bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation and workflow strategies for integrating digital therapeutics for alcohol use disorders into primary care: a qualitative study
Authors: Mogk Jessica M. , Matson Theresa E. , Caldeiro Ryan M. , Garza Mcwethy Angela M. , Beatty Tara , Sevey Brandie C. , Hsu Clarissa W. , Glass Joseph E. 
Published: May 2023

Abstract
Background
Alcohol use disorders (AUD) are prevalent and often go untreated. Patients are commonly screened for AUD in primary care, but existing treatment programs are failing to meet demand. Digital therapeutics include novel mobile app-based treatment approaches which may be cost-effective treatment options to help fill treatment gaps. The goal of this study was to identify implementation needs and workflow design considerations for integrating digital therapeutics for AUD into primary care.

Methods
We conducted qualitative interviews with clinicians, care delivery leaders, and implementation staff (n = 16) in an integrated healthcare delivery system in the United States. All participants had experience implementing digital therapeutics for depression or substance use disorders in primary care. Interviews were designed to gain insights into adaptations needed to optimize existing clinical processes, workflows, and implementation strategies for use with alcohol-focused digital therapeutics. Interviews were recorded and transcribed and then analyzed using a rapid analysis process and affinity diagramming.

Results
Qualitative themes were well represented across health system staff roles. Participants were enthusiastic about digital therapeutics for AUD, anticipated high patient demand for such a resource, and made suggestions for successful implementation. Key insights regarding the implementation of digital therapeutics for AUD and unhealthy alcohol use from our data include: (1) implementation strategy selection must be driven by digital therapeutic design and target population characteristics, (2) implementation strategies should seek to minimize burden on clinicians given the large numbers of patients with AUD who are likely to be interested in and eligible for digital therapeutics, and (3) digital therapeutics should be offered alongside many other treatment options to accommodate individual patients’ AUD severity and treatment goals. Participants also expressed confidence that previous implementation strategies used with other digital therapeutics such as clinician training, electronic health record supports, health coaching, and practice facilitation would be effective for the implementation of digital therapeutics for AUD.

Conclusions
The implementation of digital therapeutics for AUD would benefit from careful consideration of the target population. Optimal integration requires tailoring workflows to meet anticipated patient volume and designing workflow and implementation strategies to meet the unique needs of patients with varying AUD severity.
Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer
Authors: Alexander James L. , Posma Joram M. , Scott Alasdair , Poynter Liam , Mason Sam E. , Doria M. Luisa , Herendi Lili , Roberts Lauren , McDonald Julie A. K. , Cameron Simon , Hughes David J. , Liska Vaclav , Susova Simona , Soucek Pavel , der Sluis Verena Horneffer-van , Gomez-Romero Maria , Lewis Matthew R. , Hoyles Lesley , Woolston Andrew , Cunningham David , Darzi Ara , Gerlinger Marco , Goldin Robert , Takats Zoltan , Marchesi Julian R. , Teare Julian , Kinross James 
Published: May 2023

Abstract
Background and aims
The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.

Methods
A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.

Results
Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10−11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR = 1.30 × 10−12), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.

Conclusions
Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection.
Highly diverse and unknown viruses may enhance Antarctic endoliths’ adaptability
Authors: Ettinger Cassandra L. , Saunders Morgan , Selbmann Laura , Delgado-Baquerizo Manuel , Donati Claudio , Albanese Davide , Roux Simon , Tringe Susannah , Pennacchio Christa , del Rio Tijana G. , Stajich Jason E. , Coleine Claudia 
Published: May 2023

Abstract
Background
Rock-dwelling microorganisms are key players in ecosystem functioning of Antarctic ice free-areas. Yet, little is known about their diversity and ecology, and further still, viruses in these communities have been largely unexplored despite important roles related to host metabolism and nutrient cycling. To begin to address this, we present a large-scale viral catalog from Antarctic rock microbial communities.

Results
We performed metagenomic analyses on rocks from across Antarctica representing a broad range of environmental and spatial conditions, and which resulted in a predicted viral catalog comprising > 75,000 viral operational taxonomic units (vOTUS). We found largely undescribed, highly diverse and spatially structured virus communities which had predicted auxiliary metabolic genes (AMGs) with functions indicating that they may be potentially influencing bacterial adaptation and biogeochemistry.

