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BJOG-22-1117.R1: Are Kielland’s Forceps a Safe Option for Birth?
Dawn Parris
Dimitrios Siassakos

Dawn Parris

and 1 more

December 20, 2022
BJOG-22-1117.R1: Are Kielland’s Forceps a Safe Option for Birth?Kielland’s rotational forceps deliveries often divide opinion, deriving reactions akin to Marmite, the notorious UK spread. Love or hate them, as many maternity professionals do, what does the current evidence say?The aim of the meta-analysis by Giacchino et al was to estimate the risk of maternal and neonatal complications following Kielland’s births more accurately, when compared with rotational ventouse, non-rotational forceps birth and second stage caesarean section. The authors included 13 observational studies, all published after 2000 to reflect current practice and reported meta-analyses using a random-effects model to allow for clinical heterogeneity.Unsurprisingly, the authors found that Kielland’s births had lower rate of post-partum haemorrhage and of a low 5-minute Apgar score compared to second-stage caesarean. When the cervix is fully dilated, a caesarean has been yet again shown not to be the best ‘way out’, except when it becomes the only ‘way out’ after a failed attempt at instrumental vaginal birth. They also found that babies born by Kielland’s had lower prevalence of significant trauma compared to rotational ventouse, similar to Al-Wattar et al (Curr Opin Obstet Gynaecol 2015;27(6):438-44). This is hardly surprising; despite their notoriety, Kielland’s in the hands of a trained experienced accoucheur can be applied to posterior and transverse malposition, prematurity, face presentation, and in the presence of significant caput. They can also be used for ‘asynclitic occipito-anterior’, a term which has crept into practice in the last couple of decades to describe an occiput more than 45 degrees from the midline where non-rotational forceps could not and should not be used. In observational studies in single centres with expertise, including the papers included in Giacchino et al, Kielland’s are highly effective.Which brings us to key issues not addressed in the review by Giacchino et al. Who is trained nowadays to use Kielland’s safely? And are they safe enough for women’s perineum? In a national UK audit (Tempest et al. Acta Obstet Gynecol Scand 2020;99:537-45) Kiellands were used less often than other methods, particularly for transverse occiput positions. When they were used, the rate of anal sphincter injury was higher with Kielland’s compared to manual rotation.ROTATE, a multicentre RCT in the UK, aims to address these issues with robust methods, and also examine other important outcomes including mental health and continence (https://fundingawards.nihr.ac.uk/award/NIHR127818). Concurrently, innovative research with nano-sensors (Jaufuraully et al, BJOG 2022;129:71) has the potential to make rotational birth techniques safer and more effective regardless of the method used.Such research may take a while before it produces findings applicable to clinical practice. In the meantime, it remains critical to train accoucheurs appropriately, for example with courses such as ROBUST and ART&CRAFT in the UK; but also to propagate good clinical practice beyond isolated silos, before obstetricians become completely deskilled globally. A possible solution would be for centres of excellence in rotational birth to offer apprenticeships to senior obstetricians from other maternity units. Training junior accoucheurs cannot translate into safer practice unless their mentors are also trained and confident to supervise them.
An Unusual Cause of Right Ventricular Ischemia: Saphenous Venous Graft to Pulmonary A...
Tugba Aktemur
Serkan Kahraman

