bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis
Authors: Zhao Xingwang , Zhang Longlong , Wang Juan , Zhang Min , Song Zhiqiang , Ni Bing , You Yi
Published: January 2021

Background

Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE is characterized by autoimmune, inflammatory processes, and tissue destruction. Some seriously-ill patients could develop into lupus nephritis. However, the cause and underlying molecular events of SLE needs to be further resolved.

Methods

The expression profiles of GSE144390, GSE4588, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between SLE and healthy samples. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by metascape etc. online analyses. The protein–protein interaction (PPI) networks of the DEGs were constructed by GENEMANIA software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the functions of the hub gene, Weighted gene co‐expression network analysis (WGCNA) would be utilized to build a gene co‐expression network, and the most significant module and hub genes was identified. CIBERSORT tools have facilitated the analysis of immune cell infiltration patterns of diseases. The receiver operating characteristic (ROC) analyses were conducted to explore the value of DEGs for SLE diagnosis.

Results

In total, 6 DEGs (IFI27, IFI44, IFI44L, IFI6, EPSTI1 and OAS1) were screened, Biological functions analysis identified key related pathways, gene modules and co‐expression networks in SLE. IFI27 may be closely correlated with the occurrence of SLE. We found that an increased infiltration of moncytes, while NK cells resting infiltrated less may be related to the occurrence of SLE.

Conclusion

IFI27 may be closely related pathogenesis of SLE, and represents a new candidate molecular marker of the occurrence and progression of SLE. Moreover immune cell infiltration plays important role in the progession of SLE.
Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies
Authors: Merviel Philippe , James Pandora , Bouée Sarah , Le Guillou Mathilde , Rince Camille , Nachtergaele Charlotte , Kerlan Véronique
Published: January 2021

Polycystic ovary syndrome (PCOS) is marked in 30 to 40% by insulin resistance and hyperandrogenism. Myo-inositol (MI) increases insulin sensitivity, decreases hyperandrogenism and improves the menstrual cycle. Its effect during assisted reproductive technologies (ART) has been studied by many authors. We conducted a review of the literature on the impact of MI administration in PCOS women in assisted reproductive technologies. Myo-inositol is effective in normalizing ovarian function, improving oocyte and embryo quality in PCOS, however further evaluations by large multicentre randomized controlled trials are needed to assess the clinical pregnancy and live birth rates in ART.
Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes
Authors: Xu Tiantian , Song Qing , Zhou Li , Yang Wenwen , Wu Xiangyao , Qian Qianyu , Chai Hui , Han Qiang , Pan Hongzhi , Dou Xiaobing , Li Songtao
Published: January 2021

Background

Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes.

Methods

AML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference.

Results

Our data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid.

Conclusions

We demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.
Continuous monitoring of plant sodium transport dynamics using clinical PET
Authors: Ruwanpathirana Gihan P. , Plett Darren C. , Williams Robert C. , Davey Catherine E. , Johnston Leigh A. , Kronzucker Herbert J.
Published: January 2021

Background

The absorption, translocation, accumulation and excretion of substances are fundamental processes in all organisms including plants, and have been successfully studied using radiotracers labelled with 11C, 13N, 14C and 22Na since 1939. Sodium is one of the most damaging ions to the growth and productivity of crops. Due to the significance of understanding sodium transport in plants, a significant number of studies have been carried out to examine sodium influx, compartmentation, and efflux using 22Na- or 24Na-labeled salts. Notably, however, most of these studies employed destructive methods, which has limited our understanding of sodium flux and distribution characteristics in real time, in live plants. Positron emission tomography (PET) has been used successfully in medical research and diagnosis for decades. Due to its ability to visualise and assess physiological and metabolic function, PET imaging has also begun to be employed in plant research. Here, we report the use of a clinical PET scanner with a 22Na tracer to examine 22Na-influx dynamics in barley plants (Hordeum vulgare L. spp. Vulgare—cultivar Bass) under variable nutrient levels, alterations in the day/night light cycle, and the presence of sodium channel inhibitors.

Results

3D dynamic PET images of whole plants show readily visible 22Na translocation from roots to shoots in each examined plant, with rates influenced by both nutrient status and channel inhibition. PET images show that plants cultivated in low-nutrient media transport more 22Na than plants cultivated in high-nutrient media, and that 22Na uptake is suppressed in the presence of a cation-channel inhibitor. A distinct diurnal pattern of 22Na influx was discernible in curves displaying rates of change of relative radioactivity. Plants were found to absorb more 22Na during the light period, and anticipate the change in the light/dark cycle by adjusting the sodium influx rate downward in the dark period, an effect not previously described experimentally.

