bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision medicine in clinical oncology: the journey from IgG antibody to IgE
Authors: Fazekas-Singer Judit , Singer Josef , Jensen-Jarolim Erika 
Published: April 2020

Purpose of review
Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG.

Recent findings
In order to improve these therapies, ‘next-generation antibodies’ were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE.

Summary
The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.
Heterogenous Dose-escalated Prostate Stereotactic Body Radiation Therapy for All Risk Prostate Cancer
Authors: Parsai Shireen , Juloori Aditya , Sedor Geoffrey , Reddy Chandana A. , Thousand Richard , Magnelli Anthony , Berglund Ryan K. , Stovsky Mark , Klein Eric A. , Tendulkar Rahul D. , Stephans Kevin L. 
Published: April 2020

Objectives:
Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious.

Materials and Methods:
Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx.

Results:
Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%.

Conclusions:
Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.
Implementation of Maternal Blood Cell Free DNA Testing in Early Screening for Aneuploidies
Authors: Gil María del Mar , Nicolaides Kypros H. 
Published: April 2020

Abstract
In the past 9 years, several externally blinded validation and implementation studies have shown that it is now possible, through analysis of cell-free (cf) DNA in maternal blood, to effectively detect a high proportion of fetuses affected by trisomies 21, 18, and 13 at a much lower false positive rate than all other existing screening methods. This article aims to review the technical and clinical considerations for implementing cfDNA testing in routine practice, including methods of analysis, performance of the test, models for clinical implementation, and interpretation of results.
Positive Rate of Noninvasive Prenatal Screening for Pregnancies with Fetal Congenital Heart Disease and Its Impact on Pregnancy Outcome
Authors: Chen Yun , Lai Yun-Li , Shen Yi-Ping , Tian Xiao-Xian , Zheng Chen-Guang , Wei Hong-Wei 
Published: April 2020

Abstract

Objective:
To evaluate the clinical utility of noninvasive prenatal screening (NIPS) for fetuses with congenital heart disease (CHD) and impact of NIPS results on pregnancy outcome.

Methods:
This was a retrospective study of pregnant women with fetuses diagnosed with CHDs by sonographic examination, who willing to underwent NIPS as a side-test for fetal aneuploidies. From August 2016 to October 2017, in the sonographic examination center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. NIPS was offered to 117 women who carried fetuses with CHD diagnosed by fetal ultrasound (mean gestational age = 24 weeks). The pregnancy outcomes were followed-up.

Results:
NIPS positive rate in our pregnancies with CHD fetuses’ cohort is 11.1% (13/117), and the positive predictive value for aneuploidies is 85.7% (6/7). In the NIPS positive group (n = 13), all pregnancies terminated, 76.9% (10/13) of those decisions were made on ultrasound finding alone. In the NIPS negative group (n = 104), 2 lost follow-up, 79 pregnancies terminated, among which 77.2% (61/79) of the decision was made by ultrasound results alone. Twenty-three pregnancies continued and 78.3% of those fetuses carried single type CHD. In terminated pregnancies that did not considered NIPS results (71/115), 73.2% (52/71) of those carried fetuses with two or more types of CHDs.

Conclusion:
NIPS can detect common aneuploidy associated with CHD with high positive predictive value and screening yield. The NIPS result played certain meaningful roles in determining pregnancy outcomes, particularly for fetus with simplex CHD; yet the parents’ decision of pregnancy was mainly made based on ultrasound findings.
Genetic Variants of Potassium Voltage-gated Channel Subfamily J Member 11 in Gestational Diabetes Mellitus: A Case-control Study
Authors: Wei Li-Jie , Zhou Xuan , Zhu Sheng-Lan , Li Jia-Qi , Zeng Yu , Yu Jun , Wang Shao-Shuai , Feng Ling 
Published: April 2020

Abstract

Objective:
To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11 (KCNJ11) with gestational diabetes mellitus (GDM).

Methods:
Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018, in which 241 pregnant women were identified as GDM, and 391 were non-GDM. All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn, and DNA in the blood was extracted. rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses.

Results:
After adjusting age and body mass index, the variant genotypes of rs5210 in genotype models were as follows: P for dominant model was 0.945, (odd ratio: 0.987, 95% confidence intervals (CI): 0.681–1.430); P for recessive model: 0.556, (odd ratio: 1.217, 95% CI: 0.633–2.343) and P for addictive model was 0.098 (genotype AA vs. GG), (odds ratio: 1.435, 95% CI: 0.936–2.201). Weight-gain during pregnancy and total cholesterol were significantly different in recessive model (P = 0.015, P = 0.022, respectively) of all participants.