Conclusion
This catalog lays the foundation for expanding knowledge of virosphere diversity, function, spatial ecology, and dynamics in extreme environments. This work serves as a step towards exploring adaptability of microbial communities in the face of a changing climate.
Association of virome dynamics with mosquito species and environmental factors
Authors: Liu Qing , Cui Feng , Liu Xiang , Fu Yumei , Fang Wenjing , Kang Xun , Lu Hong , Li Siping , Liu Biao , Guo Wei , Xia Qianfeng , Kang Le , Jiang Feng 
Published: May 2023

Abstract
Background
The pathogenic viruses transmitted by mosquitoes cause a variety of animal and human diseases and public health concerns. Virome surveillance is important for the discovery, and control of mosquito-borne pathogenic viruses, as well as early warning systems. Virome composition in mosquitoes is affected by mosquito species, food source, and geographic region. However, the complex associations of virome composition remain largely unknown.

Results
Here, we profiled the high-depth RNA viromes of 15 species of field-caught adult mosquitoes, especially from Culex, Aedes, Anopheles, and Armigeres in Hainan Island from 2018 to 2020. We detected 57 known and 39 novel viruses belonging to 15 families. We established the associations of the RNA viruses with mosquito species and their foods, indicating the importance of feeding acquisition of RNA viruses in determining virome composition. A large fraction of RNA viruses were persistent in the same mosquito species across the 3 years and different locations, showing the species-specific stability of viromes in Hainan Island. In contrast, the virome compositions of single mosquito species in different geographic regions worldwide are visibly distinct. This is consistent with the differences in food sources of mosquitoes distributed broadly across continents.

Conclusions
Thus, species-specific viromes in a relatively small area are limited by viral interspecific competition and food sources, whereas the viromes of mosquito species in large geographic regions may be governed by ecological interactions between mosquitoes and local environmental factors.
TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma
Authors: Menevse Ayse N. , Ammer Laura-Marie , Vollmann-Zwerenz Arabel , Kupczyk Marcell , Lorenz Julia , Weidner Lorraine , Hussein Abir , Sax Julian , Mühlbauer Jasmin , Heuschneider Nicole , Rohrmus Celine , Mai Laura S. , Jachnik Birgit , Stamova Slava , Volpin Valentina , Durst Franziska C. , Sorrentino Antonio , Xydia Maria , Milenkovic Vladimir M. , Bader Stefanie , Braun Frank K. , Wetzel Christian , Albert Nathalie L. , Tonn Joerg-Christian , Bartenstein Peter , Proescholdt Martin , Schmidt Nils O. , Linker Ralf A. , Riemenschneider Markus J. , Beckhove Philipp , Hau Peter 
Published: May 2023

AbstractGlioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It is particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) is upregulated in GB and correlates with malignancy and poor prognosis, but also with increased immune infiltration. Here, we studied the role of TSPO in the regulation of immune resistance of human GB cells. The role of TSPO in tumor immune resistance was experimentally determined in primary brain tumor initiating cells (BTICs) and cell lines through genetic manipulation of TSPO expression and subsequent cocultures with antigen specific cytotoxic T cells and autologous tumor-infiltrating T cells. Death inducing intrinsic and extrinsic apoptotic pathways affected by TSPO were investigated. TSPO-regulated genes mediating apoptosis resistance in BTICs were identified through gene expression analysis and subsequent functional analyses. TSPO transcription in primary GB cells correlated with CD8+ T cell infiltration, cytotoxic activity of T cell infiltrate, expression of TNFR and IFNGR and with the activity of their downstream signalling pathways, as well as with the expression of TRAIL receptors. Coculture of BTICs with tumor reactive cytotoxic T cells or with T cell-derived factors induced TSPO up-regulation through T cell derived TNFα and IFNγ. Silencing of TSPO sensitized BTICs against T cell-mediated cytotoxicity. TSPO selectively protected BTICs against TRAIL-induced apoptosis by regulating apoptosis pathways. TSPO also regulated the expression of multiple genes associated with resistance against apoptosis. We conclude that TSPO expression in GB is induced through T cell-derived cytokines TNFα and IFNγ and that TSPO expression protects GB cells against cytotoxic T cell attack through TRAIL. Our data thereby provide an indication that therapeutic targeting of TSPO may be a suitable approach to sensitize GB to immune cell-mediated cytotoxicity by circumventing tumor intrinsic TRAIL resistance.
An impact assessment of the COVID-19 pandemic on Japanese and US hotel stocks
Authors: Kanamura Takashi 
Published: May 2023