Conclusions

We demonstrate the utility of clinical PET/CT scanners for real-time monitoring of the temporal dynamics of sodium transport in plants. The effects of nutrient deprivation and of ion channel inhibition on sodium influx into barley plants are shown in two proof-of-concept experiments, along with the first-ever 3D-imaging of the light and dark sodium uptake cycles in plants. This method carries significant potential for plant biology research and, in particular, in the context of genetic and treatment effects on sodium acquisition and toxicity in plants.
The watch-and-wait strategy versus surgical resection for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy
Authors: Wang Qiao-xuan , Zhang Rong , Xiao Wei-wei , Zhang Shu , Wei Ming-biao , Li Yong-heng , Chang Hui , Xie Wei-hao , Li Li-ren , Ding Pei-rong , Chen Gong , Zeng Zhi-fan , Wang Wei-hu , Wan Xiang-bo , Gao Yuan-hong
Published: January 2021

Background

The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection.

Methods

Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan–Meier method with the log rank test.

Results

A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%,P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%,P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group,P = 0.874), 3-year disease-specific survival (99% vs. 96%,P = 0.643) and overall survival (99% vs. 96%,P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group.

Conclusion

The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.
A novel frequent BRCA1 recurrent variant c.5117G > A (p.Gly1206Glu) identified after 20 years of BRCA1/2 research in the Baltic region: cohort study and literature review
Authors: Loza P. , Irmejs A. , Daneberga Z. , Miklasevics E. , Berga-Svitina E. , Subatniece S. , Maksimenko J. , Trofimovics G. , Tauvena E. , Ukleikins S. , Gardovskis J.
Published: January 2021

Background

Several recent studies in the Baltic region have found extended spectrum of pathogenic variants (PV) of the BRCA1/2 genes. The aim of current study is to analyze the spectrum of the BRCA1/2 PV in population of Latvia and to compare common PV between populations of the Baltic region.

Methods

We present a cohort of 9543 unrelated individuals including ones with cancer and unaffected individuals from population of Latvia, who were tested for three most common BRCA1 founder PV. In second line testing, 164 founder negative high-risk individuals were tested for PV of the BRCA1/2 using next generation sequencing (NGS). Local spectrum of the BRCA1/2 PV was compared with the Baltic region by performing a literature review.

Results

Founder PV c.5266dupC, c.4035delA or c.181 T > G was detected in 369/9543 (3.9%) cases. Other BRCA1/2 PV were found in 44/164 (26.8%) of NGS cases. Four recurrent BRCA1 variants c.5117G > A (p.Gly1706Glu), c.4675G > A (p.Glu1559Lys), c.5503C > T (p.Arg1835*) and c.1961delA (p.Lys654fs) were detected in 18/44 (41.0%), 5/44 (11.4%), 2/44 (4.5%) and 2/44 (4.5%) cases respectively. Additionally, 11 BRCA1 PV and six BRCA2 PV were each found in single family.

Conclusions

By combining three studies by our group of the same cohort in Latvia, frequency of the BRCA1/2 PV for unselected breast and ovarian cancer cases is 241/5060 (4.8%) and 162/1067 (15.2%) respectively. The frequency of three “historical” founder PV is up to 87.0% (369/424). Other non-founder PV contribute to at least 13.0% (55/424) and this proportion probably will rise by increasing numbers of the BRCA1/2 sequencing. In relative numbers, c.5117G > A is currently the third most frequent PV of the BRCA1 in population of Latvia, overcoming previously known third most common founder variant c.181 T > G. In addition to three BRCA1 founder PV, a total of five recurrent BRCA1 and two recurrent BRCA2 PV have been reported in population of Latvia so far. Many of the BRCA1/2 PV reported in Latvia are shared among other populations of the Baltic region.
Comprehensive understanding of the effects of metallic cations on enzymatic hydrolysis of humic acid-pretreated waste wheat straw
Authors: Tang Wei , Wu Xinxing , Huang Caoxing , Ling Zhe , Lai Chenhuan , Yong Qiang
Published: January 2021

Background

Humic acids (HA) have been used in biorefinery process due to its surfactant properties as an aid to the pretreatment of lignocellulose, with results indicating a positive effect on delignification. However, the HA remaining on the surface of the pretreated lignocellulose has also been shown to provide a negative effect on ensuing enzymatic digestibility. Hence, a strategy of complexing metallic cations with HA prior to enzymatic hydrolysis was proposed and demonstrated in this work in an effort to provide a means of HA mitigation that does not involve significant water consumption via extensive washing.

