bluuebunny/crossref_metadata_2025 huggingface dataset:
Indiana community health workers: challenges and opportunities for workforce development
Authors: Rodriguez Natalia M. , Ruiz Yumary , Meredith Ashley H. , Kimiecik Carlyn , Adeoye-Olatunde Omolola A. , Kimera Lynnet Francesca , Gonzalvo Jasmine D.
Published: January 2022

Background

An interest in, and the need for, Community Health Workers (CHWs) in the United States is growing exponentially. CHWs possess a unique ability to relate to and build trust with communities in order to improve clinical outcomes, while building individual and community capacity. Given their critical role in addressing social determinants of health, expanding the CHW workforce is crucial. However, creating CHW jobs, facilitating training and certification, and establishing sustainable financing models to support this workforce has been challenging.

Methods

A mixed-methods study consisting of an online survey and focus group discussions assessed the strengths, practices, and challenges to CHW workforce sustainability and expansion in the state of Indiana, including perspectives from both CHWs and employers.

Results

Across 8 topics, mixed data analysis revealed 28 findings that were both complementary and unique across focus group and survey results. Results highlighted CHW skills and attributes, illustrated the recruitment and hiring process, and provided insight into measuring outcomes and outputs. Findings also indicated a need to build position validation, professional development, and billing and reimbursement capacity.

Conclusion

Building and sustaining the CHW workforce will require creating an evidence base of roles and impact, increasing awareness of existing reimbursement mechanisms, and sharing best practices across employer organizations to promote optimal recruitment, training, supervision, career development, and funding strategies.
Impact of a school-based health intervention program on body composition among South African primary schoolchildren: results from the KaziAfya cluster-randomized controlled trial
Authors: Long Kurt Z. , Beckmann Johanna , Lang Christin , Seelig Harald , Nqweniso Siphesihle , Probst-Hensch Nicole , Müller Ivan , Pühse Uwe , Steinmann Peter , du Randt Rosa , Walter Cheryl , Utzinger Jürg , Gerber Markus
Published: January 2022

Background

The prevalence of overweight and obesity is increasing among African children potentially predisposing them to greater obesity and non-communicable diseases (NCDs) in adulthood. This risk may be higher among growth-impaired children who may have greater fat mass. Therefore, we examined the effects of school-based physical activity (PA) promotion and multi-micronutrient supplementation (MMNS) on body composition among South African children enrolled in a longitudinal school-based randomized controlled trial.

Methods

Children were cluster-randomized by class to one of four groups: (a) a physical activity group (PA), (b) a multi-micronutrient supplementation group (MMNS), (c) a physical activity + multi-micronutrient supplementation group (PA + MMNS), and (d) control group, and were being followed for 3 years. Linear random effects regression models with random intercepts for school classes tested the associations of each intervention arm with overall fat mass (FM), fat-free mass (FFM), truncal fat mass (TrFM), and truncal fat-free mass (TrFFM) at 9 months (T2) for boys and girls. These differences were then explored among children who differed in height velocity (HV).

Results

A total of 1304 children (614 girls, 667 boys) in twelve clusters were assessed at baseline and after 9 months follow-up (T2). At baseline, approximately 15% of children were classified as overweight or obese while approximately 38% of children were classified as mildly stunted or moderately/severely stunted. Among girls, promotion of PA was associated with reduced FM and TrFM at T2 while MMNS was associated with increased FFM. Children with reduced HV in the PA arm had reduced FM while children in the MMNS arm with lower HV had increased FFM compared to children in the control arm. Similarly, children with lower HV in the MM and PA groups had reduced TrFM compared to children in the control arm.

Conclusions

Our study suggests that the promotion of school-based physical activity programs and micronutrient supplementation can reduce childhood adiposity and so reduce the risk of obesity and chronic diseases later in adulthood.

Trial registration

ISRCTN, ISRCTN29534081. Registered on August 9, 2018. The trial was designed, analyzed, and interpreted based on the CONSORT protocol (Additional file 1: CONSORT checklist for randomized trial)
Malaria hospitalisation in East Africa: age, phenotype and transmission intensity
Authors: Kamau Alice , Paton Robert S. , Akech Samuel , Mpimbaza Arthur , Khazenzi Cynthia , Ogero Morris , Mumo Eda , Alegana Victor A. , Agweyu Ambrose , Mturi Neema , Mohammed Shebe , Bigogo Godfrey , Audi Allan , Kapisi James , Sserwanga Asadu , Namuganga Jane F. , Kariuki Simon , Otieno Nancy A. , Nyawanda Bryan O. , Olotu Ally , Salim Nahya , Athuman Thabit , Abdulla Salim , Mohamed Amina F. , Mtove George , Reyburn Hugh , Gupta Sunetra , Lourenço José , Bejon Philip , Snow Robert W.
Published: January 2022

Background

Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity.

