bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to potentially traumatic events and PTSD symptomatology in Norwegian 11–13-year-olds: results from the Bergen Child Study
Authors: Skandsen Annika , Sand Liv , Teicher Martin H. , Heradstveit Ove , Bøe Tormod
Published: March 2023

Background

Exposure to potentially traumatic experiences (PTEs) is common among children and adolescents, but relatively little is known about the epidemiology of trauma and trauma-related psychopathology in children and youth. The present cross- sectional epidemiological study aimed to explore factors that is associated with posttraumatic stress symptoms (PTSS) in children.

Method

Data stem from the Bergen Child Study, a series of cross-sectional multi-phase surveys of children born between 1993 and 1995 in Bergen, Norway. The sample used is from the second wave of the Bergen Child Study (BCS) conducted in 2006, a two-phase study. The study entailed a detailed psychiatric evaluation using the Development and well-being assessment (DAWBA). The DAWBA was administered to parents or caregivers and covered diagnostic areas, child and family background, and child strengths. A total of 2043 parents participated.

Results

Out of the total sample, parents reported that 4.8% children had experienced PTEs at some point in their lives. The findings revealed current PTSS in 30.9% of children exposed to PTE, which was 1.5% of the total sample. None of the parents reported PTSS in their children over the threshold for diagnosing posttraumatic stress disorder (PTSD). The most common PTSS cluster was arousal reactivity (90.0%), followed by negative cognitions and mood (80%). The least frequent symptom cluster was intrusions (63.3%) and avoidance (60%). Children with PTSS were reported to live in families with significantly more family stressors (p = 0.001, d = 0.8) and had utilized significantly more sources for help relative to those without PTSS (p = 0.001, d = 0.75).

Conclusion

The present population study on children revealed a lower prevalence rate of PTEs and PTSD than previous studies. It provided findings in the field of trauma on parent- reported PTSS and PTSD symptom clusters not restricted to the clinical level of PTSD. Lastly, it highlighted how family-life stressors and support differed between those who had PTSS and those with no PTSS.
Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma
Authors: Chicco Davide , Sanavia Tiziana , Jurman Giuseppe
Published: March 2023

Neuroblastoma is a childhood neurological tumor which affects hundreds of thousands of children worldwide, and information about its prognosis can be pivotal for patients, their families, and clinicians. One of the main goals in the related bioinformatics analyses is to provide stable genetic signatures able to include genes whose expression levels can be effective to predict the prognosis of the patients. In this study, we collected the prognostic signatures for neuroblastoma published in the biomedical literature, and noticed that the most frequent genes present among them were three:AHCY,DPYLS3, andNME1. We therefore investigated the prognostic power of these three genes by performing a survival analysis and a binary classification on multiple gene expression datasets of different groups of patients diagnosed with neuroblastoma. Finally, we discussed the main studies in the literature associating these three genes with neuroblastoma. Our results, in each of these three steps of validation, confirm the prognostic capability ofAHCY,DPYLS3, andNME1, and highlight their key role in neuroblastoma prognosis. Our results can have an impact on neuroblastoma genetics research: biologists and medical researchers can pay more attention to the regulation and expression of these three genes in patients having neuroblastoma, and therefore can develop better cures and treatments which can save patients’ lives.
Current advances in understanding the molecular profile of hereditary diffuse gastric cancer and its clinical implications
Authors: Lim Hui Jun , Zhuang Lizhe , Fitzgerald Rebecca C.
Published: March 2023

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome attributed to germlineCDH1mutations that carries a high risk for early onset DGC. HDGC raises a significant health issue due to its high penetrance and mortality unless diagnosed early. The definitive treatment is to undergo prophylactic total gastrectomy which is associated with significant morbidity., highlighting the urgent need for alternative treatment methods. However, there is limited literature examining potential therapeutic strategies building on emerging insights into the molecular basis of progressive lesions in the context of HDGC. The aim of this review is to summarise the current understanding of HDGC in the context ofCDH1pathogenic variants followed by a review of the proposed mechanisms for progression. In addition, we discuss the development of novel therapeutic approaches and highlight pertinent areas for further research. A literature search was therefore performed for relevant studies examiningCDH1germline variants, second-hit mechanisms ofCDH1, pathogenesis of HDGC and potential therapeutic strategies in databases, including PubMed, ScienceDirect and Scopus. Germline mutations are mostly truncatingCDH1variants affecting extracellular domains of E-cadherin, generally due to frameshift, single nucleotide variants or splice site mutations. A second somatic hit ofCDH1most commonly occurs via promoter methylation as shown in 3 studies, but studies are limited with a small sample size. The multi-focal development of indolent lesions in HDGC provide a unique opportunity to understand genetic events that drive the transition to the invasive phenotype. To date, a few signalling pathways have been shown to facilitate the progression of HDGC, including Notch and Wnt. In in-vitro studies, the ability to inhibit Notch signalling was lost in cells transfected with mutant forms of E-cadherin, and increased Notch-1 activity correlated with apoptosis resistance. Furthermore, in patient samples, overexpression of Wnt-2 was associated with cytoplasmic and nuclear β-catenin accumulation and increased metastatic potential. As loss-of-function mutations are challenging to target therapeutically, these findings pave the way towards a synthetic lethal approach inCDH1-deficient cells with some promising results in-vitro. In future, if we could better understand the molecular vulnerabilities in HDGC, there may be opportunities to offer alternative treatment pathways to avoid gastrectomy.
The transformations of cellulose after concentrated sulfuric acid treatment and its impact on the enzymatic saccharification
Authors: Wu Shengbo , Shi Suan , Liu Ruotong , Wang Chun , Li Jing , Han Lujia
Published: March 2023

