bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficacy of Transarterial Chemoembolization in Downstaging Unresectable Hepatocellular Carcinoma to Curative Therapy: A Predicted Regression Model
Authors: LIN Hao Min , PENG Fang Yi , HUANG Bin , FANG Cheng , GAN Yu , YANG Xiao Li , LI Bo , Su Song
Published: August 2021

Background: Patients with hepatocellular carcinoma (HCC) outside the Milan criteria (MC) may be candidates for curative therapy after successful downstaging. However, there have been no studies that have examined the factors affecting the efficacy of transarterial chemoembolization (TACE) on downstaging. We aimed to identify the predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC.Methods: We performed a retrospective study on patients with unresectable HCC outside the MC who received downstaging with TACE. Clinical and laboratory variables were recorded. We identified 101 patients with unresectable HCC who underwent initial TACE, and they formed the derivation set of this study. Thirty patients who received TACE treatment with the same selection criteria served as an external validation set. We performed multivariate logistic regression analyses to identify the variables associated with successful downstaging. Then, we created a predictive model and determined its accuracy in predicting the efficiency of TACE.Results: Of the 101 patients in the study, 26 patients (25.7%) were successfully downstaged. Multivariate analysis was performed on the number of tumors (P=0.018), portal vein tumor thrombi (PVTT) (＜0.001), the size of tumors (P=0.021), hepatitis B surface antigen (HBsAg) (P=0.014), and a-fetoprotein (AFP, P=0.027), which were considered as significant predictors of successful downstaging of HCC outside the MC. Then, we constructed the predictive model. The area under the ROC curve (AUROC) for the predictive equation was 0.908 (95% confidence interval, 0.832-0.957).Conclusions: We found in our study that the number and size of tumors, PVTT, HBsAg, and AFP are good predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC.
Climate Change And Agriculture Management – Western Balkan Region Analysis
Authors: Županić Franc Željko , Radić Danka , Podbregar Iztok
Published: August 2021

Background: The aim of this paper is to analyze the possibilities of the agricultural sector of the Western Balkans, to assess compliance with the European Green Deal, which provides for the implementation of activities, which should enable the transition to the green sector and climate change mitigation. This paper is the first scientific paper to analyze agriculture and climate change in light of the EU Green Deal for the Western Balkan territory.Results: Agricultural production is one of the leading industries in the Western Balkans. In the Republic of Serbia, the total gross value of agricultural production in 2019 amounted to 5.5 billion dollars, in Albania, it is the basis of the life of the population and the system of protection against unemployment, while in Bosnia and Herzegovina 1/5 of the population is employed in this sector. Montenegro has a significant share in the gross domestic product (GDP, 8%), while in the Republic of Northern Macedonia agriculture accounts for 13% of GDP. Climate change and predictions that temperatures will increase by 4oC in the coming decades pose a risk not only to agricultural production but also to the safety of the population. If it takes into account that the agricultural production of the countries of the Western Balkans depends primarily on rain, this makes this sector particularly vulnerable. Unless appropriate measures are taken and risk management for water resources and agriculture is improved, there will be a decrease in precipitation and an increase in dry days by 20%. One of the ways to implement adequate activities is the adoption of regulations related to the creation of local energy management, which will enable the assessment of climate change and based on them to give appropriate "energy response“. Conclusions: Taking this combined and ambitious approach and using the latest developments in knowledge and innovation, the Common Agricultural Policy (CAP) aligns agriculture with the European Green Deal, which aims to create an inclusive, competitive, and environmentally friendly future for Europe. Finding renewable energy sources and improving risk management can mitigate the negative impact of climate change and prevent the loss of agrobiodiversity.
Comprehensive analysis of tumor microenvironment landscape and potential therapeutic agents based on tumor-infiltrating immune cells in colorectal cancer
Authors: Zhong Wenhui , Zhang Feng , Lu Xin , Huang Kaijun , Bi Junming , Liu Yubin
Published: August 2021