Methods

Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2–10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models.

Results

52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2–10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2–10 < 5%), five low-moderate transmission (PfPR2–10 5–9%), 20 moderate transmission (PfPR2–10 10–29%) and 12 high transmission (PfPR2–10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69–85%) and rare among children aged 10–14 years (0.7–5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines.

Conclusions

Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2–23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.
Effect of the topical administration of corticosteroids and tuberculin pre-sensitisation on the diagnosis of tuberculosis in goats
Authors: Ortega J. , Roy A. , Díaz-Castillo A. , de Juan L. , Romero B. , Sáez-Llorente J. L. , Domínguez L. , Regal P. , Infantes-Lorenzo J. A. , Álvarez J. , Bezos J.
Published: January 2022

Background

Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals. In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed.

Methods

The animals (n = 151) were distributed into three groups: (1) a group topically treated with corticosteroids 48 h after intradermal tuberculin tests (n = 53); (2) a group pre-sensitised with bovine and avian purified protein derivatives (PPDs) 3 days before the intradermal tuberculin test used for TB diagnosis (n = 48); and (3) a control group (n = 50). All the animals were tested using single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, an interferon-gamma release assay (IGRA) and a P22 ELISA.

Results

The number of SIT test reactors was significantly lower in the group treated with corticosteroids when compared to the pre-sensitised (p < 0.001) and control (p = 0.036) groups. In contrast, pre-sensitisation with bovine and avian PPDs did not cause a significant reduction in the number of SIT and CIT test reactors compared with the control group. In fact, a higher number of reactors was observed after the prior tuberculin injection in the pre-sensitised group (p > 0.05). No significant effect was observed on IGRA and P22 ELISA due to corticosteroids administration. Nevertheless, a previous PPD injection affected the IGRA performance in some groups.

Conclusions

The application of topical corticosteroid 24 h before reading the SIT and CIT tests can reduce the increase in skin fold thickness and subsequently significantly decrease the number of positive reactors. Corticosteroids used can be detected in hair samples. A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs.
Comprehensive evaluation of left ventricular deformation using speckle tracking echocardiography in normal children: comparison of three-dimensional and two-dimensional approaches
Authors: Aly Doaa , Madan Nitin , Kuzava Laura , Samrany Alison , Parthiban Anitha
Published: January 2022

Background

Three-dimensional (3D) speckle tracking echocardiography (STE) can overcome some of the inherent limitations of two-dimensional (2D) STE; however, clinical experience is lacking. We aimed to assess and compare the feasibility, agreement, and reproducibility of left ventricular (LV) global longitudinal (GLS), and regional strain by 3D vs 2D STE in normal children.

Methods

Healthy pediatric subjects (n = 105, age mean = 11.2 ± 5.5 years) were prospectively enrolled. Three-dimensional and 2D LV GLS, as well as regional strain in 16 myocardial segments were quantified. Bland Altman analysis, intra- class correlation coefficients (ICC), percent error and linear regression were used for agreement and correlation between the two techniques. Analysis and acquisition times were compared. Inter- and intra-observer reproducibility was assessed in 20 studies.

Results

There was good to excellent agreement for 2D and 3D global longitudinal strain (ICC =0.82) and modest agreement for regional strain (ICC range 0.43–0.71). Both methods had high feasibility (88.6% for 2D vs 85.7% for 3D, p = 0.21), although 3D STE required significantly shorter acquisition and analysis time than 2D STE (acquisition time 1 ± 1.2 mins vs 2.4 ± 1 mins; p = 0.03, analysis time = 3.3 ± 1 mins vs 8.2 ± 2.5 mins; p = 0.001, respectively). Inter and intra-observer reproducibility was excellent for GLS by the two techniques (ICC = 0.78–0.93) but moderate to poor for regional strain (ICC = 0.21–0.64).

Conclusion

Three-dimensional global LV strain is as feasible and reproducible as 2D strain, with good agreement yet significantly more efficient acquisition and analysis. Regional strain is less concordant and 2D and 3D values should not be used interchangeably. 3D LV GLS may represent a viable alternative in evaluation of LV deformation in pediatric subjects.
Comparisons of benefits and risks of single embryo transfer versus double embryo transfer: a systematic review and meta-analysis
Authors: Ma Shujuan , Peng Yangqin , Hu Liang , Wang Xiaojuan , Xiong Yiquan , Tang Yi , Tan Jing , Gong Fei
Published: January 2022

Background

Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET) versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those women with a defined embryo quality or advanced age.

Methods

A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane Library andClinicalTrials.govwere searched based on established search strategy from inception through February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0.

