bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of fitness training and psychosocial education intervention programs in wildland firefighting: a cluster randomised control trial
Authors: Leduc Caleb , Giga Sabir I. , Fletcher Ian J. , Young Michelle , Dorman Sandra C.
Published: July 2022

Critical to effective fire management is the protection and preparedness of highly trained wildland firefighters who routinely face extreme physical and psychological demands. To date, there is limited scientific evidence of psychosocial education intervention effectiveness in this context. The objective of the current study is to utilise a cluster randomised control trial study design to evaluate fitness training and psychosocial education intervention programs across a wildland fire season. Wildland firefighters (n = 230) were randomly assigned by their work location to one of four experimental conditions. Pre- and post-season assessments of primary (e.g. psychosocial risk factors, physical fitness and psychological capital) and secondary (e.g. work engagement, job stress and incidence of injury) outcomes facilitated comprehensive evaluation. The psychosocial education intervention program was effective at buffering participant appraisals of 12 of 13 psychosocial risk factors, namely: organisational culture, civility, psychological demands, balance, psychological support, leadership expectations, growth and development, influence, workload management, engagement, protection and safety. Participants in the psychosocial education intervention also reported lower stress relating to organisational support compared with those who not receiving the intervention program. Wildland firefighters receiving either or both intervention programs reported a significantly lower incidence rate of injury (9.9%) compared with the organisation’s 5-year average (16.0%).
IFI16-dependent STING signaling is a crucial regulator of anti-HER2 immune response in HER2+ breast cancer
Authors: Ong Li-Teng , Lee Wee Chyan , Ma Shijun , Oguz Gokce , Niu Zhitong , Bao Yi , Yusuf Mubaraka , Lee Puay Leng , Goh Jian Yuan , Wang Panpan , Yong Kylie Su Mei , Chen Qingfeng , Wang Wenyu , Ramasamy Adaikalavan , Hoon Dave S. B. , Ditzel Henrik J. , Tan Ern Yu , Lee Soo Chin , Yu Qiang
Published: July 2022

Relapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2
+
breast cancer (BC), is associated with residual disease progression due to resistance to therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling as a significant determinant of trastuzumab responses in HER2
+
BC. We show that down-regulation of immune-regulated genes (IRG) is specifically associated with poor survival of HER2
+
, but not other BC subtypes. Among IRG, IFI16 is identified as a direct target of EZH2, the underexpression of which leads to deficient STING activation and downstream CXCL10/11 expression in response to trastuzumab treatment. Dual inhibition of EZH2 and histone deacetylase (HDAC) significantly activates IFI16-dependent immune responses to trastuzumab. Notably, a combination of a novel histone methylation inhibitor with an HDAC inhibitor induces complete tumor eradication and long-term T cell memory in a HER2
+
BC mouse model. Our findings demonstrate an epigenetic regulatory mechanism suppressing the expression of the IFI16-CXCL10/11 signaling pathway that provides a survival advantage to HER2
+
BC to confer resistance to trastuzumab treatment.
Physical and in silico immunopeptidomic profiling of a cancer antigen prostatic acid phosphatase reveals targets enabling TCR isolation
Authors: Mao Zhiyuan , Nesterenko Pavlo A. , McLaughlin Jami , Deng Weixian , Burton Sojo Giselle , Cheng Donghui , Noguchi Miyako , Chour William , DeLucia Diana C. , Finton Kathryn A. , Qin Yu , Obusan Matthew B. , Tran Wendy , Wang Liang , Bangayan Nathanael J. , Ta Lisa , Chen Chia-Chun , Seet Christopher S. , Crooks Gay M. , Phillips John W. , Heath James R. , Strong Roland K. , Lee John K. , Wohlschlegel James A. , Witte Owen N.
Published: July 2022

Tissue-specific antigens can serve as targets for adoptive T cell transfer-based cancer immunotherapy. Recognition of tumor by T cells is mediated by interaction between peptide–major histocompatibility complexes (pMHCs) and T cell receptors (TCRs). Revealing the identity of peptides bound to MHC is critical in discovering cognate TCRs and predicting potential toxicity. We performed multimodal immunopeptidomic analyses for human prostatic acid phosphatase (PAP), a well-recognized tissue antigen. Three physical methods, including mild acid elution, coimmunoprecipitation, and secreted MHC precipitation, were used to capture a thorough signature of PAP on HLA-A*02:01. Eleven PAP peptides that are potentially A*02:01-restricted were identified, including five predicted strong binders by NetMHCpan 4.0. Peripheral blood mononuclear cells (PBMCs) from more than 20 healthy donors were screened with the PAP peptides. Seven cognate TCRs were isolated which can recognize three distinct epitopes when expressed in PBMCs. One TCR shows reactivity toward cell lines expressing both full-length PAP and HLA-A*02:01. Our results show that a combined multimodal immunopeptidomic approach is productive in revealing target peptides and defining the cloned TCR sequences reactive with prostatic acid phosphatase epitopes.
The new species and the third Chinese member of
Colubrina
(
C. zhaoguangii
, Rhamnaceae)
Authors: Hu Jun , Liu Wei-Li , Jiang Hong , Liu Qing , Yang Yi
Published: July 2022

