bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of influences in a medical screening programme invitation: a randomized controlled trial
Authors: Jauernik Christian Patrick , Rahbek Or Joseph , Ploug Thomas , Siersma Volkert , Brodersen John Brandt
Published: May 2023

Background

Invitations to screening programmes may include influences that are intending to increase the participation rates. This study had two objectives: (i) to assess if different categories of influences had a significant effect on the intention to participate in a screening programme for a fictitious disease and (ii) whether participants were aware of the influences, and if the intention to participate was associated to this awareness.

Methods

A seven-armed randomized controlled trial. Six hundred passers-by were randomly allocated to receive one of seven pamphlets inviting to a fictitious screening programme (neutral, relative risk reductions, misrepresentation of harms, pre-booked appointment, recommendation of participation, fear appeals, all combined). Participants were surveyed to assess (i) intention to participate (ITP) in the screening programme and (ii) awareness of an exerted influence. Chi-squared test was used to calculate the effect of the influences on ITP and the association of ITP with indicating awareness of an exerted influence and correctly locating an influence.

Results

Five hundred and eighty-nine participants were included for analysis. ITP was significantly increased (P < 0.05) in three pamphlets (misrepresentation of harms, fear appeals, all combined) [adjusted odds ratio (OR) 4.84, 95% confidence interval (CI): 2.54–9.23; OR 2.45, 95% CI: 1.31–4.59; OR 9.02, 95% CI: 4.44–18.34]. A percentage of 60.0–78.3 participants did not indicate awareness. Awareness was associated with a decreased ITP for those who could locate the influence (OR 0.39, 95% CI: 0.21–0.72) and those who failed to locate the influence (OR 0.47, 95% CI: 0.30–0.74).

Conclusion

The application of influences should be carefully considered for interventions where an informed choice is desired.
Loblolly Pine Susceptibility to Nantucket Pine Tip Moth: Do Tree Genetics Play a Role?
Authors: McCarty Elizabeth , Clabo David , Dickens David , Waldrop Cassandra , Gandhi Kamal J K , Villari Caterina
Published: May 2023

The Nantucket pine tip moth (NPTM) (Rhyacionia frustrana Comstock) is a regeneration pest of young loblolly pines (Pinus taeda L.) that causes tree deformity, shoot dieback, and growth declines. Different silvicultural techniques are used to grow loblolly pine more effectively, including improved genotypes. Some scientists and growers have hypothesized that more expensive full-sibling families (control-pollinated [CP]) seedlings may be more susceptible to NPTM than open-pollinated (OP) families. The study objective was to assess the susceptibility to NPTM of seven loblolly OP and CP families commonly planted in the southeastern United States by observing NPTM infestation rates and pine growth metrics (height, groundline diameter, volume index, and stem form) over two growing seasons. The NPTM infestation rates varied throughout both growing seasons; however, there was no difference in infestation rates among any of the families. Pine growth metrics varied among families at the time of planting; however, growth metrics did not vary after the first and second growing seasons. Results of this study suggest that NPTM management tactics, such as insecticide use, should not be prioritized based on loblolly pine families alone, as the CP families assessed in this study were not more susceptible to NPTM than OP families.
The War in Ukraine Raises Questions About Patents for Secret Inventions
Authors: Matthews Duncan , Ostapenko Hanna
Published: May 2023

Patent information must, in certain circumstances, be prevented from being made available to the public for reasons of national security. This policy imperative deviates from the conventional approach under patent law, which emphasises a bargain with society whereby patent rights are granted in return for disclosure of the invention and communication to the public. How best to achieve a balance between keeping an invention secret for reasons of national security and disclosure of the invention will depend on circumstances that may well change rapidly. The stronger the threat to national security, the more the policy tends to lean toward keeping certain inventions secret. The war in Ukraine brings this patent policy imperative sharply into focus. This opinion undertakes a historical analysis of patent law approaches for keeping inventions secret in key countries and analyses current arrangements for the patent protection of secret inventions in Ukraine. This opinion concludes that Ukraine should consider the long-term implications of keeping patented inventions secret when the war finally comes to an end, having regard to the potentially negative consequences for future innovation. This opinion also recommends that Ukraine provides reasonable compensation for patent proprietors, taking into account the economic losses associated with the fact that secrecy orders will prevent the commercialisation of otherwise potentially lucrative inventions.
An analysis of the inclusion of ear and hearing care in national health policies, strategies and plans
Authors: Canick Julia , Petrucci Beatriz , Patterson Rolvix , Saunders James , Htoo Thaw May , Omosule Ikeoluwa , Denton Alexa , Xu Mary Jue , Chadha Shelly , Young Gabrielle , Siafa Lyna , Mortel Olivier , Shamshad Alizeh , Reddy Ashwin , McCalla Monet , Prasad Kavita , Yang Hong-Ho , Pan Debbie R , Shah Jaffer , Smith Emily , Alkire Blake , Ibekwe Titus , Waterworth Chris
Published: May 2023

