bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell analysis in hypersaline brines predicts a water-activity limit of microbial anabolic activity
Authors: Paris Emily R. , Arandia-Gorostidi Nestor , Klempay Benjamin , Bowman Jeff S. , Pontefract Alexandra , Elbon Claire E. , Glass Jennifer B. , Ingall Ellery D. , Doran Peter T. , Som Sanjoy M. , Schmidt Britney E. , Dekas Anne E.
Published: December 2023

Hypersaline brines provide excellent opportunities to study extreme microbial life. Here, we investigated anabolic activity in nearly 6000 individual cells from solar saltern sites with water activities (
a
w
) ranging from 0.982 to 0.409 (seawater to extreme brine). Average anabolic activity decreased exponentially with
a
w
, with nuanced trends evident at the single-cell level: The proportion of active cells remained high (>50%) even after NaCl saturation, and subsets of cells spiked in activity as
a
w
decreased. Intracommunity heterogeneity in activity increased as seawater transitioned to brine, suggesting increased phenotypic heterogeneity with increased physiological stress. No microbial activity was detected in the 0.409-
a
w
brine (an MgCl
2
-dominated site) despite the presence of cell-like structures. Extrapolating our data, we predict an
a
w
limit for detectable anabolic activity of 0.540, which is beyond the currently accepted limit of life based on cell division. This work demonstrates the utility of single-cell, metabolism-based techniques for detecting active life and expands the potential habitable space on Earth and beyond.
Clostridium butyricum
Prazmowski can degrade and utilize resistant starch via a set of synergistically acting enzymes
Authors: Pickens Tara L. , Cockburn Darrell W.
Published: December 2023

Resistant starch is a prebiotic fiber that is best known for its ability to increase butyrate production by the gut microbiota. This butyrate then plays an important role in modulating the immune system and inflammation. However, the ability to use this resistant starch appears to be a rare trait within the gut microbiota, with only a few species such as
Ruminococcus bromii
and
Bifidobacterium adolescentis
having been demonstrated to possess this ability. Furthermore, these bacteria do not directly produce butyrate themselves, rather they rely on cross-feeding interactions with other gut bacteria for its production. Here, we demonstrate that the often-used probiotic organism
Clostridium butyricum
also possesses the ability to utilize resistant starch from a number of sources, with direct production of butyrate. We further explore the enzymes responsible for this trait, demonstrating that they exhibit significant synergy, though with different enzymes exhibiting more or less importance depending on the source of the resistant starch. Thus, the co-administration of
Clostridium butyricum
may have the ability to improve the beneficial effects of resistant starch.

IMPORTANCE

Clostridium butyricum
is seeing increased use as a probiotic, due to potential health benefits tied to its ability to produce butyrate. Here, we demonstrate that this organism can use a variety of resistant starch sources and characterize the enzymes it uses to accomplish this. Given the relative rarity of resistant starch utilizing ability within the gut and the health benefits tied to resistant starch, the combined use of this organism with resistant starch in synbiotic formulations may prove beneficial.
Innovative Telerehabilitation Enhanced Care Programme (ITECP) in young and middle-aged patients with haemorrhagic stroke to improve exercise adherence: protocol of a multicentre randomised controlled trial
Authors: Zhang Yuanxing , Jin Qiansheng , Ji Cuiling , Yuan Ping , Chen Lu
Published: December 2023

Introduction

Exercise rehabilitation is crucial for promoting the rehabilitation of limb motor function in people who had stroke and is related to a better prognosis. However, the exercise adherence of patients is low, which affects the effect of exercise rehabilitation. This study aims to evaluate the effects of the Innovative Telerehabilitation Enhanced Care Programme (ITECP) on exercise adherence in young and middle-aged patients with haemorrhagic stroke. We hypothesise that patients trained with ITECP will show greater improvement in exercise adherence and muscle strength than patients with routine exercise rehabilitation.

Methods and analysis

This is a randomised controlled, evaluator-blinded multicentre superiority trial to be implemented at four tertiary grade-A hospitals in eastern, western, northern and central China. Patients in the experimental group will receive ITECP while those in the control group will receive routine exercise rehabilitation. Both groups will receive routine care. The primary outcome measure is exercise adherence, while secondary outcome measures include muscle strength, activities of daily living, exercise self-efficacy, quality of life, rate of exercise-related adverse events and readmission. These will be measured at baseline, predischarge as well as 1 and 3 months postdischarge.

Ethics and dissemination

The study has obtained ethical approval from the Medical Ethics Committee of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School (2021-381-02). The results will be shared with young and middle-aged patients with haemorrhagic stroke, policy-makers, the general public, as well as academia.

