bluuebunny/crossref_metadata_2025 huggingface dataset:
The acupoint herbal plaster for the prevention and treatment of postoperative nausea and vomiting after PLIF with general anesthesia: study protocol for a multicenter randomized controlled trial
Authors: Xu Huiqing , Wei Xu , Zhang Ranxing , Li Ling , Zhang Zhijun , Jia Ruo , Zhang Xiaofei , Gao Xiumei , Dong Xicheng , Pan Junjun
Published: January 2021

Background

Postoperative nausea and vomiting (PONV) are common in posterior lumbar intervertebral fusion (PLIF) patients undergoing general anesthesia. The previous clinical observation has shown that a traditional acupoint herbal plaster (AHP) is beneficial to patients with PONV. This trial aims to assess the effect of the AHP for the prevention and treatment of PONV after PLIF in patients with general anesthesia.

Methods

A multicenter, parallel, randomized controlled trial (RCT) will be conducted. A total of 166 participants will be randomized to either a treatment group receiving an AHP or a control groups receiving an acupoint placebo plaster (APP) in a 1:1 ratio. The primary outcomes are the first occurrence and frequency of nausea and vomiting. The secondary outcomes include the severity grading of nausea and vomiting using a visual analog scale (VAS) measurement system, quality of life, and serological indicators. The safety evaluation is mainly about adverse events and skin reactions’ observation. Assessments will be carried out at the baseline, day 1, and day 2 (the end of the intervention). The central randomization system in the clinical trial (http://124.205.181.142:8082/xwtf/) will be used to conduct random allocation.

Discussion

This scientific methodology design of the trial is expected to provide clinical evidence to support the AHP for the prevention and treatment of PONV.

Trial registration

This study is retrospectively registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn) on 19 April 2018. ID: ChiCTR1800015768.
Efficacy of silver needle therapy for the treatment of chronic nonspecific low back pain: a prospective, single-center, randomized, parallel-controlled clinical trial
Authors: Hu Xuesong , Dong Shaoxing , Zhang Bing , Wang Xuan , Yin Yanwei , Liu Chuansheng , Yu Junmin , Wu Xing , Xu Fenghu , Meng Chao
Published: January 2021

Background

Chronic nonspecific low back pain (CNSLBP) troubles approximately 30% of people worldwide. Silver needle therapy (SNT) is a treatment method to relieve soft tissue pain through heating. Therefore, this study aimed to observe the effects of SNT on CNSLBP.

Methods

In this study, 100 patients were randomly divided into 2 groups: silver needle (SN) group and control group (n = 50). In the SN group, patients received SNT and physiotherapy, while patients received physiotherapy alone in the control group. At the 6-month follow-up, the numerical rating scale (NRS), Oswestry Disability Index (ODI), Short-Form 12 of quality of life (SF-12), the natural logarithms of low-frequency measurement (InLF), and the natural logarithms of high-frequency measurement (InHF) of heart rate variability (HRV) were recorded.

Results

In both groups, NRS, ODI, SF-12 scores, and HRV at 2 weeks after treatment were improved and maintained for 6 months. Compared with the control group, more significant improvements were observed in the NRS and SF-12 scores at 1, 2, 3, and 6 months and in the ODI scores at 1 and 2 months in the SN group (P <  0.05). However, there was no significant difference between the groups in the ODI scores at 3 and 6 months. InLF and InHF in the SN group were higher than those in the control group at 3 and 6 months (P <  0.05).

Conclusions

SNT relieved pain and improved quality of life and autonomic nerve activity, especially parasympathetic nerve, in patients with CNSLBP, without serious complications.

Trial registration

Chinese Clinical Trial Registry No.ChiCTR-OOC-17013237. Registered on November 11, 2017.
Detection of bluetongue virus in Culicoides spp. in southern Yunnan Province, China
Authors: Duan Ying Liang , Li Le , Bellis Glenn , Yang Zhen Xing , Li Hua Chun
Published: January 2021

Background

Culicoides (Diptera: Ceratopogonidae) are vectors for many arboviruses. At least 20 species are considered as vectors or potential vectors of bluetongue virus (BTV) which cause bluetongue disease in ruminants. A BTV prevalence of 30–50% among cattle and goats in tropical southern Yunnan Province, China, prompted an investigation of the potential BTV vectors in this area.

Methods

Culicoides were collected by light trapping at three sites in the tropical region of Yunnan Province. Species were identified based on morphology and DNA sequences of cytochrome c oxidase subunit 1 (cox1). PCR and quantitative PCR following reverse transcription were used to test for the presence of BTV RNA in these specimens. Phylogenetic analysis was used to analyze the cox1 sequences of Culicoides specimens infected with BTV.

