bluuebunny/crossref_metadata_2025 huggingface dataset:
The IL-6 rs12700386 polymorphism is associated with an increased risk of developing osteoarthritis in the knee in the Chinese Han population: a case-control study
Authors: Yang Hui , Zhou Xindie , Xu Dongmei , Chen Gang
Published: September 2020

Background: This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population.Methods: We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism.Results: We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥ 55 years old or with BMI ≥ 25 kg/m2. The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients.Conclusion: These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.
Tubeless Uniportal Thoracoscopic Wedge Resection with Modified Air Leak Test and Chest Tube Drainage
Authors: Liu Zhengcheng , Yang Rusong , Sun Yang
Published: September 2020

Background: To investigate whether tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage has better short-term outcomes than non-intubated approach with chest tube drainage.Methods: Data were collected retrospectively from January 2017 and December 2019. Tubeless group included 55 patients with pulmonary nodules underwent tubeless uniportal thoracoscopic wedge resection, 211 patients underwent non-intubated uniportal thoracoscopic wedge resection with chest tube drainage were included in drainage group. Peri-operative outcomes between two groups were compared. Results: After 1:1 matching, 110 patients remained for analysis, baseline demographic and clinical variables were comparable between the two groups. Mean incision size was 3 cm in both group. Mean operative time was 59.3 minutes in tubeless group and 52.8 minutes in drainage group. The detectable mean lowest SpO2 and mean peak EtCO2 during operation was acceptable in both groups. Conversion to intubated ventilation or thoracotomy was not required. No patient failed the air leak test and did not undergo a tubeless procedure. Mean postoperative hospital stay was 1.5 days in tubeless group and 2.5 days in drainage group. Residual pneumothorax or subcutaneous emphysema was not frequent and mild in tubeless group. Side effects were rare and mild, including cough and hemoptysis. No re-intervention or readmission occurred. The postoperative VAS score was significantly lower in tubeless group.Conclusions: Tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage is feasible and safe for selected patients with peripheral pulmonary nodules, it might reduce post-operation pain and lead to faster recovery.
Molecular Screening of PROKR2 Gene in Girls with Idiopathic Central Precocious Puberty.
Authors: Aiello Francesca , Cirillo Grazia , Cassio Alessandra , Mase Raffaella Di , Tornese Gianluca , Umano Giuseppina Rosaria , Giudice Emanuele Miraglia del , Grandone Anna
Published: September 2020

Background: Prokineticin receptor 2 (PROKR2) loss of function mutations have been described as cause of hypogonadotropic hypogonadism. In 2017 a first case of central precocious puberty (CPP) caused by PROKR2 heterozygous gain of function mutation was described in a 3.5-year-old girl. No other cases have been reported yet. This study performs a molecular screening in girls with early onset CPP (breast budding before 6 years of age) in order to identify possible alterations in PROKR2. Methods: We analyzed DNA of 31 girls with idiopathic CPP diagnosed via basal LH levels >0.3 IU/L or peak-LH>5IU/L after stimulation, negative for MKRN3 mutations. The Fisher exact test was used to compare allele frequency of polymorphism found to genome aggregation database (gnomAD).Results: No rare variants were identified. Five polymorphisms were found (rs6076809, rs8116897, rS3746684, rs3746682, rs3746683). All except one (i.e. rs3746682) had a minor allele frequency similar to that reported in literature. rs3746682 presented a minor allele frequency higher than described in the gnomAD (0.84 in our population vs 0.25 from gnomAD). Conclusions: As for other G-protein-coupled receptors (i.e. GPR54), mutations in PROKR2 do not seem to be a frequent cause of CPP in girls.
Adsorbed Leucaena protein on citrate modified Fe3O4 nanoparticles: synthesis, characterization, and its application as magnetic coagulant
Authors: Kristianto Hans , Reynaldi Edwin , Prasetyo Susiana , Sugih Asaf K
Published: September 2020