Results

Results showed that the enzymatic hydrolysis efficiency of waste wheat straw decreased from 81.9% to 66.1% when it was pretreated by 10 g/L HA, attributed to the inhibition ability of the residual HA on enzyme activity of cellulase with a debasement of 36.3%. Interestingly, enzymatic hydrolysis efficiency could be increased from 66.1% to 77.3% when 10 mM Fe3+was introduced to the system and allowed to associate with HA during saccharification.

Conclusions

The addition of high-priced metallic cations (Fe3+) has successfully alleviated the effect of HA on cellulase activity. It is our hope in demonstrating the complexation affinity between metallic cations and HA, future researchers and biorefinery developers will evaluate this strategy as a unit operation that could allow economic biorefining of WWS to produce valuable biochemicals, biofuels, and biomaterials.
Pain chronification and the important role of non-disease-specific symptoms in patients with systemic sclerosis
Authors: Evers Caroline , Jordan Suzana , Maurer Britta , Becker Mike Oliver , Mihai Carina , Dobrota Rucsandra , Hoederath Petra , Distler Oliver
Published: January 2021

Background

Pain is a frequent, yet inadequately explored challenge in patients with systemic sclerosis (SSc). This study aimed to conduct an extensive pain assessment, examining pain chronification and its association with disease manifestations.

Methods

Consecutive SSc patients attending their annual assessment were included. SSc-specific features were addressed as defined by the European Scleroderma Trials and Research (EUSTAR) guidelines. Pain analysis included intensity, localization, treatment, chronification grade according to the Mainz Pain Staging System (MPSS), general well-being using the Marburg questionnaire on habitual health findings (MFHW) and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).

Results

One hundred forty-seven SSc patients completed a pain questionnaire, and 118/147 patients reporting pain were included in the analysis. Median pain intensity was 4/10 on a numeric rating scale (NRS). The most frequent major pain localizations were hand and lower back. Low back pain as the main pain manifestation was significantly more frequent in patients with very early SSc (p = 0.01); those patients also showed worse HADS and MFHW scores. Regarding pain chronification, 34.8% were in stage I according to the MPSS, 45.2% in stage II and 20.0% in stage III. There was no significant correlation between chronification grade and disease severity, but advanced chronification was significantly more frequent in patients with low back pain (p = 0.024). It was also significantly associated with pathological HADS scores (p < 0.0001) and linked with decreased well-being and higher use of analgesics.

Conclusions

Our study implies that also non-disease-specific symptoms such as low back pain need to be considered in SSc patients, especially in early disease. Since low back pain seems to be associated with higher grades of pain chronification and psychological problems, our study underlines the importance of preventing pain chronification in order to enhance the quality of life.
Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy
Authors: Rugowska Anna , Starosta Alicja , Konieczny Patryk
Published: January 2021

Duchenne muscular dystrophy (DMD) is a multisystemic disorder that affects 1:5000 boys. The severity of the phenotype varies dependent on the mutation site in theDMDgene and the resultant dystrophin expression profile. In skeletal muscle, dystrophin loss is associated with the disintegration of myofibers and their ineffective regeneration due to defective expansion and differentiation of the muscle stem cell pool. Some of these phenotypic alterations stem from the dystrophin absence-mediated serine–threonine protein kinase 2 (MARK2) misplacement/downregulation in activated muscle stem (satellite) cells and neuronal nitric oxide synthase loss in cells committed to myogenesis. Here, we trace changes in DNA methylation, histone modifications, and expression of regulatory noncoding RNAs during muscle regeneration, from the stage of satellite cells to myofibers. Furthermore, we describe the abrogation of these epigenetic regulatory processes due to changes in signal transduction in DMD and point to therapeutic treatments increasing the regenerative potential of diseased muscles based on this acquired knowledge.
Differences of embedding adipose-derived stromal cells in natural and synthetic scaffolds for dermal and subcutaneous delivery
Authors: Mamsen Frederik Penzien , Munthe-Fog Lea , Kring Mikela Karen Mungal , Duscher Dominik , Taudorf Mikkel , Katz Adam J. , Kølle Stig-Frederik Trojahn
Published: January 2021

Background

In recent years, adipose-derived stromal cells (ASCs) have been heavily studied for soft tissue regeneration, augmentation, and dermal wound healing.

Methods

In this review, we investigated the trends in injectable scaffolds for ASC delivery in the dermis, and injectable or implantable scaffolds for ASC delivery in the subcutis. A total of 547 articles were screened across three databases; of these, 22 studies were found to be eligible and were included. The scaffolds were subdivided and analyzed based on their tissue placement (dermis or subcutis), delivery method (injected or implanted), and by the origin of the materials (natural, synthetic, and combinatory).

