bluuebunny/crossref_metadata_2025 huggingface dataset:
Do admission glucose levels independently predict coagulopathy in multiple trauma patients? A retrospective cohort analysis
Authors: Mayor Jorge , Gräff Pascal , Birgel Vera , Clausen Jan-Dierk , Omar-Pacha Tarek , Aktas Gökmen , Sehmisch Stephan , Mommsen Philipp
Published: February 2024

Background

Coagulopathy is prevalent in multiple trauma patients and worsens bleeding complications, leading to higher morbidity and mortality rates. Hyperglycemia upon admission predicts hemorrhagic shock and mortality in severely injured patients. This study aimed to assess admission glucose levels as an independent prognostic factor for coagulopathy in multiply injured patients.

Methods

This retrospective cohort study observed multiple trauma patients treated at a level I trauma center between January 1, 2005, and December 31, 2020. Coagulopathy was defined as an international normalized ratio (INR) > 1.4 and/or activated thromboplastin time (APTT) > 40 s. Analysis of variance compared clinical and laboratory parameters of patients with and without coagulopathy. Receiver-operating-characteristic (ROC) and multivariate logistic regression analyses identified risk factors associated with coagulopathy.

Results

The study included 913 patients, of whom 188 (20%) had coagulopathy at admission. Coagulopathy patients had higher mortality than those without (26% vs. 5.0%, p < 0.001). Mean glucose level in coagulopathy patients was 10.09 mmol/L, significantly higher than 7.97 mmol/L in non-coagulopathy patients (p < 0.001). Admission glucose showed an area under the curve (AUC) of 0.64 (95% CI [0.59–0.69], p < 0.001) with an optimal cut-off point of 12.35 mmol/L. After adjusting for other factors, patients with high admission glucose had a 1.99-fold risk of developing coagulopathy (95% CI 1.07–3.60). Other laboratory parameters associated with coagulopathy included haemoglobin, bicarbonate (HCO3), and lactate levels.

Conclusion

This study emphasizes the significance of admission blood glucose as an independent predictor of coagulopathy. Monitoring hyperglycemia can aid in identifying high-risk patients.
Keeping pace: the primary cilium as the conducting baton of the islet
Authors: Idevall-Hagren Olof , Incedal Nilsson Ceren , Sanchez Gonzalo
Published: February 2024

Primary cilia are rod-like sensory organelles that protrude from the surface of most mammalian cells, including the cells of the islet, and mounting evidence supports important roles of these structures in the regulation of beta cell function and insulin secretion. The sensory abilities of the cilium arise from local receptor activation that is coupled to intrinsic signal transduction, and ciliary signals can propagate into the cell and influence cell function. Here, we review recent advances and studies that provide insights into intra-islet cues that trigger primary cilia signalling; how second messenger signals are generated and propagated within cilia; and how ciliary signalling affects beta cell function. We also discuss the potential involvement of primary cilia and ciliary signalling in the development and progression of type 2 diabetes, identify gaps in our current understanding of islet cell cilia function and provide suggestions on how to further our understanding of this intriguing structure.

Graphical Abstract
Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum–related apoptosis through Chop and Bip/GRP78 signaling
Authors: Unal Onur , Erzurumlu Yalcin , Asci Halil , Gunduru Acar Berivan , Bedir Mehmet , Ozmen Ozlem
Published: February 2024

This study aimed to examine the protective role of nebivolol (NEB) on liver tissue against the lipopolysaccharide (LPS)-induced sepsis model in rats by targeting endoplasmic reticulum (ER) stress–related binding immunoglobulin protein (Bip), CCAAT-enhancer-binding protein homologous protein (Chop) signaling pathways. Four groups, each comprising eight rats, were established: control, LPS, LPS + NEB, and NEB. Biochemical analyses included total oxidant status (TOS), serum aspartate transaminase (AST), and alanine aminotransferase (ALT) levels. Additionally, genetic assessments involved Chop and Bip/GRP78 mRNA expression levels, while histopathological examinations were conducted. Immunohistochemistry was used to determine interleukin-1 beta (IL-1 β) and caspase-3 levels. The LPS group exhibited significantly higher AST, ALT, oxidative stress index, and TOS levels compared to the control group. Moreover, the LPS group demonstrated markedly increased Chop and Bip/GRP78 mRNA expression compared to the control group. Immunohistochemical analysis of the LPS group revealed significant upregulation in IL-1β and caspase-3 expressions compared to the control group. Additionally, the LPS group showed significant hyperemia, mild hemorrhage, and inflammatory cell infiltrations. Comparatively, the LPS+NEB group exhibited a reversal of these alterations when compared to the LPS group. Collectively, our findings, suggest that NEB holds promise as a treatment in conditions where oxidative damage, inflammation, and ER stress–related apoptosis play significant roles in the pathogenesis.

