bluuebunny/crossref_metadata_2025 huggingface dataset:
Parent-adolescent informant discrepancy on the Strengths and Difficulties Questionnaire in the UK Millennium Cohort Study
Authors: Booth Charlotte , Moreno-Agostino Dario , Fitzsimons Emla
Published: May 2023

Background

Developmental researchers often use a multi-informant approach to measure adolescent behaviour and adjustment, but informant discrepancies are common. In general population samples, it is often found that parents report more positive and less negative outcomes than adolescents themselves. This study aimed to investigate factors associated with informant discrepancy, including adolescent sex, and parental level of psychological distress and education.

Methods

Informant discrepancy on the Strengths and Difficulties Questionnaire was investigated using a Latent Difference Score (LDS) approach, which estimates the true difference between parent and adolescent reports in a structural equation model. The sample were parent-adolescent dyads from the seventh wave of the UK Millennium Cohort Study (N = 6947, 49.3% female, aged 17 years).

Results

Parents reported lower levels of difficulties (emotion symptoms, peer problems, conduct problems), and higher levels of pro-social behaviour than adolescents themselves. Conditional effects were found, as discrepancy was greater amongst parent-daughter dyads for emotion and peer problems, and greater amongst parent-son dyads for conduct problems and pro-social behaviour. Parent-adolescent discrepancy was also greater generally if parents had a lower level of psychological distress or a higher level of education.

Conclusions

In a large general population sample from the UK, it was found that adolescents tended to report more negative and less positive outcomes than parents reported about them. Conditional effects were found at the parent and adolescent level suggesting that specific informant biases are likely to impact the measurement of adolescent behaviour and adjustment across reporters.
Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study
Authors: Hajika Yuriko , Kawaguchi Yuji , Hamazaki Kenji , Kumeda Yasuro
Published: May 2023

Background

Arteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease.

Methods

This single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study.

Results

The patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced.

Conclusions

Luseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications.

Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021
Severe lumbar pain in an adolescent due to idiopathic vena cava thrombosis: a case report
Authors: Gevers Anthony , Dessart Patricia , Vanmarsenille Jean-Marie , Vande Berg Bruno , Yildiz Halil , Hatem Samar M.
Published: May 2023

Background

Lumbar back pain in an adolescent is generally musculoskeletal, that is, due to a muscle strain or scoliosis. This case describes a young individual without any previous health issues who rapidly developed a life-threatening condition, though initially presenting with “only” back pain.

Case presentation

A 16-year-old Caucasian male patient was admitted twice to the emergency department with debilitating lumbar pain without neurological or vascular symptoms. Imagery showed an extensive thrombosis of the inferior vena cava. No external cause, structural abnormality, or any systemic disease were found that predisposed the patient to this highly unusual vaso-occlusive incident.

Conclusion

Thrombosis of the inferior vena cava is a rare but life-threatening entity. It is underrecognized and associated with serious short- and long-term morbidity and mortality. Increased awareness is essential because deep vein thrombosis in children seems to cause atypical symptoms, such as spinal pain or the absence of edema of the lower limbs, as in the present case.
Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells
Authors: Baldassarro Vito Antonio , Perut Francesca , Cescatti Maura , Pinto Valentina , Fazio Nicola , Alastra Giuseppe , Parziale Valentina , Bassotti Alessandra , Fernandez Mercedes , Giardino Luciana , Baldini Nicola , Calzà Laura
Published: May 2023

Background

Greater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tissue-derived MSCs (adMSCs) with regard to potential therapeutical applications in neurology.

Methods

adMSCs were isolated from the intact adipose tissue of ten subjects undergoing abdominal plastic surgery or reduction mammoplasty. Two commercial lines were also included. We analyzed the expansion rate, production, and secretion of growth factors of interest for neurological applications (VEGF-A, BDNF, PDGF-AA and AA/BB, HGF, NGF, FGF-21, GDNF, IGF-I, IGF-II, EGF and FGF-2). To correlate these characteristics with the biological effects on the cellular targets, we used individual media conditioned with adMSCs from the various donors on primary cultures of neurons/astrocytes and oligodendrocyte precursor cells (OPCs) exposed to noxious stimuli (oxygen–glucose deprivation, OGD) to evaluate their protective and promyelinating properties, using MSC medium as a control group.

Results

The MSC secretome showed significant individual variability within the considered population with regard to PDGF-AA, PDGF-AB/BB, VEGF-A and BDNF. None of the MSC-derived supernatants affected neuron viability in normoxia, while substantial protection by high BDNF-containing conditioned MSC medium was observed in neuronal cultures exposed to OGD conditions. In OPC cultures, the MSC-derived supernatants protected cells from OGD-induced cell death, also increasing the differentiation in mature oligodendrocytes. Neuroprotection showed a positive correlation with VEGF-A, BDNF and PDGF-AA concentrations in the culture supernatants, and an inverse correlation with HGF, while OPC differentiation following OGD was positively correlated to PDGF-AA concentration.

