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Medical Research Archives

Knowledge Enterprise Journals

All preprints, ranked by how well they match Medical Research Archives's content profile, based on 11 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Recontextualizing Eukaryogenesis via Computational Analysis of RNA Processing in 16,449 Archaeal Genomes

Kannan, S.

2024-08-24 evolutionary biology 10.1101/2024.08.23.609445 medRxiv
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The analysis of proteins related to RNA processing reveals intriguing aspects of the evolutionary transition from archaea to eukaryotes. Eukaryagenesis is the process in which the first eukaryote came into existence, with multiple hypotheses on the order of events. These hypothesis often focus on the mitochondria and cell skeletal structure, without much discussion on eukaryotic signature proteins(ESP). ESP is integral in increasing the longevity of RNA and for the increase in the variety of proteins able to be produced which ultimately increases fitness of eukaryotes. 16,449 genomes and 10 proteins were acquired and BLAST was run for each superclass for each protein. BLAST scores were compared between superclasses and analyzed. Results for proteins such as Prp9, Rex3, Histone H2A, H2B, and Histone 3 indicate that there is no substantial difference between BLAST results implying a transitional state consistent with E3 model. The results for Smd3 and Ceg1 highlight that a group of Asgardarchaeota and Diaforarchaearchaea were different to other types of archaea. These groups likely underwent similar environmental pressures giving organisms with these genes higher fitness. These early genes evolved into their eukaryotic versions, while other genes like Histone 4, Abd1, and Lsm2 may have had ancestral prototypes present across archaea. Gene prototypes likely served different purposes, but the presence of such prototypes imply that evolution of the nucleus was likely independent from the presence of the mitochondria.

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Understanding dynamics of respiration amongst sexes: who breathe more efficiently?

Desai, D.; Dave, P.; Verma, A.; Mahajan, N.

2023-03-29 respiratory medicine 10.1101/2023.03.28.23287803 medRxiv
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IntroductionRespiration is a complex phenomenon requiring diaphragm, inter-costal muscles and other supporting structures. Contemplating the anatomical & physiological differences between males and females, it is essential to know how the respiratory system works in both of them. No such other study has been conducted in an Indian setup, which guided us to take up this topic. MethodologyTotal of N= 216 (Males 63, Females- 153) student were enrolled. All the participants were between the age of 17-19. Their data of Tidal volume, inspiratory reserve volume, expiratory reserve volume, maximum expiratory pressure and their vital capacity both sitting and standing were gathered and analysee. ResultsTidal volume was in males 553{+/-}56 ml and 666{+/-}60 in females(p-value = 0.031). IRV was in males 2103{+/-}139 ml and 1717{+/-}99 in females(p-value>0.0001). ERV was in males 1638{+/-}113 ml and 1323{+/-}65 in females (p-value>0.0001). VC Standing was in males 3947{+/-}155 ml and 3278{+/-}105 in females(p-value>0.0001). VC sitting was in males 3492{+/-}151 ml and 2743{+/-}107 in females(pvalue>0.0001). MEP was in males 90{+/-}8 mmHg and 64{+/-}6 mmHg in females(p-value>0.0001). Range of Pearson correlation coefficient for all=(+0.2)-(-0.2). ConclusionTidal volume was found to be higher in females than in males. Vital capacity was higher in males than in females by 700 ml in both position and vital capacity was higher by 500ml in standing than in sitting in both males and females. Body mass index weakly correlatable positively or negatively with all parameters. MEP was found to be higher in males but was weakly correlated negatively with BMI.

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Climatic-niche evolution of SARS-CoV-2

Bajaj, P.; Arya, P. C.

