Miracle-dz/UniFAR-FTUs huggingface dataset:
A framework for calculating orthogonal selectivities in multimodal systems directly from cell culture fluid

This paper presents a straightforward approach for measuring and quantifying orthogonality directly in complex cell culture fluids (CCFs) without the requirement for tracking the retention behaviors of large sets of proteins. Null‐producing CCFs were fractionated using linear salt gradients at constant pH on a set of multimodal resins. Fractions were then analyzed by ultraperformance‐reversed phase liquid chromatography and the resulting chromatograms provided host cell protein (HCP) “fingerprints. ” Using these fingerprints, an inner product vector‐based approach was employed to quantify the degree of orthogonality between pairs of resins and operating conditions for these large HCP protein sets. To compare resin orthogonality behavior in different expression systems, the Chinese hamster ovary and Pichia pastoris null‐producing CCFs were examined. Orthogonality in multimodal systems was found to strongly depend on the expression system and the HCPs being screened. We also identified several unexpected pairs of multimodal resins within the same family that exhibited significant orthogonality. Furthermore, “self‐orthogonality” was evaluated between resins operated at different pHs, and important operating regimes were identified for maximizing orthogonal selectivities. The framework developed in this paper for calculating orthogonality without the need for labor‐intensive HCP tracking has important implications for efficient process development and resin/operating condition selection for both monoclonal antibody (mAb) polishing steps and non‐mAb processes. In addition, this study provides a tool to unlock the untapped potential of multimodal resins by aiding in their rational selection and incorporation. Finally, the orthogonality framework here can facilitate the development of sets of next‐generation multimodal resins specifically designed to provide highly orthogonal and efficient separations tailored for different expression systems.
Prevalence and molecular characterization of Wolbachia in field-collected Aedes albopictus, Anopheles sinensis, Armigeres subalbatus, Culex pipiens and Cx. tritaeniorhynchus in China

Wolbachia are maternally transmitted intracellular bacteria that can naturally and artificially infect arthropods and nematodes. Recently, they were applied to control the spread of mosquito-borne pathogens by causing cytoplasmic incompatibility (CI) between germ cells of females and males. The ability of Wolbachia to induce CI is based on the prevalence and polymorphism of Wolbachia in natural populations of mosquitoes. In this study, we screened the natural infection level and diversity of Wolbachia in field-collected mosquitoes from 25 provinces of China based on partial sequence of Wolbachia surface protein (wsp) gene and multilocus sequence typing (MLST). Among the samples, 2489 mosquitoes were captured from 24 provinces between July and September, 2014 and the remaining 1025 mosquitoes were collected month-by-month in Yangzhou, Jiangsu province between September 2013 and August 2014. Our results showed that the presence of Wolbachia was observed in mosquitoes of Aedes albopictus (97.1%, 331/341), Armigeres subalbatus (95.8%, 481/502), Culex pipiens (87.0%, 1525/1752), Cx. tritaeniorhynchus (17.1%, 14/82), but not Anopheles sinensis (n = 88). Phylogenetic analysis indicated that high polymorphism of wsp and MLST loci was observed in Ae. albopictus mosquitoes, while no or low polymorphisms were in Ar. subalbatus and Cx. pipiens mosquitoes. A total of 12 unique mutations of deduced amino acid were identified in the wsp sequences obtained in this study, including four mutations in Wolbachia supergroup A and eight mutations in supergroup B. This study revealed the prevalence and polymorphism of Wolbachia in mosquitoes in large-scale regions of China and will provide some useful information when performing Wolbachia-based mosquito biocontrol strategies in China.
Device-related infections in a pediatric intensive care unit

Abstract To estimate the prevalence of the most frequent infections related to device utilization and their antimicrobial sensitivity panel, and to investigate the overall incidence of device associated infection rates per 1000 device days, at the pediatric intensive care unit of the Jordan University of Science and Technology. This is a retrospective study from a single pediatric intensive care unit. Data were collected in relation to bloodstream infections associated with central venous catheters, pneumonia associated with ventilator endotracheal tubes, and urinary tract infections associated with Foley catheters, between January 2013 and December 2018, according to the center of disease control and prevention protocols. During the 5-year study, 3195 patients were admitted to the pediatric intensive care unit for a total of 16,487 days. Forty-six patients (1.4%) developed 55 infections, with a median incidence rate of 7.4, 3.7, and 0.7 per 1000 days for central line associated infections, ventilator associated pneumonia, and catheter associated infections, respectively. The commonest isolated microorganisms were gram-negative bacteria in 89.1% of cases, and fungi in 10.9% of cases. Among the resistant bacterial isolates, 59.2% were multidrug resistant, and 32.6% were extended spectrum beta lactamase producers Klebsiella pneumoniae and Eschericia coli. High infection rates were related to Acinetobacter baumannii and K pneumoniae, associated with high resistance to cephalosporins. Susceptibility was highest to tigecycline and imipenem at 42.9% and 32.7% respectively. Microbial isolates are commonly associated with healthcare device insertions in pediatric intensive care unit, invasive bacterial infections associated with critical morbidity and mortality. Further studies on device associated infections are recommended for regional profiling purposes.
Effect of variable domain charge on in vitro and in vivo disposition of monoclonal antibodies

