bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive Gaussian Kernels also Have Gaussian Minimizers
Authors: Barthe Franck , Wolff Paweł
Published: February 2022

We study lower bounds on multilinear operators with Gaussian kernels acting on Lebesgue spaces, with exponents below one. We put forward natural conditions when the optimal constant can be computed by inspecting centered Gaussian functions only, and we give necessary and sufficient conditions for this constant to be positive. Our work provides a counterpart to Lieb’s results on maximizers of multilinear operators with real Gaussian kernels, also known as the multidimensional Brascamp-Lieb inequality. It unifies and extends several inverse inequalities.
GLUT1 Immunohistochemistry Is a Highly Sensitive and Relatively Specific Marker for Erythroid Lineage in Benign and Malignant Hematopoietic Tissues
Authors: Kaumeyer Benjamin A , Fidai Shiraz S , Thakral Beenu , Wang Sa A , Arber Daniel A , Cheng Jason X , Gurbuxani Sandeep , Venkataraman Girish
Published: February 2022

Objectives

Glucose transporter 1 (GLUT1), a glucose transporter, is an abundant protein in erythrocytes with expression beginning early in erythropoiesis. We sought to evaluate the utility of GLUT1 immunohistochemistry (IHC) as a diagnostic marker for identifying erythroid differentiation in hematopoietic tissues, including neoplastic erythroid proliferations.

Methods

A variety of benign and neoplastic bone marrow biopsy specimens containing variable proportions of erythroid precursors were selected (n = 46, including 36 cases of leukemia). GLUT1 IHC was performed using a commercially available polyclonal antibody. Each case was evaluated for staining of erythroid precursors, nonerythroid hematopoietic cells, and blasts. A GATA1/GLUT1 double stain was performed on one case to confirm coexpression of GLUT1 on early erythroid precursors. Staining was compared with other erythroid markers, including glycophorin C.

Results

GLUT1 demonstrated strong membranous staining in erythroid precursors of all cases, which was restricted largely to the erythroid lineage. Of the 36 leukemia cases, all 6 cases of pure erythroid leukemia and both cases of therapy-related acute myeloid leukemia with erythroid differentiation showed positive GLUT1 staining in blasts. Otherwise, only lymphoblasts in B-lymphoblastic leukemia showed weak to moderate granular cytoplasmic staining (four of five cases).

Conclusions

GLUT1 IHC is a highly sensitive and relatively specific marker for erythroid lineage in benign and neoplastic bone marrow biopsy specimens.
Genetic structure of the endemicDipterocarpus condorensisrevealed by microsatellite markers
Authors: Minh Nguyen Duc , Lan Phan Nguyen Hong , Minh Nguyen Tam
Published: February 2022

Anthropogenic disturbances in tropical forests often affect the genetic diversity of a species. Dipterocarpus condorensis is an endangered species in the tropical forests of south-eastern Vietnam, both from its over-exploitation and habitat loss. Therefore, knowledge of population genetic diversity and population structure is essential for identifying the species conservation measures. In the present study, we evaluated genetic diversity and population structure using nine microsatellites for 183 individual trees from eight populations, representing the distribution range of D. condorensis in Vietnam. Two clustering approaches (Bayesian analysis and discriminant analysis of principal components) revealed that all studied individuals clustered into three genetic groups, which were related to gene flow across the range of D. condorensis in the lowland tropical forests of south-eastern Vietnam. Limited gene flow was implicated in anthropogenic disturbance. Genetic differentiation among populations was relatively low (the Weir and Cockerham index of 0.122 and the Hedrick index of 0.149) and showed significant differentiation. The genetic variability of the populations was low (HO = 0.298 and HE = 0.324), which suggested the negative effects of habitat degradation and over-exploitation. Our studies also determined that D. condorensis populations can have undergone recent bottlenecks. We recommend conservation activities for this species based on these results.
Sensory neurons have an axon initial segment that initiates spontaneous activity in neuropathic pain
Authors: Nascimento Ana I. , Da Silva Tiago F. , Fernandes Elisabete C. , Luz Liliana L. , Mar Fernando M. , Safronov Boris V. , Sousa Monica M.
Published: February 2022