2020-10-28 evolutionary biology 10.1101/2020.06.18.147074 medRxiv
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COVID-19 pandemic has been extensively studied by many researchers. However, it is still unclear why it was restricted to higher latitudes during the initial days and later cascaded in the tropics. Here, we analyzed 176 SARS-CoV-2 genomes across different latitudes and climate (Koppens climate) that provided insights about within species virus evolution and its relation to abiotic factors. Two genetically variant groups, named as G1 and G2 were identified, well defined by four mutations. The G1 group (ancestor), is mainly restricted to warm and moist, temperate climate (Koppens C climate) while its descendent G2 group surpasses the climatic restrictions of G1, initially cascading into neighboring cold climate (D) of higher latitudes and later into hot climate of the tropics (A). It appears that the gradation of temperate climate (Cfa-Cfb) to cold climate (Dfa-Dfb) drives the evolution of G1 into G2 variant group which later adapted to tropical climate (A) as well. It seems this virus followed inverse latitudinal gradient in the beginning due to its preference towards temperate (C) and cold climate (D). Our work elucidates virus evolutionary studies combined with climatic studies can provide crucial information about the pathogenesis and natural spreading pathways in such outbreaks which is hard to achieve through individual studies. Mutational insights gained may help design an efficacious vaccine. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/147074v3_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@f39a3org.highwire.dtl.DTLVardef@1910598org.highwire.dtl.DTLVardef@6516corg.highwire.dtl.DTLVardef@cbb48c_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefThe authors elucidate adaptation of SARS-CoV-2 to different climates by studying phylogenetics and the distribution of strains on Koppens climate map. HighlightsO_LIPhylogenetic network divides SARS-CoV-2 strains into two variant groups, G1 and G2. C_LIO_LIG1 strains is restricted to Koppens "temperate" climate (mainly Cfa-Cfb). C_LIO_LIG2 strains has evolved from G1 to sustain in other climates mainly "humid-continental" (Dfa-Dfb) and "tropical-savannah" (Aw) climate. C_LI

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The genetic equidistance and maximum genetic diversity hypothesis: Smoke and mirrors?

Zhang, Y.

2023-02-15 evolutionary biology 10.1101/2023.02.14.528494 medRxiv
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As a novel molecular evolution model that was claimed to have an advantage over the molecular clock hypothesis1-3, the maximum genetic diversity (MGD) hypothesis was utilized to study the modern human origins4. Nevertheless, there are serious problems with this hypothesis and both it and its derivative studies should be treated with caution.

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Study About The Effects Of Smoking On Sleep Apnea In A Sample Of Syrian Society

Al Chaar, D. O.; Al Chaar, m.; Al bardan, h.; Al Chaar, A.

2024-02-18 respiratory medicine 10.1101/2024.02.16.24302743 medRxiv
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BackgroundTo explore whether the use of cigarettes affects the prevalence of obstructive sleep apnea (OSA) in adults. MethodsA questionnaire-based cross-sectional study was conducted among 233 participants. The questionnaire link was published on November 13, 2023 on social media sites and the Internet.The adults were divided into four groups: noncurrent smokers, current electronic cigarettes (e-cigarette) users only, current conventional cigarettes (c-cigarette) users only, and dual users. OSA was assessed by three main signs and symptoms from the questionnaire. Multivariable logistic regression after adjusting for covariates was conducted to investigate the association of OSA with different smoking patterns. The sample size was calculated as 233 to a population of 12,900000 with a margin error of 5% and a confidence interval of 95% using a sample size calculator. ResultsAmong the 233 participants, the prevalence of OSA was higher among smokers compared to non-smokers. the distribution of the prevalence of OSA among continuous smokers (16%), intermittent smokers (36%), and passive smokers (24%). As for those undiagnosed with OSA, the percentage of smokers was 40%, passive smoking was 12.9%, and intermittent smokers were 17.1%. As for OSA patients who were non-smokers, they constituted 24%. By calculating the P-VALUE, which amounted to < 0.001, which indicates a relationship between smoking and sleep apnea. ConclusionOur study found that 68% of sleep apnea patients were smokers, with 24% passive smoking, 36% smoking regular cigarettes, 24% smoking hookah, and 8% smoking electronic cigarettes, which confirmed that sleep apnea is more related to smoking regular cigarettes than Electronic cigarettes

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Analyzing the amplification of Auditory sensation in visually impaired individuals and comparison with normal individuals

Desai, D.