Tugba Aktemur

and 3 more

December 20, 2022
Saphenous venous graft to pulmonary artery fistula is a rare condition.Below we report a casewith saphenous venous graft to left pulmonary artery fistula presenting with coronary ischemia and right heart failure in the literature. 61 year-old male patient was admitted to our emergency department with exertional chest pain. He had previous history of coronary artery bypass graft (CABG) operation.The transthorasic echocardiogram displayed normal left ventricular ejection fraction (55%) .However, right ventricular systolic functional parameters were decreased, tricuspid annular plane systolic excursion (TAPSE)  and tricuspid annular systolic velocity were found as 13mm and 7 cm/sec,respectively. Coronary angiography represented critical stenosis in native coronary arteries.Left internal mammarian arterial graft (LIMA) to LAD remains to be patent. Aorto-CXA saphenous venous graft was also patent. Aorto-RCA and LAD septal sequential saphenous venous graft was patent in RCA course, a fistula from Aorto-RCA and LAD septal sequential venos graft to left pulmonary artery was observed. Coronary computed tomography clearly represented the fistula from venus graft to pulmonary artery. The patient was discussed by Heart Team and re-operation was decided, the patient declined the operation and he was discharged from the hospital under medical therapy. Acquired coronary artery fistulas mostly develop after CABG surgery ; moreover, they may be related to trauma ,neoplasmor infection.They may develop in various areas,there are several data reporting coronary artery fistulas from LIMA or saphenous grafts to pulmonary artery. To the best of our knowledge, this current case was the first case report demonstrating the saphenous venous graft fistulazation without venous aneurysm to pulmonary artery linked to right ventricle failure and coronary ischemia togetherness without any other underlying cause to explain the right heart failure.
Is Omicron really mild? - Comparative analysis of comorbidities and disease outcomes...
Vikas Manchanda
Srestha Mitra

Vikas Manchanda

and 7 more

December 20, 2022
Introduction Multiple variants of SARS-CoV-2 from Alpha to Omicron have an estimated 6.1 million deaths globally till date. However, variants have been found to vary in transmissibility and severity. The present study deals with comparison of morbidity and mortality with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants. Methods An observational retrospective cohort study was conducted on a cohort of laboratory confirmed patients of SARS-CoV-2 diagnosed by qRT-PCR of nasopharyngeal swabs in periods; April-2021 & January-2022; that were sequenced and variants were recorded. Patients were invited for a telephonic interview after voluntary and informed consent was obtained from each participant wherein, the demographics, co-morbidities, oxygen requirement and mortality outcomes of the patients were enquired about. Results A total of 200 patients, with 100 from each period were included in the study. Major comorbidities in patients included hypertension, diabetes mellitus and pulmonary disease. Patients who succumbed to the Delta variant (26%) were higher as compared to the Omicron variant (10%); with the elderly (68 ± 9.7 years) having mortality during the Omicron variant. A significantly increased risk for mortality was observed in comorbidities in both Delta and Omicron variants with hypertension (OR:1.3;5.44), diabetes mellitus (OR:0.99;1.94), chronic pulmonary disease (OR:1.6;2.25), chronic kidney disease (OR:3.18;0.89), and smoking (OR:1.74;1.55). Conclusion The study concluded that the Omicron has potential of high transmissibility and milder disease for the population by large, however, it is not a milder strain for patients with comorbidities having a higher risk of adverse outcomes than that of the previously dominant Delta variant.
KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among C...
Ming Yue
Zepei Feng

Ming Yue

and 10 more

December 20, 2022
Background: Killer-cell immunoglobulin-like receptors 2DL4 ( KIR2DL4) and the human leukocyte antigen class I-G ( HLA-G) display vital parts in immune responses against HCV infection. We select four potentially functional SNPs of KIR/HLA to explore the associations between KIR2DL4/HLA-G genetic variants and HCV infection results. Methods: In the present case-control investigation, KIR2DL4-rs660773, KIR2DL4-rs660437, HLA-G-rs9380142, and HLA-G-rs1707 SNPs were sorted as genotype in a total of 2225 high-risk subjects, involving 1778 paid blood donors and 447 drug users. The SNPs were functionally annotated using bioinformatics analysis. Results: Following adjusting by age, sex, ALT, AST, IFNL4-rs12979860, IFNL4-rs8099917, and the infection route, the logistic regression analysis (LRA) discovered that KIR2DL4-rs660773 and HLA-G-rs9380142 were correlated with vulnerability to HCV infection (all P <0.05). In a locus-dosage way, compared with subjects carrying the rs9380142-AA or rs660773-AA genotypes, subjects with rs9380142-AG or rs660773-AG/GG (all P <0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142-AGrs660773-AG/GG) was correlated with an elevated incidence of HCV infection ( Ptrend<0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype ( P= 0.002) were higher in susceptibility to infect HCV.nThe SNPinfo web server estimated that rs660773 is a transcription factor binding site (TFBS), whereas rs9380142 is a potential microRNA-binding site. Conclusion: In the Chinese high-risk population, KIR2DL4 rs660773 and HLA-G rs9380142 polymorphisms are related to HCV susceptibility .
eDNA metabarcoding of avocado flowers: ‘Hass’ it got potential to survey arthropods i...
Joshua Kestel
Phil  Bateman

