bluuebunny/crossref_metadata_2025 huggingface dataset:
Zum ethischen Paradigmenwechsel in der Debatte um (erbliches) Genome-Editing an Embryonen in vitro
Authors: Schickl Hannah
Published: December 2023

Eine medizinische Anwendung von Genome-Editing (GE) an menschlichen Embryonen in vitro im Reproduktionskontext ist durch die Entdeckung einer entsprechenden Nutzung von CRISPR/Cas (Jinek et al. 2012; siehe Fehse et al., Kap. 7; siehe auch Fehse et al. 2021) in den Bereich des Machbaren gerückt. Spätestens seit 2015 wurde die Möglichkeit, genetische Erkrankungen durch die „Korrektur“ von Genen vor deren Ausbruch ggf. auch für Nachkommen zu „heilen“, international sowohl unter Wissenschaftlern als auch in den Medien und innerhalb der Gesellschaft intensiv diskutiert. Aufgrund des rasanten Fortschritts der Forschung und Anwendung von CRISPR/Cas auch an menschlichen Zellen kam es dabei jeweils ausgelöst durch aufsehenerregende neue Versuche innerhalb weniger Jahre zu zwei bemerkenswerten Umbrüchen in der Debatte. Das erste, 2015 berichtete GE an nicht lebensfähigen menschlichen Embryonen im Forschungskontext (Liang et al. 2015) führte innerhalb der Wissenschaftscommunity zu Unsicherheiten und zog Rufe nach einem zeitlich befristeten Moratorium vor allem für den Anwendungskontext (Baltimore et al. 2015; Lander 2015; Reich et al. 2015), aber auch nach einem kompletten Verbot selbst für den Forschungskontext (Lanphier et al. 2015) nach sich. Ein Moratorium sollte dazu genutzt werden, Diskussionen anzustoßen, um zu einer Entscheidung über die ethische Zulässigkeit von Keimbahninterventionen (KBI) sowie zu einem breiten gesellschaftlichen Konsens zu deren Erwünschtheit zu finden. Zu diesem Zeitpunkt war man sich selbst auf der medizinischen Ebene unklar darüber, „ob und inwieweit es nützliche klinische Anwendungen für Keimbahnanwendungen gibt“ (NCoB 2015: 16). Entsprechend groß war die Verunsicherung auf der ethischen Ebene, sodass zum Teil davon ausgegangen wurde, es ließe sich in diesem Fall überhaupt nicht zwischen „moralisch richtig“ und „moralisch falsch“ unterscheiden (Reich et al. 2015: 21). Die wiederholten Rufe nach einer gesellschaftlichen Debatte durch Gremien, die zur Klärung ebensolcher ethischer und rechtlicher Fragen eingesetzt wurden (u. a. NASEM 2015; EGE 2016; DER 2017; CCNE et al. 2020; EGE 2021), waren Ausdruck dieser Verunsicherung und muteten eher wie ein Versuch an, wenigstens eine Forderung aufzustellen. Dabei mangelte es an einer Spezifizierung, warum und wie die Gesellschaft einbezogen werden sollte (Kaelin 2018), die Rufe blieben phrasenhaft, akzeptanzheischend.
Retrovirale Vektoren – Effiziente Gentaxis für unterschiedliche Gentherapien
Authors: Morgan Michael A. , Galla Melanie , Fehse Boris , Schambach Axel
Published: December 2023

Die genetische Information, die als Bauplan für das menschliche Leben dient, ist in der chromosomalen DNA eines jeden Zellkerns und in der DNA unserer zellulären Kraftwerke, den Mitochondrien, gespeichert. Im menschlichen Körper ist die Expression der Gene gut reguliert und ihr orchestriertes Zusammenspiel erlaubt die Spezialisierung unserer Zellen und Gewebe. Gemäß dem Grundprinzip der Biologie wird während der Genexpression die genetische Information von der stabilen DNA-Form in eine transiente Informationsstruktur, die RNA, umgeschrieben. Es existiert eine Reihe unterschiedlicher Arten von RNA mit verschiedensten Funktionen in der Zelle. Insbesondere kann die sog. „messenger“ oder Boten-RNA (mRNA) in Proteine übersetzt werden, die den verschiedenen Zelltypen in unserem Körper ihre morphologischen, physiologischen und funktionellen Eigenschaften, den sog. Phänotyp, verleihen (siehe Abb. 3.1). Für die Steuerung der Genexpression sind bestimmte genetische Strukturen und Elemente erforderlich, die als Promotoren und Enhancer-Sequenzen bezeichnet werden. Mithilfe solcher Elemente ist es auch möglich, künstlich zu steuern, wie hoch oder niedrig ein Gen exprimiert wird, und auch ein Gen in bestimmten Zelltypen an- oder auszuschalten. Dieses Wissen über Genstruktur und -expression wird für medizinische Zwecke wie die Gentherapie genutzt.
Sleeping Beauty: Ein „springendes Gen“ für Anwendungen in der Gentechnik
Authors: Nurieva Wasifa , Sandoval-Villegas Nicolás , Ivics Zoltán
Published: December 2023

