bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurosarcoidosis presenting as CRVO combined CRAO: a biopsy-proven case report of a Chinese patient
Authors: Feng Chaoyi , Chen Qian , Liu Wei , Bi Yingwen , Qian Jiang , Wang Min , Sun Xinghuai , Tian Guohong
Published: August 2020

Background

Neurosarcoidosis is a rare systemic disorder that can affect the eye and other organs, including the central nervous system. Neurosarcoidosis infiltrating the optic nerve presenting as central retinal vein occlusion combined with artery ischaemia has not been reported in the literature previously. We describe a Chinese patient presenting with acute monocular vision loss, in whom an optic nerve biopsy confirmed the diagnosis of neurosarcoidosis.

Case presentation

A 47-year-old woman complained of acute decreased vision in her left eye over the course of 1 month. She reported that her vision deteriorated quickly within first 3 days of consulting an ophthalmologist at a local hospital. She was diagnosed with central retinal vein occlusion after funduscopic examination and fundus fluorescein angiography, and the vision in her left eye further deteriorated to no light perception. An orbital magnetic resonance imaging showed an abnormal T1-weighted image of the optic nerve after contrast enhancement. She was referred to a neuro-ophthalmologist for further evaluation. After routine blood tests ruled out infectious and metastatic diseases, she was prescribed 500 mg/d methylprednisolone for 5 days, but her vision did not improve. As she could still not perceive light, an optic nerve biopsy was performed, and the histopathology revealed non-necrotising granuloma that was consistent with neurosarcoidosis.

Conclusions

Isolated optic nerve infiltration by neurosarcoidosis without the involvement of the central nervous system or other systemic organs is challenging to diagnose. Biopsy of the optic nerve sheath is crucial for the final diagnosis of neurosarcoidosis. Therefore, a comprehensive ophthalmologic and systemic examination and work-up for inflammation of the eye, chest, and central nervous system should be conducted for atypical cases.
Evaluating practioners’ preferences regarding vascular emergency access in newborn infants in the delivery room: a national survey
Authors: Haase Bianca , Springer Laila , Poets Christian Friedrich
Published: August 2020

Background

Venous access during neonatal emergencies in the delivery room (DR) can be accomplished through an umbilical venous catheter (UVC) or an intraosseous (IO) access. Preference of one over the other is unclear. We wanted to evaluate practioners’ views.

Methods

An anonymous online questionnaire was circulated to healthcare professionals with different background and experience, all working in neonatal intensive care units in Germany. The web-based survey consisted of 13 questions and data collection was performed using an online tool.

Results

We received 502 completed questionnaires, 152 (30%) were from neonatologists, the remainder from residents, fellows and neonatal nurses. For resuscitation of term newborns in the DR 61% of neonatologists vs. 53% of non-neonatologists were in favour of UVC instead of an IO as an emergency access. UVC placement was rated (very) difficult to impossible by 60% of neonatologists and 90% of non-neonatologists (p < 0.05). All respondents cited lack of experience as the main reason for feeling reluctant to place an UVC or IO access, the latter only being taken into consideration in term infants.

Conclusions

UVC placement in the DR is rated more often difficult to use by non-neonatologists than by neonatologists, apparently related to lack of experience. IO access was only considered for resuscitating term infants due to lacking practice and missing approval for birth weights < 3000 g. Frequent training might improve these clinical skills.
Implementing internet- and tele-based interventions to prevent mental health disorders in farmers, foresters and gardeners (ImplementIT): study protocol for the multi-level evaluation of a nationwide project
Authors: Freund Johanna , Titzler Ingrid , Thielecke Janika , Braun Lina , Baumeister Harald , Berking Matthias , Ebert David Daniel
Published: August 2020

Background

Farmers are a vulnerable population for developing depression or other mental health disorders due to a variety of risk factors in their work context. Beyond face-to-face resources, preventive internet- and tele-based interventions could extend available treatment options to overcome barriers to care. The German Social Insurance Company for Agriculture, Forestry and Horticulture (SVLFG) implements several guided internet- and mobile-based interventions and personalised tele-based coaching for this specific target group provided by external companies within a nation-wide prevention project for their insured members. The current study aims to evaluate the implementation process and to identify determinants of successful implementation on various individual and organisational levels.