Natural coagulants from plants resources have gained a lot of attention as it is renewable, biodegradable, non-hazardous, lower cost, and less sludge generated compared to chemical coagulants. However there are still some drawbacks, namely long settling time and possible increase of dissolved organic carbon in the treated water. In this paper we tried to address these drawbacks by utilizing citrate modified Fe3O4 to adsorb protein from Leucaena leucocephala as the active coagulating agent. The effect of trisodium citrate concentration and protein adsorption pH to the adsorbed protein was investigated. It was found that the trisodium citrate concentration of 0.5 M and pH 4.0 gave the highest protein adsorption. The obtained magnetic coagulant was furthermore characterized using SEM, XRD, FTIR, and TEM, to observe the characteristics before and after protein adsorption. Furthermore the effect of pH (2.0 to 10.0) and coagulant dosage (60 to 600 mg L-1) to the removal of synthetic Congo red wastewater and sludge volume formation was investigated. It was found that pH 3.0 was the best pH for coagulation due to charge neutralization mechanism of leucaena protein. Furthermore the highest removal was obtained at dosage 420 mg L-1 with 80% removal. This result was comparable with crude extract of leucaena with half settling time (20 min) and lower increase of permanganate value, indicating lower increase of dissolved organics in the treated water.
A preliminary multicenter evaluation of endoscopic sublay repair for ventral hernia from China
Authors: Tang Rui , Jiang Huiyong , WU Weidong , Wang Tao , Meng Xiangzhen , Liu Guozhong , Cai Xiaoyan , Liu Jianwen , Cui Xijun , Si Xianke , Liu Nan , Wei Nina
Published: September 2020

Background: For ventral hernia, endoscopic sublay repair (ESR) may overcome the disadvantages of open sublay and laparoscopic intraperitoneal onlay mesh repair. This retrospective study presents the preliminary multicenter results of ESR from China. The feasibility, safety, and effectiveness of ESR were evaluated; its surgical points and indications were summarized.Methods: The study reviewed 156 ventral hernia patients planned to perform with ESR in ten hospitals between March 2016 and July 2019. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed.Results: ESR was performed successfully in 153 patients, 135 with totally extraperitoneal sublay (TES) and 18 with transabdominal sublay (TAS). In 19 patients, TES was performed with the total visceral sac separation (TVS) technique, in which the space separation is carried out along the peritoneum, avoiding damage to the aponeurotic structure. Endoscopic transversus abdominis release (eTAR) was required in 17.0% of patients, and only 18.3% of patients required permanent mesh fixation. The median operative time was 135 min. Most patients had mild pain and resume eating soon after operation. No severe intraoperative complications occurred. Bleeding in the extraperitoneal space occurred in two patients and was stopped by nonsurgical treatment. Seroma and chronic pain were observed in 5.23% and 3.07% of patients. One recurrence occurred after TAS repair for an umbilical hernia.Conclusion: ESR is feasible, safe, and effective for treating ventral hernias when surgeons get the relevant surgical skills, such as the technique of “partition breaking,” TVS, and eTAR. Small-to-medium ventral hernias are the major indications.
The relationship between consciousness and the ascending reticular activating system in patients with traumatic brain injury
Authors: Jang Sung Ho , KWON YOUNGHYEON
Published: September 2020

Background: We investigated the relationship between consciousness and the ascending reticular activating system(ARAS) by using diffusion tensor tractography(DTT) in patients with traumatic brain injury(TBI).Methods: Twenty-six patients with TBI and 13 healthy control subjects were recruited for this study. Glasgow Coma Scale(GCS) scores were used for evaluation of subject consciousness state at the chronic stage of TBI(at DTT scanning), According to the GCS score, the patient group was divided into two subgroups: A(14 patients;impaired consciousness:GCS score<15, and B(12 patients;intact consciousness;GCS score=15). Fractional anisotropy(FA) and tract volume(TV) values were assessed in the lower dorsal and upper ARAS.Results: The FA values of the lower dorsal ARAS and the upper ARAS in patient subgroup A were significantly lower than those in patient subgroup B and the control group(p<0.05). However, the FA and TV values for the lower dorsal ARAS and the upper ARAS were not significantly different between patient subgroup B and the control group(p>0.05). The FA value of the lower dorsal ARAS(r=0.473,p<0.05) and the TV of upper ARAS(r=0.484,p<0.05) had moderate positive correlations with the GCS score. The FA value of the upper ARAS had a strong positive correlation with the GCS score of the patient group(r=0.780,p<0.05).Conclusions: We detected a close relationship between consciousness at the chronic stage of TBI and injuries of the lower dorsal and upper ARAS(especially, the upper ARAS) in patients who showed impaired consciousness at the onset of TBI. We believe that our results can be useful during the development of therapeutic strategies for patients with impaired consciousness following TBI.
A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.
Authors: Flossmann Gabriele , Wurmser Christine , Pausch Hubert , Tenghe Amabel , Dodenhoff Jörg , Dahinten Günther , Götz Kay-Uwe , Russ Ingolf , Fries Ruedi
Published: September 2020

Background: Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts.Results: A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10-43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (BMP15; Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10-83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth.Conclusion: Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.
The contributions of entorhinal cortex and hippocampus to error driven learning
Authors: Ku Shih-pi , Hargreaves Eric , Wirth Sylvia , Suzuki Wendy
Published: September 2020