Ear- and hearing-related conditions pose a significant global health burden, yet public health policy surrounding ear and hearing care (EHC) in low- and middle-income countries is poorly understood. The present study aims to characterize the inclusion of EHC in national health policy by analysing national health policies, strategies and plans in English, French, Spanish, Portuguese and Arabic. Three EHC keywords were searched, including ear*, hear* and deaf*. The terms ‘human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)’, ‘tuberculosis’ and ‘malaria’ were included as comparison keywords as these conditions have historically garnered political priority in global health. Of the 194 World Health Organization Member States, there were 100 national policies that met the inclusion criteria of document availability, searchable format, language and absence of an associated national EHC strategy. These documents mentioned EHC keywords significantly less than comparison terms, with mention of hearing in 15 documents, ears in 11 documents and deafness in 3 documents. There was a mention of HIV/AIDS in 92 documents, tuberculosis in 88 documents and malaria in 70 documents. Documents in low- and middle-income countries included significantly fewer mentions of EHC terms than those of high-income countries. We conclude that ear and hearing conditions pose a significant burden of disease but are severely underrepresented in national health policy, especially in low- and middle-income countries.
Organizational narratives and self-legitimation in international organizations
Authors: von Billerbeck Sarah
Published: May 2023

A growing literature has examined how international organizations (IOs) use narratives for self-legitimation—legitimation aimed not at external audiences but at IO staff themselves. However, little work examines why some self-legitimation narratives ‘stick’ and others fade away or are challenged by counter-narratives. I address this question by focusing on the content of self-legitimation narratives. First, I describe the lifecycle of self-legitimation narratives in IOs, showing how they can be endorsed, rejected or challenged by legitimacy audiences. Next, I posit a three-part typology of narrative content: purpose, performance and politics. Drawing on 87 interviews with IO staff, I argue that narratives of purpose, which focus on organizational values and norms, are more likely to be endorsed and become dominant, while those that focus on performance or politics are more likely to be rejected or challenged. Where this happens, legitimacy agents must adjust narrative content in line with audience demands. I illustrate this with two case-studies from the United Nations. I conclude with the policy implications of these findings, in particular the importance for IO leaders to align internal messaging with the values and normative expectations of staff or risk staff demotivation and cynicism, ultimately imperiling organizational effectiveness.
The path of least resistance: why international institutions maintain dialogue forums
Authors: Coni-Zimmer Melanie , Deitelhoff Nicole , Schumann Diane
Published: May 2023

Dialogue forums have been mushrooming in international economic institutions as a strategy to enhance their legitimacy. Promoted as deliberative spaces allowing for an open, direct exchange with civil society actors, forums have since been criticized as mere talking shops or public relations events. The article analyses why the forums are still maintained despite widespread criticism, with a particular focus on audiences, legitimation agents and the organizational field as sources and driving forces of legitimation strategies. Our findings on the Civil Society Policy Forum, organized by the IMF and the World Bank, and the Civil 20, one of the G20 engagement groups, highlight strong interactive effects between these sources: civil society actors have been pressing for the maintenance of forums as deliberative spaces. Additional pressure on institutions arise from the organizational field, with the inclusion of non-state actors increasingly becoming a norm. International economic institutions react strategically to these external demands by choosing the path of least resistance: maintaining dialogue forums helps showcasing their openness without granting much influence to civil society actors.
Diversification's legitimation challenges: ASEAN and its Myanmar predicament
Authors: Ba Alice D
Published: May 2023

International organizations (IOs) confront complex legitimation challenges with the diversification of audiences and actors asserting judgment and input. Drawing on Lenz and Söderbaum's agents-audience-environment (AAE) conceptualization of legitimation strategies, this discussion advances understandings of how diversification affects IO legitimation and legitimation strategies. Particular attention is given to their special sensitivity to internal IO diversification processes whose constitutive changes affect both the agent and audience ends of strategy. It especially highlights three commonly found sources of internal IO diversification: domestic change, new membership and new purposes. Providing illustration is the Association of Southeast Asian Nations (ASEAN) and its 30+ year-long efforts to defend and legitimate the organization's choices vis-à-vis its most internationally criticized member, Myanmar, and to manage the delegitimating effects of association. The discussion highlights three periods of contrasting internal diversification and effects on ASEAN's legitimation strategies: the first characterized by the least diversification and defiant affirmation of internal founding norms; the second by membership-, purpose- and audience-diversification, and strategies of reconciliation; and the third by diversification's accentuation of member-states' dual roles as agents and audiences of legitimation with growing reliance on informal workarounds, strategic ambiguation and defensive depoliticization as especially illustrated by ASEAN's responses to Myanmar's 2021 coup.
What's driving the democratic recession in Asia?
Authors: Fong Brian C H
Published: May 2023