Results

Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared with DET, SET decreased the probability of a live birth (OR = 0.78, 95% CI: 0.71–0.85,P < 0.001,n = 62), and lowered the rate of multiple pregnancy (0.05, 0.04–0.06,P < 0.001,n = 45). In the sub-analyses of age stratification, both the differences of LBR (0.87, 0.54–1.40,P = 0.565,n = 4) and MPR (0.34, 0.06–2.03,P = 0.236,n = 3) between SET and DET groups became insignificant in patients aged ≥40 years. No significant difference in LBR for single GQE versus two embryos of mixed quality [GQE + PQE (non-good quality embryo)] (0.99, 0.77–1.27,P = 0.915,n = 8), nor any difference of MPR in single PQE versus two PQEs (0.23, 0.04–1.49,P = 0.123,n = 6). Moreover, women who conceived through SET were associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage (0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1 < 7 rate (0.12, 0.02-0.93) or neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET.

Conclusions

In women aged < 40 years or if any GQE is available, SET should be incorporated into clinical practice. While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40 years, current evidence is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed.
Genome-scale CRISPR screens identify host factors that promote human coronavirus infection
Authors: Grodzki Marco , Bluhm Andrew P. , Schaefer Moritz , Tagmount Abderrahmane , Russo Max , Sobh Amin , Rafiee Roya , Vulpe Chris D. , Karst Stephanie M. , Norris Michael H.
Published: January 2022

Background

The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as of December 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as antigenically novel SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design.

Methods

To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. Gene knockdown, CRISPR knockout, and small molecule testing in Vero, HEK293, and human small airway epithelial cells were used to verify our findings.

Results

While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. The website https://sarscrisprscreens.epi.ufl.edu/ was created to allow visualization and comparison of SARS-CoV2 CRISPR screens in a uniformly analyzed way. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. The role of EDC4 and XRN1 in coronavirus replication in human small airway epithelial cells was verified. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens.

Conclusions

Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development.
Purification and characterization of antibacterial surfactin isoforms produced by Bacillus velezensis SK
Authors: Barale Sagar S. , Ghane Savaliram G. , Sonawane Kailas D.
Published: January 2022

Bacillus velezensis SK having broad-spectrum antimicrobial activity has been isolated from soil. The efficient extraction of antimicrobial compounds produced in various mediums has been done using Diaion HP-20 resin. Further, characterization of an antimicrobial compound by TLC, FTIR, in-situ bioautography analysis revealed the presence of cyclic lipopeptides, which is then purified by the combination of silica gel, size exclusion, dual gradient, and RP-HPLC chromatography techniques. Growth kinetic studies showed that Bacillus velezensis SK produces a mixture of lipopeptides (1.33 gL−1). The lipopeptide exhibits good pH (2–10) and temperature stability up to 80 °C. LC–ESI–MS analysis of partially purified lipopeptide identified variant of surfactin, further analysis of purified chromatographic fractions revealed the occurrence of most abundant C15-surfactin homologues (m/z 1036.72 Da). The isolated surfactin exhibits good antimicrobial activity (1600 AU/ml) against drug-resistant food-born B. cereus and human pathogen Staphylococcus aureus. Hence, identified strain B. velezensis SK and its potent antibacterial surfactin lipopeptide could be used in various food and biomedical applications.
(Re)production of symbolic boundaries between native and non-native teachers in the TESOL profession
Authors: Wright Natalia
Published: January 2022

Although various attempts to confront non-native teachers of English (NNESTs) marginalisation in the language teaching profession have taken place over the past few years, the English language teaching (ELT) domain clearly demonstrates quite the opposite; remaining structured and articulated by boundaries that are shaped by language ideologies, it marks an exclusion of non-native English teachers from participating in the field of foreign language teaching on equal terms with native English-speaking teachers (NESTs). Using a Bourdieusian lens (Bourdieu and Passeron in Reproduction in education, society and culture, Sage, London, 1990; Bourdieu in Language and symbolic power, Harvard University Press, Cambridge, 1991), this paper examines the way symbolic violence is exercised through exclusionary and discriminatory practices that arbitrarily impose the culture of a dominant group and result in the production and reproduction of symbolic boundaries between native and non-native teachers of English. In doing so, it calls for greater awareness among language educators of the power dynamics behind the simplistic ‘native’/’non-native’ dichotomies. Since nothing has been done so far to reconcile the two, the author believes that a continuous perception of NESTs and NNESTs as two different professional classes might serve the interest of those who wish to maintain such polarisation.
Grid power quality enhancement using an ANFIS optimized PI controller for DG
Authors: Bilgundi Srishail K. , Sachin R. , Pradeepa H. , Nagesh H. B. , Likith Kumar M. V.
Published: January 2022

