bluuebunny/crossref_metadata_2025 huggingface dataset:
Slowing down or returning to normal? Life expectancy improvements in Britain compared to five large European countries before the COVID-19 pandemic
Authors: Minton Jon , Hiam Lucinda , McKee Martin , Dorling Danny
Published: December 2022

Introduction or background

Life expectancy is an important summary measure of population health. In the absence of a significant event like war or disease outbreak, trends should, and historically have, increase over time, albeit with some fluctuations.

Sources of data

Data were extracted from the human mortality database for life expectancy at birth and age 65 years from 1980 to the latest available year for England & Wales, Scotland (Great Britain), France, Spain, Italy, the Netherlands and Germany.

Areas of agreement

It is well established that life expectancy improvements in Great Britain have stalled in recent years, and that a similar stalling was seen in other high-income countries during the mid-2010s.

Areas of controversy

The significance and causes of the slowdown in improvement in life expectancy in Britain are disputed. First, was Britain’s slowdown in progress in life expectancy in the 2010s a deviation ‘from’ earlier sustained improvements or simply returning to normal (slower) improvement rates following faster gains in the 2000s? Second, did other European countries have slowdowns comparable to that in Britain?

Growing points

Life expectancy, as a summary measure, conceals inequalities. Other measures, such as lifespan disparity, complement it in understanding changing trends. While annual fluctuations in life expectancy are expected, continued stalls should raise concern. The three British nations examined were the only ones among these European countries to experience stalling of life expectancy gains in both sexes.

Areas timely for developing research

While it is clear that Britain is making less progress in health than similar countries, more research is needed to explain why.
A mutation in DOK7 in congenital myasthenic syndrome forms aggresome in cultured cells, and reduces DOK7 expression and MuSK phosphorylation in patient-derived iPS cells
Authors: Zhang Shaochuan , Ohkawara Bisei , Ito Mikako , Huang Zhizhou , Zhao Fei , Nakata Tomohiko , Takeuchi Tomoya , Sakurai Hidetoshi , Komaki Hirofumi , Kamon Masayoshi , Araki Toshiyuki , Ohno Kinji
Published: December 2022

At the neuromuscular junction, the downstream of tyrosine kinase 7 (DOK7) enhances the phosphorylation of muscle-specific kinase (MuSK) and induces clustering of acetylcholine receptors (AChRs). We identified a patient with congenital myasthenic syndrome (CMS) with two heteroallelic mutations in DOK7, c.653-1G>C in intron 5 and c.190G>A predicting p.G64R in the pleckstrin homology domain. iPS cells established from the patient (CMS-iPSCs) showed that c.653-1G>C caused in-frame skipping of exon 6 (120 bp) and frame-shifting activation of a cryptic splice site deleting seven nucleotides in exon 6. p.G64R reduced the expression of DOK7 to 10% of wild-type DOK7, and markedly compromised AChR clustering in transfected C2C12 myotubes. p.G64R-DOK7 made insoluble aggresomes at the juxtanuclear region in transfected C2C12 myoblasts and COS7 cells, which were co-localized with molecules in the autophagosome system. A protease inhibitor MG132 reduced the soluble fraction of p.G64R-DOK7 and enhanced the aggresome formation of p.G64R-DOK7. To match the differentiation levels between patient-derived and control induced pluripotent stem cells (iPSCs), we corrected c.190G>A (p.G64R) by CRISPR/Cas9 to make isogenic iPSCs while retaining c.653-1G>C (CMS-iPSCsCas9). Myogenically differentiated CMS-iPSCs showed juxtanuclear aggregates of DOK7, reduced expression of endogenous DOK7 and reduced phosphorylation of endogenous MuSK. Another mutation, p.T77M, also made aggresome to a less extent compared with p.G64R in transfected COS7 cells. These results suggest that p.G64R-DOK7 makes aggresomes in cultured cells and is likely to compromise MuSK phosphorylation for AChR clustering.
RAfilter: an algorithm for detecting and filtering false-positive alignments in repetitive genomic regions
Authors: Yang Jinbao , Zhao Xianjia , Jiang Heling , Yang Yingxue , Hou Yuze , Pan Weihua
Published: December 2022

Telomere to telomere (T2T) assembly relies on the correctness of sequence alignments. However, the existing aligners tend to generate a high proportion of false-positive alignments in repetitive genomic regions which impedes the generation of T2T-level reference genomes for more important species. In this paper, we present an automatic algorithm called RAfilter for removing the false-positives in the outputs of existing aligners. RAfilter takes advantage of rare k-mers representing the copy-specific features to differentiate false-positive alignments from the correct ones. Considering the huge numbers of rare k-mers in large eukaryotic genomes, a series of high-performance computing techniques such as multi-threading and bit operation are used to improve the time and space efficiencies. The experimental results on tandem repeats and interspersed repeats show that RAfilter was able to filter 60%–90% false-positive HiFi alignments with almost no correct ones removed, while the sensitivities and precisions on ONT datasets were about 80% and 50% respectively.
The root meristem growth factorBrRGF6positively regulates Chinese cabbage to infection of clubroot disease caused byPlasmodiophora Brassicae
Authors: Ge Wenjie , Zhang Jing , Feng Hui , Wang Yilian , Ji Ruiqin
Published: December 2022