Der Begriff „Transposition“ stammt aus dem Lateinischen („transponere“) und bedeutet „versetzen“. Entsprechend handelt es sich bei Transposons um DNA-Abschnitte mit der Fähigkeit, ihre Position im Genom zu verändern. Solche mobilen genetischen Elemente kommen in verschiedenen Organismen vor und können eine hocheffiziente Integration ihrer Gene in das Genom ihrer Wirtszellen vermitteln. Als experimentelle Werkzeuge werden von Transposons abgeleitete DNA-Transfervehikel auf regulierte und leistungsstarke Weise für die stabile Einführung unterschiedlicher DNA-Sequenzen, z. B. selektierbarer Markergene und therapeutischer Genkonstrukte, in die Genome von Zielzellen genutzt. Transposons eröffnen somit mehrere Möglichkeiten für Genommodifikationen in Menschen und bei Tieren, Bakterien und Pflanzen. Als Beispiel sei die Erzeugung transgener Zellen in Gewebekulturen für verschiedene Forschungsziele genannt. Dieser Ansatz kann auch für die Herstellung pluripotenter Stammzellen und die Erzeugung von Tieren mit vererbbaren genetischen Veränderungen für die Grundlagen- sowie die angewandte Forschung und schließlich für die Therapie genetischer Erkrankungen beim Menschen eingesetzt werden. Da die Transposonkomponenten i. d. R. als nackte Nukleinsäuren (DNA und RNA) oder rekombinante Proteine vorliegen, ist ihre Verwendung einfach, sicher und z. B. im Vergleich mit viralen Vektoren wirtschaftlich konkurrenzfähig.
Genome-Editing – Gentherapie 2.0 oder nur eine Wunschvorstellung?
Authors: Fehse Boris , Grünewald Julian , Petri Karl
Published: December 2023

Die Idee, vererbbare Krankheiten durch eine Korrektur der ihnen zugrunde liegenden genetischen Defekte zu behandeln oder ihren Ausbruch im Idealfall sogar zu verhindern, wurde seit Beginn der 1960er-Jahre diskutiert, u. a. in Arbeiten der beiden Nobelpreisträger Joshua Lederberg (Lederberg 1966) und Edward Tatum (Tatum 1966). Beide erwogen potenzielle Vor- und Nachteile sowohl der Keimbahnkorrektur als auch einer somatischen Gentherapie, also der Behandlung betroffener Körperzellen. Dabei gingen sie von der Vision einer exakten Korrektur der fehlerhaften Erbinformation aus – ein Ansatz, der später als Genomchirurgie bezeichnet wurde, während man heute eher von Genome-Editing spricht. Auch wenn es sich angesichts des Fehlens der technischen Möglichkeiten ihrer Umsetzung zunächst tatsächlich eher um eine theoretische Vision handelte, die nicht zuletzt aus philosophischer Sicht diskutiert wurde, war den Protagonisten bereits bewusst, dass sich durch die (schon damals rasante) Entwicklung der Molekularbiologie relativ bald die Möglichkeit ergeben würde, Gene gezielt zu modifizieren.
Publishing on the ModHub
Authors: Brumbaugh Zander , Leithner Manuel
Published: December 2023

You have now successfully created six mods and should feel confident in bringing your own ideas for mod creations to life. In this chapter, we will explore how to publish your creations to the ModHub for others to download and play while potentially earning revenue with your mod’s success.
Getting Started with the GIANTS Editor
Authors: Brumbaugh Zander , Leithner Manuel
Published: December 2023

The GIANTS Editor is the main application you will use to create mods. In the editor, you can run scripts, preview and manipulate models, and stage your creations before publishing them to the ModHub. In this chapter, we will explore the features and tools of the GIANTS Editor. Familiarizing yourself with the interfaces that mod creators work with is the first step in the path to making your own.
The Lua Programming Language
Authors: Brumbaugh Zander , Leithner Manuel
Published: December 2023

The LUA language is a fast, procedural programming language used by the GIANTS Engine and many other applications. LUA was originally created in 1993 due to software trade barriers in Brazil, which prevented many from buying specialized software from outside the country. Because of this, the language was designed to be highly customizable with a simple API in the C programming language so that programmers could easily make changes to fit their needs.
Bayesian inference for form-factor fits regulated by unitarity and analyticity
Authors: Flynn J. M. , Jüttner A. , Tsang J. T.
Published: December 2023

Abstract

We propose a model-independent framework for fitting hadronic form-factor data, which is often only available at discrete kinematical points, using parameterisations based on to unitarity and analyticity. In this novel approach the latter two properties of quantum-field theory regulate the ill-posed fitting problem and allow model-independent predictions over the entire physical range. Kinematical constraints, for example for the vector and scalar form factors in semileptonic meson decays, can be imposed exactly. The core formulae are straight-forward to implement with standard math libraries. We take account of a generalisation of the original Boyd Grinstein Lebed (BGL) unitarity constraint for form factors and demonstrate our method for the exclusive semileptonic decay Bs→ Kℓν, for which we make a number of phenomenologically relevant predictions, including the CKM matrix element |Vub|.
Gluon TMD fragmentation function into quarkonium
Authors: Echevarria Miguel G. , Romera Samuel F. , Scimemi Ignazio
Published: December 2023

Abstract

We compute the gluon transverse-momentum-dependent fragmentation function (TMDFF) at next-to-leading order (NLO) into heavy quarkonium in the color-octet $$ {}^3{S}_1^{\left[8\right]} $$

S
1

8

3

channel, based on the NRQCD factorization approach. The spurious rapidity divergences are explicitly shown to cancel in a well-defined TMDFF, which incorporates the needed soft factor. We also compute the integrated gluon FF at NLO in the same $$ {}^3{S}_1^{\left[8\right]} $$