Background

The dense structure of cellulose lowers its reactivity and hinders its applications. Concentrated sulfuric acid is an ideal solvent to dissolve cellulose and thus has been used widely to treat cellulose. However, the changes of cellulose after reaction with concentrated sulfuric acid at near-limit S/L ratio and its effect on enzymatic saccharification still need further investigation.

Results

In this study, the interactions between cellulose (Avicel) and 72% sulfuric acid at very low acid loading conditions of 1:2 to 1:3 (S/L ratio) were studied for the enhanced production of glucose. The Avicel gradually transformed from cellulose I structure to cellulose II structure during the sulfuric acid treatment. Other physicochemical characteristics of Avicel also changed dramatically, such as the degree of polymerization, particle size, crystallinity index, and surface morphology. After acid treatment, both the yield and productivity of glucose from cellulose increased significantly under a very low enzyme loading of 5 FPU/g-cellulose. The glucose yields for raw cellulose and acid-treated (30 min) were 57% and 85%, respectively.

Conclusion

Low loadings of concentrated sulfuric acid were proven to be effective to break the recalcitrance of cellulose for enzymatic saccharification. A positive correlation between cellulose CrI and glucose yield was found for concentrated sulfuric acid-treated cellulose, which was opposite to previous reports. Cellulose II content was found to be an important factor that affects the conversion of cellulose to glucose.
Clinical advances in epigenetic therapies for lymphoma
Authors: Rosenthal Allison C. , Munoz Javier L. , Villasboas J. C.
Published: March 2023

Background

Advances in understanding of cancer biology, genomics, epigenomics, and immunology have resulted in development of several therapeutic options that expand cancer care beyond traditional chemotherapy or radiotherapy, including individualized treatment strategies, novel treatments based on monotherapies or combination therapy to reduce toxicities, and implementation of strategies for overcoming resistance to anticancer therapy.

Results

This review covers the latest applications of epigenetic therapies for treatment of B cell, T cell, and Hodgkin lymphomas, highlighting key clinical trial results with monotherapies and combination therapies from the main classes of epigenetic therapies, including inhibitors of DNA methyltransferases, protein arginine methyltransferases, enhancer of zeste homolog 2, histone deacetylases, and the bromodomain and extraterminal domain.

Conclusion

Epigenetic therapies are emerging as an attractive add-on to traditional chemotherapy and immunotherapy regimens. New classes of epigenetic therapies promise low toxicity and may work synergistically with other cancer treatments to overcome drug resistance mechanisms.

Graphical Abstract
Chylothorax due to thrombosis of the jugular and subclavian veins in a patient with gastric cancer: a case report
Authors: Ünal M. , Ünal E. , Imholz A. L. T.
Published: March 2023

Background

Chylothorax is a rare condition due to leakage of chyle in the thoracic cavity. When large amounts of chyle leak into the thoracic cavity, it can lead to severe respiratory, immune, and metabolic complications. Chylothorax has many potential underlying etiologies, and the most common causes are traumatic chylothorax and lymphoma. Venous thrombosis of the upper extremities is a rare cause of a chylothorax.

Case presentation

A 62-year-old Dutch man with a medical history of gastric cancer, treated with neoadjuvant chemotherapy and surgery 13 months prior, presented with dyspnea and a swollen left arm. Computed tomography thorax showed bilateral pleural effusion that was more prominent on the left side. The computed tomography scan further revealed thrombosis of the left jugular and subclavian veins and osseal masses suggesting cancer metastasis. Thoracentesis was performed to confirm the suspicion of gastric cancer metastasis. The obtained fluid was milky with a high level of triglycerides, but contained no malignant cells; hence, the diagnosis of the pleural effusion was chylothorax. Treatment with anticoagulation and a medium-chain-triglycerides diet was started. Furthermore, bone metastasis was confirmed with a bone biopsy.