The axon initial segment is a specialized compartment of the proximal axon of CNS neurons where action potentials are initiated. However, it remains unknown whether this domain is assembled in sensory dorsal root ganglion neurons, in which spikes are initiated in the peripheral terminals. Here we investigate whether sensory neurons have an axon initial segment and if it contributes to spontaneous activity in neuropathic pain. Our results demonstrate that myelinated dorsal root ganglion neurons assemble an axon initial segment in the proximal region of their stem axon, enriched in the voltage-gated sodium channels Nav1.1 and Nav1.7. Using correlative immunofluorescence and calcium imaging, we demonstrate that the Nav1.7 channels at the axon initial segment are associated with spontaneous activity. Computer simulations further indicate that the axon initial segment plays a key role in the initiation of spontaneous discharges by lowering their voltage threshold. Finally, using a Cre-based mouse model for time-controlled axon initial segment disassembly, we demonstrate that this compartment is a major source of spontaneous discharges causing mechanical allodynia in neuropathic pain. Thus, an axon initial segment domain is present in sensory neurons and facilitates their spontaneous activity. This study provides a new insight in the cellular mechanisms that cause pathological pain and identifies a new potential target for chronic pain management.
The cerebellum and cognition: further evidence for its role in language control
Authors: Yuan Qiming , Li Hehui , Du Boqi , Dang Qinpu , Chang Qianwen , Zhang Zhaoqi , Zhang Man , Ding Guosheng , Lu Chunming , Guo Taomei
Published: February 2022

The cognitive function of the human cerebellum could be characterized as enigmatic. However, researchers have attempted to detail the comprehensive role of the cerebellum in several cognitive processes in recent years. Here, using functional magnetic resonance imaging (fMRI) and transcranial direct current stimulation (tDCS), we revealed different functions of bilateral cerebellar lobules in bilingual language production. Specifically, brain activation showed the bilateral posterolateral cerebellum was associated with bilingual language control, and an effective connectivity analysis built brain networks for the interaction between the cerebellum and the cerebral cortex. Furthermore, anodal tDCS over the right cerebellum significantly optimizes language control performance in bilinguals. Together, these results reveal a precise asymmetrical functional distribution of the cerebellum in bilingual language production, suggesting that the right cerebellum is more involved in language control. In contrast, its left counterpart undertakes a computational role in cognitive control function by connecting with more prefrontal, parietal, subcortical brain areas.
Combined lenalidomide/bortezomib for multiple myeloma complicated by fulminant myocarditis: a rare case report of widely used chemotherapy
Authors: Verbesselt Matthias , Meekers Evelyne , Vandenberghe Peter , Delforge Michel , Vandenbriele Christophe
Published: February 2022

Background

Drug-induced myocarditis is a rare complication of certain cancer treatments, characterized by the development of myocardial inflammation shortly after initiation of treatment, potentially leading to heart failure and/or malignant arrhythmias. The development of eosinophilic myocarditis after administration of lenalidomide has been described and bortezomib has been associated with the development of cardiomyopathies and atherosclerosis.

Case summary

A 69-year-old woman, recently diagnosed with multiple myeloma underwent local radiotherapy for a pathological fracture of the 4th lumbar vertebra and was treated with bortezomib–lenalidomide–dexamethasone. Within 19 days after therapy initiation, she presented with gastrointestinal symptoms, an erythematous pruritic rash, and general fatigue. Surprisingly, routine electrocardiogram (ECG) showed upwardly concave ST-elevation in I and aVL and ST-depressions in II, III, and aVF. Troponin levels were markedly elevated to 5470 ng/L. Complete blood count revealed eosinophilia. Based on further cardiac work-up, including echocardiography, coronary angiography, and cardiac magnetic resonance imaging (MRI) showing positive T2 imaging and patchy subepicardial late gadolinium enhancement, she was diagnosed with hypersensitivity myocarditis. Additional endomyocardial heart biopsy did not reveal any abnormalities, probably due to sampling error. After discontinuation of chemotherapy and prompt treatment with high doses of corticosteroids, the patient recovered.

Discussion

Diagnosis of drug-induced myocarditis can be challenging and even long known widely used (chemo)therapy should be considered a potential trigger. Early diagnosis and treatment are crucial, warranting alertness for suggestive symptoms. Cardiac biomarkers, ECG monitoring, and cardiac MRI are key to confirm the diagnosis. In patients with preserved left ventricular systolic function, two-dimensional speckle tracking echocardiography can provide additional diagnostic information. Every patient presenting with eosinophilia and/or acute onset of auto-immune symptoms after initiation of therapy with lenalidomide/bortezomib deserves prompt cardiac screening. The gold standard remains an endomyocardial biopsy, although sampling error may occur.
The surgical anatomy of hearts with isomeric atrial appendages—implications for surgical management
Authors: Spicer Diane E , Chowdhury Ujjwal Kumar , Anderson Robert H , Pandey Niraj Nirmal , Sankhyan Lakshmi Kumari , George Niwin , Goja Shikha , Malik Vishwas
Published: February 2022

OBJECTIVES

The most severe combinations of cardiac malformations exist in individuals having jumbled-up thoracic and abdominal organs. These patients make up 2 distinct syndromes. As yet, the consensus is lacking on how best to describe the subsets. The subsets are frequently grouped together in terms of ‘heterotaxy’. The surgical approaches to the subsets, however, are markedly different. We reviewed our experiences with regard to the anatomy as observed in the autopsy room, by the analysis of computed tomographic studies, and in the operating room, to assess whether the lesions might be segregated on the basis of isomerism of the atrial appendages.