Trial registration number

Chinese Clinical Trials Registry (ChiCTR 2200066498).
Determinants of access to and use of gestational diabetes mellitus services in Kenya: a multimethod case study protocol
Authors: Obongo Angela , Tallarek Marie , Spallek Jacob
Published: December 2023

Introduction

Gestational diabetes mellitus (GDM) is a growing public health issue in many low and middle-income countries (LMICs), making up about 90% of the global burden of GDM. Additionally, LMICs’ healthcare systems are already overwhelmed by the prevalence of communicable diseases. It is crucial to understand the patterns of GDM in sub-Saharan African countries. Early detection, lifestyle and medication interventions, regular prenatal visits and effective postpartum management can help avert the future development of type 2 diabetes. GDM services present opportunities for preventive and treatment strategies for women with GDM. However, various factors contribute to challenges and obstacles in accessing GDM services, particularly suboptimal postpartum screening and follow-up. This study aims to investigate the societal and healthcare factors that facilitate or hinder access to and use of GDM services, as well as the factors that promote or obstruct the management and treatment of GDM, in Kenya, using a postcolonial theoretical approach.

Methods and analysis

The proposed study design is a multimethod case study of Kenyan GDM services. Data analysis is descriptive and thematic using SPSS software and qualitative content analysis. Data will be drawn from document reviews from the National Health Services (NHS), conversations with experts, on-site observations, semistructured questionnaires and face-to-face interviews. The study subjects are purposively sampled healthcare providers (n=15) working in clinics and hospitals offering diabetes services, purposively sampled women who have been diagnosed with GDM identified from health records (n=15) and NHS experts (n=2). The study will take place in maternal healthcare services sites in national referral hospitals and/or private hospitals (two urban and two semiurban hospitals) in Nairobi and Kisumu, Kenya.

Ethics and dissemination

The study has obtained ethical approval from the ethical committees of three institutions: Brandenburg University of Technology Cottbus-Senftenberg (EK2021-03) in Germany and Jaramogi Oginga Odinga Teaching and Referral Hospital (ISERC/1B/VOL.II/558/21) and Maseno University (MSU/DRPI/MUERC/00969/21) in Kenya. A research permit has been granted by the National Commission for Science, Technology and Innovation in Kenya. Participation in the study requires a signed informed consent form. The study findings will be shared with the scientific community and the study sites through scientific journals, academic presentations and public health and diabetes-related posters.
Study protocol for a feasibility study of microinterventions in smartphone-based assessments to reduce depressive rumination
Authors: Höller Inken , Spangenberg Lena
Published: December 2023

Introduction

Depression as well as suicidal ideation and behaviours share several precipitating and maintaining factors and are subject to the influence of overlapping constructs. One of these transdiagnostic constructs is rumination. For the treatment of rumination, a variety of interventions are already available. However, not everyone with a need receives psychotherapeutic treatment. And even if they do: implementing learnt strategies alone at home can be challenging for patients. Therefore, this study aims to test the feasibility of delivering microinterventions for the reduction of rumination in a smartphone-based setting with the goal to make these interventions accessible to a larger number of people and support their use in everyday life.

Methods and analysis

The study’s design is an uncontrolled-within-group design. Participants with at least mild depressive symptoms and reported rumination will be included and recruited via outpatient clinics as well as in the general population. The aim is to recruit at least N=70 participants. Participants first undergo a short telephone screening, a baseline assessment, a 7-day smartphone-based assessment including microinterventions in case participants report rumination and a postassessment. For feasibility purposes, primary outcomes relate to participants’ compliance, their evaluation of the smartphone-based assessment as well as the microinterventions delivered during the assessment. As a secondary goal, clinical utility will be examined. Clinical outcomes (eg, depressive symptoms, rumination) will be measured at baseline and postassessment.

Ethics and dissemination

The ethics committee of the institute of psychology of the university of Duisburg-Essen and University of Leipzig has approved the study. Study results will be disseminated to healthcare communities, in peer-reviewed science journals and at conferences.

Trial registration number

DRKS00031743.
Brief digital self-care intervention for health anxiety in a Swedish Medical University Clinic: a prospective single-group feasibility study
Authors: Österman Susanna , Hentati Amira , Forsell Erik , Axelsson Erland , Hedman-Lagerlöf Erik , Lindefors Nils , Ivanov Volen Z , Kraepelien Martin
Published: December 2023

Objectives

In routine psychiatric care in Stockholm, Sweden, a comprehensive therapist-guided intervention for clinically significant health anxiety is implemented. However, there is a need for more easily accessible self-care interventions to improve treatment dissemination. This study aimed to transform an existing therapist-guided digital intervention into a self-care intervention, reducing patient burden and used clinical resources while maintaining quality and safety.

Design

An uncontrolled feasibility study.

Setting

Conducted at Karolinska Institutet, a medical university in Sweden, with nationwide recruitment trough online advertisements.

Participants

Twenty-five adults used the self-care intervention and underwent telephone assessments, along with completing self-rated questionnaires.