Results

Approximately 67,000 specimens of Culicoides were collected, of which 748 were tested for the presence of BTV. Five specimens, including two of Culicoides jacobsoni, one of C. tainanus and two of C. imicola, were identified as infected with BTV. No specimens of C. (subgenus Trithecoides) or C. oxystoma tested were positive for BTV infection.

Conclusions

To our knowledge this is the first report of C. jacobsoni as a potential BTV vector and the fourth report of an association between C. tainanus and BTV, as well as the first direct evidence of an association between BTV and C. imicola in Asia. A fourth potential cryptic species within C. tainanus was identified in this study. Further analysis is required to confirm the importance of C. jacobsoni and C. tainanus in BTV epidemiology in Asia.

Graphical Abstract
Detection of heartworm antigen without cross-reactivity to helminths and protozoa following heat treatment of canine serum
Authors: Gruntmeir Jeff M. , Thompson Nina M. , Long Maureen T. , Blagburn Byron L. , Walden Heather D. S.
Published: January 2021

Background

Detection ofDirofilaria immitis, or heartworm, through antigen in sera is the primary means of diagnosing infections in dogs. In recent years, the practice of heat-treating serum prior to antigen testing has demonstrated improved detection of heartworm infection. While the practice of heat-treating serum has resulted in earlier detection and improved sensitivity for heartworm infections, it has been suggested that heat treatment may cause cross reactivity withA. reconditumand intestinal helminth infections of dogs. No studies have assessed the potential cross-reactivity of these parasites with heartworm tests before and after heat treatment using blood products and an appropriate gold standard reference.

Methods

Canine sera (n=163) was used to evaluate a heartworm antigen-ELISA (DiroCHEK®) and potential cross-reactivity with common parasitic infections. The heartworm status and additional parasite infections were confirmed by necropsy and adult helminth species verified morphologically or by PCR, and feces evaluated by centrifugal fecal flotation.

Results

Intestinal parasites were confirmed in 140 of the dogs by necropsy, and 130 by fecal flotation.Acanthocheilonema reconditummicrofilariae were confirmed in 22 dogs. Prevalence of heartworm infection confirmed by necropsy was 35.6% (58/163). In the 105 dogs without heartworms, specificity remained unchanged at 100% both before and after heat treatment despite confirmed infections withA. reconditum,Ancylostoma caninum,Ancylostoma brasiliense,Trichuris vulpis,Toxocara canis,Dipylidium caninum,Spirometra mansonoides,Macracanthorynchus ingens,Cystoisosporasp.,Giardiasp., andSarcocystissp.

Conclusions

These findings suggest that the use of heat treatment improves sensitivity of heartworm tests and is unlikely to cause false positive antigen results due toAcanthocheilonema reconditum, intestinal helminths, and protozoal parasites in dogs.

Graphical Abstract
Transcriptome-wide association study identifies susceptibility genes for rheumatoid arthritis
Authors: Wu Cuiyan , Tan Sijian , Liu Li , Cheng Shiqiang , Li Peilin , Li Wenyu , Liu Huan , Zhang Feng’e , Wang Sen , Ning Yujie , Wen Yan , Zhang Feng
Published: January 2021

Objective

To identify rheumatoid arthritis (RA)-associated susceptibility genes and pathways through integrating genome-wide association study (GWAS) and gene expression profile data.

Methods

A transcriptome-wide association study (TWAS) was conducted by the FUSION software for RA considering EBV-transformed lymphocytes (EL), transformed fibroblasts (TF), peripheral blood (NBL), and whole blood (YBL). GWAS summary data was driven from a large-scale GWAS, involving 5539 autoantibody-positive RA patients and 20,169 controls. The TWAS-identified genes were further validated using the mRNA expression profiles and made a functional exploration.

Results

TWAS identified 692 genes with PTWAS values < 0.05 for RA. CRIPAK (PEL = 0.01293, PTF = 0.00038, PNBL = 0.02839, PYBL = 0.0978), MUT (PEL = 0.00377, PTF = 0.00076, PNBL = 0.00778, PYBL = 0.00096), FOXRED1 (PEL = 0.03834, PTF = 0.01120, PNBL = 0.01280, PYBL = 0.00583), and EBPL (PEL = 0.00806, PTF = 0.03761, PNBL = 0.03540, PYBL = 0.04254) were collectively expressed in all the four tissues/cells. Eighteen genes, including ANXA5, AP4B1, ATIC (PTWAS = 0.0113, downregulated expression), C12orf65, CMAH, PDHB, RUNX3 (PTWAS = 0.0346, downregulated expression), SBF1, SH2B3, STK38, TMEM43, XPNPEP1, KIAA1530, NUFIP2, PPP2R3C, RAB24, STX6, and TLR5 (PTWAS = 0.04665, upregulated expression), were validated with integrative analysis of TWAS and mRNA expression profiles. TWAS-identified genes functionally involved in endoplasmic reticulum organization, regulation of cytokine production, TNF signaling pathway, immune response-regulating signaling pathway, regulation of autophagy, etc.