Conclusion:
No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women. But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels. However, more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.
Metformin in Pregnancy with Diabetes—Opinions from Several Latest Guidelines
Authors: Feng Ye , Yang Hui-Xia 
Published: April 2020

Abstract
Pregnancy complicated with diabetes is associated with adverse maternal and fetal outcomes. Good control of glucose level during pregnancy contributes to improve maternal and fetal outcomes and break the vicious cycle of “diabetes begetting diabetes”. The first line antidiabetic drug in pregnancy is insulin, which is expensive and inconvenient to use. Lots of clinical trials and meta-analyses have constantly confirmed the safety and efficacy of metformin in pregnancy. Several guidelines across the world have been discussing metformin as an alternative to insulin in pregnancy. This article summarizes the opinions about metformin from several latest guidelines.
The Activation of Peroxisome Proliferator-activated Receptor γ Enhances Insulin Signaling Pathways Via Up-regulating Chemerin Expression in High Glucose Treated HTR-8/SVneo Cells
Authors: Zhou Xuan , Wei Li-Jie , Li Jia-Qi , Zhang Jing-Yi , Zhu Sheng-Lan , Zhang Hui-Ting , Jia Jing , Yu Jun , Wang Shao-Shuai , Feng Ling 
Published: April 2020

Abstract

Objective:
To investigate whether peroxisome proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone and GW1929, activate the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase1/2 (ERK1/2) pathway by upgrading the expression of chemerin.

Methods:
The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration (25 mmol/L) to mimic gestational diabetic phenotypes. We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin, that are chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor1 (GPR1). And recombinant human chemerin, PPARγ agonists (rosiglitazone, 10 μmol/L and GW1929, 10 μmol/L) and PPARγ inhibitor (GW9662, 5 μmol/L) were additionally added to the medium, respectively. The existence of chemerin was verified by immunocytochemistry, and the expressions of PPARγ, chemerin, and its receptors as well as insulin signaling-related factors PI3K, AKT2, and MAPK (ERK1/2) were detected by real time quantitative-polymerase chain reaction and western blot.

Results:
Chemerin existed in the HTR-8/SVneo cells. Effects of chemerin on PI3K-AKT pathway and MAPK (ERK1/2) pathway were dependent on the density of chemerin. When rosiglitazone and GW1929 were added to the medium, the mRNA levels of PI3K, AKT2, and MAPK1 were upregulated (P < 0.05). Conversely, GW9662 downregulated the mRNA levels of AKT2 and MAPK1 (P < 0.05). Rosiglitazone and GW1929 increased the protein levels of PPARγ, chemerin, CMKLR1 and GPR1 (P < 0.05). Rosiglitazone and GW1929 had no effect on the expression of PI3K p110β and phospho-AKT2 without CMKLR1 (P
> 0.05). Meanwhile, the expression of phospho-ERK2 remained unaffected in the absence of GPR1 (P
> 0.05).

Conclusion:
Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.
Interactions Between Gut Microbiota and Hosts and Their Role in Infectious Diseases
Authors: Lv Long-Xian , Jiang Hui-Yong , Yan Ren , Li Lanjuan 
Published: April 2020

Abstract
Major infectious diseases, such as viral hepatitis, acquired immune deficiency syndrome, and tuberculosis, are difficult to eliminate within a short period. Dengue fever, global influenza pandemic, and ebola and other high-threat pathogens are now the main threats to human health as well. Therefore, it is particularly important to find new strategies for the prevention and treatment of infectious diseases. The human gut tract contains trillions of microbial cells, including bacteria, archaea, fungi and viruses. These microbes are defined as gut microbiota and play an important role in human development, immunity, metabolism and diseases. In this review, we analyzed the mechanisms by which alterations in gut microbiota affect infectious diseases and how infectious diseases regulate the structure and function of gut microbiota. Finally, we summarized and discussed methods used for the diagnosis, prevention and treatment of infectious diseases based on the alteration of gut microbiota.
Azithromycin Exerts Bactericidal Activity and Enhances Innate Immune Mediated Killing of MDR Achromobacter xylosoxidans
Authors: Ulloa Erlinda R. , Kousha Armin , Tsunemoto Hannah , Pogliano Joe , Licitra Carmelo , LiPuma John J. , Sakoulas George , Nizet Victor , Kumaraswamy Monika 
Published: April 2020