METHODS AND RESULTS

A review of our findings from the examination of specimens from several archives, along with investigation of a large cohort of patients being prepared for surgical treatment, showed that individuals can uniformly be segregated into subgroups on the basis of isomeric arrangement of the atrial appendages. In all instances, this was made possible by using the criterion of the extent of the pectinate muscles within the appendages as judged relative to the atrial vestibules. Segregation on this basis, which correlated excellently with the bronchial arrangement, sets the scene for an appropriate description of the remainder of the heart, providing the cardiac surgeon with all the inferences required for appropriate surgical intervention.

CONCLUSIONS

When assessing individuals having the features of so-called ‘heterotaxy’, it is possible to segregate the groups into subsets of individuals having either isomeric right or left atrial appendages. This approach provides the framework for the assessment of appropriate surgical management.
A discrete fracture hybrid model for forecasting diffusion-induced seismicity and power generation in enhanced geothermal systems
Authors: Karvounis Dimitrios , Wiemer Stefan
Published: February 2022

We describe a 3-D discrete fracture hybrid model (DFHM) that returns forecasts of both induced seismicity and of power generation in an Enhanced Geothermal System (EGS). Our model considers pore-pressure increase as the mechanism driving induced seismicity, similarly to other hybrid models, but it uses discrete fracture modelling for flow and heat that allows accurate and realistic transient solutions of pore pressure and temperature in fractured reservoirs. Earthquakes and flow are thus considered as closely coupled processes. In the DFHM model, the creation phase of an EGS is described as a Markovian process with a transitional probability that encapsulates the irreducible uncertainty with regards to induced seismicity. We conditioned this transitional probability on field observations from the 2006 EGS project in Basel, achieving a good match with observations of seismicity evolution. Specifically, our model effectively reproduces and explains the observed long-term exponential decay of seismicity after the well was shut in, suggesting that pore pressure diffusion in a critically stressed fractured reservoir is sufficient to explain long-lasting post-injection seismic activity as observed in Basel. We then investigate alternative injection scenarios, using Monte Carlo simulations to capture the uncertainties in fault locations and stressing conditions. We show that the number of induced events depends not only on the total injected volume but also on the injection strategy. We demonstrate that multistage injection schemes are superior to single-stage ones, since the former are associated with less seismic risk and can generate at least the same revenue in the long term.
Joint inversion of receiver functions and surface wave dispersion in the Recôncavo–Tucano basin of NE Brazil: implications for basin formation
Authors: Döring M F , Julià J , Evain M
Published: February 2022

The crustal structure of the Recôncavo–Tucano basin, an aborted rift system that developed in NE Brazil during extension related to the opening of the South Atlantic Ocean, has been investigated through local constraints from receiver functions developed at 18 seismic stations in the region. Gravity modelling has proved unable to unequivocally localize crustal thinning under the basin depocentre and, together with a general lack of sediments from a putative thermal sag phase, this has led to a range of basin formation models invoking either pure or simple shear or a combination of both. In particular, the ‘flexural cantilever’ model has assumed simple shear extension in the upper crust and pure shear extension in the lower crust and mantle, enabling local erosion of the rift flanks after footwall uplift and regional erosion of the thermal sag phase after magmatic underplate of the basin's crust. Our results reveal that the crust is over 40 km thick beneath the Tucano and Recôncavo basins and that it contains a thick (5–8 km) layer of high velocity (Vs > 4.0 km s–1) material below ∼35 km depth. These observations contrast with structure immediately West (São Francisco Craton) and East (Borborema Province) of the basin, for which crustal thicknesses average 42 and 36 km, respectively, lower crustal velocities are below 4.0 km s–1, and local instances of crust as thin as 33.5 km are observed. We propose, in agreement with the ‘flexural cantilever’ model, that the fast velocity layer making the basin's lowermost crust resulted from mafic underplating after stretching and thinning during the syn-rift phase, restoring crustal thickness to pre-rift values (or larger) and providing the necessary buoyancy to trigger regional uplift. Moreover, although not pervasive, instances of thin crust along the footwall could be related to rift flank erosion. We thus conclude that, regardless of the mode of extension in the upper crust, our results favour models of basin formation invoking extension of the lower crust by pure shear.
IVF under COVID-19: treatment outcomes of fresh ART cycles
Authors: Youngster Michal , Avraham Sarit , Yaakov Odelia , Landau Rabbi Moran , Gat Itai , Yerushalmi Gil , Sverdlove Rachael , Baum Micha , Maman Ettie , Hourvitz Ariel , Kedem Alon
Published: February 2022

STUDY QUESTION

Does prior severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles?