A novel species of Rhamnaceae,
Colubrina zhaoguangii
, is discovered in Sichuan, China, during the biodiversity investigations of the Second Tibetan Plateau Scientific Expedition and Research. Detailed descriptions and illustrations of the new species are presented herein. To date, the new species is only found in dry-warm river valleys of the Jinsha River basin in the Hengduan Mountains region (HDM). Compared with the other two known Chinese
Colubrina
species,
C. zhaoguangii
features by the habit of twisted shrub and tiny leaves with emarginate apex. In morphology, the new species highly resembles
C. alluaudii
endemic in Madagascar and
C. viridis
in northwestern Mexico, whereas it is distinguished from these two relatives by its minutely white scales on the leaf blades. The discovery of
C. zhaoguangii
reminds us again that the bottom region is also important for biodiversity conservation in HDM and should be a flora survey priority.
Approximation of discontinuous inverse operators with neural networks
Authors: Massa Paolo , Garbarino Sara , Benvenuto Federico
Published: July 2022

In this work we deal with parametric inverse problems, which consist in recovering a finite number of parameters describing the structure of an unknown object, from indirect measurements. State-of-the-art methods for approximating a regularizing inverse operator by using a dataset of input–output pairs of the forward model rely on deep learning techniques. In these approaches, a neural network (NN) is trained to predict the value of the sought parameters directly from the data. In this paper, we show that these methods provide suboptimal results when a regularizing inverse operator is discontinuous with respect to the Euclidean topology. Hence, we propose a two-step strategy for approximating it by means of a NN, which works under general topological conditions. First, we embed the parameters into a subspace of a low-dimensional Euclidean space; second, we use a NN to approximate a homeomorphism between the subspace and the image of the parameter space through the forward operator. The parameters are then retrieved by applying the inverse of the embedding to the network predictions. The results are shown for the problem of x-ray imaging of solar flares with data from the Spectrometer/Telescope for Imaging X-rays. In this case, the parameter space is homeomorphic to a Moebius strip. Our simulation studies show that the use of a NN for predicting the parameters directly from the data yields systematic errors due to the non-Euclidean topology of the parameter space. The proposed strategy overcomes the discontinuity issues and furnishes stable and accurate reconstructions.
Performance analysis for unconstrained analysis based approaches*
Authors: Ge Huanmin , Chen Wengu , Li Dongfang , Wu Fengyan
Published: July 2022

Efficient recovery of sparse signals from underdetermined linear systems has received extensive attentions in recent decade. This paper considers the stable recovery of a signal
x
, which is not k-sparse itself but is k-sparse in terms of a Parseval frame
D
, from the observations
y
=
Ax
+
e
via three unconstrained minimization approaches. We show that if the sensing matrix
A
satisfies the restricted isometry property adapted to
D
with

δ

t
k

<

t
−
1

t
+
8

for any t > 1, then these three approaches can stably recover
x
. As a consequence, when t = 2 and 3, our result significantly improves existing best sufficient conditions. Furthermore, we theoretically characterize the recovery errors of these methods.
Performance of metal-semiconductor-metal structured diamond deep-ultraviolet photodetector with a large active area
Authors: Feng Mengyang , Jin Peng , Meng Xianquan , Xu Pengfei , Huo Xiaodi , Zhou Guangdi , Qu Pengfei , Wu Ju , Wang Zhanguo
Published: July 2022

In this work, the uniformity is significantly improved of the photoresist film spinning-coated on the small-size diamond wafer by inlaying the diamond wafer into a 1-inch polytetrafluoroethylene substrate; consequently, the utilizable surface area of the diamond wafer is remarkably increased. As a result, the interdigital electrodes of 2.5 mm × 2.5 mm in dimension are prepared on the single crystal diamond (5 mm × 5 mm × 0.5 mm) and a metal–semiconductor–metal structured diamond deep-ultraviolet photodetector with a large active area of 3.093 mm2 has been fabricated. Compared to the maximum values of the interdigital-typed intrinsic diamond deep-ultraviolet photodetectors, the active area is increased by more than six times, and the photocurrent reaches the order of milliampere, which is about two orders of magnitude larger. Meanwhile, the responsivity and external quantum efficiency are 56.3 A W−1 and 328, respectively, at 50 V bias under 3.125 μW mm−2 213 nm illumination, and the corresponding mobility-lifetime product of the diamond wafer is 1.11 × 10−5 cm2 V−1. As the voltage continued to increase, which still maintained an upward trend and did not appear saturated; the corresponding responsivity is up to 275.9 A W−1 at 120 V. In addition, the ultraviolet-visible light discrimination ratio is 1.4 × 104 at 10 V, and the carrier transit time between interdigital electrodes is measured to be only about 1 ns (excited by a 213 nm pulse laser), which shows that the photodetector has an ultrafast response speed.
DeTransUnet: attenuation correction of gated cardiac images without structural information
Authors: Wang Bo , Lu Lijun , Liu Huafeng
Published: July 2022