Intervention

The newly developed 8-week self-care intervention was designed to be user-friendly without therapist guidance, and to facilitate high levels of behavioural engagement.

Primary and secondary outcome measures

Indicators of quality and safety, including changes in health anxiety severity (primary), clinician time, participant adherence, perceived credibility/satisfaction with the intervention and adverse events, were benchmarked against a previous study of the more comprehensive intervention it was based on.

Results

Compared with the original guided intervention, the self-care intervention was condensed in terms of text (up to 70% less reading), duration (8 weeks instead of 12) and number of exercises. Quality indicators were similar to the original version. Most participants worked actively with core components in the self-care intervention. Within-group effects on health anxiety from pretreatment to the 3-month follow-up were large (g=1.37; 95% CI 0.74 to 2.00). No serious adverse events were reported.

Conclusions

This brief digital self-care intervention shows potential for increasing access to treatment for individuals with health anxiety while reducing the burden on patients and clinical resources. Future studies should investigate the optimal type of intervention and support for different individuals, and if non-inferiority can be established.

Trial registration number

NCT05446766.
Interpregnancy weight change and risks of stillbirth and infant mortality: a protocol of a systematic review and meta-analysis
Authors: Tang Yu , Islam Nabil , Luo Rong , Wen Shi Wu , Guo Yanfang
Published: December 2023

Introduction

Interpregnancy weight change may impact two important adverse perinatal outcomes: stillbirth and infant mortality. This systematic review aims to synthesise the existing evidence on the association between interpregnancy weight change and stillbirth and infant mortality.

Methods and analysis

This systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). A comprehensive literature search of four online databases (Embase, Cochrane Libraries, Web of Science and Medline) will be conducted from inception to October 2023. Observational (longitudinal, cohort, case–control) and randomised controlled trials will be included. Interpregnancy weight/body mass index change between two consecutive pregnancies will be the exposure. The primary outcomes will be the incidence of stillbirth and infant mortality in subsequent pregnancy. The Cochrane Risk of Bias tool will be used to assess the risk of bias in the randomised controlled studies and the Risk of Bias in Non-Randomised Studies of Interventions tool will be used for observational studies. If there are sufficient data, a meta-analysis will be conducted to estimate the pooled effect size. Otherwise, qualitative descriptions of individual studies will be summarised. The heterogeneity will be statistically assessed using a χ2test and I2statistic.

Ethics and dissemination

Ethics approval is not required for this study as all results will be based on published papers. No primary data collection will be needed. Study findings will be presented at scientific conferences or published in a peer-reviewed scientific journal.

Trial registration number

A registration for this review has been submitted to PROSPERO under CRD42020222977.
Quality improvement collaboratives as part of a quality improvement intervention package for preterm births at sub-national level in East Africa: a multi-method analysis
Authors: Mandu Rogers , Miller Lara , Namazzi Gertrude , Twum-Danso Nana , Achola Kevin Jacton Abidha , Cooney Isabella , Butrick Elizabeth , Santos Nicole , Masavah Leakey , Nyakech Alphonce , Kirumbi Leah , Waiswa Peter , Walker Dilys
Published: December 2023

Background

Quality improvement collaboratives (QIC) are an approach to accelerate the spread and impact of evidence-based interventions across health facilities, which are found to be particularly successful when combined with other interventions such as clinical skills training. We implemented a QIC as part of a quality improvement intervention package designed to improve newborn survival in Kenya and Uganda. We use a multi-method approach to describe how a QIC was used as part of an overall improvement effort and describe specific changes measured and participant perceptions of the QIC.

Methods

We examined QIC-aggregated run charts on three shared indicators related to uptake of evidence-based practices over time and conducted key informant interviews to understand participants’ perceptions of quality improvement practice. Run charts were evaluated for change from baseline medians. Interviews were analysed using framework analysis.

Results

Run charts for all indicators reflected an increase in evidence-based practices across both countries. In Uganda, pre-QIC median gestational age (GA) recording of 44% improved to 86%, while Kangaroo Mother Care (KMC) initiation went from 51% to 96% and appropriate antenatal corticosteroid (ACS) use increased from 17% to 74%. In Kenya, these indicators went from 82% to 96%, 4% to 74% and 4% to 57%, respectively. Qualitative results indicate that participants appreciated the experience of working with data, and the friendly competition of the QIC was motivating. The participants reported integration of the QIC with other interventions of the package as a benefit.

Conclusions

In a QIC that demonstrated increased evidence-based practices, QIC participants point to data use, friendly competition and package integration as the drivers of success, despite challenges common to these settings such as health worker and resource shortages.