Background: Tumor-infiltrating immune cells (TIIC) are the major components of the tumor microenvironment (TME) and play vital roles in the tumorigenesis and progression of colorectal cancer (CRC). Increasing evidence has elucidated their significances in predicting prognosis and therapeutic efficacy. Nonetheless, the immune infiltrative landscape of CRC remains largely unknown. Methods: All the RNA-seq transcriptome data and full clinical annotation of 1213 colorectal cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO) database. The “CIBERSORT” and “estimate” R package were applied to calculate 22 infiltrated immune cell fractions and stromal and immune score. Three TIIC patterns were determined by Unsupervised clustering methods. Through using principal-component analysis, TIIC scores were established. Data for potential agents comes from the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) and Cancer Therapeutics Response Portal database (CTRP). Results：In this study, we identified three distinct TIIC patterns characterized by distinct immunological features in 1213 CRC samples from multiple platforms. Base on the TIIC-related gene signatures from three clusters, we constructed a scoring system to quantify the immune infiltration level of individual samples in the CRC cohort and the clinical benefits of different groups. The high TIIC score group was marked by increased immune activation status and favorable prognosis. Conversely, low TIIC score group was featured with immune-desert phenotype and poor prognosis, along with the activation of transforming growth factor-β (TGF-β), WNT, ECM receptor interaction, and VEGF signaling pathways. Meanwhile, the high TIIC score group was also correlated with enhanced efficacy of immunotherapy. Additional, four chemotherapy drugs, seven CTRP-derived drug compounds and six PRISM-derived drug compounds were identified as potential drug for CRC among high and low TIIC subgroups.Conclusions: Collectively, as an effective prognostic biomarker and predictive indicator, the TIIC score plays an important role in the evaluation of CRC prognosis and the response of immunotherapy. Investigation of the TIIC patterns might provide us a promising target for improving immunotherapeutic efficacy in CRC.
Thalamocortical Connection Changes with Recovery of Impaired Consciousness in a Stroke Patient with Parietal Lobe Injury
Authors: Jang Sung Ho , Chang Chul Hoon , Lee Sung Jun
Published: August 2021

A 52-year-old female patient underwent craniectomy and hematoma removal for a spontaneous intracerebral hemorrhage in the left parietal lobe, as well as intraventricular and subarachnoid hemorrhages (Fig. 1-A). Brain magnetic resonance images obtained three months after onset showed leukomalactic lesions in the left parieto-occipital lobes (Fig. 1-A). Initially, the patient was in a vegetative state with a Coma Recovery Scale-revised score of 11 (auditory function: 2, visual function: 4, motor function: 2, verbal function: 1, communication: 0, and arousal: 2) (1). Subsequently, she underwent comprehensive rehabilitation, which included neurotropic drug treatments (armodafinil, pramipexole, amantadine, levodopa, and baclofen) and physical and occupational therapies (including tilt table standing). In addition, transcranial direct current stimulation was administered by using a neuroConn DC-stimulator. The anode was placed on the left parietal lobe (centered on the supraparietal lobule) and the cathode was placed on the opposite supraorbital region. The transcranial direct current stimulation intensity was 2 mA and the duration was 20 minutes/session with one session/day and seven sessions/week. Repetitive transcranial magnetic stimulation using a MagPro stimulator was applied to mid-portion of the right intraparietal sulcus at a frequency of 10 Hz with an 80% motor threshold intensity and 160 pulses for 8 minutes/session with one session/day and seven sessions/week. After one month of rehabilitation, the patient had recovered to a nearly normal conscious state with a Coma Recovery Scale-revised score of 21 (auditory function: 4, visual function: 5, motor function: 5, verbal function: 2, communication: 2, arousal: 3) [1]. The patient’s sister provided signed, informed consent, and the study protocol was approved by our institutional review board.
Excessive Blood Loss After Revision Hip Arthroplasty is Related to the use of Closed Suction Drainage: A Prospective Randomized Study
Authors: Bartosz Paweł , Grzelecki Dariusz , Chaberek Sławomir , Para Marcin , Marczyński Wojciech , Białecki Jerzy
Published: August 2021

Background:Suction drainage after primary total hip arthroplasties (THA) offers no benefits. Revision hip arthroplasties (RHA) are more demanding procedures and associated with greater blood loss compared to primary cases. There is still a lack of literature regarding the application of drainage in RHA.Material and Methods:A total of 40 patients who underwent RHA were included in this prospective study. Simple randomization with an allocation ratio 1:1 was performed. Primary outcomes: total blood loss, hemoglobin drop, joint hematoma size in USG, infection. Secondary outcomes: blood transfusion rate, soft tissue hematomas, C-reactive protein levels, Visual Analogue Scale before and on 3rd day after surgery, Harris Hip Score before and 6 weeks after surgery. An intention to treat analysis was performed, with a 2-year follow up.Results:Statistically significant differences between groups was in blood loss: drainage 1559.78 ml, non-drainage 1058.27 ml, (p=0.029) and hemoglobin level on 1st day after surgery: drainage 10.58 g/dl, non-drainage 11.61 g/dl (p=0.0496). In terms of the other analyzed parameters, statistical differences were not found. Conclusion:Our study revealed that the use of suction drainage may lead to higher blood loss in the early postoperative period. Further studies are needed to evaluate our results.
Association of Adverse Childhood Experiences (ACEs) With Obesity And Underweight In Children
Authors: Hanć Tomasz , Bryl Ewa , Szcześniewska Paula , Dutkiewicz Agata , Borkowska Aneta Rita , Paszyńska Elżbieta , Słopień Agnieszka , Dmitrzak-Weglarz Monika
Published: August 2021