ABSTRACT A growing body of evidence supports the important role of molecular charge on antibody pharmacokinetics (PK), yet a quantitative description of the effect of charge on systemic and tissue disposition of antibodies is still lacking. Consequently, we have systematically engineered complementarity-determining regions (CDRs) of trastuzumab to create a series of variants with an isoelectric point (pI) range of 6.3–8.9 and a variable region (Fv) charge range of −8.9 to +10.9 (at pH 5.5), and have investigated in vitro and in vivo disposition of these molecules. These monoclonal antibodies (mAbs) exhibited incrementally enhanced binding to cell surfaces and cellular uptake with increased positive charge in antigen-negative cells. After single intravenous dosing in mice, a bell-shaped relationship between systemic exposure and Fv charge was observed, with both extended negative and positive charge patches leading to more rapid nonspecific clearance. Whole-body PK experiments revealed that, although overall exposures of most variants in the tissues were very similar, positive charge of mAbs led to significantly enhanced tissue:plasma concentration ratios for most tissues. In well-perfused organs such as liver, spleen, and kidney, the positive charge variants show superior accumulation. In tissues with continuous capillaries such as fat, muscle, skin, and bone, plasma concentrations governed tissue exposures. The in vitro and in vivo disposition data presented here facilitate better understanding of the impact of charge modifications on antibody PK, and suggest that alteration in the charge may help to improve tissue:plasma concentration ratios for mAbs in certain tissues. The data presented here also paves the way for the development of physiologically based pharmacokinetic models of mAbs that incorporate charge variations.
The 100 Most-Cited Articles in Liposuction

Supplemental digital content is available in the text. Background Liposuction is one of the most common cosmetic surgical procedures performed worldwide. Despite previous citation analyses in plastic surgery, the most-cited works in liposuction have not yet been qualitatively or quantitatively appraised. We hypothesized that use of validated outcome measures and levels of evidence would be low among these articles. Thus, we performed a bibliometric analysis aiming to comprehensively review the most-cited liposuction literature, evaluating characteristics and quality of the top 100 articles. Methods The 100 most-cited articles in liposuction were identified on Web of Science, across all available journals and years (1950–2020). Study details, including the citation count, main subject, and outcome measures, were extracted from each article by 2 independent reviewers. The level of evidence of each study was also assessed. Results The 100 most-cited articles in liposuction were cited by a total of 4809 articles. Citations per article ranged from 602 to 45 (mean, 92). Most articles were level of evidence 4 (n = 33) or 5 (n = 35), representative of the large number of case series, expert-opinion articles, and narrative reviews. Ten articles achieved level of evidence 3, 22 articles achieved level of evidence 2, and none reached level 1. The main subject was operative technique in 63 articles, followed by outcomes in 32 articles. Five articles assessed the metabolic effects of liposuction. Only 1 article used a validated objective cosmetic outcome measure, and none used validated patient-reported outcome measures. Conclusions This analysis provides an overview of the top cited liposuction literature. Overall, level of evidence was low, and no articles achieved the highest level of evidence. Improving the quality of literature requires prioritization of better-designed studies and incorporation of validated outcome measures, which will increase patient satisfaction and ensure provision of excellent, reproducible clinical care.
Memories off the top of your head

Description Cortical layer 1 has a special role in long-term memory Memories are generally considered to be embodied in the connection strengths between neurons. Finding the exact synaptic connections responsible for memories out of hundreds of trillions at first appears impossible. But new research may be taking us a step closer. Specific brain areas under the neocortex are known to be required for memory formation (including the hippocampus and basal ganglia), while long-term memory relating to facts and knowledge (semantic memory) is thought to reside in the neocortex (1). However, the precise location of semantic memory is still unknown, preventing researchers from understanding how and where memories are formed.
Enhancement of the superconducting transition temperature by Re doping in Weyl semimetal 
MoTe2