Conclusions

Despite the limited number of adMSC donors, this study showed significant individual variability in the biological properties of interest for neurological applications for adMSC secretome, an under-researched aspect which may represent an important step in the translation of MSC-derived acellular products to clinical practice. We also showed the potential protection capability of MSC conditioned medium on neuronal and oligodendroglial lineages exposed to oxygen–glucose deprivation. These effects are directly correlated to the concentration of specific growth factors, and indicate that the remyelination should be included as a primary target in MSC-based therapies.
ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1
Authors: Chen Yaru , Zhou Jiawei , Wu Shang , Wang Lei , Chen Gaogui , Chen Dake , Peng Xianwen , Miao Yi-Liang , Mei Shuqi , Li Fenge
Published: May 2023

Background

ISGylation is a post-translational protein modification that regulates many life activities, including immunomodulation, antiviral responses, and embryo implantation. The exact contribution of ISGylation to folliculogenesis remains largely undefined.

Results

Here, Isg15 knockout in mice causes hyperfertility along with sensitive ovarian responses to gonadotropin, such as increases in cumulus expansion and ovulation rate. Moreover, ISG15 represses the expression of ovulation-related genes in an ISGylation-dependent manner. Mechanistically, ISG15 binds to ADAMTS1 via the ISG15-conjugating system (UBA7, UBE2L6, and HERC6), ISGylating ADAMTS1 at the binding sites Lys309, Lys593, Lys597, and Lys602, resulting in ADAMTS1 degradation via a 20S proteasome-dependent pathway.

Conclusion

Taken together, the present study demonstrates that covalent ISG15 conjugation produces a novel regulatory axis of ISG15-ADAMTS1 that enhances the degradation of ADAMTS1, thereby compromising ovulation and female fertility.
Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Authors: Semikasev Eugen , Ahlemeyer Barbara , Acker Till , Schänzer Anne , Baumgart-Vogt Eveline
Published: May 2023

Peroxisomes are eukaryotic organelles that rapidly change in number depending on the metabolic requirement of distinct cell types and tissues. In the brain, these organelles are essential for neuronal migration and myelination during development and their dysfunction is associated with age-related neurodegenerative diseases. Except for one study analysing ABCD3-positive peroxisomes in neurons of the frontal neocortex of Alzheimer disease (AD) patients, no data on other brain regions or peroxisomal proteins are available. In the present morphometric study, we quantified peroxisomes labelled with PEX14, a metabolism-independent peroxisome marker, in 13 different brain areas of 8 patients each either with low, intermediate or high AD neuropathological changes compared to 10 control patients. Classification of patient samples was based on the official ABC score. During AD-stage progression, the peroxisome density decreased in the area entorhinalis, parietal/occipital neocortex and cerebellum, it increased and in later AD-stage patients decreased in the subiculum and hippocampal CA3 region, frontal neocortex and pontine gray and it remained unchanged in the gyrus dentatus, temporal neocortex, striatum and inferior olive. Moreover, we investigated the density of catalase-positive peroxisomes in a subset of patients (> 80 years), focussing on regions with significant alterations of PEX14-positive peroxisomes. In hippocampal neurons, only one third of all peroxisomes contained detectable levels of catalase exhibiting constant density at all AD stages. Whereas the density of all peroxisomes in neocortical neurons was only half of the one of the hippocampus, two thirds of them were catalase-positive exhibiting increased levels at higher ABC scores. In conclusion, we observed spatiotemporal differences in the response of peroxisomes to different stages of AD-associated pathologies.

Graphical Abstract
A potential immunotherapeutic and prognostic biomarker for multiple tumors including glioma: SHOX2
Authors: Wu Xiaocong , Chen Hui , You Chao , Peng Zongjun
Published: May 2023

Background

Short stature homeobox 2 (SHOX2) is significant gene in the development and progression of multiple types of tumors. Nonetheless, the biological role of SHOX2 within pan-cancer datasets has not been investigated. Thus, comprehensive bioinformatics analyses of pan-cancer datasets were conducted to explore how SHOX2 regulates tumorigenesis.

Methods

A variety of tumor datasets and online analytical tools, including SangerBox, TIMER2, LinkedOmic, GEPIA2 and cBioPortal, were applied to explore SHOX2 expression in various tumors. To ascertain the connections between SHOX2 expression and genetic alterations, SHOX2-related genes and tumor immunity, the pan-cancer datasets were examined. In vitro assays were applied to verify the biological functions of SHOX2 in glioma cells via CCK-8, wound healing, Transwell and colony formation assays.

Results

Analyses found that SHOX2 was overexpressed in multiple cancer types. SHOX2 expression level was significantly correlated with isocitrate dehydrogenase (IDH), 1p/19q, O6-methylguanine DNA methyltransferase (MGMT) status and new types of glioma patients. High mRNA expression levels of SHOX2 were associated with a poor prognosis in multiple tumor patients. KEGG enrichment analysis showed that SHOX2-related genes were associated with cell cycle and DNA damage repair. Genetic alterations of SHOX2 were identified in multiple types of cancers, including duplications and deep mutations. Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. CCK-8, wound healing, Transwell and colony formation experiments showed that SHOX2 knockdown inhibited glioma cell proliferation, migration, invasion and colony formation abilities.

