bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis
Authors: Qi Simin , Guan Xiaoqing , Zhang Jia , Yu Dehua , Yu Xuefei , Li Qinglin , Yin Wenjuan , Cheng Xiang-Dong , Zhang Weidong , Qin Jiang-Jiang
Published: March 2022

Background

Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet.

Methods

Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR.

Results

UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models.

Conclusions

These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.
Revision surgeries for tumor endoprostheses around the knee joint: a mid-long-term follow-up of 20 cases
Authors: Zan Pengfei , Wang Hongsheng , Cai Zhengdong , Shen Jiakang , Sun Wei
Published: March 2022

Background

Tumor endoprostheses of the knee joint after limb salvage surgery is associated with high rates of complications, which has introduced great challenges to a delayed revision surgery. The aim of the study was to summarize the failures, functional outcomes and prosthetic survival in revision tumor endoprostheses of the knee joint.

Methods

The clinical data of 20 patients with malignant tumors who received prosthetic revisions after limb salvage surgery from January, 2000 until January, 2018 were retrospectively reviewed. The cohort was constituted of 11 male and 9 female patients with a mean age of 34.1 years (range, 16 to 66 years). Infection cases received two-stage revisions after removing prostheses initially, while all other cases received one-stage revisions. Revision reasons and complications were well documented and analyzed.

Results

All patients received complete follow-up with a mean time of 64.7 months (range, 27 to 155 months). A total of 6 (6/20, 30.0%) patients experienced a second complication after revision surgery, of whom, one patient with deep infection experienced repeated infections after prosthetic revision and received amputation surgery; one patient revised of prosthetic fracture experienced an infection and received a second-stage infection revision; one case revised of prosthetic loosening had deep infection receiving anti-infective therapy with prostheses still in position; one case having wound complication healed after receiving two times of debridement surgery; one MBGCT patient experienced a second aseptic loosening 6 years after the initial loosening thus undergoing a second revision; a recurrent osteosarcoma patient died of pulmonary metastasis 3 years after revision surgery. Kaplan-Meier survival curve indicated a 5-year survival rate of initial prostheses was 75%. The Musculoskeletal Tumor Society (MSTS-93) score [20.9 (range, 15 to 27 scores)] at 1 year after revision surgeries was significantly improved (p < 0.001) when compared with the score [17.2 (range, 13 to 21 scores)] before revisions.

Conclusion

Prosthetic mechanical problems, aseptic loosening and infections were primary reasons for revisions after tumor endoprostheses of the knee joint. Although revision surgeries were complicated while still associated with high risk of failure, which remains the remedy strategy for limb salvage and functional recovery in those patients.
RUNX3-mediated circDYRK1A inhibits glutamine metabolism in gastric cancer by up-regulating microRNA-889-3p-dependent FBXO4
Authors: Liu Haofeng , Xue Qiu , Cai Hongzhou , Jiang Xiaohui , Cao Guangxin , Chen Tie , Chen Yuan , Wang Ding
Published: March 2022

Background

Targeting glutamine metabolism is previously indicated as a potential and attractive strategy for gastric cancer (GC) therapy. However, the underlying mechanisms responsible for the modification of glutamine metabolism in GC cells have not been fully elucidated. Accordingly, the current study sought to investigate the physiological mechanisms of RUNX3-mediated circDYRK1A in glutamine metabolism of GC.

Methods

Firstly, GC tissues and adjacent normal tissues were obtained from 50 GC patients to determine circDYRK1A expression in GC tissues. Next, the binding affinity among RUNX3, circDYRK1A, miR-889-3p, and FBXO4 was detected to clarify the mechanistic basis. Moreover, GC cells were subjected to ectopic expression and knockdown manipulations of circDYRK1A, miR-889-3p, and/or FBXO4 to assay GC cell malignant phenotypes, levels of glutamine, glutamic acid, and α-KG in cell supernatant and glutamine metabolism-related proteins (GLS and GDH). Finally, nude mice were xenografted with GC cells to explore the in vivo effects of circDYRK1A on the tumorigenicity and apoptosis.

Results

circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC.

Conclusion

In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.
“The DEA would come in and destroy you”: a qualitative study of fear and unintended consequences among opioid prescribers in WV
Authors: Sedney Cara L. , Haggerty Treah , Dekeseredy Patricia , Nwafor Divine , Caretta Martina Angela , Brownstein Henry H. , Pollini Robin A.
Published: March 2022

Background

West Virginia has one of the highest rates of opioid overdose related deaths and is known as the epicenter of the opioid crisis in the United States. In an effort to reduce opioid-related harms, SB 273 was signed in 2018, and aimed to restrict opioid prescribing in West Virginia. SB 273 was enacted during a time when physician arrests and convictions had been increasing for years and were becoming more prevalent and more publicized. This study aims to better understand the impact of the legislation on patients and providers.

