm with respect to VerT, then relapsed by 0.7 in the post-facemask period, thereby yielding of a mean advancement of 2.7 at T2. The sagittal relationship significantly changed after RME + facemask protraction (3.8° of ANB and 5.189 mm of Wits). Although both Wits and ANB values worsened over time, the improvement from T0 is still appreciable at T2.

Conclusion

Despite the physiological relapse due to mandibular growth, the long-term cephalometric follow-up confirms the maintenance of all positive outcomes of the previous orthopaedic treatment with hybrid RME and facemask.
Clustering of distance sensors to transfer training data for relative position and orientation measurement devices
Authors: Amagai Sogo , Ye Qiwei , Fukuoka Yuji , Warisawa Shin’ichi , Fukui Rui
Published: September 2022

Car-sharing services have recently attracted considerable attention. We proposed a platooning system to reduce the number of vehicle distributors. The platooning system uses a measurement device embedded with low-cost infrared distance sensors to measure the relative position and orientation of vehicles. The relative positions and orientations are obtained from the training data. However, preparing training data is time consuming. In this study, a sensor clustering method that selects sensors with similar output characteristics is proposed. Consequently, a set of training data are used repetitively for all relative positions and orientation measurement devices embedded with sensors with similar output characteristics. The verification experiment of the sensor clustering revealed that the calculation range restriction is the key technique. Platooning has been successful in various courses by using sensors with similar output characteristics. Based on the results, the proposed clustering method can effectively collect sensors with similar output characteristics and it realizes the training data transfer to the newly manufactured devices. In addition, it has the potential to improve production efficiency for the mass production of relative position and orientation measurement devices.
Microcystic serous cystadenoma mimicking pancreatic neuroendocrine neoplasm: report of a resected case with preoperative diagnostic difficulty and review of the literature
Authors: Nakamura Shinichiro , Murata Yasuhiro , Uchida Katsunori , Nishikawa Kenichiro , Iizawa Yusuke , Fujii Takehiro , Tanemura Akihiro , Kuriyama Naohisa , Kishiwada Masashi , Mizuno Shugo
Published: September 2022

Background

Microcystic pancreatic serous cystadenoma (SCA) can be managed without surgery in selected patients. However, the preoperative diagnosis of microcystic SCA remains challenging, and it is potentially misdiagnosed as other pancreatic cystic neoplasms or solid tumors, especially small microcystic SCA.

Case presentation

This was a case of a 27-year-old male patient with microcystic SCA causing difficulty in the differential diagnosis from pancreatic neuroendocrine neoplasm (pNEN). A pancreatic tail mass was incidentally discovered on abdominal ultrasound (US). A contrast-enhanced computed tomography (CT) scan revealed a solid tumor measuring 13 mm with early enhancement in the arterial phase at the pancreatic tail. The tumor showed low intensity on T1-weighted magnetic resonance image, high intensity on T2-weighted image, and a slightly hyperechoic mass on endoscopic US (EUS). EUS-fine needle aspiration (EUS-FNA) did not lead to a definitive diagnosis. The tumor was clinically diagnosed as a pNEN, and a laparoscopic spleen-preserving distal pancreatectomy using the Warshaw technique was performed. The final histopathological diagnosis was microcystic SCA.

Conclusion

Small microcystic SCA is difficult to distinguish from a hypervascular pancreatic tumor such as pNEN on imaging studies, and it is necessary to focus on the tumor echogenicity of EUS to differentiate microcystic SCA from pNEN preoperatively.
Insulin edema after initiation of hybrid closed-loop insulin pump therapy with continuous glucose monitoring: a case report
Authors: Vasigh Mostafa , Hopkins Rachel
Published: September 2022

Background

Insulin edema is a rare complication which can present after initiation or intensification of insulin therapy in people with diabetes. Initiation of closed-loop hybrid insulin pump therapy can result in rapid improvement in glycemic control for people with diabetes. We present a case in which transition to a closed-loop hybrid insulin pump system, followed by significant improvement in glycemic control, led to development of insulin edema in a person with type 1 diabetes.

Case presentation

We present a 51-year-old woman with type 1 diabetes of 16 years duration, on insulin pump therapy for more than 10 years, who presented for follow-up 7 weeks after transitioning to a hybrid closed-loop insulin pump system with continuous glucose monitoring (CGM). She complained of weight gain and bilateral lower extremity edema which had started two weeks after the change in pump modality. Laboratory studies and echocardiogram did not reveal any etiology of the acute edema. HbA1c was 3.3% lower than the previous measurement 15 weeks earlier, and there was a significant increase in the daily total insulin dose. With exclusion of other causes of acute edema, the patient was diagnosed with insulin edema and started on hydrochlorothiazide. On follow up, her lower extremity edema significantly improved although her weight did not return to baseline.

Conclusion

To our knowledge, this is the first case of insulin edema reported in a person with type 1 diabetes using CGM and a hybrid closed-loop insulin pump system. The increase in total daily insulin dose, rapid improvement of glycemic control, and lack of hypoglycemic episodes were important factors to consider in evaluation of this case. Use of hybrid closed-loop systems can help achieve rapid improvement in glycemic control in people with diabetes. This case suggests that consideration should be given to adjusting initial blood glucose targets when starting these remarkable new technologies in people with baseline poor glycemic control.
Should they stay or should they go? A case study on international students in Germany
Authors: Krannich Sascha , Hunger Uwe
Published: September 2022

International students are conceived as essential contributors to the development of their countries of origin after they finished their studies abroad. Political decision-makers of the countries of origin therefore take measures that students will eventually return to their home countries and bring back their gained knowledge and consequently contribute to development back home. However, is a return always the best way to contribute to development in the country of origin or can international graduates contribute equally from abroad or through their high mobility between different countries? This article aims to address this question on the basis of an intensive three years mixed-methods-based investigation in six countries – Germany as country of study and Colombia, Georgia, Ghana, Indonesia and Israel/Palestinian territories as countries of origin. We investigated a specific German scholarship program, which gives scholarships to international students from the Global South to study in Germany. Although a return to the country of origin is a precondition for the scholarship, our study indicates that not only return migration, but also remains and circular migration can create beneficial circumstances that former students practice diverse development-related functions and therefore contribute to the development in their country of origin in a specific way. Here, it is important to recognize that scholarship programs do not only offer the opportunity to fund studying abroad, but they can be also designed for the needs of scholars during, before and after their studies, which would also benefit their developmental contributions.