bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency in China
Authors: Zhao Jing , Setchell Kenneth D. R. , Gong Ying , Sun Yinghua , Zhang Ping , Heubi James E. , Fang Lingjuan , Lu Yi , Xie Xinbao , Gong Jingyu , Wang Jian-She
Published: October 2021

Background

Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy.

Methods

The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder.

Results

In all, 34 of the 44 variants identified in HSD3B7 were novel. A total of 32 patients presented early with neonatal cholestasis, and 7 presented after 1-year of age with liver failure (n = 1), liver cirrhosis (n = 3), cholestasis (n = 1), renal cysts and abnormal liver biochemistries (n = 1), and coagulopathy from vitamin K1 deficiency and abnormal liver biochemistries (n = 1). Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 of 35 patients. Thirty-three patients were treated with oral chenodeoxycholic acid (CDCA) resulting in normalization of liver biochemistries in 24, while 2 showed a significant clinical improvement, and 7 underwent liver transplantation or died. Remarkably, renal lesions in 6 patients resolved after CDCA treatment, or liver transplantation. There were no significant correlations between genotype and clinical outcomes.

Conclusions

In what is the largest cohort of patients with HSD3B7 deficiency thus far studied, renal lesions were a notable clinical feature of HSD3B7 deficiency and these were resolved with suppression of atypical bile acids by oral CDCA administration.
Severe deforming dermatitis in a kitten caused by Caryospora bigenetica
Authors: Saari Seppo , Schildt Kirsti , Malkamäki Sanna , Andersin Ulla , Sukura Antti
Published: October 2021

Background

Caryospora bigeneticais an intracellular protozoan parasite, which in its primary hosts, typically snakes, is found it the intestine. Extraintestinal multiplication with the development of tissue cysts takes place in secondary hosts, which are normally prey for snakes. Natural infection in domestic animals has been reported only in dogs; this is the first report ofC. bigeneticainfection in a cat.

Case presentation

A stray kitten developed nodular dermatitis after being adopted by a shelter. Firm swelling, nodules, and crusts were present mainly on the nasal bridge, eyelids, and pinnae. Histopathology and cytology revealed severe pyogranulomatous inflammation with abundant intracellular organisms suggestive of apicomplexan protozoa. Treatment with clindamycin 13 mg/kg twice daily was initiated, but the cat was euthanized because of the worsening condition. Transmission electron microscopy confirmed parasite’s apicomplexan origin postmortem, and the causative agent was identified asC. bigeneticaby polymerase chain reaction and DNA sequencing.

Conclusions

We present the first case of a naturally occurring infection withC. bigeneticain a cat. Although the definitive etiological diagnosis relied on molecular identification, the abundance of unsporulated oocysts and caryocysts and the parasite's effective reproduction within macrophages and in several other cell types might have enabled differentiation from other protozoal infections and allowed a presumptive diagnosis through cytology and histopathology.
Management of asymptomatic hypoglycemia with 40% oral dextrose gel in near term at-risk infants to reduce intensive care need and promote breastfeeding
Authors: Meneghin Fabio , Manzalini Martina , Acunzo Miriam , Daniele Irene , Bastrenta Petrina , Castoldi Francesca , Cavigioli Francesco , Zuccotti Gian Vincenzo , Lista Gianluca
Published: October 2021

Background

Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge.

Methods

In our ward, we prospectively compared a group of near-term neonates, (Gr2,n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1,n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome.

Results

In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p <  0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively.

Conclusions

In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.
Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial
Authors: Hood Anna M. , Stotesbury Hanne , Kölbel Melanie , DeHaan Michelle , Downes Michelle , Kawadler Jamie M. , Sahota Satwinder , Dimitriou Dagmara , Inusa Baba , Wilkey Olu , Pelidis Maria , Trompeter Sara , Leigh Andrea , Younis Janine , Drasar Emma , Chakravorty Subarna , Rees David C. , Height Sue , Lawson Sarah , Gavlak Johanna , Gupta Atul , Ridout Deborah , Clark Christopher A. , Kirkham Fenella J.
Published: October 2021

Background

Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA.

Methods

The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry.

Discussion

Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA.

Trial registration

ClinicalTrials.govNCT04351698. Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020
Estimands in published protocols of randomised trials: urgent improvement needed
Authors: Kahan Brennan C. , Morris Tim P. , White Ian R. , Carpenter James , Cro Suzie
Published: October 2021

Background

An estimand is a precise description of the treatment effect to be estimated from a trial (the question) and is distinct from the methods of statistical analysis (how the question is to be answered). The potential use of estimands to improve trial research and reporting has been underpinned by the recent publication of the ICH E9(R1) Addendum on the use of estimands in clinical trials in 2019. We set out to assess how well estimands are described in published trial protocols.