The extant literature explains autocratization either through domestically or internationally-driven explanations. The former focuses on studying autocratic strongmen's executive aggrandizement or promissory coups from a domestic perspective, while the latter highlights the critical role of autocratic powers in promoting autocratic practices to neighboring countries from an international perspective. Transcending such a dichotomous approach, this study endeavors to explore the coupling of domestic and international drivers in causing autocratization in the context of Asia through a comparative analysis of Cambodia, the Philippines, Myanmar and Thailand. The comparative analysis indicates that domestic politics spearheads autocratization (that is, the role of autocratic strongmen in spearheading autocratization through executive aggrandizement or promissory coups), while international politics consolidates such autocratization (that is, the role of autocratic powers in consolidating autocratization pathway through their exporting influence). With the rising rivalry between democratic and autocratic powers, there are more pressing needs than ever to integrate domestic and international perspectives in autocratization studies.
Ideology, grand strategy and the rise and decline of Ethiopia's regional status
Authors: Gebreluel Goitom
Published: May 2023

Ethiopia transformed from a state on the verge of collapse at the end of the Cold War into one of the world's fastest-developing economies and a regional power in the Horn of Africa in less than two decades. Since 2018 its economic, military and diplomatic status have, however, become significantly compromised yet again. What explains these significant fluctuations in regional power status? Drawing on policy documents and in-depth interviews with diplomatic, military and political officials from the Horn of Africa this article conducts a comparative analysis of the nature and variation of Ethiopia's regional power status under the Ethiopian People's Revolutionary Democratic Front (EPRDF) in 2000–2018 and the Prosperity Party (PP) in 2018–2022. The findings illustrate that the fluctuations in regional power were primarily caused by different grand strategies, which in turn reflected the priorities of the EPRDF's developmental state and the PP's restorative nationalist ideologies. These grand strategic concepts shaped Ethiopian government policies on key issues like defence doctrine, status-seeking, economic development, and rivalry and alliance management. These policies had a direct and significant impact on Ethiopia's state capacity, its ability to project military power and its diplomatic influence.
Centering Transgender and Gender Non-Conforming Experience, Access, & Safety in Ecological Fieldwork
Authors: Matsuda Shayle B
Published: May 2023

Synopsis

Efforts to make ecological sciences more diverse, equitable, and inclusive require us to identify who is being left out and take action to rectify harmful situations. Recruitment of trainees from underrepresented groups alone is insufficient without ensuring a safe and supportive environment where we can flourish. Fieldwork is a critical component and often a requirement for career advancement in ecological sciences, but for transgender and gender non-conforming (TGnC) individuals, it can be disproportionately harmful. TGnC individuals face barriers and gendered violence before, during, and after fieldwork, and our experiences are often lost in current discussions of underrepresented groups in the field. In this article, I discuss the importance of an intersectional framework that focuses on planning, open communication, and trust, to address both the barriers TGnC trainees’ experience with travel, accommodations, and access to medical care, along with their experiences of perceived and actual violence by colleagues and strangers. Additionally, I propose direct actions that those in power, such as Principal Investigators, field station managers, and mentors, can take to ensure a safe and welcoming fieldwork environment that supports TGnC trainees’ physical, emotional, and professional well-being.
Totally Nonnegative Critical Varieties
Authors: Galashin Pavel
Published: May 2023

We study totally nonnegative parts of critical varieties in the Grassmannian. We show that each totally nonnegative critical variety $\operatorname{Crit}^{\geqslant 0}_f$ is the image of an affine poset cyclohedron under a continuous map and use this map to define a boundary stratification of $\operatorname{Crit}^{\geqslant 0}_f$. For the case of the top-dimensional positroid cell, we show that the totally nonnegative critical variety $\operatorname{Crit}^{\geqslant 0}_{k,n}$ is homeomorphic to the second hypersimplex $\Delta _{2,n}$.
Characteristic Foliation on Hypersurfaces With Positive Beauville–Bogomolov–Fujiki Square
Authors: Abugaliev Renat
Published: May 2023

Let $Y$ be a smooth hypersurface in a projective irreducible holomorphic symplectic manifold X of dimension 2n. The characteristic foliation $F$ is the kernel of the symplectic form restricted to Y. In this article, we prove that a generic leaf of the characteristic foliation is dense in Y if Y has positive Beauville–Bogomolov–Fujiki square.
A machine learning approach to determine resilience utilizing wearable device data: analysis of an observational cohort
Authors: Hirten Robert P , Suprun Maria , Danieletto Matteo , Zweig Micol , Golden Eddye , Pyzik Renata , Kaur Sparshdeep , Helmus Drew , Biello Anthony , Landell Kyle , Rodrigues Jovita , Bottinger Erwin P , Keefer Laurie , Charney Dennis , Nadkarni Girish N , Suarez-Farinas Mayte , Fayad Zahi A
Published: May 2023

Objective

To assess whether an individual’s degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device.

Materials and Methods

Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New York City. Subjects wore an Apple Watch for the duration of their participation. Surveys were collected measuring resilience, optimism, and emotional support at baseline.