2023-03-14 rehabilitation medicine and physical therapy 10.1101/2023.03.10.23287122 medRxiv
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BackgroundIt is commonly believed that if a person loses one of their basic senses like sight or hearing, other senses will be amplified to compensate the loss. It has been proven that this amplification does indeed help the person up to an extent, but this increase in the senses as compared to other individuals, who have all senses intact, has not been quantified. AimO_LITo estimate and compare Auditory Acuity between visually impaired and normal people C_LIO_LITo calculate the amount of amplification in the Auditory sense in the visually impaired individuals in compared to Normal Individuals C_LI MethodologyA Cross Sectional Case-control Pilot Experimental Study was carried out using a method that has been developed by the authors, wherein a pure tone sound at a specific intensity was brought inwards towards the subject from multiple directions and the distance was measured where the participant could hear the sound and was noted. The same experiment was carried out in Normal Individuals with normal 6/6 vision and these measurements were compared. Positon of nose in respect to the direction of sound source was used to denote the results in angles made by the two. A pure tone of 256 Hz, of 30db was used as the sound source and the distance from the subject was measured in meters. ResultsOut of total 60 individuals in the study, 45 had some degree of blindness. In both groups, the highest sensitivity is at 0{degrees} followed by 45{degrees}-315{degrees}, then comes 90{degrees}-270{degrees} and 135{degrees}-215{degrees} to put nose position of 180{degrees} at least amount of sensitivity. A 10% amplification in the distance is present between any and all type of visually impaired individuals and normal individuals whereas totally blind individuals have around 20% amplification compared to normal individuals in the distance to appreciate the sound. ConclusionA visible difference can be seen in the distance where a total blind person can hear, which is higher than the distance at which a normal individual can hear. High loss of vision, low loss of vision and one eye blind individuals come in the range between these two. Although, the results are not statistically significant, they are clinically present, and a with a larger sample size, a better assessment of this amplification can be done.

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Cytotoxicity and resistance evolution of a novel antifungal carbon nanoparticle

Poudel Sharma, S.; Paudyal, S.; Domena, J.; Zhou, Y.; Cleven, E. C.; Agatemor, C.; Van Dyken, J. D.; Leblanc, R. M.

2024-02-12 evolutionary biology 10.1101/2024.02.11.579833 medRxiv
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Antifungal drug resistance is a major problem in healthcare and agriculture. Synthesizing new drugs is one of the major mitigating strategies for overcoming this problem. In this context, carbon-dots (CDs) are a newer category of nanoparticles that have wide applications, potentially including use as antibiotics. However, there is a lack of understanding of the effect of long-term use of CDs as antimicrobials, particularly the ability of microbes to evolve resistance to antibiotic CDs. In this study, we synthesized novel florescent the bottom-up method using two antifungal drugs fluconazole and nourseothricin sulphate (ClonNAT). We first extensively characterized the physical properties of the newly synthesized carbon dots, Flu-Clo CDs. We measured the cytotoxicity of Flu-Clo CDs on budding yeast Saccharomyces cerevisiae and determined that it had comparable antifungal inhibition with extensively used drug fluconazole. Furthermore, we demonstrate that Flu-CLO CDs are not cytotoxic to human fibroblasts cell lines. Then, we quantified the ability of yeast to evolve resistance to Flu-Clo CDs. We evolved replicate laboratory yeast populations for 250 generations in the presence of Flu-Clo CDs or aqueous fluconazole. We found that yeast evolved resistance to Flu-Clo CDs and aqueous fluconazole at similar rates. Further, we found that resistance to Flu-Clo CDs conferred cross-resistance to aqueous fluconazole. Overall, the results demonstrate the efficacy of CDs as potential antifungal drugs. We can conclude that yeast populations can adapt quickly to novel antibiotics including CD based antibiotics, including CD-based antibiotics indicating the importance of proper use of antimicrobials in combating infections.

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Ribosomal proteins could explain the phylogeny of Bacillus species

Ng, W.