Joshua Kestel

and 5 more

December 20, 2022
In the face of global biodiversity declines, surveys of beneficial and antagonistic arthropod diversity as well as the ecological services that they provide are increasingly important in both natural and agro-ecosystems. Conventional survey methods used to monitor these communities often require extensive taxonomic expertise and are time-intensive, potentially limiting their application in industries such as agriculture, where arthropods often play a critical role in productivity (e.g. pollinators, pests and predators). Environmental DNA (eDNA) metabarcoding of a novel substrate, crop flowers, may offer an accurate and high throughput alternative to aid in the detection managed and unmanaged arthropod taxa (e.g. flower-visiting insects and potential pollinators). Here, we compared the arthropod communities detected with eDNA metabarcoding of flowers, from an agricultural species (Persea americana - ‘Hass’ avocado), with two conventional survey techniques; Digital Video Recording (DVR) devices and pan traps. In total, 80 eDNA flower samples, 96 hours of DVRs and 48 pan trap samples were collected. Across the three methods, 49 arthropod families were identified, of which 12 were unique to the eDNA dataset. Alpha diversity levels did not differ across the three survey methods although taxonomic composition varied significantly, with only 12% of arthropod families found to be common across all three methods. This study demonstrates that eDNA metabarcoding of flowers to detect visiting arthropods, although in a developmental stage, can complement traditional survey methods and increase the diversity of taxa detected with implications for both natural and agro-ecosystems.
The WZA: A window-based method for characterizing genotype-environment association
Tom Booker
Sam Yeaman

Tom Booker

and 3 more

August 07, 2021
Genotype environment association (GEA) studies have the potential to identify the genetic basis of local adaptation in natural populations. Specifically, GEA approaches look for a correlation between allele frequencies and putatively selective features of the environment. Genetic markers with extreme evidence of correlation with the environment are presumed to be tagging the location of alleles that contribute to local adaptation. In this study, we propose a new method for GEA studies called the weighted-Z analysis (WZA) that combines information from closely linked sites into analysis windows in a way that was inspired by methods for calculating FST. We analyze simulations modelling local adaptation to heterogeneous environments to compare the WZA with existing methods. In the majority of cases we tested, the WZA either outperformed single-SNP based approaches or performed similarly. In particular, the WZA outperformed individual SNP approaches when a small number of individuals or demes was sampled. We apply the WZA to previously published data from lodgepole pine and identified candidate loci that were not found in the original study.
Real-Time Management Dashboard as a tool for process improvement at the Outpatient le...
Lívia Loamí Ruyz Jorge de Paula
Milena Portella Camargo Labriola

Lívia Loamí Ruyz Jorge de Paula

and 7 more

December 20, 2022
Background: Specialized outpatient clinics account for about 30% of the total number of visits in the entire Brazilian health system. The Real-Time Management Dashboard (RTMD) is a tool that has great potential to deal with process errors, improve patient care and reduce costs, but its use is still concentrated in the hospital sector on a small scale. The aim of this study was to study the implementation and results of indicators of waiting for time and achievement of goals with the help of RTMD in a specialized ambulatory care outpatient unit. Method: This is a longitudinal study in which the analysis of waiting time indicators for consultations and exams was carried out in September and October, between 2012 and 2021. Information on user satisfaction with the time of service in the studied period was also evaluated. Results: A total of 277,925 records from 80,432 patients were analyzed. It could be observed that the monitoring of waiting time indicators through the RTMD contributed to better control of the flow of patients within the ambulatory unit with a decrease in the delay rate after the implementation of the immediate action protocol and waiting time classified as excellent by 97.1% of users with respect to the satisfaction rating. In addition, the RTMD contributed to the achievement of consultation and examination goals over the 10-year period of study. Conclusion: The RTMD proved to be a promising tool for the management of processes within medical specialty outpatient clinics. Keywords: Clinical Decision Support; Medical Informatics; Primacy Health Care; Public Health
Distribution and difference of medical resources among provinces in China
deng wang Yao
RuiYang Yu