Methods

The current study includes two groups of participants: 1) insured persons with an observable need for prevention services, and 2) staff-participants who are involved in the implementation process. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR) will be used to track and evaluate the implementation process. A mixed-method approach will provide insights on individual and organizational level (e.g. degree of normalization, readiness for change) and helps to identify determinants of successful implementation. In-depth insights on experiences of the participants (e.g. acceptance, satisfaction, barriers and facilitating factors of intervention use) will be yielded through qualitative interviews. Focus groups with field workers provide insights into barriers and facilitators perceived during their consultations. Furthermore, intervention as well as implementation costs will be evaluated. According to the stepwise, national rollout, data collection will occur at baseline and continuously across 24 months.

Discussion

The results will show to what extent the implementation of the internet- and tele-based services as a preventive offer will be accepted by the participants and involved employees and which critical implementation aspects will occur within the process. If the implementation of the internet- and tele-based services succeeds, these services may be feasible in the long-term.

Trial registration

German Clinical Trial Registration: DRKS00017078. Registered on 18.04.2019.
Comparison of Hydroxyethyl starch 130/0.4 (6%) with commonly used agents in an experimental Pleurodesis model
Authors: Kapicibasi Hasan Oğuz , Kiraz Hasan Ali , Gök Nazli Demir
Published: August 2020

Background

Hydroxyethyl Starch (HES) 130/0.4 (6%) is a commonly used intravascular volume expander with anti-inflammatory and antioxidant properties. In this study, we aimed to compare the histopathologic activity of HES 130/0.4 (6%) with various widely-used agents in pleurodesis.

Methods

Forty male Wistar-Albino rats were divided into five groups: controls, povidone-iodine recipients (PI group), sterile talcum recipients (Talcum group), autologous blood recipients (AB group) and HES 130/0.4 (6%) recipients (HES group). Thirty days after application of agents, pleural and lung tissues were resected. Evaluation was performed via macroscopic scoring (adhesion) and specimens were stained with H&E for microscopic examination (inflammation and fibrosis).

Results

HES recipients had significantly higher adhesion compared to controls (lower grade 0, higher grade 1 frequency vs. controls), they were found to have significantly lower frequency of grade 2 adhesion (vs. PI, Talc and AB) and grade 3 adhesion (vs. AB), indicating that the adhesion-generating properties of HES were only superior to the control group. HES recipients had significantly higher inflammatory grades compared to controls (lower grade 0, higher grade 1 frequency), while they had lower grades compared to the PI, Talc and AB groups. Although the PI, Talc and AB groups were statistically similar in most comparisons, we observed a trend towards higher success with the use of Talc and especially AB.

Conclusion

Our results do not support a role for HES in pleurodesis. We believe that the autologous blood method remains as an effective and successful procedure without side effects.
Biphasic clinical course of a ruptured right gastric artery aneurysm caused by segmental arterial mediolysis: a case report
Authors: Kohara Yuichiro , Fujimoto Koji , Katsura Hikotaro , Komatsubara Takashi , Ichikawa Kazuhito , Higashiyama Hiroshi
Published: August 2020

Background

Gastric artery aneurysms are rarely caused by segmental arterial mediolysis (SAM), a condition that often involves multiple vessels. The clinical course of SAM after vessel rupture may vary depending on the involved vessels. For example, the “double-rupture phenomenon” observed following the rupture of the splenic artery aneurysm manifests as a biphasic and relatively slow clinical course. Even in cases of rupture of gastric artery aneurysm, the double-rupture phenomenon has only been reported in two cases so far. However, the rupture was not caused by SAM in either case. Herein, we present the apparent first case of a right gastric artery (RGA) aneurysm rupture caused by SAM that presented with a biphasic clinical course, possibly due to the double-rupture phenomenon.

Case presentation

A 54-year-old woman was transferred to the emergency department with severe abdominal pain and a cold sweat for a duration of 3 h. She had developed mild abdominal pain and nausea 3 days earlier. Her vital signs were stable. Physical examination revealed tenderness in the epigastric area. Abdominal contrast-enhanced computed tomography revealed an RGA aneurysm with contrast media extravasation. A diagnosis of hemoperitoneum following a ruptured RGA aneurysm was made, and the patient underwent angiography. However, this modality did not reveal any extravasation from the RGA due to an interruption in the peripheral branch of the artery. Nevertheless, to prevent major bleeding, we performed coil embolization at the point of interruption in the RGA, which we suspected to be a ruptured aneurysm. A distal gastrectomy with Roux-en-Y reconstruction for aneurysm resection was performed the following day. There were no postoperative complications, and the patient was discharged 17 days after surgery. Histologically, the RGA demonstrated multiple vacuoles in the medial muscle layer, which were characteristic of SAM.