2020-07-26 evolutionary biology 10.1101/2020.07.25.221481 medRxiv
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Protein translation is a highly conserved process in biology. As participants of translation, ribosomal proteins in the large and small subunits of the ribosomes are likely to be highly conserved; thus, could they be endowed with sufficient sequence diversity to chronicle the evolutionary history of different species in the same or different genus? Using different Bacillus species as a model system, this study sought to examine if ribosomal proteins could reproduce the maximum likelihood phylogeny described by 16S rRNA of the investigated Bacillus species. Bacillus species investigated were Bacillus amyloliquefaciens, Bacillus cereus, Bacillus licheniformis, Bacillus megaterium, Bacilluspumilus, Bacillus subtilis, and Bacillus thuringiensis. Results revealed that ribosomal proteins could be categorized into four different groups depending on their extent in reproducing the 16S rRNA phylogeny of the different Bacillus species. The first group comprises ribosomal protein that could reproduce all the phylogenetic positions of the Bacillus species accurately. These ribosomal proteins were ribosomal protein L6, L7/12, L9, L13, L24, L32, S3, S9, S12, S15, S16, S17, and S18. Ribosomal proteins that hold partial phylogenetic significance constitutes the second group where the ribosomal proteins could reproduce the major branches of the 16S rRNA phylogenetic tree but differ in the placement of one or two Bacillus species. In general, this group of ribosomal proteins had difficulty differentiating B. licheniformis and B. pumilus at the sequence level. Members of this group of ribosomal protein include ribosomal protein L22, L29, L30, L31 Type B, L33, L35, S1, S4, S5, S6, S7, S8, S11, S13, S19, and S20. The third group of ribosomal proteins were those which were highly conserved at the sequence level, and which could not differentiate the different Bacillus species. These ribosomal proteins were ribosomal protein L5, L36, S2, S10, and S21. Finally, there were also ribosomal proteins that randomly placed the different Bacillus species into phylogenetic positions not in sync with those depicted by the 16S rRNA phylogenetic tree. These ribosomal proteins were ribosomal protein L7Ae, L17, L20, L23, L27, L28, L31, L34 and S14 Type Z. Overall, members of all four groups of ribosomal proteins came from both the large and small ribosome subunits which meant that evolutionary forces exerted selective pressure on both subunits but at differing extents. Collectively, specific ribosomal proteins could reproduce the phylogeny of different Bacillus species as described by the gold standard phylogenetic marker, 16S rRNA, which highlighted that co-evolutionary processes could be at work in shaping the evolution of ribosomal proteins and rRNA in close contact with each other in the ribosome. Subject areasecology, biochemistry, biotechnology, microbiology, cell biology Significance of the work16S rRNA is the gold standard phylogenetic marker used to inform the evolutionary relationships between different species across the three domains of life. Given that 16S rRNA is nestled in the ribosomes together with a consortium of ribosomal proteins each with unique structural and enzymatic functions, could ribosomal proteins be used similarly as phylogenetic markers for informing species divergence and relationships? Specifically, as part of the highly conserved ribosome important to protein translation, do ribosomal proteins possess sufficient sequence diversity to help chronicle the evolutionary relationships between different species? By reconstructing the maximum likelihood phylogenetic tree of different Bacillus species, this study revealed that ribosomal proteins fall into four categories concerning their utility for informing phylogeny between different species of the same genus. Specifically, there existed ribosomal proteins able to accurately reproduce the phylogenetic tree described by 16S rRNA. On the other hand, there were ribosomal proteins that hold only partial phylogenetic significance where they could reproduce the major branches of the reference phylogenetic tree but differ in the placement of one or two species along the tree. Besides the above two categories, they were also ribosomal proteins whose sequence diversity was not sufficient to help differentiate between different Bacillus species. Finally, another class of ribosomal proteins did not chronicle the evolutionary trajectories of the different species resulting in phylogenetic tree with random placement of the different species. Overall, evolutionary forces likely exerted different selection forces on different ribosome subunits as well as individual ribosomal protein that resulted in the differentiation of their utility as phylogenetic markers of different species of the same genus. Co-evolution between ribosomal proteins as well as between ribosomal proteins and rRNA might underpin part of the evolutionary history chronicled by individual ribosomal proteins, thereby, endowing them with phylogenetic significance. HighlightsO_LIRibosomal proteins were found to be useful in describing the phylogeny of different Bacillus species compared to the gold standard phylogenetic marker, 16S rRNA. C_LIO_LIBy examining the maximum likelihood phylogenetic tree reconstructed, ribosomal proteins could be categorized into four groups with differing phylogenetic significance. C_LIO_LIThe first group comprises ribosomal proteins able to accurately reproduce all the phylogenetic positions of different Bacillus species relative to 16S rRNA phylogenetic tree. This group include ribosomal protein L6, L7/12, L9, L13, L24, L32, S3, S9, S12, S15, S16, S17, and S18. C_LIO_LIThe second group refers to ribosomal proteins able to reproduce the major branches of the 16S rRNA phylogenetic tree but lacks in the correct placement of one or two Bacillus species. These ribosomal proteins were L22, L29, L30, L31 Type B, L33, L35, SI, S4, S5, S6, S7, S8, Sll, S13, S19, and S20. C_LIO_LIThe third group of ribosomal proteins are ones with highly conserved sequence unable to differentiate between different Bacillus species. It comprised ribosomal proteins L5, L36, S2, S10, and S21. C_LIO_LIThe final group of ribosomal proteins did not chronicle the evolutionary forces acting on the different Bacillus species and generated phylogenetic trees with random placement of the different Bacillus species. These ribosomal proteins were L7Ae, L17, L20, L23, L27, L28, L31, L34 and S14 Type Z. C_LI