Chinese cabbage has a high annual demand in China. However, clubroot disease caused by the infection of Plasmodiophora brassicae seriously affects its yield. Transcriptome analysis identified a root meristem growth factor 6 (BrRGF6) as significantly up-regulated in Chinese cabbage roots infected with Plasmodiophora brassicae. Quantitative reverse-transcription polymerase chain reaction and in situ hybridization analysis showed higher BrRGF6 expression in susceptible materials than in resistant materials. After Plasmodiophora brassicae infection, BrRGF6 expression was significantly up-regulated, especially in susceptible materials. Gene function analysis showed that the roots of Arabidopsis mutant rgf6 grew faster than the wild-type, and delayed the infection progress of Plasmodiophora brassicae. A Protein, nuclear transcription factor Y subunit C (BrNF-YC), was screened from yeast two-hybrid library of Chinese cabbage induced by Plasmodiophora brassicae, and verified to interact with BrRGF6 by yeast two-hybrid co-transfer. Yeast one-hybrid and β-Glucuronidase activity analysis showed that BrNF-YC could directly bind to and strongly activate the promoter of BrRGF6. Transgenic verification showed that BrRGF6 or BrNF-YC silenced Chinese cabbage significantly decreased the expression of BrRGF6, accelerated root development, and reduced incidence of clubroot disease. However, after overexpression of BrRGF6 or BrNF-YC, the phenotype showed a reverse trend. Therefore, BrRGF6 silencing accelerated root growth and enhanced resistance to clubroot disease, which was regulated by BrNF-YC.
Correction of beam overlap-induced athwart distortion in multibeam sonars
Authors: Boyra Guillermo , Martínez Udane , Uranga Jon , Moreno Gala , Peña Héctor
Published: December 2022

A method is proposed to estimate and correct athwart-beam distortion of multibeam sonars to advance sonar-based abundance estimation. We illustrate its application using data from a Simrad SN90 multibeam sonar aboard a tropical tuna purse-seiner, targeting mixed fish aggregations around drifting Fish Aggregating Devices (dFADs) in the Atlantic Ocean. To calculate the distortion in the horizontal swath, athwart-beam measurements were compared with the more accurate simultaneous along-beam measurements. For the vertical swath correction, we used as reference a vertically oriented single, split beam echosounder simultaneously monitoring the same aggregations. Along-to-athwart ratios of ∼0.6 and ∼0.3 were estimated for the horizontal and vertical swaths, respectively, at ranges involved during purse-seine operations in this fleet (from ∼225 to ∼325 m). Additionally, equations were developed to analytically describe the athwart distortion due to overlap between contiguous beams. Once corrected for distortion, typical school morphology measures were provided for tuna aggregations around dFADs.
VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas
Authors: Noda Ryuichi , Akabane Atsuya , Kawashima Mariko , Uchino Keita , Tsunoda Sho , Segawa Masafumi , Inoue Tomohiro
Published: December 2022

Objective

Antiangiogenic vascular endothelial growth factor receptor tyrosine kinase inhibitors play an essential role in systemic therapy for renal cell carcinoma. Given the anti-edematous effect of bevacizumab, an antiangiogenic antibody targeting vascular endothelial growth factor, vascular endothelial growth factor receptor tyrosine kinase inhibitors should exert therapeutic effects on radiation-induced brain injury after stereotactic radiosurgery. This preliminary study aimed to investigate the therapeutic effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor against radiation-induced brain injury.

Methods

Magnetic resonance images for six patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors who were diagnosed with radiation-induced brain injury following gamma knife radiosurgery were retrospectively reviewed.

Results

The median brain edema volume and tumour mass volume in the pre-tyrosine kinase inhibitor period were 57.6 mL (range: 39.4–188.2) and 3.2 mL (range: 1.0–4.6), respectively. Axitinib, pazopanib (followed by cabozantinib) and sunitinib were administered in four, one and one cases, respectively. The median brain edema volume and tumour mass volume in the post-tyrosine kinase inhibitor period were 4.8 mL (range: 1.5–27.8) and 1.6 mL (range: 0.4–3.6), respectively. The median rates of reduction in brain edema volume and tumour mass volume were 90.8% (range: 51.9–97.6%) and 57.2% (range: 20.0–68.6%), respectively. The post-tyrosine kinase inhibitor values for brain edema volume (P = 0.027) and tumour mass volume (P = 0.008) were significantly lower than the pre-tyrosine kinase inhibitor values. Changes in volume were correlated with tyrosine kinase inhibitor use.