Conclusion

SHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.
The comparative and correlation study of postmortem ethanol levels between axillosubclavian blood and femoral venous blood in forensic autopsy cases at Thammasat University Hospital, Thailand
Authors: Tangsermkijsakul Aphinan , Pipatchotitham Tossanai
Published: May 2023

Background

Femoral venous blood (FVB) is accepted as a standard sample for postmortem ethanol analysis, but owing to the nature of unnatural death cases, FVB may not always be obtainable, and subclavian blood might be used for alternative specimens. This study investigated the correlation between postmortem ethanol concentrations in FVB and axillosubclavian blood (ASB) from autopsy cases in the tropical climate of Central Thailand. Two other factors potentially affecting the correlation, the time of death and ethanol absorption state, were also investigated. FVB, ASB, and vitreous humor were collected from 100 subjects between May 2021 and May 2022. Subjects with decomposition signs and large open wounds were excluded. ASB was drawn from the axillosubclavian vein at the thoracic outlet. Ethanol concentrations in all samples were measured by headspace GC-FID.

Results

Ethanol concentrations in ASB were statistically identical to those in FVB (p = 0.6761) and their relationship was statistically correlated (r = 0.9818, p < 0.001). The correlation was not statistically influenced by time since death or absorptive statuses. The diagnostic study to assess the practical application of ASB instead of FVB at a cut-off concentration above 50 mg/dL yielded an area under the ROC curve of 0.96.

Conclusions

Our study indicated that ASB can be used as an alternative specimen for postmortem ethanol analysis when FVB is unavailable in dead bodies that are in a tropical climate.
Clinical and radiological profile of cavernous sinus syndrome: a study from eastern part of India
Authors: Rodge Vinayak Narayan , Mukherjee Adreesh , Biswas Samar , Majumdar Suchitra , Gangopadhyay Goutam
Published: May 2023

Background

Cavernous sinus syndrome (CSS) consists of a variable combination of involvement of the 3rd-to-6th cranial nerves. The etiologies vary across studies, and it has a significant impact on the outcome. This study was done to delineate the etiology, clinico-radiological profile and outcome of CSS. In this prospective study, patients were recruited consecutively over 2 years, and were followed up for at least 6 months. MRI of the brain and orbit with contrast was done, and other relevant investigations were performed to arrive at a specific etiology. Tolosa-Hunt Syndrome (THS) was defined in accordance with the second edition of the International Classification of Headache Disorders (ICHD-II).

Results

Of the 92 patients studied, THS was the predominant diagnosis, followed by Tuberculosis, fungal infection, aneurysm, neoplastic and Sjögren’s syndrome. Cranial nerves commonly involved were 3rd, 4th, 6th and 5th. The optic nerve was affected in 54.3% of patients. The non-THS patients showed the greater occurrence of proptosis, complete ophthalmoplegia, involvement of optic nerve and cranial nerves 7th–10th. Nasal blockage was present in fungal infection. MRI revealed more frequent involvement of orbit in non-THS cases. Bony erosions, ICA narrowing, intracranial extension and involvement of paranasal sinus were seen in fungal infection and neoplasm. THS patients improved with corticosteroid therapy, although, there was recurrence in 8 patients.

Conclusions

THS and tuberculosis were the most common cause of CSS. Clinical and radiological features were useful in distinguishing among the etiologies. Most of the patients responded to treatment, although, recurrence was seen in THS.
Perfusion index (PI) measured in the brachial plexus blocks performed by ultrasonography: investigation of correlation with block success
Authors: Bozdağ Akif , Doğukan Mevlüt , Bıçakçıoğlu Murat , Nakır Hamza , Duran Mehmet , Uludağ Öznur
Published: May 2023

Background

Brachial plexus block is one of the peripheral nerve blocks commonly used in regional anesthesia. We aimed to investigate whether the perfusion index (PI) measurement can be used to evaluate the adequacy of the upper limb blocks accompanied by ultrasonography. Thirty-three patients between the ages of 18 and 65 who were in the ASA I–II group who will have a hand, forearm, and arm operation were included in the study. An appropriate type of brachial plexus block was applied to these patients under the guidance of ultrasonography. After the block application was completed, the sensory and motor blocks were evaluated at the 5th, 10th, and 20th min. In addition, perfusion indices measured from both extremities of the patient were recorded at the 5th, 10th, and 20th min.

Results

In 32 of 33 patients who underwent brachial plexus block, our block was successful, and perfusion index measurements in the applied limb increased continuously from the 5th min over the 20-min observation period. In one patient who failed the block and in the arm group without block, no statistically significant difference was detected in the 5th, 10th, and 20th min perfusion index measurements.

Conclusions

Perfusion index measurement is a very valuable and usable method to evaluate the success of peripheral nerve blocks early, easily, and objectively.
Nasogastric tube feeding under physical restraint: comprehensive audit and case series across in-patient mental health units in England
Authors: Fuller Sarah J. , Tan Jacinta , De Costa Huw , Nicholls Dasha
Published: May 2023

Aims and method

To identify the clinical characteristics of patients receiving nasogastric tube (NGT) feeding under physical restraint. Clinicians participated via professional networks and subsequent telephone contact. In addition to completing a survey, participants were invited to submit up to ten case studies.