SUMMARY ANSWER

SARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long-term negative effect on oocyte yield (>180 days postinfection).

WHAT IS KNOWN ALREADY

A single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes.

STUDY DESIGN, SIZE, DURATION

Retrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle postinfection), between October 2020 and June 2021, matched to non-diagnosed controls.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Patients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle and clinical pregnancy rates, were compared between groups.

MAIN RESULTS AND THE ROLE OF CHANCE

One hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; P = 0.169) and mature oocyte rate (78% versus 82%; P = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; P = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (P = 0.018, Slope = −4.08, 95% CI −7.41 to −0.75), although the sample size was small.

LIMITATIONS, REASONS FOR CAUTION

A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group.

WIDER IMPLICATIONS OF THE FINDINGS

The study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos and clinical pregnancy rates, in fresh ART cycles, except for a possible long-term negative effect on oocyte yield when retrieval occurs >180 days post-SARS-CoV-2 infection. Further studies are warranted to support these findings.

STUDY FUNDING/COMPETING INTEREST(S)

None.

TRIAL REGISTRATION NUMBER

0010-21-HMC, 0094-21-ASF.
A novel intramolecular negative regulation of mouse Jak3 activity by tyrosine 820
Authors: Sekine Yuichi , Kikkawa Kazuna , Witthuhn Bruce A , Kashiwakura Jun-ichi , Muromoto Ryuta , Kitai Yuichi , Fujimuro Masahiro , Oritani Kenji , Matsuda Tadashi
Published: February 2022

Jak3, a member of the Janus kinase family, is essential for the cytokine receptor common gamma chain (γc)-mediated signaling. During activation of Jak3, tyrosine residues are phosphorylated and potentially regulate its kinase activity. We identified a novel tyrosine phosphorylation site within mouse Jak3, Y820, which is conserved in human Jak3, Y824. IL-2-induced tyrosine phosphorylation of Jak3 Y824 in human T cell line HuT78 cells was detected by using a phosphospecific, pY824, antibody. Mutation of mouse Jak3 Y820 to alanine (Y820A) showed increased autophosphorylation of Jak3 and enhanced signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and transcriptional activation. Stably expressed Jak3 Y820A in F7 cells, an IL-2 responsive mouse pro-B cell line Ba/F3, exhibited enhanced IL-2-dependent cell growth. Mechanistic studies demonstrated that interaction between Jak3 and STAT5 increased in Jak3 Y820A compared to wild-type Jak3. These data suggest that Jak3 Y820 plays a role in negative regulation of Jak3-mediated STAT5 signaling cascade upon IL-2-stimulation. We speculate that this occurs through an interaction promoted by the tyrosine phosphorylated Y820 or a conformational change by Y820 mutation with either the STAT directly or with the recruitment of molecules such as phosphatases via a SH2 interaction. Additional studies will focus on these interactions as Jak3 plays a crucial role in disease and health.
No Fair! Distinguishing Between the Pursuit of Status and Equity in International Relations
Authors: Rathbun Brian , Rathbun Nina Srinivasan , Pomeroy Caleb
Published: February 2022

Status-seeking behavior, the pursuit of a higher position on an international social hierarchy as perceived and defined by members of a community, has received considerable attention in recent years. Yet, much of what this recent literature calls status-seeking is difficult to distinguish from something else: the pursuit of fairness. We disentangle status-seeking from fairness-seeking by identifying where a pure status-seeking and a fairness-seeking argument diverge—in the degree to which state actors demand exclusive rights and privileges. Survey experiments of the Russian public concerning the country's membership in the G8 as well as a case study of Germany's behavior in the first Moroccan crisis provide strong support for our “biased fairness” account. Derived from the behavioral economics and psychology literature, it maintains that leaders demand entitlements that match their status and find any such denial as less fair than an equivalent discrepancy for other countries. However, once assured of what they deserve, they do not demonstrate any tendency to exclude others, the hallmark of the status motivation. Convergent evidence at multiple levels of analysis, country contexts, and widely different time periods gives strong indications that fairness concerns are driving much of what is attributed to status-seeking.
Evaluation of formic acid sandwich (FA-sandwich): A pretreatment method for filamentous fungi, for the identification of clinically relevant filamentous fungi by two MALDI-TOF MS systems
Authors: Peng Dan , Zhu Xiaobin , Liu Yanhua , Li Xiaoning , Chen Guoqiang , Li Yirong , Xiao Xiao
Published: February 2022