Conclusion

We identified multiple candidate genes and pathways, providing novel clues for the genetic mechanism of RA.
Obesity, leptin, and deregulation of microRNA in lipid metabolisms: their contribution to breast cancer prognosis
Authors: Taroeno-Hariadi Kartika W. , Hardianti Mardiah S. , Sinorita Hemi , Aryandono Teguh
Published: January 2021

Obesity and Metabolic Syndrome have been associated with cardiovascular, diabetes and cancer incidence. Obesity is a state of inflammation. There are cross-talks between adipocyte, adipokines, pro-inflammatory cytokines, insulin, leptin, and other growth factors to initiate signals for proliferation, anti-apoptosis, and angiogenesis. Those networks lead to cancer initiation, promotion, progression, and metastasis. Post menopause women with breast cancer commonly have overweight, obesity, and metabolic syndrome, which are previously reported as conditions to be associated with breast cancer prognosis. MicroRNAs (miRNAs), small non-coding RNA that regulate gene expression, are known to play important roles either in metabolic or carcinogenesis process in patients with breast cancer. Some miRNAs expressions are deregulated in persons either with obesity, breast cancer, or breast cancer with co-morbid obesity. This literature review aimed at reviewing recent publications on the role of obesity, leptin, and microRNA deregulation in adverse prognosis of breast cancer. Understanding the influence of deregulated miRNAs and their target genes in patients with breast cancer and obesity will direct more studies to explore the potential prognostic role of obesity in breast cancer from epigenetic points of view.
Correlation of glycemic regulation and endotrophin in patients with type 2 Diabetes; pilot study
Authors: Yoldemir Sengul Aydin , Arman Yucel , Akarsu Murat , Altun Ozgur , Ozcan Mustafa , Tukek Tufan
Published: January 2021

Background

Endotrophin is one of the extracellular matrix proteins secreted by adipose tissue. In this study, we aimed to investigate the effects of changes in blood glucose levels on serum endotrophin levels secreted by adipose tissue and thus on diabetes.

Methods

In this prospective pilot study included 78 patients with type 2 diabete (T2D) with hemoglobin A1c level > 9 %. Lifestyle changes were recommended and appropriate medical treatment was initiated to all patients in order to reach the target HbA1c level. Data of anthropometric measurements, urinary albumin creatinine ratio (UACR), serum lipid parameters and endotrophin were collected in patients; all examinations were repeated after 3 months. Analysis was performed using Paired-Samles T test and Spearman tests.

Results

Of patients, 23 were female (54.8 %) and 19 were male (45.2 %). Mean age was 55.2 years, with mean diabetes age of 8.14 ± 5.35 years. After 3 months follow-up, HbA1c, fasting glucose, C-reactive protein(CRP), UACR and endotrophin levels were observed to clearly reduce. The variation in serum endotrophin levels examined at the start of the study and in the 3rd month was identified to have a positive correlation with the variation in HbA1c and UACR levels (r = 0.342, p = 0.02; r = 0.484, p = 0.001). Multiple linear regression analysis showed percentage variation values (δ)-endotrophin levels were only independently correlated with (δ)-UACR (model r2 = 0.257, p value = 0.00).

Conclusions

Endotrophin levels decreased significantly with the decrease in HbA1c. Unexpectedly, this reduction in endotrophin levels is closely related to the decrease in UACR, regardless of blood glucose regulation. We think that studies targeting endotrophin will contribute to the diagnosis, treatment and follow-up of diabetic nephropathy in the future.
Evaluation of CAMPYLOBACTER QUIK CHEK™ rapid membrane enzyme immunoassay to detect Campylobacter spp. antigen in stool samples
Authors: Franco Justine , Bénejat Lucie , Ducournau Astrid , Mégraud Francis , Lehours Philippe , Bessède Emilie
Published: January 2021

Campylobacter spp. enteritis is the most frequent bacterial enteritis in both adults and children and is sometimes a source of severe complications. Its diagnosis by culture suffers from a lack of sensitivity and delays the result, preventing an early initiation of optimal antibiotic therapy in some cases. Our aim was to test a new rapid immuno-enzymatic method for Campylobacter spp. diagnosis in comparison to a composite reference standard (CRS). Stool samples from the French National Reference Center for Campylobacter and Helicobacter were tested with the CAMPYLOBACTER QUIK CHEK™ (Abbott). The CRS used to consider a case positive for Campylobacter spp. was a positive culture and, in case of a negative culture, a positive result obtained with both an ELISA and a molecular test. One hundred and eight stools were included: 53 were positive according to the CRS. If performed alone, culture would have missed 5 cases which the CAMPYLOBACTER QUIK CHEK™ detected. Finally, the CAMPYLOBACTER QUIK CHEK™ showed a sensitivity of 96.2% and a specificity of 94.5% and is relevant for clinical practice. Given the characteristics of the new method, it can be used as a screening method for Campylobacter spp. detection.
Feasibility of salivary cortisol collection in patients and companions attending dementia diagnostic meetings in memory clinics
Authors: Pavlickova H. , Russell A. E. , Lightman S. , McCabe R.
Published: January 2021

Objectives

Receiving a diagnosis of dementia is life-changing for the individual and their companion. The aim of the study was to explore the feasibility of collecting salivary cortisol from patients who are informed if they have dementia and their companions. Patients and companions collected nine saliva samples in three batches: 1–2 weeks before, immediately before, and immediately after the diagnostic meeting. Each batch consisted of three samples taken in the evening, after awaking and 30 mins post-waking.