deng wang Yao

and 3 more

December 20, 2022
Objective: To explore the distribution and difference of medical resources among 31 provinces (municipalities) in China. Methods and process: According to the health resource indicators of 31 provinces in China Health Statistical Yearbook and China Statistical Yearbook, we described and analyzed the total amount of medical and health resources, per capita medical and health resources and high-quality medical resources. By using cluster analysis and RSR (Rank-sum ratio) comprehensive evaluation method, the difference of medical resources among 31 provinces in China in 2020 was calculated, and the medical resources of each province were classified, compared and analyzed to describe the difference. Results and conclusions:(1) From the perspective of total medical resources, the total medical resources in the western region are far less than those in the eastern region, showing a situation of “more in the east and less in the west”. Provinces with large populations have large medical resources. Developed cities such as Beijing and Shanghai have great advantages in medical and health financial resources, while provinces in remote areas are extremely backward in human, material and financial resources.(2)Unbalanced distribution of high-quality medical resources: tertiary hospitals are mainly concentrated in eastern and central China. The number and scale of tertiary hospitals in western China are obviously backward. China’s top 100 hospitals are mainly distributed in the first tier and economically developed cities. Beijing, Shanghai and Guangzhou accounted for half of the top 100 hospitals. Nearly half of China’s provinces have no hospitals on the “Top 100” list. (3) Per capita medical resources vary greatly. The per capita level of medical resources in the three northeastern provinces (Inner Mongolia, Qinghai, Sichuan, Beijing and Shanghai) is relatively high. The per capita level of medical resources in Anhui, Jiangxi, Guangdong, Ningxia and other provinces is low.
Clinical misdiagnosis of influenza infection with a confusing clinical course: A case...
Arefeh Babazadeh
Zeinab Mohseni Afshar

Arefeh Babazadeh

and 4 more

December 20, 2022
Influenza A infection can mimic coronavirus disease 2019 (COVID-19) in case of their signs and symptoms, making it almost impossible to distinguish them clinically, necessitating using high-precision assays in such patients. Clinicians should be careful in treating such patients merely based on their unspecific manifestations.
The core gut microbiome changes throughout life cycle and season of bark beetle Ips t...
Tereza Veselská
Karel Švec

Tereza Veselská

and 8 more

December 20, 2022
Ips typographus, the most serious pest of spruce forests in Europe, is associated with microorganisms facilitating its invasion and development inside spruce tissues. Despite the importance of I. typographus, little is known about its core gut microbiome. Hereby, we describe the composition of bacterial and fungal microbiomes throughout I. typographus life cycle in spring and summer generations. We used cultivation technique and molecular identification in combination with DNA and RNA metabarcoding to achieve deep inside into the beetle’s microbiome composition and structure. As it is not known whether microbiome forms stable communities inside the beetle’s gut, we observed gut epithelium for biofilm formation with Transmission Electron Microscopy. Cultivation technique together with DNA and RNA metabarcoding indicated similar dominant taxa. The bacterial community belongs almost exclusively to the phylum Proteobacteria (newly Pseudomonadota) and the most common orders and genera are Enterobacteriales (Erwinia and Serratia), Pseudomonadales (Pseudomonas) and Xanthomonadales (Pseudoxanthomonas, Stenotrophomonas). Yeasts (Saccharomycetes) highly dominated the fungal microbiome, followed by Sordariomycetes represented mainly by Ophiostoma bicolor and Endoconidiophora polonica. The most common yeasts were Wickerhamomyces bisporus, Kuraishia molischiana, Nakazawaea ambrosiae, Yamadazyma spp. and Cyberlindnera sp. The proportions of the dominant taxa belonging to the core microbiome of I. typographus change throughout its life cycle and generations. We did not observe any biofilm formation on gut epithelium, which suggests that microbial cells pass through the beetle’s gut with chyme. We propose that species belonging to the core microbiome has similar functions and alternate in the I. typographus ecosystem depending on environmental conditions.
Exploring mechanisms of spatial segregation between body size groups within fish popu...
Hsiao-Hang Tao
Chun-Wei Chang