Conclusion

Our case report demonstrates chylothorax as a rare cause of dyspnea in a patient with pleural effusion and a history of cancer. Therefore, this diagnosis should be considered in all patients with a history of cancer with new-onset pleural effusion and thrombosis of the upper extremities or clavicular/mediastinal lymphadenopathy.
Nanomedicine for autophagy modulation in cancer therapy: a clinical perspective
Authors: López-Méndez Tania B. , Sánchez-Álvarez Miguel , Trionfetti Flavia , Pedraz José L. , Tripodi Marco , Cordani Marco , Strippoli Raffaele , González-Valdivieso Juan
Published: March 2023

In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances in biomaterials tailored for drug delivery have the potential to overcome the limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal in determining cell fate and adaptation to different challenges, and despite the fact that it is frequently dysregulated in cancer, antitumor therapeutic strategies leveraging on or targeting this process are scarce. This is due to many reasons, including the very contextual effects of autophagy in cancer, low bioavailability and non-targeted delivery of existing autophagy modulatory compounds. Conjugating the versatile characteristics of nanoparticles with autophagy modulators may render these drugs safer and more effective for cancer treatment. Here, we review current standing questions on the biology of autophagy in tumor progression, and precursory studies and the state-of-the-art in harnessing nanomaterials science to enhance the specificity and therapeutic potential of autophagy modulators.
A fine-grained task scheduling mechanism for digital economy services based on intelligent edge and cloud computing
Authors: Zhang Xiaoming
Published: March 2023

Digital economy is regarded countries as an inevitable choice to promote economic growth and provides new opportunities and new paths for the high-quality development of economy. For the Chinese market, the strong base behind cloud computing is the unstoppable development trend of the digital economy. In digital economy, the cloud as infrastructure becomes the base of the pyramid to build the digital economy. To relieve the pressure on the servers of the digital economy and develop a reasonable scheduling scheme, this paper proposes a fine-grained task scheduling method for cloud and edge computing based on a hybrid ant colony optimization algorithm. The edge computing task scheduling problem is described, and assumptions are set to simplify the difficulty of a scheduling solution. The multi-objective function is solved by using a hybrid ant colony optimization algorithm which solves computational problems by finding the optimal solution with the help of graphs. Ant colony optimization algorithm is easy to use and effective in scheduling problems. The proposed scheduling model includes an end-device layer and an edge layer. A terminal device layer consists of devices used by the clients that may generate computationally intensive tasks and are sometime uncapable to complete the tasks. The proposed scheduling policy migrates these tasks to a suitable place where they can be completed while meeting the latency requirements. The CPUs of the idle users on the end-device layer are used for other CPU-overloaded terminals. The simulation results, in terms of energy consumptions, and task scheduling delays, show that the task scheduling performance is better under the application of this method and the obtained scheduling scheme is more reasonable.
Experimental community coalescence sheds light on microbial interactions in soil and restores impaired functions
Authors: Huet Sarah , Romdhane Sana , Breuil Marie-Christine , Bru David , Mounier Arnaud , Spor Ayme , Philippot Laurent
Published: March 2023

Background

Microbes typically live in communities where individuals can interact with each other in numerous ways. However, knowledge on the importance of these interactions is limited and derives mainly from studies using a limited number of species grown in coculture. Here, we manipulated soil microbial communities to assess the contribution of interactions between microorganisms for assembly of the soil microbiome.

Results

By combining experimental removal (taxa depletion in the community) and coalescence (mixing of manipulated and control communities) approaches, we demonstrated that interactions between microorganisms can play a key role in determining their fitness during soil recolonization. The coalescence approach not only revealed the importance of density-dependent interactions in microbial community assembly but also allowed to restore partly or fully community diversity and soil functions. Microbial community manipulation resulted in shifts in both inorganic nitrogen pools and soil pH, which were related to the proportion of ammonia-oxidizing bacteria.

Conclusions

Our work provides new insights into the understanding of the importance of microbial interactions in soil. Our top-down approach combining removal and coalescence manipulation also allowed linking community structure and ecosystem functions. Furthermore, these results highlight the potential of manipulating microbial communities for the restoration of soil ecosystems.
The classification study of Xowun patterns and their naming of Qajar houses in Dezful
Authors: Sarrafzadeh Ahmad , Didehban Mohammad , Vasigh Behzad
Published: March 2023

Purpose

Motifs are influenced beliefs and how individuals interact with architectural features. Additionally, decorations have been emphasized as a critical component of traditional architecture. The studying architecture in Dezful, which incorporates Xowun decorations and its historical context, motivates this study. The motifs are influenced by ideas derived from Dezful's traditional society's worldview. Therefore, in addition to documenting patterns, the study of these factors affecting the formation can be considered as research objectives.

Methodology

The present study is a method for studying patterns and name of Xowun decoration. In this method, the name and pattern of the designs are matched and the factors affecting them are explained. Finally, a conclusion is made based on logical inference and research findings.

Results

The research findings describe the hidden ideas within each of the decorative groups of Xowun decoration and represent a distinct architecture level within a valuable historical context. Furthermore, the research evidence includes a comparison of the naming and patterns associated with Xowun decoration.