Results

ASCs embedded in scaffolds generally showed improved viability. Neovascularization in the transplanted tissue was greater when undifferentiated ASCs were embedded in a combinatory scaffold or if differentiated ASCs were embedded in a natural scaffold. ASCs embedded in natural materials underwent more adipogenic differentiation than ASCs embedded in synthetic scaffolds, indicating an etiologically unknown difference that has yet to be described. Increased mechanical strength of the scaffold material correlated with improved outcome measurements in the investigated studies. Wound healing studies reported reduced healing time in all except one article due to contraction of the control wounds.

Conclusions

In future clinical trials, we recommend embedding ASCs in injectable and implantable scaffolds for enhanced protection, retained viability, and improved therapeutic effects.

Trial registration

This review was registered with PROSPERO: ID=CRD42020171534.

Graphical abstract

The use of scaffolds as a vehicle for ASC delivery generally improved cell viability, angiogenesis, and wound healing in vivo compared to utilizing ASCs alone. ASCs embedded in natural materials induced more adipogenesis than ASCs embedded in synthetic materials. Adipogenic-induced ASCs further increased this effect. The included studies indicate that the seeded scaffold material influences the differentiation of ASCs in vivo. All studies investigating the mechanical strength of ASC scaffolds reported improved outcome measurements with improved mechanical strength. The results suggest that scaffolds, in general, are favorable for ASC delivery. We recommend initiating clinical studies using scaffolds based on mechanical properties and tunability to improve ASC viability. For fat regeneration, natural scaffolds are recommended.
Transplantation of retinal pigment epithelium and photoreceptors generated concomitantly via small molecule-mediated differentiation rescues visual function in rodent models of retinal degeneration
Authors: Surendran Harshini , Nandakumar Swapna , Reddy K Vijay Bhaskar , Stoddard Jonathan , Mohan K Varsha , Upadhyay Pramod K. , McGill Trevor J. , Pal Rajarshi
Published: January 2021

Background

Age-related macular degeneration (AMD) is a result of degeneration/damage of the retinal pigment epithelium (RPE) while retinitis pigmentosa (RP), an inherited early-onset disease, results from premature loss of photoreceptors. A promising therapeutic approach for both is the replacement of lost/damaged cells with human induced pluripotent stem cell (hiPSC)-derived retinal cells.

Methods

The aim of this study was to investigate the in vivo functionality of RPE and photoreceptor progenitor (PRP) cells derived from a clinical-grade hiPSC line through a unified protocol. De novo-generated RPE and PRP were characterized extensively to validate their identity, purity, and potency.

Results

RPE expressed tight junction proteins, showed pigmentation and ciliation, and secreted polarization-related factors vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). PRP expressed neural retina proteins and cone and rod markers, and responded to KCl-induced polarization. Transcriptomic analysis demonstrated an increase in the expression of mature retinal tissue-specific genes coupled with concomitant downregulation of genes from undesired lineages. RPE transplantation rescued visual function in RCS rats shown via optokinetic tracking and photoreceptor rescue. PRP transplantation improved light perception in NOD.SCID-rd1 mice, and positive electroretinography signals indicated functional photoreceptor activity in the host’s outer nuclear layer. Graft survival and integration were confirmed using immunohistochemistry, and no animals showed teratoma formation or any kind of ectopic growth in the eye.

Conclusions

To our knowledge, this is the first demonstration of a unified, scalable, and GMP-adaptable protocol indicating strong animal efficacy and safety data with hiPSC-derived RPE and PRP cells. These findings provide robust proof-of-principle results for IND-enabling studies to test these potential regenerative cell therapies in patients.
Characterization of efficient xylanases from industrial-scale pulp and paper wastewater treatment microbiota
Authors: Wang Jia , Liang Jiawei , Li Yonghong , Tian Lingmin , Wei Yongjun
Published: January 2021