Hsiao-Hang Tao

and 2 more

December 20, 2022
Ample evidence has indicated shifts in distribution of fish populations in response to environmental stress. However, most studies focused at the whole population scale. This neglects the spatial dynamics between groups of different body size (body size groups), that fundamentally shapes the spatial structure of a population. Here, we explored the mechanisms that modulate spatial dynamics of body size groups, and applied our analyses to three North Sea fish populations which experienced severe declines in biomass from 1977 to 2019: Atlantic cod (Gadus morhua), haddock (Melanogrammus aeglefinus), and whiting (Merlangius merlangius). All three populations exhibited strong declines in the overlapped area between body size groups in winter over 43 years, yet their mechanisms differed. These declines were either due to (1) different magnitudes of contraction of the distribution area of body size groups; and/or (2) different speeds and directions of spatial shift among various body size groups, both increasing spatial segregation within populations. These patterns were either associated with ocean warming, and/or declining population biomass, and such associations often varied according to distinct body size groups. Our analytical approach provides a powerful tool for identifying vulnerable populations under environmental stress and can be generalized to study a variety of size/age structured populations at various ecosystem types.
The promise and challenges of characterising genome-wide structural variants: A case...
Jana Wold
Joseph Guhlin

Jana Wold

and 4 more

March 12, 2023
There is growing interest in the role of structural variants (SVs) as drivers of local adaptation and speciation. From a biodiversity genomics perspective, the characterisation of genome-wide SVs provides an exciting opportunity to complement single nucleotide polymorphisms (SNPs). However, little is known about the impacts of SV discovery and genotyping strategies on the characterisation of genome-wide SV diversity within and among populations. Here, we explore a near whole-species resequence dataset, and long-read sequence data for a subset of highly represented individuals in the critically endangered kākāpō (Strigops habroptilus). We demonstrate that even when using a highly contiguous reference genome, different discovery and genotyping strategies can significantly impact the type, size and location of SVs characterised genome-wide. Further, we found that the mean number of SVs in each of two kākāpō lineages differed both within and across generations. These combined results suggest that genome-wide characterisation of SVs remains challenging at the population-scale. We are optimistic that increased accessibility to long-read sequencing and advancements in bioinformatic approaches including multi-reference approaches like genome graphs will alleviate at least some of the challenges associated with resolving SV characteristics below the species level. In the meantime, we address caveats, highlight considerations, and provide recommendations for the characterization of genome-wide SVs in biodiversity genomic research.
SYNTHETIC BIOLOGY APPROACHES FOR MAMMALIAN CELL FACTORY ENGINEERING
Laura Segatori
Bhagyashree Bachhav

Laura Segatori

and 3 more

December 20, 2022
The production of high-quality recombinant proteins is critical to maintaining a continuous supply of biopharmaceuticals, such as therapeutic antibodies. Engineering mammalian cell factories presents a number of limitations typically associated with proteotoxic stress induced upon aberrant accumulation of off-pathway protein folding intermediates, which eventually culminate with the induction of apoptosis. Recent progress in mammalian synthetic biology provides unique opportunities to endow cells with programmable, user-defined behaviors, thereby addressing some of the challenges of current methods. In this review, we will discuss advances in synthetic biology to design efficient strategies for biomanufacturing.
Chromosome-level genome assembly of freshwater pearl mussel, Hyriopsis cumingii, prov...
Zhiyi Bai
Ying Lu