Conclusions

An RGA aneurysm rupture should be considered a differential diagnosis in patients presenting with hemoperitoneum with a slow or biphasic clinical course.
Silodosin improves functional consequences of lower urinary tract obstruction secondary to benign prostate hypertrophy, a proof of concept study in the spontaneously hypertensive rat supplemented with testosterone
Authors: Assaly Rana , Faugeroux Julie , Laurin Miguel , Compagnie Sandrine , Alexandre Laurent , Giuliano François , Behr-Roussel Delphine
Published: August 2020

Background

The main purpose of this study is to investigate the effect of silodosin on the urodynamic consequences in a previously established model of lower urinary tract symptoms associated with benign prostate hyperplasia, the spontaneously hypertensive rats (SHR) supplemented with testosterone.

Methods

Three groups of animals (8-week-old; n = 10/group) were considered: Wistar Kyoto (control) rats (WKY), SHR supplemented with testosterone at 3 mg/kg/day and treated with either vehicle (SHR-T, n = 10) or silodosin at 0.1 mg/kg/day (SHR-T + silodosin, n = 10) by oral gavage for 6 weeks. Cystometry experiments were performed. The bladder was harvested, weighed and paraffin-embedded for morphometric analysis. The prostate was also harvested and weighed.

Results

The number of animals included in the analysis were n = 10/10 for WKY and n = 7–8/10 for each SHR rats supplemented with testosterone group. SHR-T displayed a significant decrease in the intercontraction interval, infused volume and mean flow rate whereas the frequency of non-voiding contractions was increased. Silodosin improved the voiding behavior of SHR-T by significantly increasing the intercontraction interval, the infused volume and the mean flow rate and decreasing the number of non-voiding contractions. SHR-T displayed a significant increase in prostate and bladder weights and a 15% increase in the detrusor wall area compared to WKY.

Conclusions

Chronic silodosin treatment relieved storage symptoms in SHR supplemented with testosterone and decreased the frequency of non-voiding detrusor contractions during the filling phase.
Synergistic interaction of hTGF-β3 with hBMP-6 promotes articular cartilage formation in chitosan scaffolds with hADSCs: implications for regenerative medicine
Authors: Huang Yijiang , Seitz Daniel , Chevalier Yan , Müller Peter E. , Jansson Volkmar , Klar Roland M.
Published: August 2020

Background

Human TGF-β3 has been used in many studies to induce genes coding for typical cartilage matrix components and accelerate chondrogenic differentiation, making it the standard constituent in most cultivation media used for the assessment of chondrogenesis associated with various stem cell types on carrier matrices. However, in vivo data suggests that TGF-β3 and its other isoforms also induce endochondral and intramembranous osteogenesis in non-primate species to other mammals. Based on previously demonstrated improved articular cartilage induction by a using hTGF-β3 and hBMP-6 together on hADSC cultures and the interaction of TGF- β with matrix in vivo, the present study investigates the interaction of a chitosan scaffold as polyanionic polysaccharide with both growth factors. The study analyzes the difference between chondrogenic differentiation that leads to stable hyaline cartilage and the endochondral ossification route that ends in hypertrophy by extending the usual panel of investigated gene expression and stringent employment of quantitative PCR.

Results

By assessing the viability, proliferation, matrix formation and gene expression patterns it is shown that hTGF-β3 + hBMP-6 promotes improved hyaline articular cartilage formation in a chitosan scaffold in which ACAN with Col2A1 and not Col1A1 nor Col10A1 where highly expressed both at a transcriptional and translational level. Inversely, hTGF-β3 alone tended towards endochondral bone formation showing according protein and gene expression patterns.

Conclusion

These findings demonstrate that clinical therapies should consider using hTGF-β3 + hBMP-6 in articular cartilage regeneration therapies as the synergistic interaction of these morphogens seems to ensure and maintain proper hyaline articular cartilage matrix formation counteracting degeneration to fibrous tissue or ossification. These effects are produced by interaction of the growth factors with the polysaccharide matrix.
A remarkable case of thyrotoxicosis initially caused by graves’ disease followed by a probable TSHoma – a case report
Authors: Quinn Mark , Bashari Waiel , Smith Diarmuid , Gurnell Mark , Agha Amar
Published: August 2020

Background

Graves’ disease is the commonest cause of thyrotoxicosis whilst thyrotropin (TSH)-producing pituitary adenomas (thyrotropinomas, TSHomas) are very rare and account for just 1–2% of all pituitary adenomas. Coexistence of a TSHoma and Graves’ disease has been very rarely reported. Here, we report a case of a patient whose initial presentation with primary thyrotoxicosis due to Graves’ disease, was subsequently followed by a relapse of thyrotoxicosis due to a probable TSHoma.