Abstract
Azithromycin (AZM), the most commonly prescribed antibiotic in the United States, is thought to have no activity against multidrug-resistant Gram-negative pathogens such as Achromobacter xylosoxidans (AX) per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth. Here we provide the first report of AZM bactericidal activity against carbapenem-resistant isolates of AX, with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment. This pharmaceutical activity, evident in eukaryotic tissue culture media, is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood, serum, and neutrophils. Additionally, AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable bacteria. In an illustrative case, AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis, sternal osteomyelitis, and aortic graft infection. Our study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents, adversely affecting patient outcomes. We conclude that AZM merits further exploration in the treatment of drug-resistant AX infections. Novel approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered, especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality.
Scabies Evaluated by Dermoscopy and Fluorescence Microscopy: A Case Report
Authors: Zhang Li-Wen , Wang Wen-Ju , Liu Xue-Ying , Xu Lei , Zheng Lu , Li Cong-Hui , Lu Yong-Hong 
Published: April 2020

Abstract

Introduction:
Scabies is an infectious skin disorder caused by the mite Sarcoptes scabiei. The diagnosis of scabies is often confirmed by microscopic detection of scabies mites, eggs, or feces.
We herein describe the diagnosis of scabies in a boy with the assistance of dermoscopy and fluorescence microscopy.

Case presentation:
A 16-year-old Chinese boy presented with a 2-month history of extensive papules and excoriations with intense pruritus on the trunk and limbs. Dermoscopy showed a sinuous burrow in the finger webs with a brown jet-shaped triangular structure at the end. A fluorescence microscopy revealed a hatching egg and a mite. The boy was diagnosed with scabies and treated with 5% sulfur ointment.

Discussion:
The use of dermoscopy in patients with scabies reveals a sinuous burrow with a brown jet-shaped triangular structure composed of the pigmented head and anterior legs of the mite[1]. A fluorescence microscopy revealed mites and eggs with blue fluorescence after staining, allowing us to easily identify scabies.

Conlcusion:
The combination of dermoscopy-guided tape testing with fluorescence staining technology may enhance the diagnostic accuracy and efficiency of scabies.
Papillon-Lefèvre Syndrome: A Case Report
Authors: Zhao Yu-Lei , Feng Zhao , Hu Bin , Chen Liu-Qing 
Published: April 2020

Abstract

Introduction:
Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterized by a diffuse palmoplantar hyperkeratosis and early periodontal destruction. Only a few PLS cases are reported by dermatological clinicians due to its rarity.
Here, we reported a 16-year-old Chinese boy presented with diffuse transgradient palmoplantar hyperkeratosis since 4 years of age.

Case presentation:
The patient had also experienced recurrent episodes of swollen gums with premature loss of teeth. He is treated with multidisciplinary approaches. On follow-up, he continued to have recurrent gingival inflammation.

Discussion:
The etiopathogenesis of PLS is obscure and its management presents a special challenge, which call for in-depth studies that will reveal the complex interactions of genetic, immunologic, and microbiological factors involved in pathogenesis of PLS.

Conclusion:
PLS is a very rare genodermatosis with characterized palmoplantar hyperkeratosis. Dermatological clinicians should be aware of this rare clinical entity to promote its early diagnosis.
Co-occurrence of Vitiligo and Psoriasis in an 11-Year-Old Girl: A Case Report
Authors: Li Rong , Zhang Jia-An , Jiang Yi-Qun , Wu Min-Zhi , Chen Kun 
Published: April 2020

Abstract

Introduction:
Vitiligo and psoriasis are common skin diseases, while its co-occurrence in one patient is rare. Here, we reported a patient with co-occurrence of vitiligo and psoriasis.

Case presentation:
An 11-year-old girl developed depigmented patches on her right chin for 6 months. The noticed areas of depigmented skin steadily increased in size with no clinical symptoms. Wood's lamp examination and laser scanning confocal revealed the clinical diagnosis of co-occurrence of vitiligo and psoriasis.

Discussion:
Speculations related to co-pathogenesis of vitiligo and psoriasis are still elusive, some explanations of this phenomenon like of isomorphic reaction, shared genetic basis of autoimmunity and inflammation, shared cellular immune pathways including Th1, Th17 and related cellular molecules such as TNF-α, IFN-α, IL-17 have been reported.