Results

22.7% (N = 10) of 44 invited patients and nine companions agreed, with 18.2% patients (N = 8) and 15.9% companions (N = 7) providing samples. Participants found that saliva collection was demanding and disrupted routines. On a purely descriptive level, some indications of an increased cortisol stress response in patients diagnosed with dementia were found in this very small sample. Researchers should expect low recruitment rates in this elderly population. Simpler collection procedures, e.g. pre-labelled packages with date/time, possible omission of morning samples and objective rather than self-report assessment of waking and saliva collection times—using actigraphy wrist-watches bleeps to prompt people at the timepoints and electronic track caps—might improve adherence and improve the accuracy of timepoints when swabs were actually collected.
Ulam–Hyers stabilities of a differential equation and a weakly singular Volterra integral equation
Authors: Ege Ozgur , Ayadi Souad , Park Choonkil
Published: January 2021

In this work we study the Ulam–Hyers stability of a differential equation. Its proof is based on the Banach fixed point theorem in some space of continuous functions equipped with the norm $\|\cdot \|_{\infty }$

∥
⋅
∥

∞

. Moreover, we get some results on the Ulam–Hyers stability of a weakly singular Volterra integral equation using the Banach contraction principle in the space of continuous functions $C([a,b])$
C
(
[
a
,
b
]
)
.
Investigation of the p-Laplacian nonperiodic nonlinear boundary value problem via generalized Caputo fractional derivatives
Authors: Matar M. M. , Abbas M. I. , Alzabut J. , Kaabar M. K. A. , Etemad S. , Rezapour S.
Published: January 2021

A newly proposed p-Laplacian nonperiodic boundary value problem is studied in this research paper in the form of generalized Caputo fractional derivatives. The existence and uniqueness of solutions are fully investigated for this problem using some fixed point theorems such as Banach and Schauder. This work is supported with an example to apply all obtained new results and validate their applicability.
Seasonal dynamics of iron and phosphorus in reservoir sediments in Eucalyptus plantation region
Authors: Norgbey Eyram , Li Yiping , Zhu Ya , Nwankwegu Amechi S. , Bofah-Buah Robert , Nuamah Linda
Published: January 2021

Background

Iron (Fe) and phosphorus (P) dynamics in sediments have direct and indirect impacts on water quality. However, the mobility of P and Fe in reservoir sediments in Eucalyptus plantation region remains unclear. This study examined P and Fe pollution in sediments in a Eucalyptus plantation region using the novel planar optode, the ZrO-Chelex DGT, and the DIFS model.

Results

Direct in situ investigations showed that the levels of labile P and Fe were smaller in the Eucalyptus species-dominated sediments (X2) compared to sediments without Eucalyptus species (X1). The mean concentration of labile P and Fe decreased by 25% and 42% from X1 to X2. The decrement was insignificant (p = 0.20) in the surface sediment concentration for labile P. The significant disparity for DGT-Fe (Fe2+) (p = 0.03) observed in the surface sediments could be attributed to the Eucalyptus species’ elevated organic matter (tannins) concentration at X2, which reacted and consumed labile Fe. For both regions, the maximum concentration of labile P and Fe occurred in November (autumn). The reductive decomposition of Fe/Mn oxides was recognized as the main driver for their high P efflux in July and November. Low concentration of labile P and Fe was observed in December (winter) due to the adsorption of Fe/Mn oxides. The concentration of labile Fe synchronizes uniformly with that of labile P in both sediments indicating the existence of a coupling relationship (r > 0.8, p < 0.01) in both regions. The positive diffusion fluxes in both regions suggested that the sediments release labile P and Fe. The fluxes of labile P and Fe in both regions were substantially higher (p < 0.05) in the summer (anoxic period) than winter (aerobic period), indicating that hypoxia and redox conditions influenced the seasonal efflux of labile P and Fe. From the DIFS model, the replenishment ability of reactive P was higher during the anoxic period (R = 0.7, k1 = 79.4 day− 1, k-1 = 0.2 day− 1) than the aerobic period (R = 0.4, k1 = 14.2 day− 1, k-1 = 0.1 day− 1), suggesting that oxygen inhibited the efflux of P in the sediments.