Grid frequency variation causes phase angle deviation in current with respect to voltage. This is sensed at the phase-locked loop in the controller. In past studies the effect of grid frequency variation is neglected while designing the controller for power quality restoration. When modern grids are connected to large numbers of non-linear loads and various types of distributed generation (DG), it results in continuous variation in grid frequency. Thus it is necessary to consider the grid frequency variation for effective power quality restoration. However, tuning of conventional PI controller gains considering frequency variation is very difficult. Thus it is necessary to develop an adaptive intelligent nonlinear controller to tackle the effects of frequency variation, voltage distortion and non-linear load simultaneously. This paper presents the importance of considering the effects of the frequency variation, grid voltage distortion and non-linear load, while designing and deploying a controller for power quality restoration. The proposed controller supplies power to local load as well as transferring surplus power to the grid from DG along with the additional benefit of improving grid power quality. A DG with an ANFIS optimized PI current controller for power quality enhancement is proposed. The method is economical as it requires no additional hardware. Results are compared with PI, PI-RC and fuzzy current controllers to validate the effectiveness of the proposed controller.
Focused ultrasound neuromodulation on a multiwell MEA
Authors: Saccher Marta , Kawasaki Shinnosuke , Onori Martina Proietti , van Woerden Geeske M. , Giagka Vasiliki , Dekker Ronald
Published: January 2022

Background

Microelectrode arrays (MEA) enable the measurement and stimulation of the electrical activity of cultured cells. The integration of other neuromodulation methods will significantly enhance the application range of MEAs to study their effects on neurons. A neuromodulation method that is recently gaining more attention is focused ultrasound neuromodulation (FUS), which has the potential to treat neurological disorders reversibly and precisely.

Methods

In this work, we present the integration of a focused ultrasound delivery system with a multiwell MEA plate.

Results

The ultrasound delivery system was characterised by ultrasound pressure measurements, and the integration with the MEA plate was modelled with finite-element simulations of acoustic field parameters. The results of the simulations were validated with experimental visualisation of the ultrasound field with Schlieren imaging. In addition, the system was tested on a murine primary hippocampal neuron culture, showing that ultrasound can influence the activity of the neurons.

Conclusions

Our system was demonstrated to be suitable for studying the effect of focused ultrasound on neuronal cultures. The system allows reproducible experiments across the wells due to its robustness and simplicity of operation.
Ischemic cholangitis during Osler-Weber-Rendu disease: a case report
Authors: Kharmach Oussama , Borahma Mohamed , Lagdali Nawal , Benelbarhdadi Imane , Ajana Fatima-Zohra
Published: January 2022

Background

Osler-Weber-Rendu disease (OWRD) is a rare autosomal dominant genetic disease that causes skin and mucosal telangiectasias and visceral arteriovenous malformations. These shunts can lead to high-output heart failure, portal hypertension, biliary or mesenteric ischemia. We report the case of a patient with OWRD complicated by ischemic cholangitis and biloma.

Case presentation

A 50-year-old female patient with personal history of spontaneous epistaxis and gingival bleeding, family history of Osler-Weber-Rendu disease (OWRD) in mother, and epistaxis in siblings. She consulted for intermittent and minimal biliary colic. Physical exam found mucocutaneous telangiectasia. Abdominal Doppler ultrasound/CT angiography showed arteriovenous shunts in the liver between hepatic artery and hepatic vein, hepatic artery and portal vein. Other sites of arteriovenous malformations were found in the nostril and jejunum. The diagnosis of OWRD was made. The evolution after 1 year was marked by the appearance of a slight anicteric cholestasis. MRCP found intrahepatic bilomas with associated ischemic cholangitis of segment VII. We decided to continue monitoring only.

Conclusion

The management of OWRD is based on screening for visceral arteriovenous malformations and on symptomatic measures that are often disappointing. Ischemic cholangitis is a rare complication, the diagnosis is based on imaging, liver transplantation is the only therapeutic alternative in this cases.
Secondary Students’ Reasoning on Pedigree Problems
Authors: Timm Justin , Wools Katharina , Schmiemann Philipp
Published: January 2022

In this qualitative analysis, propositions concerning pedigrees from two groups of secondary students with varying degrees of experience in genetics were categorized. Differences in strategic approaches between groups demonstrate graphically which family members the students used to make their decisions. A variety of typical but unreliable arguments made by students are discussed.
Changes in brain function during negative emotion processing in the long-term course of depression
Authors: Enneking Verena , Klug Melissa , Borgers Tiana , Dohm Katharina , Grotegerd Dominik , Frankenberger Lisa Marie , Hülsmann Carina , Lemke Hannah , Meinert Susanne , Leehr Elisabeth J. , Opel Nils , Goltermann Janik , Richter Maike , Waltemate Lena , Böhnlein Joscha , Sindermann Lisa , Repple Jonathan , Bauer Jochen , Thomas Mareike , Dannlowski Udo , Redlich Ronny
Published: January 2022

Background

Relapses in major depression are frequent and are associated with a high burden of disease. Although short-term studies suggest a normalisation of depression-associated brain functional alterations directly after treatment, long-term investigations are sparse.