AbstractThis study proposes two new regime-switching volatility models to empirically analyze the impact of the COVID-19 pandemic on hotel stock prices in Japan compared with the US, taking into account the role of stock markets. The first model is a direct impact model of COVID-19 on hotel stock prices; the analysis finds that infection speed negatively affects Japanese hotel stock prices and shows that the regime continues to switch to high volatility in prices due to COVID-19 until September 2021, unlike US stock prices. The second model is a hybrid model with COVID-19 and stock market impacts on the hotel stock prices, which can remove the market impacts on regime-switching volatility; this analysis demonstrates that COVID-19 negatively affects hotel stock prices regardless of whether they are in Japan or the US. We also observe a transition to a high-volatility regime in hotel stock prices due to COVID-19 until around summer 2021 in both Japan and the US. These results suggest that COVID-19 is likely to affect hotel stock prices in general, except for the influence of the stock market. Considering the market influence, COVID-19 directly and/or indirectly affects Japanese hotel stocks through the Japanese stock market, and US hotel stocks have limited impacts from COVID-19 owing to the offset between the influence on hotel stocks and no effect on the stock market. Based on the results, investors and portfolio managers should be aware that the impact of COVID-19 on hotel stock returns depends on the balance between the direct and indirect effects, and varies from country to country and region to region.
Understanding who is and isn’t involved and engaged in health research: capturing and analysing demographic data to diversify patient and public involvement and engagement
Authors: Keane Annie , Islam Safina , Parsons Suzanne , Verma Arpana , Farragher Tracey , Forde Davine , Holmes Leah , Cresswell Katharine , Williams Susannah , Arru Paolo , Howlett Emily , Turner-Uaandja Hannah , MacGregor Issy , Grey Tracy , Arain Zahra , Scahill Maura , Starling Bella 
Published: May 2023

Abstract
Background
Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. The aim of this study was to develop to capture and analyse the characteristics of who does and doesn’t take part in patient and public involvement and engagement (PPIE) activities.

Methods
As part of its strategic focus on diversity and inclusion, Vocal developed a questionnaire to assess the demographics of people taking part in its PPIE activities. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. The questionnaire was implemented across Vocal activities between December 2018 and March 2022. In that time. Vocal was working with approximately 935 public contributors. 329 responses were received: a return rate of 29.3%. Analysis of findings and comparison against local population demographic data, and available national data related to public contributors to health research, was performed.

Results
Results show that it is feasible to assess the demographics of people who take part in PPIE activities, through a questionnaire system. Further, our emerging data indicate that Vocal are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in health research, as compared to available national data. Specifically, Vocal involves more people of Asian, African and Caribbean heritage, and includes a wider range of ages in its PPIE activities. More women than men are involved in Vocal’s work.

Conclusion
Our ‘learn by doing’ approach to assessing who does and doesn’t take part in Vocal’s PPIE activities has informed our practice and continues influence our strategic priorities for PPIE. Our system and learning reported here may be applicable and transferable to other similar settings in which PPIE is carried out. We attribute the greater diversity of our public contributors to our strategic priority and activities to promote more inclusive research since 2018.
Structured content and data management—enhancing acceleration in drug development through efficiency in data exchange
Authors: Beierle Jill , Algorri Marquerita , Cortés Marisol , Cauchon Nina S. , Lennard Andrew , Kirwan J. Paul , Oghamian Shirley , Abernathy Michael J. 
Published: May 2023

AbstractInnovation in pharmaceutical therapeutics is critical for the treatment of serious diseases with unmet medical need. To accelerate the approval of these innovative treatments, regulatory agencies throughout the world are increasingly adopting the use of expedited pathways and collaborative regulatory reviews. These pathways are primarily driven by promising clinical results but become challenging for Chemistry, Manufacturing, and Controls (CMC) information in regulatory submissions. Condensed and shifting timelines present constraints that require new approaches to the management of regulatory filings. This article emphasizes technological advances that have the potential to tackle the underlying inefficiencies in the regulatory filing eco-system.Structured content and data management (SCDM) is highlighted as a foundation for technologies that can ease the burden on both sponsors and regulators by streamlining data usage in regulatory submissions. Re-mapping of information technology infrastructure will improve the usability of data by moving away from document-based filings towards electronic data libraries. Although the inefficiencies of the current regulatory filing eco-system are more evident for products that are filed using expedited pathways, it is envisioned that the more widespread adoption of SCDM, across standard filing and review processes, will improve overall efficiency and speed in the compilation and review of regulatory submissions.
“I Have Constant Fear”: A National Qualitative Study on the Impact of COVID-19 on Cancer Care and Potential Solutions to Improve the Cancer Care Experience During the COVID-19 Pandemic
Authors: Rodriguez Gladys M. , Kumar Dhanya , Patel Manali I. 
Published: May 2023