This work presents the emergence of superconductivity in Re substituted topological Weyl semimetal MoTe$_{2}$. Re substitution for Mo sites lead to a sizable enhancement in the superconducting transition temperature (T$_{c}$). A record high T$_{c}$ at ambient pressure in a 1T$'$-MoTe$_{2}$ (room temperature structure) related sample is observed for the Mo$_{0.7}$Re$_{0.3}$Te$_{2}$ composition (T$_{c}$ = 4.1 K, in comparison MoTe$_{2}$, shows a T$_{c}$ of 0.1 K). The experimental and theoretical studies indicate that Re substitution is doping electrons and facilitates the emergence of superconductivity by enhancing the electron-phonon coupling and density of states at the Fermi level. Our findings, therefore, open a new way to further manipulate and enhance the superconducting state together with the topological states in 2D van der Waals materials.
Assessment of the Risk of Breast Cancer Development Applying NCI Tool among Iraqi Women

Objective: As part of the bioinformatics studies, we utilized National Cancer Institute (NCI)’s Breast Cancer Risk Assessment Tool to estimate the five-year period and lifetime risk of breast cancer development among Iraqi risky women. Methods: Totally, 110 risky women aged 21-67 (mean=36±7.4) years were interviewed by a series of questions regarding the risk of breast cancer development. Moreover, 100 cases with mutation in the BRCA1 or BRCA2 genes were included. Results: Our results demonstrated that the patient’s estimated risk of breast cancer development during the next five years and lifetime (until the age 90 years) included 0.96% (p=0.211) and 9.97% (p=0.002), respectively being relatively low. Accordingly, the lifetime risk for the breast cancer development was significantly higher (10.38%) than that of 5-year. However, the age of patients was not significantly associated to the breast cancer development as there was no significant difference among various age groups. Conclusion: It was concluded that long-term or lifetime period plays as a significant risk factor for developing breast cancer among female patients who had had a screening episode in Iraq.
Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews

BACKGROUND This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). PURPOSE To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. DATA SOURCES We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. STUDY SELECTION Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. DATA EXTRACTION One reviewer appraised and extracted data; data were checked by a second. DATA SYNTHESIS Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. LIMITATIONS Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. CONCLUSIONS There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.
The evolution of division of labour in structured and unstructured groups

Recent theory has overturned the assumption that accelerating returns from individual specialisation are required to favour the evolution of division of labour. Yanni et al., 2020, showed that topologically constrained groups, where cells cooperate with only direct neighbours such as for filaments or branching growths, can evolve a reproductive division of labour even with diminishing returns from individual specialisation. We develop a conceptual framework and specific models to investigate the factors that can favour the initial evolution of reproductive division of labour. We find that selection for division of labour in topologically constrained groups: (1) is not a single mechanism to favour division of labour—depending upon details of the group structure, division of labour can be favoured for different reasons; (2) always involves an efficiency benefit at the level of group fitness; and (3) requires a mechanism of coordination to determine which individuals perform which tasks. Given that such coordination must evolve prior to or concurrently with division of labour, this could limit the extent to which topological constraints favoured the initial evolution of division of labour. We conclude by suggesting experimental designs that could determine why division of labour is favoured in the natural world.
Association between Smokeless Tobacco Use and Risk of Periodontitis in Asian Countries: A Systematic Review and Meta-Analysis

Background: Individual studies conducted in Asian countries have reported higher risk of periodontitis among smokeless tobacco (SLT) users in comparison to non-users. Therefore, a systematic review was conducted to summarize the available evidence on this topic. Methods: Prominent electronic databases were searched using pre-decided MeSH terms and keywords. Screening of titles and abstracts, full text reading, quality assessment and data extraction was done by two investigators independently. The Newcastle-Ottawa scale was used for risk of bias assessment of eligible studies. Meta-analysis was performed for four periodontal outcomes (periodontal pocket depth, loss of attachment, clinical attachment level and gingival recession). A sensitivity analysis was also performed. Results: Of the 546 citations, 367 were screened for eligibility. Finally, 89 studies were shortlisted for full text reading, of which, 36 were found eligible for qualitative analysis. Most of the studies were conducted in India (n=22), were of cross-sectional design (n=33), utilized purposive sampling and 24 studies were included for meta-analysis (n=28) and done on hospital-based population (n=26). Only 13 (37.1%) studies achieved a score of more than 50% (5/10 stars) on quality assessment scale. SLT users had higher odds of greater periodontal pocket depth greater than 4 mm (OR=3.64), gingival recession (OR=1.71) and loss of attachment 4-5 mm (OR=2.83) and mean difference of 1.7 mm for Clinical Attachment Level compared to non-users. Conclusion: The studies included in this review suggests that SLT users have poorer periodontal health in comparison to non-users. But most of this evidence comes from cross-sectional studies. Longitudinal studies with rigorous methodology are required to support this elucidation. Registration: This systematic review protocol has been registered in PROSPERO (CRD42019122964).
Microwave observations reveal the deep extent and structure of Jupiter’s atmospheric vortices