Results

The survey response rate from in-patient units was 100% and 143 case studies were submitted. An estimated 622 patients received NGT feeding under restraint in England in 2020–2021. The most common diagnosis was anorexia nervosa (68.5–75.7%), with depression, anxiety and autism spectrum disorder the most frequent comorbidities. Patients receiving the intervention ranged from 11 to 60 years in age (mean 19.02 years). There was wide variation in duration of use, from once to daily for 312 weeks (mode 1 week; mean 29.1 weeks, s.d. = 50.8 weeks).

Clinical implications

NGT feeding under restraint is not uncommon in England, with variation in implementation. Further research is needed to understand how the high comorbidity and complexity contribute to initiation and termination of the intervention.
Family Matters: Germline Testing in Thoracic Cancers
Authors: Hathaway Feighanne , Martins Renato , Sorscher Steven , Bzura Aleksandra , Dudbridge Frank , Fennell Dean A.
Published: May 2023

Most thoracic cancers arise via a series of stepwise somatic alterations driven by a well-defined carcinogen (ie, tobacco or asbestos for lung cancer and mesothelioma, respectively). A small proportion can emerge on a background of pathogenic germline variants (PGVs), which have the property of heritability. In general, PGVs may be initially suspected on the basis of the presence of specific clinical features. Such gene × environment interactions significantly increase the risk of developing lung cancer (1.5- to 3.2-fold). PGVs have been discovered involving the actionable driver oncogene, epidermal growth factor receptor (EGFR), with an EGFR T790M PGV rate of 0.3%-0.9% in the nonsquamous non–small-cell lung cancer subtype. Its appearance during routine somatic DNA sequencing in those patients who have not had a previous tyrosine kinase inhibitor should raise suspicion. In patients with sporadic mesothelioma, BAP1 is the most frequently mutated tumor driver, with a PGV rate between 2.8% and 8%, associated with a favorable prognosis. BAP1 PGVs accelerate mesothelioma tumorigenesis after asbestos exposure in preclinical models and may be partly predicted by clinical criteria. At present, routine germline genetic testing for thoracic cancers is not a standard practice. Expert genetic counseling is, therefore, required for patients who carry a PGV. Ongoing studies aim to better understand the natural history of patients harboring PGVs to underpin future cancer prevention, precise counseling, and cancer management with the goal of improving the quality and length of life.
Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients
Authors: Overkamp Maarten , Houben Lisanne H P , Aussieker Thorben , van Kranenburg Janneau M X , Pinckaers Philippe J M , Mikkelsen Ulla R , Beelen Milou , Beijer Sandra , van Loon Luc J C , Snijders Tim
Published: May 2023

Context

Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass.

Objective

To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients.

Methods

Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry.

Results

Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 μm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 μm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (−12% ± 12% and −20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 μm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 μm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05).

Conclusion

The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.
Effect of Simvastatin Treatment on Mitochondrial Function and Inflammatory Status of Human White Adipose Tissue
Authors: Christensen Ida Bager , Blom Ida , Dohlmann Tine Lovsø , Finger Fabian , Helge Jørn W , Gerhart-Hines Zachary , Dela Flemming , Larsen Steen
Published: May 2023

Background

Statin therapy has shown pleiotropic effects affecting both mitochondrial function and inflammatory status. However, few studies have investigated the concurrent effects of statin exposure on mitochondrial function and inflammatory status in human subcutaneous white adipose tissue.

Objectives

In a cross-sectional study, we investigated the effects of simvastatin on mitochondrial function and inflammatory status in subcutaneous white adipose tissue of 55 human participants: 38 patients (19 females/19 males) in primary prevention with simvastatin (> 40 mg/d, > 3 mo) and 17 controls (9 females/8 males) with elevated plasma cholesterol. The 2 groups were matched on age, body mass index, and maximal oxygen consumption.

Methods

Anthropometrics and fasting biochemical characteristics were measured. Mitochondrial respiratory capacity was assessed in white adipose tissue by high-resolution respirometry. Subcutaneous white adipose tissue expression of the inflammatory markers IL-6, chemokine (C-C motif) ligand 2 (CCL2), CCL-5, tumor necrosis factor-α, IL-10, and IL-4 was analyzed by quantitative PCR.

Results

Simvastatin-treated patients showed lower plasma cholesterol (P < .0001), low-density lipoprotein (P < .0001), and triglyceride levels (P = .0116) than controls. Simvastatin-treated patients had a lower oxidative phosphorylation capacity of mitochondrial complex II (P = .0001 when normalized to wet weight, P < .0001 when normalized to citrate synthase activity [intrinsic]), and a lower intrinsic mitochondrial electron transport system capacity (P = .0004). Simvastatin-treated patients showed higher IL-6 expression than controls (P = .0202).