Purpose: The aim of the study was to test the hypothesis that adverse childhood experiences (ACEs) are related to both obesity and underweight from childhood, and that the association of ACEs with weight abnormalities is modulated by type of ACEs, sex and socioeconomic status (SES) indices. Methods: The relations between ACEs (0 vs ≥1), ACE accumulation and ACE type with weight status and z scores BMI were assessed in 503 children aged 6-12 years from Poznan, Poland. The effects of interaction of ACEs with sex and SES on z scores BMI were included in the analyses. Results: ACEs were significantly related to both obesity and underweight, in unadjusted analysis, and when sex and SES indices, such as size of place of residence, people per room in household, and parental education were controlled. The relation of ACEs with z scores BMI was modulated by ACE type, parental subjective assessment of economic situation of a family and parental education. ACE accumulation was not related to an increase of obesity or underweight rate, or z scores BMI. Conclusion: The study implicates the need for both obesity and underweight prevention in individuals with adverse experiences as early as in childhood.
Peak Systolic Velocity at Arterial Doppler Ultrasound in Pediatric Liver Transplantation: as Predictor of Acute Severe Complications.
Authors: Coma Ana , Anton-Jimenez Alba , Escudero-Fernandez Jose Miguel , Quintero Jesus , Molino Jose Andres , Ortega Juan , Hidalgo Ernest , Charco Ramon , Vazquez Elida
Published: August 2021

The objective of this study is to determine whether hepatic artery Doppler ultrasound parameters can predict arterial complications in the immediate period after a liver transplantation in children.A retrospective review of the pediatric liver database at our tertiary-care pediatric hospital was performed. The study included 57 pediatric patients who underwent liver transplantation from 2016 to 2020. Clinical, laboratory and Doppler findings were recorded daily the first 5 days after transplantation. Especial attention was focused on extrahepatic post-anastomotic Peak Systolic Velocity (PSV) and intrahepatic Resistive Index (RI). Forty-nine liver transplant recipients were analyzed. Patients with acute hepatic artery complications, including acute thrombosis and stenosis, had lower PSV values at 3 and 4 days after surgery compared to the group with non-complications, with a statistical significance (p=.015). Receiver operating characteristic (ROC) curve analysis determined an optimal cut-off value of PSV less than 30 cm/s to discriminate children with and without acute hepatic arterial complications, which is lower than that proposed in adults. It correlates with acute arterial stenosis and thrombosis in children even before RI, clinical symptoms or laboratory anomalies appear.
Renal Infarction Associated with Atrial Fibrillation Following ICD Implantation: A Case Report and Literature Review
Authors: Huang Yingshuo , Sun Ying
Published: August 2021

Background: Atrial fibrillation increases the risk of thromboembolism in the kidney. Renal infarction in atrial fibrillation receiving implantable cardioverter defibrillator (ICD) treatment is rarely seen.Case Presentation: We reported a case of a 76-year-old woman who presented with palpitations and short of breath with ECG showing paroxysmal atrial fibrillation (AF) and long RR interval. The patient was diagnosed congestive heart failure with NYHA class III-IV and received an ICD implantation as the onset of ventricular tachycardia. The seventh after ICD implantation operation, she complained of right lower abdominal pain with fever and blood WBC increased. Right renal infarction was confirmed after abdominal enhancement computed tomography scan. Anticoagulation therapy was given immediately, the patient had an stable international normalized ratio (INR) and mild elevated serum creatinine levels during follow-up.Conclusion: This case enlightened us some comprehension about the strategy for periprocedural anticoagulation and prevention of thromboembolism in the elderly with paroxysmal atrial fibrillation. Renal infarction and anticoagulation strategies for atrial fibrillation during perioperation were reviewed in this paper.
Green Nanoparticles Synthesized From Endophytic Fungi (Colletotrichum Gloeosporioides) Break Antibiotic Resistance in Pathogenic E. Coli
Authors: N Mohamed Juvad , S Ranjani , Hemalatha S
Published: August 2021

Green Nanotechnology synthesizes nanoparticles from a myriad of perspectives or sources including plants and microscopic structures as well as biologically active compounds. Endophytic fungi are organisms that really can mimic and produce secondary metabolites similar to their hosts. In this study, we focus on the Endophytic fungal mediated silver nanoparticles (CgAgNPs) synthesized by using aqueous extract of endophyte Colletotrichum gloeosporioides. Synthesized nanoparticles were characterized using a UV-Vis spectrophotometer and SEM. To assess the efficacy of CgAgNPs, antimicrobial assays were performed against Escherichia coli ATCC 25922 and antibiotic resistant pathogenic clinical strains of E. coli. In order to find the interaction ability of fungal metabolites with CTX-M-15 and AmpC gene products In silico inspections were done through Molecular docking. Lipinski screening and ADMET analysis were performed for fungal metabolites to screen the lead compounds and drug ability to analyze the pharmacokinetic properties.
Facklamia Hominis Pyelonephritis in a Pediatric Patient: First Case Report and Review of the Literature
Authors: Cavazos Samantha Perez , Saldaña Daniela Cisneros , Villaseñor Fernando Espinosa , Bejarano José Iván Castillo , Aparicio Denisse Natalie Vaquera , Alanís Hugo Sánchez , Santos Abiel Homero Mascareñas de los
Published: August 2021