Case

A sixty-eight year old woman was referred to our department with classical features of thyrotoxicosis. Initial biochemistry confirmed hyperthyroxinaemia [free thyroxine (fT4) 20.4 pmol/L (reference range 7.0–16.0)] and a suppressed TSH [< 0.02mIU/L (0.50–4.20)]. A technetium pertechnetate uptake scan was consistent with Graves’ Disease. She was treated with carbimazole for 18 months and remained clinically and biochemically euthyroid. After stopping carbimazole her fT4 started to rise but TSH remained normal. Laboratory assay interference was excluded. A TRH stimulation test demonstrated a flat TSH response and pituitary MRI revealed a microadenoma. Remaining pituitary hormones were in the normal range other than a slightly raised IGF-1. An 11C-methionine PET/CT scan coregistered with volumetric MRI (Met-PET-MRICR) demonstrated high tracer uptake in the left lateral sella region suggestive of a functioning adenoma. The patient declined surgery and was unable to tolerate cabergoline or octreotide. Thereafter, she has elected to pursue a conservative approach with periodic surveillance.

Conclusion

This is a very unusual case of thyrotoxicosis caused by two different processes occurring in the same patient. It highlights the importance of considering dual pathology when previously concordant thyroid function tests become discordant. It also highlights a potential role of Met-PET-MRICR in the localisation of functioning pituitary tumours.
Reorganizing territorial healthcare to avoid inappropriate ED visits: does the spread of Community Health Centres make Walk-in-Clinics redundant?
Authors: Ugolini Cristina , Leucci Anna Caterina , Nobilio Lucia , Bertè Gianfranco
Published: August 2020

Background

Community care has recently been restructured with the development of Community Health Centres (CHCs), forcing a general rethink on the survival of previous organizational solutions adopted to reduce inappropriate ED access, for example Walk-in-Clinics (WiCs).

Methods

We focus on the Italian Emilia-Romagna Region that has made huge investments in CHC development, whilst failing to proceed at a uniform rate from area to area. Estimating panel count data models for the period 2015–2018, we pursue two goals. First we test the existence of a “CHC effect”, choosing five urban cities with different degree of development of the CHC model and assessing whether, all else being equal, patients treated by GPs who have their premises inside the CHC show a lower need to seek inappropriate care (Aim 1). Second, we focus our attention on Walk-in-Clinics, investigating the long-established WiC in the city of Parma that currently coexists with three CHCs recently established in the same catchment area. In this case we try to assess whether, and to what extent, the progressive development of the CHCs in the city of Parma has been affecting the dynamics of WiC access (Aim 2).

Results

As regards Aim 1, we show that CHCs reduce the probability of inappropriate patient access to emergency care. As regards Aim 2, in the city of Parma patients whose GP belongs to the CHC are less likely to visit the WiC on a workday, with no significant change during the weekend when CHCs are closed, questioning the need to maintain them both in the same area when the CHC model is fully implemented.

Conclusions

Our results confirm the hypothesis that expanding access to primary care settings diminishes inappropriate ED use. In addition, our findings suggest that where CHCs and WiCs coexist in the same area, it may be advisable to implement strategies that bring WiC activities into step with CHC-based general primary care reforms to avoid duplication.
PCV cap proteins fused with calreticulin expressed into polymers in Escherichia coli with high immunogenicity in mice
Authors: Liu Chang , Liu Yunchao , Feng Hua , Zhao Baolei , Chen Yumei , Huang Huimin , Wang Pan , Deng Ruiguang , Zhang Gaiping
Published: August 2020

Background

Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus diseases (PCVDs) which causes huge yearly economic losses in the swine industry. Capsid protein (Cap) is the major structural protein of PCV2 that can induce a protective immune response. Therefore, developing a novel and safe subunit vaccine against PCV2 infection is needed.