Conclusion:
The analysis and summary of the underlying association in co-occurrence of psoriasis and vitiligo may amplify future therapeutic options for both disease.Clinicians should pay attention to the methods that could simultaneously improve these two conditions.
Behçet Disease with Generalized Polymorphous Cutaneous Lesions: A Case Report
Authors: Wang Li-Wei , Luo Ling-Ling , Zhang Wei , Zeng Xue-Si , Cui Pan-Gen 
Published: April 2020

Introduction:
Behçet disease is a chronic multisystem vasculitis disease, however generalized polymorphous cutaneous lesions are uncommon.
Here, we reported a case of Behçet disease with multiple parts of the body and complex lesions, which may lead to misjudging in clinical diagnosis.

Case report:
A 69-year-old man presented with a seven-year history of recurrent generalized polymorphous mucocutaneous lesions (erythematous papules, nodules, ulcers, and necrosis) over his entire body, and the lesions had been painful for the past three years. Based on the past medical history, clinical presentation, histological examination excluded other diseases, and the 2014-amended International Criteria for Behget disease, the patient had a score of 6 points and was diagnosed as Behçet disease.

Discussion:
The common clinical feature in patients with Behçet syndrome is the presence of recurrent and usually painful mucocutaneous ulcers. Other clinical manifestations of this disorder are more variable among different patients. A diagnosis of generalized polymorphous cutaneous lesions should remain on the list of differential diagnosis of Behçet disease after excluding other diseases.

Conclusion:
The mucocutaneous lesions of Behçet disease are often preceded by other manifestations, and timely diagnosis may benefit early treatment and prognosis.
Bullous Pemphigoid With Nail Damage Associated With Kaposi Sarcoma: A Case Report
Authors: Hu Feng-Xia , Liang Jun-Qin , Abudoureyimu Dilinuer , Wu Cao-Ying , Kang Xiao-Jing 
Published: April 2020

Introduction:
Bullous pemphigoid is an acquired autoimmune bullous skin disease that occurs in the elderly, and nail involvement is relatively rare. Kaposi sarcoma(KS) is a rare opportunistic tumor in patients with iatrogenic immunosuppression and is rarely associated with autoimmune bullotic disease.
Here we reported of a 73-year-old female with bullous pemphigoid with nail damage and KS.

Case presentation:
The patient was diagnosed with bullous pemphigoid based on her history, bullous pemphigoid antibody, and skin pathological examination. And nail involvement occurred 20 days prior to the recurrence of the disease. Moreover, KS occurred during high-dose glucocorticoid therapy in this patient.

Discussion:
The patient was admitted to hospital because of a five-month history of erythema and blisters and a one-month history of nodules and plaques. The diagnosis of bullous pemphigoid was followed by treatment with glucocorticoids and intravenous gamma globulin. During treatment, the disease recurred due to discontinuation of glucocorticoids. There were erythema and blisters all over the body, and purple nodules, plaques appeared in the base of some blisters. Pathological examination of nodules was consistent with KS. In addition, nail involvement occurred 20 days before recurrence. The particularity of this case lies in the simultaneous occurrence of nail involvement, bullous pemphigoid, and KS.

Conclusion:
Patients with autoimmune bullous skin disease may suddenly develop abnormal nails, and such patients should be vigilant about recurrence of the disease. Doctors should be aware of the possibility of KS when rapidly progressing purplish red plaques or nodules appear in patients receiving high doses of corticosteroids or immunosuppressants.
Automated Contact Tracing: a game of big numbers in the time of COVID-19
Authors: Kim Hyunju , Paul Ayan 
Published: April 2020

ABSTRACTOne of the more widely advocated solutions for slowing down the spread of COVID-19 has been automated contact tracing. Since proximity data can be collected by personal mobile devices, the natural proposal has been to use this for automated contact tracing providing a major gain over a manual implementation. In this work, we study the characteristics of voluntary and automated contact tracing and its effectiveness for mapping the spread of a pandemic due to the spread of SARS-CoV-2. We highlight the infrastructure and social structures required for automated contact tracing to work. We display the vulnerabilities of the strategy to inadequate sampling of the population, which results in the inability to sufficiently determine significant contact with infected individuals. Of crucial importance will be the participation of a significant fraction of the population for which we derive a minimum threshold. We conclude that relying largely on automated contact tracing without population-wide participation to contain the spread of the SARS-CoV-2 pandemic can be counterproductive and allow the pandemic to spread unchecked. The simultaneous implementation of various mitigation methods along with automated contact tracing is necessary for reaching an optimal solution to contain the pandemic.