Methods

We reviewed 50 trial protocols published in October 2020 in Trials and BMJ Open. For each protocol, we determined whether the estimand for the primary outcome was explicitly stated, not stated but inferable (i.e. could be constructed from the information given), or not inferable.

Results

None of the 50 trials explicitly described the estimand for the primary outcome, and in 74% of trials, it was impossible to infer the estimand from the information included in the protocol. The population attribute of the estimand could not be inferred in 36% of trials, the treatment condition attribute in 20%, the population-level summary measure in 34%, and the handling of intercurrent events in 60% (the strategy for handling non-adherence was not inferable in 32% of protocols, and the strategy for handling mortality was not inferable in 80% of the protocols for which it was applicable). Conversely, the outcome attribute was stated for all trials. In 28% of trials, three or more of the five estimand attributes could not be inferred.

Conclusions

The description of estimands in published trial protocols is poor, and in most trials, it is impossible to understand exactly what treatment effect is being estimated. Given the utility of estimands to improve clinical research and reporting, this urgently needs to change.
Biotinylation of the Neospora caninum parasitophorous vacuole reveals novel dense granule proteins
Authors: Yang Congshan , Wang Chenrong , Liu Jing , Liu Qun
Published: October 2021

Background

Neospora caninum is an obligate intracellular parasite that invades host cells and replicates within the parasitophorous vacuole (PV), which resists fusion with host cell lysosomal compartments. To modify the PV, the parasite secretes an array of proteins, including dense granule proteins (GRAs). The vital role of GRAs in the Neospora life cycle cannot be overestimated. Despite this important role, only a subset of these proteins have been identified, and most of their functions have not been elucidated. Our previous study demonstrated that NcGRA17 is specifically targeted to the delimiting membrane of the parasitophorous vacuole membrane (PVM). In this study, we utilize proximity-dependent biotin identification (BioID) to identify novel components of the dense granules.

Methods

NcGRA17 was BirA* epitope-tagged in the Nc1 strain utilizing the CRISPR/Cas9 system to create a fusion of NcGRA17 with the biotin ligase BirA*. The biotinylated proteins were affinity-purified for mass spectrometric analysis, and the candidate GRA proteins from BioID data set were identified by gene tagging. To verify the biological role of novel identified GRA proteins, we constructed the NcGRA23 and NcGRA11 (a–e) knockout strains using the CRISPR/Cas9 system and analyzed the phenotypes of these mutants.

Results

Using NcGRA17-BirA* fusion protein as bait, we have identified some known GRAs and verified localization of 11 novel GRA proteins by gene endogenous tagging or overexpression in the Nc1 strain. We proceeded to functionally characterize NcGRA23 and NcGRA11 (a–e) by gene knockout. The lack of NcGRA23 or NcGRA11 (a–e) did not affect the parasite propagation in vitro and virulence in vivo.

Conclusions

In summary, our findings reveal that BioID is effective in discovering novel constituents of N. caninum dense granules. The exact biological functions of the novel GRA proteins are yet unknown, but this could be explored in future studies.

Graphical abstract
Phylogenetic relationships of the nematode subfamily Phascolostrongylinae from macropodid and vombatid marsupials inferred using mitochondrial protein sequence data
Authors: Sukee Tanapan , Beveridge Ian , Koehler Anson V. , Hall Ross , Gasser Robin B. , Jabbar Abdul
Published: October 2021

Background

The subfamily Phascolostrongylinae (Superfamily Strongyloidea) comprises nematodes that are parasitic in the gastrointestinal tracts of macropodid (Family Macropodidae) and vombatid (Family Vombatidae) marsupials. Currently, nine genera and 20 species have been attributed to the subfamily Phascolostrongylinae. Previous studies using sequence data sets for the internal transcribed spacers (ITS) of nuclear ribosomal DNA showed conflicting topologies between the Phascolostrongylinae and related subfamilies. Therefore, the aim of this study was to validate the phylogenetic relationships within the Phascolostrongylinae and its relationship with the families Chabertiidae and Strongylidae using mitochondrial amino acid sequences.

Methods

The sequences of all 12 mitochondrial protein-coding genes were obtained by next-generation sequencing of individual adult nematodes (n = 8) representing members of the Phascolostrongylinae. These sequences were conceptually translated and the phylogenetic relationships within the Phascolostrongylinae and its relationship with the families Chabertiidae and Strongylidae were inferred from aligned, concatenated amino acid sequence data sets.

Results

Within the Phascolostrongylinae, the wombat-specific genera grouped separately from the genera occurring in macropods. Two of the phascolostrongyline tribes were monophyletic, including Phascolostrongylinea and Hypodontinea, whereas the tribe Macropostrongyloidinea was paraphyletic. The tribe Phascolostrongylinea occurring in wombats was closely related toOesophagostomumspp., also from the family Chabertiidae, which formed a sister relationship with the Phascolostrongylinae.