Xylanases are widely used enzymes in the food, textile, and paper industries. Most efficient xylanases have been identified from lignocellulose-degrading microbiota, such as the microbiota of the cow rumen and the termite hindgut. Xylanase genes from efficient pulp and paper wastewater treatment (PPWT) microbiota have been previously recovered by metagenomics, assigning most of the xylanase genes to the GH10 family. In this study, a total of 40 GH10 family xylanase genes derived from a certain PPWT microbiota were cloned and expressed in Escherichia coli BL21 (DE3). Among these xylanase genes, 14 showed xylanase activity on beechwood substrate. Two of these, PW-xyl9 and PW-xyl37, showed high activities, and were purified to evaluate their xylanase properties. Values of optimal pH and temperature for PW-xyl9 were pH 7 and 60 ℃, respectively, while those for PW-xyl37 were pH 7 and 55 ℃, respectively; their specific xylanase activities under optimal conditions were 470.1 U/mg protein and 113.7 U/mg protein, respectively. Furthermore, the Km values of PW-xyl9 and PW-xyl37 were determined as 8.02 and 18.8 g/L, respectively. The characterization of these two xylanases paves the way for potential application in future pulp and paper production and other industries, indicating that PPWT microbiota has been an undiscovered reservoir of efficient lignocellulase genes. This study demonstrates that a metagenomic approach has the potential to screen efficient xylanases of uncultured microorganisms from lignocellulose-degrading microbiota. In a similar way, other efficient lignocellulase genes might be identified from PPWT treatment microbiota in the future.
Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study
Authors: Tanaka Sébastien , Stern Jules , Bouzid Donia , Robert Tiphaine , Dehoux Monique , Snauwaert Aurélie , Zappella Nathalie , Cournot Maxime , Lortat-Jacob Brice , Augustin Pascal , Atchade Enora , Tran-Dinh Alexy , Meilhac Olivier , Montravers Philippe
Published: January 2021

Background

High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome.

Methods

A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient’s hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed.

Results

A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04–1.57) mmol/l; day 1 HDL-C = 0.44 (0.29–0.70) mmol/l; day 3 HDL-C = 0.30 (0.25–0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42–0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91–3.33) mmol/l; day 1 LDL-C = 1.0 (0.58–1.50) mmol/l; day 3 LDL-C = 1.04 (0.64–1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26–2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p < 0.001 and p = 0.007, respectively). No link was found between prior lipid profile and mortality.

Conclusions

We showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.
Complete moment convergence of moving average processes for m-WOD sequence
Authors: Guan Lihong , Xiao Yushan , Zhao Yanan
Published: January 2021

In this paper, the complete moment convergence for the partial sum of moving average processes $\{X_{n}=\sum_{i=-\infty }^{\infty }a_{i}Y_{i+n},n\geq 1\}$
{

X
n

=

∑

i
=
−
∞

∞

a
i

Y

i
+
n

,
n
≥
1
}
is established under some mild conditions, where $\{Y_{i},-\infty < i<\infty \}$
{

Y
i

,
−
∞
<
i
<
∞
}
is a sequence of m-widely orthant dependent (m-WOD, for short) random variables which is stochastically dominated by a random variable Y, and $\{a_{i},-\infty < i<\infty \}$
{

a
i

,
−
∞
<
i
<
∞
}
is an absolutely summable sequence of real numbers. These conclusions promote and improve the corresponding results from m-extended negatively dependent (m-END, for short) sequences to m-WOD sequences.
Minimal set of periods for continuous self-maps of the eight space
Authors: Llibre Jaume , Sá Ana
Published: January 2021

Let $G_{k}$

G
k

be a bouquet of circles, i.e., the quotient space of the interval $[0,k]$
[
0
,
k
]
obtained by identifying all points of integer coordinates to a single point, called the branching point of $G_{k}$

G
k

. Thus, $G_{1}$

G
1

is the circle, $G_{2}$

G
2

is the eight space, and $G_{3}$

G
3

is the trefoil. Let $f: G_{k} \to G_{k}$
f
:

G
k

→

G
k

be a continuous map such that, for $k>1$
k
>
1
, the branching point is fixed.

If $\operatorname{Per}(f)$
Per
(
f
)
denotes the set of periods of f, the minimal set of periods of f, denoted by $\operatorname{MPer}(f)$
MPer
(
f
)
, is defined as $\bigcap_{g\simeq f} \operatorname{Per}(g)$

⋂

g
≃
f

Per
(
g
)
where $g:G_{k}\to G_{k}$
g
:

G
k

→

G
k

is homological to f.

The sets $\operatorname{MPer}(f)$
MPer
(
f
)
are well known for circle maps. Here, we classify all the sets $\operatorname{MPer}(f)$
MPer
(
f
)
for self-maps of the eight space.
Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC)
Authors: Zhengqi Qiu , Zezhi Guo , Lei Jiang , He Qiu , Jinyao Pan , Ying Ao
Published: January 2021