Conclusion

Our results indicated that hypoxia, Eucalyptus species (organic matter (tannins)), and redox conditions influenced the seasonal mobility of sediment labile P and Fe. Our findings provided an insight into the mobility of labile P and Fe in Eucalyptus-dominated sediments and, moreover, serves as a reference for developing future studies on Eucalyptus-dominated sediments.
The impact of project ECHO on physician preparedness to treat opioid use disorder: a systematic review
Authors: Puckett Hunter M. , Bossaller Jenny S. , Sheets Lincoln R.
Published: January 2021

Opioid use disorder (OUD) is a medical condition that has evolved into a serious and deadly epidemic in the United States. Both medical and psychological interventions are called for to end this growing epidemic, but too few health care professionals are trained to treat OUD. One proven model of training physicians and cross-disciplinary teams in treating a variety of disorders is exemplified by Project ECHO (Extension for Community Healthcare Outcomes), a collaborative tele-mentoring program in which specialists train health-care workers to treat medical conditions, especially those that affect underserved populations. This systematic review found that Project ECHO has the potential to effectively extend current services to patients suffering from OUD, but that there is also a gap in knowledge regarding this type of training. The articles that we reviewed all presented evidence that Project ECHO improves healthcare provider preparedness to treat OUD, especially in regard to improving knowledge and self-efficacy.
Carriage of antimicrobial-resistant bacteria in a high-density informal settlement in Kenya is associated with environmental risk-factors
Authors: Omulo Sylvia , Lofgren Eric T. , Lockwood Svetlana , Thumbi Samuel M. , Bigogo Godfrey , Ouma Alice , Verani Jennifer R. , Juma Bonventure , Njenga M. Kariuki , Kariuki Samuel , McElwain Terry F. , Palmer Guy H. , Call Douglas R.
Published: January 2021

Background

The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi—Kenya, characterized by high population density, high burden of respiratory disease and diarrhea.

Methods

Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥ 18 years) and one child (≤ 5 years) participated per household. Biweekly interviews (n = 1516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2341 stool, 2843 hand swabs and 1490 drinking water samples collected. Presumptive E. coli (n = 34,042) were isolated and tested for susceptibility to nine antibiotics.

Results

Eighty percent of presumptive E. coli were resistant to ≥ 3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27–0·80 log10 and 0·22–0·51 log10 respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log10 depending on the antibiotic tested).

Conclusions

Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.
Stenotrophomonas maltophilia bacteremia in children: risk factors and mortality rate
Authors: Alsuhaibani Mohammed , Aljarbou Alanoud , Althawadi Sahar , Alsweed Abdulrahman , Al-Hajjar Sami
Published: January 2021

Purpose

Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized and immunocompromised patients. However, little is known about the impact of S. maltophilia bacteremia in pediatric patients. Therefore, we aimed to identify risk factors for mortality, antibiotics susceptibility to S. maltophilia, and mortality rates in pediatric patients with S. maltophilia bacteremia.

Methods

We conducted a retrospective cohort study by identifying all S. maltophilia positive blood cultures in the microbiology laboratory database between January 2007 and December 2018 from hospitalized pediatric patients (age 1–14 years). After identifying patients with S. maltophilia bacteremia, medical charts were reviewed for demographics, clinical data, and outcomes within seven days of bacteremia diagnosis. Risk factors associated with mortality in S. maltophilia bacteremia patients were determined using univariate and multivariate analyses.

Findings

Sixty-eight pediatric patients with S. maltophilia bacteremia were identified. All infections were nosocomial infections, and (88.2%) bacteremia cases were catheter-related bloodstream infections. On multivariate analysis, ICU admission prior to bacteremia episode and neutropenia were the major risk factors associated with mortality. S. maltophilia was the most susceptible to trimethoprim and sulfamethoxazole (TMP/SMX, 94.1%), followed by levofloxacin (85.7%). The overall mortality rate within seven days of S. maltophilia bacteremia diagnosis was 33.8%.

Conclusion

S. maltophilia bacteremia is a devastating emerging infection associated with high mortality among hospitalized children. Therefore, early diagnosis and prompt management based on local susceptibility data are crucial. Various risk factors, especially ICU admission prior to bacteremia episode and neutropenia, are associated with S. maltophilia bacteremia mortality.
A mixed community of skin microbiome representatives influences cutaneous processes more than individual members
Authors: Loomis Kristin H. , Wu Susan K. , Ernlund Amanda , Zudock Kristina , Reno Allison , Blount Kianna , Karig David K.
Published: January 2021

Background

Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses.

Results

The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host.