Background

Pyelonephritis is one of the most serious bacterial illnesses during childhood. Gram-negative organisms account for up to 90% of the cases. Gram-positive bacteria are uncommon causes of urinary tract infections, and only a few cases caused by Facklamia hominis have been reported in the literature.
Case presentation:

A five-year-old girl with tracheostomy and gastrostomy and past medical history of congenital lymphangioma presented with a two-week history of with intermittent fever, frequent urination, and vesical tenesmus. Diagnosis of pyelonephritis was made. Urine culture reported colonies with alpha-hemolysis in blood agar at 48-hours of incubation and Facklamia hominis was identified by MALDI-TOF. The patient was successfully treated with gentamicin.
Conclusions

This is the first reported case of pyelonephritis by Facklamia hominis in a child, and the second involving infection in a pediatric patient. Although this pathogen is uncommon, current treatment of F. hominis is a challenge for physicians. This case illustrates the requirement to standardize identification and treatment of care to avoid treatment failure and antimicrobial resistance.
Emergency Cardiopulmonary Resuscitation of Out-of Hospital Cardiac Arrest: Why Should we Care
Authors: Huang Luxiao , Chen Jinyao , Yu Baojun , Tang Chunfu , Ma Xiaoliang
Published: August 2021

Background: Cardiopulmonary resuscitation (CPR) plays an essential role in the treatment of sudden cardiac arrest (SCA), we aimed to evaluate the influencing factors on the effects of CPR in patients with SCA, to provide insights into the management of SCA.Methods: Patients who underwent CPR in the emergency department of our hospital from January 1, 2019 to June 30, 2021 were selected. We collected and analyzed the clinical characteristics of CPR patients. Logistic regression analyses were conducted to identify the risk factors of CPR failure.Results: A total of 308 CPR patients were included, the incidence of CPR success was 35.71%. There were significant differences in the age, time to the start of CPR, the type of heart rhythm in the first monitoring, duration of CPR and cumulative adrenaline dosage between CPR success and failure group (all P<0.05). No significant differences in the gender, cause of cardiac arrest and ventilation methods were found (all P>0.05). Logistic regression analyses indicated that age≥65y(OR2.132, 95CI%1.127~4.334), time to the start of CPR≥12min(OR2.503, 95CI%1.015~3.583), unable to defibrillation(OR1.856, 95CI%1.107~3.031), duration of CPR≥40min(OR2.162, 95CI%1.242~4.178), cumulative adrenaline dosage≥6mg(OR1.627, 95CI%1.151~2.472) were the independent risk factors of CPR failure(all P<0.05).Conclusions: The success and failure of CPR are affected by many factors. Early and effective interventions should be taken for these influencing factors in clinical practice. Due to the limitation of sample size, future large-sample and multi-center studies need to further explore the relevant influencing factors of CPR.
Clinical Characteristics of Healthcare Workers with SARS-CoV-2 Infection after Vaccination with BNT162b2 Vaccine
Authors: Lombardi Andrea , Renisi Giulia , Consonni Dario , Oggioni Massimo , Bono Patrizia , Renteria Sara Uceda , Piatti Alessandra , Pesatori Angela Cecilia , Castaldi Silvana , Muscatello Antonio , Riboldi Luciano , Ceriotti Ferruccio , Gori Andrea , Bandera Alessandra
Published: August 2021

Background: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has hardly affected the entire world. Vaccines against COVID-19 appear as a tool able to curb out the mortality and to reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset.Methods: Retrospective cohort study among the healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano, vaccinated with the BNT162b2 vaccine who developed SARS-CoV-2 infection (documented through positive RT-PCR on NPSs). Results: Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them the presence of SARS-CoV-2 anti-nucleocapside (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, in average 42.2 days after the completion of vaccination, with a mean value of 2,055 U/mL (SD 1,927.3). SARS-CoV-2 infection was ascertained in average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptoms (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported.Conclusions: Infections occurring after vaccination with BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of a specific viral variants, with several lineages represented.
Factors Influencing the Uptake of Short Term Contraceptives Among Women in Afghanistan: Further Analysis of Afghanistan Demographic and Health Survey 2015 (A Cross Sectional Study)
Authors: Noormal Ahmad Siyar , Winkler Volker , Eshraqi Ali Maisam , Deckert Andreas , Sadaat Iftekhar , Dambach Peter
Published: August 2021