Objective. Myocardial perfusion imaging (MPI) with positron emission tomography (PET) is a non-invasive imaging method, and it is of great significance to the diagnosis and prognosis of coronary heart disease. Attenuation correction (AC) for PET images is a necessary step for further quantitative analysis. In order not to use magnetic resonance (MR) or computed tomography (CT) images for AC, this work proposes DeTransUnet to obtain AC PET images directly from no-attenuation corrected (NAC) PET images. Approach. The proposed DeTransUnet is a 3D structure which combines the multi-scale deformable transformer layers and the 3D convolutional neural network (CNN). And it integrates the advantages of transformer with long-range dependence and CNN suitable for image calculation. The AC images using CT images for AC and scatter correction (SC) and are considered as training labels, while the NAC images are reconstructed without AC and SC. Standard uptake value (SUV) values are calculated for both NAC and AC images to exclude the influence of weight and injection dose. With NAC SUV images as the inputs of the DeTransUnet, the outputs of DeTransUnet are AC SUV images. Main results. The proposed DeTransUnet was performed on an MPI gated-PET dataset, and the results were compared with Unet2D and Unet2.5D. The metrics of the whole image and the left ventricular myocardium show that the proposed method has advantages over other deep learning methods. Significance. The proposed DeTransUnet is a novel AC framework that does not require CT or MR images. It can be used as an independent AC method on PET/MR instrument. In addition, when CT images contain defects or cannot be registered with PET images on PET/CT instrument, DeTransUnet is able to repair the defects and keep consistent with the NAC images.
Runaway electron deconfinement in SPARC and DIII-D by a passive 3D coil
Authors: Izzo V.A. , Pusztai I. , Särkimäki K. , Sundström A. , Garnier D.T. , Weisberg D. , Tinguely R.A. , Paz-Soldan C. , Granetz R.S. , Sweeney R.
Published: July 2022

The operation of a 3D coil—passively driven by the current quench (CQ) loop voltage—for the deconfinement of runaway electrons (REs) is modeled for disruption scenarios in the SPARC and DIII-D tokamaks. Nonlinear magnetohydrodynamic (MHD) modeling is carried out with the NIMROD code including time-dependent magnetic field boundary conditions to simulate the effect of the coil. Further modeling in some cases uses the ASCOT5 code to calculate advection and diffusion coefficients for REs based on the NIMROD-calculated fields, and the DREAM code to compute the runaway evolution in the presence of these transport coefficients. Compared with similar modeling in Tinguely et al (2021 Nucl. Fusion
61 124003), considerably more conservative assumptions are made with the ASCOT5 results, zeroing low levels of transport, particularly in regions in which closed flux surfaces have reformed. Of three coil geometries considered in SPARC, only the n = 1 coil is found to have sufficient resonant components to suppress the runaway current growth. Without the new conservative transport assumptions, full suppression of the RE current is maintained when the thermal quench MHD is included in the simulation or when the RE current is limited to 250kA, but when transport in closed flux regions is fully suppressed, these scenarios allow RE beams on the order of 1–2 MA to appear. Additional modeling is performed to consider the effects of the close ideal wall. In DIII-D, the CQ is modeled for both limited and diverted equilibrium shapes. In the limited shape, the onset of stochasticity is found to be insensitive to the coil current amplitude and governed largely by the evolution of the safety-factor profile. In both devices, prediction of the q-profile evolution is seen to be critical to predicting the later time effects of the coil.
Investigation of the rheological parameters of a complex homogenate (dough model) prepared from flour and fractions of an electrochemically activated water
Authors: Pogorelov A G , Chernykh V Ya , Bulavina T A , Suvorov O A , Kuznetsov A L , Ipatova L G
Published: July 2022

One of the directions for improving existing and creating new technologies for bakery products can be associated with the regulation of dough making processes through the use of electrochemically activated (ECA) water during kneading. By the ECA water method in the zone of one of the electrodes (anode or cathode) of the diaphragm reactor, respectively, anolyte or catholyte is obtained, which have a number of anomalous properties during the relaxation period. The ECA method allows you to purposefully change the structure of water, pH and redox potential, catalytic, biological and chemical activity. The purpose of the research is to study the effect of ECA water fractions on the rheological parameters of a heterophase homogenate during the formation of its structure during kneading before readiness and after the kneading operation. Conditional and classical rheological characteristics were determined using a texture analyzer device. In the work, the rheodynamics of mixing wheat bakery flour of the highest grade with various fractions of ECA water was established. It was revealed that the anodic and cathodic fractions of the ECA water, depending on the duration of treatment and the pH and RP indices, have a different effect on the structural, mechanical and rheological characteristics of the flour homogenate. The freshly prepared activated water fraction after 30 min of anodic treatment (sample A30) had a greater effect on the rheodynamics of the wheat dough kneading. The dough formed using the specified water sample was characterized by maximum stability, increased by 58% compared to other samples. The homogenate formed with the A30 sample is characterized by the longest dough kneading time to readiness (2.8 min), the highest dough stability during kneading (9.8 min) and, accordingly, the highest flour quality indicator (QN 73 mm). At the same time, the dough-thinning index reaches the minimum values of 40/62, which confirms the tendency for a decrease in the activity of wheat flour amylases in terms of the "Falling Number" indicator.
Techno chemical characteristics of secondary raw materials formed when cutting rainbow trout
Authors: Sokolov A V , Dvoryaninova O P , Sukharev I N , Shubkin S Yu , Zakharov V L
Published: July 2022