Results

We evaluated data from 329 subjects (mean age 37.4 years, 37.1% male). Across all testing sets, gradient-boosting machines (GBM) and extreme gradient-boosting models performed best for high- versus low-resilience prediction, stratified on a median Connor-Davidson Resilience Scale-2 score of 6 (interquartile range = 5–7), with an AUC of 0.60. When predicting resilience as a continuous variable, multivariate linear models had a correlation of 0.24 (P = .029) and RMSE of 1.37 in the testing data. A positive psychological construct, comprised of resilience, optimism, and emotional support was also evaluated. The oblique random forest method performed best in estimating high- versus low-composite scores stratified on a median of 32.5, with an AUC of 0.65, a sensitivity of 0.60, and a specificity of 0.70.

Discussion

In a post hoc analysis, machine learning models applied to physiological metrics collected from wearable devices had some predictive ability in identifying resilience states and a positive psychological construct.

Conclusions

These findings support the further assessment of psychological characteristics from passively collected wearable data in dedicated studies.
Concentrations of vitamin B12 and folate in maternal serum and fetal fluids, metabolite interrelationships, and hepatic transcript abundance of key folate and methionine cycle genes: the impacts of maternal nutrition during the first 50 d of gestation
Authors: Syring Jessica G , Crouse Matthew S , Neville Tammi L , Ward Alison K , Dahlen Carl R , Reynolds Lawrence P , Borowicz Pawel P , McLean Kyle J , Neville Bryan W , Caton Joel S
Published: May 2023

Adequate maternal nutrition is key for proper fetal development and epigenetic programming. One-carbon metabolites (OCM), including vitamin B12, folate, choline, and methionine, play a role in epigenetic mechanisms associated with developmental programming. This study investigated the presence of B12 and folate in maternal serum, allantoic fluid (ALF), and amniotic fluid (AMF), as well as how those concentrations in all three fluids correlate to the concentrations of methionine–folate cycle intermediates in heifers receiving either a control (CON) or restricted (RES) diet for the first 50 d of gestation and fetal hepatic gene expression for methionine–folate cycle enzymes. Angus cross heifers (n = 43) were estrus synchronized, bred via artificial insemination with semen from a single sire, and randomly assigned to one of two nutrition treatments (CON = 20, RES = 23). Heifers were ovariohysterectomized on either day 16 (n = 14), 34 (n = 15), or 50 of gestation (n = 14), where samples of maternal serum (n = 42), ALF (n = 29), and AMF (n = 11) were collected and analyzed for concentrations of folate and B12. Concentrations of B12 and folate in ALF were greater (P < 0.05) in RES compared to CON. For ALF, folate concentrations were also greater (P < 0.01) on day 34 compared to day 50. There was a significant (P = 0.04) nutrition × fluid interaction for B12 concentrations where concentrations were greatest in restricted ALF, intermediate in control ALF, and lowest in CON and RES serum and AMF. Folate concentrations were greatest (P < 0.01) in ALF, intermediate in serum, and lowest in AMF. Additionally, positive correlations (P < 0.05) were found between ALF and AMF folate concentrations and AMF concentrations of methionine, serine, and glycine. Negative correlations (P < 0.05) between AMF folate and serum homocysteine were also observed. Both positive and negative correlations (P < 0.05) depending on the fluid evaluated were found between B12 and methionine, serine, and glycine concentrations. There was a downregulation (P = 0.05) of dihydrofolate reductase and upregulation (P = 0.03) of arginine methyltransferase 7 gene expression in RES fetal liver samples compared with CON fetal liver on day 50. Combined, these data show restricted maternal nutrition results in increased B12 and folate concentrations present in fetal fluids, and increased expression of genes for enzymes within one-carbon metabolism.
A fatal case of poisoning with a cathinone derivative: α-PiHP and its postmortem distribution in body fluids and organ tissues
Authors: Wachholz Paulina , Celiński Rafał , Bujak-Giżycka Beata , Skowronek Rafał , Pawlas Natalia
Published: May 2023

New psychoactive substances continue to appear on the drug market, and alpha-pyrrolidinoisohexanophenone (α-PiHP) is one of the most popular cathinone derivatives. In this article, we report a case of death caused by α-PiHP. Based on the toxicological results of the studied case along with autopsy, histopathological findings and crime-scene information, fatal intoxication with α-PiHP was accepted as the final cause of death. α-PiHP and its metabolite (OH-α-PiHP) were detected and quantified in all postmortem materials (blood collected from the heart, the femoral vein and the dural venous sinuses; vitreous humor; cerebrospinal fluid; cerebral cortex; brainstem; cerebellum; bile; liver; kidney; heart; pancreas; spleen; thyroid gland; lung; adipose tissue; stomach and intestine). To date, this is the first case of determination of α-PiHP and its metabolite in postmortem specimens. In our opinion, α-PiHP and its metabolite concentration database can be helpful in the interpretation of fatal cases.
Hybrid neural network-based metaheuristics for prediction of financial markets: a case study on global gold market
Authors: Mousapour Mamoudan Mobina , Ostadi Ali , Pourkhodabakhsh Nima , Fathollahi-Fard Amir M , Soleimani Faezeh
Published: May 2023