Objective: The aim of this study is to assess factors that influence the uptake of short term contraceptives among married women aged between 15-49 years in Afghanistan.Method: The cross sectional Afghanistan 2015 Demographic and Health Survey provided the dataset for this analysis. We included 22,974 women and applied multivariable logistic regression to investigate the influencing factors for the uptake of short term contraceptives.Results: 95% of Afghan women knew at least one type of contraception but only 16% were using short term contraceptives. Short term contraceptive use was most prevalent among women in the age group between 30 and 40 who were educated, employed, and rich. Most of users were living in the western parts of Afghanistan and belong to Balooch and Pashtun ethnic groups. Media exposure and women empowerment were also positively associated with the use of short term contraceptives. However, we did not find an association with living in urban or rural settings.Conclusion: FP in Afghanistan requires multisectorial efforts, tailored to the needs of women stemming from low and middle socioeconomic status. Health promotion 5 activities, empowering women, strengthening education, and training of FP service providers on effective counseling are good options to address the issue.
Child-onset Hemifacial Spasm-a case report
Authors: Sun Tao , Li Ning , Liu Jinlong , Yang Chao
Published: August 2021

BackgroundHemifacial spasm (HFS) is a common cranial nerve disease, with peak onset in the forty to sixty years old and child-onset HFS is rare. HFS brings many negative effects on the physical and mental health of patients. Here, we report a 10-year-old case of primary HFS patient.Case PresentationHere we report an 11-year-old HFS case last for more than 1 year. An 11-year-old girl complained of frequently involuntary twitch in lower eyelid as the girl was 10 years old, then symptom worsen gradually involved right upper lip in recently months. The girl’s daily life was badly influenced. Brain magnetic resonance imaging indicated that AICA compressed right facial nerve. The patient was treated with carbamazepine 200mg per day, and symptom gradually relieve. But bad treatment compliance appeared, and we introduced the advantages and disadvantages of botulinum toxin and MVD to her parents. However, considering the young age, above mentioned options are not considered for the time being. And more observations of medications treatment were needed to guide further treatment.ConclusionChild-onset hemifacial spasm is rare and the case we report is one of the youngest known cases of such disease. For such patients, medication is the first choice, but the exact mechanisms remain to be further explored.
Plasmodium circumsporozoite protein enhances the efficacy of gefitinib in lung adenocarcinoma cells by inhibiting autophagy via proteasomal degradation of LC3B
Authors: Lu Xiao , Zhang Jiao , Liu Quanxing , Zhou Dong , Deng Xufeng , Yang Guixue , Li Manyuan , Liu xiaoqing , Dai Jigang , Zheng Hong
Published: August 2021

Background: Almost all patients with lung adenocarcinoma (LUAD) develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, LDH, flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, the apoptosis rate, and stemness. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and Western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cyclohexane, MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and stemness were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib . When LUAD cells were treated with the ubiquitin-specific inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro . Conclusions: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.
Nonlinear characteristics of a multi-degree-of-freedom wind turbine’s gear transmission system involving friction
Authors: Zhang Qiang , Wang Xiaosun , Cheng Shaobo , Xie Fuqi , Wu Shijing
Published: August 2021

In this study, a 42-degree-of-freedom (42-DOF) translation-torsion coupling dynamics model of the wind turbine’s compound gear transmission system considering time-varying meshing friction, timevarying meshing stiffness, meshing damping, meshing error and backlash is proposed. Considering the different meshing between internal and external teeth of planetary gear, the time-varying meshing stiffness is calculated by using the cantilever beam theory. An improved mesh friction model takes account into the mixing of elastohydrodynamic lubrication (EHL) and boundary lubrication to calculate the time-varying mesh friction. The bifurcation diagram is used to analyze the bifurcation and chaos characteristics of the system under the excitation frequency as bifurcation parameter. Meanwhile, the dynamic characteristics of the gear system are identified from the time domain diagrams, phase diagrams, Poincare maps and amplitude-frequency spectrums of the gear system. The results show that the system has complex bifurcation and chaotic behaviors including periodic, quasi-periodic, chaotic motion. The bifurcation characteristics of the system become complicated and the chaotic region increases considering the effects of friction in the high frequency region.
Giant Primary Apocrine Carcinoma of Frontal Region: Clinical Presentation, Surgical Treatment and Review of the Literature
Authors: Popović Dragana Petrović , Novaković Marijan , Stojičić Milan , Brašanac Dimitrije , Elbaz Mirjana Petrović , Nikolić-Živanović Maja
Published: August 2021