Zhiyi Bai

and 12 more

December 20, 2022
China is the largest producer of pearls, accounted for over 90% of world’s total pearl production. The triangle sail mussel (Hyriopsis cumingii), the most important species for freshwater pearl culture in China, is a well-known mussel recognized for pearl production with high yield and quality. Here, we reported a high-quality chromosome-level genome assembly of H. cumingii. The size of assembled genome was as large as 3.38 Gb with a scaffold N50 length of 3.19 Mb, and 2.04 Gb genome sequences were anchored onto 19 linkage groups. A total of 37,681 protein-coding genes and 50.86% of repeat elements were predicted and annotated. The expansive of 752 gene families compared to the most closely related Dreissena rostriformis, with a divergence time of 18.5 million years, might reveal an extensive set of genes associated to biomineralization, of which 237 genes were under strong positive selection in H. cumingii genome. Notably, the fibrillin gene family exhibited expansion and positive selection simultaneously, and multiple high expression after mantle implantation, suggesting the reason for outstanding biomineralization ability of H. cumingii. Furthermore, one fibrillin gene was confirmed as involving in deposition of calcium carbonate and formation of amorphous crystal during initial biomineralization based on RNA silencing and In vitro carbonate calcium crystallization assay. Fibrillin genes also diverse our attention from calcium deposition guided by matrix protein to interlamellar membrane configuration for understanding pearl formation. These findings provide a valuable genomic resource for carbonate biomineralization studies and fill the gap on freshwater mussel genome for evolutionary studies.
Leadless pacing: also an option for the young?
Karel Breeman
Reinoud E. Knops

Karel Breeman

and 2 more

December 20, 2022
Editorial accompanying ‘Implantation of a leadless pacemaker in young adults’
Ectodermal dysplasia ‑ A case report from Nepal
Kamala  Acharya
Sapana  Karn

Kamala Acharya

and 2 more

December 20, 2022
Ectodermal dysplasia (ED) is a rare genetic disorder with abnormal development of two or more ectodermal derivatives. These include defects in skin, nails, hair, teeth and sweat glands. A multidisciplinary approach is required for management of such cases. A case of 9 years old boy with ED is reported here.
The potential of ecoregional range maps for boosting taxonomic coverage in large-scal...
Stefan Pinkert