Conclusion

Simvastatin treatment was linked to mitochondrial respiratory capacity in human subcutaneous white adipose tissue, but no clear link was found between statin exposure, respiratory changes, and inflammatory status of adipose tissue.
Remnant Cholesterol Is Associated With Gestational Diabetes Mellitus: A Cohort Study
Authors: Wang Weiming , Li Na , Wang Xiaoyi , Zhang Xu , Tu Menghan , Lin Lixia , Li Qian , Zhang Huaqi , Liu Jin , Yang Xuefeng , Hao Liping , Yang Nianhong
Published: May 2023

Context

The association between remnant cholesterol (RC) and gestational diabetes mellitus (GDM) risk is unclear.

Objective

This study investigated the association between RC and GDM.

Methods

We used data from the Tongji Maternal and Child Health Cohort, a prospective cohort study in China. Fasting lipid concentrations were measured around 16 weeks’ gestation. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. GDM was diagnosed by a 75-g oral glucose tolerance test at 24 to 28 weeks’ gestation. Log-Poisson regression models were performed to estimate relative risks (RRs) of GDM across quartiles of RC levels and triglyceride (TG) levels after adjustment for potential confounders. TG and RC were mutually adjusted.

Results

Among 2528 women, 256 (10.1%) developed GDM. The adjusted RRs (95% CIs) for GDM across increasing quartiles of RC were 1.00 (reference), 1.35 (0.91, 1.99), 1.68 (1.16, 2.45), and 1.73 (1.19, 2.50), respectively. Compared to pregnant women without 3 risk indicators (TG <2.08 mmol/L, RC <0.40 mmol/L, and pre-BMI <24.0 kg/m2), the risk of GDM was elevated in those with normal pre-BMI but high RC (aRR: 1.54; 95% CI: 1.08, 2.19) or high TG (aRR: 2.15; 95% CI: 1.33, 3.49). For those with all 3 risk indicators, the risk of GDM was the highest (aRR: 4.80; 95% CI: 3.20, 7.18).

Conclusion

Elevated RC levels were associated with the increased risk of GDM and independent of traditional risk factors. Pregnant women with high pre-BMI, high TG, and high RC were at greatly increased risk of GDM.
Combined Double-Barrel Superficial Temporal Artery to M4 Bypass and Parent Artery Occlusion for the Treatment of Complex Intracranial Aneurysms in Internal Carotid Artery and Middle Cerebral Artery: A Retrospective Case Series
Authors: Wu Zhimin , Ling Cong , Liao Zhi , Sun Jun , Qiao Jia , Chen Chuan , Wang Hui
Published: May 2023

BACKGROUND:

Very little research has been conducted to assess the efficacy of combined double-barrel superficial temporal artery (STA) to M4 bypass and parent artery occlusion (PAO) in the treatment of complex intracranial aneurysms.

OBJECTIVE:

To determine whether this operation could become a reasonable flow replacement therapy and have longer-term benefits.

METHODS:

A series of double-barrel STA-M4 bypasses performed between 2016 and 2021 were reviewed. Preoperative digital subtraction angiography (DSA), computed tomography angiography (CTA), computed tomography perfusion (CTP), and balloon test occlusion were routinely performed for a thorough evaluation of individual benefits and risks. After bypass, the proximal end of the parent artery was permanently occluded with the coil. Augmentation and patency of STA were reassessed by postoperative DSA, CTA, and CTP. The blood flow volume of STA was measured by ultrasound at admission and a 3-month follow-up.

RESULTS:

This study included 12 consecutive patients (5 males, 7 females) who successfully underwent double-barrel STA-M4 bypass, including 8 complex aneurysms in the internal carotid artery (ICA) and 4 in the middle cerebral artery (MCA). Postoperative angiography and CTP suggested that all the STAs were patent, and there was a significant improvement in perfusion after the operation (P < .05). Ultrasonic measurement at the 3-month follow-up showed that the blood flow provided by STA was 76.3 to 190.5 mL/min. Postoperative ischemia was found in 1 patient, but she recovered after treatment.

CONCLUSION:

Double-barrel STA to M4 bypass can provide adequate flow for the parent artery area, which may be a reasonable flow replacement therapy for some complex intracranial aneurysms in ICA and MCA.
Clinical Outcomes After Ultra-Early Cranioplasty Using Craniectomy Contour Classification as a Patient Selection Criterion
Authors: Patel Pious D. , Khanna Omaditya , Gooch M Reid , Glener Steven R. , Mouchtouris Nikolaos , Momin Arbaz A. , Sioutas Georgios , Amllay Abdelaziz , Barsouk Adam , El Naamani Kareem , Yudkoff Clifford , Wyler David A. , Jallo Jack I , Tjoumakaris Stavropoula , Jabbour Pascal M. , Harrop James S.
Published: May 2023

BACKGROUND:

Although not a technically difficult operation, cranioplasty is associated with high rates of complications. The optimal timing of cranioplasty to mitigate complications remains the subject of debate.

OBJECTIVE:

To report outcomes between patients undergoing cranioplasty at ultra-early (0-6 weeks), intermediate (6 weeks to 6 months), and late (>6 months) time frames. We report a novel craniectomy contour classification (CCC) as a radiographic parameter to assess readiness for cranioplasty.