Methods

Twenty semi-structured interviews were conducted with opioid-prescribing primary care physicians and specialists practicing throughout West Virginia.

Results

Four themes emerged, 1. Fear of disciplinary action, 2. Exacerbation of opioid prescribing fear due to restrictive legislation, 3. Care shifts and treatment gaps, and 4. Conversion to illicit substances. The clinicians recognized the harms of inappropriate prescribing and how this could affect their patients. Decreases in opioid prescribing were already occurring prior to the law implementation. Disciplinary actions against opioid prescribers resulted in prescriber fear, which was then exacerbated by SB 273 and contributed to shifts in care that led to forced tapering and opioid under-prescribing. Providers felt that taking on patients who legitimately required opioids could jeopardize their career.

Conclusion

A holistic and patient-centered approach should be taken by legislative and disciplinary bodies to ensure patients are not abandoned when disciplinary actions are taken against prescribers or new legislation is passed.
Bittersweet: relevant amounts of the common sweet food additive, glycerol, accelerate the growth of PC3 human prostate cancer xenografts
Authors: DeGuzman Ariel , Lorenson Mary Y. , Walker Ameae M.
Published: March 2022

Objective

In a study of potential prostate cancer therapeutics, glycerol was used to increase the density of one solution. Glycerol alone was therefore one of the controls. Tumors of human PC3 castrate-resistant prostate cancer cells were initiated in male nude mice and grown for 12 days. Mice were then sorted such that mean tumor weights were the same in each group, and osmotic minipumps delivering 0.25 µL/h of either saline or glycerol were then implanted subcutaneously.

Results

Contrary to our initial assumption that glycerol would be without effect, tumors grew more rapidly in the glycerol group such that tumors were twice the size of those in the saline group after 4 weeks. Given the dose delivered, analysis of the literature suggests this effect was not via the conversion of glycerol to glucose but possibly via a reduction in oxidative damage in the growing tumor. Our data demonstrate that amounts of glycerol that could reasonably be derived from the diet promote the growth of these tumors. Given the increasing use of glycerol in foods and beverages, we present these data to stimulate interest in an epidemiological study in the human population examining glycerol consumption and the aggressiveness of prostate cancer.
Exposure to Trypanosoma parasites induces changes in the microbiome of the Chagas disease vector Rhodnius prolixus
Authors: Eberhard Fanny E. , Klimpel Sven , Guarneri Alessandra A. , Tobias Nicholas J.
Published: March 2022

Background

The causative agent of Chagas disease, Trypanosoma cruzi, and its nonpathogenic relative, Trypanosoma rangeli, are transmitted by haematophagous triatomines and undergo a crucial ontogenetic phase in the insect’s intestine. In the process, the parasites interfere with the host immune system as well as the microbiome present in the digestive tract potentially establishing an environment advantageous for development. However, the coherent interactions between host, pathogen and microbiota have not yet been elucidated in detail. We applied a metagenome shotgun sequencing approach to study the alterations in the microbiota of Rhodnius prolixus, a major vector of Chagas disease, after exposure to T. cruzi and T. rangeli focusing also on the functional capacities present in the intestinal microbiome of the insect.

Results

The intestinal microbiota of R. prolixus was dominated by the bacterial orders Enterobacterales, Corynebacteriales, Lactobacillales, Clostridiales and Chlamydiales, whereas the latter conceivably originated from the blood used for pathogen exposure. The anterior and posterior midgut samples of the exposed insects showed a reduced overall number of organisms compared to the control group. However, we also found enriched bacterial groups after exposure to T. cruzi as well as T rangeli. While the relative abundance of Enterobacterales and Corynebacteriales decreased considerably, the Lactobacillales, mainly composed of the genus Enterococcus, developed as the most abundant taxonomic group. This applies in particular to vectors challenged with T. rangeli and at early timepoints after exposure to vectors challenged with T. cruzi. Furthermore, we were able to reconstruct four metagenome-assembled genomes from the intestinal samples and elucidate their unique metabolic functionalities within the triatomine microbiome, including the genome of a recently described insect symbiont, Candidatus Symbiopectobacterium, and the secondary metabolites producing bacteria Kocuria spp.

Conclusions

Our results facilitate a deeper understanding of the processes that take place in the intestinal tract of triatomine vectors during colonisation by trypanosomal parasites and highlight the influential aspects of pathogen-microbiota interactions. In particular, the mostly unexplored metabolic capacities of the insect vector’s microbiome are clearer, underlining its role in the transmission of Chagas disease.
Dead-reckoning elucidates fine-scale habitat use by European badgers Meles meles
Authors: Magowan E. A. , Maguire I. E. , Smith S. , Redpath S. , Marks N. J. , Wilson R. P. , Menzies F. , O’Hagan M. , Scantlebury D. M.
Published: March 2022

Background

Recent developments in both hardware and software of animal-borne data loggers now enable large amounts of data to be collected on both animal movement and behaviour. In particular, the combined use of tri-axial accelerometers, tri-axial magnetometers and GPS loggers enables animal tracks to be elucidated using a procedure of ‘dead-reckoning’. Although this approach was first suggested 30 years ago by Wilson et al. (1991), surprisingly few measurements have been made in free-ranging terrestrial animals. The current study examines movements, interactions with habitat features, and home-ranges calculated from just GPS data and also from dead-reckoned data in a model terrestrial mammal, the European badger (Meles meles).