The article assesses the biotechnological potential of the minor parts formed when cutting rainbow trout. It was found that the share of secondary parts accounts for 52.2%. This result allows showing the relevance and expediency of developing measures for their rational use and involvement in the production of products for various purposes. Research has been carried out on the chemical, amino acid, and mineral compositions of the minor parts of rainbow trout. The study results showed that the minor parts of rainbow trout have a high biological value of protein. The content of all essential amino acids is rich in macro-and microelements. It is shown that a high mass fraction of protein (15.41-58.46%) in the minor parts of rainbow trout opens excellent prospects for organizing their collection, accumulation, and processing.
Lean method for development of thermal treatment regimes for canned food from aquatic organisms for industry autoclaves
Authors: Kaychenov A , Stolyanov A , Zhuk A
Published: July 2022

The article describes the lean method developed by the authors, which can be used in the development and scientific substantiation of experimental canned food heat treatment regimes for an industrial autoclave at the preliminary selection stage. The ways for improving the lean method to modernized using methods and means of automation are considered. The modernized method application will allow the fishing enterprises to increase efficiency within the lean production concept. The laboratory autoclave AVK-30M, the industrial autoclave ASCAMAT-230 and their automatic control systems are described. The description of experimental study for the development canned food heat treatment regimes is considered.
Difference in the composition of the volatile odor fraction of tilapia meat samples grown under aquaculture conditions in Russia and China
Authors: Sokolov A V , Dvoryaninova O P , Solovyova E A , Syanov D A , Storublevtsev S A
Published: July 2022

China is one of the leading suppliers of fish and seafood to Russia. A strong example is tilapia fish. This relatively inexpensive fish, due to the small amount of its cultivation in the Russian Federation, is completely imported from China. However, at present, the lack of an adequate level of control over the movement of raw materials through production chains and their processing at Chinese enterprises, the import of tilapia is temporarily stopped. In this regard, a comparative assessment of the quality of tilapia grown under aquaculture conditions in Russia and China at all stages of industrial processing is relevant. In order to assess the quality of fish raw materials, a multisensory system “electronic nose” was used, which is based on a multilevel neural semiotic model that describes the mechanism of the human olfactory bulb. The use of chemical sensors allowed recording early signs of changes in the organoleptic parameters of tilapia meat. The studies showed that the meat of tilapia grown in Russia is subject to less destruction during storage at a temperature of 4 ° C than meat of tilapia grown under the agricultural conditions in China.
Analysis and optimization of the structure of liquid phase flows in extractors of multiple irrigation of the oil-containing material with an extractant
Authors: Tsebrenko K N , Derevenko V V , Sevryugina N I
Published: July 2022

The analysis of the flows structure in extractors operating by the method of multiple irrigation of the oil-containing material with an extractant (extractive agent) has been carried out. The features of the mass transfer process are considered using experimental data on the equilibrium: in the system the oil-containing material is the extractant and the kinetics of the extraction of the oil-bearing material. Experimental data of the concentration of miscella at each stage of a belt extractor operating according to the method of multi-stage irrigation were obtained under production conditions. Based on the data obtained, a working line of the extraction process for this extractor (extraction unit) was constructed, which made it possible to substantiate the ways of improving the structure of the liquid phase flows in it. The improvement of the streams structure of the liquid phase of the belt extractors is carried out on the basis of mathematical modeling of the process of extracting oil from the oil-containing material. We take into account the effect of reverse recirculation of the extractant and the dynamics of moving the extractant in the solid phase in the zone of no irrigation. It is shown that it is possible to intensify the extraction process by organizing an additional injection of the extractant at the last stage of the extractor. A numerical experiment was carried out on the basis of the developed mathematical model, which takes into account the additional injection of the solvent. As a result, it was found that the proposed solution allows reducing the oil content of the meal to 0.8%.
Study of ascorbic acid stabilization conditions in fresh juices
Authors: Kaisheva N S , Kaishev A Sh , Larsky M V , Karpenko V A
Published: July 2022

For the first time the possibility of using purified pectins to stabilize ascorbic acid (AA) in fresh juices was considered and proved. The purpose of the study was to analyze the possibility of using purified pectins to stabilize AA in fresh juices with a concentration of 1⋅10-6-1⋅10-4g/ml. The work used AA, oxalic acid (OA), as well as beet (BP), citrus (CP) and apple (AP) pectins. There was no interfering effect of pectins on AA determination by differential UV spectroscopy. The specific absorption rate of AA (727) was determined, according to which the AA content in model solutions with auxiliary substances during storage was estimated. The optimal weight ratio AA:AP 1:16 used for blending fresh juices, in which the AA concentration was previously determined by titration with 2.6-dichlorophenolindophenolate sodium, was established. It was revealed that AP contributes to the pH shift to the optimal pH area for AA 4.5-8.0; increase of juice viscosity by 5-148% and storage life by 3.3-59 times. The relative error of definitions did not exceed ±5.6%.
Processing of after-alcohol vinasse for environmentally friendly environment
Authors: Kaishev A Sh , Kaisheva N Sh , Larsky M V , Karpenko V A
Published: July 2022