PURPOSE The COVID-19 pandemic has greatly affected cancer care delivery for patients, including cancellation or delays in surveillance imaging, clinic visits, and treatments. Yet, gaps remain in understanding the extent of the impact of the COVID-19 pandemic on patients with cancer and potential ways to overcome these impacts. METHODS We conducted semistructured, in-depth, one-on-one qualitative interviews among adults with a past or current history of cancer in the United States. Participants from a parent quantitative survey were purposively sampled to participate in a qualitative interview. Interview questions addressed (1) experiences with cancer care delivery during the COVID-19 pandemic; (2) unmet concerns regarding care and other impacts; and (3) approaches to improve patient experiences. We conducted inductive thematic analysis. RESULTS Fifty-seven interviews were conducted. Four themes emerged: (1) concern regarding the risk of COVID-19 infection among patients with cancer and their families; (2) disruptions in care increased patients' anxiety about poor cancer outcomes and death from cancer; (3) significant social and economic impacts; and (4) increased social isolation and anxiety about the future. Suggestions for current clinical practice include (1) clear communication on patients' health risks; (2) increased attention to mental health needs and access to mental health services; and (3) routine use of telemedicine as frequently as possible when clinically appropriate. CONCLUSION These rich findings reveal the significant impact of the COVID-19 pandemic on patients with cancer and potential approaches to mitigate the impact from the patient perspective. The findings not only inform current cancer care delivery but also health system responses to future public health or environmental crises that may pose a unique health risk for patients with cancer or disrupt their care.
Gamma spectroscopy of even-even Ytterbium isotopes
Authors: Efstathiou Margarita , Karadimas Angelos , Zyriliou Aikaterini , Vasileiou Polytimos , Mertzimekis Theodoros , Chalil Achment , Pelonis Stefanos 
Published: May 2023

The even-even Ytterbium isotopes lack spectroscopic information with the increase of the neutron number and they are well deformed nuclei, presenting rotational properties. In this mass region of the nuclear chart predictions have shown rare phenomena related to nuclear structure, such as shape coexistence. In this work the population of excited states were investigated in the even-even Yb isotopes via the 2n-transfer reaction 168-174Yb (18O, 16O) 170-176Yb. The measurements were carried out at the 9 MV Tandem accelerator at the Horia Hulubei National Institute of Physics and Nuclear Engineering (IFIN-HH) in Romania. The deduced gamma-ray angular distributions in the ground state bands are found to correspond with transitions, as expected
Prevalence of feeding disorders in healthy infants and children under 3 years of age based on a questionnaire study
Authors: Kamińska-Sobczak Aleksandra , Trafalska Elżbieta , Gaszyńska Ewelina 
Published: May 2023

Introduction and purpose
Depending on the source, feeding disorders are common reasons to visit a pediatrician - reported in 2-60% of generally healthy children. This study was designed in order to assess the incidence of feeding difficulties in a group of healthy children aged 6-36 months from the Łódź region and to identify factors that may be related to feeding disorders.
Material and method
The research tool of this study was a questionnaire designed by the authors which consisted of 4 personal data questions, 9 questions about the perinatal and neonatal period, 36 feeding questions, 10 questions about child development and weight gain, 10 questions about previous medical history, 30 questions about symptoms, 8 questions about misbehavior during feeding and 14 sociodemographic questions.
Results
215 parents completed questionnaires. However, 10 of them were rejected because those participants met the exclusion criteria. Finally, 205 children were enrolled in the study. The difficulties in feeding were confirmed by the parents of 66 participants. Children with feeding difficulties were more often attended to specialist ambulatories, had been diagnosed with food allergies, and underwent speech therapy and rehabilitation. Additionally, the analysis showed that feeding disorders in mothers and the occurrence of stressful situations in the family were more frequent in children whose parents reported feeding difficulties.
Conclusions
The incidence of feeding difficulties, in the group of healthy children aged 6-36 months from the Łódź region, was higher than reported in other studies. Therefore there is an urgent need to educate parents on feeding recommendations to modify eating behaviors and overcome feeding disorders, followed by some practical advice on appropriate diet adjustment.