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify microorganisms. However, unlike bacteria and yeast where identification results can be obtained rapidly and accurately by using a simple direct-coating pretreatment method, the traditional pretreatment methods for filamentous fungi are more complex, involving ethanol, formic acid, acetonitrile, and a protein extraction process by centrifugation, i.e., the EtOH-FA full extraction. This cumbersome pretreatment for filamentous fungi is a major reason for the lack of widespread use of MALDI-TOF MS for the identification of filamentous fungi in clinical settings. The present study describes an alternative method, the FA-sandwich, and demonstrates that the approach is efficient and effective. 148 clinical filamentous fungal isolates collected from three large general hospitals in Hubei Province, China, were processed by the FA-sandwich method and identified by two MALDI-TOF MS platforms, Autof ms and Vitek MS. The FA-sandwich allowed a 93.9% species-level identification with Autof ms, and 97.3% species-level identification rates were found for Vitek MS when the IVD, the RUO and in-house databases are used in combination. Further comparison of the ease of FA-sandwich with the EtOH-FA full extraction showed that the FA-sandwich is a more convenient, time- and reagent-saving, and sensitive pretreatment method. These findings indicate that the FA-sandwich method is suitable for pretreating filamentous fungi followed by MALDI-TOF MS identification in clinical microbiology laboratories.

Lay summary

The FA-sandwich method improves the efficiency of identification of filamentous fungi using MALDI-TOF MS while ensuring identification accuracy. The method is easy to perform and very suitable for detecting mold in the microbiology laboratory with the goal of promoting timely and accurate therapies.
Cosmic ray irradiation of comet nuclei: a possible source of cometary outbursts at large heliocentric distances
Authors: Pavlov A K , Belousov D V , Tsurkov D A , Lomasov V N
Published: February 2022

The effect of radical accumulation in ice, under high energy particle irradiation at low temperature followed by the energy release during heating, has been proposed as a possible cause of cometary outbursts. Water ice samples were subjected to 15 MeV protons to simulate the cosmic ray irradiation of comet nuclei. The irradiation with 0.9 MeV electrons was performed to model a similar process on icy satellites located in radiation belts of planets. We observed the release of accumulated energy 20 J g−1 during the heating of the proton-irradiated ice with two pulses of fast self-heating of the sample at 84 and 110 K. Similar energy release occurred between 82 and 110 K in the electron-irradiated ice. Our calculations suggest that the recombination of radicals accumulated in the surface layer of a comet nucleus under cosmic ray bombardment can trigger the cometary outbursts far from the Sun.
Calibration requirements for Epoch of Reionization 21-cm signal observations – II. Analytical estimation of the bias and variance with time-correlated residual gains
Authors: Kumar Jais , Dutta Prasun , Choudhuri Samir , Roy Nirupam
Published: February 2022

Observation of redshifted 21-cm signals from neutral hydrogen holds the key to understanding the structure formation and its evolution during the reionization and post-reionization era. Apart from the presence of orders of magnitude larger foregrounds in the observed frequency range, the instrumental effects of the interferometers combined with the ionospheric effects present a considerable challenge in the extraction of 21-cm signals from strong foregrounds. The systematic effects of time- and frequency-correlated residual gain errors originating from the measurement process introduce a bias and enhance the variance of the power spectrum measurements. In this work, we study the effect of time-correlated residual gain errors in the presence of strong foreground. We present a method to produce analytic estimates of the bias and variance in the power spectrum. We use simulated observations to confirm the efficacy of this method and then use it to understand various effects of the gain errors. We find that as the standard deviation in the residual gain errors increases, the bias in the estimation supersedes the variance. It is observed that an optimal choice of the time over which the gain solutions are estimated minimizes the risk. We also find that the interferometers with higher baseline densities are preferred instruments for these studies.
Genome-wide association, prediction and heritability in bacteria with application toStreptococcus pneumoniae
Authors: Mallawaarachchi Sudaraka , Tonkin-Hill Gerry , Croucher Nicholas J , Turner Paul , Speed Doug , Corander Jukka , Balding David
Published: February 2022