Stefan Pinkert

and 3 more

December 20, 2022
INTRODUCTIONInformation about species’ geographical distribution is central to many ecological and evolutionary questions and underpins effective conservation decision‐making (Meyer et al., 2015; Jetz et al., 2019; Oliver et al., 2021; Jetz et al., 2022). Ideally, distributional data for a species is contiguous in space and time and covers its entire global distribution, at a scale reasonable to inform conservation action and research (Jetz et al., 2019). Expert range maps (ExpRMs) arguably come closest to this standard (Rondinini et al., 2006). These maps of aggregated knowledge and field experience about a species range have been the most frequently used type of distributional data in global-scale biogeographical analyses, biodiversity research, and area-based conservation (Hurlbert & Jetz, 2007; Herkt et al., 2017; Jung et al., 2021). Nevertheless, their limited taxonomic scope critically hampers conclusions about the vast majority of species on our planet (Dauby et al., 2017).The importance of ExpRMs in conservation stems from their use in assessing crucial measures of a species’ threat status by the International Union for the Conservation of Nature [IUCN Red List criterion B; see Schatz (2002)]. The IUCN is the largest provider of ExpRMs, currently holding ranges for approximately 115,000 species (iucn.org retrieved March 11, 2022). Given the lack of monitoring data to assess species range size (i.e., B1 - extent of occurrence) and population density (B2 - area of occupancy), these measures are often estimated using ExpRMs. In addition, changes in these measures over time are used to further track population declines and range contractions. Within IUCN specialists groups, experts draw simplified polygons around occurrence records and then refine and/or extend these polygons based on ecological knowledge of the species in concert with habitat layers (Hawkins et al., 2008; IUCN Standards and Petitions Subcommittee, 2022). Typically, many experts are involved in the generation and evaluation of range maps ensuring that IUCN ExpRMs generally provide a reliably high-quality representation of species’ distributions. Other sources of ExpRMs, especially for plant and invertebrate taxa, include monographies of taxa as well as regional and global field guides (e.g., Scott, 1997; Glassberg, 2017).Over the last few years, an increasing effort has been put into mobilizing range maps from literature sources under metadata standards to not only make them publicly available but also for clarifying decisions of the production process (see birdlife.org or mol.org digitized expert ranges; Marsh et al., 2022). However, due in part to the immense work necessary to produce or digitize each ExpRM, their availability is often limited to more popular or well-studied taxa. Currently, comprehensive and high quality ExpRMs are available for a large proportion of vertebrate species (IUCN.org), whereas they are available only for a few selected plants and invertebrates subgroups and typically limited in their geographical extent (e.g. mol.org/patterns).Species occurrence data, particularly from museum collections and citizen science efforts, have grown rapidly in recent decades. The Global Biodiversity Information Facility hosts occurrence records for 1,723,634 animal and plant species (gbif.org retrieved March 11, 2022). Approaches integrating ExpRMs with increasingly complete, spatially explicit, and readily available occurrence data promise unique advances for incorporating a significant proportion of all species on Earth into large-scale assessments on the status and trend of biodiversity. The IUCN has adopted two alternative integrative approaches to address limitations of transparency and reproducibility of ExpRMs. First, hydro basin layers are used to infer species’ ranges from intersections with observation- and literature-based occurrence records. Although hydro basin-based ranges are limited to species affiliated with lotic (running) waters, this approach vastly improved the availability of baseline distributional data for the assessment of species’ threat status of crabs, crayfishes, shrimps, and Odonata (IUCN.org). Secondly, simple, non-parametric occurrence-based estimates such as Minimum Convex Hulls (MCVs) have been proposed as range estimates to calculate the extent of occurrence and the area of occupancy of species (Dauby et al., 2017; see also ala.org.au). However, both alternatives do not resolve the internal structure of species’ ranges that result from barriers to dispersal, geological differences, and ecological gradients and are therefore likely to significantly overestimate the true species range in many cases. As a result, these range surrogates should be more sensitive (i.e., cover more suitable habitat or potential presences) but less precise (i.e., have a lower occupancy of suitable habitat) than ExpRMs, at least for data-rich species (see Figure 1).We propose the use of terrestrial ecoregions to develop alternative ExpRM surrogates, what we denominate Ecoregional Range Maps (EcoRMs). Ecoregions define the natural extent of areas with similar environmental conditions and distinct ecological communities. Freshwater, marine, and terrestrial ecoregions are established baseline layers used in conservation efforts by the World Wildlife Fund and The Nature Conservancy as well as in assessments of the progress of conservation strategies (e.g., Sayre et al., 2014; Dinerstein et al., 2020). Being based on broad geological and ecological zonation, ecoregions imply a high surrogacy value for species distributions of a broad spectrum of organisms but their congruence with single species distributions and biodiversity patterns has thus far not been evaluated.Here, we statistically compare the sensitivity and precision of MCVs and EcoRMs based on predicted absence-presence information from ExpRMs and SDMs at the species-level as well as congruence in the resulting species richness patterns. We generally expect MCVs to cover areas with a high proportion of true presences (i.e., to have a higher precision), but EcoRMs to cover a higher overall number of species’ true presences (i.e., to have a higher sensitivity). In addition, we investigate the spatial dependence as well as the relationships of sensitivities and precision with the number of underlying occurrence records. With these evaluations, we aim to inform applications about the potential of non-parametric, readily applicable, updateable, and occurrence-based alternatives to ExpRMs and SDMs for boosting the integration of data-poor species into both conservation and ecological research.
Pharmacokinetics, bioequivalence, and safety studies of gefitinib tablet formulations...
Ping Du
Zhixia  Zhao

Ping Du

and 6 more

December 20, 2022
Aims: A randomized, open-label, two-period, two-sequence crossover study was carried out for evaluating the bioequivalence of test (T) and reference (R) formulation of gefitinib in healthy Chinese volunteers. Methods: A total of eighty subjects were enrolled and randomized into two sequence groups. All subjects were orally administered of T or R formulation at dose of 250 mg. The plasma samples were obtained at before and after administration until post-dose 168 hour, and the drug concentrations were analyzed using validated high-performance liquid chromatography-tandem mass spectrometry method. Results: The 90% confidence interval of the geometric mean ratios were all within the range of 0.80-1.25 under fasting and fed conditions. As for the safety of both formulations, no serious or unexpected adverse events occurred during the study. Conclusions: Overall, the T formulation was bioequivalent with R formulation under fasting and fed conditions.
A Sinonasal NUT Midline Carcinoma in an 84-year-old Man Undergoing Radiation and Prot...
Katherynn Zhang
Francisco Laxague