Computational models proposed that the medial temporal lobe (MTL) contributes importantly to error-driven learning, though little direct in-vivo evidence for this hypothesis exists. To test this, we recorded in the entorhinal cortex (EC) and hippocampus (HPC) as monkeys performed a task using an error-driven learning strategy, defined as better performance after error relative to correct trials. Error-detection signals were more prominent in the EC relative to the HPC. Early in learning hippocampal but not EC neurons signaled error-driven learning by increasing their population stimulus-selectivity following error relative to correct trials. This same pattern was not seen in another learning task where error-driven learning was not used. After learning, different populations of cells in both the EC and HPC signaled long-term memory with enhanced stimulus-selective responses. These results suggest prominent but differential contributions of EC and HPC to learning from errors and a particularly important role of the EC in error-detection.
Repetitive emissions of rising-tone chorus waves in the inner magnetosphere
Authors: Lu Quanming , Wang Xueyi , Chen Lunjin , Gao Xinliang , Lin Yu , Wang S.
Published: September 2020

Chorus waves are well known for their significant roles in the radiation belts of the Earth and other magnetized planets, including acceleration of electrons to relativistic energies, and precipitation of energetic electrons into the ionosphere to produce diffuse and pulsating aurora. They typically occur in the form of discrete and repetitive quasi-monochromatic emissions with a frequency chirping, which was discovered more than 50 years ago. However, until now there is still no satisfactory explanations for repetitive emissions of chorus waves. In this report, chorus emissions excited by energetic electrons with a temperature anisotropy are studied by both a one-dimensional \(\delta f\) simulation and theoretical model in a dipole magnetic field. The two models have unanimously demonstrated that a continuous injection of energetic electrons caused by an azimuthal drift is essential for the repetitive emissions of chorus waves. Consistent with satellite observations, both discrete and continuous spectra can be reproduced. An intense injection of energetic electrons will lead to a decrease of the time separation between the chorus elements, and the chorus emissions evolve from a discrete to a continuous spectrum when the injection is sufficiently strong.
Age-related Differences in Monocyte DNA Methylation and Immune Function in Healthy Kenyan Adults and Children
Authors: Dobbs Katherine Rose , Embury Paula , Koech Emmily , Ogolla Sidney , Munga Stephen , Kazura James Walter , Dent Arlene Elizabeth
Published: September 2020

Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profi 24 les in monocytes from young adults and children from western Kenya.Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles.Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.
Eucalyptus Productivity Increase in China Comes From Newly Afforested Plantations
Authors: Chen Wei , Zheng Qihui , Dang Yongfeng , Sakai Tetsuro
Published: September 2020

Eucalyptus trees are a major fast-growing species in southern China. The ecological problems associated with constantly developing new Eucalyptus plantations have been the focus of extensive debate. In this study, we used spatial analysis and geostatistical methods along with four continuous national forest resource inventories and meteorological data to analyze dynamic changes in the distribution of Eucalyptus plantations in China. The productivity levels of Eucalyptus plantations were compared at different time periods by measuring annual mean productivity in permanent sample plots to provide baseline data related to the scientific management of Eucalyptus plantations. Results showed that the area of Eucalyptus plantations increased constantly in China from 1998 to 2013, expanding from 60.7 × 104 hm2 in 1998 to more than 445.5 × 104 hm2 in 2013. The productivity of Eucalyptus plantations was positively correlated with temperature and rainfall, but negatively correlated with elevation. However, these changes did not necessarily indicate an improvement in the management quality of Eucalyptus plantations, because they were mainly caused by an increased in the proportion of newly reclaimed areas for Eucalyptus afforestation and the constantly decreasing area of original Eucalyptus plantations, to which sufficient attention must be given.
Evaluation of China's Hubei Control Strategy for COVID-19 Epidemic: An Observational Study
Authors: Liu Yu , Zheng Fangfang , Du Zhicheng , Li Jinghua , Gu Jing , Jiang Mei , Yoneoka Daisuke , Gilmour Stuart , Hao Yuantao
Published: September 2020