Conclusion

The study's findings indicated that society's attitudes toward Xowun decorations influence the decoration names. Therefore, Xowun decoration can be classified into Geometric pattern, Animal-related pattern, Pattern related to plants and nature, Belief and religious model, pattern of combined geometries, Pattern influenced by construction technique. Additionally, most motifs in Xowun decorations are related to plant patterns (40.65%), while the lowest percentage is related to animal patterns (4.87%).
Coelomocytes of the Oligochaeta earthworm Lumbricus terrestris (Linnaeus, 1758) as evolutionary key of defense: a morphological study
Authors: Alesci Alessio , Capillo Gioele , Fumia Angelo , Albano Marco , Messina Emmanuele , Spanò Nunziacarla , Pergolizzi Simona , Lauriano Eugenia Rita
Published: March 2023

Metazoans have several mechanisms of internal defense for their survival. The internal defense system evolved alongside the organisms. Annelidae have circulating coelomocytes that perform functions comparable to the phagocytic immune cells of vertebrates. Several studies have shown that these cells are involved in phagocytosis, opsonization, and pathogen recognition processes. Like vertebrate macrophages, these circulating cells that permeate organs from the coelomic cavity capture or encapsulate pathogens, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, they produce a range of bioactive proteins involved in immune response and perform detoxification functions through their lysosomal system. Coelomocytes can also participate in lithic reactions against target cells and the release of antimicrobial peptides. Our study immunohistochemically identify coelomocytes of Lumbricus terrestris scattered in the epidermal and the connective layer below, both in the longitudinal and in the smooth muscle layer, immunoreactive for TLR2, CD14 and α-Tubulin for the first time. TLR2 and CD14 are not fully colocalized with each other, suggesting that these coelomocytes may belong to two distinct families. The expression of these immune molecules on Annelidae coelomocytes confirms their crucial role in the internal defense system of these Oligochaeta protostomes, suggesting a phylogenetic conservation of these receptors. These data could provide further insights into the understanding of the internal defense system of the Annelida and of the complex mechanisms of the immune system in vertebrates.
Anticancer properties of cannabidiol and Δ9-tetrahydrocannabinol and synergistic effects with gemcitabine and cisplatin in bladder cancer cell lines
Authors: Whynot Erin G. , Tomko Andrea M. , Dupré Denis J.
Published: March 2023

Introduction

With the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and Δ9-tetrahydrocannabinol, with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, can produce desirable synergistic effects. We also evaluated if co-treatment with different cannabinoids resulted in synergistic effects.

Methods

We generated concentration curves with several drugs, including several cannabinoids, to identify the range at which they could exert anti-tumor effects in bladder cancer cell lines. We tested the cytotoxic effects of gemcitabine (up to 100 nM), cisplatin (up to 100 μM), and cannabinoids (up to 10 μM) in T24 and TCCSUP cells. We also evaluated the activation of the apoptotic cascade and whether cannabinoids have the ability to reduce invasion in T24 cells.

Results

Cannabidiol, Δ9-tetrahydrocannabinol, cannabichromene, and cannabivarin reduce cell viability of bladder cancer cell lines, and their combination with gemcitabine or cisplatin may induce differential responses, from antagonistic to additive and synergistic effects, depending on the concentrations used. Cannabidiol and Δ9-tetrahydrocannabinol were also shown to induce apoptosis via caspase-3 cleavage and reduce invasion in a Matrigel assay. Cannabidiol and Δ9-tetrahydrocannabinol also display synergistic properties with other cannabinoids like cannabichromene or cannabivarin, although individual cannabinoids may be sufficient to reduce cell viability of bladder cancer cell lines.

Discussion

Our results indicate that cannabinoids can reduce human bladder transitional cell carcinoma cell viability, and that they can potentially exert synergistic effects when combined with other agents. Our in vitro results will form the basis for future studies in vivo and in clinical trials for the development of new therapies that could be beneficial for the treatment of bladder cancer in the future.
Cannabidiol improves haloperidol-induced motor dysfunction in zebrafish: a comparative study with a dopamine activating drug
Authors: Hasumi Akihiro , Maeda Hideyuki
Published: March 2023

Background

Cannabidiol (CBD) extracted from the cannabis plant is believed to have a medicinal value due to its neuroprotective effect via anti-inflammatory and antioxidant action. Recent behavioral studies in rats have reported that CBD mediates serotonin (5-HT1A) receptor action to improve motor dysfunction induced by dopamine (D2) receptor blockade. In particular, its effect on D2 receptor blockade in the striatum is an important function associated with neurological disorders resulting from various extrapyramidal motor dysfunctions. Dopaminergic neurodegeneration associated with this site is known for inducing Parkinson’s disease (PD), which often affects the elderly. It is also known to cause drug-induced Parkinsonism. This study examines the ameliorating effect of CBD, which does not act directly on D2 receptors, against drug-induced motor dysfunction induced by the antipsychotic drug (haloperidol).

Methods

We created a drug-induced Parkinsonism model in zebrafish larvae using an antipsychotic drug (haloperidol). We evaluated the distance traveled and repetitive light-stimulation response. Furthermore, we examined whether administration of several concentrations of CBD ameliorates symptoms of the Parkinsonism model and compared its effects with those of antiparkinsonian drug ropinirole.

Results

CBD concentrations equal to half of haloperidol’s resulted in an almost complete reversal of haloperidol-induced motor dysfunction, as measured by the distance traveled by the zebrafish and their response to light-stimulus. While ropinirole also significantly reversed haloperidol’s effects at the same concentration as CBD, CBD was more effective than ropinirole.