Background: Primary cutaneous apocrine carcinoma (PCAC), a subtype of sweat gland carcinoma, is an extremely rare malignant neoplasm. Distinguishing apocrine carcinoma from breast carcinoma metastasis is difficult even for pathologist. Most arise in regions of high apocrine gland density like axilla, and rarely on the scalp and eyelid, but it’s possible to occur elsewhere on the skin. Primary cutaneous apocrine carcinoma of the scalp is a rare malignancy most often reported in the literature as case reports or small case series. Giant form of primary cutaneous apocrine carcinoma in frontal region is not described in literature, to the best of our knowledge. There no established protocols for primary cutaneous apocrine carcinoma treatment.Case presentation: We report a case giant primary cutaneous apocrine carcinoma localized in frontal region. Definitive diagnosis of primary cutaneous apocrine carcinoma is made by biopsy with microscopic and immunohistochemical analysis. Wide surgical excision and reconstruction with large local transposition flap and split thickness skin grafts for secondary defect were our therapy of choice.Conclusion: Primary cutaneous apocrine carcinoma is very rare malignancy and giant form in not described yet. Surgical treatment provided the patients with the tumor free status as well satisfactory aesthetical appearances and quality of living.
Soil moisture as determinant of the seasonal soil co2 emission: evidence from central siberia
Authors: Makhnykina Anastasia Vladimirovna , Tychkov Ivan Ivanovich , Prokushkin Anatoly Stanislavovich , Pyzhev Anton Igorevich , Vaganov Eugene Alexandrovich
Published: August 2021

Background

The soils of the boreal zone contain significant reserves of carbon, therefore, their response to current climate changes will significantly affect the sustainability of forest ecosystems and the future concentration of CO 2 in the atmosphere. When modeling soil emission, it is necessary to focus on the main soil environment factors. In this paper, a simple exponential model of the soil CO 2 emissions growth was modified by introducing an additional parameter - the threshold soil moisture in different types of ecosystems based on the direct measurements.

Results

The developed model adequately reflects the dynamic changes in soil emission for different types of ecosystems. This result was achieved by including moisture as a second environmental factor besides temperature, describing changes in soil CO 2 emissions during the summer period. The error of direct measurements for all measuring seasons was about 20% of the values of direct measurements of the CO 2 flux. Note that such a high error was observed once per season in early and mid-June, reaching 60-80% on some days. Our models demonstrate in the season with the highest amount of precipitation the smallest differences in modeled fluxes about 15-20%, which indirectly indicates that the emission flux is not inhibited by insufficient moisture in this season.

Conclusions

The final model application depends on the characteristics of the microclimatic conditions of a particular ecosystem, namely, a factor that has a limiting effect on the biological processes. When studying the functional role of boreal forest ecosystems the moisture conditions consideration is crucial to explain the atmospheric CO 2 emission processes.
Topical instillation of cell-penetrating peptide-conjugated melphalan blocks metastases of retinoblastoma
Authors: Jiang Kuan , Fan Xingyan , Hu Yang , Yao Shengyu , Liu Yu , Zhan Changyou , Lu Weiyue , Wei Gang
Published: August 2021

Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved comparable tumor inhibition effects to intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases. In contrast, the mice treated with intravitreally injected melphalan suffered more brain metastases related death, probably due to the “inside-out” diffusion of injected melphalan expelling the tumor outside the eye. The ocular absorption of 89WP-conjugated melphalan and other small molecules, both hydrophobic and hydrophilic, occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.
Droplet Nuclei Caustic Formations In Exhaled Vortex Rings
Authors: Papoutsakis Andreas , Gavaises Manolis
Published: August 2021

Vortex ring structures occur in light or hoarse cough configurations. These instances consist of short impulses of exhaled air resulting to a self-contained structure that can travel large distances. The present study is the first implementation of the second order Fully Lagrangian Approach (FLA) for three-dimensional realistic flow-fields obtained by means of Computational Fluid Dynamics (CFD) and provides a method to calculate the occurrence and the intensity of caustic formations. The carrier phase flow field is resolved by means of second order accurate Direct Numerical Simulation (DNS) based on a Finite Difference approach for the momentum equations, while a spectral approach is followed for the Poisson equation using Fast Fourier Transform (FFT). The effect of the undulations of the carrier phase velocity due to large scale vortical structures and turbulence is investigated. The evaluation of the higher order derivatives needed by the second order FLA is achieved by prefabricated least squares second order interpolations in the three dimensions. The method allows for the simulation of the clustering of droplets and droplet nuclei exhaled in ambient air in conditions akin to light cough. Given the ambiguous conditions of vortex-ring formation during cough instances, three different formation numbers n = UT /D are assumed, i.e. underdeveloped (n = 2), ideal (n = 3.7) and over-developed VRs (n = 6). The formation of clusters results in the spatial variance of the airborne viral load. This un-mixing of exhumed aerosols is related to the formation of localised high viral load distributions that can be linked to super-spreading events.
miR-188-3p-targeted Regulation of ATG7 Affects Cell Autophagy in Patients With Non-obstructive Azoospermia
Authors: Wang Yuan , Tian Chengcheng , Jiao Yunyun , Liu Minrui , Ma Xueshan , Jin Haixia , Su Yingchun , Zhang Xiangyang , Niu Wenbin , Yao Guidong , Sun Yingpu , Song Wenyan
Published: August 2021