Conclusion

The current phylogenetic relationship within the subfamily Phascolostrongylinae supports findings from a previous study based on ITS sequence data. This study contributes also to the understanding of the phylogenetic position of the subfamily Phascolostrongylinae within the Chabertiidae. Future studies investigating the relationships between the Phascolostrongylinae and Cloacininae from macropodid marsupials may advance our knowledge of the phylogeny of strongyloid nematodes in marsupials.

Graphical Abstract
Multi-omics colocalization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus
Authors: Soliai Marcus M. , Kato Atsushi , Helling Britney A. , Stanhope Catherine T. , Norton James E. , Naughton Katherine A. , Klinger Aiko I. , Thompson Emma E. , Clay Selene M. , Kim Soyeon , Celedón Juan C. , Gern James E. , Jackson Daniel J. , Altman Matthew C. , Kern Robert C. , Tan Bruce K. , Schleimer Robert P. , Nicolae Dan L. , Pinto Jayant M. , Ober Carole
Published: October 2021

Background

Genome-wide association studies (GWASs) have identified thousands of variants associated with asthma and other complex diseases. However, the functional effects of most of these variants are unknown. Moreover, GWASs do not provide context-specific information on cell types or environmental factors that affect specific disease risks and outcomes. To address these limitations, we used an upper airway epithelial cell (AEC) culture model to assess transcriptional and epigenetic responses to rhinovirus (RV), an asthma-promoting pathogen, and provide context-specific functional annotations to variants discovered in GWASs of asthma.

Methods

Genome-wide genetic, gene expression, and DNA methylation data in vehicle- and RV-treated upper AECs were collected from 104 individuals who had a diagnosis of airway disease (n=66) or were healthy participants (n=38). We mapped cis expression and methylation quantitative trait loci (cis-eQTLs and cis-meQTLs, respectively) in each treatment condition (RV and vehicle) in AECs from these individuals. A Bayesian test for colocalization between AEC molecular QTLs and adult onset asthma and childhood onset asthma GWAS SNPs, and a multi-ethnic GWAS of asthma, was used to assign the function to variants associated with asthma. We used Mendelian randomization to demonstrate DNA methylation effects on gene expression at asthma colocalized loci.

Results

Asthma and allergic disease-associated GWAS SNPs were specifically enriched among molecular QTLs in AECs, but not in GWASs from non-immune diseases, and in AEC eQTLs, but not among eQTLs from other tissues. Colocalization analyses of AEC QTLs with asthma GWAS variants revealed potential molecular mechanisms of asthma, including QTLs at the TSLP locus that were common to both the RV and vehicle treatments and to both childhood onset and adult onset asthma, as well as QTLs at the 17q12-21 asthma locus that were specific to RV exposure and childhood onset asthma, consistent with clinical and epidemiological studies of these loci.

Conclusions

This study provides evidence of functional effects for asthma risk variants in AECs and insight into RV-mediated transcriptional and epigenetic response mechanisms that modulate genetic effects in the airway and risk for asthma.
Compositional variation of the human fecal microbiome in relation to azo-reducing activity: a pilot study
Authors: Zahran Sara A. , Ali-Tammam Marwa , Ali Amal E. , Aziz Ramy K.
Published: October 2021

Background

Through an arsenal of microbial enzymes, the gut microbiota considerably contributes to human metabolic processes, affecting nutrients, drugs, and environmental poisons. Azoreductases are a predominant group of microbiota-derived enzymes involved in xenobiotic metabolism and drug activation, but little is known about how compositional changes in the gut microbiota correlate with its azo-reducing activity.

Results

To this end, we used high-throughput 16S rRNA amplicon sequencing, with Illumina MiSeq, to determine the microbial community composition of stool samples from 16 adults with different azo-reducing activity. High azo-reducing activity positively
correlated with the relative abundance of phylum Firmicutes (especially genera Streptococcus and Coprococcus) but negatively with phylum Bacteroidetes (especially genus Bacteroides). Typical variations in the Firmicutes-to-Bacteroidetes and Prevotella-to-Bacteroides ratios were observed among samples. Multivariate analysis of the relative abundance of key microbial taxa and other diversity parameters confirmed the Firmicutes proportion as a major variable differentiating high and non-azo-reducers, while Bacteroidetes relative abundance was correlated with azo-reduction, sex, and BMI.