Graphical abstract
Revisiting the Multifaceted Roles of Bacteriocins
Authors: Arbulu Sara , Kjos Morten
Published: February 2024

Bacteriocins are gene-encoded antimicrobial peptides produced by bacteria. These peptides are heterogeneous in terms of structure, antimicrobial activities, biosynthetic clusters, and regulatory mechanisms. Bacteriocins are widespread in nature and may contribute to microbial diversity due to their capacity to target specific bacteria. Primarily studied as food preservatives and therapeutic agents, their function in natural settings is however less known. This review emphasizes the ecological significance of bacteriocins as multifunctional peptides by exploring bacteriocin distribution, mobility, and their impact on bacterial population dynamics and biofilms.
Reinforcement learning for block decomposition of planar CAD models
Authors: DiPrete Benjamin C. , Garimella Rao , Cardona Cristina Garcia , Ray Navamita
Published: February 2024

The problem of hexahedral mesh generation of general CAD models has vexed researchers for over 3 decades and analysts often spend more than 50% of the design-analysis cycle time decomposing complex models into simpler blocks meshable by existing techniques. The decomposed blocks are required for generating good quality meshes (tilings of quadrilaterals or hexahedra) suitable for numerical simulations of physical systems governed by conservation laws. We present a novel AI-assisted method for decomposing (segmenting) planar CAD (computer-aided design) models into well shaped rectangular blocks. Even though the simple examples presented here can also be meshed using many conventional methods, we believe this work is proof-of-principle of a AI-based decomposition method that can eventually be generalized to complex 2D and 3D CAD models. Our method uses reinforcement learning to train an agent to perform a series of optimal cuts on the CAD model that result in a good quality block decomposition. We show that the agent quickly learns an effective strategy for picking the location and direction of the cuts and maximizing its rewards. This paper is the first successful demonstration of an agent autonomously learning how to perform this block decomposition task effectively, thereby holding the promise of a viable method to automate this challenging process for more complex cases.
Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias
Authors: Alhourani Nawar , Wolfes Julian , Könemann Hilke , Ellermann Christian , Frommeyer Gerrit , Güner Fatih , Lange Philipp Sebastian , Reinke Florian , Köbe Julia , Eckardt Lars
Published: February 2024

Despite impressive developments in the field of ventricular arrhythmias, there is still a relevant number of patients with ventricular arrhythmias who require antiarrhythmic drug therapy and may, e.g., in otherwise drug and/or ablation refractory situations, benefit from agents known for decades, such as mexiletine. Through its capability of blocking fast sodium channels in cardiomyocytes, it has played a minor to moderate antiarrhythmic role throughout the recent decades. Nevertheless, certain patients with structural heart disease suffering from drug-refractory, i.e., mainly amiodarone refractory ventricular arrhythmias, as well as those with selected forms of congenital long QT syndrome (LQTS) may nowadays still benefit from mexiletine. Here, we outline mexiletine’s cellular and clinical electrophysiological properties. In addition, the application of mexiletine may be accompanied by various potential side effects, e.g., nausea and tremor, and is limited by several drug-drug interactions. Thus, we shed light on the current therapeutic role of mexiletine for therapy of ventricular arrhythmias and discuss clinically relevant aspects of its indications based on current evidence.

Graphical abstract
Cost-effectiveness of a multidimensional post-discharge disease management program for heart failure patients—economic evaluation along a one-year observation period
Authors: Egelseer-Bruendl T. , Jahn B. , Arvandi M. , Puntscher S. , Santamaria J. , Brunelli L. , Weissenegger K. , Pfeifer B. , Neururer S. , Rissbacher C. , Huber A. , Fetz B. , Kleinheinz C. , Modre-Osprian R. , Kreiner K. , Siebert U. , Poelzl G.
Published: February 2024

Objective

This study aimed to assess the cost-effectiveness of the telemedically assisted post-discharge management program (DMP) HerzMobil Tirol (HMT) for heart failure (HF) patients in clinical practice in Austria.

Methods

We conducted a cost-effectiveness analysis along a retrospective cohort study (2016–2019) of HMT with a propensity score matched cohort of 251 individuals in the HMT and 257 in the usual care (UC) group and a 1-year follow-up. We calculated the effectiveness (hospital-free survival, hospital-free life-years gained, and number of avoided rehospitalizations), costs (HMT, rehospitalizations), and the incremental cost-effectiveness ratio (ICER). We performed a nonparametric sensitivity analysis with bootstrap sampling and sensitivity analyses on costs of HF rehospitalizations and on costs per disease-related diagnosis (DRG) score for rehospitalizations.