This study attempts to evaluate the prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC) by means of publicly available data from The Cancer Genome Atlas (TCGA). Clinical pathologic features and PHYH expression were downloaded from the TCGA database and relationships between them were analyzed by univariate and multivariate Cox regression analyses. Gene Set Enrichment Analysis (GSEA) and gene–gene interactions were also performed between tissues with different PHYH expression levels. PHYH expression levels were significantly lower in patient with ccRCC compared with normal tissues (p = 1.156e−19). Kaplan–Meier survival analysis showed that high expression of PHYH had a better prognosis than low expression (p = 9e−05). Moreover, PHYH expression was also significantly associated with high grade (G2-4, p = 0.025), high stage (StageIII & IV, p = 5.604e−05), and high level of stage_T (T3-4, p = 4.373e−05). Univariate and multivariate Cox regression analyses indicated that PHYH could be acted as an independent prognostic factor (p < 0.05). Nomogram including clinical pathologic features and PHYH expression were also provided. GSEA revealed that butanoate metabolism, histidine metabolism, propanoate metabolism, pyruvate metabolism, tryptophan metabolism, PPAR signalling pathway, and renin–angiotensin system were differentially enriched in PHYH high-expression phenotype. ICGC database was utilized to verify the expression level and survival benefit of PHYH (both p < 0.05). We suspect that elevated PHYH expression may be served as a potential prognostic molecular marker of better survival in ccRCC. Besides, alpha-oxidation was closely regulated by PHYH, and PPAR signalling, pyruvate metabolism, butanoate metabolism, and RAS might be the key pathways regulated by PHYH in CCRC.
Avoiding a Med-Wreck: a structured medication reconciliation framework and standardized auditing tool utilized to optimize patient safety and reallocate hospital resources
Authors: Elbeddini Ali , Almasalkhi Sarah , Prabaharan Thulasika , Tran Cindy , Gazarin Mohamed , Elshahawi Ahmed
Published: January 2021

Background

The incidence of preventable adverse drug events (ADE) is approximately one medication error per patient per hospital-day. A quality medication reconciliation (MedRec) process is a crucial intervention used to reduce ADE in the hospital and community setting. Amid the coronavirus disease 2019 (COVID-19) pandemic, preventing medication errors is vital to avoid patient readmission, reduce disease complications, and reduce cost and patient burden on the healthcare system.

Objectives

To develop a standardized MedRec framework that can be implemented in all healthcare settings to reduce patient and staff harm during COVID-19. Also, to create a standardized auditing tool used to assess the quality of the MedRec process and allow for continuous quality improvement.

Methods

A multi-site gap analysis (MGA) was performed to collect observational data that were collected from four different healthcare sites (two hospitals, a long-term care facility, and a community pharmacy). MGA consists of collecting data across several sites which answer a standardized questionnaire. A standardized MedRec framework and auditing tool were developed based on the gaps observed in each site and literature reviews.

Results

A standardized MedRec process was not implemented in any of the observed sites. The healthcare sites lacked a designated MedRec team and training related to the MedRec process leading to multiple discrepancies at discharge. Patients were not counselled on changes to home medications, and a discharge report was often not provided upon discharge. Communication mechanisms between community pharmacies and hospital physicians are not available or easily accessible.

Conclusion

The proposed structured MedRec framework is vital to reduce medication errors and patient harm amid COVID-19. Moreover, the comprehensive auditing tool developed in this study allows for continuous quality improvement resulting in superior quality care, reduction of workflow inefficiencies, cost savings on hospital readmissions, and overall enhanced healthcare system performance.
Glymphatic system, AQP4, and their implications in Alzheimer’s disease
Authors: Silva Inês , Silva Jéssica , Ferreira Rita , Trigo Diogo
Published: January 2021

Lacking conventional lymphatic system, the central nervous system requires alternative clearance systems, such as the glymphatic system, which promotes clearance of interstitial solutes. Aquaporin-4 water channels (AQP4) are an integral part of this system and related to neuropathologies, such as Alzheimer’s disease (AD). The clearance of Alzheimer’s associated proteins amyloid β and tau is diminished by glymphatic system impairment, due to lack of AQP4. Even though AQP4 mislocalisation (which affects its activity) is a phenotype of AD, it remains a controversial topic, as it is still unclear if it is a phenotype-promoting factor or a consequence of this pathology. This review provides important and updated knowledge about glymphatic system, AQP4 itself, and their link with Alzheimer’s disease. Finally, AQP4 as a therapeutic target is proposed to ameliorate Alzheimer’s Disease and other neuropathologies AQP4-related.
The curious case of C-88: impacts of a potato variety on farmers in Yunnan, China
Authors: Myrick Stephanie , Pradel Willy , Li Canhui , Suarez Victor , Hareau Guy , Larochelle Catherine , Norton George W. , Alwang Jeffrey
Published: January 2021

Background

Limited analysis has been conducted of the role of agricultural research in promoting Chinese agricultural growth in less-favored areas. This paper analyzes how a particular potato variety generates benefits to producers and discusses how these benefits may have contributed to poverty reduction in Yunnan province. Cooperation 88 (C88) is a high-yielding, late blight-resistant variety that was developed through a partnership between the International Potato Center and Yunnan Normal University in Kunming, China.