Conclusion

This study is the first to demonstrate the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery.
Modelling stellar activity with Gaussian process regression networks
Authors: Camacho J D , Faria J P , Viana P T P
Published: December 2022

Stellar photospheric activity is known to limit the detection and characterization of extrasolar planets. In particular, the study of Earth-like planets around Sun-like stars requires data analysis methods that can accurately model the stellar activity phenomena affecting radial velocity (RV) measurements. Gaussian Process Regression Networks (GPRNs) offer a principled approach to the analysis of simultaneous time series, combining the structural properties of Bayesian neural networks with the non-parametric flexibility of Gaussian Processes. Using HARPS-N solar spectroscopic observations encompassing three years, we demonstrate that this framework is capable of jointly modelling RV data and traditional stellar activity indicators. Although we consider only the simplest GPRN configuration, we are able to describe the behaviour of solar RV data at least as accurately as previously published methods. We confirm the correlation between the RV and stellar activity time series reaches a maximum at separations of a few days, and find evidence of non-stationary behaviour in the time series, associated with an approaching solar activity minimum.
Radio jet–ISM interaction and positive radio-mechanical feedback in Abell 1795
Authors: Tamhane Prathamesh D , McNamara Brian R , Russell Helen R , Combes Francoise , Qiu Yu , Edge Alastair C , Maiolino Roberto , Fabian Andrew C , Nulsen Paul E J , Johnstone R , Carniani Stefano
Published: December 2022

We present XSHOOTER observations with previous ALMA, MUSE, and HST observations to study the nature of radio jet triggered star formation and the interaction of radio jets with the interstellar medium in the brightest cluster galaxy (BCG) in the Abell 1795 cluster. Using HST UV data, we determined an ongoing star formation rate of 9.3 M⊙ yr−1. The star formation follows the global Kennicutt–Schmidt law; however, it has a low efficiency compared to circumnuclear starbursts in nearby galaxies with an average depletion time of ∼1 Gyr. The star formation and molecular gas are offset by ∼1 kpc indicating that stars have decoupled from the gas. We detected an arc of high linewidth in ionized gas where electron densities are elevated by a factor of ∼4 suggesting a shock front driven by radio jets or peculiar motion of the BCG. An analysis of nebular emission line flux ratios suggests that the gas is predominantly ionized by star formation with a small contribution from shocks. We also calculated the velocity structure function (VSF) of the ionized and molecular gases using velocity maps to characterize turbulent motion in the gas. The ionized gas VSF suggests that the radio jets are driving supersonic turbulence in the gas. Thus radio jets cannot only heat the atmosphere on large scales and may quench star formation on longer time-scales while triggering star formation in positive feedback on short time-scales of a few million years.
Investigation of the connection between X-ray binaries and compact star clusters in NGC 628
Authors: Avdan S , Akyuz A , Acar S , Akkaya Oralhan I , Allak S , Aksaker N
Published: December 2022

We investigated for a possible connection between the types of X-ray binaries (XRBs) and the properties of compact star clusters in the nearby galaxy NGC 628. Using Chandra archival data covering the years 2001–2018, 75 X-ray sources were detected within the field of view of observations. A total of 69 XRBs, one of which is an ultraluminous X-ray source (ULX), were found to be in the luminosity range of 3 × 1036 ≤ LX ≤ 2 × 1039 erg s−1. We identified the optical counterpart(s) of 15 of the 42 XRBs that coincide with the HST field of view via improved astrometry. We classified 15 of them as HMXBs based on the presence of the optical counterparts. The remaining sources with no optical counterparts were classified as LMXBs. We also search compact star clusters in this galaxy using the multiband optical images drawn from HST archives. 864 compact star clusters were identified and their ages and masses were determined by applying the best-fit SSP (Simple Stellar Population) model to their colour–colour diagram. We found that in NGC 628, HMXBs are associated with younger star clusters and LMXBs with older ones. Our findings support a connection between different types of XRBs and cluster ages, already known to exist for other galaxies.
Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth
Authors: Zisi Asimina , Kanellis Dimitris C , Moussaud Simon , Karlsson Ida , Carén Helena , Bräutigam Lars , Bartek Jiri , Lindström Mikael S
Published: December 2022

Background

High-grade gliomas are malignant brain tumors characterized by aggressiveness and resistance to chemotherapy. Prognosis remains dismal, highlighting the need to identify novel molecular dependencies and targets. Ribosome biogenesis (RiBi), taking place in the nucleolus, represents a promising target as several cancer types rely on high RiBi rates to sustain proliferation. Publicly available transcriptomics data of glioma patients revealed a positive correlation between RiBi rates and histological grades. We, therefore, hypothesized that glioma cells could be susceptible to RiBi inhibition.

Methods

Transcriptomics data from glioma patients were analyzed for RiBi-related processes. BMH-21, a small molecule inhibitor of RNA pol I transcription, was tested in adult and pediatric high-grade glioma cell lines and a zebrafish transplant model. Cellular phenotypes were evaluated by transcriptomics, cell cycle analysis, and viability assays. A chemical synergy screen was performed to identify drugs potentiating BMH-21-mediated effects.