Results

Base-case analysis showed that HMT resulted in an average of 42 additional hospital-free days, 40 additional days alive, and 0.12 avoided hospitalizations per patient-year compared with UC during follow-up. The average HMT costs were EUR 1916 per person. Mean rehospitalization costs were EUR 5551 in HMT and EUR 6943 in UC. The ICER of HMT compared to UC was EUR 4773 per life-year gained outside the hospital. In a sensitivity analysis, HMT was cost-saving when “non-HF related costs” related to the DMP were replaced with average costs.

Conclusions

The economic evaluation along the cohort study showed that the HerzMobil Tirol is very cost-effective compared to UC and cost-saving in a sensitivity analysis correcting for “non-HF related costs.” These findings promote a widespread adoption of telemedicine-assisted DMP for HF.

Graphical abstract
Exercise, cancer, and the cardiovascular system: clinical effects and mechanistic insights
Authors: Wernhart Simon , Rassaf Tienush
Published: February 2024

Cardiovascular diseases and cancer are the leading causes of death in the Western world and share common risk factors. Reduced cardiorespiratory fitness (CRF) is a major determinant of cardiovascular morbidity and cancer survival. In this review we discuss cancer- induced disturbances of parenchymal, cellular, and mitochondrial function, which limit CRF and may be antagonized and attenuated through exercise training. We show the impact of CRF on cancer survival and its attenuating effects on cardiotoxicity of cancer-related treatment. Tailored exercise programs are not yet available for each tumor entity as several trials were performed in heterogeneous populations without adequate cardiopulmonary exercise testing (CPET) prior to exercise prescription and with a wide variation of exercise modalities. There is emerging evidence that exercise may be a crucial pillar in cancer treatment and a tool to mitigate cardiotoxic treatment effects. We discuss modalities of aerobic exercise and resistance training and their potential to improve CRF in cancer patients and provide an example of a periodization model for exercise training in cancer.
Environmental drivers of biogeography and community structure in a Mid-Atlantic estuary
Authors: Oleynik Haley A. , Bizzarro Joseph J. , Hale Edward A. , Carlisle Aaron B.
Published: February 2024

Estuaries include some of the most productive yet anthropogenically impacted marine ecosystems on the planet, and provide critical habitat to many ecologically and economically important marine species. In order to elucidate ecological function in estuaries, we must understand what factors drive community dynamics. Delaware Bay is the third largest estuary in the United States and hosts over 200 species of migrant and resident fishes and invertebrates. The Delaware Division of Fish and Wildlife has conducted two long-term trawl surveys at monthly intervals in Delaware Bay since 1966. The two surveys collect data on environmental conditions, species composition, and number of fishes and macroinvertebrates across different size classes and life histories. Using a suite of multivariate approaches including hierarchical cluster analysis, canonical correlation analysis, and permutational multivariate analysis of variance, we characterized the fish and macroinvertebrate community in Delaware Bay and found that community composition and environmental conditions varied across spatial and seasonal scales. We identified four distinct biogeographic regions, based on environmental conditions and community composition, which were consistent across surveys. We found that the community was driven primarily by gradients in temperature and salinity and that abundant, frequently occurring species in the Bay have well-defined environmental associations. Our work represents the first attempt to use an existing historical survey to better understand how environmental parameters influence diversity and distribution of macrofauna within Delaware Bay, providing insight into how abiotic variables, influenced by climate, may impact the Delaware Bay ecosystem and similar estuarine ecosystems worldwide.
Minimal Roman Dominating Functions: Extensions and Enumeration
Authors: Abu-Khzam Faisal N. , Fernau Henning , Mann Kevin
Published: February 2024

Roman domination is one of the many variants of domination that keeps most of the complexity features of the classical domination problem. We prove that Roman domination behaves differently in two aspects: enumeration and extension. We develop non-trivial enumeration algorithms for minimal Roman dominating functions with polynomial delay and polynomial space. Recall that the existence of a similar enumeration result for minimal dominating sets is open for decades. Our result is based on a polynomial-time algorithm for Extension Roman Domination: Given a graph $$G=(V,E)$$

G
=
(
V
,
E
)

and a function $$f:V\rightarrow \{0,1,2\}$$

f
:
V
→
{
0
,
1
,
2
}

, is there a minimal Roman dominating function $$\tilde{f}$$

f
~

with $$f\le \tilde{f}$$

f
≤

f
~

? Here, $$\le $$
≤
lifts $$0< 1< 2$$

0
<
1
<
2

pointwise; minimality is understood in this order. Our enumeration algorithm is also analyzed from an input-sensitive viewpoint, leading to a run-time estimate of $$\mathcal {O}(1.9332^n)$$

O
(
1
.

9332
n

)

for graphs of order n; this is complemented by a lower bound example of $$\Omega (1.7441^n)$$

Ω
(
1
.