Aims

To examine brain function during negative emotion processing in association with course of illness over a 2-year span.

Method

In this prospective case–control study, 72 in-patients with current depression and 42 healthy controls were investigated during a negative emotional face processing paradigm, at baseline and after 2 years. According to their course of illness during the study interval, patients were divided into subgroups (n = 25 no-relapse, n = 47 relapse). The differential changes in brain activity were investigated by a group × time analysis of covariance for the amygdala, hippocampus, insula and at whole-brain level.

Results

A significant relapse × time interaction emerged within the amygdala (PTFCE-FWE = 0.011), insula (PTFCE-FWE = 0.001) and at the whole-brain level mainly in the temporal and prefrontal cortex (PTFCE-FWE = 0.027), resulting from activity increases within the no-relapse group, whereas in the relapse group, activity decreased during the study interval. At baseline, the no-relapse group showed amygdala, hippocampus and insula hypoactivity compared with healthy controls and the relapse group.

Conclusions

This study reveals course of illness-associated activity changes in emotion processing areas. Patients in full remission show a normalisation of their baseline hypo-responsiveness to the activation level of healthy controls after 2 years. Brain function during emotion processing could further serve as a potential predictive marker for future relapse.
Clinical Utility of Genomic Testing in Cancer Care
Authors: Pritchard Daryl , Goodman Clifford , Nadauld Lincoln D.
Published: January 2022

PURPOSE

In the era of personalized medicine, physicians rely on their understanding of clinical utility to assess the value of rapidly evolving genetic and genomic tests. Current definitions of the clinical utility of genetic testing sufficiently capture a range of benefits and risks that derive from positive and negative results of tests that assess one gene or a few genes. However, these definitions of clinical utility are inadequate to recognize the wider scope of benefits that accrue from more comprehensive genomic tests, which can develop data sets that inform clinical decision making as well as population health and scientific advancement in novel ways.

METHODS

An expert roundtable discussion with leaders from multiple sectors of the health care ecosystem was convened to develop a contemporary, fuller definition of the clinical utility of genomic testing in cancer care.

RESULTS

We present an updated definition and offer recommendations for successful implementation.

CONCLUSION

Applying this expanded definition will encourage evidence-based use of genomic testing in cancer care by helping physicians and other health care decision makers account for the broader range of benefits and risks of testing for individual patients, health systems, population health, and scientific advancement.
Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers
Authors: Drilon Alexander , Tan Daniel S. W. , Lassen Ulrik N. , Leyvraz Serge , Liu Yongmei , Patel Jyoti D. , Rosen Lee , Solomon Benjamin , Norenberg Ricarda , Dima Laura , Brega Nicoletta , Shen Lin , Moreno Victor , Kummar Shivaani , Lin Jessica J.
Published: January 2022

PURPOSE

Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers.

MATERIALS AND METHODS

Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial ( NCT02576431 ) and a phase I adult trial ( NCT02122913 ). The primary end point was objective response rate (ORR).

RESULTS

By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2.

CONCLUSION

Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.
Luminosity and physics considerations on HL-LHC–and HE-LHC–based μp colliders
Authors: Kaya Umit , Ketenoglu Bora , Sultansoy Saleh , Zimmermann Frank
Published: January 2022

Construction of the future muon collider tangential to the Large Hadron Collider will give opportunity to realize μp collisions at multi-TeV center-of-mass energies. Using the nominal parameters of high-luminosity and high-energy upgrades of the LHC, as well as the design parameters of muon colliders, it is shown that L
μp of the order of 1033 cm−2s−1 is achievable for different options with

from 4.58 TeV to 12.7 TeV. Certainly, the proposed μp colliders have a huge potential for clarifying QCD basics and searches for new physics.
Adrenal Vein Sampling With Gadolinium Contrast Medium in a Patient With Florid Primary Aldosteronism and Iodine Allergy
Authors: Yoshida Yuichi , Nagai Satoshi , Shibuta Kanako , Miyamoto Shuhei , Maruno Miyuki , Takaji Ryo , Hata Shinro , Nishida Haruto , Miyamoto Shotaro , Ozeki Yoshinori , Okamoto Mitsuhiro , Gotoh Koro , Masaki Takayuki , Shin Toshitaka , Mimata Hiromitsu , Daa Tsutomu , Asayama Yoshiki , Shibata Hirotaka
Published: January 2022