Conclusions

This pilot study showed that stool samples with higher azo-reducing activity were enriched in Firmicutes but with relatively fewer Bacteroidetes. More samples and studies from different geographical areas are needed to bolster this conclusion. Better characterization of different azoreductase-producing gut microbes will increase our knowledge about the fate and differential human responses to azodye-containing drugs or orally consumed chemicals, thus contributing to efforts towards implementing microbiome testing in precision medicine and toxicology.
Comparison of the efficiency and performance of two systems and three membranes for blood feeding mosquitoes
Authors: Seck Fatoumata , Cailleau Aurélie , Diallo Mawlouth , Dia Ibrahima
Published: October 2021

Objective

Due to different concerns in using appropriate mosquito blood feeding techniques, this work focused on evaluating the effectiveness of two artificial mosquito feeding systems (Rutledge and Hemotek) and three different membranes (Parafilm, mouse and chicken skins). Female mosquitoes from an An. coluzzii strain aged between 2 and 5 days were exposed to blood with the two systems at time intervals (5, 10, 15, 20, 25 and 30 min) with blood used on the day of collection, the next day and 2 days after.

Results

Our results showed that the Hemotek system gave better blood feeding rates than the Rutledge system. Among the three membranes, the blood feeding rates with chicken and mouse skins were higher than those provided by the Parafilm membrane. Likewise, blood stored 1 day after collection gave higher levels than blood used on the day of collection and 2 days after. Regardless of the system, the lowest blood feeding rates were observed at 5 min compared to the other exposure times.
Gallbladder volvulus: a case report
Authors: Croce Phillip , Licata Samuel
Published: October 2021

Background

Gallbladder volvulus is a rare pathology first reported by Wendel in 1898. Although the main pathological process associated with gallbladder volvulus is not known, there is clinical evidence suggesting that lack of gallbladder adhesions to the liver leads to an eventual twisting around the cystic bile duct (a process that seems to favor older female populations).

Case presentation

In this report, an 81-year-old Caucasian elderly female presented to the emergency department with acute/severe right upper quadrant pain, which was also accompanied by an elevated leukocyte count. Relevant imaging showed a distended gallbladder with gallbladder wall thickening and a dilated common bile duct. The patient was subsequently admitted to the hospital for acute cholecystitis and scheduled for surgery the next day. Upon laparoscopic surgery, the gallbladder was black and gangrenous with no visible adhesions to the liver. Further inspection demonstrated that the gallbladder had twisted clockwise around the cystic bile duct.

Conclusions

While many previous cases have been reported since Wendel, further case studies are nevertheless important to help guide proper clinic evaluation and pinpoint the potential for a gallbladder volvulus.
On the existence of mild solutions for nonlocal differential equations of the second order with conformable fractional derivative
Authors: Atraoui Mustapha , Bouaouid Mohamed
Published: October 2021

In the work (Bouaouid et al. in Adv. Differ. Equ. 2019:21, 2019), the authors have used the Krasnoselskii fixed point theorem for showing the existence of mild solutions of an abstract class of conformable fractional differential equations of the form: $\frac{d^{\alpha }}{dt^{\alpha }}[\frac{d^{\alpha }x(t)}{dt^{\alpha }}]=Ax(t)+f(t,x(t))$

d
α

d

t
α

[

d
α

x
(
t
)

d

t
α

]
=
A
x
(
t
)
+
f
(
t
,
x
(
t
)
)
, $t\in [0,\tau ]$
t
∈
[
0
,
τ
]
subject to the nonlocal conditions $x(0)=x_{0}+g(x)$
x
(
0
)
=

x
0

+
g
(
x
)
and $\frac{d^{\alpha }x(0)}{dt^{\alpha }}=x_{1}+h(x)$

d
α

x
(
0
)

d

t
α

=

x
1

+
h
(
x
)
, where $\frac{d^{\alpha }(\cdot)}{dt^{\alpha }}$

d
α

(
⋅
)

d

t
α

is the conformable fractional derivative of order $\alpha \in\, ]0,1]$
α
∈

]
0
,
1
]
and A is the infinitesimal generator of a cosine family $(\{C(t),S(t)\})_{t\in \mathbb{R}}$

(
{
C
(
t
)
,
S
(
t
)
}
)

t
∈
R

on a Banach space X. The elements $x_{0}$

x
0

and $x_{1}$

x
1

are two fixed vectors in X, and f, g, h are given functions. The present paper is a continuation of the work (Bouaouid et al. in Adv. Differ. Equ. 2019:21, 2019) in order to use the Darbo–Sadovskii fixed point theorem for proving the same existence result given in (Bouaouid et al. in Adv. Differ. Equ. 2019:21, 2019) [Theorem 3.1] without assuming the compactness of the family $(S(t))_{t>0}$

(
S
(
t
)
)

t
>
0

and any Lipschitz conditions on the functions g and h.
Heritability and genetic variance estimation of Osteosarcoma (OSA) in Irish Wolfhound, using deep pedigree information
Authors: Momen Mehdi , Kohler Nyah L. , Binversie Emily E. , Dentino Mariellen , Sample Susannah J.
Published: October 2021

Background

Osteosarcoma (OSA) is a devastating disease that is common in the Irish Wolfhound breed. The aim of this study was to use a pedigree-based approach to determine the heritability of OSA in the Irish Wolfhound using data from a large publically available database.