One of the industrial sources of intoxication polluting the environment is vinasse – a secondary raw material formed during the alcoholic processing of grain in 12 times the volume of alcohol produced. Due to the low content of dry substances (up to 8%), low shelf life (up to 2 days), seasonality of consumption in livestock, the transportation, especially the liquid phase of vinasse, is not economically profitable, which causes the need for its disposal or processing and determines the relevance of this study. Based on the chemical composition of vinasse, the purpose of the study is to study the possibility of obtaining pectins from it as biologically active compounds, which would reduce the volume of vinasse released into the environment thus ensuring its protection. The purpose of the study was fulfilled by solving the following tasks: development of a method of pectins release from vinasse, assessment of their physicochemical and biological properties, determination of chemical and microbiological safety of vinasse wastes. The study included technological, physicochemical, chemical, biological methods. Vinasse fractions were obtained according to the developed method of vinasse processing based on vortex extraction, concentration of extractions, alcohol release of the end products, pectins from liquid (yield 3.1%) and solid (yield 2.9%), which ensured a 20-fold reduction in the volume of vinasse. The characteristics of pectins were established: authenticity, loss in mass during drying, pH, molar mass, content of pectic acid, functional groups, binding properties. The safety and gastroprotective activity of pectins was established. Mother solutions after the release of pectins were estimated to be less than 3.9 times the chemical consumption of oxygen and satisfactory microbiological purity, which made it possible to evaluate them as safe industrial waste.
Lifetime Exposure to Welding Fumes and Risk of Some Rare Cancers
Authors: Kendzia Benjamin , Kaerlev Linda , Ahrens Wolfgang , Merletti Franco , Eriksson Mikael , Guénel Pascal , Lynge Elsebeth , Costa-Pereira Altamiro , Morales Suárez-Varela Maria , Jöckel Karl-Heinz , Stang Andreas , Behrens Thomas
Published: July 2022

We investigated the association between exposure to welding fumes and the risk of biliary tract, male breast, bone, and thymus cancer, as well as cancer of the small intestine, eye melanoma, and mycosis fungoides, among men in a European, multicenter case-control study. From 1995–1997, 644 cases and 1,959 control subjects from 7 countries were studied with respect to information on welding and potential confounders. We linked the welding histories of the participants with a measurement-based exposure matrix to calculate lifetime exposure to welding fumes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models, conditional on country and 5-year age groups, and adjusted for education and relevant confounders. Regular welding was associated with an increased risk of cancer of the small intestine (OR = 2.30, 95% CI: 1.17, 4.50). Lifetime exposure to welding fumes above the median of exposed controls was associated with an increased risk of cancer of the small intestine (OR = 2.00, 95% CI: 1.07, 3.72) and male breast (OR = 2.07, 95% CI: 1.14, 3.77), and some elevation in risk was apparent for bone cancer (OR = 1.92, 95% CI: 0.85, 4.34) with increasing lifetime exposure to welding fumes. Welding fumes could contribute to an increased risk of some rare cancers.
Transporting a Prediction Model for Use in a New Target Population
Authors: Steingrimsson Jon A , Gatsonis Constantine , Li Bing , Dahabreh Issa J
Published: July 2022

We considered methods for transporting a prediction model for use in a new target population, both when outcome and covariate data for model development are available from a source population that has a different covariate distribution compared with the target population and when covariate data (but not outcome data) are available from the target population. We discuss how to tailor the prediction model to account for differences in the data distribution between the source population and the target population. We also discuss how to assess the model’s performance (e.g., by estimating the mean squared prediction error) in the target population. We provide identifiability results for measures of model performance in the target population for a potentially misspecified prediction model under a sampling design where the source and the target population samples are obtained separately. We introduce the concept of prediction error modifiers that can be used to reason about tailoring measures of model performance to the target population. We illustrate the methods in simulated data and apply them to transport a prediction model for lung cancer diagnosis from the National Lung Screening Trial to the nationally representative target population of trial-eligible individuals in the National Health and Nutrition Examination Survey.
A clinician’s guide for counseling patients on results of a multigene pharmacogenomic panel
Authors: Ho Teresa T , Bell Gillian , Gammal Roseann S , Gregornik David , Wake Dyson T , Dunnenberger Henry M
Published: July 2022

Purpose

This article explores approaches to pharmacogenomic counseling for patients who have undergone multigene panel testing by describing the collective experience of 5 institutions.