Methods

Qualitative and quantitative methods are used to analyze determinants of adoption of C88, and to estimate impacts of adoption on producer well-being. A unique farm-household database is used to document the determinants of C88 adoption and disadoption. The quantitative assessment is supplemented with a qualitative analysis of the potato value chain to understand how seed availability and concern for processing attributes contributed to and eventually constrained diffusion. Market-level information was used in an economic surplus model to quantify the substantial economic impact of C88 over 20 years since its release.

Results

C88 spread rapidly in Yunnan following its release and was widely adopted by commercially oriented farmers. Disadoption began after 2010 with limited seed availability driving the shift toward newer varieties. Farmers, however, appreciate the ease of marketing, the 15% higher yields, and late-blight resistance associated with C88 suggesting that seed constraints are countervailing the economic benefits of the variety. Total impact on Yunnan potato farmers of the variety was estimated to be around $2.5 billion for the 1996–2015 period.

Conclusions

On per-person terms among C88 growing farm households, the economic advantage of the variety is likely to have contributed to poverty reduction. The aggregate impact of C88 diffusion occurred during a period of rapid poverty reduction in Yunnan and yield and disease-resistance benefits of C88 likely contributed to this reduction.
Seismic illumination of small-throw seismogenic faults, Anadarko Basin, Oklahoma
Authors: Patel Swetal , Kolawole Folarin , Walter Jacob I. , Chen Xiaowei , Marfurt Kurt J.
Published: January 2021

Substantial increase in the occurrence of injection-induced seismicity across Central and Eastern United States in the past decade, has highlighted a need for novel approaches to geophysical subsurface imaging of potentially seismogenic faults. Active clusters of seismicity illuminate linear fault segments within the sedimentary cover and crystalline basement that were unknown until seismicity began. Such surprises are due to the limited availability of 3D seismic reflection surveys and the difficulty of imaging relatively shallow earthquake events from sparse seismic monitoring arrays. The Sooner Trend Anadarko Basin Canadian Kingfisher Counties (STACK) play of the Anadarko Basin, Oklahoma, provides an opportunity to investigate these earthquake-prone basement faults. Modern high-quality seismic data acquired to map unconventional resource plays in the STACK enable us to assess the detailed subsurface structure. Furthermore, because of increased earthquake risk from anthropogenic activities in the past decade, state regulatory agencies have deployed a dense array of seismic monitoring stations, which allows us to integrate earthquake data with seismic reflection data for analysis of active faulting. We have mapped structural deformation using a suite of seismic attributes, including multispectral coherence, volumetric curvature, and aberrancy, in a 3D seismic reflection data set covering 625 sq mi of the STACK area. To unravel the relationship between the structures and seismicity, we use relocated locally recorded earthquakes and compute the focal mechanism solution for the events. Our results reveal previously unmapped small-throw (<120 m) fault segments with dominant north–south, northwest, and northeast trends, most of which extend from the basement up into the shallower sedimentary Hunton and Woodford Formations. Because of the small offset, we find that aberrancy and the curvature attribute best illuminate the basement-rooted faults in the sedimentary cover. Fault segments with significant vertical offset are better illuminated by band-limited multispectral coherence. We argue that the inherited structure of these faults makes them mostly illuminable by flexure-related seismic attributes, especially within the sedimentary cover. The integration of the illuminated faults with relocated earthquakes and focal mechanism solutions shows that the illuminated faults that have hosted intrasedimentary and/or basement seismicity are reactivated by strike-slip faulting. We hypothesize that careful attribute mapping of faults and related flexures, integrated with recent seismic activity data, and an understanding of the local stress and geomechanical properties, can help mitigate seismic hazards in similar intraplate geological settings where small-throw faults predominate.
Mississippian Meramec lithologies and petrophysical property variability, stack trend, Anadarko Basin, Oklahoma
Authors: Miller Michael J. , Pranter Matthew J. , Gupta Ishank , Devegowda Deepak , Marfurt Kurt J. , Sondergeld Carl , Rai Chandra , McLain Chris T. , Packwood James , Larese Richard E.
Published: January 2021