Methods

Research was undertaken in farmland in Northern Ireland. Two badgers (one male, one female) were live-trapped and fitted with a GPS logger, a tri-axial accelerometer, and a tri-axial magnetometer. Thereafter, the badgers’ movement paths over 2 weeks were elucidated using just GPS data and GPS-enabled dead-reckoned data, respectively.

Results

Badgers travelled further using data from dead-reckoned calculations than using the data from only GPS data. Whilst once-hourly GPS data could only be represented by straight-line movements between sequential points, the sub-second resolution dead-reckoned tracks were more tortuous. Although there were no differences in Minimum Convex Polygon determinations between GPS- and dead-reckoned data, Kernel Utilisation Distribution determinations of home-range size were larger using the former method. This was because dead-reckoned data more accurately described the particular parts of landscape constituting most-visited core areas, effectively narrowing the calculation of habitat use. Finally, the dead-reckoned data showed badgers spent more time near to field margins and hedges than simple GPS data would suggest.

Conclusion

Significant differences emerge when analyses of habitat use and movements are compared between calculations made using just GPS data or GPS-enabled dead-reckoned data. In particular, use of dead-reckoned data showed that animals moved 2.2 times farther, had better-defined use of the habitat (revealing clear core areas), and made more use of certain habitats (field margins, hedges). Use of dead-reckoning to provide detailed accounts of animal movement and highlight the minutiae of interactions with the environment should be considered an important technique in the ecologist’s toolkit.
Clinical translation of patient-derived tumour organoids- bottlenecks and strategies
Authors: Foo Malia Alexandra , You Mingliang , Chan Shing Leng , Sethi Gautam , Bonney Glenn K. , Yong Wei-Peng , Chow Edward Kai-Hua , Fong Eliza Li Shan , Wang Lingzhi , Goh Boon-Cher
Published: March 2022

Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting. Unsuitable methods of tissue acquisition, disparities in establishment rates and a lengthy timeline are the limiting factors for use of PDTOs in clinical application. Potential strategies to overcome this include liquid biopsies via circulating tumour cells (CTCs), an automated organoid platform and optical metabolic imaging (OMI). These proposed solutions accelerate and optimize the workflow of a clinical organoid drug screening. As such, PDTOs have the potential for potential applications in clinical oncology to improve patient outcomes. If remarkable progress is made, cancer patients can finally benefit from this revolutionary technology.
Potential mechanisms underlying sleep disturbance in young people with borderline personality disorder features: an exploratory study
Authors: Jenkins Claire A. , Thompson Katherine N. , Nicholas Christian L. , Hartmann Jessica A. , Chanen Andrew M.
Published: March 2022

Background

Sleep disturbance is common among young people (15–25 years) with features of borderline personality disorder (BPD). However, the mechanisms underlying sleep disturbance in BPD remain unknown. Understanding these underlying processes is essential to guide the development of sleep-improvement interventions and to optimise their efficacy through identifying beneficial treatment targets. This exploratory study aimed to investigate potential underlying mechanisms to inform future hypotheses, research development, and provide insight into potential treatment targets to improve sleep in young people with BPD. This study explored the indirect roles of emotion regulation difficulties, depression, anxiety and stress in the relationship between BPD features and sleep disturbance in young people.

Methods

Sleep was measured subjectively (self-report questionnaires) and objectively (10 days wrist actigraphy) in 40 young people with BPD features and 38 healthy young people. Participants also completed the Difficulties in Emotion Regulation Scale and the Depression, Anxiety and Stress Scale.

Results

Mediation analyses revealed that impulse control difficulties, limited emotion regulation strategies and anxiety indirectly affected the relationship between group (BPD vs. healthy) and subjective sleep disturbance in young people. Lack of emotional awareness and anxiety contributed to associations between group and objectively longer time in bed and bedtime variability, respectively.