Technical analysis indicators are popular tools in financial markets. These tools help investors to identify buy and sell signals with relatively large errors. The main goal of this study is to develop new practical methods to identify fake signals obtained from technical analysis indicators in the precious metals market. In this paper, we analyze these indicators in different ways based on the recorded signals for 10 months. The main novelty of this research is to propose hybrid neural network-based metaheuristic algorithms for analyzing them accurately while increasing the performance of the signals obtained from technical analysis indicators. We combine a convolutional neural network and a bidirectional gated recurrent unit whose hyperparameters are optimized using the firefly metaheuristic algorithm. To determine and select the most influential variables on the target variable, we use another successful recently developed metaheuristic, namely, the moth-flame optimization algorithm. Finally, we compare the performance of the proposed models with other state-of-the-art single and hybrid deep learning and machine learning methods from the literature. Finally, the main finding is that the proposed neural network-based metaheuristics can be useful as a decision support tool for investors to address and control the enormous uncertainties in the financial and precious metals markets.
Natural disasters, risk and migration: evidence from the 2017 Pohang earthquake in Korea
Authors: Kim Hyejin , Lee Jongkwan
Published: May 2023

Using the 2017 Pohang earthquake in South Korea as a natural experiment, we examined the responses of the population. By constructing a counterfactual of Pohang using synthetic controls, we found that the earthquake significantly decreased the local population. To investigate the mechanisms of population decrease, we gathered administrative data on the universe of address changes and self-reported reasons for migration. While out-migration due to changes in the residential environment increased significantly, job-related migration showed little change. This out-migration also led to a depreciation in rental housing prices. Our results suggest that local residents perceived the earthquake as a negative amenity.
Economic Contribution Analysis of Urban and Community Forestry in the Southern United States in 2019
Authors: Parajuli Rajan , Chizmar Stephanie , Lamica Austin , Wiseman Eric , Gordon Jason , Ochuodho Thomas , Schons Stella Zucchetti , Henderson James E , Mehmood Sayeed , Johnson Lara
Published: May 2023

As populations in developing areas continue to increase in recent years, urban and community forestry (U&CF) has received considerable attention due to the ecological, social, and economic significance of trees and green landscapes in urban and semi-urban settings. Based on a regional survey of private, public, and nonprofit businesses and agencies involved in U&CF, we first developed a complete profile of the U&CF sector in the southern United States (SUS) and then estimated the economic contribution of U&CF businesses and activities to the thirteen-state regional economy. We estimated that, in 2019, U&CF in the SUS contributed about $23.2 billion in value added with a total jobs support of over 349,200. Based on the current economic contributions and the number of cities and towns in each state, we also categorized thirteen states into four different tiers. Results not only underscore the economic significance of U&CF businesses and activities in the SUS, but also serve as a baseline to track future trends and performance of U&CF in terms of various business metrics.
Gynoid Fat Distribution and Adipocyte Trapping May Explain Virological Failure With Intramuscular Long-Acting Cabotegravir and Rilpivirine
Authors: de Malliard Isabelle , Houist Anne-Laure , Peytavin Gilles , L’Yavanc Thomas , Bouvier Magali , Cappy Pierre , Lelièvre Jean-Daniel , Feredj Elsa , Vindrios William , Gallien Sebastien , Melica Giovanna
Published: May 2023

Intramuscular long-acting antiretroviral drugs can improve adherence to lifelong antiretroviral treatment. Nevertheless, adipose tissue thickness and distribution play a critical role with injectable drugs. We describe a virological failure with cabotegravir and rilpivirine in a Black African woman with human immunodeficiency virus type 1 with gynoid fat distribution (ie, adipose tissue prevailing in the pelvis and hip area) and body mass index <30 kg/m2.
Enterococci in Diabetic Foot Infections: Prevalence, Clinical Characteristics, and Outcomes
Authors: Perzon Ofer , Cahn Avivit , Gellman Yechiel N , Leibovitch Michal , Peled Shahar , Elishoov Ofer , Haze Amir , Olshtain-Pops Karen , Elinav Hila
Published: May 2023

Background

Diabetic foot infections (DFIs) are frequently polymicrobial, yet the relevance of each isolated pathogen, remains ill-defined. Specifically, the prevalence and pathogenicity of enterococcal DFIs and the impact of targeted antienterococcal treatment remain elusive.

Methods

We collected demographic, clinical, and outcome-related data on patients admitted with DFIs to the Hadassah Medical Center diabetic foot unit between 2014 and 2019. The primary outcome was a composite of in-hospital death or major amputation. Secondary outcomes included any amputation, major amputation, length of stay (LOS), and 1-year major amputation or mortality rate.

Results

Enterococci were isolated in 35% of 537 eligible DFI case patients, who were notable for a higher prevalence of peripheral vascular disease, increased levels of C-reactive protein, and higher Wagner scores. Infection in enterococci-positive individuals was mostly polymicrobial (96.8% vs 61.0% in non–enterococci-infected patients; P < .001). Enterococci-infected patients were more likely to undergo amputation (72.3% vs 50.1%; P < .001) and had longer hospital stays (median LOS, 22.5 vs 17 days; P < .001), but the primary end point of major amputation or in-hospital death did not differ between groups (25.5% vs 21.0%; P = .26). Appropriate antienterococcal antibiotics were used in 78.1% of enterococci-infected patients and, compared with results in untreated patients, were associated with a trend toward a lower rate of major amputations (20.4% vs 34.1%; P = .06) but longer hospitalization (median LOS, 24 vs 18 days; P = .07).