Background: To fight against COVID-19, many policymakers are wavering on stricter public health interventions. However, relying on these measures but different strategies, both in and out of China’s Hubei province basically contained the epidemic in late February 2020. This study aimed to assess the response process and estimate time-varying effect of Hubei control strategy to provide insights for intervention design and implementation.Methods: We retrospectively compared the spread and control of COVID-19 between China’s Hubei (excluding Wuhan) and non-Hubei areas using data that includes case reports, human mobility, and public health interventions from 1 January to 29 February, 2020. The static and dynamic risk assessment models were developed to statistically investigate the effect trends of Hubei control strategy on case growth after adjusting importation risk and response timing with non-Hubei strategy as a contrast.Results: The analysis detected much higher but differential importation risk in Hubei. The response timing largely coincided with the importation risk in non-Hubei areas, but Hubei areas showed an opposite pattern. A careful and comprehensive comparison showed that Hubei control strategy implemented interventions characterized by unprecedentedly strict and ‘monitored’ self-quarantine at home, while non-Hubei strategy included physical distancing measures to reduce contact among individuals within or between populations. In contrast with non-Hubei control strategy, Hubei strategy showed a much higher, non-linear and gradually diminishing protective effect with at least 3 times fewer cases.Conclusions: A risk-based control strategy is crucial to design an effective response for COVID-19 control. Our study demonstrates that the stricter Hubei strategy can achieve much better control effectiveness. These findings highlight the health benefits of precise and differentiated strategies informed by constant monitoring of outbreak risk and policy impacts.
Vitamin D Deficiency is Associated with Increased COVID-19 Severity: Prospective Screening of At-Risk Groups is Medically Indicated
Authors: Pepkowitz Samuel H , Hobel Calvin J , MS James M Mirocha , Kimia.Sobhani  , BS Carissa A Huynh , Jawanda Harneet , Hasan Wohaib
Published: September 2020

Non-classical actions of Vitamin D are involved in regulation of the immune system including a role in mitigation of excessive inflammation. We hypothesized that vitamin D deficiency existing prior to SARS-CoV-2 infection could contribute to patients developing severe pulmonary compromise as a result of dysfunctional hyperinflammation. Serum vitamin D concentrations of patients experiencing such severe COVID-19 manifestations that they required ICU care at any point of their hospitalization were compared to serum vitamin D concentrations of patients achieving discharge without the need for any ICU care. Having serum vitamin D < 20 ng/mL was significantly associated with increased COVID-19 severity, p=0.001. It is conjectured that population groups know to have low serum vitamin D should be prospectively screened for deficiency and if found emergently treated. Such action could both decrease the maximum severity suffered by infected individuals and lessen the strain on medical resources by decreasing the percentage of COVID-19 hospital admissions requiring ICU care.
Grey-box linear modeling to analyze functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal HD-tDCS in healthy humans
Authors: Arora Yashika , Hayashibe Mitsuhiro , Muthalib Makii , Chowdhury Shubhajit Roy , Perrey Stephane , Dutta Anirban
Published: September 2020

The mechanism of action for the cerebral vasculature hemodynamic response to the electric field effects during transcranial direct current stimulation (tDCS) has been less explored. We postulate that such a mechanistic understanding of the cerebrovascular reactivity (CVR) to tDCS can facilitate adequate tDCS dosing to facilitate cognitive rehabilitation in mild cognitive impairment and dementia as well as motor rehabilitation in stroke and traumatic brain injuries. This study presents a system identification approach to evaluate CVR under high-definition (HD) tDCS using a physiologically constrained model based on a multi-compartmental neurovascular system of vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. The physiologically detailed model generated vessel oscillations in the frequency range of 0.05 – 0.2 Hz driven by nonlinear calcium dynamics. Then, model linearization was performed to develop a grey-box linear model for evaluating the acute effects of HD-tDCS based on the CVR data from healthy humans. CVR was measured using functional near-infrared spectroscopy (fNIRS) with optodes in the vicinity of 4x1 HD-tDCS electrodes. The grey-box linear model response of vessel response through the synaptic potassium pathway was found comparable to known hemodynamic responses. Then, the grey-box linear model was fitted to the CVR to anodal HD-tDCS found from the normalized changes in the fNIRS-total haemoglobin (tHb) concentration (blood volume) in eleven healthy participants. We found that the model pathway from perivascular potassium to the vessel circumference presented the best fNIRS-tHb fit with the least mean square error. The fitted grey-box linear model response presented an initial dip in the vessel response that provided a mechanistic understanding of the fNIRS-tHb changes at the onset of HD-tDCS, which needs to be validated in the future with functional magnetic resonance imaging in conjunction with HD-tDCS.
The Effect of Using Instagram Influencers in Building Conseva’s Brand Awareness
Authors: Tjandrawibawa Paulina
Published: September 2020

Rapid growth of social media development leads to abundant brands’ promotion for their products or services. One of the many ways is promotion through influencers on Instagram. Recently, it is known that companies using Influencer marketing tend to keep going up since such particular way is considered to be quite effective to increase brand awareness. However, the average data obtained from various journals and articles is data from medium to large scale companies both locally and internationally. Therefore, this study was conducted to examine whether the use of Instagram influencers to increase brand awareness is also effective for micro-scale local brands by taking examples from one of Surabaya lifestyle brands called Conseva. This research was conducted with a quantitative method focusing on collecting numerical data to see the results of the growth of followers and visits obtained by Conseva before and after using Instagram influencers. If the number of Instagram followers and visits to Conseva increases, it means that brand awareness has also increased and vice versa.
Cenários especulativos pós-pandêmicos
Authors: Preger Guilherme de Figueiredo
Published: September 2020