7441
n

)

.
Edema related to treatment with psychotropic drugs
Authors: Engel Johanna , Haack Beatrice , Zolk Oliver , Greiner Timo , Heinze Martin , Toto Sermin , Seifert Johanna , Bleich Stefan , Glocker Catherine , Grohmann Renate , Schneider Michael , Stübner Susanne
Published: February 2024

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries (“Arzneimittelsicherheit in der Psychiatrie”, AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.
Protective factors for suicidal ideation: a prospective study from adolescence to adulthood
Authors: Bakken Victoria , Lydersen Stian , Skokauskas Norbert , Sund Anne Mari , Kaasbøll Jannike
Published: February 2024

Adolescent suicidality is associated with negative outcomes in adulthood. Suicide prevention has traditionally focused on identifying risk factors, yet suicide rates have remained stable. With suicidality often going undetected—especially suicidal ideation, further knowledge about protective factors is needed. The main objective of this study was to investigate potential protective factors for suicidal ideation from adolescence to adulthood. The study employed longitudinal population survey data, “Youth and Mental Health Study” consisting of self-reports at two-time points (mean age 14.9, SD = 0.6 and 27.2, SD = 0.6) (n = 2423 and n = 1198). Protective factors (at individual, social and environmental level) were selected based on a priori knowledge. Internal consistency of scales was analyzed using McDonald’s omega. We used a linear mixed model with suicidal ideation as the dependent variable, time-points, a protective factor variable and their interaction as covariates, and individual participant as random effects. We adjusted for sex and also conducted separate analyses for males and females. The Benjamini–Hochberg procedure was used to adjust p-values for multiple hypotheses. Investigated protective factors were associated with temporal change in suicidal ideation (significant interactions). For both sexes, less emotion-orientated coping, higher self-perception scores, greater levels of physical activity and higher school wellbeing/connectedness were protective factors for suicidal ideations. Secure attachment and higher family function were protective factors for females only. The effects in adolescence were mostly maintained in adulthood. In this study, several protective factors for suicidal ideation persisted into adulthood, with distinct differences between males and females.
Barriers to and facilitators of user engagement with web-based mental health interventions in young people: a systematic review
Authors: Ho Thi Quynh Anh , Le Long Khanh-Dao , Engel Lidia , Le Ngoc , Melvin Glenn , Le Ha N. D. , Mihalopoulos Cathrine
Published: February 2024

Many young people (YP) are diagnosed with mental illnesses and require support. Web-based mental health interventions (W-MHIs) have been increasingly utilized by YP, healthcare providers, and parents due to reasons including convenience and anonymity. W-MHIs are effective in improving mental health in YP. However, real-world engagement with W-MHIs remains low. Therefore, understanding barriers/facilitators of user engagement with W-MHIs is necessary to promote W-MHIs and help users gain optimal benefits through higher engagement. This review aims to identify barriers/facilitators of user engagement with W-MHIs in YP aged 10–24 years. A systematic search of five databases for English language, peer-reviewed publications was conducted between January 2010 and February 2023. Studies examining factors influencing user engagement with W-MHIs, described as barriers or facilitators, were included. Study quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was performed. Of 4088 articles identified, 69 studies were included. Barriers/facilitators were reported by young people (63 studies), providers (17 studies), and parents/caregivers (8 studies). YP perceived that usefulness and connectedness were the most common facilitators, whereas low-perceived need was the most reported barrier. Both providers and parents reported that perceived usefulness for YP was the most common facilitator, whereas concerns about program effectiveness and privacy were noted as barriers. This review found that program- and individual-related factors were important determinants of engagement with W-MHIs. This review provides guidance on the future design and development of new interventions, narrowing the gap between existing W-MHIs and unmet needs of users.
LINC00942 inhibits ferroptosis and induces the immunosuppression of regulatory T cells by recruiting IGF2BP3/SLC7A11 in hepatocellular carcinoma
Authors: Jin Dong , Hui Yongfeng , Liu Di , Li Nan , Leng Junzhi , Wang Genwang , Wang Qi , Lu Zhenhui
Published: February 2024