Mississippian Meramec reservoirs of the Sooner Trend in the Anadarko (Basin) in Canadian and Kingfisher Counties (STACK) play are comprised of silty limestones, calcareous siltstones, argillaceous calcareous siltstones, argillaceous siltstones, and mudstones. We found that core-defined reservoir lithologies are related to petrophysics-based rock types derived from porosity-permeability relationships using a flow-zone indicator approach. We classified lithologies and rock types in noncored wells using an artificial neural network (ANN) with overall accuracies of 93% and 70%, respectively. We observed that mudstone-rich rock type 1 exhibits high clay and relatively low calcite, whereas calcareous-rich rock type 3 has high calcite and low clay content with rock type 2 falling in between as a balance between rock types 1 and 3. Results of the ANN were applied to a suite of well logs in noncored wells in which we generated lithology and rock-type logs for the Meramec. We identified that the Meramec consists of seven stratigraphic units characterized as strike-elongate, shoaling-upward parasequences; each parasequence is capped by a marine-flooding surface. The lower three parasequences (lower Meramec) form a retrogradational parasequence set that back steps to the northwest and is capped by a maximum flooding surface. The upper Meramec is characterized by parasequences that form an aggradational to progradational stacking pattern followed again by a retrogradational trend. We predict that the parasequence stacking, associated lithology distribution, and diagenetic cements appear to control the spatial distribution of petrophysical properties (porosity, permeability, and water saturation), pore volume, and hydrocarbon pore volume (HCPV). Calcareous-rich lithologies exhibit lower porosity, permeability, HCPV, and higher water saturation. We deduced that argillaceous-rich lithologies that occur near the maximum flooding surface are the most favorable reservoir intervals because they exhibit relatively higher porosity, permeability, HCPV, and lower water saturation. Productivity could not be directly correlated to rock types as operational and completion factors as well as overpressure and oil phase play important roles on production.
Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition
Authors: Pietzner Maik , Budde Kathrin , Rühlemann Malte , Völzke Henry , Homuth Georg , Weiss Frank U , Lerch Markus M , Frost Fabian
Published: January 2021

Purpose

Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota.

Design

Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry.

Results

Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines.

Conclusion

These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.
Stellate Ganglion Block as a Diagnostic and Therapeutic Option in Chronic Pericardial Pain: A Case Report
Authors: Feigin Guy , Wang Ning Nan , Flamer David
Published: January 2021

The underlying pathophysiology and treatment of chronic pericardial chest pain remains unclear. We describe a clinical case of a 38-year-old patient with chronic chest pain in the context of Marfan syndrome, status post–valve-sparing aortic root repair, and recurrent pericarditis. The patient suffers from chronic pericardial pain secondary to recurrent pericarditis refractory to pharmacotherapy. A left-sided stellate ganglion block (SGB) was performed for both diagnostic and therapeutic purposes. Postprocedure follow-up demonstrated significant analgesic benefit at 8 months after the procedure.
The p.E152K-STIM1 mutation deregulates Ca2+ signaling contributing to chronic pancreatitis
Authors: Burgos Miguel , Philippe Reginald , Antigny Fabrice , Buscaglia Paul , Masson Emmanuelle , Mukherjee Sreya , Dubar Pauline , Le Maréchal Cédric , Campeotto Florence , Lebonvallet Nicolas , Frieden Maud , Llopis Juan , Domingo Beatriz , Stathopulos Peter B. , Ikura Mitsuhiko , Brooks Wesley , Guida Wayne , Chen Jian-Min , Ferec Claude , Capiod Thierry , Mignen Olivier
Published: January 2021

Since deregulation of intracellular Ca2+ can lead to intracellular trypsin activation, and stromal interaction molecule-1 (STIM1) protein is the main regulator of Ca2+ homeostasis in pancreatic acinar cells, we explored the Ca2+ signaling in 37 STIM1 variants found in three pancreatitis patient cohorts. Extensive functional analysis of one particular variant, p.E152K, identified in three patients, provided a plausible link between dysregulated Ca2+ signaling within pancreatic acinar cells and chronic pancreatitis susceptibility. Specifically, p.E152K, located within the STIM1 EF-hand and sterile α-motif domain, increased the release of Ca2+ from the endoplasmic reticulum in patient-derived fibroblasts and transfected HEK293T cells. This event was mediated by altered STIM1–sarco/endoplasmic reticulum calcium transport ATPase (SERCA) conformational change and enhanced SERCA pump activity leading to increased store-operated Ca2+ entry (SOCE). In pancreatic AR42J cells expressing the p.E152K variant, Ca2+ signaling perturbations correlated with defects in trypsin activation and secretion, and increased cytotoxicity after cholecystokinin stimulation.

This article has an associated First Person interview with the first author of the paper.