Whole-genome sequencing has facilitated genome-wide analyses of association, prediction and heritability in many organisms. However, such analyses in bacteria are still in their infancy, being limited by difficulties including genome plasticity and strong population structure. Here we propose a suite of methods including linear mixed models, elastic net and LD-score regression, adapted to bacterial traits using innovations such as frequency-based allele coding, both insertion/deletion and nucleotide testing and heritability partitioning. We compare and validate our methods against the current state-of-art using simulations, and analyse three phenotypes of the major human pathogen Streptococcus pneumoniae, including the first analyses of minimum inhibitory concentrations (MIC) for penicillin and ceftriaxone. We show that the MIC traits are highly heritable with high prediction accuracy, explained by many genetic associations under good population structure control. In ceftriaxone MIC, this is surprising because none of the isolates are resistant as per the inhibition zone criteria. We estimate that half of the heritability of penicillin MIC is explained by a known drug-resistance region, which also contributes a quarter of the ceftriaxone MIC heritability. For the within-host carriage duration phenotype, no associations were observed, but the moderate heritability and prediction accuracy indicate a moderately polygenic trait.
COVID-19 vaccination: is it mandatory or optional?
Authors: Situmorang Dominikus David Biondi
Published: February 2022

In Indonesia, controversy about the COVID-19 vaccination is still going on, there is a group of people who believe in this vaccine, and another group chooses not to believe. There are those who support this as mandatory, but there are also those who think that this is optional. Hopefully through this letter, we can all respect the decisions of every human being who has free will and has full rights over their own life.
Invited review: a carcass and meat perspective of crossbred beef × dairy cattle
Authors: Foraker Blake A , Frink Jenna L , Woerner Dale R
Published: February 2022

Crossbreeding dairy cows with beef sires has greatly altered the consist of U.S. dairy-influenced slaughter cattle and generated an influx of crossbred beef × dairy cattle to the U.S. fed beef slaughter supply in 2021. This review provides a summary of our observations of carcass and meat traits in the recent U.S. beef × dairy crossbred population and, based on these observations, exposes future opportunities for consideration. Strip loin steaks from beef × dairy cattle can be marketed alongside conventional beef products in retail display without consumer discrimination based on color or steak shape previously experienced in steaks from straightbred dairy cattle. Additionally, beef from crossbred beef × dairy cattle cannot be discriminated against for eating quality attributes (tenderness, flavor, and juiciness) as it exhibits similar, if not improved, performance of these attributes to beef from conventional beef cattle. We have also demonstrated that live expression of beef-type versus dairy-type character within the beef × dairy crossbred population has minimal effect on eating quality. With proper genetic selection and management, crossbred beef × dairy cattle can capture carcass premiums from an optimal combination of carcass quality (marbling) and red meat yield. Future beef × dairy crossbred mating and management systems should emphasize increases in total carcass muscling and reductions in liver abscess prevalence. A story of quality, sustainability, and traceability in the large and constant supply of beef from crossbred beef × dairy cattle may present profitable branding and marketing opportunities for these products.
Open anatomical reduction by anterior transverse mini approach for the treatment of distal humeral epiphyseal separation in young children
Authors: Chen Kai , Chen Xin , Su Yuxi
Published: February 2022

The treatment of distal humeral epiphyseal separation (DHES) in young children includes closed reduction and cast immobilization or fixation by Kirschner (K) wire with the assistance of an elbow joint arthrogram. In this study, we aimed to introduce and evaluate open reduction using an anterior transverse mini approach in the treatment of DHES in young children. We retrospectively analyzed the clinical data of patients diagnosed with DHES at our hospital between January 2015 and December 2019. After applying the inclusion and exclusion criteria, 70 patients were included in this study. The fracture type was classified using DeLee’s classification. The conservative group (14 patients; group A) underwent closed reduction and cast immobilization. Open surgery was performed using an anterior mini-transverse approach, and K-wires were used for fixation in group B (56 patients). After 3–5 weeks, the K-wires were removed following radiographic confirmation of callus formation. All elbow functions were evaluated using Flynn’s criteria. Complications such as cubitus varus, nerve palsies, incision infection, and K-wire skin irritation were analyzed. According to DeLee’s classification, in group A, five, four, and five patients were of types A, B, and C, respectively. In group B, 11, 10, and 35 patients were of types A, B, and C, respectively. There was a significant difference in Flynn’s criteria (P = 0.0007). In groups A and B, five and four patients developed cubitus varus, respectively, with a significant difference observed in the complication rate (P = 0.0127). Five patients developed K-wire skin irritation. Nerve injury was not observed in either group. One patient in group B had avascular necrosis of the trochlea. Open anatomic reduction via the anterior mini-transverse approach can be a choice of treatment for DHES in young children. Level of evidence: IV.
Paired box 5 increases the chemosensitivity of esophageal squamous cell cancer cells by promoting p53 signaling activity
Authors: Zhang Weiwei , Yan Wenji , Qian Niansong , Han Quanli , Zhang Weitao , Dai Guanghai
Published: February 2022

Background:

Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.