Hepatocellular carcinoma (HCC) is a common malignant tumor with a high recurrence rate and a poor prognosis. Long intergenic nonprotein coding RNA 942 (LINC00942) is reported to be related to ferroptosis and the immune response in HCC and serves as an oncogene in various cancers. This research aimed to explore the contribution of LINC00942 in HCC progression. Functional assays were used to evaluate the functional role of LINC00942 in vitro and in vivo. Mechanistic assays were conducted to assess the association of LINC00942 with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) and solute carrier family 7 member 11 (SLC7A11) and the regulatory pattern of LINC00942 in HCC cells. LINC00942 was found to exhibit upregulation in HCC tissue and cells. LINC00942 facilitated HCC cell proliferation, suppressed ferroptosis, and converted naive CD4+ T cells to inducible Treg (iTreg) cells by regulating SLC7A11. Furthermore, SLC7A11 expression was positively modulated by LINC00942 in HCC cells. IGF2BP3 was a shared RNA-binding protein (RBP) for LINC00942 and SLC7A11. The binding between the SLC7A11 3′ untranslated region and IGF2BP3 was verified, and LINC00942 was found to recruit IGF2BP3 to promote SLC7A11 mRNA stability in an m6A-dependent manner. Moreover, mouse tumor growth and proliferation were inhibited, and the number of FOXP3+CD25+ T cells was increased, while ferroptosis was enhanced after LINC00942 knockdown in vivo. LINC00942 suppresses ferroptosis and induces Treg immunosuppression in HCC by recruiting IGF2BP3 to enhance SLC7A11 mRNA stability, which may provide novel therapeutic targets for HCC.
Effect of cancer cachexia on first-line chemotherapy in patients with advanced pancreatic cancer: a claims database study in Japan
Authors: Furuse Junji , Osugi Fumihiko , Machii Koji , Niibe Koji , Endo Toshimitsu
Published: February 2024

Background

Cancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood.

Methods

This is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment.

Results

A total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94–146) in the cachexia group and 143 days (95% CI 134–152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979–1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP.

Conclusion

Cancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment.

Clinical Trial Registration clinicaltrials.jp: UMIN000045820.
Discrete network models of endothelial cells and their interactions with the substrate
Authors: Jakob Raphael , Britt Ben R. , Giampietro Costanza , Mazza Edoardo , Ehret Alexander E.
Published: February 2024

Endothelial cell monolayers line the inner surfaces of blood and lymphatic vessels. They are continuously exposed to different mechanical loads, which may trigger mechanobiological signals and hence play a role in both physiological and pathological processes. Computer-based mechanical models of cells contribute to a better understanding of the relation between cell-scale loads and cues and the mechanical state of the hosting tissue. However, the confluency of the endothelial monolayer complicates these approaches since the intercellular cross-talk needs to be accounted for in addition to the cytoskeletal mechanics of the individual cells themselves. As a consequence, the computational approach must be able to efficiently model a large number of cells and their interaction. Here, we simulate cytoskeletal mechanics by means of molecular dynamics software, generally suitable to deal with large, locally interacting systems. Methods were developed to generate models of single cells and large monolayers with hundreds of cells. The single-cell model was considered for a comparison with experimental data. To this end, we simulated cell interactions with a continuous, deformable substrate, and computationally replicated multistep traction force microscopy experiments on endothelial cells. The results indicate that cell discrete network models are able to capture relevant features of the mechanical behaviour and are thus well-suited to investigate the mechanics of the large cytoskeletal network of individual cells and cell monolayers.
Ecotypic variation in multiple traits of European beech: selection of suitable provenances based on performance and stability
Authors: Liepe Katharina J. , van der Maaten Ernst , van der Maaten-Theunissen Marieke , Kormann Jonathan M. , Wolf Heino , Liesebach Mirko
Published: February 2024

Induced by climate change associated disturbances and further promoted by changes in forest management, the proportion of European beech, a highly competitive climax species, is increasing in Central Europe. However, its climatic stability is questioned by the recent loss of vitality. In this regard, the evaluation of seed sources used for reforestation receives great attention. Here, we present a multi-trait evaluation of height, basal area and stem quality assessed over 25 years for 85 provenances grown at three sites in northern, western and eastern Germany. Considerable provenance differentiation exists, explaining 21% (proportion of trees with acceptable stem form) to 45% (basal area) of the variance on single sites and 20 to 39% across sites, while provenance by environment interactions are absent. On the landscape level, this results in distinct patterns with spatially adjacent provenances showing a similar trait expression. These patterns are highly similar for height and basal area but divergent for stem form. They could be directly linked to geographic variables with multivariate regression tree analysis that captured 58% of the phenotypic variation, delineating eleven ‘ecotypes’ shaped by local adaptation. A selection based on two multi-trait indices gives highly concordant results. Particularly, the intermediate elevations of the central highlands in Western Germany host highly suitable provenances. Lower elevation provenances from continental climates in the south-east profit from the transfer to favorable growing conditions. Since the majority of provenances was already exposed to elevated temperatures compared to their origin during the observation period, this study gives a first indication for the potential benefits of assisted migration facing climate change.
Die Ausgestaltung der Regelungen über Erlaubnisse und Bewilligungen im Wasserhaushaltsgesetz
Authors: Gentile Matteo
Published: February 2024