Conclusions

These preliminary findings suggest that targeting emotional dysregulation (impulse control, strategies, emotional awareness) and anxiety might be beneficial for improving sleep in this population.
Genetic analysis toward more nutritious barley grains for a food secure world
Authors: Thabet Samar G. , Alomari Dalia Z. , Brinch-Pedersen Henrik , Alqudah Ahmad M.
Published: March 2022

Background

Understanding the relationships between nutrition, human health and plant food source is among the highest priorities for public health. Therefore, enhancing the minerals content such as iron (Fe), zinc (Zn) and selenium (Se) in barley (Hordeum vulgareL.) grains is an urgent need to improve the nutritive value of barley grains in overcoming malnutrition and its potential consequencing. This study aimed to expedite biofortification of barley grains by elucidating the genetic basis of Zn, Fe, and Se accumulation in the grains, which will contribute to improved barley nutritional quality.

Results

A genome-wide association study (GWAS) was conducted to detect the genetic architecture for grain Zn, Fe, and Se accumulations in 216 spring barley accessions across two years. All the accessions were genotyped by single nucleotide polymorphisms (SNPs) molecular markers. Mineral heritability values ranging from moderate to high were revealed in both environments. Remarkably, there was a high natural phenotypic variation for all micronutrient accumulation in the used population. High-LD SNP markers (222 SNPs) were detected to be associated with all micronutrients in barley grains across the two environments plus BLUEs. Three genomic regions were detected based on LD, which were identified for the most effective markers that had associations with more than one trait. The strongest SNP-trait associations were found to be physically located within genes that may be involved in grain Zn and Fe homeostasis. Two putative candidate genes were annotated as Basic helix loop helix (BHLH) family transcription factor and Squamosa promoter binding-like protein, respectively, and have been suggested as candidates for increased grain Zn, Fe, and Se accumulation.

Conclusions

These findings shed a light on the genetic basis of Zn, Fe, and Se accumulation in barley grains and have the potential to assist plant breeders in selecting accessions with high micronutrient concentrations to enhance grain quality and, ultimately human health.
Hyperchloremic metabolic acidosis due to saline absorption during laser enucleation of the prostate: a case report
Authors: Tabuchi Makiko , Morozumi Kohei , Maki Yuichi , Toyoda Daisuke , Kotake Yoshifumi
Published: March 2022

Background

Recent technological advancements have enabled the use of electrolyte solutions such as saline or buffered electrolyte solution during transurethral resection or laser enucleation of the prostate. However, saline absorption may cause hyperchloremic metabolic acidosis.

Case presentation

A male in his late seventies underwent holmium laser enucleation of the prostate under a combination of subarachnoid block and general anesthesia. Intraoperatively, abdominal distension prompted the attending anesthesiologist to consider the possibility of SGA malposition, and the trachea was intubated. Oropharyngeal and neck edema was observed, and laboratory examination revealed considerable acidosis with hyperchloremia. Further evaluation confirmed the absorption of a large amount of saline into the circulation via the perforated bladder. Application of the simplified Stewart approach clearly suggested that hyperchloremia was the principal cause of metabolic acidosis. The dilution of albumin attenuated acidosis.

Conclusions

Absorption of normal saline during laser enucleation of prostate caused hyperchloremic metabolic acidosis and airway edema.
Neuroprotective activity of Ipomoea cairica leaf extract against cadmium chloride-induced biochemical changes in the brain of male Wistar rats
Authors: Ilesanmi Omotayo B. , Odewale Temitope Temiloluwa , Avwioroko Oghenetega J. , Alqarni Mohammed , Obaidullah Ahmad J. , Atanu Francis O. , Binang Toyin , Batiha Gaber El-Saber
Published: March 2022

Background

Exposure to cadmium is implicated in the etiology of some neurodegenerative diseases. Compounds isolated from Ipomoea cairica extract are neuroprotective. However, there is no reported neuroprotective activity of the crude extract of I. cairica (ICE). We investigated the neuroprotective activity of I. cairica extract against cadmium-induced biochemical changes in the brain of male Wistar rats. Thirty-six animals were divided into four groups of 9 animals per group: group I (Control); group II (3.5 mg/kg CdCl2); group III (100 mg/kg ICE + CdCl2); and group IV (250 mg/kg ICE + CdCl2). Animals were pretreated with 100 and 250 mg/kg ICE before co-administration with cadmium chloride.

Results

CdCl2 treatment caused a significant increase in acetylcholineesterase activity, lipid peroxidation, beta-amyloid aggregation, caspase 3 and 9, p53, and glutamate concentration. In addition, CdCl2 caused a significant decrease in catalase activity, superoxide dismutase, glutathione-S-transferase, Na+/K+ ATPase, and glutamate dehydrogenase. ICE was able to reduce the neuronal damaging effect of CdCl2 by acting as an antioxidant, antiapoptotic, anticholinesterase, and antiexcitotoxicity.