S
1

8

3

channel, and show that the matching coefficient of the TMDFF onto the FF at large transverse momentum is the expected one. These results are relevant to perform precise and sensible phenomenological studies of transverse-momentum spectra of quarkonium production, for which the production mechanism through fragmentation plays a relevant role, like in the future Electron-Ion Collider.
Triple-collinear splittings with massive particles
Authors: Dhani Prasanna K. , Rodrigo Germán , Sborlini German F. R.
Published: December 2023

Abstract

We analyze in detail the most singular behaviour of processes involving triple-collinear splittings with massive particles in the quasi-collinear limit, and present compact expressions for the splitting amplitudes and the corresponding splitting kernels at the squared-amplitude level. Our expressions fully agree with well-known triple-collinear splittings in the massless limit, which are used as a guide to achieve the final expressions. These results are important to quantify dominant mass effects in many observables, and constitute an essential ingredient of current high-precision computational frameworks for collider phenomenology.
Comparison between stapled hemorrhoidopexy and harmonic scalpel hemorrhoidectomy in the management of third- and fourth-degree piles: a randomized clinical trial
Authors: Nada Mohamed Ali Mohamed , Awad Philobater Bahgat Adly , Kirollos Andrew Morcos Azmy , Abdelaziz Mostafa Mohamed , Mohamed Karim Mohamed Saad , Awad Kerolos Bahgat Adly , Hassan Basma Hussein Abdelaziz
Published: December 2023

Background

This study compared the results of stapled hemorrhoidopexy (SH) and harmonic scalpel hemorrhoidectomy (HSH) in the management of grade III and grade IV piles regarding the time of the procedure, postoperative pain, patient satisfaction, wound infection, bleeding, incontinence, and recurrence within 1 year.

Patients and methods

This was a single-blind, prospective, randomized, controlled, single-center trial conducted from January to December 2022 that included 50 (68.75%) male and 20 (31.25%) female patients with third- and fourth-degree piles.

Results

The patients were divided into two groups of 35 patients each. Group I underwent SH and group II underwent HSH. The mean age of group I was 42.94 years and of group II, 42.20 years. The mean time of the procedure was 24.42 min ± 2.367 for SH and 31.48 min ± 2.21 for HSH. Postoperative pain in group I was lower than in group II during the first 2 weeks, but there was persistent mild pain in most patients in group I at the 2‑week follow-up. In group II there was significant improvement in pain after 2 weeks, with higher patient satisfaction. Wound infection was detected in 3 (5%) patients in group I and no patients in group II (p = 0.077). Postoperative bleeding occurred in 4 (11.4%) patients in group I in the form of spotting after defecation only during the first postoperative month; no bleeding was detected in group II (p = 0.039). There were 3 (15%) cases of flatus incontinence but after taking a detailed history these were found to be cases of urgency to defecate rather than incontinence. There were 7 (20%) cases of recurrence at the 1‑year follow-up in group I and 1 (2.9%) case in group II (p = 0.024).

Conclusion

Compared with SH, HSH was safer, easier, and associated with a lower incidence of recurrence after 1 year and with higher patient satisfaction.
Detection of saffron adulteration by other plant species using SPME-GC-HRMS
Authors: Filatova Maria , Hajslová Jana , Stupak Michal
Published: December 2023

Saffron, a spice obtained by drying the scars of saffron flowers (Crocus sativus L.), is by far the most valuable spice in the world, and, not surprisingly, it often becomes an object of adulteration. In this study, non-target screening of volatile compounds in 38 authentic saffron samples and 25 samples of plant materials, potential saffron adulterants (safflower, calendula, capsicum and turmeric) was performed using headspace solid-phase microextraction for sample extraction followed by gas chromatography coupled to high-resolution mass spectrometry (HS-SPME-GC-HRMS) for non-target volatiles screening. The chemometric analysis of generated data by principal component analysis (PCA) and partial least squares discriminative analysis (PLS-DA) showed good separation of authentic saffron from potential plant adulterants. Significant compounds (‘markers’) for each group of these plants, as well as for saffron were tentatively identified. The target screening of selected ‘markers’ in model admixtures enabled simple and reliable detection levels as low as 2% w/w of safflower, calendula, capsicum or turmeric present in saffron.
Nitrous oxide emissions and N-cycling gene abundances in a drip-fertigated (surface versus subsurface) maize crop with different N sources
Authors: Guardia Guillermo , García-Gutiérrez Sandra , Vallejo Antonio , Ibáñez Miguel A. , Sanchez-Martin Laura , Montoya Mónica
Published: December 2023