Das Gestattungsregime für Gewässerbenutzungen im Wasserhaushaltsgesetz ist hochgradig komplex.
Es erscheint mit seinen unterschiedlichen Zulassungsformen (Erlaubnis, gehobene Erlaubnis und Bewilligung),
deren Erteilung noch dazu an eine nahezu kaum beschränkbare Vielzahl von tatbestandlichen Voraussetzungen
anknüpft und zu guter Letzt auf der Rechtsfolgenseite auch noch von einer im Bewirtschaftungsermessen
der Wasserbehörde liegenden Entscheidung abhängt. Dieses Regime soll nachfolgend skizziert und
kritisch hinterfragt werden.
Advancing Adolescent and Young Adult HIV Prevention and Care and Treatment Through Use of Multi-level Theories and Frameworks: A Scoping Review and Adapted HIV Ecological Framework
Authors: Denison Julie A. , Willis Kalai , DeLong Stephanie M. , Sievwright Kirsty M. , Agwu Allison L. , Arrington-Sanders Renata , Kaufman Michelle R. , Prabhu Sandeep , Williams Ashlie M. , Fields Errol L. , Alexander Kamila A. , Lee Lana , Yang Cui ,   The Johns Hopkins University Center for AIDS Research Adolescent and Young Adult Scientific Working Group
Published: February 2024

While multi-level theories and frameworks have become a cornerstone in broader efforts to address HIV inequities, little is known regarding their application in adolescent and young adult (AYA) HIV research. To address this gap, we conducted a scoping review to assess the use and application of multi-level theories and frameworks in AYA HIV prevention and care and treatment empirical research. We systematically searched five databases for articles published between 2010 and May 2020, screened abstracts, and reviewed eligible full-text articles for inclusion. Of the 5890 citations identified, 1706 underwent full-text review and 88 met the inclusion criteria: 70 focused on HIV prevention, with only 14 on care and treatment, 2 on both HIV prevention and care and treatment, and 2 on HIV-affected AYA. Most authors described the theory-based multi-level framework as informing their data analysis, with only 12 describing it as informing/guiding an intervention. More than seventy different multi-level theories were described, with 38% utilizing socio-ecological models or the eco-developmental theory. Findings were used to inform the adaptation of an AYA World Health Organization multi-level framework specifically to guide AYA HIV research.
Deep learning for cancer cell detection: do we need dedicated models?
Authors: Karol Michal , Tabakov Martin , Markowska-Kaczmar Urszula , Fulawka Lukasz
Published: February 2024

This article proposes a novel concept for a two-step Ki-67/lymphocytes classification cell detection pipeline on Ki-67 stained histopathological slides utilizing commonly available and undedicated, in terms of the medical problem considered, deep learning models. Models used vary in implementation, complexity, and applications, allowing for the use of a dedicated architecture depending on the physician’s needs. Moreover, generic models’ performance was compared with the problem-dedicated one. Experiments highlight that with relatively small training datasets, commonly used architectures for instance segmentation and object detection are competitive with a dedicated model. To ensure generalization and minimize biased sampling, experiments were performed on data derived from two unrelated histopathology laboratories.
Routine Outcome Monitoring from Psychotherapists’ Perspectives: A Framework Analysis Study of Expected Benefits and Difficulties
Authors: Valdiviezo-Oña Jorge , Unda-López Alejandro , Montesano Adrián , Evans Chris , Paz Clara
Published: February 2024

Psychotherapists’ attitudes and expectations towards routine outcome monitoring can impact the likelihood of its fruitful implementation. While existing studies have predominantly focused on Europe and North America, research in Latin America remains limited. The aim of this study is to explore therapists’ expected benefits and difficulties prior to implementing a routine outcome monitoring system in a university psychotherapy service in Ecuador. An exploratory and descriptive cross-sectional qualitative study was carried out with 20 participants aged 21 to 47. Semi-structured interviews were conducted to explore participants’ knowledge about routine outcome monitoring, their expectations of the difficulties, benefits, usability and risks of using a monitoring system, as well as their expectations about their role in the process. The data analysis adhered to the framework analysis methodology, leading to the identification of six overarching themes, 36 specific themes and 82 subthemes. The interviews highlighted a spectrum of positive and negative expectations at several levels: institutional/general, therapeutic process, therapists, and clients. Perceived benefits encompassed various aspects, including the availability of supplementary information, continuous adaptation of the therapeutic process, facilitation of organization and treatment planning, opportunities for professional development, and fostering patient trust and empowerment. On the other hand, anticipated difficulties comprised concerns such as discomfort among therapists and clients, increased workload, system usage and technical difficulties, and the risk of excessive quantification. Overall, participants expressed more anticipated benefits than difficulties. We present recommendations that can support and optimize the current local implementation efforts of routine outcome monitoring, both within this service and in other settings. These recommendations consider ways to meet positive expectations and address or mitigate negative ones.
Are Genetic and Environmental Risk Factors for Psychopathology Amplified in Children with Below-Average Intelligence? A Population-Based Twin Study
Authors: Bruins Susanne , van Bergen Elsje , Masselink Maurits W. , Barzeva Stefania A. , Hartman Catharina A. , Otten Roy , Rommelse Nanda N. J. , Dolan Conor V. , Boomsma Dorret I.
Published: February 2024