Results

BMH-21 reduced glioma cell viability, induced apoptosis, and impaired the growth of transplanted glioma cells in zebrafish. Combining BMH-21 with TMZ potentiated cytotoxic effects. Moreover, BMH-21 synergized with Fibroblast Growth Factor Receptor (FGFR) inhibitor (FGFRi) Erdafitinib, a top hit in the chemical synergy screen. RiBi inhibition using BMH-21, POLR1A siRNA, or Actinomycin D revealed engagement of the FGFR–FGF2 pathway. BMH-21 downregulated FGFR1 and SOX2 levels, whereas FGF2 was induced and released from the nucleolus.

Conclusions

This study conceptualizes the implementation of RiBi inhibition as a viable future therapeutic strategy for glioma and reveals an FGFR connection to the cellular response upon RiBi inhibition with potential translational value.
The Role of Magma Mixing in the Petrogenesis of Eocene Ultrapotassic Lavas, Western Yunnan, SW China
Authors: Yang Zongpeng , Hou Tong , Wang Dachuan , Marxer Felix , Wang Meng , Chebotarev Dmitry , Zhang Zhaochong , Zhang Hongluo , Botcharnikov Roman , Holtz François
Published: December 2022

Magma mixing is a widespread magmagenic process. However, its significance in the formation of ultrapotassic magmas has been largely overlooked so far as they are commonly thought to originate directly from the mantle and ascend rapidly through the crust. The Hezhong ultrapotassic lavas in Western Yunnan (SW China) are (basaltic) trachy-andesitic in composition. These rocks display porphyritic textures with olivine, clinopyroxene (Cpx), spinel, and phlogopite occurring as both phenocryst and glomerocryst. Disequilibrium textures and complex zonation of crystals are commonly observed. Specifically, based on the textural and compositional characteristics, olivines can be classified into three different populations: two populations are characterized by highly to moderately magnesian olivines with normal chemical core-rim zonation (Fo~94–86 to Fo~89–79 and Fo~91–89 to Fo~86–84, respectively). The third population lacks obvious crystal zonation, but individual crystals exhibit some compositional variety at lower Fo contents (Fo83–76). Similarly, four populations of Cpx and two populations of spinel phenocrysts are recognized in terms of texture and composition. Notably, Cpx with reverse zoning contains a ‘green-core’ surrounded by a colourless mantle and rim. Hence, based on the variations of mineral assemblage, types of inclusions, and chemical compositions, all phenocryst/glomerocryst minerals can be divided into three groups. Mineral Group I (MG I) consists of high Fo cores of olivine, cores of the zoned spinel, and phlogopite. MG II only includes the green cores of reversed zoned Cpx (green-core Cpx), and MG III is composed of micro phenocrysts without obvious zoning and rims of large phenocrysts. Comparing these mineral groups with relevant minerals occurring in typical temporally and spatially associated igneous rocks, we suggest that the MG I and II could have been derived from magmas with compositions resembling an olivine lamproite and a trachyte, respectively. The overall bulk-rock geochemical and isotopic features of Hezhong lavas also agree with a mixing process between these two endmembers. Hence, we infer that mixing between these two magmas played a key role in the petrogenesis of the ultrapotassic Hezhong lavas and that the MG III crystallized from the mixed magmas. Our study highlights the complex formation of ultrapotassic magmas inferring that caution must be taken when using bulk chemical magma compositions are to deduce source signatures.
A Conceptual Model for Spine Surgery Recovery
Authors: Brintz Carrie E. , Coronado Rogelio A. , Schlundt David G. , Haug Jenkins Christine , Bird Mackenzie L. , Bley Jordan A. , Pennings Jacquelyn S. , Wegener Stephen T. , Archer Kristin R.
Published: December 2022

Study Design.

Qualitative interview study.

Objective.

The aim was to develop a conceptual model for Spine Surgery Recovery in order to better understand why patients undergo lumbar spine surgery and what factors influence patient satisfaction.

Summary of Background Data.

Quantitative studies have assessed patients’ expectations for lumbar spine surgery outcomes, with greater expectation fulfillment leading to higher satisfaction. However, there is limited literature using qualitative methods to understand the patient perspective from the decision to undergo lumbar spine surgery through long-term recovery.

Materials and Methods.

Semistructured phone interviews were conducted with 20 participants (nine females, mean age ±SD=61.2±11.1 yr) and three focus groups with 12 participants (nine females, mean age ±SD=62.0±10.9 yr). Sessions were audio recorded and transcribed. Two independent researchers coded the transcripts using a hierarchical coding system. Major themes were identified and a conceptual model was developed.

Results.

A total of 1355 coded quotes were analyzed. The decision to have lumbar spine surgery was influenced by chronic pain impact on daily function, pain coping, and patient expectations. Results demonstrated that fulfilled expectations and setting realistic expectations are key factors for patient satisfaction after surgery, while less known constructs of accepting limitations, adjusting expectations, and optimism were found by many patients to be essential for a successful recovery. Emotional factors of fear, anxiety, and depression were important aspects of presurgical and postsurgical experiences.