Surface drip fertigation has demonstrated promising results regarding the mitigation of nitrous oxide (N2O) emissions. The use of subsurface irrigation may offer the possibility of reducing these emissions further due to the modification of the soil moisture profile and N allocation, both of which affect the biochemical processes leading to N2O fluxes. However, the mitigation potential of subsurface irrigation combined with different mineral nitrogen (N) fertilizers (ammonium or nitrate-based, use of nitrification inhibitors) still needs to be evaluated. To respond to this need, a 2-year field experiment was set up in central Spain to test two different drip-fertigation systems (surface and subsurface at 30 cm depth) and four N fertilization treatments (control, calcium nitrate, and ammonium sulfate with or without the nitrification inhibitor 3,4-dimethylpyrazole phosphate, DMPP) in an irrigated maize (Zea mays L.) crop. Nitrous oxide emissions, mineral N concentrations (ammonium, NH4+, and nitrate, NO3−), and abundance of key N genes involved in nitrification and denitrification processes were measured in two soil layers (0–20 and 20–40 cm). Regardless of the irrigation system, ammonium sulfate gave the highest cumulative N2O losses in both campaigns, while calcium nitrate and the use of DMPP were the most effective strategies to abate N2O fluxes in the first and second years, respectively. Differences between irrigation systems were not statistically significant for cumulative N2O emissions, despite the clear effect on topsoil mineral N (higher NH4+ and NO3− concentrations in surface and subsurface drip, respectively). Nitrous oxide emissions were positively correlated with soil NH4+ concentrations. Gene abundances were not a trustworthy predictor of N2O losses in the 1st year, although a clear inhibitory effect of fertilization on microbial communities (i.e., ammonia oxidizers, nitrite reducers, and N2O reducers) was observed during this campaign. During the second year, nitrifying and denitrifying genes were affected by irrigation (with higher abundances in the 20–40 cm layer in subsurface than in surface drip) and by the addition of DMPP (which had a detrimental effect on gene abundances in both irrigation systems that disappeared after the fertigation period). In conclusion, the use of DMPP or calcium nitrate instead of ammonium sulfate may enhance the chances for an additional mitigation in both surface and subsurface irrigation systems.
A comparative evaluation of the sniffing, the simple head extension and the head hyperextension positions for laryngoscopic view and intubation difficulty in adults undergoing direct laryngoscopy
Authors: Hadhoud Y. H. , Baraka Mohamed A. , Saleh Mohamed , Refaat Ahmed M.
Published: December 2023

Objective

This work aimed to compare between the laryngoscopy positions; sniffing, simple head extension and head hyperextension positions to assess whether the laryngeal view, intubation time and intubation difficulty could improve with one of these positions than the others.

Design

Prospective randomized three arms clinical trial.

Setting

Operation room, the phoniatrics unit [removed for blind peer review].

Participants

The study included 75 cases with 25 cases in each group. Group "A" with head in the sniffing position, Group "B" with the head in simple extension position, Group "C" with head in hyperextension position.

Results

The three groups were compared regarding intubation time and laryngoscopic view time. Intubation time showed statistically significant difference between the three groups. Mean of sniffing group (No. = 25) was 13.19 s (± 3.35). Mean of simple extension group (No. = 25) was 11.29 s (± 3.14). Mean of Hyperextension group (No. = 25) was 14.39 s (± 4.14). Laryngoscopic view time showed statistically highly significant difference between the three groups. Mean of sniffing group (No. = 25) was 17.19 s (± 7.27). Mean of simple group (No. = 25) was 12.18 s (± 4.46). Mean of hyperextension group (No. = 25) was 17.08 s (± 6.51).

Conclusion

Comparing the sniffing, the simple extension and the hyperextension positions, the simple extension position showed the best time regarding intubation time and laryngoscopic view time.
COVID-19 classification based on a deep learning and machine learning fusion technique using chest CT images
Authors: Salama Gerges M. , Mohamed Asmaa , Abd-Ellah Mahmoud Khaled
Published: December 2023

Coronavirus disease (COVID-19), impacted by SARS-CoV-2, is one of the greatest challenges of the twenty-first century. COVID-19 broke out in the world over the last 2 years and has caused many injuries and killed persons. Computer-aided diagnosis has become a necessary tool to prevent the spreading of this virus. Detecting COVID-19 at an early stage is essential to reduce the mortality risk of patients. Researchers seek to find rapid solutions based on techniques of Machine Learning and Deep Learning. In this paper, we introduced a hybrid model for COVID-19 detection based on machine learning and deep learning models. We used 10 different deep CNN network models to extract features from CT images. We extract features from different layers in each network and find the optimum layer that gives the best-extracted features for each CNN network. Then, for classifying these features, we used five different classifiers based on machine learning. The dataset consists of 2481 CT images divided into COVID-19 and non-COVID-19 categories. Three folds are extracted with a different size between testing and training. Through experiments, we define the best layer for all used CNN networks, the best network, and the best-used classifier. The measured performance shows the superiority of the proposed system over the literature with a highest accuracy of 99.39%. Our models are tested with the three folds that gained maximum average accuracy. The result is 98.69%.
Kompetenzen in Psychotherapeutischer Medizin und Psychotherapie erwerben
Authors: Löffler-Stastka Henriette , Finger-Ossinger Margarete , Meischl Tobias
Published: December 2023

Psychisch Erkrankte werden von Psychotherapeut:innen sowie Ärzt:innen und Fachärzt:innen mit einer Ausbildung in psychotherapeutischer Medizin behandelt. Die entsprechende Ausbildung sieht ein Training sowohl intuitiven als auch analytischen Denkens vor. In kontinuierlicher fallorientierter Arbeit werden die Fähigkeiten zu komplexem, vernetztem Denken vermittelt, die es benötigt, um Patient:innen einen Weg ins Behandlungsnetz zu vermitteln, forschungsbasiert adäquat zu behandeln, Therapieadhärenz zu etablieren und zu halten. Die Ausbildungswege sind mit ihren unterschiedlichen Wegen in der beruflichen Sozialisation dargestellt, die didaktischen Elemente herausgearbeitet und auf Basis lerntheoretischer Überlegungen diskutiert.
Clinical, oral immunological and microbiological shifts during and after pregnancy
Authors: Meriç Pınar , Silbereisen Angelika , Emingil Gülnur , Öztürk Veli-Özgen , Bostanci Nagihan
Published: December 2023

Objectives

Physiological changes and shifts in the oral microbiota composition during pregnancy may affect the maternal immune system. Uncomplicated pregnancy is associated with a T-helper (Th) 2 predominant cytokine regulation (anti-inflammatory), while oral health deterioration during pregnancy is reflected by severe gingival inflammation, a primarily Th1 cytokine phenotype (pro-inflammatory), and oral microbiome alterations. This prospective observational study aimed to evaluate Th cytokine shifts and changes in the oral microbiota composition in saliva of women before and after birth.