Description Measuring the depth of Jupiter’s storms The atmosphere of Jupiter consists of bands of winds rotating at different rates, punctuated by giant storms. The largest storm is the Great Red Spot (GRS), which has persisted for more than a century. It has been unclear whether the storms are confined to a thin layer near the top of the atmosphere or if they extend deep into the planet. Bolton et al. used microwave observations from the Juno spacecraft to observe several storms and vortices. They found that the storms extended below the depths at which water and ammonia are expected to condense, implying a connection with the deep atmosphere. Parisi et al. analyzed gravity measurements taken while Juno flew over the GRS. They detected a perturbation in the planet’s gravitational field caused by the storm, finding that it was no more than 500 kilometers deep. In combination, these results constrain how Jupiter’s meteorology links to its deep interior. —KTS Observations of storms in Jupiter’s atmosphere indicate that they extend deeper into the planet than expected. Jupiter’s atmosphere has a system of zones and belts punctuated by small and large vortices, the largest being the Great Red Spot. How these features change with depth is unknown, with theories of their structure ranging from shallow meteorological features to surface expressions of deep-seated convection. We present observations of atmospheric vortices using the Juno spacecraft’s Microwave Radiometer. We found vortex roots that extend deeper than the altitude at which water is expected to condense, and we identified density inversion layers. Our results constrain the three-dimensional structure of Jupiter’s vortices and their extension below the clouds.
Fecal Microbiome Composition Does Not Predict Diet‐Induced TMAO Production in Healthy Adults

Background Trimethylamine‐N‐oxide (TMAO) is a small molecule derived from the metabolism of dietary nutrients by gut microbes and contributes to cardiovascular disease. Plasma TMAO increases following consumption of red meat. This metabolic change is thought to be partly because of the expansion of gut microbes able to use nutrients abundant in red meat. Methods and Results We used data from a randomized crossover study to estimate the degree to which TMAO can be estimated from fecal microbial composition. Healthy participants received a series of 3 diets that differed in protein source (red meat, white meat, and non‐meat), and fecal, plasma, and urine samples were collected following 4 weeks of exposure to each diet. TMAO was quantitated in plasma and urine, while shotgun metagenomic sequencing was performed on fecal DNA. While the cai gene cluster was weakly correlated with plasma TMAO (rho=0.17, P=0.0007), elastic net models of TMAO were not improved by abundances of bacterial genes known to contribute to TMAO synthesis. A global analysis of all taxonomic groups, genes, and gene families found no meaningful predictors of TMAO. We postulated that abundances of known genes related to TMAO production do not predict bacterial metabolism, and we measured choline‐ and carnitine‐trimethylamine lyase activity during fecal culture. Trimethylamine lyase genes were only weakly correlated with the activity of the enzymes they encode. Conclusions Fecal microbiome composition does not predict systemic TMAO because, in this case, gene copy number does not predict bacterial metabolic activity. Registration URL: https://www.clinicaltrials. gov; Unique identifier: NCT01427855.
Effect of Laparoscopic Pancreaticoduodenectomy in Elderly People

Supplemental digital content is available in the text. Abstract Pancreaticoduodenectomy is considered to be the most complicated operation in abdominal surgery. The purpose of this study was to evaluate the safety and efficacy of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients. We searched PubMed, Embase, and Cochrane Library databases for relevant studies that were published before June 2020. Seven cohort studies were eligible with 3200 patients. The result of meta-analysis showed that, for the elderly, severe complications, clinical pancreas fistula, and delayed gastric emptying in the LPD group were significantly lower than those in the open pancreaticoduodenectomy (OPD) group. There was no significant difference in postoperative bleeding, reoperation, and readmission between the 2 groups. For the LPD, the mortality, delayed gastric emptying, and severe complication in elder patients were significantly higher than those in young patients. There was no significant difference in postoperative bleeding, R0 rate, reoperation rate, and readmission rate between the aged and the young. Therefore, LPD can reduce postoperative complications in elderly patients compared with OPD, which can be used as a potential alternative to OPD in elderly patients. However, laparoscopic approach cannot eliminate the high risk of postoperative death and severe complications caused by age. More high-quality studies need to be done for further verification.