Conclusion.

Our Spine Surgery Recovery conceptual model provides guidance for future research and clinical practice to optimize treatment and improve overall patient satisfaction. Recommendations based on this model include the assessment of patient expectations and mental well-being throughout postoperative recovery as well as preoperatively to help set realistic expectations and improve satisfaction. Educational, acceptance-based or positive psychological interventions may be potentially beneficial for addressing key factors identified in this model.
Insulin sensitivity, β cell function, and adverse pregnancy outcomes in women with gestational diabetes
Authors: Shen Yun , Zheng Yanwei , Su Yingying , Jiang Susu , Ma Xiaojing , Hu Jiangshan , Li Changbin , Huang Yajuan , Teng Yincheng , Bao Yuqian , Tao Minfang , Zhou Jian
Published: December 2022

Background:

The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.

Methods:

This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.

Results:

Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16–1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24–0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes.

Conclusions:

We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.
2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment
Authors: Zhou Liya , Lu Hong , Song Zhiqiang , Lyu Bin , Chen Ye , Wang Jiyao , Xia Jun , Zhao Zhan
Published: December 2022

Background:

Helicobacter pylori (H. pylori) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection.

Methods:

This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the RIGHT statement and AGREE II as reporting and conduct guides to ensure the guideline's completeness and transparency.

Results:

Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy.

Conclusions:

The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders’ values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges.

Registration:

GIN website, https://guidelines.ebmportal.com/node/69996.
A meta-analysis of the haemodynamics of primary hypertension in children and adults
Authors: Li Ye , Haseler Emily , McNally Ryan , Sinha Manish D. , Chowienczyk Phil J.
Published: December 2022

We performed a systematic review and meta-analysis to determine the relative contributions of elevated cardiac output and systemic vascular resistance to hypertension in children and adults. This included 27 studies on 11 765 hypertensive and normotensive children and adults in whom cardiac output was measured. Cardiac output but not systemic vascular resistance was elevated in hypertensive compared to normotensive children and young adults (difference in means 1.15 [0.78–1.52] l/min, P < 0.001). In older hypertensive adults, both were elevated compared to normotensive individuals (0.40 [0.26–0.55] l/min, P < 0.001 and 3.21 [1.91–4.51] mmHg min/l, P < 0.001 for cardiac output and systemic vascular resistance, respectively). The main haemodynamic alteration in primary hypertension (including obesity-hypertension) in both children and young to middle-aged adults is an elevation of cardiac output. With longer duration and greater severity of hypertension there may be progression from a ‘cardiac’ to a ‘vascular’ phenotype with increased systemic vascular resistance.
Corneal Biomechanics in Primary Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-analysis
Authors: Liu Min-Xin , Zhou Miao , Li Dan-Lin , Dong Xing-Xuan , Liang Gang , Pan Chen-Wei
Published: December 2022

Précis:

Normal tension glaucoma patients had softer corneas than normal controls, whereas high-tension glaucoma and ocular hypertension patients had stiffer corneas.

Purpose:

To comprehensively identify the corneal biomechanical differences of patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT) using the Ocular Response Analyzer or the Corvis ST.

Methods:

The electronic databases PubMed, Embase, and Web of Science were comprehensively searched for studies comparing corneal biomechanical differences between POAG and OHT patients with normal controls by Ocular Response Analyzer or Corvis ST. The weighted mean differences and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed according to the subtypes of POAG, including high-tension glaucoma (HTG) and normal tension glaucoma (NTG).

Results:

Thirty-one case-control studies were ultimately included, with 2462 POAG patients, 345 OHT patients, and 3281 normal controls. The corneal hysteresis (CH), corneal resistance factor (CRF), and highest concavity time (HC-t) were all lower in POAG patients than in normal controls. The CH, time at the second applanation (A2t), HC-t, highest concavity radius (HC-R), and deformation amplitude at the highest concavity (HC-DA) were lower in OHT patients, while the CRF, time at the first applanation (A1t), and stiffness parameter at the first applanation (SP-A1) were greater in OHT patients than in normal controls. The subgroup analyses showed that the CH, A2t, length at the second applanation (A2L), and HC-DA were lower in HTG, and the CH, CRF, A1t, and HC-t were lower in NTG patients than in normal controls.

Conclusion:

The corneas of NTG patients are more deformable than normal controls, whereas the corneas of HTG and OHT patients are stiffer.
Bacterial Contamination of the Wristwatches Among Clinical and Preclinical Undergraduate Medical Students
Authors: Kumar Naveen , Aithal Ashwini , Azim Nurzadatil Ijmal Binti Zainal , Ravintheran Pavitra a/p , Sofian Abu Emmil Qawarizmi Bin Abu , Lawrence Ling Ley Jit , Narasimhaswamy Nagalakshmi
Published: December 2022

Background

Wristwatches and white coats have been found to harbor a great number of bacteria. Hence, it has raised our concern about the contribution of wristwatches to iatrogenic infections in patients. The aim of this study was to determine the type of microbial contamination present on the wristwatches of clinical and preclinical medical students.