Apresenta em termos genéricos três cenários econômicos e sociais para o período de pós-pandemia do coronavírus: o velho normal, o novo normal e o anômalo. O método para a construção dos cenários é o da fabulação especulativa. Observa-se que os dois primeiros cenários são variações de um mesmo paradigma e apenas o último pode ser considerado realmente uma “equivocação” do paradigma atual. O cenário anômalo, embora mais “improvável”, se configura o único realista a longo prazo. Nesse cenário estuda-se como o conceito de redes solidárias pode ser potencializado por uma reapropriação das plataformas digitais. Os conceitos de tecnologia social e economia solidária fornecem a melhor descrição de integração para um cenário anômalo. Termina com um esboço de uma proposta eficaz para a renda básica universal.
The Rationale for Use of Amiodarone and its Derivatives for the Treatment of Chagas’ Disease and Leishmaniasis
Authors: Benaim Gustavo , Paniz-Mondolfi Alberto E. , Sordillo Emilia Mia
Published: September 2020

The repurposing or repositioning of previously-approved drugs has become an accepted strategy for
the expansion of the pharmacopeia for neglected diseases. Accordingly, amiodarone, an inexpensive and extensively-
used class III antiarrhythmic has been proposed as a treatment for Chagas’ disease and leishmaniasis.
Amiodarone has a potent trypanocidal and leishmanicidal action, mainly acting through the disruption of parasite
intracellular Ca2+ homeostasis, which is a recognized target of different drugs that have activity against trypanosomatids.
Amiodarone collapses the mitochondrial electrochemical potential (Δφm) and induces the rapid
alkalinization of parasite acidocalcisomes, driving a large increase in the intracellular Ca2+ concentration. Amiodarone
also inhibits oxidosqualene cyclase activity, a key enzyme in the ergosterol synthesis pathway that is essential
for trypanosomatid survival. In combination, these three effects lead to parasite death. Dronedarone, a
drug synthesized to minimize some of the adverse effects of amiodarone, displays trypanocidal and leishmanicidal
activity through the same mechanisms, but curiously, being more potent on Leishmaniasis than its predecessor.
In vitro studies suggest that other recently-synthesized benzofuran derivatives can act through the same
mechanisms, and produce similar effects on different trypanosomatid species. Recently, the combination of
amiodarone and itraconazole has been used successfully to treat 121 dogs naturally-infected by T. cruzi, strongly
supporting the potential therapeutic use of this combination against human trypanosomatid infections.
Peptide and Small Molecule Inhibitors Targeting Myeloid Cell Leukemia 1 (Mcl-1) as Novel Antitumor Agents
Authors: Lu Xing , Liang Hong , Orvig Chris , Chen Zhen-Feng
Published: September 2020

Myeloid cell leukemia 1 (Mcl-1) is a member of the Bcl-2 family of proteins
with anti-apoptotic activity. It plays a key role in the regulation of the intrinsic pathway of
apoptosis. Moreover, Mcl-1 is correlated with the progression and drug-resistance of
various cancers. The development of inhibitors of Mcl-1 may provide effective cancer
therapies. While the inhibitors of other Bcl-2 anti-apoptotic proteins have been well
explored, the discovery of Mcl-1inhibitors with high selectivity has been challenging. In
this review, we summarize the recent literature on small molecule and peptide inhibitors
of Mcl-1, which are divided into different types including peptide inhibitors, gossypol
derivatives, marinopyrrole derivatives, S1 derivatives, indole derivatives, quinoline
derivatives, S63845, AZD5991, AMG176, etc. Their biological activities are also
summarized. Mcl-1 is a valid drug target and inhibition of Mcl-1 with a small molecule
inhibitor is a promising strategy for cancer therapy.
Preparation and Evaluation of Possible Antioxidant Activities of Rose Traditional Tablet“(Qurs-e-Vard)” A Selected Traditional Persian Medicine (TPM) Formulation via Various Procedures
Authors: Talebi Marjan , Zarshenas Mohammad M. , Yazdani Elahe , Moein Mahmoodreza
Published: September 2020

Background:

Free radicals can lead to liver dysfunction. Quality control of traditional
formulations ensures their safe, pure, and pharmaceutical efficacy. “Qurs-e-Vard”, containing petals
of Rosa damascena Mill., fruits of Rhus coriaria L. and roots of Glycyrrhiza glabra L. has
been suggested as a hepatoprotective preparation in Traditional Persian Medicine (TPM).