Conclusions

CBD-induced motor dysfunction improvement via D2 receptor blockade is a potential novel mechanism for the treatment of haloperidol-induced motor dysfunction.
Camel milk products: innovations, limitations and opportunities
Authors: Seifu Eyassu
Published: March 2023

Camel milk is the mainstay for millions of people in arid and semi-arid environments. In these areas, it is mainly consumed raw or after it spontaneously turns sour. Although some attempts have been made to produce dairy products from camel milk, processing of camel milk is generally considered to be difficult and the quality of the final products made from camel milk do not correspond to their bovine milk counterparts. This paper reports a comprehensive analysis of the literature on camel milk products and presents synthesis of the latest developments, limitations pertaining processing and opportunities for development of new and improved camel milk products. The protein composition and colloidal structure of camel milk differs from cow milk. It is characterized by absence of β-lactoglobulin, low κ-casein content, high proportion of β-casein, larger casein micelles and smaller fat globules. These differences lead to the difficulty of making dairy products from camel milk using the same technologies as for bovine milk. Some of the challenges of camel milk processing include poor stability of the milk during UHT treatment, impaired rennetability, formation of weak and fragile curd during coagulation, longer fermentation time, and low thermal stability of the milk during drying. Despite these difficulties, it has now become possible to produce a range of commercial and traditional dairy products from camel milk. Some of the strategies that could be applied to improve the quality and characteristics of camel milk products are discussed.

Graphical Abstract
Lean Body Mass in Boys With Prader-Willi Syndrome Increases Normally During Spontaneous and Induced Puberty
Authors: Noordam Cees , Stephan Anika , Eiholzer Urs
Published: March 2023

Context

Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, and hypothalamic dysfunction combined with specific dysmorphisms. In PWS, growth hormone treatment is given primarily to improve body composition, yet lean body mass (LBM) does not normalize. Male hypogonadism is frequent in PWS and becomes evident during puberty. While LBM increases in normal boys during puberty, it is not known whether LBM and muscle mass concomitantly increase in PWS during spontaneous or induced puberty.

Objective

To describe the peripubertal increment in muscle mass in boys with PWS undergoing growth hormone treatment.

Design

Single-center, retrospective descriptive study, using data from 4 years before until 4 years after onset of puberty.

Setting

Primary referral centre for PWS.

Patients

Thirteen boys diagnosed with genetically proven PWS. The mean age at onset of puberty was 12.3 years; the mean observation period before (after) onset of puberty was 2.9 (3.1) years.

Intervention

Puberty was induced upon pubertal arrest. All boys received internationally standardized growth hormone treatment.

Main Outcome Measure

Lean mass index (LMI) determined by dual energy X-ray absorptiometry.

Results

LMI increased by 0.28 kg/m2 per year before puberty and by 0.74 kg/m2 per year after the onset of puberty. The time before puberty explained less than 10% of the variation in LMI, whereas the time after puberty onset explained about 25%.

Conclusion

Boys with PWS showed a recognizable increment in LMI during both spontaneous and induced puberty compared with the prepubertal phase, which was within the trajectories of normal boys. Therefore, timely testosterone substitution in the absence or at arrest of puberty during growth hormone treatment is important to optimize peak LBM in PWS.
Association of Gestational Diabetes With the Dynamic Changes of Gut Microbiota in Offspring From 1 to 6 Months of Age
Authors: Song Qiying , Zhou Tao , Chen Shaoyun , Liao Ying , Huang Hongli , Xiao Bin , Zhang Jian V , Ma Liya , Zhu Yuanfang
Published: March 2023

Aims

The present study aimed to prospectively evaluate the influence of gestational diabetes mellitus (GDM) on the gut microbiota in 1- and 6-month-old offspring, as well as the dynamic changes from 1 to 6 months of age.

Methods

Seventy-three mother-infant dyads (34 GDM vs 39 non-GDM) were included in this longitudinal study. Two fecal samples were collected for each included infant at home by the parents at 1 month of age (“M1 phase”) and again at 6 months of age (“M6 phase”). Gut microbiota were profiled by 16S rRNA gene sequencing.

Results

Although no significant differences were observed in diversity and composition between GDM and non-GDM groups in the M1 phase, we observed differential structures and composition in the M6 phase between the 2 groups (P < .05), with lower levels of diversity, 6 depleted and 10 enriched gut microbes among infants born to GDM mothers. The dynamic changes in alpha diversity from the M1 to M6 phase were also significantly different according to GDM status (P < .05). Moreover, we found that the altered gut bacteria in the GDM group were correlated with infants’ growth.

Conclusion

Maternal GDM was associated not only with the community structure and composition in the gut microbiota of offspring at a specific time point, but also with the differential changes from birth to infancy. Altered colonization of the GDM infants’ gut microbiota might affect their growth. Our findings underscore the critical impact of GDM on the formation of early-life gut microbiota and on the growth and development of infants.
DIS3 Variants are Associated With Primary Ovarian Insufficiency: Importance of Transcription/Translation in Oogenesis
Authors: Johnstone Erica Boiman , Gorsi Bushra , Coelho Emily , Moore Barry , Farr Ashley M , Cooper Amber R , Mardis Elaine R , Rajkovic Aleksander , Chow Clement Y , Yandell Mark , Welt Corrine K
Published: March 2023

Context

A genetic etiology accounts for the majority of unexplained primary ovarian insufficiency (POI).