Methods

Sterile cotton swabs dipped in saline were used to collect samples from the wristwatches of 50 undergraduate medical students (25 clinical and 25 preclinical) of MMMC (Manipal Campus). The sample was cultured on blood agar and MacConkey's agar plates. Bacterial colonies were identified by Gram stain and biochemical tests. Antibiotic sensitivity tests were performed by Kirby-Bauer disk diffusion method.

Results

All the samples collected from wristwatches of preclinical students had coagulase-negative Staphylococcus (CONS), and 12% of samples had growth of Staphylococcus aureus. Likewise, clinical students’ wristwatch also had CONS and S. aureus (24%). However, few clinical students’ wristwatch samples yielded the growth of Escherichia coli (12%), Pseudomonas aeruginosa (4%), and Acinetobacter species (4%). Staphylococcus aureus isolates were methicillin resistant. Escherichia coli strains were observed to be extended spectrum beta-lactamase-producing strains. All gram-negative bacteria were sensitive to carbapenem.

Conclusions

Although wristwatches of both clinical and preclinical students had normal flora such as CONS and S. aureus, few clinical students carried drug resistant E. coli, P. aeruginosa, and Acinetobacter species, which are dangerous pathogens in the health care settings. Therefore, wristwatches seem to be a potential source of cross-infection in a clinical setting. The results indicate that there is a need for better compliance of hand hygiene maintenance.
Pulmonary Cryptococcosis Complicating Severe Coronavirus Infectious Disease 2019
Authors: Osborn Rebecca , Angarone Michael , Kling Kendall , Hawkins Claudia
Published: December 2022

Many case reports have detailed fungal infections associated with coronavirus infectious disease-2019 (COVID-19); however, few reports have described cryptococcal infection in individuals with COVID-19. The use of immunomodulatory medications as part of COVID-19 treatment including corticosteroids and tocilizumab increases the risk of invasive fungal infections. Herein we review the existing reports of cryptococcal infection in the setting of COVID-19 and present a case of a previously immunocompetent patient who was diagnosed with pulmonary cryptococcosis after being treated with prolonged corticosteroids for severe COVID-19 and organizing pneumonia.
A Second Reported Case of Catabacter hongkongensis Bactermia in the United States
Authors: Crowley Marci G. , Nakanishi Yukihiro , Pasikhova Yanina , Greene John N. , Armaghani Avan J.
Published: December 2022

Catabacter hongkongensis is a rare bacterium that was first described in 2007. Since that time, there have been less than 20 case reports worldwide. This bacterium inhabits the gastrointestinal tract, and therefore, most cases present with gastrointestinal pathology, including bowel obstruction, acute cholecystitis, and colonic perforation. The treatment is typically surgical intervention and antibiotics. Here, we present a case of C. hongkongensis in a patient undergoing treatment for breast cancer who presented with acute appendicitis.
Multisystem Inflammatory Syndrome (Post–COVID Vaccination/Infection)
Authors: Manian Sreenidhi Vanyaa , Alagesan Murali , Nair Krishna S.
Published: December 2022

Multisystem inflammatory syndrome (MIS) was initially described in children (MIS-C) with recent COVID-19 infection as a Kawasaki-like illness associated with fever, gastrointestinal symptoms, shock, left ventricle systolic dysfunction, and elevated inflammatory markers.
1
Similar cases of MIS have been described in young to middle-aged adults also presenting with fever, gastrointestinal symptoms, and shock with vasoplegia, left ventricle systolic dysfunction, and elevated inflammatory markers.
2
Many of these patients had history of recent COVID-19 infection or vaccination and had positive SARS-CoV-2 antibody tests. We report 3 cases of MIS-(C/A) after either infection or vaccination with different presentations and outcomes with similar line of management.
A Novel Approach to PDMP Reporting: Adapting Opioid Quality Measures to PDMP Data
Authors: Gabriel Meghan , Montavon Joel , Digmann Rachel , Ferris Lindsey M. , Spiro Shelly
Published: December 2022

Objective:

The SUPPORT Act provided resources for developing prescription drug monitoring programs (PDMPs) capable of reporting on four specific opioid quality measures. Therefore, the objective of this pilot study was to map, test, and adapt these claims-based opioid quality measures specified for health plan performance to PDMP data for state-level performance.

Materials and Methods:

Maryland PDMP and claims from Maryland Medicaid beneficiaries continuously enrolled from April 1, 2019, to March 31, 2020.

Results:

The measure rates as specified using claims data are closely aligned with the measure rates when mapped and adapted to PDMP data. The Concurrent Use of Opioids and Benzodiazepines measure rates were 14.49% and 15.31%, the OHD rates were 12.44% and 13.54%, the OHDMP rates were 0.01% and 0.40%, and the Use of Opioids from Multiple Providers in Persons Without Cancer rates were 0.12% and 3.03% for the claims-based and adapted measures, respectively.