Multigene panel pharmacogenomic testing has the potential to unlock a myriad of information about a patient’s past, present, and future drug response. The multifaceted nature of drug response coupled with the complexity of genetic results necessitates some form of patient education through pharmacogenomic counseling. Published literature regarding disclosure of pharmacogenomic test results is limited. This article compares the counseling practices of pharmacists from 5 different institutions with pharmacogenomics clinics whose experience represents perspectives ranging from academia to community clinical environments. Overarching counseling themes discussed during result disclosure center around (1) pharmacogenomic results, (2) gene-drug interactions, (3) gene-drug-drug interactions, (4) drug changes (5) future, familial, or disease-risk implications, (6) updates in the interpretation and application of pharmacogenomic results, (7) gauging patient comprehension, and (8) sharing results and supplemental information.

Conclusion

Dedicating time to counseling patients on the results of a multigene pharmacogenomic panel is important given the lifelong applications of a test that is generally performed only once. The content and methods of disclosing test results shared by the experiences of pharmacists at 5 different institutions serve as guide to be further refined as research addresses effective communication strategies that enhance patient comprehension of pharmacogenomic results.
Synchronizing spermatogenesis in the mouse
Authors: Griswold Michael , Hogarth Cathryn
Published: July 2022

The formation of spermatozoa starts with a germ-line stem cell creating a pool of progenitor cells or undifferentiated spermatogonia. There is a requirement for these progenitor cells to be stimulated by retinoic acid (RA) to enter differentiation and ultimately form spermatocytes, undergo meiosis, form spermatids, and ultimately spermatozoa. After the stimulation by RA, which occurs at sites in the seminiferous tubules, it takes ~35 days to complete this complex process. As a result, the adult testis contains germ cells in all possible states of differentiation, and the isolation of individual cell types or study of functional aspects of the cycle of the seminiferous epithelium is very difficult. We describe the use of WIN 18 446—an inhibitor of RA synthesis followed by injection of RA as a mechanism for the synchronization of spermatogenesis to one to three stages of the cycle of the seminiferous epithelium. The result is that only one to four germ cell types are prevalent during the first wave of spermatogenesis. In the adult only a predictable few stages of the cycle are present throughout the entire testis enriching the targeted cells or stages of the cycle.
Increasing the use of perioperative risk scoring in emergency laparotomy: nationwide quality improvement programme
Authors: Nally Deirdre M , Lonergan Peter E , O’Connell Emer P , McNamara Deborah A ,   the SURGical Improvement Network (SURGIN), Elwahab S Abd , Bass G , Burke E , Cagney D , Canas A , Cronin C , Cullinane C , Devane L , Fearon N , Fowler A , Fullard A , Hechtl D , Kelly M , Lenihan J , Murphy E , Neary C , O'Connell R , O'Neill M , Ramkaran C , Troy A , Tully R , White C , Yadav H
Published: July 2022

Background

Emergency laparotomy is associated with high morbidity and mortality. The early identification of high-risk patients allows for timely perioperative care and appropriate resource allocation. The aim of this study was to develop a nationwide surgical trainee-led quality improvement (QI) programme to increase the use of perioperative risk scoring in emergency laparotomy.

Methods

The programme was structured using the active implementation framework in 15 state-funded Irish hospitals to guide the staged implementation of perioperative risk scoring. The primary outcome was a recorded preoperative risk score for patients undergoing an emergency laparotomy at each site.

Results

The rate of patients undergoing emergency laparotomy receiving a perioperative risk score increased from 0–11 per cent during the exploratory phase to 35–100 per cent during the full implementation phase. Crucial factors for implementing changes included an experienced central team providing implementation support, collaborator engagement, and effective communication and social relationships.

Conclusions

A trainee-led QI programme increased the use of perioperative risk assessment in patients undergoing emergency laparotomy, with the potential to improve patient outcomes and care delivery.
Negative symptoms, striatal dopamine and model-free reward decision-making in schizophrenia
Authors: Brandl Felix , Knolle Franziska , Avram Mihai , Leucht Claudia , Yakushev Igor , Priller Josef , Leucht Stefan , Ziegler Sibylle , Wunderlich Klaus , Sorg Christian
Published: July 2022

Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, impaired influences of both model-based and model-free reward predictions on decision-making (‘reward prediction influence’, RPI) underlie negative symptoms. We focused on psychotic remission, because psychotic symptoms might confound reward-based decision-making. Moreover, we hypothesized that impaired model-based/model-free RPIs depend on alterations of both associative striatum dopamine synthesis and storage (DSS) and executive functioning. Both factors influence RPI in healthy subjects and are typically impaired in schizophrenia.

Twenty-five patients with schizophrenia with pronounced negative symptoms during psychotic remission and 24 healthy controls were included in the study. Negative symptom severity was measured by the Positive and Negative Syndrome Scale negative subscale, model-based/model-free RPI by the two-stage decision task, associative striatum DSS by 18F-DOPA positron emission tomography and executive functioning by the symbol coding task.

Model-free RPI was selectively reduced in patients and associated with negative symptom severity as well as with reduced associative striatum DSS (in patients only) and executive functions (both in patients and controls). In contrast, model-based RPI was not altered in patients.