Trial registration number

NCT03112018.
Role of community-based health clubs in promoting patients’ health education for diabetes self-care management: an interventional qualitative study in a Ugandan urban setting
Authors: Lubega Martin , Ogwok James , Nabunya Brenda , Mbalinda Scovia Nalugo
Published: December 2023

Background

Self-care management support is a core component of the Chronic Care Model that emphasises the need for empowering and preparing patients to manage their healthcare. In diabetes mellitus (DM) management, health education towards self-care empowers patients to make day-to-day decisions on their own disease and live with a healthy lifestyle. Although several strategies have been undertaken to improve the management of DM in Uganda, little has been done to empower patients to manage their own health. Community-based health clubs have been suggested as a novel way of improving diabetes management especially in settings with uneven distribution of healthcare facilities and inaccessibility to healthcare services that limit patients’ awareness of the disease and self-care management. This interventional study was aimed at exploring the role of community-based health clubs in promoting patients’ health education for diabetes self-care management.

Methods

A cross-sectional qualitative study was conducted among 20 participants using focus group discussions with each having six to eight members. Only patients with diabetes who seek routine diabetes healthcare services at Wakiso Health Centre IV and had participated in the 8-week community-based health clubs’ health education sessions were recruited for the study. The audio-recordings were transcribed verbatim and translated into English; thematic data analysis was conducted to generate codes and themes. Similar codes were merged and a group consensus was reached on coding discrepancies.

Results

Three major themes on the role of health clubs in promoting patients’ health education were merged from the study. These include promoting sharing of experiences among patients, improving awareness of healthy self-care practices and offering sufficient patient–health worker interaction time.

Conclusions

This is the first publication reporting on the role of community-based health clubs in promoting patients’ health education towards diabetes self-care management in Uganda. The ability to share experiences among patients, improve patients’ awareness on healthy living practices and the increased health worker–patient interaction time contribute heavily to the capacity-building for self-care among patients.
Are in-market control systems for sunscreens adequate for consumer protection? A review of the legal framework regulating sun protection factor labels in Europe
Authors: Bacardit Aleix
Published: December 2023

Public health authorities and regulations in Europe protect the population against the damaging effects of excessive solar ultraviolet radiation through, among other means, monitoring marketed sunscreens and enforcing compliance with sun protection factor labelling requirements. In-market control processes are fundamental and complementary to other public health initiatives in a context of suboptimal sunscreen use in real-world settings. However, the laboratory testing method used for determining the sun protection factor of sunscreens is known to produce variability of results. The combination of an inherently variable testing method with the necessary rigidity of regulations generates volatility in the decision-making process followed by regulators during official in-market controls and exposes sunscreens to be susceptible to accidental mislabelling challenges. This leads to a paradoxical situation that may leave most sunscreens incorrectly labelled in the market and to a potential dilemma for authorities. The issue may get further amplified when non-official sources echo and broadcast uncontrolled messages about sunscreens to the public. Amending current regulation with a tolerance level to compare results that accommodates the variability of results from sun protection factor tests would ease decision-making, bring robustness to an uncertain legal landscape, make more efficient the efforts to convey consistent public health messages about the benefits of sunscreen use and better protect users. There are precedents of using tolerance levels for regulatory decision-making in other fields, and a review of the applicable legal landscape in Europe reveals that implementing it for sunscreens would only require one change to current cosmetics law.
Commentary on oncolytic viruses: past, present, and future
Authors: Larson Christopher , Oronsky Bryan , Reid Tony R
Published: December 2023

Whither oncolytic viruses? From the peak of their popularity in the early 2000s, when the ONYX-015 adenovirus had just entered the clinic, and then again in 2015 when the Food and Drug Administration-approved talimogene laherparepvec (also known as OncoVEXGM-CSF), which briefly revived interest, oncolytic viruses (OVs) have mostly fallen out of favor despite the many pharmaceutical companies with OVs in development.

This commentary enumerates and addresses the core conceptions, perceptions, and misconceptions that characterize the current ‘trough of disillusionment’ in which the field of anticancer virotherapy finds itself and suggests reasons for optimism.
Real-world evaluation of Brainomix e-Stroke software
Authors: Mallon Dermot , Fallon Matthew , Blana Eirini , McNamara Cillian , Menon Arathi , Ip Chak Lam , Garnham Jack , Yousry Tarek , Cowley Peter , Simister Robert , Doig David
Published: December 2023

Background and purpose

Brainomix e-Stroke is an artificial intelligence-based decision support tool that aids the interpretation of CT imaging in the context of acute stroke. While e-Stroke has the potential to improve the speed and accuracy of diagnosis, real-world validation is essential. The aim of this study was to prospectively evaluate the performance of Brainomix e-Stroke in an unselected cohort of patients with suspected acute ischaemic stroke.

Methods

The study cohort included all patients admitted to the University College London Hospital Hyperacute Stroke Unit between October 2021 and April 2022. For e-ASPECTS and e-CTA, the ground truth was determined by a neuroradiologist with access to all clinical and imaging data. For e-CTP, the values of the core infarct and ischaemic penumbra were compared with those derived from syngo.via, an alternate software used at our institution.