Results

In this study, the Cap gene was bound to the truncated calreticulin (CRT) (120–250 aa/120–308 aa) at the N/C terminal, and then the CRT-Cap fusion genes were expressed in Escherichia coli (E.coli). The size-exclusion chromatography and dynamic light scattering (DLS) data showed that the purified recombinant CRT-Cap fusion protein (rP5F) existed in the form of polymers. Immunization with rP5F stimulated high levels of PCV2 specific antibody and neutralization antibody in mice, which were almost identical to those induced by the commercial subunit and inactivated vaccines. The lymphocyte proliferation and cytokine secretion were also detected in rP5F immunized mice. According to the results of PCV2-challenge experiment, the virus loads significantly decreased in mice immunized with rP5F. The data obtained in the current study revealed that rP5F had the potential to be a subunit vaccine candidate against PCV2 in the future.

Conclusions

We have successfully expressed Cap-CRT fusion proteins in E.coli and optimized rP5F could form into immunogenic polymers. Mice immunized with rP5F efficiently induced humoral and part of cellular immune responses and decreased the virus content against PCV2-challenge, which suggested that rF5P could be a potential subunit vaccine candidate.
A machine learning framework for genotyping the structural variations with copy number variant
Authors: Zheng Tian , Zhu Xiaoyan , Zhang Xuanping , Zhao Zhongmeng , Yi Xin , Wang Jiayin , Li Hongle
Published: August 2020

Background

Genotyping of structural variation is an important computational problem in next generation sequence data analysis. However, in cancer genomes, the copy number variant(CNV) often coexists with other types of structural variations which significantly reduces the accuracy of the existing genotype methods. The bias on sequencing coverage and variant allelic frequency can be observed on a CNV region, which leads to the genotyping approaches that misinterpret the heterozygote as a homozygote. Furthermore, other data signals such as split mapped read, abnormal read will also be misjudged because of the CNV. Therefore, genotyping the structural variations with CNV is a complicated computational problem which should consider multiple features and their interactions.

Methods

Here we proposed a computational method for genotyping indels in the CNV region, which introduced a machine learning framework to comprehensively incorporate a set of data features and their interactions. We extracted fifteen kinds of classification features as input and different from the traditional genotyping problem, here the structure of variant may fall into types of normal homozygote, homozygous variant, heterozygous variant without CNV, heterozygous variant with a CNV on the mutated haplotype, and heterozygous variant with a CNV on the wild haplotype. The Multiclass Relevance Vector Machine (M-RVM) was used as a machine learning framework combined with the distribution characteristics of the features.

Results

We applied the proposed method to both simulated and real data, and compared it with the existing popular softwares include Gindel, Facets, GATK, and also compared with other machine learning cores: Support Vector Machine, Lanrange-SVM with OVO multiple classification, Naïve Bayes and BP Neural Network. The results demonstrated that the proposed method outperforms others on accuracy, stability and efficiency.

Conclusion

This work shows that the genotyping of structural variations on the CNV region cannot be solved as a traditional genotyping problem. More features should be used to efficiently complete the five-category task. According to the result, the proposed method can be a practical algorithm to correct genotype structural variations with CNV on the next generation sequence data. The source codes have been uploaded at https://github.com/TrinaZ/Mixgenotypefor academic usage only.
MicroRNA-214-3p inhibits the stem-like properties of lung squamous cell cancer by targeting YAP1
Authors: Lu Tingting , Yang Ying , Li Ziming , Lu Shun
Published: August 2020

Background

Emerging evidence reveals that microRNAs (miRNAs) play a crucial role in tumor progression, but the underlying mechanism of microRNAs in lung squamous cell cancer (LSCC) remains unclear.

Method

Western-blotting and quantitative real-time PCR (q-PCR) were carried out to detect mRNA and protein expression. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony-forming assay or sphere-forming assay, respectively.

Results

MiR-214-3p was markedly de-regulated in LSCC tissues and was inversely related to the level of Yes-associated protein1 (YAP1), which is the core transcription regulator of the Hippo signaling pathway. Kaplan–Meier survival curves illustrated that patients with high miR-214-3p expression demonstrated more favorable clinical outcomes. MiR-214-3p overexpression (OE) repressed proliferation and cancer stem-like cells (CSCs) properties in vitro and in vivo xenograft mouse model. Mechanistically, luciferase activity assay revealed that miR-214-3p directly targets YAP1 by specifically binding on the 3′ UTR of YAP1.