Conclusions

This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts.
Microdiversity and phylogeographic diversification of bacterioplankton in pelagic freshwater systems revealed through long-read amplicon sequencing
Authors: Okazaki Yusuke , Fujinaga Shohei , Salcher Michaela M. , Callieri Cristiana , Tanaka Atsushi , Kohzu Ayato , Oyagi Hideo , Tamaki Hideyuki , Nakano Shin-ichi
Published: January 2021

Background

Freshwater ecosystems are inhabited by members of cosmopolitan bacterioplankton lineages despite the disconnected nature of these habitats. The lineages are delineated based on > 97% 16S rRNA gene sequence similarity, but their intra-lineage microdiversity and phylogeography, which are key to understanding the eco-evolutional processes behind their ubiquity, remain unresolved. Here, we applied long-read amplicon sequencing targeting nearly full-length 16S rRNA genes and the adjacent ribosomal internal transcribed spacer sequences to reveal the intra-lineage diversities of pelagic bacterioplankton assemblages in 11 deep freshwater lakes in Japan and Europe.

Results

Our single nucleotide-resolved analysis, which was validated using shotgun metagenomic sequencing, uncovered 7–101 amplicon sequence variants for each of the 11 predominant bacterial lineages and demonstrated sympatric, allopatric, and temporal microdiversities that could not be resolved through conventional approaches. Clusters of samples with similar intra-lineage population compositions were identified, which consistently supported genetic isolation between Japan and Europe. At a regional scale (up to hundreds of kilometers), dispersal between lakes was unlikely to be a limiting factor, and environmental factors or genetic drift were potential determinants of population composition. The extent of microdiversification varied among lineages, suggesting that highly diversified lineages (e.g., Iluma-A2 and acI-A1) achieve their ubiquity by containing a consortium of genotypes specific to each habitat, while less diversified lineages (e.g., CL500-11) may be ubiquitous due to a small number of widespread genotypes. The lowest extent of intra-lineage diversification was observed among the dominant hypolimnion-specific lineage (CL500-11), suggesting that their dispersal among lakes is not limited despite the hypolimnion being a more isolated habitat than the epilimnion.

Conclusions

Our novel approach complemented the limited resolution of short-read amplicon sequencing and limited sensitivity of the metagenome assembly-based approach, and highlighted the complex ecological processes underlying the ubiquity of freshwater bacterioplankton lineages. To fully exploit the performance of the method, its relatively low read throughput is the major bottleneck to be overcome in the future.
Composition of weighted finite transducers in MapReduce
Authors: Elghadyry Bilal , Ouardi Faissal , Verel Sébastien
Published: January 2021

Weighted finite-state transducers have been shown to be a general and efficient representation in many applications such as text and speech processing, computational biology, and machine learning. The composition of weighted finite-state transducers constitutes a fundamental and common operation between these applications. The NP-hardness of the composition computation problem presents a challenge that leads us to devise efficient algorithms on a large scale when considering more than two transducers. This paper describes a parallel computation of weighted finite transducers composition in MapReduce framework. To the best of our knowledge, this paper is the first to tackle this task using MapReduce methods. First, we analyze the communication cost of this problem using Afrati et al. model. Then, we propose three MapReduce methods based respectively on input alphabet mapping, state mapping, and hybrid mapping. Finally, intensive experiments on a wide range of weighted finite-state transducers are conducted to compare the proposed methods and show their efficiency for large-scale data.
Prosthetic rehabilitation of a patient with cleidocranial dysplasia using dental implants—a clinical report
Authors: Schnutenhaus Sigmar , Götz Werner , Luthardt Ralph G.
Published: January 2021

Adult patients with oral manifestations of untreated syndromic malformations usually exhibit a high degree of suffering. In this clinical report, we describe the implant-supported prosthetic treatment of a patient with cleidocranial dysplasia, a rare autosomal-dominant inherited malformation syndrome. Therapy for oral manifestations of cleidocranial dysplasia should be started in early childhood; however, the 26-year-old patient in the present study had not undergone orthodontic therapy in childhood. The treatment measures performed prior to this study were limited to the removal of several permanent teeth. Surgical pretreatment, placement of six implants each in the maxilla and mandible, and prosthetic restoration are described. The implantation was guided using a three-dimensional template. Long-term immediate temporary restoration and immediate loading of the implants were performed. The definitive prosthetic restoration was completed using fixed, acrylic resin-veneered screw-retained fixed dental prostheses. The clinical and radiological parameters observed in this case suggest that surgical and prosthetic procedure concepts from implantology can be adopted for patients with CCD.
Validation of the Arabic version of swallowing quality of life questionnaire
Authors: Abdou Rania Mohamed , Elsayed Heba Elsayed , Adel Sally Mohamed
Published: January 2021

Background

Dysphagia is caused by sensorimotor function disruption of swallowing. In 2000, McHorney et al. first developed the SWAL-QOL (swallowing quality of life questionnaire). It is considered to be one of the initial self-rated tools which is dysphagia-specific.