Results

1163 studies were performed in 551 patients admitted during the study period. Of these, 1130 (97.2%) were successfully processed by e-Stroke in an average of 4 min. For identifying acute middle cerebral artery territory ischaemia, e-ASPECTS had an accuracy of 77.0% and was more specific (83.5%) than sensitive (58.6%). The accuracy for identifying hyperdense thrombus was lower (69.1%), which was mainly due to many false positives (positive predictive value of 22.9%). Identification of acute haemorrhage was highly accurate (97.8%) with a sensitivity of 100% and a specificity of 97.6%; false positives were typically caused by areas of calcification. The accuracy of e-CTA for large vessel occlusions was 91.5%. The core infarct and ischaemic penumbra volumes provided by e-CTP strongly correlated with those provided by syngo.via (ρ=0.804—0.979).

Conclusion

Brainomix e-Stroke software provides rapid and reliable analysis of CT imaging in the acute stroke setting although, in line with the manufacturer’s guidance, it should be used as an adjunct to expert interpretation rather than a standalone decision-making tool.
Determining early marine survival and predation by endothermic predators on acoustically tagged Atlantic salmon (Salmo salar) post-smolts
Authors: English Greg , Wilson Brent M. , Lawrence Michael J. , Black Matt , Hawkes James P. , Hardie David C. , Daniels Jason M. , Carr Jonathan W. , Rycroft Claire , Crossin Glenn T. , Whoriskey Fred G. , den Heyer Cornelia E. , Bordeleau Xavier , McKindsey Christopher W. , Trudel Marc
Published: December 2023

Many Atlantic salmon ( Salmo salar) populations have experienced significant declines for decades throughout North America and Europe. Mortality due to marine mammal predation during their early marine life could be an important factor contributing to these declines and limiting their population recoveries. However, quantifying predation events, and particularly the extent of marine mammal predation on Atlantic salmon, remains a challenge. In this study, we estimated the contribution of mesothermic and endothermic species predation to the mortality of Atlantic salmon post-smolts during their early marine life using acoustic telemetry. Predation events were inferred from changes in temperatures and depths experienced by acoustically tagged hatchery-reared Atlantic salmon smolts. No salmon were consumed by mesothermic predators, with most endothermic predation events being classified as marine mammals. Post-smolt mortality during the study period was low overall in both years (13.1%–16.7%), with endothermic predation accounting for 33.1%–42.9% of all marine mortality events (5.2%–5.6% mortality). Our results suggest that the current low return of adult Atlantic salmon observed in this area in recent years was not heavily influenced by endothermic predation on post-smolts in the first weeks at sea.
Compact stars in $$f(T) = T +\xi T^\beta $$ gravity
Authors: de Araujo J. C. N. , Fortes H. G. M.
Published: December 2023

The Teleparallel Theory is equivalent to General Relativity, but whereas in the latter gravity has to do with curvature, in the former gravity is described by torsion. As is well known, there is in the literature a host of alternative theories of gravity, among them the so called extended theories, in which additional terms are added to the action, such as for example in the f(R) and f(T) gravities, where R is the Ricci scalar and T is the scalar torsion, respectively. One of the ways to probe alternative gravity is via compact objects. In fact, there is in the literature a series of papers on compact objects in f(R) and f(T) gravity. In particular, there are several papers that consider $$f(T) = T + \xi T^2$$

f

(
T
)

=
T
+
ξ

T
2

, where $$\xi $$
ξ
is a real constant. In this paper, we generalise such extension considering compact stars in $$f (T ) = T + \xi T^\beta $$

f

(
T
)

=
T
+
ξ

T
β

gravity, where $$\xi $$
ξ
and $$\beta $$
β
are real constants and looking out for the implications in their maximum masses and compactness in comparison to the General Relativity. Also, we are led to constrain the $$\beta $$
β
parameter to positive integers which is a restriction not imposed by cosmology.
Reframing China’s Territory and Sovereignty in Cyberspace: Exploring Conceptual Territorialization and Claims of Cyber Sovereignty
Authors: HWANG JI-JEN
Published: December 2023

The Chinese government has implemented a range of cyberspace management policies in recent years in an effort to claim what it refers to as its “cyber sovereignty.” Beijing bases this on its understanding of cyberspace as an additional geographical battlefield. This paper investigates how cyberspace may be regarded from this perspective and discusses how the Chinese government endeavors to manage its cyberspace and legitimizes this control through the adoption of cyber laws. The analysis shows that China’s sovereignty claims over cyberspace can be supported by four recognized factors of territorialization. These include authority, cyber culture, functional borders, and individuals. This study illustrates that these sovereignty claims can indeed be justified despite China’s current inability to completely explain them. The territorialization of cyberspace is a complex and evolving issue, however, and finding a way forward will require cooperation and understanding among all the stakeholders.
FIRM-SPECIFIC RISK, GROWTH OPTIONS, AND INNOVATION RENT
Authors: MISHRA CHANDRA S.
Published: December 2023