Conclusions

Enterococci are common in DFIs and associated with higher rates of amputation and longer hospitalization. A reduction in major amputation rates with appropriate enterococci treatment is suggested retrospectively, meriting validation by future prospective studies.
A Phase Ib Dose-Escalation Study of LCL161 Plus Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies
Authors: Johnson Melissa L , Patel Manish R , Aljumaily Raid , Jones Suzanne F , Burris, III Howard A , Spigel David R
Published: May 2023

Background

This was an open-label, multicenter, single-arm phase Ib dose-escalation study of oral LCL161 administered in combination with oral topotecan in patients with relapsed/refractory small cell lung cancer (SCLC) and select gynecological cancers.

Methods

Cohorts of 3-6 patients initiated treatment with LCL161 and topotecan in escalating doses. LCL161 was administered orally on days 1, 8, and 15 of each 21-day cycle; topotecan was administered orally for the first 5 days of each 21-day cycle.

Results

A total of 35 patients were enrolled in 6 cohorts; 30 patients were female; 4 patients had SCLC and 19 patients had ovarian cancer. Median prior lines of therapy were 3 (1-10). Median duration of treatment was 7.1 weeks (0.1-174). The most frequent grade 3/4 treatment-related adverse events were thrombocytopenia (51.43%) and anemia (31.43%). ORR was 9.7%; 58% of patients had SD. The study was stopped early before the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) were determined.

Conclusion

The addition of LCL161 to oral topotecan caused more myelosuppression when dosed together than what was associated with either drug alone. Moreover, the drug combination did not improve outcomes. The study was terminated early (ClinicalTrials.gov Identifier: NCT02649673).
Shear stress regulation of nanoparticle uptake in vascular endothelial cells
Authors: Zhang Hongping , Hu Ziqiu , Wang Jinxuan , Xu Jianxiong , Wang Xiangxiu , Zang Guangchao , Qiu Juhui , Wang Guixue
Published: May 2023

Nanoparticles (NPs) hold tremendous targeting potential in cardiovascular disease and regenerative medicine, and exciting clinical applications are coming into light. Vascular endothelial cells (ECs) exposure to different magnitudes and patterns of shear stress (SS) generated by blood flow could engulf NPs in the blood. However, an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies. Here, the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted. The mechanism of SS affecting NP uptake through regulating the cellular ROS level, endothelial glycocalyx and membrane fluidity is summarized, and the molecules containing clathrin and caveolin in the engulfment process are elucidated. SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine. This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
ADD2 RESEARCH AND DEVELOPMENT LTD v DSPACE DIGITAL SIGNAL PROCESSING & CONTROL ENGINEERING GMBH
Authors:   Patents Court
Published: May 2023

H1 Patents — European Patents — Automotive simulation circuitry — Validity — Infringement — Secondary Infringement — Means essential — Construction — Common general knowledge — Mindset — Obviousness — Insufficiency — Amendment — Added matter — Statutory defence to damages and/or profits under s.62(3) of the Patents Act 1977 — Ownership — Assignments without consideration — Whether assignment ultra vires as an unlawful distribution — Effect of later confirmatory assignment — Pre-action conduct
Differential engagement of the posterior cingulate cortex during cognitive restructuring of negative self- and social beliefs
Authors: Agathos James , Steward Trevor , Davey Christopher G , Felmingham Kim L , Ince Sevil , Moffat Bradford A , Glarin Rebecca K , Harrison Ben J
Published: May 2023

Negative self-beliefs are a core feature of psychopathology, encompassing both negative appraisals about oneself directly (i.e. self-judgment) and negative inferences of how the self is appraised by others (i.e. social judgment). Challenging maladaptive self-beliefs via cognitive restructuring is a core treatment mechanism of gold-standard psychotherapies. However, the neural mechanisms underlying the restructuring of these two kinds of negative self-beliefs are poorly understood. Eighty-six healthy participants cognitively restructured self-judgment and social-judgment negative self-belief statements during 7 Tesla functional magnetic resonance imaging scanning. Cognitive restructuring broadly elicited activation in the core default mode network (DMN), salience and frontoparietal control regions. Restructuring self-judgment relative to social-judgment beliefs was associated with comparatively higher activation in the ventral posterior cingulate cortex (PCC)/retrosplenial cortex, while challenging social-judgment statements was associated with higher activation in the dorsal PCC/precuneus. While both regions showed increased functional connectivity with the supplementary and pre-supplementary motor areas during restructuring, the dorsal PCC displayed greater task-dependent connectivity with distributed regions involved in salience, attention and social cognition. Our findings indicate distinct patterns of PCC engagement contingent upon self- and social domains, highlighting a specialized role of the dorsal PCC in supporting neural interactions between the DMN and frontoparietal/salience networks during cognitive restructuring.
Evaluation of a Bacillus-based direct-fed microbial probiotic on in vitro rumen gas production and nutrient digestibility of different feedstuffs and total mixed rations
Authors: Cappellozza Bruno I , Joergensen Jens N , Copani Giuseppe , Bryan Keith A , Fantinati Paolo , Bodin Jean-Christophe , Khahi Mohammad Malek , NinoDeGuzman Carlos , Arriola Kathy G , Lima Laís O , Farooq Samia , Vyas Diwakar
Published: May 2023