Background: Studies have found that ATG7 knockout mice have defects in acrosome development, and the sperm formed by them are similar to human round-headed sperm. miR-188-3p expression is alleviated in the testis tissues of NOA samples. It is unclear whether ATG7 gene is related to non-obstructive azoospermia and whether miR-188-3p and ATG7 have direct target regulation relationship to affect spermatogenesis.Methods: The testicular tissues of 14 non-obstructive azoospermia (NOA) patients and 13 healthy patients were collected for basic scientific research from October 2017 to June 2018. High-throughput sequencing, qRT-PCR, Western blot, immunohistochemical staining, immunofluorescence, electron microscope, and luciferase experiment were performed to confirm the correlation between miR-188-3p and ATG7 in non-obstructive azoospermia.Results: ATG7 was highly expressed in NOA group. ATG7 protein was localized in the cytoplasm of spermatogenic cells at various levels, and the expression in NOA group was dramatically higher than that of normal individuals. After overexpression of miR-188-3p, the ATG7 3'UTR-WT luciferase activity was impeded; while the ATG7 3'UTR-MUT luciferase activity had no significant difference. LC3 and Beclin-1 gene and protein expression in the NOA samples were elevated in comparison with the normal samples; LC3 was mainly located in the cytoplasm of spermatogenic cells at all levels. LC3 and Beclin-1 genes expression after miR-188-3p overexpression were prominently in comparison with the normal samples; after miR-188-3p was inhibited, LC3 and Beclin-1 expressions were dramatically higher. The degree of LC3 punctate aggregation in the miR-188-3p mimic NC samples was greater, and that in the miR-188-3p inhibitor group was greater. The number of autophagosomes of the miR-188-3p mimic samples was less compared with the mimic NC group.Conclusion: We demonstrated here that the ATG7 gene was located in all levels of spermatogenic cells and was highly expressed in the NOA group. The expression of ATG7 gene was negatively correlated with miR-188-3p that may regulate the target gene ATG7 to participate in autophagy and affect the occurrence of NOA.
Assessment of Plasma Neurofilament Light as a Biomarker of Neuronal Injury in Young Adults with Perinatal HIV Infection
Authors: Ruiz-Saez Beatriz , Martín-Bejarano Manuela , Aragon Ana Martínez , Gisslen Magnus , Zetterberg Henrik , Blennow Kaj , de Ory Santiago Jiménez , Alvarez-Losada Susana , Muñoz-Fernández Mª Angeles , Melero Helena , Ramos Jose Tomás , Navarro Maria Luisa , González-Tomé Maria Isabel
Published: August 2021

Background: Higher plasma concentration of neurofilament light (pNfL) is associated with neurodegeneration. However, to our knowledge, up to now, there are no data in HIV patients with infection due to vertical transmission. This is the first study to report pNfL in a cohort of HIV perinatally infected (PHIV) young adults compared with non-HIV (HIV-) controls.Methods: Thirty-three PHIV patients and 25 age-matched HIV- were recruited to this cross-sectional study. Plasma NfL concentrations were compared between both groups. In a subgroup of 48 participants (25 PHIV patients and 23 HIV-), brain volumes through magnetic resonance imaging (MRI) and neuropsychological testing (NT), were also conducted and compared with pNfL values.Plasma NfL concentration was measured using Single Molecule Array (Simoa) immunoassay.NT included fluid intelligence and processing speed through the WAIS-IV Coding subtest, and the Stroop Test.ResultsFifty-eight participants were included, median age 20.7 years [IQR 17.8-23.4]. 100% of the patients were under antiretroviral treatment (cART) and 85% had viral load <50 copies/ml.Although no statistically significant differences were found between patients and controls regarding pNfL concentration, there was a trend towards higher levels in patients with viral load >50 copies/ml.With regard to brain volumes and NT, in the PHIV group, lower white matter volumes and lower score in the coding subtest were associated with higher pNfL values. ConclusionsMost PHIV adolescents under cART have similar levels of pNfL than HIV-. As reported in adults, those with HIV-RNA >50 copies/ml showed higher values and lower white matter volumes that may imply an ongoing CNS injury. Plasma NfL could be a feasible biomarker of CNS injury in PHIV patients with unsuppressed viral load.
High Mortality Among Patients With Severe COVID-19 and Do-not-intubate Orders Despite Use of Remdesivir and Dexamethasone
Authors: Holm Nanna , Israelsen Simone Bastrup , Lund Tamara Theresia , Kristiansen Klaus Tjelle , Krogh-Madsen Rikke , Benfield Thomas , Kronborg Gitte
Published: August 2021