Results provide evidence for impaired model-free reward prediction influence as a mechanism for negative symptoms in schizophrenia as well as for reduced associative striatum dopamine and executive dysfunction as relevant factors. Data suggest potential treatment targets for patients with schizophrenia and pronounced negative symptoms.
A case report of myocarditis secondary to eosinophilic granulomatosis with polyangiitis
Authors: Condurache Dorina-Gabriela , Raisi-Estabragh Zahra , Baslas Rohit , Hamdulay Shahir
Published: July 2022

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. Cardiac involvement is the major cause of morbidity and mortality in these patients. Early recognition and treatment initiation for such manifestations are key to improved patient outcomes.

Case summary

We report the case of a 60-year-old man with a history of therapy-resistant asthma and rhinitis. He presented with acute chest pain, sinus tachycardia, and marked peripheral eosinophilia. Transthoracic echocardiogram (TTE) showed segmental anterior left ventricular (LV) wall motion abnormalities with impaired systolic function (LV ejection fraction 45%) and a small pericardial effusion. Invasive coronary angiography revealed unobstructed coronary arteries. Cardiac magnetic resonance imaging confirmed the TTE findings and demonstrated oedema and active inflammation of the anterior and anteroseptal LV segments [Short inversion time recovery (STIR)-T2] and an unusual pattern of non-ischaemic late gadolinium enhancement extending across multiple coronary territories. Autoantibody testing detected a positive P-ANCA and myeloperoxidase (MPO) antibodies. Overall, the investigation findings supported a diagnosis of ANCA-positive EGPA with acute myocardial involvement. He was initially treated with high-dose corticosteroids, cyclophosphamide, and rituximab. The patient had a good symptomatic and biochemical (normalized troponin T and MPO titre) recovery. In addition, subsequent TTE showed improvement of LV systolic function and resolution of regional wall motion abnormalities.

Discussion

In this case, prompt diagnosis facilitated early initiation of immunosuppressive therapy and disease remission. CMR provides non-invasive assessment of myocardial tissue characterization and, used in conjunction with other tools, can be instrumental in detecting myocardial involvement in EGPA.
Dynamic improvement of an acute exacerbated subaortic pressure gradient after intravenous propranolol and cibenzoline, recorded using a pressure wire: a case report
Authors: Harano Yoshihiro , Kawase Yoshiaki , Matsuo Hitoshi
Published: July 2022

Background

Beta-blockers and Class 1A antiarrhythmics decrease the subaortic pressure gradient in hypertrophic obstructive cardiomyopathy. However, real-time monitoring of the pressure gradient transition during intravenous therapy, based on cardiac catheterization, has never been reported.

Case summary

A 52-year-old man, with an history of hypertension, was transferred to our hospital, complaining of angina. A 12-lead electrocardiogram showed diffuse ST-segment depression, and transthoracic echocardiography revealed a thickened left ventricular outflow tract (LVOT) septum, resulting in LVOT obstruction which had never been diagnosed. Besides, severe mitral regurgitation (MR) due to systolic anterior motion was detected. Emergent cardiac catheterization revealed normal coronary arteries and severe MR. Simultaneous pressure measurements were taken at the ascending aorta (using a coronary catheter) and left ventricle (using a pressure wire). The subaortic systolic pressure gradient was 147 mmHg: 251 mmHg in the left ventricle and 104 mmHg in the aorta. Intravenous cibenzoline, following propranolol, was administered to ameliorate the pressure gradient, following which his chest pain disappeared immediately; the pressure gradient decreased to 13 mmHg. Further, severe MR was diminished. Oral bisoprolol and cibenzoline administration effectively stabilized his condition after catheterization.

Discussion

Monitoring the simultaneous pressure between the left ventricle and aorta with a pressure wire revealed drastic improvement in the subaortic systolic pressure gradient. Owing to the soft, fine structure, the pressure wire allowed recording of the subaortic pressure gradient stably with less frequent premature ventricular contractions. Furthermore, this method could decrease the burden of catheter-related complications by eliminating the need for multiple atrial punctures.
iCOMIC: a graphical interface-driven bioinformatics pipeline for analyzing cancer omics data
Authors: Anilkumar Sithara Anjana , Maripuri Devi Priyanka , Moorthy Keerthika , Amirtha Ganesh Sai Sruthi , Philip Philge , Banerjee Shayantan , Sudhakar Malvika , Raman Karthik
Published: July 2022

Despite the tremendous increase in omics data generated by modern sequencing technologies, their analysis can be tricky and often requires substantial expertise in bioinformatics. To address this concern, we have developed a user-friendly pipeline to analyze (cancer) genomic data that takes in raw sequencing data (FASTQ format) as input and outputs insightful statistics. Our iCOMIC toolkit pipeline featuring many independent workflows is embedded in the popular Snakemake workflow management system. It can analyze whole-genome and transcriptome data and is characterized by a user-friendly GUI that offers several advantages, including minimal execution steps and eliminating the need for complex command-line arguments. Notably, we have integrated algorithms developed in-house to predict pathogenicity among cancer-causing mutations and differentiate between tumor suppressor genes and oncogenes from somatic mutation data. We benchmarked our tool against Genome In A Bottle benchmark dataset (NA12878) and got the highest F1 score of 0.971 and 0.988 for indels and SNPs, respectively, using the BWA MEM—GATK HC DNA-Seq pipeline. Similarly, we achieved a correlation coefficient of r = 0.85 using the HISAT2-StringTie-ballgown and STAR-StringTie-ballgown RNA-Seq pipelines on the human monocyte dataset (SRP082682). Overall, our tool enables easy analyses of omics datasets, significantly ameliorating complex data analysis pipelines.
Magnetic Resonance Imaging Proxies for Segmental Instability in Degenerative Lumbar Spondylolisthesis Patients
Authors: Forbech Elmose Signe , Oesterheden Andersen Mikkel , Sigmundsson Freyr G. , Yacat Carreon Leah
Published: July 2022

Study design:

Retrospective cohort study.