Results

The pedigree used for this study included 5110 pure-bred Irish Wolfhounds, including 332 dogs diagnosed with OSA and 360 control dogs; dogs were considered controls if they lived over 10 years of age and were not reported to have developed OSA. The estimated heritability of OSA in the Irish Wolfhound was 0.65.

Conclusion

The results of this study indicate that OSA in the Irish Wolfhound is highly heritable, and support the need for future research investigating associated genetic mutations.
Phytochemicals and in vitro anti-apoptotic properties of ethanol and hot water extracts of Cassava (Manihot esculenta Crantz) peel biogas slurry following anaerobic degradation
Authors: Olaniyan Oluwaseyi Paul , Ajayi Ebenezer Idowu O.
Published: October 2021

Background

Wastes emanating from cassava (Manihot Esculenta Crantz) processing in African countries significantly contribute to environmental pollution, besides, such toxic wastes contribute to greenhouse gas emission. Although cassava peel has been successfully used as a raw material in mushroom cultivation, feedstock for livestock, biogas production but the bio-transformed products recovered from the anaerobic digestion of cassava wastes, especially the peels have often been overlooked. Therefore, this research aimed at quantifying the secondary metabolites in the slurry recovered from ethanol and hot water extraction of cassava peel subjected to biogas production, in vitro, for anti-apoptotic properties.

Methods

Fresh cassava peels were allowed to ferment anaerobically to produce three states of matter; gas, solid, and liquid/slurry. The slurry was extracted using 95 % ethanol and 100 oC hot water to obtain crude extracts, which were then subjected to anti-apoptotic screening using the mitochondrial swelling assay. The qualitative phytochemical analysis of the crude extracts was done using standard methods. Further characterization of the crude extracts was done by FTIR for the chemical elucidation of the functional groups present.

Results

The qualitative phytoconstituents revealed that the slurry extracts are naturally enriched with alkaloids, steroids, flavonoids, and saponins. The infrared spectrum of the crude extracts revealed the presence of hydroxyl, alkane, carboxyl groups in the ethanol extract, and hydroxyl, alkene, amide, carbonyl groups in the hot water extract. In the presence and absence of exogenous Ca2+, both extracts of the slurry induced liver mitochondrial permeability transition pore opening albeit at low amplitude swelling as the mean absorbance was less than one (at 540 nm).

Conclusions

Based on these results obtained, the crude extracts of cassava peel biogas slurry have been proven to possess bioactive compounds that could induce liver mitochondrial permeability transition pore opening, in vitro.
Comparison of the frequencies of ENU-induced point mutations in male germ cells and inherited germline mutations in their offspring
Authors: Masumura Kenichi , Ando Tomoko , Toyoda-Hokaiwado Naomi , Ukai Akiko , Nohmi Takehiko , Honma Masamitsu
Published: October 2021

Background

Gene mutations induced in germ cells may be transmitted to the next generation and cause adverse effects such as genetic diseases. Certain mutations may result in infertility or death in early development. Thus, the mutations may not be inheritable. However, the extent to which point mutations in male germ cells are transmitted to the next generation or eliminated during transmission is largely unknown. This study compared mutation frequencies (MFs) in sperm of N-ethyl-N-nitrosourea (ENU)-treated gpt delta mice and de novo MFs in the whole exome/genome of their offspring.

Results

Male gpt delta mice were treated with 10, 30, and 85 mg/kg of ENU (i.p., weekly × 2) and mated with untreated females to generate offspring. We previously reported a dose-dependent increase in de novo MFs in the offspring estimated by whole exome sequencing (WES) (Mutat. Res., 810, 30–39, 2016). In this study, gpt MFs in the sperm of ENU-treated mice were estimated, and the MFs per reporter gene were converted to MFs per base pair. The inherited de novo MFs in the offspring (9, 26 and 133 × 10− 8/bp for 10, 30, and 85 mg/kg ENU-treated groups, respectively) were comparable to those of the converted gpt MFs in the sperm of ENU-treated fathers (6, 16, and 69 × 10− 8/bp). It indicated that the gpt MFs in the ENU-treated father’s sperm were comparable to the inherited de novo MFs in the offspring as estimated by WES. In addition, de novo MFs in the offspring of 10 mg/kg ENU-treated and control fathers were estimated by whole genome sequencing (WGS), because WES was not sufficiently sensitive to detect low background MF. The de novo MF in the offspring of the ENU-treated fathers was 6 × 10− 8/bp and significantly higher than that of the control (2 × 10− 8/bp). There were no significant differences in de novo MFs between gene-coding and non-coding regions. WGS analysis was able to detect ENU-induced characteristic de novo base substitutions at a low dose group.