METHODS:

A single-institution retrospective analysis of patients undergoing cranioplasty was performed. Patients were stratified into ultra-early (within 6 weeks of index craniectomy), intermediate (6 weeks to 6 months), and late (>6 months) cranioplasty cohorts. We have devised CCC scores, A, B, and C, based on radiographic criteria, where A represents those with a sunken brain/flap, B with a normal parenchymal contour, and C with “full” parenchyma.

RESULTS:

A total of 119 patients were included. There was no significant difference in postcranioplasty complications, including return to operating room (P = .212), seizures (P = .556), infection (P = .140), need for shunting (P = .204), and deep venous thrombosis (P = .066), between the cohorts. Univariate logistic regression revealed that ultra-early cranioplasty was significantly associated with higher rate of functional independence at >6 months (odds ratio 4.32, 95% CI 1.39-15.13, P = .015) although this did not persist when adjusting for patient selection features (odds ratio 2.90, 95% CI 0.53-19.03, P = .234).

CONCLUSION:

In appropriately selected patients, ultra-early cranioplasty is not associated with increased rate of postoperative complications and is a viable option. The CCC may help guide decision-making on timing of cranioplasty.
Adjustable, Dynamic Subcortical Stimulation Technique for Brain Tumor Resection: A Case-Series
Authors: Silverstein Justin W. , Shah Harshal A. , Greisman Jacob D. , Dadario Nicholas B. , Barbarevech Kristiana , Park Jung , D'Amico Randy S.
Published: May 2023

BACKGROUND AND OBJECTIVES:

Subcortical stimulation (SCS) is the gold standard neuromonitoring technique for intraoperative identification of descending white matter tracts. Dynamic SCS confers several advantages over more commonly used static devices; however, current commercially available devices for dynamic SCS have not been widely adopted.

METHODS:

We fashioned a dynamic SCS device using a stainless-steel suction and commonly available materials and assessed its efficacy in a series of 14 patients with brain tumors. The device was used to provide continuous SCS during tumor resection. Preoperative and postoperative motor function were characterized, and preoperative and postoperative imaging were analyzed to determine extent of tumor resection and proximity to motor-eloquent structures. Inferential statistics were used to correlate study parameters.

RESULTS:

Fourteen patients (12 male and 2 female, median age 52.5 years) were analyzed. The lowest intraoperative SCS intensities were 10 to 15 mA (3 surgeries), 5 to 10 mA (4 surgeries), and <5 mA (2 surgeries). SCS with this device did not elicit motor evoked potentials in 5 surgeries because of distance from the corticospinal tract (CST) and served as negative controls. Three patients (21.4%) experienced new postoperative motor deficits immediately after surgery that resolved by discharge. We observed no instances of mechanical CST injury resulting in permanent postoperative motor deficits using this technique and no correlation between lower SCS intensity and the presence of new motor impairments after surgery. No patient experienced an intraoperative seizure.

CONCLUSION:

The novel dynamic SCS device is easily adoptable and allows accurate intraoperative identification of the CST, facilitating safe resection of tumors near motor-eloquent structures.
A dynamical systems treatment of transcriptomic trajectories in hematopoiesis
Authors: Freedman Simon L. , Xu Bingxian , Goyal Sidhartha , Mani Madhav
Published: May 2023

Inspired by Waddington's illustration of an epigenetic landscape, cell-fate transitions have been envisioned as bifurcating dynamical systems, wherein exogenous signaling dynamics couple to the enormously complex signaling and transcriptional machinery of a cell to elicit qualitative transitions in its collective state. Single-cell RNA sequencing (scRNA-seq), which measures the distributions of possible transcriptional states in large populations of differentiating cells, provides an alternate view, in which development is marked by the variations of a myriad of genes. Here, we present a mathematical formalism for rigorously evaluating, from a dynamical systems perspective, whether scRNA-seq trajectories display statistical signatures consistent with bifurcations and, as a case study, pinpoint regions of multistability along the neutrophil branch of hematopoeitic differentiation. Additionally, we leverage the geometric features of linear instability to identify the low-dimensional phase plane in gene expression space within which the multistability unfolds, highlighting novel genetic players that are crucial for neutrophil differentiation. Broadly, we show that a dynamical systems treatment of scRNA-seq data provides mechanistic insights into the high-dimensional processes of cellular differentiation, taking a step toward systematic construction of mathematical models for transcriptomic dynamics.
Genetic knockdown of genes that are obscure, conserved and essential using CRISPR interference methods in the fission yeast S. pombe
Authors: Ishikawa Ken , Soejima Saeko , Saitoh Shigeaki
Published: May 2023