Katherynn Zhang

and 7 more

December 20, 2022
A document by Katherynn Zhang. Click on the document to view its contents.
How to assess pharmacogenomic tests for implementation in the NHS
Sonali Sanghvi
Robin Ferner

Sonali Sanghvi

and 6 more

December 20, 2022
● Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. ● Implementation of testing into routine practice across a healthcare system requires consideration of the evidence, clinical utility, cost-effectiveness, and operational requirements. ● A national approach to providing pharmacogenomic test recommendations and centralised commissioning will reduce inequity and duplication, but must be transparent and evidence based
Comment on: Impact of telehealth visits on hydroxyurea response in sickle cell anemia
Muhammad Rafay Shahzad Cheema

Muhammad Rafay Shahzad Cheema

December 20, 2022
A document by Muhammad Rafay Shahzad Cheema. Click on the document to view its contents.
Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardl...
Ian Pavord
Arnaud Bourdin

Ian Pavord

and 13 more

December 20, 2022
Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation. The LIBERTY ASTHMA TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who had participated in a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Methods: This analysis includes patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose inhaled corticosteroids (ICS) at parent study baseline (PSBL) and enrolled in TRAVERSE. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (pre-BD) FEV 1 (L), asthma control (5-item asthma control questionnaire), and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Results: Of patients with type 2 asthma (n=1,666) in this analysis, 891 (53.5%) were receiving high‑dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab vs placebo were 0.517 vs. 1.883 (phase 2b) and 0.571 vs. 1.300 (QUEST) over 52 weeks of the parent study, and remained low throughout TRAVERSE (0.313–0.494). Improvements in pre-BD FEV 1 from PSBL were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Conclusions: Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.
Conformational changes in the AdeB transmembrane efflux pump by amphiphilic peptide M...
Mohammad Reza Shakibaie
Farzan Modaresi

Mohammad Reza Shakibaie

and 4 more

December 20, 2022
No report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR) Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain of A. baumannii was subjected to minimum inhibitory concentration (MIC) against 12 antibiotics as well as MP-B. Expression of the a deB gene in the absence and presence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 µg/ml) associated with a 20-fold decrease in its expression at sub-MIC of MP-B. The stereochemical analysis using several automated servers confirmed that the AdeB is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. The best model that showed high accuracy (Z=1.2, C=1.41, TM=0.99, and RMSD=4.4) was selected for docking purposes using the Site Map tool, and the correct protein-peptide complexes were simulated in the BioLiP platform. The molecular docking via AutoDock/Vina suggested that MP-B form H-bound with amino acid residues of the AdeB helix-5 and caused a shift in the dihedral angle by distances of 9.0 Å, 9.3 Å, and 9.6 Å, respectively. This shift was detected by the AlphaFold 2 tool and influenced the overall druggability of the protein. From the results, we concluded that, MP-B can be a good candidate for inhibition of bacterial efflux pump.
Role of SARS-CoV-2 Virus in Brain Cells: A Brief Review
Ali Azargoonjahromi

Ali Azargoonjahromi

December 20, 2022
Ali Azargoonjahromi** Shiraz University of Medical Sciences, Shiraz, Iran.Abstract SARS-CoV-2 virus—the virus causes COVID-19 infection—can via sundry mechanisms shrink the various areas of the brain. The published evidence to date indicates that the virus can enter the central nervous system (CNS) through sundry ways such as the olfactory nerve or hematogenous route. The virus can influence neurons and glial cells such as astrocytes, oligodendrocytes, and microglia, thereby impeding their normal functions. The results of such impediments are some adverse effects reported, namely agitation, altered consciousness, headaches, dizziness, brain fog, and mental disorders. It also can induce neurodegenerative disorders via triggering demyelination and other risk factors. To lessen the time of recovery or treat COVID-19 infection, many drugs have been investigated thus far. Of these, Paxlovid has been approved by FDA. It reduces not only the chance of hospitalization or death from a coronavirus infection but also the risk of long-term sickness. Herein several mechanisms by which SARS-CoV-2 virus affects the brain cells, neurons and glial cells, will be discussed. Keywords: SARS-CoV-2; COVID-19; Infection; Central Nervous System; Neuron
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