Material and methods

Saliva (n = 96) was collected before and 6 months after birth, and medical, oral health, and periodontal status were assessed. In a multiplex immunoassay, 10 cytokines were simultaneously analyzed and cumulative Th1 and Th2 cytokine levels and Th1/Th2 ratio were calculated for all groups. Putative periodontal pathogens (n = 6) were evaluated by quantitative real-time polymerase chain reaction.

Results

Th2 cytokine levels were significantly lower (p = 0.014) while pro-inflammatory cytokine levels were significantly higher (p < 0.01) during pregnancy than postpartum. Similar Th1 levels were found between the groups (p = 0.143). Th1 and Th2 cytokines positively correlated with periodontal parameters (p < 0.001) and levels of studied bacteria during pregnancy (p < 0.05).

Conclusions

This study identified a significantly increased Th1/Th2 cytokine ratio during pregnancy and a positive association with putative periodontal pathogens. This immunological and microbiological deregulation in the oral milieu during pregnancy is suggestive of a destructive inflammatory periodontal profile.

Study registration

Clinical Trials.gov (Record BAP-2015).

Clinical relevance

Understanding altered oral immunological and microbiological regulation patterns during pregnancy may help improve the inflammatory periodontal profile in pregnant women.
Targeted proteomics in a population-based study identifies serum PECAM-1 and TRIM21 as inflammation markers for periodontitis
Authors: Reckelkamm Stefan Lars , Kamińska Inga , Baumeister Sebastian-Edgar , Ponce-de-Leon Mariana , Ehmke Benjamin , Rodakowska Ewa , Baginska Joanna , Nolde Michael , Kamiński Karol Adam
Published: December 2023

Objectives

Periodontitis (PD) can cause systematic inflammation and is associated with various metabolic processes in the body. However, robust serum markers for these relationships are still lacking. This study aims to identify novel circulating inflammation-related proteins associated with PD using targeted proteomics.

Materials and methods

We used population-based, cross-sectional data from 619 participants of the Polish Longitudinal University Study (Bialystok PLUS). Mean pocket probing depth (mPPD) and proportion of bleeding on probing (pBOP) served as exposure variables. Fifty-two inflammation-related proteins were measured using the Olink Target 96 Cardiovascular III and the Olink Target 96 Immune Response panels. Associations between periodontal measures and proteins were tested using covariate-adjusted linear regression models.

Results

At a false discovery rate of < 0.05, we identified associations of mPPD and pBOP with platelet-endothelial cell adhesion molecule-1 (PECAM-1) and tripartite motif–containing protein 21 (TRIM21).

Conclusion

This study revealed novel associations between PD and serum levels of PECAM-1 and TRIM21. Our results suggest that these proteins might be affected by molecular processes that take place in the inflamed periodontium.

Clinical relevance

Novel associations of PECAM-1 and TRIM21 with PD indicate promising serum markers for understanding the disease’s pathophysiological processes and call for further biomedical investigations.
Phase 2 study of ibrutinib plus venetoclax in Japanese patients with relapsed/refractory mantle cell lymphoma
Authors: Goto Hideki , Ito Satoshi , Kizaki Masahiro , Yamaguchi Masaki , Fukuhara Noriko , Kato Koji , Saito Toko , Terui Yasuhito , Okubo Sumiko , Soshin Tomomi , Zeng Jiewei , Honda Hideyuki , Badawi Mohamed , Ross Jeremy A. , Izutsu Koji
Published: December 2023

Background

Despite high response rates to initial therapy, most patients with mantle cell lymphoma (MCL) experience relapsed or refractory (R/R) disease. Here, we report the efficacy, safety, and pharmacokinetics of the Phase 2, single-arm M20-075 study (NCT04477486) of ibrutinib and venetoclax combination therapy in Japanese patients with R/R MCL.

Methods

Patients received 560 mg ibrutinib and 400 mg venetoclax (after a 5-week ramp-up from 20 mg) once daily for up to 104 weeks. Primary endpoint was complete response (CR) rate by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) rate, progression-free survival (PFS), overall survival (OS), safety including dose-limiting toxicity (DLT) assessment in the first six patients, and pharmacokinetic parameters. Full analysis set (FAS) comprised all treated patients. Per protocol set (PPS) excluded treated patients with non-evaluable disease at baseline by IRC.

Results

Thirteen patients were treated (FAS n = 13; PPS, n = 12). Median age was 71 years, patients had a median of two prior treatments. After a median follow-up of 9.6 months, IRC-assessed CR rate and ORR were both 83% (PPS). All six MRD-evaluable patients had uMRD. Median DOR, PFS, and OS were unreached. The most common Grade ≥ 3 treatment-emergent adverse event (TEAE) was neutropenia (23%); 1 patient discontinued due to squamous cell carcinoma of the lung. No DLTs, tumor lysis syndrome, or deaths related to TEAEs were observed.