Objective

We hypothesized a genetic cause of POI for a sister pair with primary amenorrhea.

Design

The study was an observational study. Subjects were recruited at an academic institution.

Subjects

Subjects were sisters with primary amenorrhea caused by POI and their parents. Additional subjects included women with POI analyzed previously (n = 291). Controls were recruited for health in old age or were from the 1000 Genomes Project (total n = 233).

Intervention

We performed whole exome sequencing, and data were analyzed using the Pedigree Variant Annotation, Analysis and Search Tool, which identifies genes harboring pathogenic variants in families. We performed functional studies in a Drosophila melanogaster model.

Main Outcome

Genes with rare pathogenic variants were identified.

Results

The sisters carried compound heterozygous variants in DIS3. The sisters did not carry additional rare variants that were absent in publicly available datasets. DIS3 knockdown in the ovary of D. melanogaster resulted in lack of oocyte production and severe infertility.

Conclusions

Compound heterozygous variants in highly conserved amino acids in DIS3 and failure of oocyte production in a functional model suggest that mutations in DIS3 cause POI. DIS3 is a 3′ to 5′ exoribonuclease that is the catalytic subunit of the exosome involved in RNA degradation and metabolism in the nucleus. The findings provide further evidence that mutations in genes important for transcription and translation are associated with POI.
miRNAs in the Beta Cell—Friends or Foes?
Authors: Karagiannopoulos Alexandros , Cowan Elaine , Eliasson Lena
Published: March 2023

Type 2 diabetes (T2D) develops due to insulin resistance and an inability of the pancreatic β-cells to increase secretion of insulin and reduce elevated blood glucose levels. Diminished β-cell function and mass have been implicated in impaired β-cell secretory capacity and several microRNAs (miRNAs) have been reported to be involved in regulating β-cell processes. We believe miRNAs are nodes in important miRNA-mRNA networks regulating β-cell function and that miRNAs therefore can be targets for the treatment of T2D. MicroRNAs are short (≈19-23 nucleotides [nt]) endogenous noncoding RNAs which regulate gene expression by directly binding to the mRNA of their target genes. Under normal circumstances, miRNAs act as rheostats to keep expression of their gene targets at optimal levels for different β-cell outputs. In T2D, levels of some miRNAs are altered as part of the compensatory mechanism to improve insulin secretion. Other miRNAs are differentially expressed as part of the process of T2D pathogenesis, which results in reduced insulin secretion and increased blood glucose. In this review, we present recent findings concerning miRNAs in islets and in insulin-secreting cells, and their differential expression in diabetes, with a specific focus on miRNAs involved in β-cell apoptosis/proliferation and glucose-stimulated insulin secretion. We present thoughts around miRNA-mRNA networks and miRNAs as both therapeutic targets to improve insulin secretion and as circulating biomarkers of diabetes. Overall, we hope to convince you that miRNAs in β-cells are essential for regulating β-cell function and can in the future be of clinical use in the treatment and/or prevention of diabetes.
Late-Onset Isolated Growth Hormone Deficiency
Authors: Samuels Julie G , Chimatapu Sri Nikhita , Savage Martin O , Rapaport Robert
Published: March 2023

Two male patients, who presented at 13.5 and 13.9 years of age with growth failure and short stature, were ultimately diagnosed with isolated growth hormone deficiency (GHD). Patient 1 was first evaluated when his height declined from −0.67 SD to −1.3 SD. He had a peak growth hormone (GH) concentration to GH stimulation test (GHST) of 16.9 ng/mL (16.9 μg/L) and remained untreated. As puberty advanced, his height decreased further to −1.65 SD. A second GHST while his serum testosterone was 79 ng/dL (2.74 nmol/L) had a peak GH of 5.4 ng/mL (5.4 μg/L), consistent with GHD. He was treated with GH for 4.8 years and reached adult height of 180.5 cm (0.57 SD), gaining 2.22 SDS. Patient 2, height −2.63 SD, had an unstimulated peak GH concentration of 19 ng/mL (19 μg/L). As puberty advanced, his height decreased further to −2.96 SD. Repeat peak GH concentration was 9.2 ng/mL (9.2 μg/L) when serum testosterone was 83.9 ng/dL (2.91 nmol/L). GH treatment resulted in rapid increase of height velocity from 1.8 cm/year to 11.3 cm/year in 6 months, consistent with GHD. Both patients demonstrate that GHD may develop over time and cannot be excluded by a single GHST. Longitudinal monitoring of children with poor growth as puberty progresses is essential to uncover GHD.
Formal health care costs among older people in Ireland: methods and estimates using The Irish Longitudinal Study on Ageing (TILDA)
Authors: May Peter , Moriarty Frank , Hurley Eimir , Matthews Soraya , Nolan Anne , Ward Mark , Johnston Bridget , Roe Lorna , Normand Charles , Kenny Rose Anne , Smith Samantha
Published: March 2023

Background:Reliable data on health care costs in Ireland are essential to support planning and evaluation of services. New unit costs and high-quality utilisation data offer the opportunity to estimate individual-level costs for research and policy.