The greater the firm-specific risk, the more valuable are the innovative opportunities underlying the growth options, and the greater the innovation rent. We examine whether firm-specific risk drives the firm’s innovation rent. We find that the firm-specific risk positively moderates the association between firm innovativeness and firm surplus. Innovation rent is the change in firm surplus per unit change in the knowledge capital (accumulated R&D stock). The firm surplus is the excess market value of the firm over shareholder expectations. We further examine whether the growth options embedded in the firm’s assets mediate the association between firm innovativeness and firm surplus. Growth options positively mediate the association between knowledge capital and firm surplus. The firm-specific risk enhances the value of innovative opportunities underlying the firm’s growth options that are exercised such that the firm earns a value surplus. Our results are consistent with the strategic rent model and emerging behavioural theory.
The Next Food Revolution Is Here: Recombinant Microbial Production of Milk and Egg Proteins by Precision Fermentation
Authors: Nielsen M.B. , Meyer A.S. , Arnau J.
Published: December 2023

Animal-based agriculture and the production of protein-rich foods from animals, particularly from ruminants, are not sustainable and have serious climate effects. A new type of alternative proteins is now on the menu, namely animal proteins produced recombinantly by microbial fermentation. This new technology, precision fermentation, is projected to completely disrupt traditional animal-based agriculture. Certain milk and egg proteins along with specific meat substitute analog components produced by precision fermentation are already entering the market. This first wave of precision fermentation products targets the use of these proteins as protein additives, and several commercial players are already active in the field. The cost-efficiency requirements involve production titers above 50 g/L which are several orders of magnitude higher than those for pharmaceutical protein manufacture, making strain engineering, process optimization, and scale-up critical success factors. This new development within alternative proteins defines a new research direction integrating biotechnology, process engineering, and sustainable food protein production.
Review—Photoluminescence Spectroscopy of Mn2+-Activated Phosphors: Part I. Fundamentals
Authors: Adachi Sadao
Published: December 2023

The purpose of this review article is to present and clarify the various phosphor properties of Mn2+ activator ion in the intra-3d
5-shell electronic configuration. Even though the concepts of intra-3d
5-shell electronic configuration in Mn2+ ion are well understood at this time, some important properties of this ion in the various host materials have been hampered by a lack of definite knowledge of such phosphor systems. The Mn2+-activated phosphor properties examined in the present article can be classified into seven groups: (1) spectral feature of Mn2+-ion photoluminescence (PL) and PL excitation (PLE) transitions, (2) temperature dependence of PL intensity, (3) temperature dependence of PL decay lifetime, (4) Mn2+ concentration effects on PL properties, (5) excitonic transition-related Mn2+ luminescence, (6) crystalline morphology effects: bulk sample vs microcrystalline sample, and (7) crystalline morphology effects: quantum confinement-induced phenomena. Key expressions for theoretically analyzing PL and PLE spectral features, together with PL intensity variation with temperature, for the Mn2+ emission were discussed in detail. A detailed discussion is also given of the acceptability of such phosphor properties and behaviors from an applicational point of view.
An Intelligent Framework Based on Deep Learning for Online Quran Learning during Pandemic
Authors: Nigar Natasha , Wajid Amna , Ajagbe Sunday Adeola , Adigun Matthew O.
Published: December 2023

The COVID-19 pandemic influenced the whole world and changed social life globally. Social distancing is an effective strategy adopted by all countries to prevent humans from being infected. Al-Quran is the holy book of Muslims and its listening and reading is one of the obligatory activities. Close contact is essential in traditional learning system; however, most of the Al-Quran learning schools were locked down to minimize the spread of COVID-19 infection. To address this limitation, in this paper, we propose a novel system using deep learning to identify the correct recitation of individual alphabets, words from a recited verse and a complete verse of Al-Quran to assist the reciter. Moreover, in the proposed approach, if the user recites correctly, his/her voice is also added to the existing dataset to leverage proposed approach effectiveness. We employ mel-frequency cepstral coefficients (MFCC) to extract voice features and long short-term memory (LSTM), a recurrent neural network (RNN) for classification. The said approach is validated using the Al-Quran dataset. The results demonstrate that the proposed system outperforms the state-of-the-art approaches with an accuracy rate of 97.7%. This system will help the Muslim community all over the world to recite the Al-Quran in the right way in the absence of human help due to similar future pandemics.
Figure S5 from Inhibition of BCL2 Family Members Increases the Efficacy of Copper Chelation in BRAFV600E-Driven Melanoma
Authors: Kim Ye-Jin , Tsang Tiffany , Anderson Grace R. , Posimo Jessica M. , Brady Donita C.
Published: December 2023