We evaluated the effects of a Bacillus-based direct-fed microbial (DFM) on total in vitro gas production, dry matter (DM), neutral detergent fiber (NDF), and starch disappearance of different feedstuffs and total mixed rations (TMR) in three different experiments. In experiment 1, six single fiber-based feedstuffs were evaluated: alfalfa hay, buffalo grass, beet pulp, eragrostis hay, oat hay, and smutsvinger grass. Experimental treatments were control (with no probiotic inoculation; CON) or incubation of a probiotic mixture containing Bacillus licheniformis and B. subtilis (3.2 × 109 CFU/g; DFM). The calculation of DFM dose under in vitro conditions was based on the assumption of a rumen capacity of 70 liter and the dose of 3 g of the DFM mixture/head/d (9.6 × 109 CFU). Total in vitro gas production, DM, and NDF disappearance were evaluated at 24- and 48 h posttreatment incubation. Mean treatment effects were observed at 24- and 48 h gas production (P < 0.0001), as DFM incubation increased in vitro gas production by 5.0% and 6.5%, respectively. For nutrient digestibility, mean DM digestibility was increased at 48 h (P = 0.05), whereas mean NDF digestibility increased at both timepoints by incubating DFM in vitro (P ≤ 0.02). In experiment 2, nine commercial dairy TMR were collected and evaluated for the same variables and treatments described in experiment 1, with the additional analysis of starch digestibility at 7 h post in vitro incubation. The only difference was the concentration of the DFM included, being representative for a dosage of 8.8 × 109 CFU/head/d. In vitro gas production was increased only at 48 h due to DFM incubation (P = 0.05), whereas DM and NDF digestibility were improved at 24 and 48 h (P ≤ 0.02). No treatment effects were observed on in vitro starch digestibility (P = 0.31). In experiment 3, a combined analysis of DM and NDF digestibility was performed by using quality values (NDF and crude protein or CP) of 16 substrates. Regardless of CP and NDF levels of the substrates, DFM improved in vitro 24 and 48 h DM and NDF digestibility (P ≤ 0.03). In summary, incubating a Bacillus-based DFM (B. licheniformis and B. subtilis; BOVACILLUS) improved mean in vitro gas production, DM, and NDF digestibility of single feedstuffs and commercial dairy TMR, highlighting the potential of this combination of Bacillus spp. to improve nutrient utilization, mainly fiber.
Outcomes of a peer-led navigation program, PARTNER-MH, for racially minoritized Veterans receiving mental health services: a pilot randomized controlled trial to assess feasibility and acceptability
Authors: Eliacin Johanne , Burgess Diana , Rollins Angela L , Patterson Scott , Damush Teresa , Bair Matthew J , Salyers Michelle P , Spoont Michele , Chinman Matthew , Slaven James E , Matthias Marianne S
Published: May 2023

This pilot study explored the feasibility and acceptability of PARTNER-MH, which aimed to engage racially diverse Veterans in mental health services, facilitate their active participation in care, and improve their communication with providers. Fifty participants were randomized to the intervention or a waitlist control group. For primary outcomes, we assessed the feasibility of the study design and PARTNER-MH’s feasibility and acceptability. For secondary outcomes, we explored preliminary effects on patient engagement, patient activation, shared decision-making, and health-related outcomes. The study had a recruitment rate of 68%, enrollment rate of 91%, and a follow-up retention rate of 72%. For intervention feasibility and acceptability, fidelity scores were satisfactory and improved over time, session attendance was modest with 33% of participants completing ≥6 sessions, and 89% of participants were satisfied with the intervention. For secondary outcomes, patients in the intervention arm showed significant improvement on self-reported mental health and depression, compared with those in the control group at both 6- and 9-month follow-ups. However, there were no significant differences between study arms on the other measures. Pilot results provide support for future testing of PARTNER-MH in a larger trial, although modifications are needed to increase session attendance and follow-up retention rate.