Conclusions

Our findings show that Ipomoea cairica leaf can be developed and included in the natural product in the prevention of neurodegenerative diseases.
Resistomes and microbiome of meat trimmings and colon content from culled cows raised in conventional and organic production systems
Authors: Weinroth Margaret D. , Thomas Kevin M. , Doster Enrique , Vikram Amit , Schmidt John W. , Arthur Terrance M. , Wheeler Tommy L. , Parker Jennifer K. , Hanes Ayanna S. , Alekoza Najla , Wolfe Cory , Metcalf Jessica L. , Morley Paul S. , Belk Keith E.
Published: March 2022

Background

The potential to distribute bacteria resistant to antimicrobial drugs in the meat supply is a public health concern. Market cows make up a fifth of the U.S. beef produced but little is known about the entire population of bacteria (the microbiome) and entirety of all resistance genes (the resistome) that are found in this population. The objective of this study was to characterize and compare the resistomes and microbiome of beef, dairy, and organic dairy market cows at slaughter.

Methods

Fifty-four (N = 54) composite samples of both colon content and meat trimmings rinsate samples were collected over six visits to two harvest facilities from cows raised in three different production systems: conventional beef, conventional dairy, and organic dairy (n = 3 samples per visit per production system). Metagenomic DNA obtained from samples were analyzed using target-enriched sequencing (resistome) and 16S rRNA gene sequencing (microbiome).

Results

All colon content samples had at least one identifiable antimicrobial resistance gene (ARG), while 21 of the 54 meat trimmings samples harbored at least one identifiable ARGs. Tetracycline ARGs were the most abundant class in both colon content and carcass meat trimmings. The resistome found on carcass meat trimmings was not significantly different by production system (P = 0.84, R2 = 0.00) or harvest facility (P = 0.10, R2 = 0.09). However, the resistome of colon content differed (P = 0.01; R2 = 0.05) among production systems, but not among the harvest facilities (P = 0.41; R2 = 0.00). Amplicon sequencing revealed differences (P < 0.05) in microbial populations in both meat trimmings and colon content between harvest facilities but not production systems (P > 0.05).

Conclusions

These data provide a baseline characterization of an important segment of the beef industry and highlight the effect that the production system where cattle are raised and the harvest facilities where an animal is processed can impact associated microbiome and resistomes.
Functional feeds marginally alter immune expression and microbiota of Atlantic salmon (Salmo salar) gut, gill, and skin mucosa though evidence of tissue-specific signatures and host–microbe coadaptation remain
Authors: Bledsoe Jacob W. , Pietrak Michael R. , Burr Gary S. , Peterson Brian C. , Small Brian C.
Published: March 2022

Background

Mucosal surfaces of fish provide cardinal defense against environmental pathogens and toxins, yet these external mucosae are also responsible for maintaining and regulating beneficial microbiota. To better our understanding of interactions between host, diet, and microbiota in finfish and how those interactions may vary across mucosal tissue, we used an integrative approach to characterize and compare immune biomarkers and microbiota across three mucosal tissues (skin, gill, and gut) in Atlantic salmon receiving a control diet or diets supplemented with mannan-oligosaccharides, coconut oil, or both. Dietary impacts on mucosal immunity were further evaluated by experimental ectoparasitic sea lice (Lepeophtheirus salmonis) challenge.

Results

Fish grew to a final size of 646.5 g ± 35.8 during the 12-week trial, with no dietary effects on growth or sea lice resistance. Bacterial richness differed among the three tissues with the highest richness detected in the gill, followed by skin, then gut, although dietary effects on richness were only detected within skin and gill. Shannon diversity was reduced in the gut compared to skin and gill but was not influenced by diet. Microbiota communities clustered separately by tissue, with dietary impacts on phylogenetic composition only detected in the skin, although skin and gill communities showed greater overlap compared to the gut according to overall composition, differential abundance, and covariance networks. Inferred metagenomic functions revealed preliminary evidence for tissue-specific host–microbiota coadaptation, as putative microbiota functions showed ties to the physiology of each tissue. Immune gene expression profiles displayed tissue-specific signatures, yet dietary effects were also detected within each tissue and peripheral blood leukocytes. Procrustes analysis comparing sample-matched multivariate variation in microbiota composition to that of immune expression profiles indicated a highly significant correlation between datasets.

Conclusions

Diets supplemented with functional ingredients, namely mannan-oligosaccharide, coconut oil, or a both, resulted in no difference in Atlantic salmon growth or resistance to sea lice infection. However, at the molecular level, functional ingredients caused physiologically relevant changes to mucosal microbiota and host immune expression. Putative tissue-specific metagenomic functions and the high correlation between expression profiles and microbiota composition suggest host and microbiota are interdependent and coadapted in a tissue-specific manner.
Association of gene polymorphisms of ACE, AGT, and ARNT-like protein 1 with susceptibility to gestational diabetes
Authors: Ashour Esmat , Gouda Weaam , Mageed Lamiaa , Okasha Ahmed , Afify Mie , Fawzi Olfat M.
Published: March 2022

Background and aims

Gestational diabetes mellitus is well-defined as glucose intolerance first documented during pregnancy. In this study, we examined the possible associations between I/D polymorphism of the angiotensin-converting enzyme gene, the M235T variant of angiotensinogen gene, and the rs7950226 polymorphism of the ARNT-like protein-1 (BMAL1) gene and the risk for diabetes in Egyptian pregnant women.