Objective:

This study was directed at the evaluation of the phytochemical characterization, standardization,
and in vitro antioxidant activity determination of a solid formulation and its components.

Method:

Some qualitative and quantitative controls were performed like ash value, heavy metals
investigation, and microbial contamination. The phytochemical assays were used for obtaining total
phenolic and flavonoid contents with spectrophotometric methods. 2, 2-Diphenyl-1-c (DPPH)
and Nitric Oxide (NO) assays were run for determining Radical scavenging activities of the formulation
and its components. Ferric reducing antioxidant power assay (FRAP) was determined as
well.

Results:

Total phenolic contents of hydroalcoholic and aqueous extracts of the polyherbal formulation
measured respectively, (376±0.93) and (297.6±0.96) mg of gallic acid/g of dry matter. Total
flavonoid contents of the formulation were also measured (36.27±0.98) for hydroalcoholic extract
and (17.79±0.86) mg of quercetin/g of dry matter for aqueous extract. The IC50 of hydroalcoholic
and aqueous extract was obtained (88.14±1.15) and (140.78±2.98) μg/ml, respectively. NO scavenging
percentages (200μg/ml) of hydroalcoholic and aqueous extracts were measured
(59.11±2.15) and (65.08±2.35). FRAP values of hydroalcoholic and aqueous extracts were
achieved (255.24±3.45) and (134.57±3.45) μg/ml as well.

Conclusion:

Our findings indicated that this polyherbal formulation and its components have justifiable
antioxidant effects.
Comparative Proteome Profiles of Methicillin-Resistant Staphylococcus aureus in Response to Vanillic Acid and 2-Hydroxycinnamic Acid
Authors: Keman Deniz , Soyer Ferda
Published: September 2020

Background:

The ability of Staphylococcus aureus to cause severe infections and the
difficulty of the treatments due to the multiple antibiotic resistance make this bacterium a lifethreatening
human pathogen. This situation necessitates the exploration of novel antimicrobial compounds
with known targets on bacteria. Phenolic acids naturally produced in plants as secondary
metabolites are good candidates for being alternative antimicrobials for antibiotic-resistant bacteria.

Objective:

Investigation of protein profile of Methicillin-Resistant S. Aureus (MRSA) in the presence
of subinhibitory concentrations of phenolic acids.

Methods:

MRSA was subjected to subinhibitory concentrations of Vanillic Acid (VA) and 2-Hydroxycinnamic
Acid (2-HCA), separately, and the proteomic analyses were carried out by using
liquid chromatography coupled to mass spectrometry.

Results:

Both phenolic acids elicited identification of differently expressed proteins that have roles
in DNA replication, repair, RNA processing and transcription, protein synthesis, maintenance of
cell homeostasis, several metabolic reactions in energy, carbohydrate and lipid metabolisms and also
proteins related with the virulence and the pathogenicity of MRSA when compared with the control
group. The numbers of the proteins identified were 444, 375, and 426 for control, VA-treated
MRSA, and 2-HCA-treated MRSA, respectively, from which 256 were shared. While VA treatment
resulted in 149 unidentified MRSA proteins produced in control, 2-HCA treatment resulted
in 126 unidentified proteins. Data are available via ProteomeXchange with identifier PXD016922.

Conclusion:

The results obtained from this study might indicate the potential targets on bacteria
and the effective use of phenolic acids in the battle with antibiotic-resistant pathogens.
Carbon Transformations of Biochar Based Co-Composting - A Review
Authors: Pandiyan Balaganesh , Mangottiri Vasudevan , Narayanan Natarajan
Published: September 2020

Biochar-Amended Composting (BAC) plays an integral role in sustainable agricultural
practices due to its multiple benefits in crop production, soil nutrient retention, carbon sequestration
and environmental protection. Although accepted as a traditional method, there is a lack of
understanding in defining its suitability and efficiency in terms of various base-materials and conditions.
Being two carbon-based entities with plentiful nutrients and surface activity, biochar and
compost find application in agricultural fields together or separately for improving the soil properties
and crop productivity. Recent studies focus on defining the optimum conditions for their preparation,
mixing, application and monitoring under various feed, soil, crop and climatic conditions.
However, due to the complexity and specificity of the system, many influencing aspects of their
interaction are yet unknown in detail. In this review, we analyze the recent advancements in the
selection and preparation of new materials for BAC, and explain the mechanisms of Organic Matter
(OM) degradation/sequestration occurring in soil based on possible chemical/morphological
transformations of organic carbon. Most of the performance results are in agreement with the previous
records, but a few contradictions have been observed under diverse experimental conditions.
In general, BAC enhanced the mineralization of carbon and sequestration of heavy metals, and
stabilized labile fraction of OM due to the development of carbonyl, phenolic and aromatic functional
groups on its surface. In addition, aging of biochar resulted in stable N-C=O and amino
groups for the adsorption of nitrogen compounds thus decreasing the potential greenhouse gas
emissions. The study further identifies potential future research gaps in this area.
First Detection of Tobacco Mosaic Virus in Tobacco Fields in Northern Lebanon
Authors: Obeid Rami , Wehbe Elias , Rima Mohamad , Kabara Mohammad , Al Bersaoui Romeo , Sabatier Jean Marc , Fajloun Ziad , Gereige Dalya
Published: September 2020