We describe a 35-year-old woman who was allergic to iodine contrast medium and was diagnosed with primary aldosteronism (PA) based on functional confirmatory tests. She was suspected to have unilateral PA because of marked hypertension, spontaneous hypokalemia, high plasma aldosterone, reduced plasma renin activity, and a right hypodense adrenal tumor. She wanted to become pregnant and requested adrenalectomy instead of medical treatment with mineralocorticoid receptor antagonists. Localization of PA by adrenal vein sampling (AVS) was necessary, but angiography with iodine contrast medium was not possible because of her allergy. AVS was performed using gadolinium contrast agent (gadoterate meglumine) instead of iodine, in combination with computed tomography angiography (CTA). In AVS, before and after adrenocorticotropin (ACTH) loading, 12 blood samples were drawn from the right adrenal vein, left adrenal central vein, left adrenal common duct, left and right renal veins, and the lower inferior vena cava with only 5 mL of gadolinium medium. There were no complications during AVS. Examination revealed an elevated aldosterone/cortisol ratio on the right side, lateralized ratio of 7.4, and contralateral ratio of 0.76; the patient was diagnosed with right unilateral PA. She underwent right adrenalectomy and showed improvements in aldosterone level from 312.4 pg/mL to 83.0 pg/mL, potassium from 3.0 mEq/L to 3.9 mEq/L, and systolic blood pressure from 138 mm Hg to 117 mm Hg. In PA patients with iodine allergy, AVS can be performed safely and precisely using gadolinium contrast combined with CTA.
Reconsidering Lost Opportunities for Diverse Representation
Authors: Nguyen Josef
Published: January 2022

This article considers the cultural politics of frustrated potential for diverse representation in games by examining developer comments on the 1995 digital game I Have No Mouth, and I Must Scream, adapted from Harlan Ellison’s 1967 science fiction story of the same name. While Ellison’s story featured a gay man named Benny among the protagonists, the game developers adapted Benny without his original sexual identity. In a 2012 Game Informer magazine article, however, the developers reflected on their version of Benny as a “lost opportunity” for exploring gay identity. Rooted in discussion of this frustrated potential for a gay in-game Benny, this article interrogates a logic of lost opportunity for diverse representation present in game-development discourse, which manifests in a longing for more diverse characters that could have been but never came to be. This logic suggests particular ways that developers might conceive of diverse representation as simply a design issue under neoliberal logics of economic opportunity, commercial risk, and fetishized innovation—without meaningful consideration of political significance. Opposing this instrumentalization of frustrated diverse representation, this article draws on queer game studies and speculative design and literature to explore the possible contours and implications of diverse characters that never were more seriously than such comments typically do. Doing so demands more than romanticized longings for lost opportunities for diverse representation that treat this longing as the end in itself.
Type-Itemized Enumeration of Five Types of Stereoisograms and Their Simplified Diagrams for Characterizing Cubane Derivatives
Authors: Fujita Shinsaku
Published: January 2022

For discussing stereochemistry of cubane derivatives, the concept of stereoisograms controlled by the RS-stereoisomeric group $\boldsymbol{{O}}_{\boldsymbol{{h}}\tilde{\boldsymbol{{\sigma}}}\skew2\hat{\boldsymbol{{I}}}}$ (order 98) is formulated by the extension of the point group Oh (order 48). The vertical directions of a stereoisogram are concerned with chirality as the first kind of handedness, which is controlled by rotations and reflections of Oh. The horizontal directions of a stereoisogram are concerned with RS-stereogenicity as the second kind of handedness, which is controlled by an RS-stereogenic group $\boldsymbol{{O}}_{{\tilde{\boldsymbol{{\sigma}}}}}$ (order 48). The diagonal directions of a stereoisogram are concerned with sclerality/asclerality, which is controlled by an LR-permutation group $\boldsymbol{{O}}_{{\skew2\hat{\boldsymbol{{I}}}}}$ (order 48). These groups are characterized by combined-permutation representations (CPRs), which are used to calculate respective cycle indices with chirality fittingness (CI-CFs) for enumeration under the GAP system. Enumerations are conducted under O, Oh, $\boldsymbol{{O}}_{{\tilde{\boldsymbol{{\sigma}}}}}$, $\boldsymbol{{O}}_{{\skew2\hat{\boldsymbol{{I}}}}}$, and $\boldsymbol{{O}}_{\boldsymbol{{h}}\tilde{\boldsymbol{{\sigma}}}\skew2\hat{\boldsymbol{{I}}}}$. Then, the enumeration results are discussed in terms of simplified diagrams. It has been proven that there are two main categories for characterizing the appearance of five types of stereoisograms. The first category is an ascleral case which is characterized by the presence of type-I and type-IV stereoisograms. In contrast, the second category is a scleral case which is characterized by the presence of type-II, type-III, and type V stereoisograms. There also exist minor cases in which the coexistence of the first and second categories is observed.
Synthesis of an Organometallic Alkyl-Co(III) Complex with Amidoquinoline Directing Groups via C(sp3)–H Activation and Its UV–vis/NMR Spectroscopic, Crystallographic, DFT, and Electrochemical Studies
Authors: Tahara Keishiro , Takezaki Shun , Ozawa Yoshiki , Abe Masaaki
Published: January 2022