Conclusions

Despite a difference between exome/genome and exogenous reporter genes, the results indicated that ENU-induced point mutations in male germ cells could be transmitted to the next generation without severe selection.
EANM guideline for harmonisation on molar activity or specific activity of radiopharmaceuticals: impact on safety and imaging quality
Authors: Luurtsema Gert , Pichler Verena , Bongarzone Salvatore , Seimbille Yann , Elsinga Philip , Gee Antony , Vercouillie Johnny
Published: October 2021

This guideline on molar activity (Am) and specific activity (As) focusses on small molecules, peptides and macromolecules radiolabelled for diagnostic and therapeutic applications. In this guideline we describe the definition of Am and As, and how these measurements must be standardised and harmonised. Selected examples highlighting the importance of Am and As in imaging studies of saturable binding sites will be given, and the necessity of using appropriate materials and equipment will be discussed. Furthermore, common Am pitfalls and remedies are described. Finally, some aspects of Am in relation the emergence of a new generation of highly sensitive PET scanners will be discussed.
Does attitude towards wife beating determine infant feeding practices during diarrheal illness in sub-Saharan Africa?
Authors: Zegeye Betregiorgis , Adjei Nicholas Kofi , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Seidu Abdul-Aziz , Olorunsaiye Comfort Z. , Yaya Sanni
Published: October 2021

Background

Inappropriate feeding practices of children during illness remains a public health problem globally, particularly in sub-Saharan Africa (SSA). One strategy to improve child health outcomes is through women empowerment—measured by wife beating attitude. However, the role of attitude towards wife beating in child feeding practices has not been comprehensively studied. Therefore, we investigated the association between women's attitude towards wife beating and child feeding practices during childhood diarrhea in 28 countries in SSA.

Methods

We analyzed data from the Demographic and Health Survey on 40,720 children under 5 years. Bivariate and multivariate binary logistic regression analyses were applied to assess the association between women's attitude towards wife beating and child feeding practices. The results were presented using adjusted odds ratio (aOR) with 95% confidence intervals (CIs).

Results

The pooled results showed that appropriate feeding practices during diarrheal illness among under-five children was 9.3% in SSA, varying from 0.4% in Burkina Faso to 21.1% in Kenya. Regarding regional coverage, the highest coverage was observed in Central Africa (9.3%) followed by East Africa (5.5%), Southern Africa (4.8%), and West Africa (4.2%). Women who disagreed with wife-beating practices had higher odds of proper child feeding practices during childhood diarrhea compared to those who justified wife-beating practices (aOR = 2.02, 95% CI; 1.17–3.48).

Conclusion

The findings suggest that women’s disagreement with wife beating is strongly associated with proper child feeding practices during diarrheal illness in SSA. Proactive measures and interventions designed to change attitudes towards wife-beating practices are crucial to improving proper feeding practices in SSA.
Ethnoracial disparities in cognition are associated with multiple socioeconomic status-stress pathways
Authors: Letang Sarah K. , Lin Shayne S.-H. , Parmelee Patricia A. , McDonough Ian M.
Published: October 2021

Systemic racism can have broad impacts on health in ethnoracial minorities. One way is by suppressing socioeconomic status (SES) levels through barriers to achieve higher income, wealth, and educational attainment. Additionally, the weathering hypothesis proposes that the various stressful adversities faced by ethnoracial minorities lead to greater wear and tear on the body, known as allostatic load. In the present study, we extend these ideas to cognitive health in a tri-ethnic sample of young adults—when cognition and brain health is arguably at their peak. Specifically, we tested competing mediation models that might shed light on how two key factors caused by systemic racism—SES and perceived stress—intersect to explain ethnoracial disparities in cognition. We found evidence for partial mediation via a pathway from SES to stress on episodic memory, working memory capacity, and executive function in Black Americans relative to non-Hispanic White Americans. Additionally, we found that stress partially mediated the ethnoracial disparities in working memory updating for lower SES Black and Hispanic Americans relative to non-Hispanic White Americans, showing that higher SES can sometimes reduce the negative effects stress has on these disparities in some cognitive domains. Overall, these findings suggest that multiple pathways exist in which lower SES creates a stressful environment to impact ethnoracial disparities cognition. These pathways differ depending on the specific ethnoracial category and cognitive domain. The present results may offer insight into strategies to help mitigate the late-life risk for neurocognitive disorders in ethnoracial minorities.
Contribution of animal pollination to food nutrient production in Benin-West Africa
Authors: Toni Hermann Cyr , Avohou Armand , Djossa Bruno Agossou
Published: October 2021