Background:

Tobacco mosaic virus (TMV) is the most known virus in the plant mosaic
virus family and is able to infect a wide range of crops, in particular, tobacco, causing a production
loss.

Objectives:

Herein, and for the first time in Lebanon, we investigated the presence of TMV infection
in crops by analyzing 88 samples of tobacco, tomato, cucumber and pepper collected from different
regions in North Lebanon.

Methods:

Double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), revealed
a potential TMV infection of four tobacco samples out of 88 crop samples collected. However,
no tomato, cucumber and pepper samples were infected. The TMV+ tobacco samples were then
extensively analyzed by RT-PCR to detect viral RNA using different primers covering all the viral
genome.

Results and Discussion:

PCR results confirmed those of DAS-ELISA showing TMV infection of
four tobacco samples collected from three crop fields of North Lebanon. In only one of four TMV+
samples, we were able to amplify almost all the regions of viral genome, suggesting possible mutations
in the virus genome or an infection with a new, not yet identified, TMV strain.

Conclusion:

Our study is the first in Lebanon revealing TMV infection in crop fields, and highlighting the danger that may
affect the future of agriculture.
SeDeM Expert System, an Innovative Tool for Developing Directly Compressible Tablets: A Review
Authors: Singh Inderbir , Thakur Ajay Kumar , Bala Rajni , Madan Reecha
Published: September 2020

Background:

SeDeM (Sediment Delivery Model) expert system is a preformulation tool
employed for evaluating direct compression suitability of various excipients. SeDeM is a 12 parameters
derived diagram and SeDeM-ODT (Sediment Delivery Model-Orodispersible tablets) is a 15
parameters derived diagram that can be used as a research tool for reducing the product development
time. The best possible excipients for a specified pharmaceutical active ingredient could be
screened for direct compression suitability.

Objective:

SeDeM expert system has been successfully used and implemented for characterizing
galenic properties of pharmaceutical excipients, direct compression suitability of excipients, development
of ODT formulations, development of sustained-release formulations, and development of
tablets of taste-masked drugs.

Conclusion:

In the present review paper, the development and applications of SeDeM and SeDeMODT
systems have been discussed in detail.
Distributed Time-Dependent Key Management Scheme for Internet of
Things
Authors: Tamizhselvan C. , Vijayalakshmi V.
Published: September 2020

The Internet of Things (IoT) faces a variety of challenges and issues in administering security due to its heterogeneous nature and open communication medium. The fundamental security
requirement of authentication is expected to secure the communication between the devices from
anonymous access. In this article, we present a distributed time-dependent key management (DTKM)
technique for securing the communication sessions of the IoT devices. This key management technique considers the communication time and interval of the devices independently to generate session keys for authentication. Key management is preceded by the consideration of request authentication and resource utilization. Based on the communication time session, the validity of the keys is
determined and is updated with the current random number consideration for authentication. This
helps to prevent unnecessary exploitation of storage and also reduces computation time.
Unstable Osteosynthesis of a Humeral Diaphyseal Fracture as a Cause of a Pseudoarthrosis and an Extensive Bone Defect (A Case Report)
Authors: Bragina S. V. , Iskusov P. V. , Lapidus D. A. , Ivashov A. G. , Kuroptev V. G.
Published: September 2020

Relevance. The causes of the formation of a humeral diaphyseal pseudarthrosis can be various risk factors and their combination, including iatrogenic, associated with osteosynthesis technique non-compliance. This leads to instability of the metal constructions with the destructive consequences for the bone tissue and the injured limb function in general. Case presentation. A 60-year-old woman received a right humeral diaphyseal fracture with displacement (АО/АSIF 12-A3) and underwent locking intramedullary osteosynthesis. Subsequently, the fixation failure developed. In 3 years after the primary surgery, a combination of two complications was diagnosed: a nonunion and a defect of the humerus with the formation of a traumatic bone cyst in the distal part. The patient was reoperated: resection of the pseudarthrosis, removal of the right humerus cyst, and revision plate osteosynthesis with bone autografting. A positive result of treatment was obtained: fracture consolidation, reparation of the distal humerus bone structure and restoration of the right upper limb function. Conclusion. The presented clinical case demonstrates the importance of careful preoperative planning of osteosynthesis: the selection of an appropriate implant size, and adequate intraoperative blocking of the intramedullary nail to create a stable “bone-fixator” system. The careful outpatient follow-up of the patient, early detection of possible complications and timely surgical removal of the unstable implant with revision osteosynthesis are required.
The Effectiveness of Various Surgical Techniques in the Treatment of Local Knee Cartilage Lesions (Review)
Authors: Kulyaba T. A. , Bantser S. A. , Trachuk P. A. , Vorontsova T. N. , Kornilov N. N.
Published: September 2020