Characterizing functions of essential genes is challenging, as perturbing them is generally lethal. Conditional gene perturbation, including use of temperature-sensitive mutants, has been widely utilized to reveal functions of essential genes in the fission yeast Schizosaccharomyces pombe. However, recently we implemented a systematic and less time-consuming knockdown method, CRISPR interference (CRISPRi), in this organism using catalytically inactive Cas9 (dCas9). This technology has been expected to facilitate characterization of essential genes in S. pombe, although this still has not occurred. Here, CRISPRi was harnessed to study uncharacterized essential genes that are evolutionally conserved from yeasts to mammals. Transcription of these genes, which we call conserved essential obscure (ceo) genes, was repressed using conventional dCas9-mediated CRISPRi and by implementing technologies that enhance repression efficiency or alleviate limitations on small guide RNA (sgRNA) design. These CRISPRi methods successfully reduced transcription of target genes and allowed us to characterize resulting phenotypes. Knockdown of ceo genes inhibited cell proliferation and altered cellular morphology. Thus, dCas9-based CRISPRi methods utilized in this study enhanced accessibility of genetic analyses targeting essential genes in S. pombe.
Comparison of TRIBE and STAMP for identifying targets of RNA binding proteins in human andDrosophilacells
Authors: Abruzzi Katharine C. , Ratner Corrie , Rosbash Michael
Published: May 2023

RNA binding proteins (RBPs) perform a myriad of functions and are implicated in numerous neurological diseases. To identify the targets of RBPs in small numbers of cells, we developed TRIBE, in which the catalytic domain of the RNA editing enzyme ADAR (ADARcd) is fused to an RBP. When the RBP binds to an mRNA, ADAR catalyzes A to G modifications in the target mRNA that can be easily identified in standard RNA sequencing. In STAMP, the concept is the same except the ADARcd is replaced by the RNA editing enzyme APOBEC. Here we compared TRIBE and STAMP side-by-side in human andDrosophilacells. The goal is to learn the pros and cons of each method so that researchers can choose the method best suited to their RBP and system. In human cells, TRIBE and STAMP were performed using the RBP TDP-43. Although they both identified TDP-43 target mRNAs, combining the two methods more successfully identified high-confidence targets. InDrosophilacells, RBP–APOBEC fusions generated only low numbers of editing sites, comparable to the level of control editing. This was true for two different RBPs, Hrp48 and Thor (DrosophilaEIF4E-BP), indicating that STAMP does not work well inDrosophila.
Primary students’ argumentation skills on evaporation: A teaching intervention
Authors: Angeloudi Anastasia , Papageorgiou George
Published: May 2023

This paper reports the findings of a study exploring the possibilities of improving students’ argumentation skills concerning evaporation process and factors affecting evaporation by implementing two teaching schemes, with and without the use of particle theory. The participants (ages 10/11, n = 77) were students of four fifth-grade classes of two Greek regular public primary schools. The research data were collected through an open-ended written test (pre- and post-intervention) and a semi-structured interview (post-intervention). Results revealed that the improvement of students’ argumentation skills regarding the evaporation process and the factors affecting evaporation is feasible through an appropriate teaching intervention. This concerns mainly the components of claim and evidence, whereas the use of the particle theory seems to contribute further to this improvement, as well as to the improvement of the reasoning component. Implications for science education are also discussed.
Το μουσείο ως παιδαγωγικό εργαλείο για τη μάθηση: Παράγοντες που επηρεάζουν την πρόθεση αξιοποίησής του από φοιτητές τμημάτων αγωγής της πρώιμης παιδικής και εκπαίδευσης της προσχολικής και της σχολικής ηλικίας
Authors: Δημητριάδη Σοφία , Μαλαφάντης Κωνσταντίνος
Published: May 2023