Background

Pollinators play a key role in human food production by improving the yield and quality of crops. Several studies assessed the economic value of pollination services delivered by animals through yield improvement. However, little is known about the contribution of animal pollinators to nutrient production. This study assessed the contribution of animal pollination to nutrient production in Benin. Food and Agriculture Organization data on crop production and United States Department of Agriculture crop composition data of 37 leading crops were used. These crops were categorized into five classes, depending on their degree of dependence on animal pollinators for fruit production.

Results

The study showed that more than half of the studied crops (56.75%) relies at different levels on animal pollination for fruit production. Minerals, namely fluoride (83.92%) and selenium (52.62%), were the most delivered by animal-pollinated crops. Roughly 50% of lipids outputs and 24% of proteins outputs were obtained from pollinator-dependent crops. Significant outputs of fat-soluble vitamins up to 65% were also attributed to animal pollination. A low contribution of animal pollination (up to 8%) was reported for water-soluble vitamins.

Conclusion

Animal-pollinated crops significantly contribute to the supply of nutrients and consequently to nutritional and food security in Benin. Conservation of pollinators should be considered as an important component of food security programs in the country.
Elucidation of genetic diversity among some accessions of sugar beet (Beta vulgaris L.) using inter-simple sequence repeats (ISSR) markers
Authors: El-Mouhamady Almoataz Bellah Ali , Al-Kordy Magdy Ahmad , Elewa Tarik Abdel-Fatah
Published: October 2021

Background

Sugar beet is considered a very important strategic economic crop, as it comes at the second place for white sugar production in Egypt after sugar cane and the sugar percentage in its roots is 20%. This work was conducted in Egypt as a direct response to bridge the gap which began to expand significantly between the production and consumption of white sugar and the desire for the genetic improvement process to increase the productivity of this crop. Further, as serious attempt to understand the nature of the genetic diversity among a group of sugar beet accessions with different origins, it constitutes an important source for establishing a program of breeding and improving sugar beet crop under Egyptian conditions.

Results

The process of verifying the existence of significant genetic variation between the eight sugar beet varieties with various origins was carried out through a set of genetic parameters through two growing seasons besides, the data of ISSR markers profile. Further, all the sugar beet varieties were superior in all the studied traits during their evaluation over two agricultural years, where the two sugar beet accessions Oscar Poly and Rass Poly are superior in TSS % and sucrose % traits, Mont Bianco and Sultan in apparent purity % trait, Blino and Sultan in root yield and top yield traits and Rass Poly and Blino in sugar yield trait, respectively. In addition, the values of heritability in broad sense were high in all studied traits except the two traits; sucrose % and sugar yield where their results were appeared medium during both growing seasons. In the same regard, expected genetic advance values showed significant genetic progress in all studied traits during the two growing seasons. As well, highly genetic diversity was obtained between the eight sugar beet accessions through generated 169 amplified fragments from the twelve ISSR primers, 122 of them were polymorphic with 72.18% polymorphism.

Conclusions

The eight sugar beet varieties achieved remarkable and distinctive results for all traits under study during two agricultural years. However, they were differentiated and various from each other. As they differed in their superiority in all estimated traits and they proved to be fertile material for studying in this investigation and very suitable for enriching the breeding and genetic improvement program to promote the sugar beet yield in order to increase the productivity of white sugar in Egypt.
Equine grass sickness (a multiple systems neuropathy) is associated with alterations in the gastrointestinal mycobiome
Authors: McGorum Bruce C. , Chen Zihao , Glendinning Laura , Gweon Hyun S. , Hunt Luanne , Ivens Alasdair , Keen John A. , Pirie R. Scott , Taylor Joanne , Wilkinson Toby , McLachlan Gerry
Published: October 2021

Background

Equine grass sickness (EGS) is a multiple systems neuropathy of grazing horses of unknown aetiology. An apparently identical disease occurs in cats, dogs, rabbits, hares, sheep, alpacas and llamas. Many of the risk factors for EGS are consistent with it being a pasture mycotoxicosis. To identify potential causal fungi, the gastrointestinal mycobiota of EGS horses were evaluated using targeted amplicon sequencing, and compared with those of two control groups. Samples were collected post mortem from up to 5 sites in the gastrointestinal tracts of EGS horses (EGS group; 150 samples from 54 horses) and from control horses that were not grazing EGS pastures and that had been euthanased for reasons other than neurologic and gastrointestinal diseases (CTRL group; 67 samples from 31 horses). Faecal samples were also collected from healthy control horses that were co-grazing pastures with EGS horses at disease onset (CoG group; 48 samples from 48 horses).