Discussion:

This is a novel application that may be replicated in other states to support quality improvement and can have a measurable effect on stemming the drug abuse epidemic.

Conclusions:

This will facilitate data sharing of the opioid quality measure reporting within the Maryland PDMP and stakeholders responsible for caring for Maryland Medicaid beneficiaries. Owing to the encouragement by the Centers for Medicare and Medicaid Services, other states' PDMPs may require the adaptation of these measures. This will open the door for innovative state-level policy and practice interventions. The quantification of outcomes related to these measures will inform our learning healthcare system and help support the Quintuple Aim.
Incidence of Remote Near-Point of Convergence in University Athletes After Sport-Related Concussion
Authors: Hutchison Michael G. , Di Battista Alex P. , Pyndiura Kyla , Blanc Shirley , Quaid Patrick T. , Richards Doug
Published: December 2022

Objective:

Near-point of convergence (NPC) testing is an attractive screening tool in the sport setting because it is rapid, requires few resources, and is easy to administer. Remote NPC has been reported after sport-related concussion (SRC), although the incidence among a university-aged population is not well defined. The purpose of the study was to examine the incidence of remote NPC after SRC in a cohort of Canadian interuniversity athletes.

Design:

Cross-sequential.

Setting:

University.

Participants:

One hundred thirty-two university athletes [SRC, n = 68; musculoskeletal (MSK) injury, n = 64] were tested before the beginning of their competitive season and again after their injury.

Independent Variables:

Healthy athletes measured preseason were compared with athletes after SRC or MSK injury using both longitudinal and cross-sectional designs.

Main Outcome Measures:

Remote NPC (pass/fail), measured at 6 cm or greater, repeated 3 times.

Results:

After SRC, 22% of athletes failed their test postinjury (95% CI, 14%-33%). Comparatively, in the MSK group, 3% of athletes failed their test postinjury (95% CI, 1%-7%). A direct comparison of both injury groups yielded a mean 19% higher prevalence of failed NPC tests after SRC versus MSK injury (95% CI, 10%-30%). There seems to be no relationship between reported symptom burden and NPC performance after SRC.

Conclusion:

Remote NPC occurs in approximately 1 of 5 athletes after SRC and is rarely observed after MSK injury.
Concurrent syphilis, gonorrhea, and monkeypox: A case report
Authors: Rosa Dina Nohemi , Ramos Temblique Eileen Kay
Published: December 2022

Documented cases of monkeypox virus outside of Africa are rare, but as of August 22, 2022, the CDC was tracking 18,101 cases in the United States. Monkeypox rash can easily mimic other sexually transmitted infections, which may occur concurrently. This case report describes a 36-year old Caucasian man who has sex with men. The patient came in for a routine history and physical examination and disclosed a perianal rash. The patient had a medical history significant for undertreated HIV, ankylosing spondylitis, and homelessness. On examination, he had multiple perianal deep-seated ulcers that were swabbed for monkeypox and herpes simplex virus 1 and 2. Samples were also collected for syphilis, chlamydia, and gonorrhea. The swabs were positive for monkeypox and pharyngeal gonorrhea. At subsequent blood draw, he was found to have elevated titers for syphilis and a positive QuantiFERON-TB gold test. In summary, this case is a clear example of an individual with concurrent monkeypox virus and other sexually and nonsexually transmitted infections, highlighting the importance of careful identification of risk factors and testing for monkeypox virus even when the clinical presentation may depict a common sexually transmitted infection, such as the herpes simplex virus.
A Surgeon’s Armamentarium for Ocular Management in Facial Paralysis: A Comprehensive Review
Authors: Shokri Tom , Patel Shivam , Weller Christopher , Lighthall Jessyka G.
Published: December 2022

Objective:

To review the current management paradigm of the eye in patients with facial paralysis.

Methods:

A PubMed and Cochrane search was done with no date restrictions for English-language literature on facial synkinesis. The search terms used were “ocular,” “facial,” “synkinesis,” “palsy,” “neurotization,” and various combinations of the terms. A total of 65 articles were included.

Results:

Facial paralysis may result in devastating ocular sequelae. Therefore, assessment of the eye in facial paralysis is a critical component of patient management. Although the management should be individualized to the patient, the primary objective should include an ophthalmologic evaluation to implement measures to protect the ocular surface and preserve visual acuity. The degree of facial paralysis, lacrimal secretion, corneal sensation, and position of the eyelids should be assessed thoroughly. Patients with the anticipated recovery of facial nerve function may respond to more conservative temporizing measures to protect the ocular surface. Conversely, patients with expected prolonged paralysis should be appropriately identified as they will benefit from surgical reconstruction and rehabilitation of the periorbital complex. The majority of reconstructive measures within a facial surgeon’s armamentarium augment coverage of the eye but are unable to restore blink. Eyelid reanimation restores the esthetic proportionality of the eye with blinking and reestablishes protective functions necessary for ocular preservation and function.