The use of earth-abundant and inexpensive Co catalysts for carbon-hydrogen (C–H) bond activation has received increasing attention because of the advantages including air stability. Although directing groups have been effectively introduced in substrates to promote C(sp3)–H activation through chelation assistance, there is a lack of basic information about the isolated alkyl-Co complexes containing directing groups as polydentate ligands. In this study, we report the synthesis and characterization of an alkyl-Co(III) complex 2Co, prepared from a N,N′-bis(8-quinolyl)malonamide derivative, the malonyl fragment of which was disubstituted by two ethyl groups. 2Co was straightforwardly obtained from a Co(II) salt without any use of chemical oxidants but in the presence of air, through selective β-C(sp3)–H activation. The combined NMR spectroscopic and X-ray crystal structural analyses revealed that the malonamide substrate was converted into a pentadentate ligand with an N4C set, acquiring a helical configuration around the Co(III) center. The non-innocent ligand properties of 2Co were unambiguously confirmed by UV–vis spectroscopic, electrochemical, and DFT studies. Thermolysis of 2Co enabled C(sp3)–N reductive elimination in the absence of chemical oxidants. The present study provides important insights into the reactivity of alkyl-Co(III) complexes with a defined coordination geometry around the Co center toward designing elaborate C(sp3)–H functionalization systems.
Intracrystalline Kinetics Analyzed by Real-Time Monitoring of a 1,2-Dioxetane Chemiluminescence Reaction in a Single Crystal
Authors: Matsuhashi Chihiro , Fujisawa Hiroki , Ryu Meguya , Tsujii Tetsuya , Morikawa Junko , Oyama Hironaga , Uekusa Hidehiro , Maki Shojiro , Hirano Takashi
Published: January 2022

Adamantylideneadamantane 1,2-dioxetane (Adox), one of the most stable 1,2-dioxetanes, was used to investigate the kinetic properties of its chemiluminescent thermolytic reaction in the crystalline state by monitoring chemiluminescence (CL) in real time. Soon after heating of single crystals at 140 °C, it was found that the thermolytic reactions of Adox in the crystals proceeded with zero-order kinetics for several minutes. During the period showing the zero-order kinetics, CL intensities were dependent on the volumes of crystals, and the inside crystals were maintained in a thermal steady state with a constant thermal diffusivity. After this period, the heated crystals of Adox started to break showing different kinetics. This study indicates that a crystalline-state CL reaction is useful to track its progress in real time for analyzing the kinetics.
Optimization of contrast material administration for coronary CT angiography using a software-based test-bolus evaluation algorithm
Authors: Fischer Andreas M , Decker Josua A. , Schoepf Joseph , Varga-Szemes Akos , Flohr Thomas , Schmidt Bernhard , Gutjahr Ralf , Sahbaee Pooyan , Giovagnoli Dante A , Emrich Tilman , Martinez John D , Lari Kia B , Bayer Robert R , Martin Simon S
Published: January 2022

Objectives:

To evaluate the benefit of a prototype circulation time-based test bolus evaluation algorithm for the individualized optimal timing of contrast media (CM) delivery in patients undergoing coronary CT angiography (CCTA).

Methods:

Thirty-two patients (62 ± 16 years) underwent CCTA using a prototype bolus evaluation tool to determine the optimal time-delay for CM administration. Contrast attenuation, signal-to-noise ratio (SNR), objective, and subjective image quality were evaluated by two independent radiologists. Results were compared to a control cohort (matched for age, sex, body mass index, and tube voltage) of patients who underwent CCTA using the generic test bolus peak attenuation +4 s protocol as scan delay.

Results:

In the study group, the mean time delay to CCTA acquisition was significantly longer (26.0 ± 2.9 s) compared to the control group (23.1 ± 3.5 s; p < 0.01). In the study group, SNR improvement was seen in the right coronary artery (17.5 vs 13; p = 0.028), the left main (15.3 vs 12.3; p = 0.027), and the left anterior descending artery (18.5 vs 14.1; p = 0.048). Subjective image quality was rated higher in the study group (4.75 ± 0.7 vs 3.64 ± 0.5; p < 0.001).

Conclusions:

The prototype test bolus evaluation algorithm provided a reliable patient-specific scan delay for CCTA that ensured homogenous vascular attenuation, improvement in objective and subjective image quality, and avoidance of beam hardening artifacts.