Conclusion

Ibrutinib plus venetoclax exhibited high response rates and a well-tolerated safety profile in Japanese patients with R/R MCL.
Intersectional coalitions towards a just agroecology: weaving mutual aid and agroecology in Barcelona and Seville
Authors: Facchini Francesco , López-García Daniel , Villamayor-Tomas Sergio , Corbera Esteve
Published: December 2023

Although in theory social justice is considered as a core dimension of agroecological transitions, alternative food initiatives related to agroecology have been criticised for their exclusionary practices based on important social and economic biases. In this article, we adopt the lens of political intersectionality to study two cases of Agroecology-oriented Food Redistribution Coalitions in Spain that emerged to address the rising levels of food insecurity during the COVID-19 pandemic. We find that the coalitions represent a convergence of diverse social struggles, placing intersectionally marginalized groups at the centre of their activism. However, we also uncover that coalition members participate in different ways depending on their socioeconomic profiles, which could perpetuate inequalities in organizational practices. One major point of tension is the need to balance the goal of providing access to healthy and sustainable food with the affordability of such produce. This leads to the adoption of hybrid food networks that include conventionally produced food. We also highlight that while the predominance of women in these coalitions reflects the unequal distribution of food-related care work in society, the collectivization of such work through AFRCs practices points to a transformation of gender relations. Territorialized alliances between actors from urban and rural settings and between urban centers and peripheries are established through the coalitions. However, such networks fall short on involving large numbers of agroecology-oriented initiatives and providing direct encounters between consumers and producers. Overall, the article underscores the importance of addressing intersecting inequalities within alternative food initiatives and argues that intersectional coalitions offer an intriguing example of how to promote such understanding and pave the way towards (more) just agroecological transitions.
More than meat? Livestock farmers’ views on opportunities to produce for plant-based diets
Authors: Craft Rhiannon , Pitt Hannah
Published: December 2023

Promoting plant-based diets as a response to climate crisis has clear implications for producers of animal derived foods, but surprisingly little research considers their perspectives on this. Our exploration focused on farming strongly associated with meat production in Wales, UK. Mindful of polarised debates around plant-based diets, we considered dietary transition as an opportunity to produce for new markets. The first aim was to identify whether transition towards plant-based diets might trigger transformation of livestock agriculture. Findings indicate a potential trigger event once livestock farmers are certain that consumer trends and climate mitigation require change. Livestock farmers who regard their meat as climate-friendly might resist transitions felt to unfairly disadvantage them. We then considered livestock farmers’ likely capacity to produce plant crops, and how this transformational capacity might be enhanced. Participants highlighted forms of financial and environmental inflexibility, plus social norms regarding “good” Welsh farmers, combining to make transformation risky. Transformational capacity might be enhanced through levering occupational and place attachments by portraying plant crops as a revival of historic practices from traditional farming landscapes. Improved linking capacity will also be beneficial, as producing for new markets requires connections to new supply chains, and learning across divisions within rural communities. We present these preliminary insights to livestock farmers’ attitudes and transformational capacity to inform future research with them to advance just agricultural transitions. Our study indicates potential to avoid confrontational discussion of dietary transition and we hope that others will pursue its focus on opportunities for farmers.
Making waves in massive star asteroseismology
Authors: Bowman Dominic M.
Published: December 2023

Massive stars play a major role not only in stellar evolution but also galactic evolution theory. This is because of their dynamical interaction with binary companions, but also because their strong winds and explosive deaths as supernovae provide chemical, radiative and kinematic feedback to their environments. Yet this feedback strongly depends on the physics of the supernova progenitor star. It is only in recent decades that asteroseismology – the study of stellar pulsations – has developed the necessary tools to a high level of sophistication to become a prime method at the forefront of astronomical research for constraining the physical processes at work within stellar interiors. For example, precise and accurate asteroseismic constraints on interior rotation, magnetic field strength and geometry, mixing and angular momentum transport processes of massive stars are becoming increasingly available across a wide range of masses. Moreover, ongoing large-scale time-series photometric surveys with space telescopes have revealed a large diversity in the variability of massive stars, including widespread coherent pulsations across a large range in mass and age, and the discovery of ubiquitous stochastic low-frequency (SLF) variability in their light curves. In this invited review, I discuss the progress made in understanding the physical processes at work within massive star interiors thanks to modern asteroseismic techniques, and conclude with a future outlook.
Phylogenetically distant animals sleep: why do sleep researchers care?
Authors: Bechtel William
Published: December 2023

Philosophers examining mechanistic explanations in biology have identified heuristic strategies scientists use in discovering mechanisms. This paper examines the heuristic strategy of investigating phylogenetically distant model organisms, using research on sleep in fruit flies as an example. At the time sleep was discovered in flies in 2000 next to nothing was known about mechanisms regulating sleep in flies and what they could reveal about those in us. One relatively straightforward line of research focused on homologous genes in flies and humans, using those in flies to understand what roles their homologs played in controlling sleep in us. But other research focused on a higher level of organization—the neural networks involved in homeostatic and circadian control of sleep. This raises a puzzle—given that fly and vertebrate brains are organized very differently, how could sleep regulation in flies serve as an informative model of vertebrate sleep? I argue that the basic design of mechanisms such as those regulating sleep can be conserved even as the composition of the mechanism changes and that researchers can hope to use the designs deciphered in flies as heuristic models for understanding sleep in humans.
Effect of targeted acetylation on wood–water interactions at high moisture states
Authors: Fredriksson Maria , Digaitis Ramūnas , Engqvist Jonas , Thybring Emil E.
Published: December 2023