Results

Mycobiota at all 5 gastrointestinal sites comprised large numbers of fungi exhibiting diverse taxonomy, growth morphology, trophic mode and ecological guild. FUNGuild analysis parsed most phylotypes as ingested environmental microfungi, agaricoids and yeasts, with only 1% as gastrointestinal adapted animal endosymbionts. Mycobiota richness varied throughout the gastrointestinal tract and was greater in EGS horses. There were significant inter-group and inter-site differences in mycobiota structure. A large number of phylotypes were differentially abundant among groups. Key phylotypes (n = 56) associated with EGS were identified that had high abundance and high prevalence in EGS samples, significantly increased abundance in EGS samples, and were important determinants of the inter-group differences in mycobiota structure. Many key phylotypes were extremophiles and/or were predicted to produce cytotoxic and/or neurotoxic extrolites.

Conclusions

This is the first reported molecular characterisation of the gastrointestinal mycobiota of grazing horses. Key phylotypes associated with EGS were identified. Further work is required to determine whether neurotoxic extrolites from key phylotypes contribute to EGS aetiology or whether the association of key phylotypes and EGS is a consequence of disease or is non-causal.
Recombinant luteinizing hormone supplementation in assisted reproductive technology: a review of literature
Authors: Eftekhar Maryam , Tabibnejad Nasim
Published: October 2021

Background

Luteinizing hormone (LH) has the main role in ovarian function in both natural and artificial cycles. A normal LH concentration during controlled ovarian hyperstimulation is positively correlated to the number and quality of retrieved oocytes and resulting embryos.

Main body of the abstract

In this study, we reviewed whether rLH administration, adjunct to the ovarian stimulation regimen, could improve clinical outcomes. The literature review showed that rLH supplementation improves assisted reproductive technology (ART) outcomes among women with hypogonadotropic hypogonadism, and hyporesponsive women to follicle-stimulating hormone monotherapy. Besides, rLH supplementation has advantages for poor responder women 36–39 years of age. Even though the data suggested no priority regarding the LH source for improving ART outcome, women with different LH polymorphisms who did not respond similarly to ovarian stimulation may benefit from adjuvant rLH therapy.

Conclusion

rLH usage for improving ART outcome should be scrutinized via well-designed studies considering the subgroups of infertile women who benefit the most from rLH adjuvant therapy, the type of ovarian stimulation protocol to which rLH would be added, and also the exact dosage, as well as the proper timing (during or prior to a cycle).
Premature atherosclerosis and acute coronary syndrome in a child with end-stage renal disease
Authors: Becerir Tülay , Yılmaz Münevver , Girişgen İlknur , Yılmaz Neslihan , Gürses Dolunay , Ufuk Furkan , Nar Gökay , Yüksel Selçuk
Published: October 2021

Background

Although acute coronary syndrome is rare in children, it is the most important cause of mortality in children with end-stage renal disease.

Case presentation

Here, a 16-year-old pediatric patient, who has been on dialysis since the age of 3, and who was diagnosed with acute coronary syndrome and placed an emergency percutaneous transcatheter stent in the left anterior descending branch of the left coronary artery is presented. It is important that the present patient does not have any electrocardiography findings in favor of cardiovascular disease and that he cannot fully explain the complaint of chest pain due to his mental retardation.

Conclusions

Early detection of acute coronary syndrome is life-saving, especially in children with chronic kidney disease.
Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival
Authors: Liu Qiang , Shen Hongliang , Naguib Andrew , Weiss Robert M. , Martin Darryl T.
Published: October 2021

Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.
High-resolution sweep metagenomics using fast probabilistic inference
Authors: Mäklin Tommi , Kallonen Teemu , David Sophia , Boinett Christine J. , Pascoe Ben , Méric Guillaume , Aanensen David M. , Feil Edward J. , Baker Stephen , Parkhill Julian , Sheppard Samuel K. , Corander Jukka , Honkela Antti
Published: October 2021

Determining the composition of bacterial communities beyond the level of a genus or species is challenging because of the considerable overlap between genomes representing close relatives. Here, we present the mSWEEP pipeline for identifying and estimating the relative sequence abundances of bacterial lineages from plate sweeps of enrichment cultures. mSWEEP leverages biologically grouped sequence assembly databases, applying probabilistic modelling, and provides controls for false positive results. Using sequencing data from major pathogens, we demonstrate significant improvements in lineage quantification and detection accuracy. Our pipeline facilitates investigating cultures comprising mixtures of bacteria, and opens up a new field of plate sweep metagenomics.