Conclusion

MiR-214-3p plays a pivotal role in CSCs properties by targeting YAP1, which provides a potential treatment strategy for LSCC patients.
Efficacy of artemether-lumefantrine for treating uncomplicated Plasmodium falciparum cases and molecular surveillance of drug resistance genes in Western Myanmar
Authors: Wu Yanrui , Soe Myat Thut , Aung Pyae Linn , Zhao Luyi , Zeng Weilin , Menezes Lynette , Yang Zhaoqing , Kyaw Myat Phone , Cui Liwang
Published: August 2020

Background

Currently, artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment in malaria-endemic areas. However, resistance in Plasmodium falciparum to artemisinin-based combinations emerging in the Greater Mekong Sub-region is a major problem hindering malaria elimination. To continuously monitor the potential spread of ACT-resistant parasites, this study assessed the efficacy of artemether-lumefantrine (AL) for falciparum malaria in western Myanmar.

Methods

Ninety-five patients with malaria symptoms from Paletwa Township, Chin State, Myanmar were screened for P. falciparum infections in 2015. After excluding six patients with a parasite density below 100 or over 150,000/µL, 41 P. falciparum patients were treated with AL and followed for 28 days. Molecular markers associated with resistance to 4-amino-quinoline drugs (pfcrt and pfmdr1), antifolate drugs (pfdhps and pfdhfr) and artemisinin (pfk13) were genotyped to determine the prevalence of mutations associated with anti-malarial drug resistance.

Results

For the 41 P. falciparum patients (27 children and 14 adults), the 28-day AL therapeutic efficacy was 100%, but five cases (12.2%) were parasite positive on day 3 by microscopy. For the pfk13 gene, the frequency of NN insert after the position 136 was 100% in the day-3 parasite-positive group as compared to 50.0% in the day-3 parasite-negative group, albeit the difference was not statistically significant (P = 0.113). The pfk13 K189T mutation (10.0%) was found in Myanmar for the first time. The pfcrt K76T and A220S mutations were all fixed in the parasite population. In pfmdr1, the Y184F mutation was present in 23.3% of the parasite population, and found in both day-3 parasite-positive and -negative parasites. The G968A mutation of pfmdr1 gene was first reported in Myanmar. Prevalence of all the mutations in pfdhfr and pfdhps genes assessed was over 70%, with the exception of the pfdhps A581G mutation, which was 3.3%.

Conclusions

AL remained highly efficacious in western Myanmar. Pfk13 mutations associated with artemisinin resistance were not found. The high prevalence of mutations in pfcrt, pfdhfr and pfdhps suggests high-degree resistance to chloroquine and antifolate drugs. The pfmdr1 N86/184F/D1246 haplotype associated with selection by AL in Africa reached > 20% in this study. The detection of > 10% patients who were day-3 parasite-positive after AL treatment emphasizes the necessity of continuously monitoring ACT efficacy in western Myanmar.
The value of local consolidative therapy in Osimertinib-treated non-small cell lung cancer with oligo-residual disease
Authors: Zeng Ya , Ni Jianjiao , Yu Fan , Zhou Yue , Zhao Yang , Li Shuyan , Guo Tiantian , Chu Li , Yang Xi , Chu Xiao , Cai Xuwei , Zhu Zhengfei
Published: August 2020

Background

There was no study investigating real-world utilization and outcome of LCT in Osimertinib-treated NSCLC with oligo-residual disease. This study was to analyze the clinical value of local consolidative therapy (LCT) in Osimertinib-treated non-small cell lung cancer (NSCLC) patients with oligo-residual disease.

Methods

Patients receiving standard Osimertinib treatment and developing oligo-residual disease (five or fewer residual metastatic lesions) were retrospectively reviewed. Local therapies performed to the oligo-residual tumor lesions or primary lung site before Osimertinib treatment failure were considered as LCT.

Results

Of 108 patients recruited, first-line and second-line Osimertinib were administered in 25 and 83 patients, respectively, while LCT was performed in 14 patients. With a median follow-up of 43.6 months, 69 patients developed progressive disease. LCT significantly improved progression-free survival (PFS) (NR vs 12.8 months,p = 0.01) and was independently associated with prolonged PFS (HR = 0.29, 95%CI 0.12 to 0.68,p = 0.004). Patients receiving LCT had a numerically longer overall survival (OS) (85.8 vs 77.1 months,p = 0.58) and after adjusting for potentially confounding factors, LCT was associated with a non-significantly prolonged OS (HR = 0.37, 95%CI 0.12–1.16,p = 0.089). Pattern of failure analyses indicated that progressive disease developed at the originally existed oligo-residual lesions in 76.2% of the 63 patients who didn’t receive LCT and had Osimertinib treatment failure. Of note, 7 (70%) of the 10 patients who had oligo-residual cranial disease but didn’t receive LCT, developed more than five progressive lesions in the brain, which were no longer suitable for stereotactic radiosurgery.