Subjects and methods

This study recruited 160 gestational diabetes cases and 165 controls. Genomic DNA was derived from peripheral blood leukocytes and ACE gene (I/D) genotyping was performed using the method of polymerase chain reaction and the polymerase chain reaction-based restriction fragment length polymorphism was used for identifying the M235T variant of AGT gene and the rs7950226 polymorphism of the BMAL1.

Results

The II, ID, and DD genotypes of the ACE gene have significant differences in cases compared to controls (P = 0.000 and X2 = 81.77). The M235T polymorphism of the AGT gene was increased with gestational diabetes risk. Furthermore, the AA genotype of the BMAL1 rs7950226 gene was significantly related to the gestational diabetes risk (P = 0.000 and X2 = 52.82). Furthermore, the allele frequencies of the three variants have significant variances between cases and control.

Conclusion

This study suggested significant associations between ACE (DD), AGT (TT), and BMAL1 rs7950226 (AA) gene polymorphisms with gestational diabetes susceptibility and there was a possibility to identify that II + MM + GG as protective haplotypes and DD + TT + AA as risk haplotypes for gestational diabetes.
Gender-specific association of biochemical variables with depression: a population-based case-control study from North India
Authors: Chaudhary Vineet , Longkumer Imnameren , Kaur Gurjinder , Saraswathy Kallur Nava
Published: March 2022

Background

Depression is a highly prevalent mental disorder with complex aetiology. An emerging body of evidence shows that depression tends to co-occur with abnormal blood glucose levels and dyslipidaemia. This study aimed to understand the overall and gender-specific associations of abnormal glucose levels and dyslipidaemia with depression in a single Mendelian population from rural Haryana, India. To achieve the aim, a population-based case-control study, which constituted of 251 depressed (cases) and 251 non-depressed (controls) individuals, was set up. The study was conducted among the Jat community of Palwal District, Haryana (North India). Data collection was done using a pre-tested interview schedule through the household survey method. Depression status was ascertained using Beck Depression Inventory-II. Fasting blood glucose analysis and lipid profiling were done using commercial kits (Randox, USA) through spectrophotometry. Statistical analysis was done using MS-Excel 2010 and SPSS version 16.0.

Results

In the present study, overall fasting blood sugar level was not found to be associated with depression. However, high blood sugar posed a 3.6-folds elevated risk for depression among females with borderline significance (p = 0.058). Further, higher levels of TC and LDL were found to be inversely associated with depression. In the sex-wise analysis inverse association of TC and LDL with depression remained significant among males but not among females. Instead, high TG and high VLDL showed an increased risk for depression in females.

Conclusions

This study suggests gender-specific associations of some of the studied biochemical variables with depression. Longitudinal studies are warranted to explicate cause-effect relationships between the studied biochemical variables and depression.
Prognostic accuracy of visual lung damage computed tomography score for mortality prediction in patients with COVID-19 pneumonia: a systematic review and meta-analysis
Authors: Zakariaee Seyed Salman , Naderi Negar , Rezaee Danial
Published: March 2022

Background

Chest computed tomography (CT) findings provide great added value in characterizing the extent of disease and severity of pulmonary involvements. Chest CT severity score (CT-SS) could be considered as an appropriate prognostic factor for mortality prediction in patients with COVID-19 pneumonia. In this study, we performed a meta-analysis evaluating the prognostic accuracy of CT-SS for mortality prediction in patients with COVID-19 pneumonia.

Methods

A systematic search was conducted on Web of Science, PubMed, Embase, Scopus, and Google Scholar databases between December 2019 and September 2021. The meta-analysis was performed using the random-effects model, and sensitivity and specificity (with 95%CIs) of CT-SS were calculated using the study authors’ pre-specified threshold.

Results

Sensitivity estimates ranged from 0.32 to 1.00, and the pooled estimate of sensitivity was 0.67 [95%CI (0.59–0.75)]. Specificity estimates ranged from 0.53 to 0.95 and the pooled estimate of specificity was 0.79 [95%CI (0.74–0.84)]. Results of meta-regression analysis showed that radiologist experiences did not affect the sensitivity and specificity of CT-SS to predict mortality in COVID-19 patients (P = 0.314 and 0.283, respectively). The test for subgroup differences suggests that study location significantly modifies sensitivity and specificity of CT-SS to predict mortality in COVID-19 patients. The area under the summary receiver operator characteristic (ROC) curve was 0.8248.