Supplemental Figure S5. TTM reduces BCL2 protein expression and lowers the apoptotic threshold when combined with BH3 mimetics in BRAFV600E-positive melanoma.
Supplementary Tables 1 and 2 from RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis
Authors: Samanta Debangshu , Park Youngrok , Andrabi Shaida A. , Shelton Laura M. , Gilkes Daniele M. , Semenza Gregg L.
Published: December 2023

Supplementary Table S1. Oligonucleotide sequences of shRNAs targeting PHGDH. Table S2. Oligonucleotide sequence of RT-qPCR primers.
Supplementary Figure Legends from PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis
Authors: Samanta Debangshu , Park Youngrok , Andrabi Shaida A. , Shelton Laura M. , Gilkes Daniele M. , Semenza Gregg L.
Published: December 2023

Legends for Supplementary Figures S1-S6
Suoplementary Materials and Methods from RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis
Authors: Samanta Debangshu , Park Youngrok , Andrabi Shaida A. , Shelton Laura M. , Gilkes Daniele M. , Semenza Gregg L.
Published: December 2023

More detailed description of the abbreviated Materials and Methods that appears in the main text.
Suoplementary Materials and Methods from PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis
Authors: Samanta Debangshu , Park Youngrok , Andrabi Shaida A. , Shelton Laura M. , Gilkes Daniele M. , Semenza Gregg L.
Published: December 2023

More detailed description of the abbreviated Materials and Methods that appears in the main text.
Supplementary Methods from Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Mueller Adam C. , Piper Miles , Goodspeed Andrew , Bhuvane Shiv , Williams Jason S. , Bhatia Shilpa , Phan Andy V. , Van Court Benjamin , Zolman Kathryn L. , Peña Brisa , Oweida Ayman J. , Zakem Sara , Meguid Cheryl , Knitz Michael W. , Darragh Laurel , Bickett Thomas E. , Gadwa Jacob , Mestroni Luisa , Taylor Matthew R.G. , Jordan Kimberly R. , Dempsey Peter , Lucia M. Scott , McCarter Martin D. , Chiaro Marco Del , Messersmith Wells A. , Schulick Richard D. , Goodman Karyn A. , Gough Michael J. , Greene Casey S. , Costello James C. , Neto Antonio Galveo , Lagares David , Hansen Kirk C. , Van Bokhoven Adrie , Karam Sana D.
Published: December 2023

Supplementary Methods
Figure S5 from Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Mueller Adam C. , Piper Miles , Goodspeed Andrew , Bhuvane Shiv , Williams Jason S. , Bhatia Shilpa , Phan Andy V. , Van Court Benjamin , Zolman Kathryn L. , Peña Brisa , Oweida Ayman J. , Zakem Sara , Meguid Cheryl , Knitz Michael W. , Darragh Laurel , Bickett Thomas E. , Gadwa Jacob , Mestroni Luisa , Taylor Matthew R.G. , Jordan Kimberly R. , Dempsey Peter , Lucia M. Scott , McCarter Martin D. , Chiaro Marco Del , Messersmith Wells A. , Schulick Richard D. , Goodman Karyn A. , Gough Michael J. , Greene Casey S. , Costello James C. , Neto Antonio Galveo , Lagares David , Hansen Kirk C. , Van Bokhoven Adrie , Karam Sana D.
Published: December 2023

Supplementary figure
Figure S2 from Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Mueller Adam C. , Piper Miles , Goodspeed Andrew , Bhuvane Shiv , Williams Jason S. , Bhatia Shilpa , Phan Andy V. , Van Court Benjamin , Zolman Kathryn L. , Peña Brisa , Oweida Ayman J. , Zakem Sara , Meguid Cheryl , Knitz Michael W. , Darragh Laurel , Bickett Thomas E. , Gadwa Jacob , Mestroni Luisa , Taylor Matthew R.G. , Jordan Kimberly R. , Dempsey Peter , Lucia M. Scott , McCarter Martin D. , Chiaro Marco Del , Messersmith Wells A. , Schulick Richard D. , Goodman Karyn A. , Gough Michael J. , Greene Casey S. , Costello James C. , Neto Antonio Galveo , Lagares David , Hansen Kirk C. , Van Bokhoven Adrie , Karam Sana D.
Published: December 2023

Supplementary figure
Data from Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Mueller Adam C. , Piper Miles , Goodspeed Andrew , Bhuvane Shiv , Williams Jason S. , Bhatia Shilpa , Phan Andy V. , Van Court Benjamin , Zolman Kathryn L. , Peña Brisa , Oweida Ayman J. , Zakem Sara , Meguid Cheryl , Knitz Michael W. , Darragh Laurel , Bickett Thomas E. , Gadwa Jacob , Mestroni Luisa , Taylor Matthew R.G. , Jordan Kimberly R. , Dempsey Peter , Lucia M. Scott , McCarter Martin D. , Chiaro Marco Del , Messersmith Wells A. , Schulick Richard D. , Goodman Karyn A. , Gough Michael J. , Greene Casey S. , Costello James C. , Neto Antonio Galveo , Lagares David , Hansen Kirk C. , Van Bokhoven Adrie , Karam Sana D.
Published: December 2023

Abstract
Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy.
Significance:
Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease.