Clinical Trial information

The study was preregistered at Clinical Trials.gov. The study Trial registration number is ClinicalTrials.gov NCT04515771.
Therapeutic administration of mouse mast cell protease 6 improves functional recovery after traumatic spinal cord injury in mice by promoting remyelination and reducing glial scar formation
Authors: Vangansewinkel Tim , Lemmens Stefanie , Tiane Assia , Geurts Nathalie , Dooley Dearbhaile , Vanmierlo Tim , Pejler Gunnar , Hendrix Sven
Published: May 2023

Traumatic spinal cord injury (SCI) most often leads to permanent paralysis due to the inability of axons to regenerate in the adult mammalian central nervous system (CNS). In the past, we have shown that mast cells (MCs) improve the functional outcome after SCI by suppressing scar tissue formation at the lesion site via mouse mast cell protease 6 (mMCP6). In this study, we investigated whether recombinant mMCP6 can be used therapeutically to improve the functional outcome after SCI. Therefore, we applied mMCP6 locally via an intrathecal catheter in the subacute phase after a spinal cord hemisection injury in mice. Our findings showed that hind limb motor function was significantly improved in mice that received recombinant mMCP6 compared with the vehicle‐treated group. In contrast to our previous findings in mMCP6 knockout mice, the lesion size and expression levels of the scar components fibronectin, laminin, and axon‐growth‐inhibitory chondroitin sulfate proteoglycans were not affected by the treatment with recombinant mMCP6. Surprisingly, no difference in infiltration of CD4+ T cells and reactivity of Iba‐1+ microglia/macrophages at the lesion site was observed between the mMCP6‐treated mice and control mice. Additionally, local protein levels of the pro‐ and anti‐inflammatory mediators IL‐1β, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, IFNγ, and MCP‐1 were comparable between the two treatment groups, indicating that locally applied mMCP6 did not affect inflammatory processes after injury. However, the increase in locomotor performance in mMCP6‐treated mice was accompanied by reduced demyelination and astrogliosis in the perilesional area after SCI. Consistently, we found that TNF‐α/IL‐1β‐astrocyte activation was decreased and that oligodendrocyte precursor cell (OPC) differentiation was increased after recombinant mMCP6 treatment in vitro. Mechanistically, this suggests effects of mMCP6 on reducing astrogliosis and improving (re)myelination in the spinal cord after injury. In conclusion, these data show for the first time that recombinant mMCP6 is therapeutically active in enhancing recovery after SCI.
Medical School Admissions: Focusing on Producing a Physician Workforce That Addresses the Needs of the United States
Authors: Prober Charles G. , Desai Sanjay V.
Published: May 2023

The aging population, burnout, and earlier retirement of physicians along with the static number of training positions are likely to worsen the current physician shortage. There is an urgent need to transform the process for selecting medical students. In this Invited Commentary, the authors suggest that to build the physician workforce that the United States needs for the future, academic medicine should focus on building capacity in 3 overarching areas. First, medical schools need to develop a more diverse pool of capable applicants that better matches the demographic characteristics of health care trainees with those of the population, and they need to nurture applicants with diverse career aspirations. Second, medical schools should recalibrate their student selection process, aligning criteria for admission with competencies expected of medical school graduates, whether they choose to become practicing clinicians, physician–scientists, members of the public health workforce, or policy makers. Selection criteria that overweight the results of standardized test scores should be replaced by assessments that value and predict academic capacity, adaptive learning skills, curiosity, compassion, empathy, emotional maturity, and superior communication skills. Finally, to improve the equity and effectiveness of the selection processes, medical schools should leverage innovations in data science and generative artificial intelligence platforms. The ability of ChatGPT to pass the United States Medical Licensing Examination (USMLE) demonstrates the decreasing importance of memorization in medicine in favor of critical thinking and problem-solving skills. The 2022 change in the USMLE Step 1 to pass/fail plus the exodus of several prominent medical schools from the U.S. News and World Report rankings have exposed limitations of the current selection processes. Newer approaches that use precision education systems to leverage data and technology can help address these limitations.
The Influence of Caregiver Language on the Association Between Child Temperament and Spoken Language in Children Who Are Deaf or Hard of Hearing
Authors: Bowdrie Kristina , Lind-Combs Holly , Blank Andrew , Frush Holt Rachael
Published: May 2023

Objectives:

To examine the interaction between child temperament and caregiver linguistic input (i.e., syntactic complexity and lexical diversity) on receptive language in children who are deaf or hard of hearing (DHH).

Design:

Families of 59 DHH children (M
age = 5.66 years) using spoken language for communication participated in this cross-sectional study. Caregivers completed the Child Behavior Questionnaire—Short Form, which measured child temperament across three established factors (i.e., effortful control, negative affectivity, surgency-extraversion) and participated with their child in a semi-structured, dyadic play interaction that occurred during a home visit. Caregivers’ language during the play interaction was quantified based on lexical diversity and syntactic complexity. Children also completed norm-referenced receptive language measures (i.e., Comprehensive Assessment of Spoken Language-2, age-appropriate Clinical Evaluation of Language Fundamentals) during the home visit that were combined into a composite measure of child receptive language.

Results:

When caregivers used lower to moderate levels of lexical diversity, child effortful control was positively related to child receptive language. However, when caregivers used higher levels of lexical diversity, child effortful control and child receptive language were not related to each other.

Conclusions:

Family environments rich in caregiver lexical input to children might provide a protective influence on DHH child language outcomes by helping to ensure DHH children with varying self-regulatory abilities achieve better spoken language comprehension. These findings highlight the importance of encouraging caregivers to provide rich and stimulating language-learning environments for DHH children.