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Analyzing the amplification of touch sense in visually impaired individuals and comparison with normal individuals

Desai, D.

2023-03-12 rehabilitation medicine and physical therapy 10.1101/2023.03.10.23287123 medRxiv
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BackgroundIt has been said for ages that if a person loses one of the basic senses like sight or hearing, other senses are amplified to make up for it. This has been substantially proved without a doubt that amplification helps the specially-abled individual in their day-to-day life to an extent. These increases are present but have not been quantified and measured on how much the increases are present. Aim1)To estimate and compare sensitivity of touch between visually impaired and normal people and analyze the amplification if present. MethodologyA Cross-Sectional Case-control Study was carried out. Individuals with 6/6 vision and normal in other senses were first examined with the Static Two-point discrimination test to have a baseline value and then different categories of visually impaired individuals were subjected to this test. The test was carried out on the forehead and fingertips of all subjects. Their results were compared using different statistical tools. ResultsTotal 45 visually impaired individuals with various severity of blindness with 20 Normal individuals taken for the study. Two-point discrimination values for normal individuals (Fingertip=3.43{+/-}1.519,Forehead=13.531{+/-}2.364), whereas for all and any type of visually impaired individual (fingertip=2.83{+/-}0.27,Forehead=13.08{+/-}0.26)is statistically(Fingertip, p=0.0101)(Forehead, p=0.4461).R-value for time spent since the disability and degree of amplification is -0.356. ConclusionA significant difference is present between the values of test between visually impaired and normal individuals. Appreciable that with various degrees of blindness, the average values of two-point-discrimination value are different. Totally blind shows the highest sensitivity.

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The association of self-reported sleep quality and obesity in Kuwait using the Pittsburgh Sleep Quality Index (PSQI)

Alghaith, A.; Azim, R.; Ahmad, R.; Al-rashed, f.

2019-12-03 evolutionary biology 10.1101/862060 medRxiv
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Obesity is an epidemic problem facing Kuwait and other neighboring countries within the region. Lifestyle and social structure in this region differ in comparison to the western world. The hot chalinging climate favor night time activities while working hours still force a stringent early attendence. This study is specifically conducted for Kuwaits population to investigate the link between Sleep Quality (SQ) and obesity. A cross-sectional study was conducted for a sample of 1002 participants. Structured questionnaires were used in the study as a tool of research. The participants were asked about their sleep habits, sleep problems, medications, job nature and demographics. All participants consented prior to conducting the survey. In order to measure sleep quality (SQ), the Pittsburgh Sleep Quality Index (PQSI) was used. Statistical analysis was conducted between variables and the data were compared using either two-tailed t-test or one-way ANOVA followed by Tukeys multiple comparison test. Pearsons correlation coefficient r was used to assess linear dependence. 59.4% of Kuwait population reported a PSQI score higher than 5, with 57.3% of the participants reporting less than 6 hours of sleep per day. The presented data shows that both sleep quality and sleep duration are considered inadequate in comparison to international sleep quality standards. None the less, we also found strong a significant association between sleep quality and its component and obesity, while other factors such as age and gender were found insignificant. These finding suggest that sleep deprivation and disturbance could be an indirect inducing factor of obesity in Kuwait. The researchers are of the view that there is a need for more study in the area of obesity and SQ in order to handle the obesity epidemic in the country.

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13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial

Elkazzaz, M. R.; Esam-Eldin Abo-Amer, Y.; Ahmed, A.; Hayadar, T.