Introduction. To restore the knee local cartilage lesions, a large number of alternative surgical techniques are used in clinical practice: isolated debridement of the lesion area, chondrogenesis stimulation, mosaic osteochondral grafting, cell technologies, collagen membranes (matrices), and a combination of the above methods. The purpose of this article was to compare the effectiveness of various surgical methods of treating patients with local cartilage lesions of the femur based on analysis of relevant publications. Materials and Methods. The review included 85 publications of domestic and foreign authors within 2005 to 2020. The search was carried out in electronic scientific databases PubMed and eLIBRARy. Results. The medium and long term outcomes of debridement and/or various options of chondrogenesis stimulating, despite their wide popularity, in terms of clinical, radiological, and histological indicators, are inferior to all other surgical techniques. Mosaic osteochondral auto- and/or allografting, as well as transplantation of autologous chondrocytes culture with a collagen membrane, are characterized by the best 15 to 20-year outcomes, allowing most patients to maintain the same level of activity as before the lesion occurred. The combination of matrices with other cellular products or microfracturing shows similar medium-term results, but it long-term efficacy remains unknown. Conclusion. The use of debridement and/or chondrogenesis stimulation should be limited to minimal defects. From both a clinical and an economic point of view, mosaic osteochondral grafting is the optimal method for the treatment of knee local cartilage lesions with an area up to 4 to 6 cm2 . The combination of membranes with various cellular products or microfracturing is indicated in case of extensive local cartilage lesions or if mosaic osteochondral grafting is not appropriate.
Reverse Shoulder Arthroplasty with Latissimus Dorsi Transfer for Humerus Fractures Sequelae
Authors: Chirkov N. N. , Nikolaev N. S. , Kaminskii A. V. , Spiridonova O. V.
Published: September 2020

Relevance. Fractures of the proximal humerus occupy the 3rd place in the structure of fractures in the elderly. Failure to treat these injuries leads to irreversible changes in the shoulder. The main treatment for the latter is arthroplasty. The surgical treatment of this category of patients is still a difficult task. The purpose of this study was to compare the effectiveness of standard reverse arthroplasty with reverse arthroplasty in combination with the reconstruction of the external rotators of the shoulder or transposition of the latissimus dorsi. Materials and Methods. The retrospective evaluation of treatment results of 96 patients with consequences of shoulder injuries was conducted. Of these, 51 patients underwent standard reverse arthroplasty (group I), and 45 patients (group II) underwent arthroplasty with reconstruction of the external rotators of the shoulder or transposition of the latissimus dorsi. The female patients accounted for 68.8%. The duration of the injury varied from 8 months to 2.5 years, the follow-up — from 1 to 7 years (Me = 3.5). The results were assessed with VAS, ASES, UCLA scales. Results. The positive outcomes were observed in most patients. Complications: dislocations of the endoprosthesis occurred in 16.7%, infectious complications — in 5.2%, shoulder component instability — in 2.1%, fracture of the humeral diaphysis — in 3.1%, neurovascular bundle injury — in 2.1% of cases. In the patients of group I, dislocations occurred significantly more often than in the patients of group II. To reduce the risk of complications, a rational tactic has been developed for treating patients with consequences of shoulder injuries. If electroneuromyography values from the deltoid muscle were less than 40% of the contralateral side, or if mineral bone density T-score was less than 2.5 SD, arthroplasty was not performed. During arthroplasty, it is necessary to perform the direct suturing of the of the infraspinatus and teres minor tendons to the humerus. If it is impossible, the latissimus dorsi transfer is indicated. Conclusion. Reverse arthroplasty in the treatment of the humerus fractures sequelae is an effective technique. To reduce the risk of complications, it is necessary to provide the additional stability of the endoprosthesis by reconstruction of the external rotators or latissimus dorsi transfer. It is advisable to refrain from arthroplasty in cases of severe deltoid hypotrophy and severe osteoporosis.
Comment to the Article “Assessment of the Patellofemoral Joint Condition and the Possibility of its Functional Improvement after the Closed Fractures of the Patella”
Authors: Chugaev D. V.
Published: September 2020

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