Methods:Our main dataset was The Irish Longitudinal Study on Ageing (TILDA). We used participant interviews with those aged 55+ years in Wave 5 (2018) and all available end-of-life interviews (EOLI) to February 2020. We weighted observations by age, sex and last year of life at the population level. We estimated total formal health care costs by combining reported usage in TILDA with unit costs (non-acute care) and public payer reimbursement data (acute hospital admissions, medications). All costs were adjusted for inflation to 2022, the year of analysis. We examined distribution of estimates across the population, and the composition of costs across categories of care, using descriptive statistics. We identified factors associated with total costs using generalised linear models.

Results:There were 5,105 Wave 5 observations, equivalent at the population level to 1,207,660 people aged 55+ years and not in the last year of life, and 763 EOLI observations, equivalent to 28,466 people aged 55+ years in the last year of life. Mean formal health care costs in the weighted sample were EUR 8,053; EUR 6,624 not in the last year of life and EUR 68,654 in the last year of life. Overall, 90% of health care costs were accounted for by 20% of users. Multiple functional limitations and proximity to death were the largest predictors of costs. Other factors that were associated with outcome included educational attainment, entitlements to subsidised care and serious chronic diseases.

Conclusions:Understanding the patterns of costs, and the factors associated with very high costs for some individuals, can inform efforts to improve patient experiences and optimise resource allocation.
Paving the Way for Climate Neutral and Resilient Historic Districts
Authors: Egusquiza Aitziber , Lückerath Daniel , Zorita Saioa , Silverton Sophia , Garcia Gemma , Servera Emilio , Bonazza Alessandra , Garcia Igone , Kalis Antonis
Published: March 2023

Climate change is a major global threat to our society’s urban areas, with the majority of Europe's population living in cities and their cultural heritage. Historic districts of significant cultural value and the communities connected to these places have an important role to play in fostering location-based identity and economy, social cohesion, innovation, urban regeneration, and climate change adaptation. Thus, it is important to make historic districts climate resilient, by jointly considering climate change adaptation, disaster risk management, heritage management, and sustainable urban development. However, this is often a major challenge for local and regional administrators and relevant stakeholders.

This paper constitutes the first major result of the EU R&I Task Force for Climate Neutral and Resilient Historic Urban Districts. It provides an overview of the challenges faced by practitioners and researchers when jointly addressing the needs of resilient historic districts and provides an initial set of recommendations produced by the task force to address these challenges.

These challenges cover different issues around five topics (i) data availability, use and its management, (ii) the common responsibility fragmentation in policy and governance, (iii) the challenge on integrating local knowledge and traditions in resilience building, (iv) the difficulties around the co-ownership and co-production in governance and (v) the importance of mainstreaming heritage management in adaptation and resilience policies.
The Application of Guanidinium to Improve Biomolecule Quality in Fixed, Paraffin-embedded Tissue
Authors: Chung Joon-Yong , Kim Kyungeun , Ylaya Kris , Walker-Bawa Katharine E. , Perry Candice , Star Robert A. , Hewitt Stephen M.
Published: March 2023

Neutral buffered formalin (NBF) is the most common fixative in clinical applications. However, NBF damages proteins and nucleic acids, limiting the quality of proteomic and nucleic acid-based assays. Prior studies have demonstrated that BE70, a fixative of buffered 70% ethanol, has many benefits over NBF but the degradation of proteins and nucleic acids in archival paraffin blocks remain a challenge. Thus, we evaluated the addition of guanidinium salts to BE70 with the hypothesis that this may protect RNA and protein. Guanidinium salt supplemented BE70 (BE70G)-fixed tissue is comparable with that of BE70 via histology and immunohistochemistry. Western blot analysis also revealed that HSP70, AKT, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression signals in BE70G-fixed tissue were higher than those in BE70-fixed tissue. The quality of nucleic acids extracted from BE70G-fixed, paraffin-embedded tissue was also superior, and BE70G provides improved protein and RNA quality at shorter fixation times than its predecessors. The degradation of proteins, AKT and GAPDH, in archival tissue blocks is also decreased with the addition of guanidinium salt to BE70. In conclusion, BE70G fixative improves the quality of molecular analysis with more rapid fixation of tissue and enhanced long-term storage of paraffin blocks at room temperature for evaluation of protein epitopes:
Kandungan Total Fenolik dan Nilai Sun Protection Factor Ekstrak Sargassum sp.
Authors: Dharmawan Dimas , Putriana Norisca Aliza , Anggraeni Santi R.
Published: March 2023