2022-03-08 respiratory medicine 10.1101/2022.03.05.22271959 medRxiv
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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical investigation of approved drugs is a promising alternative to find a timely effective treatment. In this randomized trial, we investigated the activity of both oral and aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care treatment in patients with COVID-19 versus standard of care treatment alone. This was a randomized controlled trial conducted at Kafrelsheikh Universitys Quarantine Hospitals, Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment as a control group. The two groups were age and gender matched. There was no statistically significant difference between them in any of the baseline characteristics or laboratory parameters. The results showed that there was a high significant difference between the two groups regarding intensive care unit (ICU) admission, mortality and improvement (P<0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis retinoic acid group, whereas about 14.35% were died in the group II. All patients who received 13 cis retinoic acid noticed a high improvement (P<0.001), and the mean value for clinical improvement was 16.3{+/-}4.5 days. There was no significant difference regarding the laboratory parameters before and after 14 days of treatment in the group of patients received the standard of care treatment (P=0.66). Univariate logistic regression analysis showed overall mortality was significantly related to the patients age, serum ferritin, C-reactive protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients with COVID-19 infection, when added to the standard of care treatment.

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Language gene polymorphism pattern survey provided important information for education context in human evolution

Xia, W.; Zhang, Z.

2022-11-02 evolutionary biology 10.1101/2022.10.31.514632 medRxiv
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Study on language gene polymorphism patterns (LGPP) across different populations could provide important information on human evolution. In this study, as a preliminary observation, we adopted 148 single nucleic polymorphism (SNP) sites from 13 language genes, each with 4-13 SNPs. These SNPs were screened across 112 whole genome sequences (including 59 ancient genomes ranging from 2000 BP to 120000 BP) from five continents (Africa, Asia, Europe, North America, and South America). We found that four distinct LGPPs featured across human evolution history, though it is still to decipher whether they correspond to the three batches of out-of-Africa ancient humans and modern human; Surprisingly, ten ancient samples from the small country, Nepal, contain all 4 basic LGPPs, suggesting that the southern foothills and nearby of the Qinghai-Tibet Plateau were likely an agglomeration place for ancient humans; Chinese samples also have 3-4 basic LGPPs. Of note, some types of Neanderthals and Denisovans possessed a LGPP almost the same as modern humans.

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An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique

Pandya, M. D.; Shukla, D.; Shah, S.; Das, K.; Dave, S.; Das, J.

2023-05-05 evolutionary biology 10.1101/2023.05.04.539453 medRxiv
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A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.

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Isotope effects on radical pair performance in cryptochrome: a new hypothesis for the evolution of animal migration

Galvan, I.; Hassasfar, A.; Adams, B. L.; Petruccione, F.

2022-11-28 evolutionary biology 10.1101/2022.08.08.503164 medRxiv
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Mechanisms occurring at the atomic level are now known to drive processes essential for life, as revealed by quantum effects on biochemical reactions. Some macroscopic characteristics of organisms may thus show an atomic imprint, which may be transferred across organisms and affect their evolution. This possibility is considered here for the first time, with the aim of elucidating the appearance of an animal innovation with an unclear evolutionary origin: migratory behaviour. This trait may be mediated by a radical pair (RP) mechanism in the retinal flavoprotein cryptochrome, providing essential magnetic orientation for migration. Isotopes may affect the performance of quantum processes through their nuclear spin. Here, we consider a simple model and then apply the standard open quantum system approach to the spin dynamics of cryptochrome RP. We changed the spin quantum number (I) and g-factor of hydrogen and nitrogen isotopes to investigate their effect on RPs yield and magnetic sensitivity. Strong differences arose between isotopes with I=1 and I=1/2 in their contribution to cryptochrome magnetic sensitivity, particularly regarding Earths magnetic field strengths (25-65 {micro}T). In most cases, isotopic substitution improved RPs magnetic sensitivity. Migratory behaviour may thus have been favoured in animals with certain isotopic compositions of cryptochrome.

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Prevalence of somatosensory modulation of the cervical spine and temporomandibular joint in subjects with tinnitus: a systematic review

Segreto, M.; Giusti, A.; Bizzarri, P.