Background Moderate to severe respiratory distress among patients with coronavirus disease 2019 (COVID-19) is associated with a high mortality. Dexamethasone and remdesivir were introduced in the second wave of COVID-19 in Denmark. Methods This is a retrospective study of patients with COVID-19 and a supplemental oxygen requirement of ≥15 Liters per minute (L/min). The patients were divided in two groups corresponding to the first- and second wave of COVID-19 and analysed regarding need of ventilator support and mortality dependent on orders to Do Intubate (DI) or Do Not Intubate (DNI), respectively. Results The study included 178 patients. The mortality was 24% for patients with DI orders (n=115) and 81% for patients with DNI orders (n=63) increasing to 98% (n=46) for patients with DNI orders and very high flow oxygen requirements (≥30 L/min). Use of constant continuous positive airway pressure (cCPAP) increased from 71% in the first wave to 91% in the second wave (p<0.001) whereas the use of mechanical ventilation (MV) decreased from 54% to 28% (p=0.005). Conclusion The mortality was high for patients with DNI orders and respiratory distress with very high levels in supplemental oxygen in both the first and second wave of COVID-19 despite treatment with dexamethasone and remdesivir and improved prognosis for patients with DI orders. Hence careful evaluation on transition to palliative care must be considered for these patients. Study Registration The study was retrospectively registered and approved by the Danish Patient Safety Authority (record no. 31-1521-309) and the Regional Data Protection Center (record no. WZ20017637-2020-37).
Simulating Dynamic Facial Expressions of Pain From Visuo-Haptic Interactions With a Robotic Patient
Authors: Tan Yongxuan , Rérolle Sibylle , Lalitharatne Thilina Dulantha , Zalk Nejra Van , Jack Rachael E. , Nanayakkara Thrishantha
Published: August 2021

Medical training simulators can provide a safe and controlled environment for medical students to practice their physical examination skills. Visual feedback of involuntary pain expressions in response to physical palpation on an affected area of a patient is an important source of information for physicians. However, most existing robotic medical training simulators that can capture physical examination behaviours in real-time cannot display facial expressions or comprise a limited range of patient identities in terms of ethnicity and gender. Together, these limitations restrict the utility of medical training simulators because they do not provide medical students with a representative diversity both of pain facial expressions and face identities, which could result in biased practice. Further, these limitations restrict the utility of such medical simulators to be used to detect and correct early signs of bias in medical training. Here, for the first time, we present a robotic system that can simulate facial expressions of pain in response to palpations, displayed on a range of patient face identities. We use the unique approach of modelling dynamic pain facial expressions using the data-driven psychophysical method of reverse correlation and incorporating the visuo-haptic interactions of users performing palpation to a robot medical simulator. Specifically, participants performed palpation actions on the abdomen phantom of simulated patients, which triggered the real-time display of 6 pain-related facial Action Units (AUs) on a robotic face (MorphFace), each controlled by two pseudo randomly generated transient parameters: rate of change β and activation delay τ. Participants then rated the appropriateness of the facial expression displayed in response to their palpations on a 4-point scale. Each participant (n = 16, 4 Asian female, 4 Asian male, 4 White female and 4 White male) performed 200 palpation trials on 4 patient identities (Black female, Black male, White female and White male) simulated using MorphFace. Results showed that a gradual decrease of β and increase of τ from upper face AUs (around the eyes) to those in the lower face (around the mouth) is rated to be appropriate by all participants. We found that transient parameter values that generated the appropriate pain facial expressions as rated by participants, palpation forces, and delays between palpation actions varied across gender and ethnicity of participant-simulated patient pairs. These findings suggest that gender and ethnicity biases affect the participants’ palpation strategies and their perception of the pain facial expressions displayed on MorphFace. We anticipate our approach could be utilised to generate physical examination models with diverse patient demographic groups to reduce erroneous judgments in medical students, and provide focused training to address these errors.
Trend Analysis of Hydro-meteorological Parameters in the Jhelum River Basin, North Western Himalayas
Authors: umar Sheikh , Lone M A , Goel N K , Zakwan Mohammad
Published: August 2021

The Jhelum River basin drains the entire Kashmir valley and is susceptible to floods, surrounded Himalayan Mountain range. The trend analysis of Hydro-meteorological data is crucial for planning and management of various activities (agriculture, design of hydraulic structures) in the basin. The purpose of the present study is to analyze the trends in the annual maximum and annual average discharge, annual maximum, and annual average rainfall for the Jhelum River basin. The trend analysis was performed by using Mann-Kendall (M-K), Sen’s slope, and innovative trend analysis (ITA) at various Hydro-meteorological stations. The outcomes of trend analysis using the ITA test showed non-monotonic trends at various stations for different time series data and bring forth more significant data to analyze changes in Hydro-meteorological data. Moreover, the overall trend shows a significant decreasing trend in annual average rainfall and discharge, while annual maximum rainfall and discharge revealed a significant increasing trend via ITA. The trend analysis depicts changes in Hydro-meteorological data which would be useful for future management of water resources. Moreover, changes in the discharges in the Jhelum River are due to climatic change and anthropogenic activities in the basin.