Seaweed or macroalgae is one of the natural products with biological activities such as antioxidant, antibacterial, and immunostimulant. One of them is the brown alga Sargassum sp. This brown alga produces secondary metabolites such as flavonoids and their derivatives as well as polyphenols. These compounds have many roles in counteracting ultraviolet radiation and have the potential to be developed as active ingredients of sunscreen. This study aimed to determine the total phenolic content and the Sun Protection Factor (SPF) value of Sargassum sp. originating from Pameungpeuk beach, Garut Regency. The SPF value is used to categorize how efficiently a material prevents exposure to ultraviolet radiation. Total phenolic content was measured using Follin Ciocalteu reagent with gallic acid standard. The Sargassum sp extract sample contained total phenolic of 149,04±5,14 mg GAE/g. The SPF value of Sargassum sp extract was calculated using the Mansur equation at a wavelength of 290-320 nm. The obtained SPF value of extract was 33,2±3,11 which equals to oxybenzone. The value indicated an ultra-protection capability and the potency of extract for further development as UV filter.   Rumput laut atau makroalga merupakan salah satu bahan alam dengan aktivitas biologis seperti antioksidan, aktivitas antibakteri dan imunostimulan. Salah satunya adalah alga cokelat  jenis Sargassum sp. Alga cokelat ini menghasilkan metabolit sekunder seperti  flavanoid  dan turunannya serta polifenol dan turunannya. Senyawa-senyawa tersebut banyak berperan dalam menangkal radiasi ultraviolet dan berpotensi dikembangkan sebagai bahan aktif tabir surya. Penelitian ini bertujuan untuk mengetahui kandungan total fenolik dan nilai Sun Protection Factor (SPF) dari Sargassum sp yang berasal dari pantai Pameungpeuk, Kabupaten Garut. Kandungan total fenolik diukur dengan menggunakan reagen Follin Ciocalteu dan menggunakan standar baku asam galat. Sampel ekstrak Sargassum sp mengandung total fenolik sebesar 149,04±5,14 mg GAE/g. Nilai SPF digunakan untuk mengkategorikan seberapa efisien sebuah bahan dalam menangkal paparan radiasi sinar ultraviolet. Nilai SPF ekstrak Sargassum sp dihitung menggunakan menggunakan persamaan Mansur pada panjang gelombang 290-320 nm. Nilai SPF yang didapatkan yaitu 33,2±3,11 yang tergolong ke dalam kategori ultra.
Comparison of Satellite-Derived Bathymetry Algorithm Accuracy Using Sentinel-2 Multispectral Satellite Image
Authors: Prasetya Muhammad Iqra , Siregar Vincentius Paulus , Agus Syamsul Bahri
Published: March 2023

The utilization of satellite image data and image data processing techniques has become an efficient alternative to obtain bathymetric data in a broad and complicated area. This study aimed to determine the algorithm's performance in the waters of Lambasina Island. Atmospheric and radiometric correction using the Dark Object Subtraction (DOS) method for initial processing of Sentinel-2 images. The multispectral channel used, namely the blue, green, and red bands, was tested by regression using field observation data. The algorithms used to estimate bathymetry include Lyzenga, Stumpf, and Support Vector Machine (SVM). The test results of the three algorithms showed that the support vector machine algorithm was the best algorithm for estimating bathymetry after the Stumpf and Lyzenga algorithms. The correlation results of the SVM algorithm in the waters of the small Lambasina island got a correlation coefficient of determination R2 = 0.81 and the large Lambasina waters area R2 = 0.82. The second-best algorithm was Stumpf, with a correlation coefficient of determination of R2 = 0.79 in the waters of the small Lambasina island and R2 = 0.80 in the waters of the large Lambasina island. Lyzenga's algorithm got the correlation coefficient of determination R2 = 0.78 on small Lambasina Islands and large Lambasina Islands with a determination correlation coefficient value of R2 = 0.79.
Translocation of tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses towards improvement of gamma-ray attenuation features in high-density glass shields
Authors: ALMisned Ghada , Rabaa Elaf , Sen Baykal Duygu , Ilik Erkan , Kilic Gokhan , Zakaly Hesham M. H. , Ene Antoaneta , Tekin Huseyin Ozan
Published: March 2023

This study investigates the effect of substituting tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses whose densities varies from 5.0879 to 5.3246 g/cm3 on gamma-ray absorption properties. A range of fundamental absorption parameters, including attenuation coefficients, half-value layer thicknesses, effective atom and electron numbers, effective conductivity, exposure, and energy absorption buildup factors, were studied for five different glass samples with varying substitution ratios. The ratio of tungsten(vi) oxide to gadolinium(iii) fluoride varied between 0 and 20 mol%, as well as the TeO2 ratio in the composition was maintained between 90 and 80 mol%. The sample with the composition of 80–20 mol% TeO2/WO3, which attained the maximum density value with 20 mol% WO3 addition, showed the highest gamma-absorption capabilities based on the obtained findings in the range of 0.015–15 MeV. In consideration of the mechanical and physical properties of WO3 in tellurite glasses, it can be concluded that WO3 incorporation is a crucial monotonic process that may be utilized to further improve the properties of glass shields.