2023-08-28 rehabilitation medicine and physical therapy 10.1101/2023.08.26.23294605 medRxiv
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BackgroundTinnitus is defined as the perception of a sound without a corresponding external acoustic stimulus and is considered a symptom rather than a disease. In some individuals, it can be evoked or modulated by input from the somatosensory, somatomotor, and visual-motor systems. This has led to the introduction of the term: somatosensory modulation of tinnitus. In these cases, the psychoacoustic attributes of tinnitus (loudness and pitch) can change as a result of external stimuli such as strong contractions of the muscles of the head, neck, limbs, orofacial movements, and eye movements. The temporomandibular joint and cervical spine, along with the head, appear to be the musculoskeletal anatomical regions most commonly underlying somatic tinnitus. This review aims to evaluate the prevalence of somatosensory modulation of the cervical spine and temporomandibular joint in subjects with tinnitus. MethodsThe databases investigated for the review were: Embase, Pubmed, Scopus, and Web of Science. Observational studies investigating the prevalence of somatosensory modulation of the cervical spine and temporomandibular joint in subjects with tinnitus were included. No time limit was entered into the search and no age or language restrictions were applied. Results14 studies met the eligibility criteria on which the review was based. In 5 studies, the prevalence of tinnitus modulation was reported with one or more maneuvers involving TMJ, in 3 studies with one or more maneuvers involving the cervical spine and 7 studies reported the prevalence of modulation following maneuvers for both somatic regions. ConclusionThe present study confirmed that tinnitus perception and intensity can be somatically modulated in a subpopulation of individuals. The cervical spine and the ATM play a key role in the modulation of tinnitus and, based on the data collected on individual districts, the ATM appears to be the most frequently involved somatic region.

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Evaluation of Flow Control Using PID versus Fuzzy Logic in an Electropneumatic Circuit for Pulmonary Ventilation Applications

Molino, J. J.; Lescher, A.; Gonzalez, L.; Griffith, I.; Rojas, A.; Quijano, D.

2025-01-08 respiratory medicine 10.1101/2025.01.07.25320144 medRxiv
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High-tech commercial mechanical ventilators are designed to provide a constant and accurate flow, thus ensuring the precision of ventilatory treatment. Therefore, this research aims to evaluate the flow control in a prototype electro-pneumatic unit for mechanical ventilator applications using a PID versus a Fuzzy Logic method. Specifically, the intention is to determine if there is evidence of superior performance of fuzzy logic control over PID in this application. For this reason, the methodology is based on measurement and numerical analysis. The design of this research is quasi-experimental and conducted in a laboratory. Thus, samples of the data of the variables were taken at convenience under a pre-established scheme and conditions. In terms of the type of study, it is considered quantitative, experimental, and applied. The main results show that according, the Bland-Altman analysis both controllers meet the accuracy limits of commercial equipment. However, the fuzzy logic controller presented better standard deviation and difference limits, demonstrating greater reliability in the accuracy of results. Additionally, the PID control demonstrated quicker response times with a shorter settling time (between 0.32 and 0.43 seconds) than in the fuzzy logic control (between 0.43 and 0.77 seconds); moreover, the fuzzy control presents an improvement in the volume of 900 mL, highlighting the efficiency of this controller in conditions of higher demand. The results show that both the PID and Fuzzy Logic controllers meet the stability conditions of the Jury Test. The systems poles are within the unit circle of the Z plane, confirming the controllers stability. Also, the curve of the fuzzy control in the Nyquist analysis is farther away from the origin and from the point (-1, 0j) than the curve of the PID control, indicating better stability and a more robust system against variations or disturbances.

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New insights on species divergence in red panda

Joshi, B. D.; Dalui, S.; Singh, S. K.; Mukherjee, T.; Chandra, K.; Sharma, L. K.; Thakur, M.

2020-08-28 evolutionary biology 10.1101/2020.08.27.268607 medRxiv
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With the recent classification of red panda into two phylogenetic species, we propose Siang river as a potential boundary for species divergence between the Himalayan red panda (Ailurus fulgens) and the Chinese red panda (Ailurus styani). Bayesian based phylogeny and MJ network splited all the sequences into two distinct clusters in accordance to the origin of the samples collected from the east and west side of the Siang river. The clade 1, that represented Himalayan red panda, was formed by inclusion of samples originated from the north West Bengal, Sikkim, and central Arunachal Pradesh and South Tibet. While, clade 2 represented Chinese red panda by inclusion of the samples originated from Dibang valley of eastern Arunachal Pradesh, India and Southwest China. We suggest being associated with diverse habitats, threats and transboundary distribution, both species of red panda require regional as well as multilateral cooperation for making species survival plan.