Methods:

To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.

Results:

PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = −0.189, P = 0.011 for cg00464519 and r = −0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.

Conclusions:

As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.
Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease
Authors: Pan Xiaoli , Zhang Yanqiao
Published: February 2022

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.
Accuracy and applications of sequencing and genotyping approaches for CYP2A6 and homologous genes
Authors: Langlois Alec W.R. , El-Boraie Ahmed , Fukunaga Koya , Mushiroda Taisei , Kubo Michiaki , Lerman Caryn , Knight Jo , Scherer Steven E. , Chenoweth Meghan J. , Tyndale Rachel F.
Published: February 2022

Objectives

We evaluated multiple genotyping/sequencing approaches in a homologous region of chromosome 19, and investigated associations of two common 3’-UTR CYP2A6 variants with activity in vivo.

Methods

Individuals (n = 1704) of European and African ancestry were phenotyped for the nicotine metabolite ratio (NMR), an index of CYP2A6 activity, and genotyped/sequenced using deep amplicon exon sequencing, SNP array, genotype imputation and targeted capture sequencing. Amplicon exon sequencing was the gold standard to which other methods were compared within-individual for CYP2A6, CYP2A7, CYP2A13, and CYP2B6 exons to identify highly discordant positions. Linear regression models evaluated the association of CYP2A6*1B and rs8192733 genotypes (coded additively) with logNMR.

Results

All approaches were ≤2.6% discordant with the gold standard; discordant calls were concentrated at few positions. Fifteen positions were discordant in >10% of individuals, with 12 appearing in regions of high identity between homologous genes (e.g. CYP2A6 and CYP2A7). For six, allele frequencies in our study and online databases were discrepant, suggesting errors in online sources. In the European-ancestry group (n = 935), CYP2A6*1B and rs8192733 were associated with logNMR (P < 0.001). A combined model found main effects of both variants on increasing logNMR. Similar trends were found in those of African ancestry (n = 506).

Conclusion

Multiple genotyping/sequencing approaches used in this chromosome 19 region contain genotyping/sequencing errors, as do online databases. Gene-specific primers and SNP array probes must consider gene homology; short-read sequencing of related genes in a single reaction should be avoided. Using improved sequencing approaches, we characterized two gain-of-function 3’-UTR variants, including the relatively understudied rs8192733.
Changes in the Healthcare Environment Prompt Leaders to Think Digitally
Authors: Gannotta Richard J.
Published: February 2022

Hospitals have been facing an epic crisis, with the COVID-19 pandemic overwhelming emergency departments and forcing the implementation of surge protocols to manage care delivery and treatment. These realities have affected both inpatient care delivery and caregiver effectiveness. The need to reevaluate clinical operations is challenging the healthcare delivery structure and its leadership to think differently—digitally. Supporting care for patients in the home has played an important role in mitigating many safety and access issues, accelerating telehealth adoption and solidifying its place in the ongoing transformation of healthcare delivery. As this shift continues to unfold, it is also bringing an opportunity to improve clinical outcomes, patient satisfaction, and cost reduction efforts as well as advance access and promote diversity, equity, and inclusion in the US healthcare delivery system.
Sustainable Digital Health Demands Cybersecurity Transformation
Authors: DeFord Drexel
Published: February 2022

Technology has become a mission-critical part of healthcare business operations. The electronic health record, medical equipment, revenue cycle, enterprise resource planning, marketing, legal, planning and building new facilities… every component today is dependent on automated tools. When computer systems go offline, everyone feels the stress of conducting business and delivering care without access to all the information they need. Downtimes are especially dangerous for patients.

While there are many reasons that these systems go offline, cybersecurity breaches are primary culprits. Logically then, digital innovation becomes unsustainable in healthcare without cybersecurity transformation. What was good enough at one time is not acceptable anymore. As healthcare has accelerated toward digital dependence, particularly through the COVID-19 pandemic, cybersecurity threats have also increased. The time to transform cybersecurity is now.