The SWAL-QOL has been translated into many languages such as Dutch, French, Chinese, Swedish, Persian, German, and Arabic (its linguistic validation was tested only but its validation and reliability has not been determined). The aim of this study was to determine the validity and reliability of the Arabic version of SWAL-QOL (ASWAL-QOL) in adult patients complaining of oropharyngeal dysphagia. Patients were enrolled from the outpatient swallowing clinic of Main University hospitals starting from the first of March 2018 to the end of May 2019. According to these criteria, sums of 100 patients were involved in the study and they completed the ASWAL-QOL together with Dysphagia Handicap Index (DHI).

Results

There was a strong correlation between the eating desire, eating duration, and food selection in ASWAL-QOL and the functional domain in (DHI). This was found as well between mental health and social functioning in ASWAL-QOL and emotional domain in (DHI) that was used for convergent validity. While checking reliability, nearly most of the domains demonstrated stability over short term as well as excellent internal consistency reliability.

Conclusion

The current study illustrated that the ASWAL-QOL questionnaire is a valid and reliable tool to evaluate the impact of difficulties in swallowing on the quality of life in patients suffering from oropharyngeal dysphagia.
Single nucleotide polymorphisms (SNPs) in endoplasmic reticulum (ER) stress response genes to predict first-line treatment outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from the MAVERICC and FIRE-3 trials.
Authors: Battaglin Francesca , Arai Hiroyuki , Millstein Joshua , Stintzing Sebastian , Parikh Aparna Raj , Wang Jingyuan , Kawanishi Natsuko , Soni Shivani , Wu Zhang , Mancao Christoph , Heinemann Volker , Lenz Heinz-Josef
Published: January 2021

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Background: ER stress, triggered by the disruption of intracellular protein homeostasis, promotes the activation of a highly conserved adaptive program called unfolded protein response (UPR). UPR signaling has been reported to contribute to tumor initiation and progression, as well as microenvironment remodeling and chemoresistance in multiple cancer types, including CRC. Several studies point to a direct role of the UPR in tumor angiogenesis and an interaction with EGFR signaling. We therefore hypothesized that genetic variants in ER stress response genes may predict first-line treatment outcome in mCRC pts. Methods: The impact on outcome of 17 functional SNPs in 8 core genes of the ER stress response pathway ( IRE1, PERK, ATF6, XBP1, CHOP, GRP78, GADD34, ATF4) was analyzed on a total of 560 pts enrolled in two independent randomized first-line trials: MAVERICC (FOLFIRI/bevacizumab, [bev] n = 163; FOLFOX6/bev, n = 161), and FIRE-3 (FOLFIRI/bev, n = 107; FOLFIRI/cetuximab [cet], n = 129). Genomic DNA from blood samples of pts was genotyped through the OncoArray, a custom array manufactured by Illumina. The association between SNPs and clinical outcomes was evaluated using Cox regression and log-rank tests. The SNP*treatment interaction was assessed in both trials. Results: IRE1 rs16947383 any T allele variant was associated with shorter progression free survival (PFS) and overall survival (OS) compared to the C/C genotype in pts treated with FOLFIRI/bev in the MAVERICC trial both in uni- and multivariate analysis: 10.5 vs 14.1 months for PFS, adjusted hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.12-2.99, adjusted P-value = 0.02; 23.8 vs 38.4 months for OS, adjusted HR 2.12, 95%CI 1.1-4.09, adjusted P-value = 0.02. The association with OS was validated in the FIRE-3 FOLFIRI/bev arm where any T allele carriers showed significantly shorter OS compared to the C/C genotype in both uni- and multivariate analysis: 21.1 vs 44.2 months, adjusted HR 2.06, 95%CI 1.01-4.18, adjusted P-value = 0.05. This effect was not observed in MAVERICC FOLFOX6 and FIRE-3 cet cohorts. A significant interaction was found between IRE1 rs16947383 and treatment on OS in both trials: P = 0.04 in MAVERICC (FOLFIRI vs FOLFOX6), and P = 0.03 in FIRE-3 (bev vs cet). In the MAVERICC FOLFOX6/bev arm, XBP1 rs2239815 and PERK rs6731022 SNPs were associated with shorter PFS and OS, while GADD34 rs610308 with longer OS, in multivariable analysis ( P < 0.05). Conclusions: Our results provide evidence that germline polymorphisms in ER stress response genes may have a predictive value in mCRC pts receiving first-line bev-based treatment and contribute to modulate anti-VEGF efficacy.
Racial differences in tumor biology and treatment of gastric cancer in the United States.
Authors: Tseng Joshua , Miller James , Feng Xiaoxi , Gangi Alexandra , Gong Jun , Burch Miguel
Published: January 2021