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Metadichol(R) induced expression of the TLR family of receptors in PBMCs

Raghavan, P. R.

2024-04-07 cell biology 10.1101/2024.04.04.588068 medRxiv
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Toll-like receptors (TLRs) are fundamental components of the innate immune system and function as the primary sensors of invading pathogens by recognizing prevalent microbial compounds. The expression of all ten transcription factors belonging to the TLR family (1-10), with the exception of TLR4, exhibited an inverted U-shaped reaction to metadichol, a nanoemulsion composed of long-chain alcohol, as determined by the Q-RT{square}PCR assay. The response pattern suggested that low, moderate, and high concentrations directly affect TLR expression. This may indicate a dual-phase or dose-dependent effect on the immune system regarding TLR regulation. Compounds targeting TLRs can stimulate or inhibit these receptors, thereby affecting the immune response. Adjusting immunological activation, crucial for therapeutic purposes in conditions such as inflammation, cancer, infection, allergies, and autoimmune diseases, requires an inverse U-shaped response. Currently, no single-molecule examples can elicit the activation of every Toll-like receptor (TLR). This study examined the expression levels of all ten Toll-like receptors (TLRs), MYD88, and the downstream genes IRAK4, TRAF3, and TRIF. Metadichol expresses all the 15 genes.

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Effect of EBV-transformation on Oxidative Phosphorylation Physiology in Human Cell lines

Crawford, D. L.; Weinstein, R. N.

2019-12-16 evolutionary biology 10.1101/2019.12.16.878025 medRxiv
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5.7%
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AO_SCPLOWBSTRACTC_SCPLOWDo the immortalized and cryopreserved white blood cells that are part of the 1,000 Human Genomes Project represent a valuable cellular physiological resource to investigate the importance of genome wide sequence variation? While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans physiologies. Fortunately, physiological measures can be done on the immortalized and preserved cells from each of the more than 1,000 individuals that are part of Human Genome project. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The questions we address here are whether EBV transformations significantly alters the cellular physiology so that 1) replicate transformations within an individual are significantly different, and 2) whether the variance among replicates obscures the variation among individuals. To address these questions, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible for most inborn metabolic diseases. The data presented here demonstrate that there are small but significant effects of EBV-transformations on some OxPhos parameters. In spite of significant variation due to transformations, there is greater and significant variation among individuals in their OxPhos metabolism. Thus, the LCLs from the 1,000 Human Genome project could provide valuable insights into the natural variation of cellular physiology because there is statistically significant variation among individuals when using these EBV-transformed cells.

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Tracing the Indian Population Ancestry by cis-linked Mutations in HBB Gene

Panja, A.; Chowdhury, P.; Basu, A.

2021-04-21 evolutionary biology 10.1101/2021.04.18.440318 medRxiv
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BackgroundHuman left their genetic footprints during the time of migration throughout the different countries all over the world. Human evolution was studied through various markers. India is a country of rich heritage and cultural diversity. The modern Indian population is derived from two ancestral groups, viz.-Ancestral North Indians (ANI) and Ancestral South Indians (ASI). AimFinding out the migratory route of the modern Indian population by studying cis acting mutations of human beta-globin (HBB) genes. Subjects and methodsA total of 120 thalassemia subjects were enrolled. DNA sequencing was done for mutation detection in the HBB gene. Some previous literature reviews were gone through for tracing mutations, all over the world and in the Indian subcontinent. ResultsNine thalassemia patients were found where HBB:c.92G>C and HBB:c.-92C>G mutations co-exist together in cis condition. Only one patient had HBB:c.51delC and HBB:c.33C>A. The pedigree analysis confirmed the presence of these mutations in cis condition and vertical transmission from one generation to the next. Literature reviews also reassure the co-existence of these mutations from different countries. ConclusionThe co-existence of these cis acting mutations helps to point out the possible migratory route of ANI population after venturing out of Africa.