Conclusions:

Ocular preservation is the primary priority in the initial management of the patient with facial paralysis. An accurate assessment is a critical component in identifying the type of paralysis and developing an individualized treatment plan.
Theshhlimb enhancer is activated in patterned limb regeneration but not in hypomorphic limb regeneration inXenopus laevis
Authors: Tada Reimi , Higashidate Takuya , Amano Takanori , Ishikawa Shoma , Yokoyama Chifuyu , Nara Saki , Ishida Koshiro , Kawaguchi Akane , Ochi Haruki , Ogino Hajime , Yakushiji-Kaminatsui Nayuta , Sakamoto Joe , Kamei Yasuhiro , Tamura Koji , Yokoyama Hitoshi
Published: December 2022

Xenopusyoung tadpoles regenerate a limb with the anteroposterior (AP) pattern, but metamorphosed froglets regenerate a hypomorphic limb after amputation. The key gene for AP patterning,shh, is expressed in a regenerating limb of the tadpole but not in that of the froglet. Genomic DNA in theshhlimb-specific enhancer, MFCS1 (ZRS), is hypermethylated in froglets but hypomethylated in tadpoles:shhexpression may be controlled by epigenetic regulation of MFCS1. Is MFCS1 specifically activated for regenerating the AP-patterned limb? We generated transgenicXenopus laevislines that visualize the MFCS1 enhancer activity with a GFP reporter. The transgenic tadpoles showed GFP expression inhoxd13-andshh-expressing domains of developing and regenerating limbs, whereas the froglets showed no GFP expression in the regenerating limbs despite havinghoxd13expression. Genome sequence analysis and co-transfection assays using cultured cells revealed that Hoxd13 can activateXenopusMFCS1. These results suggest that MFCS1 activation correlates with regeneration of AP-patterned limbs and that re-activation of epigenetically inactivated MFCS1 would be crucial to confer the ability to non-regenerative animals for regenerating a properly patterned limb.
Efficient mapping of the thalamocortical monosynaptic connectivityin vivoby tangential insertions of high-density electrodes in cortex
Authors: Sibille Jérémie , Gehr Carolin , Kremkow Jens
Published: December 2022

Thalamus provides the principal input to cortex, thus understanding the mechanisms of cortical computations in behaving animals requires to characterize the thalamocortical connectivityin vivo. We show that tangential insertions of high-density electrodes into mouse cortex capture the activity of thalamocortical axons simultaneously with their synaptically connected cortical neurons. Multiple thalamic synaptic inputs to cortical neurons can be measured providing an efficient approach for mapping the thalamocortical connectivityin vivo.
Molecular and spatial design of early skin development
Authors: Jacob Tina , Annusver Karl , Czarnewski Paulo , Dalessandri Tim , Kastriti Maria Eleni , Levron Chiara Levra , Mikkola Marja L , Rendl Michael , Lichtenberger Beate M , Donati Giacomo , Björklund Åsa , Kasper Maria
Published: December 2022

A wealth of specialized cell populations within the skin facilitates its hair producing, protective, sensory and thermoregulatory functions, but how the vast cell-type diversity and tissue architecture develops is largely unexplored. Here, with single-cell transcriptomics, spatial cell-type assignment and cell-lineage tracing we deconstruct early embryonic mouse skin during the key transitions from seemingly uniform developmental precursor states to a multilayered, multilineage epithelium and complex dermal identity. We reveal the spatiotemporal emergence of hair-follicle-inducing, muscle-supportive, and fascia-forming fibroblasts. We also uncover the formation of the panniculus carnosus muscle, sprouting blood vessels without pericyte coverage, and the earliest residence of mast and dendritic immune cells in skin. Finally, we reveal an unexpected epithelial heterogeneity within the early single-layered epidermis and a signaling-rich periderm layer. Overall, this cellular blueprint of early skin development establishes histological landmarks – essential for placing cells in their spatial tissue context – and highlights unprecedented dynamical interactions among skin cells.
DPM1 through SERPINB5 modulates desmosomal adhesion and epidermal differentiation
Authors: Rathod Maitreyi , Franz Henriette , Beyersdorfer Vivien , Wanuske Marie-Therès , Fischer Karen Leal , Hanns Pauline , Stüdle Chiara , Zimmermann Aude , Buczak Katarzyna , Schinner Camilla , Spindler Volker
Published: December 2022

Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes. In a 3D organotypic human epidermis model, loss of DPM1 caused impaired differentiation with abnormally increased cornification, reduced thickness of non-corneal layers, and formation of intercellular gaps in the epidermis. Using proteomic approaches, SERPINB5 was identified as DPM1-dependent interaction partner of desmoplakin. Mechanistically, SERPINB5 reduced desmoplakin phosphorylation at serine 176, which was required for strong intercellular adhesion. These results uncover a novel role of the DPM complex in linking desmosomal adhesion with epidermal differentiation.