Conclusion

Among Osimertinib-treated NSCLC patients having oligo-residual lesions, LCT could improve local control and significantly increase PFS, which need to be verified by further investigations.
The relationship between ACL reconstruction and meniscal repair: quality of life, sports return, and meniscal failure rate—2- to 12-year follow-up
Authors: Rodríguez-Roiz Juan M. , Sastre-Solsona Sergi , Popescu Dragos , Montañana-Burillo Jordi , Combalia-Aleu Andres
Published: August 2020

Background

Few studies have approached in a long-term follow-up of meniscal repair at an amateur level, specially studying variables as a quality of life and failure rate. The purpose of this review is to study medium to long-term clinical results in patients at amateur sports patients, that have required meniscal sutures at our center, with or without ACL reconstruction. We evaluate the objective function of the knee, as well as patients’ return to sports activities, quality of life, and the rate of failed repair and study of the possible reasons.

Methods

This was an observational retrospective study. Ninety-two patients who regularly perform amateur sports activities (Tegner 4 to 7) were assessed, with a minimum follow-up period of 2 years, divided into 2 groups: group 1, isolated meniscal suture (43 cases) and group 2, associated to ACL reconstruction (49 cases). Each patient made this test in 2019: Lysholm and Tegner (validated for Spanish) before a knee injury and after surgery, motivation to return to sports activity (Likert scale with 3 items: low, regular, or high), and quality of life through SD-12 test.

Results

High return to amateur sports rate (92%) was even higher in the isolated meniscal repair group in comparison to the group with associated ACL. We have not found statistically significant differences between sports return and age, gender, injured meniscus, chondral injuries, preoperative Tegner score, or motivation. No significant differences in physical or mental health fields between both groups. Meniscal repair failed in 12 patients (13%). Higher rate of failure in isolated bucket-handle tear injuries (p < 0.0062). No statistically significant association was found between the other variables studied.

Conclusions

Good results with 92% of sports return, low rate of complications, and low retear rate, even lower when is associated with ACL reconstruction and in external meniscus repair, and high values at SF-12 between 2 groups.
The lateral habenula is critically involved in histamine-induced itch sensation
Authors: Ko Hyoung-Gon
Published: August 2020

Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injection enhances Fos (+) cells in posterior portion within parvocellular and central subnuclei of the medial division (LHbM) of the LHb. Moreover, chemogenetic suppression of LHbM reduced scratching behavior induced by histamine injection. These results suggest that LHb is required for processing itch information to induce histaminergic itchy response.
miRNA expression profile changes in the peripheral blood of monozygotic discordant twins for epithelial ovarian carcinoma: potential new biomarkers for early diagnosis and prognosis of ovarian carcinoma
Authors: Tuncer Seref Bugra , Erdogan Ozge Sukruoglu , Erciyas Seda Kilic , Saral Mukaddes Avsar , Celik Betul , Odemis Demet Akdeniz , Turkcan Gozde Kuru , Yazici Hulya
Published: August 2020

Background

Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs.

Methods

The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.

Results

After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.

Conclusions

The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. ThemiRNA expressionprofiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data.

There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.
The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789
Authors: Flores-Alanis Alejandro , Sandner-Miranda Luisa , Delgado Gabriela , Cravioto Alejandro , Morales-Espinosa Rosario
Published: August 2020

Objective

In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans.

Results

Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved.
Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner
Authors: Zhang Xiaoyuan , Du Renle , Luo Na , Xiang Rong , Shen Wenzhi
Published: August 2020

Background

The widely recognized anti-cancer potential of aspirin has created a broad interest to explore the clinical benefits of aspirin in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anti-cancer potential of aspirin remains limited.

Methods

Cancer stemness assays which contained ALDH, side population, chemo-resistance, sphere formation, and tumorigenesis were performed to validate aspirin function in vitro and in vivo. Histone modification assay was performed to check the effect of aspirin on histone methylation as well as the activity of HDAC and KDM6A/B. Inhibitor in vivo assay was performed to evaluate therapeutic effects of various inhibitor combination manners.