Conclusion

Our results have shown that CT-SS has acceptable prognostic accuracy for mortality prediction in COVID-19 patients. This simple scoring method could help to improve the management of high-risk patients with COVID-19.
Core components of a Community of Practice to improve community health worker performance: a qualitative study
Authors: Hennein Rachel , Ggita Joseph M. , Turimumahoro Patricia , Ochom Emmanuel , Gupta Amanda J. , Katamba Achilles , Armstrong-Hough Mari , Davis J. Lucian
Published: March 2022

Background

Communities of Practice (CoPs) offer an accessible strategy for healthcare workers to improve the quality of care through knowledge sharing. However, not enough is known about which components of CoPs are core to facilitating behavior change. Therefore, we carried out a qualitative study to address these important gaps in the literature on CoPs and inform planning for an interventional study of CoPs.

Methods

We organized community health workers (CHWs) from two tuberculosis (TB) clinics in Kampala, Uganda, into a CoP from February to June 2018. We conducted interviews with CoP members to understand their perceptions of how the CoP influenced delivery of TB contact investigation. Using an abductive approach, we first applied inductive codes characterizing CHWs’ perceptions of how the CoP activities affected their delivery of contact investigation. We then systematically mapped these codes into their functional categories using the Behavior Change Technique (BCT) Taxonomy and the Behavior Change Wheel framework. We triangulated all interview findings with detailed field notes.

Results

All eight members of the CoP agreed to participate in the interviews. CHWs identified five CoP activities as core to improving the quality of their work: (1) individual review of feedback reports, (2) collaborative improvement meetings, (3) real-time communications among members, (4) didactic education sessions, and (5) clinic-wide staff meetings. These activities incorporated nine different BCTs and five distinct intervention functions. CHWs reported that these activities provided a venue for them to share challenges, exchange knowledge, engage in group problem solving, and benefit from social support. CHWs also explained that they felt a shared sense of ownership of the CoP, which motivated them to propose and carry out innovations. CHWs described that the CoP strengthened their social and professional identities within and outside the group, and improved their self-efficacy.

Conclusions

We identified the core components and several mechanisms through which CoPs may improve CHW performance. Future studies should evaluate the importance of these mechanisms in mediating the effects of CoPs on program effectiveness.
Intralesional doxycycline and bleomycin hydrochloride in the treatment of cystic hygroma
Authors: Nabi Ashfaque , Ferdous K. M. N. , Khan Naila Atik , Hasan Nazmul , Islam M. Kabirul
Published: March 2022

Purpose

Cystic lymphangioma is a common congenital lymphatic malformation. The aim of the study was to compare the safety and efficacy of doxycycline and bleomycin in the treatment of cystic hygroma.

Methods

A total of 60 children with cystic hygroma were included in the study after fulfillment of inclusion and exclusion criteria from July 2016 to June 2018. They were randomly assigned to the doxycycline group (group A = 30 children) or the bleomycin group (group B = 30 children). The comparative parameters between the two groups were the reduction of size of the lesion, adverse effects of both drugs, and treatment cost between groups. All patients were followed up for 6 months.

Results

Median age was 10.00 months in group A and 8.50 months in group B (p=0.841) Male to female ratio was 1.76:1. There was a significant reduction in the median size of the lesion in both groups after treatment (p<0.001). 86.7% of patients had an excellent response in group A whereas 60% in group B had an excellent response (P=0.049). There was more adverse effect in group B than group A (63.3% vs 36.7%, P=0.04).

Conclusion

Doxycycline monotherapy had a higher rate of excellent clinical outcomes with fewer side effects than bleomycin and was more cost-effective.
Endocrine, metabolic, and hepatic dysfunction in patients with COVID-19 pneumonia with severe and critically ill status
Authors: Elesdoudy Ahmed
Published: March 2022

Background

Management of endocrine and hepatic disorders is very important for better management of patient with COVID-19 infections. Hepatic and endocrine dysfunction needs clinical assessment, continued monitoring, and specific treatment. It is important to understand clearly the potential mechanisms causing hepatic and endocrine injury

Objectives

To assess the endocrine and hepatic dysfunctions in patient with COVID-19 pneumonia with severe and critically ill status.

Methods

This retrospective analytical study was performed on 75 patients admitted to intensive care or high dependency units (ICU/HDU) in Obaidullah Hospital, Ministry of Health, United Arab Emirates. All patients were subjected to the following on admission: history taking, general and local examinations, routine laboratory studies (CBC, liver function tests, and kidney function tests), and other laboratory tests: C-reactive protein (CRP), D-dimer, Chest X-ray. Endocrine and hepatic function tests and other laboratory studies are repeated daily to show the progress of endocrine and hepatic functions.