Acetylation is a wood modification used to increase the durability. Although it is known that the wood moisture content is lowered, the exact mechanisms behind the increased durability are not known. However, since fungi need water in different locations for different purposes the location and state of water is most probably of importance in addition to the total moisture content. In a previous study, we used targeted acetylation to alter the wood–water interactions in different parts of the wood structure in water saturated and hygroscopic moisture states. The main range for fungal degradation is, however, between these moisture ranges. This study investigated the effect of targeted acetylation on location, state and amount of water at non-saturated, high moisture states using the pressure plate technique. Specimens were modified using acetic anhydride by two approaches: (1) uniform modification (2) interface modification acting on the cell wall-lumen interface. They were then conditioned to eight moisture states between 99.64 and 99.98% relative humidity in both absorption and desorption and the location and state of water was studied using Low Field Nuclear Magnetic Resonance, X-ray computed tomography and Differential Scanning Calorimetry. Capillary water was present at all the included moisture states for all specimen types, but the amounts of capillary water in absorption were small. Increasing degree of interface modification increased the amount of capillary water compared to untreated wood. In addition, the uniformly modified wood often had higher amounts of capillary water than the untreated wood. The amount of cell wall water was decreased by uniform modification, but slightly or not reduced by the interface modification. The combination of targeted modification and conditioning to high well-defined moisture states thus gave very different amounts of capillary water and cell wall water depending on the conditioning history (absorption or desorption) and choice of modification. This opens new possibilities for designing materials and moisture states for fungal degradation experiments of wood.
50 Years of uranium isotopic reference materials at JRC-Geel
Authors: Richter S. , Hennessy C. , Truyens J. , Jacobsson U. , Venchiarutti C. , Bujak R. , Aregbe Y.
Published: December 2023

The history of uranium isotopic reference materials from JRC-Geel during the last 50 years is reviewed by presenting certification methods and relevant applications. The certified isotope ratios are traceable to the SI via gravimetrical preparation, either directly through gravimetrical mixing of highly enriched materials, or indirectly using existing gravimetrically prepared reference materials for calibration of mass spectrometers used for certification measurements. Due to developments of mass spectrometers and analytical methods, certification measurements have improved regarding precision, uncertainties and accuracy. This has led to a comprehensive set of uranium isotopic reference materials available for nuclear safety, security and the scientific community.
Muscone inhibits angiotensin II–induced cardiac hypertrophy through the STAT3, MAPK and TGF-β/SMAD signaling pathways
Authors: Liu Yi-jiang , Xu Jia-jia , Yang Cui , Li Yan-lin , Chen Min-wei , Liu Shi-xiao , Zheng Xiang-hui , Luo Ping , Li Rui , Xiao Di , Shan Zhong-gui
Published: December 2023

Background

Muscone is a chemical monomer derived from musk. Although many studies have confirmed the cardioprotective effects of muscone, the effects of muscone on cardiac hypertrophy and its potential mechanisms are unclear.The aim of the present study was to investigate the effect of muscone on angiotensin (Ang) II-induced cardiac hypertrophy.

Methods and results

In the present study, we found for the first time that muscone exerted inhibitory effects on Ang II-induced cardiac hypertrophy and cardiac injury in mice. Cardiac function was analyzed by echocardiography measurement, and the degree of cardiac fibrosis was determined by the quantitative real-time polymerase chain reaction (qRT-PCR), Masson trichrome staining and western blot assay. Secondly, qRT-PCR experiment showed that muscone attenuated cardiac injury by reducing the secretion of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Moreover, western blot analysis found that muscone exerted cardio-protective effects by inhibiting phosphorylation of key proteins in the STAT3, MAPK and TGF-β/SMAD pathways. In addition, CCK-8 and determination of serum biochemical indexes showed that no significant toxicity or side effects of muscone on normal cells and organs.

Conclusions

Muscone could attenuate Ang II-induced cardiac hypertrophy, in part, by inhibiting the STAT3, MAPK, and TGF-β/SMAD signaling pathways.
Differential phosphorus acquisition strategies of nine cover crop species grown in a calcareous and a decalcified chernozem
Authors: Raniro Henrique Rasera , Santner Jakob
Published: December 2023

Background and aims

Cover cropping is a strategy to increase soil phosphorus (P) use efficiency in agroecosystems. We investigated adaptations on P acquisition strategies of nine cover crops grown in a calcareous and a non-calcareous chernozem with low available P.

Methods

Through a 108-day pot experiment using a calcareous and a decalcified chernozem, we evaluated black oat (Avena strigosaSchreb.), white lupin (Lupinus albusL.), narrow-leaf lupin (Lupinus angustifoliusL.), phacelia (Phacelia tanacetifoliaBenth.), berseem clover (Trifolium alexandrinumL.), buckwheat (Fagopyrum esculentumMoench), linseed (Linum usitatissimumL.), ramtil (Guizotia abyssinica[Lf] Cass.) and white mustard (Sinapis albaL.) for their dry biomass production, tissue P concentration and uptake, and effects on soil pH, phosphatase activity, mycorrhiza infection rate and soil P fractions.