Results

In regards to in vitro studies, aspirin diminishes cancer cell stemness properties which include reducing the ALDH+ subpopulation, side population, chemo-resistance, and sphere formation in three cancer types. In regards to in vivo studies, aspirin decreases tumor growth and metastasis and prolongs survival. In addition, our results showed that aspirin inhibits inflammation-related stemness gene expression (especially ICAM3) identified by a high-throughput siRNA platform. In regards to the underlying molecular mechanism of action, aspirin reduces histone demethylase (KDM6A/B) expression that mediates histone methylation and suppresses gene expression via a COX-independent manner. In regards to therapeutic strategies, aspirin combined HDM inhibitors, ICAM3 downstream signaling Src/PI3K inhibitors, or ICAM3 inhibitor Lifitigrast prevents cancer progression in vivo.

Conclusions

The aforementioned findings suggest a molecular model that explains how aspirin diminishes cancer cell stemness properties. These findings may provide novel targets for therapeutic strategies involving aspirin in the prevention of cancer progression.
Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome
Authors: Accarie Alison , l’Homme Bruno , Benadjaoud Mohamed Amine , Lim Sai Kiang , Guha Chandan , Benderitter Marc , Tamarat Radia , Sémont Alexandra
Published: August 2020

Background

Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss, and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality.

Methods

Human MSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24, and 48 h after lethal whole-body irradiation (10 Gy). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3), and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods.

Results

We demonstrated that MSC-derived extracellular vesicle treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Gy whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium.

Conclusions

MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.
Triple nostrils in a calf
Authors: Tsuka Takeshi , Saito Ai , Okamoto Yoshiharu , Sunden Yuji , Morita Takehito , Nishimura Ryo , Murahata Yusuke , Azuma Kazuo , Yamashita Masamichi , Osaki Tomohiro , Ito Norihiko , Imagawa Tomohiro
Published: August 2020

Background

Nasal abnormalities are rare in bovines. In humans, nasal deformities are mainly classified as proboscis lateralis or supernumerary nostrils. This report discusses the etiology of triple nostrils in a calf, based on computed tomography, magnetic resonance imaging, and endoscopy.

Case presentation

A female Holstein calf presented with triple nostrils. The following abnormalities were observed: (1) formation of a small and flat blind-ended middle nostril between the right and left nostrils; (2) presence of a hair-bearing surface on the muzzle; (3) abnormal curvature of the nasal septum, resulting in a narrower right nasal cavity due to transformation of the nasal bones; and (4) formation of a bone-like structure within the nasal septum. These findings were similar to those of supernumerary nostrils in humans.

Conclusions

To the best of our knowledge, this represents the first description of a calf with triple nostrils. The use of imaging modalities is necessary for investigating the etiology of triple nostrils.
Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients
Authors: Hussien Marwa T. , Shaban Shimaa , Temerik Doaa F. , Helal Shaaban R. , Mosad Eman , Elgammal Sahar , Mostafa Abeer , Hassan Eman , Ibrahim Abeer
Published: August 2020

Background

Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues.

Results

Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS.

Conclusion

Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.
Sonopartogram versus conventional partogram for monitoring progress of labor: a prospective observational study
Authors: Sweed Mohamed S. , Allam Ihab F. , Ashoush Sherif A. , Marwan Osama A. , NasrElDin Eman A.
Published: August 2020

Background

Repeated digital vaginal examination during labor may be uncomfortable for women and increases the risk of ascending infection. Transperineal ultrasound can assess fetal head descent, position, and cervical dilatation without these side effects. This study was conducted to evaluate the accuracy of transperineal ultrasound in monitoring labor progress.

Results

The study included 40 primigravida women in labor. Fair correlation was found between the assessment of fetal head station by vaginal examination (VE) and fetal head perineal distance (HPD) by transperineal ultrasound (TPUS) (Kendall’s tau-b (τ) = − 0.299, 95% CI = − 0.479 to − 0.0863, p value = .0063) (Spearman rho = − .3844, p value = .0143; r2 = 0.1478). Strong correlation was found between the cervical dilatation assessed by VE and by TPUS (Pearson’s r = .8601, 95% CI = 0.7493 to 0.9240, p value < .0001, r2 = 0.7396). There is moderate agreement between VE and TPUS as regards the assessment of head position on the face-clock [weighted kappa (κ) = .557, 95% CI = .362 to.753].

Conclusion

Transperineal ultrasound can be used as an alternative to repeated digital examination for assessment of labor progress.