There is a negative association between intelligence and psychopathology. We analyzed data on intelligence and psychopathology to assess this association in seven-year-old Dutch twin pairs (ranging from 616 to 14,150 depending on the phenotype) and estimated the degree to which genetic and environmental factors common to intelligence and psychopathology explain the association. Secondly, we examined whether genetic and environmental effects on psychopathology are moderated by intelligence. We found that intelligence, as assessed by psychometric IQ tests, correlated negatively with childhood psychopathology, as assessed by the DSM-oriented scales of the Child Behavior Check List (CBCL). The correlations ranged between − .09 and − .15 and were mainly explained by common genetic factors. Intelligence moderated genetic and environmental effects on anxiety and negative affect, but not those on ADHD, ODD, and autism. The heritability of anxiety and negative affect was greatest in individuals with below-average intelligence. We discuss mechanisms through which this effect could arise, and we end with some recommendations for future research.
Climate change from an ectotherm perspective: evolutionary consequences and demographic change in amphibian and reptilian populations
Authors: Hayden Bofill Sofía I. , Blom Mozes P. K.
Published: February 2024

Understanding how natural populations will respond to contemporary changes in climate is becoming increasingly urgent and of fundamental importance for the preservation of future biodiversity. Among vertebrates, amphibians and reptiles are more sensitive to environmental perturbations than endotherms and ectotherm diversity will likely be disproportionally impacted by climate change. Notwithstanding concerns surrounding the climate change resilience of ectotherm populations, accurately predicting future population trajectories based on contemporary ecological and physiological data alone remains challenging and much can be learnt by studying how populations have responded to climate change in the past. Genomic approaches can now assay the genetic diversity of contemporary population at an unprecedented scale but to date have been relatively underutilised when studying the demographic history of amphibians and reptiles. In this review, we first summarise how changing climatic conditions may influence the ectotherm phenotype and how this can translate to changes in fitness and population dynamics. We then discuss how the relative role of past climate in shaping ectotherm diversity has traditionally been approached in a phylogeographic context and how expanding genomic resources for ectotherm species can be leveraged to improve the study of past demography for many amphibian and reptilian groups. An integrative approach that links known proximate effects on phenotype due to climate change, with past changes in demographic trajectories will ultimately enable us to generate more accurate models of future population change and improve our ability to assess climate change resilience for many ectotherm groups.
Uncertainties of Drag Coefficient Estimates Above Sea Ice from Field Data
Authors: Blein Sébastien , Guemas Virginie , Brooks Ian M. , Elvidge Andrew D. , Renfrew Ian A.
Published: February 2024

Surface turbulent exchanges play a key role on sea ice dynamics, on ocean and sea ice heat budgets and on the polar atmosphere. Uncertainties in parameterizations of surface turbulent fluxes are mostly held by the transfer coefficients and estimates of those transfer coefficients from field data are required for parameterization development. Measurement errors propagate through the computation of transfer coefficients and contribute to its total error together with the uncertainties in the empirical stability functions used to correct for stability effects. Here we propose a methodology to assess their contributions individually to each coefficient estimate as well as the total drag coefficient uncertainty and we apply this methodology on the example of the SHEBA campaign. We conclude that for most common drag coefficient values (between $$1.0\times 10^{-3}$$

1.0
×

10

-
3

and $$2.5\times 10^{-3}$$

2.5
×

10

-
3

), the relative total uncertainty ranges from 25 and 50$$\%$$
%
. For stable or unstable conditions with a stability parameter $$|\zeta |>1$$

|
ζ
|
>
1

on average, the total uncertainty in the neutral drag coefficient exceeds the neutral drag coefficient value itself, while for $$|\zeta |<1$$

|
ζ
|
<
1

the total uncertainty is around 25$$\%$$
%
of the drag coefficient. For closer-to-neutral conditions, this uncertainty is dominated by measurement uncertainties in surface turbulent momentum fluxes which should therefore be the target of efforts in uncertainty reduction. We also propose an objective data-screening procedure for field data, which consists of retaining data for which the relative error on neutral drag coefficient does not exceed a given threshold. This method, in addition to the commonly used flux quality control procedure, allows for a reduction of the drag coefficient dispersion compared to other data-screening methods, which we take as an indication of better dataset quality.
Potential interplay between tumor size and vitamin D receptor (VDR) polymorphisms in breast cancer prognosis: a prospective cohort study
Authors: Lindgren Hampus , Ademi David , Godina Christopher , Tryggvadottir Helga , Isaksson Karolin , Jernström Helena
Published: February 2024

Purpose

Vitamin D has some anticancer properties that may decrease breast cancer risk and improve prognosis. The aim was to investigate associations between four previously studied VDR SNPs (Taq1, Tru91, Bsm1, and Fok1) and prognosis in different groups of breast cancer patients.