Advances in knowledge:

The prototype contrast bolus evaluation and optimization tool estimated circulation time-based time-delay improves the overall quality of CCTA.
The impact of brain atrophy on the outcomes of mechanical thrombectomy
Authors: Monteiro Andre , Waqas Muhammad , Rai Hamid H. , Baig Ammad A. , Dossani Rimal H. , Cappuzzo Justin M. , Levy Elad I. , Siddiqui Adnan H.
Published: January 2022

Objective:

Pre-existing brain atrophy may affect the outcomes of patients treated with mechanical thrombectomy (MT) for large-vessel-occlusion because it is an indicator of low brain reserve. We performed a systematic literature review to assess the impact of brain atrophy on MT-related clinical outcomes.

Methods:

We conducted a systematic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to March 2021 using keywords with Boolean operators(“brain atrophy”; “atrophy”; “white matter”; and “thrombectomy”). Articles published in English that evaluated the impact of pre-existing brain atrophy on outcomes of MT-treated acute ischemic stroke were eligible for inclusion.

Results:

Four articles were included. Brain atrophy index was a predictor of mortality (odds ratio [OR]:1.81–1.87, 95% confidence interval [CI]:1.16–2.93) after adjustments for age and white matter lesions. Global cortical atrophy scale was an independent predictor of futile recanalization (OR 1.15, 95% CI 1.08–1.22) in multivariate-adjusted logistic regression. Automated measurement of CSF identified increasing volumes associated with reduced 3-month functional independence and higher modified Rankin scale scores. STandards for ReportIng Vascular changes on Neuroimaging criteria for brain atrophy were associated with unfavorable outcome in ordinal-shift analysis (OR 2.72, 95% CI 1.25–5.91).

Conclusions:

The few studies available highlight heterogeneity of neuroimaging methodologies for assessing brain atrophy and difficulty addressing the multiple confounders involved in clinical outcomes. More consistent, accurate investigation is needed before proposing brain atrophy as a possible parameter to improve patient selection for MT.

Advances in knowledge:

Brain atrophy is associated with many of the clinical confounders frequently present in patients with acute ischemic stroke. Heterogeneity in classification methodologies for brain atrophy and complexity analyzing multiple clinical confounders make it difficult to assess the true impact of this radiological finding on MT-related outcomes.
Effects of sampling intensity and biomass levels on the precision of acoustic surveys in the Mediterranean Sea
Authors: BARRA MARCO , BONANNO ANGELO , HATTAB TAREK , SARAUX CLAIRE , IGLESIAS5 MAGDALENA , LEONORI IOLE , TIČINA VJEKOSLAV , BASILONE GUALTIERO , DE FELICE ANDREA , FERRERI ROSALIA , MACHIAS ATHANASSIOS , VENTERO ANA , COSTANTINI ILARIA , JURETIĆ TEA , PYROUNAKI MARIA MYRTO , BOURDEIX JEAN-HERVE , GAŠPAREVIĆ DENIS , KAPELONIS ZACHARIAS , CANDUCI GIOVANNI , GIANNOULAKI MARIANNA
Published: January 2022

Acoustic surveys represent the standard fishery-independent method worldwide for evaluating the biomass and spatial distribution of small pelagic fish populations. Considering the peculiarities of the spatial behaviour of pelagic fishes, the efficiency of the survey design in determining their biomass and spatial distribution is related to its ability to capture the portion of the patches accounting for larger part of the total biomass. Yet, the spatial structure of the patches could be strongly influenced by ecosystem characteristics as well as by changes in total biomass related to a density-dependent mechanism. This is of particular interest for anchovy and sardine which are known for their wide fluctuations and high sensitivity to the environment. In this study, we analysed the efficiency of acoustic surveys, targeting European anchovy (Engraulis encrasicolus) and European sardine (Sardina pilchardus), in 10 different areas of the Mediterranean Sea across three years of different biomass levels. Using the geostatistical Coefficient of Variation (CVgeo) of the average occurrence probability of high/medium density values, we showed different patterns in terms of survey design efficiency among areas and species. Anchovy usually showed lower CVgeo than sardine, but in the Alboran Sea. In 4 out of 20 cases, CVgeo values showed a consistent decrease with increasing biomass while in the remaining cases the CVgeo did not follow any clear pattern suggesting the presence of important environmental effects. Higher survey design efficiency was found in high productive sectors influenced by river run-off, letting us to hypothesize that higher productivity along with the presence of well-localized enrichment mechanisms could favour a spatially consistent distribution and coherent organization of fish population leading to higher precision estimates with a given transect design. While most surveys displayed CVgeo close to 10% or less even at low biomass, evidencing generally good performances of the survey design, a few areas exhibited higher CVgeo, yielding discussions about a potential need to decrease the inter-transect distance, always keeping in mind that survey should be as synoptic as possible.