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Background: Racial disparities for gastric cancer are often identified in the literature. Although patients in Asia consistently demonstrate a survival benefit compared to those in the West, Asian patients in the US still retain this advantage, which suggests that tumor biology may be a major factor. The goal of our study is to identify racial differences in patient demographics, tumor biology and treatment for gastric cancer in the United States. Methods: The National Cancer Database was queried from 2006-2016 for patients with a diagnosis of gastric adenocarcinoma. Patient demographics, tumor characteristics, and treatment patterns were compared by patient ethnicity (White, Black, Hispanic, and Asian) with Kruskal-Wallis test and Pearson’s chi-squared test. Kaplan-Meier survival curves used to assess overall survival, and cox regression used to identify independent prognostic factors for survival. Results: 116,717 patients with gastric cancer identified; 78,066 were White, 17,486 were Black, 8,494 were Asian, and 12,671 were Hispanic. White patients were most likely to be older than 70 and have proximal tumors, and least likely to have diffuse type adenocarcinoma. Hispanic and Black patients were most likely to present with metastases. Asian patients were most likely to receive surgery and least likely to receive chemotherapy or radiotherapy. Stage for stage, Asians had the longest median survival, followed by Hispanic, Black, and White patients. Prognostic factors associated with a survival benefit include Asian ethnicity (HR 0.72, 95% CI 0.68-0.74), Hispanic ethnicity (HR 0.76, 95% CI 0.73-0.79), Black ethnicity (HR 0.95, 95% CI 0.93-0.98), private insurance (HR 0.91, 95% CI 0.87-0.96), higher income (HR 0.85, 95% CI 0.82-0.88), treatment at academic center (HR 0.87, 95% CI 0.83-0.91), higher-volume centers (HR 0.90, 95% CI 0.87-0.93), receiving surgery (HR 0.42, 95% CI 0.41-0.43), chemotherapy (HR 0.56, 95% CI 0.55-0.57), and radiation (HR 0.96, 95% CI 0.93-0.98). Conclusions: Treatment differences between Eastern and Western countries for gastric cancer persist between ethnic groups within the United States, with Asian patients retaining a survival benefit. Black and Hispanic patients present with aggressive disease and unfavorable socioeconomic factors that are detrimental to overall survival.
A phase I study to evaluate the safety of multiantigen stimulated tumor specific cell therapy (MASCT-I) in subjects with advanced gastric cancer.
Authors: Bu Zhaode , Jia Ziyu , Ji Ke , Ji Xin , Zhang Ji , Wu Xiaojiang , Kong Yanjun , Zhu Aimin , Li Xiaoshuang , Ji Jiafu
Published: January 2021

200

Background: Gastric cancer was the fifth cancer world wide and the third leading cause of cancer-related death. PD-1 antibody has been approved for treatment in gastric cancer patients with positive expression of PD-L1 and microsatellite instability. MASCT-I (Multi-Antigen Stimulated Cell Therapy-I Injection) is an autologous non-engineered immune cell therapy for solid tumor, it is composed of multiple-antigen peptides(15 tumor associated antigens) loaded mature dendritic cells (DCs) and in vitro DC stimulated and proliferated effector T cells, the combination of MASCT-I and PD1 antibody could have a synergistic anti-tumor effect. Methods: This is a single center, phase I trial to explore the safety and tolerance of the combination of MASCT-I and PD-1 antibody in advanced gastric cancer (NCT03393416). 15 patients with PD-L1 expression or microsatellite instability were enrolled between April 2018, and June 2019. Camrelizumab was administered once every two weeks, DC and T cells were sequential administered once a month. Therapy continued until the disease progresses. Results: Only adverse reaction below grade 2 was observed related to MASCT-I,such as fever, fatigue etc. Abnormal liver function and reactive capillary hyperplasia may be related to Camrelizumab. Among the 15 patients, the longest treatment duration was 18.9 months, and the median progression-free survival (mPFS) was 3.93 months, among which, mPFS of patients with microsatellite instability is 10.23 months, mPFS of patients expressing PD-L1 is 2.35 months, which is slightly higher than the historical data of Camrelizumab alone in the treatment of advanced gastric cancer (8 weeks for mPFS). The patient 1002 always had high content of CD8+ cells and NK cells and the positive immune response in their bodies, which may plays a role in killing the tumor cells. Conclusions: The combination of MASCT-I and Camrelizumab in the treatment of advanced gastric cancer or gastroesophageal junction cancer is a safe treatment regimen, and its efficacy deserves further study. Clinical trial information: NCT03393416.
Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.
Authors: Chin Keisho , Kato Ken , Cho Byoung Chul , Takahashi Masanobu , Okada Morihito , Lin Chen-Yuan , Kadowaki Shigenori , Ahn Myung-Ju , Hamamoto Yasuo , Doki Yuichiro , Yen Chueh-Chuan , Kubota Yutaro , Kim Sung-Bae , Hsu Chih-Hung , Holtved Eva , Xynos Ioannis , Matsumura Yasuhiro , Takazawa Akira , Kitagawa Yuko
Published: January 2021

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Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.