Objective:

The aim was to investigate whether findings on magnetic resonance imaging (MRI) can be proxies (MRIPs) for segmental instability in patients with degenerative lumbar spinal stenosis (LSS) and/or degenerative spondylolisthesis (LDS) L4/L5.

Background:

LDS has a heterogeneous nature. Some patients have a dynamic component of segmental instability associated with LDS. Studies have shown that MRI can show signs of instability.

Methods:

Patients with LSS or LDS at L4/L5 undergoing decompressive surgery±fusion from 2010 to 2017, with preoperative standing lateral spine radiographs and supine lumbar MRI and enrolled in Danish national spine surgical database, DaneSpine. Instability defined as slip of >3 mm on radiographs. Patients divided into two groups based upon presence of instability. Outcome measures: radiograph: sagittal slip (mm). MRIPs for instability: sagittal slip >3 mm, facet joint angle (°), facet joint effusion (mm), disk height index (%), and presence of vacuum phenomena. Optimal thresholds for MRIPs was determined by receiver operating characteristic (ROC) curves and area under the curve (AUC). Logistic regression to investigate association between instability and MRIPs.

Results:

Two hundred thirty-two patients: 47 stable group and 185 unstable group. The two groups were comparable with regard to baseline patient-reported outcome measures. Thresholds for MRIPs: bilateral facet joint angle ≥46°; bilateral facet effusion ≥1.5 mm and disk height index ≥13%. Logistic regression showed statistically significant association with MRIPs except vacuum phenomena, ROC curve AUC of 0.951. By absence of slip on MRI logistic regression showed statistically significant association between instability on radiograph and the remaining MRIPs, ROC curve AUC 0.757.

Conclusion:

Presence of MRIPs for instability showed statistically significant association with instability and excellent ability to predict instability on standing radiograph in LSS and LDS patients. Even in the absence of slip on MRI the MRIPs had a good ability to discriminate presence of instability.
DEEP LEARNING-BASED PREDICTION OF OUTCOMES FOLLOWING NONCOMPLICATED EPIRETINAL MEMBRANE SURGERY
Authors: Kim Soo Han , Ahn Honggi , Yang Sejung , Soo Kim Sung , Lee Jong Hyuck
Published: July 2022

Purpose:

We used deep learning to predict the final central foveal thickness (CFT), changes in CFT, final best corrected visual acuity, and best corrected visual acuity changes following noncomplicated idiopathic epiretinal membrane surgery.

Methods:

Data of patients who underwent noncomplicated epiretinal membrane surgery at Severance Hospital from January 1, 2010, to December 31, 2018, were reviewed. Patient age, sex, hypertension and diabetes statuses, and preoperative optical coherence tomography scans were noted. For image analysis and model development, a pre-trained VGG16 was adopted. The mean absolute error and coefficient of determination (R2) were used to evaluate the model performances. The study involved 688 eyes of 657 patients.

Results:

For final CFT, the mean absolute error was the lowest in the model that considered only clinical and demographic characteristics; the highest accuracy was achieved by the model that considered all clinical and surgical information. For CFT changes, models utilizing clinical and surgical information showed the best performance. However, our best model failed to predict the final best corrected visual acuity and best corrected visual acuity changes.

Conclusion:

A deep learning model predicted the final CFT and CFT changes in patients 1 year after epiretinal membrane surgery. Central foveal thickness prediction showed the best results when demographic factors, comorbid diseases, and surgical techniques were considered.
“Learn the Signs. Act Early.”: Updates and Implications for Physical Therapists
Authors: Kretch Kari S. , Willett Sandra L. , Hsu Lin-Ya , Sargent Barbara A. , Harbourne Regina T. , Dusing Stacey C.
Published: July 2022

Purpose:

In early 2022, the Centers for Disease Control and Prevention (CDC) updated their developmental surveillance milestone checklists. The purpose of this article is to clarify and interpret the updates from a physical therapist perspective and to discuss implications of the new milestones for physical therapists.

Summary of Key Points:

The CDC's updated checklists provide clear, consistent, easy to use, and evidence-based developmental milestones to prompt discussion with families. The new checklists do not represent a lowering of standards and will likely increase, not decrease, referrals for screening, evaluation, and services. Crawling has been removed from the milestone checklists, as the current evidence suggests that crawling is highly variable and not essential for development.

Conclusions and Recommendations for Clinical Practice:

The updated milestone checklists will facilitate bringing vital services to children who need them. Physical therapists should support our primary care colleagues in implementing this useful program.