Results

Cover crops differed in several parameters between the two soils. Dry biomass varied from 3.3 (white lupin) to 41.6 g pot-1(mustard). Tissue P concentrations ranged from 0.046% (mustard) to 0.24% (clover). Species affected pH of both soils, ranging from − 0.66 to + 0.24. Acid phosphatase activity was higher in the decalcified soil, while alkaline phosphatases were higher in the calcareous soil. Root mycorrhizal infection rates ranged from 0 to > 50%. Most plants explored soil labile P exclusively, with organic P mineralization being more relevant in the calcareous soil.

Conclusion

We confirm that cover crops favoured distinct strategies to access the predominant soil labile P forms in each soil. Mycorrhizal species were particularly efficient in the decalcified soil, while species with high phosphatase secretion accessed higher Po, especially in the calcareous soil.
SyDog-Video: A Synthetic Dog Video Dataset for Temporal Pose Estimation
Authors: Shooter Moira , Malleson Charles , Hilton Adrian
Published: December 2023

We aim to estimate the pose of dogs from videos using a temporal deep learning model as this can result in more accurate pose predictions when temporary occlusions or substantial movements occur. Generally, deep learning models require a lot of data to perform well. To our knowledge, public pose datasets containing videos of dogs are non existent. To solve this problem, and avoid manually labelling videos as it can take a lot of time, we generated a synthetic dataset containing 500 videos of dogs performing different actions using Unity3D. Diversity is achieved by randomising parameters such as lighting, backgrounds, camera parameters and the dog’s appearance and pose. We evaluate the quality of our synthetic dataset by assessing the model’s capacity to generalise to real data. Usually, networks trained on synthetic data perform poorly when evaluated on real data, this is due to the domain gap. As there was still a domain gap after improving the quality of the synthetic dataset and inserting diversity, we bridged the domain gap by applying 2 different methods: fine-tuning and using a mixed dataset to train the network. Additionally, we compare the model pre-trained on synthetic data with models pre-trained on a real-world animal pose datasets. We demonstrate that using the synthetic dataset is beneficial for training models with (small) real-world datasets. Furthermore, we show that pre-training the model with the synthetic dataset is the go to choice rather than pre-training on real-world datasets for solving the pose estimation task from videos of dogs.
The transnational prosocial activities of elite African footballers: an exploratory study of the costs and the benefits
Authors: Ejekwumadu Ikechukwu
Published: December 2023

This paper explored the costs and the benefits of elite African players’ prosocial activities in their home countries. Through the players’ Twitter and Instagram posts and qualitative interviews, their prosocial activities were examined with regard to the costs and benefits for their career and life courses. The findings show that African players’ transnational prosocial acts are both altruistic (placing costs) and mutualistic (generating benefits). This exploratory paper adds to the existing literature by pointing out both the material and non-material consequences of players’ transnational social responsibility activities. Further, it reveals the complex implications of these practices. For example, while participation in the national team is often viewed primarily from the perspective of positive and beneficial contributions to players’ careers, it may also pose a very significant cost to African players, as they risk jeopardising their club careers. The practical implication of this study is that football governing bodies need to do more to eliminate administrative practices that discriminate against players based on their nationality and also ensure that African players who choose to honour national team duties are protected from undue disadvantages at their clubs arising from their international duties.
Effects of spectators on the performance of a dance routine
Authors: Engler Celine , Pelzer Fabian , Kaczmarek Christian , Schaefer Sabine
Published: December 2023

Sports like dancing and gymnastics are often performed in front of an audience. It is therefore an important question whether spectators help or hinder movement execution. Previous research suggests that the influence of spectators on motor performance depends on the type of task, with condition-based tasks being facilitated, and coordination-based tasks being inhibited (for a recent review, see van Meurs, Greve, & Strauss, 2022). We tested a group of female carnival dancers (N = 15, Mage = 19; age range between 15 and 35 years) over the course of a competitive season. The same dance choreography was performed at four timepoints, each time with and without spectators. Dance performances were videotaped and afterwards rated by 7 qualified raters, who were blinded concerning the experimental condition. Raters noted an increased quality of the dance with increasing practice (linear and cubic trend). Concerning social facilitation effects, dance performance was either improved (timepoint 2) or unchanged (timepoints 1, 3, and 4) in front of the audience. Our results indicate that a complex coordination task like the carnival dance may be facilitated when being watched. Future research should address whether these findings can be replicated in other aesthetic sports (like gymnastics), whether they are influenced by gender, and how individual performances influence the group outcome.
The Role of ICP Monitoring in Minimally Invasive Surgery for the Management of Intracerebral Hemorrhage
Authors: Zhang Ge , Li Yunjie , Chen Danyang , Wu Zhuojin , Pan Chao , Zhang Ping , Zhao Xingwei , Tao Bo , Ding Han , Meng Cai , Chen Diansheng , Liu Wenjie , Tang Zhouping
Published: December 2023

Intracerebral hemorrhage (ICH) is the second major stroke type, with high incidence, high disability rate, and high mortality. At present, there is no effective and reliable treatment for ICH. As a result, most patients have a poor prognosis. Minimally invasive surgery (MIS) is the fastest treatment method to remove hematoma, which is characterized by less trauma and easy operation. Some studies have confirmed the safety of MIS, but there are still no reports showing that it can significantly improve the functional outcome of ICH patients. Intracranial pressure (ICP) monitoring is considered to be an important part of successful treatment in traumatic brain diseases. By monitoring ICP in real time, keeping stable ICP could help patients with craniocerebral injury get a good prognosis. In the course of MIS treatment of ICH patients, keeping ICP stable may also promote patient recovery. In this review, we will take ICP monitoring as the starting point for an in-depth discussion.