Κατά το μεγαλύτερο μέρος της ζωής μας μαθαίνουμε έξω από το επίσημο-τυπικό εκπαιδευτικό σύστημα, δηλαδή τα σχολεία, σε περιβάλλοντα μη-τυπικής ακόμα και άτυπης εκπαίδευσης και μέσα από τη δόμηση εμπειριών. Το μουσείο αποτελεί μια μη-τυπική και ταυτόχρονα ιδιαίτερα επικοινωνιακή μορφή αγωγής και εκπαίδευσης που απευθύνεται σε όλες τις ηλικίες, σε πολλές περιπτώσεις ακόμη και σε παιδιά ηλικίας κάτω των 2 ετών. Το σύγχρονο μουσείο αναγνωρίζεται ως εκπαιδευτικός οργανισμός και διαρκώς ενισχύει και εκσυγχρονίζει το έργο του προς την κατεύθυνση αυτή. Ωστόσο, από την πλευρά του σύγχρονου σχολείου εντοπίζονται ορισμένα ζητήματα κυρίως ως προς τον ρόλο των εκπαιδευτικών απέναντι στο μουσείο και την παιδαγωγική αξιοποίησή του από τους ίδιους. Η παρούσα ερευνητική εργασία εξετάζει τις στάσεις και τις αντιλήψεις μελλοντικών παιδαγωγών για το μουσείο και τη μουσειακή εμπειρία ως παιδαγωγικό εργαλείο, επιχειρώντας να φωτίσει τους παράγοντες που επηρεάζουν την πρόθεσή τους να το αξιοποιήσουν στην τάξη. Ως ερευνητικό πλαίσιο χρησιμοποιήθηκε το μοντέλο της θεωρίας της προσχεδιασμένης συμπεριφοράς (TPB). Τον πληθυσμό μας αποτέλεσαν τεταρτοετείς και άνω φοιτητές των πανεπιστημιακών τμημάτων αγωγής της πρώιμης παιδικής και εκπαίδευσης της προσχολικής και της σχολικής ηλικίας, ενώ το δείγμα μας επιλέχθηκε με τυχαία δειγματοληψία. Η ανάλυση και στατιστική επεξεργασία των δεδομένων έγινε με τη μέθοδο ανάλυσης μοντέλων Δομικών Εξισώσεων (Structural Equation Modeling - SEM). Τα αποτελέσματα έδειξαν αυξημένη πρόθεση των μελλοντικών παιδαγωγών να αξιοποιήσουν το μουσείο και την μουσειακή εμπειρία ως παιδαγωγικό εργαλείο, ενώ οι στάσεις, τα υποκειμενικά πρότυπα και ο αντιλαμβανόμενος συμπεριφορικός έλεγχος εξηγούν το 76,7% της διακύμανσης της πρόθεσης. Τα ευρήματα προσφέρουν ποικίλες πληροφορίες που μπορούν να συνεισφέρουν σημαντικά στον σχεδιασμό εκπαιδευτικής πολιτικής για την κάθε βαθμίδα εκπαίδευσης, η οποία θα ευθυγραμμίζεται με τις σύγχρονες διεθνείς τάσεις για βιωματικές προσεγγίσεις και αξιοποίηση μη-τυπικών μορφών μάθησης, εστιάζοντας παράλληλα στην παιδεία και τον πολιτισμό.
High copy number of multi-drug resistance genes in spent coffee grounds used in organic composting
Authors: Hou Jinpao , Chiu Yuen Ting , Lam Kit-ling , Kwong Ki-ying , Lau Johnny Hoi-lung , Marafa Lawal M. , Tsui Stephen Kwok-wing , Mo Ian Wing-yin , Chan Ping Lung
Published: May 2023

Background: The demand for organic composts made of animal manure and food waste, such as spent coffee grounds, is increasing as organic farming is gaining popularity. One of the potential public health hazards of using these organic composts is the dissemination of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Animal manure is generally believed to be the primary source of these bacteria and genes since antibiotics are commonly used in animal farming. However, there is little concrete evidence supporting this claim. Here, we examined this argument by characterising the resistome of the raw materials, namely, chicken manure (CF), spent coffee grounds (COFFEE), and chopped grass (GRASS) commonly used in Hong Kong for preparing organic composts.

Methods: Three independent samples of the three raw materials were collected from an organic farm in Hong Kong. DNA of the samples were extracted and sequenced by metagenomic sequencing. The resistome of the samples was analysed using the resistome analysis pipeline ARGs-OAP v2.0. The abundance and the richness of the ARGs among the samples were compared using one-way ANOVA with Tukey post-hoc test.

Results: COFFEE carried the highest copy number of ARGs per cell (2.771–3.539) and was significantly higher than that of CF (1.991–2.617) and GRASS (0.491–0.537). Multi-drug resistance genes predominated the resistome of COFFEE, for which the richness of the resistome was the lowest among the three materials (150–154 ARG subtypes). It was significantly lower than that of CF (203–229 ARG subtypes) but not that of GRASS (153–203 ARG subtypes).

Conclusions: Contrary to the general belief that animal manure is the primary source of antibiotic resistance genes in organic composts, it was found that COFFEE carried the highest copy number of ARGs among the three materials, and multi-drug resistance genes predominated the resistome of COFFEE.
Organizing training workshops on gene literature retrieval, profiling, and visualization for early career researchers
Authors: Al Ali Fatima , Marr Alexandra K , Tatari-Calderone Zohreh , Alfaki Mohamed , Toufiq Mohammed , Roelands Jessica , Syed Ahamed Kabeer Basirudeen , Bedognetti Davide , Marr Nico , Garand Mathieu , Rinchai Darawan , Chaussabel Damien
Published: May 2023

Early-career researchers must acquire the skills necessary to effectively search and extract information from biomedical literature. This ability is for instance crucial for evaluating the novelty of experimental results, and assessing potential publishing opportunities. Given the rapidly growing volume of publications in the field of biomedical research, new systematic approaches need to be devised and adopted for the retrieval and curation of literature relevant to a specific theme. In this context, we present a hands-on training curriculum aimed at retrieval, profiling, and visualization of literature associated with a given topic. The curriculum was implemented in a workshop in January 2021. Here we provide supporting material and step-by-step implementation guidelines with the ISG15 gene literature serving as an illustrative use case. Workshop participants can learn several skills, including: 1) building and troubleshoot PubMed queries in order to retrieve the literature associated with a gene of interest; 2) identifying key concepts relevant to given themes (such as cell types, diseases, and biological processes); 3) measuring the prevalence of these concepts in the gene literature; 4) extracting key information from relevant articles, and 5) developing a background section or summary on the basis of this information. Finally, trainees can learn to consolidate the structured information captured through this process for presentation via an interactive web application.