Results

The age range of the studied group was between 35 years and 107 years with mean age 59.98 ± 12.88. The sex distribution was (42 male, 56%) and (33 female, 44%). The associated comorbidities were 4 patients had bronchial asthma (5.3%), 12 patients had chronic kidney disease (16%), 30 patients had diabetes mellitus (40%), 26 patients had hypertension (34.7%), 2 patient had hypothyroidism (2.7%), 12 patient had ischemic heart disease (16%), and 21 patients did not have any comorbidities (28%). There was significant difference between glucose level, thyroid stimulating hormone and free t4 before and after admission (P values are 0.001, 0.04, and 0.023 respectively). There was significant difference between serum electrolytes before and after admission (P value = 0.001). There was significant difference between liver function test before and after admission (P values are 0.004, 0.001, and 0.001)

Conclusions

Hepatic, pancreatic, thyroid functions, and electrolytes are affected by COVID-19 infection. These could act as surrogate biomarkers for better management of hepatic, pancreatic, thyroid functions and electrolytes disturbances in patients with COVID-19 infection.
Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma
Authors: Teachey David T. , Devidas Meenakshi , Wood Brent L. , Chen Zhiguo , Hayashi Robert J. , Hermiston Michelle L. , Annett Robert D. , Archer J. Hunter , Asselin Barbara L. , August Keith J. , Cho Steve Y. , Dunsmore Kimberly P. , Fisher Brian T. , Freedman Jason L. , Galardy Paul J. , Harker-Murray Paul , Horton Terzah M. , Jaju Alok I. , Lam Allison , Messinger Yoav H. , Miles Rodney R. , Okada Maki , Patel Samir I. , Schafer Eric S. , Schechter Tal , Singh Neelam , Steele Amii C. , Sulis Maria Luisa , Vargas Sarah L. , Winter Stuart S. , Wood Charlotte , Zweidler-McKay Patrick , Bollard Catherine M. , Loh Mignon L. , Hunger Stephen P. , Raetz Elizabeth A.
Published: March 2022

PURPOSE

To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL.

PATIENTS AND METHODS

Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients.

RESULTS

AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600).

CONCLUSION

Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.
Branched-Chain Amino Acids and Their Interactions With Lipid Metabolites for Increased Risk of Gestational Diabetes
Authors: Li Ninghua , Li Jing , Wang Hui , Liu Jinnan , Li Weiqin , Yang Kai , Huo Xiaoxu , Leng Junhong , Yu Zhijie , Hu Gang , Fang Zhongze , Yang Xilin
Published: March 2022

Objective

We aimed to explore associations of branched-chain amino acids (BCAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high BCAAs and lipidomics markers had interactive effects on the risk of GDM.

Methods

We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women in Tianjin, China. Blood samples were collected at their first antenatal care visit (median 10 gestational weeks). Serum BCAAs, saturated fatty acids (SFA) and lysophosphatidylcholines (LPC) were measured by liquid chromatography–tandem mass spectrometry analysis. Conditional logistic regression was performed to examine associations of BCAAs with the risk of GDM. Interactions between high BCAAs and high SFA16:0 for GDM were examined using additive interaction measures.

Results

High serum valine, leucine, isoleucine, and total BCAAs were associated with markedly increased risk of GDM (OR of top vs bottom tertiles: 1.91 [95% CI, 1.22-3.01]; 1.87 [1.20-2.91]; 2.23 [1.41-3.52]; 1.93 [1.23-3.02], respectively). The presence of high SFA16:0 defined as ≥ 17.1 nmol/mL (ie, median) markedly increased the ORs of high leucine alone and high isoleucine alone up to 4.56 (2.37-8.75) and 4.41 (2.30-8.43) for the risk of GDM, with significant additive interaction. After adjustment for LPCs, the ORs were greatly elevated (6.33, 2.25-17.80 and 6.53, 2.39-17.86) and the additive interactions became more significant.

Conclusion

BCAAs in early pregnancy were positively associated with the risk of GDM, and high levels of leucine and isoleucine enhanced the risk association of high SFA16:0 with GDM, independent of LPCs.
On the Impact of Public Housing on Income Segregation in France
Authors: Beaubrun-Diant Kevin , Maury Tristan-Pierre
Published: March 2022

This article provides a geographic analysis of the contribution of public housing to income segregation in France from 1999 to 2015. The analysis is conducted with several segregation indices and at different geographic scales. Surprisingly, it appears that while home tenure (public vs. private housing) segregation has been decreasing, income segregation has been rising. With segregation decomposition techniques, we provide evidence that this is partly due to an increasing concentration of low-income households in public housing, which cancels out the effect of the spatial dispersion of public housing. Indeed, while public housing has become more homogeneously distributed geographically, which should help to reduce income segregation, the distribution of income within public (and private) housing has changed: households living in public housing were poorer in 2015 than in 1999. We also provide evidence of a sorting effect—the process of allocating public housing that is not random—so that the richest neighborhoods or municipalities receive wealthier-than-average public tenants.