Methods

VDR genotyping of 1,017 breast cancer patients included 2002–2012 in Lund, Sweden, was performed using Oncoarray. Follow-up was until June 30, 2019. Clinical data and patient information were collected from medical records and questionnaires. Cox regression was used for survival analyses.

Results

Genotype frequencies were as follows: Fok1 (AA 15.7%, AG 49.1%, GG 35.1%), Bsm1 (CC 37.2%, CT 46.1%, TT 16.7%), Tru91 (CC 77.8%, CT 20.7%, TT 1.5%), and Taq1 (AA 37.2%, AG 46.2%, GG 16.6%). During follow-up there were 195 breast cancer events. The homozygous variants of Taq1 and Bsm1 were associated with reduced risk of breast cancer events (adjusted HR = 0.59, 95% CI 0.38–0.92 for Taq1 and adjusted HR = 0.61, 95% CI 0.40–0.94 for Bsm1). The G allele of the Fok1 was associated with increased risk of breast cancer events in small tumors (pT1, adjusted HR = 1.83, 95% CI 1.04–3.23) but not in large tumors (pT2/3/4, adjusted HR = 0.80, 95% CI 0.41–1.59) with a borderline interaction (Pinteraction = 0.058). No interactions between VDR genotypes and adjuvant treatments regarding breast cancer prognosis were detected.

Conclusion

VDR genotypes were associated with breast cancer prognosis and the association might be modified by tumor size. Further research is needed to confirm the findings and elucidate their potential clinical implications.
There is no word for ‘nature’ in our language: rethinking nature-based solutions from the perspective of Indigenous Peoples located in Canada
Authors: Reed Graeme , Brunet Nicolas D. , McGregor Deborah , Scurr Curtis , Sadik Tonio , Lavigne Jamie , Longboat Sheri
Published: February 2024

Support for nature-based solutions (NbS) has grown significantly in the last 5 years. At the same time, recognition for the role of Indigenous Peoples in advancing ‘life-enhancing’ climate solutions has also increased. Despite this rapid growth, the exploration of the intersection of NbS and Indigenous Peoples has been much slower, as questions remain about the ability of NbS to be implemented while respecting Indigenous rights, governance, and knowledge systems, including in their conceptualizations. To address this knowledge gap, we draw on 17 conversational interviews with Indigenous leaders, including youth, women, technicians, and knowledge keepers from what is currently known as Canada to explore Indigenous conceptualizations of nature, nature-based solutions, and the joint biodiversity and climate crisis. Three drivers of the biodiversity and climate crisis were identified: structural legacy of colonization and capitalism, a problem of human values, and climate change as a cumulative impact from industrial disturbances. Building on this understanding, our findings indicate that shifting towards Indigenous conceptualizations of NbS as systems of reciprocal relationships would: challenge the dichotomization of humans and nature; emphasize the inseparability of land, water, and identity; internalize the principle of humility and responsibility; and invest in the revitalization of Indigenous knowledge systems. As the first exploration of Indigenous conceptualizations of nature within NbS literatures, we close with four reflections for academics, advocates, leaders, activists, and policymakers to uplift Indigenous climate solutions for a just, equitable, and resilient future.
Comparison of ex vivo bioluminescence imaging, Alu-qPCR and histology for the quantification of spontaneous lung and bone metastases in subcutaneous xenograft mouse models
Authors: Haider Marie-Therese , Freytag Vera , Krause Linda , Spethmann Tanja , Gosau Tobias , Beine Mia C. , Knies Christine , Schröder-Schwarz Jennifer , Horn Michael , Riecken Kristoffer , Lange Tobias
Published: February 2024

Bioluminescence imaging (BLI) is a non-invasive state-of-the-art-method for longitudinal tracking of tumor cells in mice. The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based Alu-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~ 0.75 cm³ and mice were sacrificed ~ 3 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLIHi bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLILo bone) were prepared for Alu-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (r ~ 0.8) vs. bone metastasis detection (r ~ 0.4). However, the BLI values of the BLIHi and BLILo bones correlated very strongly (r ~ 0.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology/Alu-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.