See related commentary by Garcia Garcia et al., p. 3158
LncRNA CASC2 Alleviates Renal Interstitial Inflammation and Fibrosis through MEF2C Downregulation-Induced Hinderance of M1 Macrophage Polarization
Authors: Hu Jinping , Zhang Xiaoyan , Ma Feng , Huang Chen , Jiang Yali
Published: December 2023

Introduction: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) alleviates the progression of diabetic nephropathy by inhibiting inflammation and fibrosis. This study investigated how CASC2 impacts renal interstitial fibrosis (RIF) through regulating M1 macrophage (M1) polarization. Method: Nine-week-old mice underwent unilateral ureteral obstruction (UUO) establishment. Macrophages were induced toward M1 polarization using lipopolysaccharide (LPS) in vitro and cocultured with fibroblasts to examine how M1 polarization influences RIF. LnCeCell predicted that CASC2 interacted with myocyte enhancer factor 2 C (MEF2C), which was validated by dual-luciferase reporter assay. CASC2/MEF2C overexpression was achieved by lentivirus-expressing lncRNA CASC2 injection in vivo or CASC2 and MEF2C transfection in vitro. Renal injury was evaluated through biochemical analysis and hematoxylin-eosin/Masson staining. Macrophage infiltration and M1 polarization in the kidney and/or macrophages were detected by immunofluorescence, flow cytometry, and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR). Expressions of CASC2, MEF2C, and markers related to inflammation/M1/fibrosis in the kidney/macrophages/fibroblasts were analyzed by qRT-PCR, fluorescence in situ hybridization, enzyme-linked immunosorbent assay, and/or Western blot. Result: In the kidneys of mice, CASC2 was downregulated and macrophage infiltration was promoted time-dependently from days 3 to 14 post-UUO induction; CASC2 overexpression alleviated renal histological abnormalities, hindered macrophage infiltration and M1 polarization, downregulated renal function markers serum creatinine and blood urea nitrogen and inflammation/M1/fibrosis-related makers, and offset UUO-induced MEF2C upregulation. LncRNA CASC2 overexpression inhibited fibroblast fibrosis and M1 polarization in cocultured fibroblasts with LPS-activated macrophages. Also, CASC2 bound to MEF2C and inhibited its expression in LPS-activated macrophages. Furthermore, MEF2C reversed the inhibitory effects of lncRNA CASC2 overexpression. Conclusion: CASC2 alleviates RIF by inhibiting M1 polarization through directly downregulating MEF2C expression. CASC2 might represent a promising value of future investigations on treatment for RIF.
Early Postoperative Complications of One-Stage Substitution Urethroplasty with Oral Mucosa Graft: A Monocentric Retrospective Study
Authors: Kunz Inga , Wirtz Lisa-Marie , Roggenbuck Ulla , Krege Susanne , Kroepfl Darko
Published: December 2023

Introduction: We report early postoperative complications (PCs) (≤90 days) of one-stage oral mucosa graft (OMG) urethroplasty in treatment of acquired anterior urethral strictures. Material and Methods: In this study, we evaluated 530 males who underwent one-stage substitution urethroplasty (SU) between September 1996 and October 2020. Medical records were reviewed to identify and classify early PCs based on the Clavien-Dindo classification (CDC). We subdivided the PCs into three groups with different kinds of complications which allowed us a more detailed analysis concerning general surgical complications (GSCs), donor site morbidity (DSM) and complications specific for free graft urethroplasty (CSUs). The influence of patient demographics, stricture characteristics and operative procedure on the occurrence of PCs was analysed. Results: Early (90-day) PCs occurred in 90 (16.98%) patients, whereas only 19 patients (3.58%) experienced serious events (CDC grades III and IV). Early complications include 4.5% GSCs, 1.7% DSM and 10.8% CSUs. Only stricture length turned out to be an independent statistically significant risk factor for the occurrence of early PCs. There was a trend towards a higher rate of complications in patients with ASA III compared to ASA I. Conclusion: The incidence of severe early complications in patients undergoing one-stage SU with OMG is low.
Adenokarzinome der Lunge: Feinstaubbelastung fördert Tumorentwicklung
Authors: Hekmat Khosro
Published: December 2023

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.