The first thing for healthcare leaders to understand is this: You do not have a malware problem or a ransomware problem—you have a cybersecurity adversary problem. It is important to learn everything about the organizations attacking you, including their structure, motivation, and goals. Armed with those insights, you are more likely to be able to defend your health system. By transforming your cybersecurity program, you will build a foundation on which you can thrive as a modern healthcare operation.
Contact Lenses for Ocular Surface Disease
Authors: Wang Xueyang , Jacobs Deborah S.
Published: February 2022

Ocular surface disease can be difficult to manage, causing patients discomfort and vision loss. Therapeutic contact lenses are an important treatment option that is often neglected because it is conventional wisdom that eyes that are dry or irritated are not good candidates for contact lens. In this focused review, we consider the substantial literature on the use of bandage soft contact lenses (BSCL), scleral lenses, and customized prosthetic devices in the management of ocular graft-vs-host disease. Reports on BSCLs for recurrent corneal erosion are reviewed, as is literature on scleral lenses and prosthetic replacement of the ocular surface ecosystem treatment for Stevens–Johnson syndrome. Clinical pearls for fitting BSCLs are presented, and the issue of antibiotic prophylaxis is considered.
Mechanisms Underlying Contact Lens-Related Keratitis Caused by Pseudomonas aeruginosa
Authors: Suzuki Takashi , Inoue Hidenori
Published: February 2022

Infectious keratitis is a severe complication associated with contact lens (CL) wear, and can progress rapidly with suppurative infiltration, resulting in the loss of vision. Contact lens wearers with poor and improper care are susceptible to develop infectious keratitis. Gram-negative bacilli such as Pseudomonas aeruginosa, have an ability to form biofilms on CL cases and CLs. Moreover, P. aeruginosa has various virulence factors such as type III secretion system (TTSS) which is an important factor for pathogenicity in keratitis. The effector proteins of TTSS have been identified, namely ExoU, ExoS, ExoT, and ExoY. Pseudomonas aeruginosa strains with ExoU show resistance to disinfection. The strains isolated from CL-related keratitis have higher ExoU gene positivity. Expression of elastase and swarming motility of P. aeruginosa isolates significantly correlates with focus size of keratitis. In addition to education of lens care for the CL wearer, development of CL cleaning solutions targeting suppression of virulence factors are needed for prevention of CL-related keratitis in the future.
Corneal hysteresis: ready for prime time?
Authors: Jammal Alessandro A. , Medeiros Felipe A.
Published: February 2022

Purpose of the review

This review summarizes recent findings on corneal hysteresis, a biomechanical property of the cornea. Corneal hysteresis measurements can be easily acquired clinically and may serve as surrogate markers for biomechanical properties of tissues in the back of the eye, like the lamina cribrosa and peripapillary sclera, which may be related to the susceptibility to glaucomatous damage.

Recent findings

Several studies have provided evidence of the associations between corneal hysteresis and clinically relevant outcomes in glaucoma. Corneal hysteresis has been shown to be predictive of glaucoma development in eyes suspected of having the disease. For eyes already diagnosed with glaucoma, lower corneal hysteresis has been associated with higher risk of progression and faster rates of visual field loss over time. Such associations appear to be stronger than those for corneal thickness, suggesting that corneal hysteresis may be a more important predictive factor. Recent evidence has also shown that cornealcorrected intraocular pressure measurements may present advantages compared to conventional Goldmann tonometry in predicting clinically relevant outcomes in glaucoma.

Given the evidence supporting corneal hysteresis as an important risk factor for glaucoma development and its progression, practitioners should consider measuring corneal hysteresis in all patients at risk for glaucoma, as well as in those already diagnosed with the disease.
Role of artificial intelligence in the diagnosis and management of kidney disease: applications to chronic kidney disease and acute kidney injury
Authors: Tangri Navdeep , Ferguson Thomas W.
Published: February 2022

Purpose of review

Chronic kidney disease (CKD) and acute kidney injury (AKI) are global public health problems associated with a significant burden of morbidity, healthcare resource use, and all-cause mortality. This review explores recently published studies that take a machine learning approach to the diagnosis, management, and prognostication in patients with AKI or CKD.

Recent findings

The release of novel therapeutics for CKD has highlighted the importance of accurately identifying patients at the highest risk of progression. Many models have been constructed with reasonable predictive accuracy but have not been extensively externally validated and peer reviewed. Similarly, machine learning models have been developed for prediction of AKI and have found sufficient accuracy. There are issues to implementing these models, however, with conflicting results with respect to the relationship between prediction of an AKI outcome and improvements in the occurrence of other adverse events, and in some circumstances potential harm.

Artificial intelligence models can help guide management of CKD and AKI, but it is important to ensure that they are broadly applicable and generalizable to various settings and associated with improved clinical decision-making and outcomes.