bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of climate on soil viral communities in Australia on a regional scale
Authors: Bi Li , He Zi‐Yang , Nguyen Bao Anh Thi , Chan Lok Hang , Na Shuo , He Ji‐Zheng , Hu Hang‐Wei
Published: October 2024

Viruses play a crucial role in regulating microbial communities and ecosystem functioning. However, the biogeographic patterns of viruses and their responses to climate factors remain underexplored. In this study, we performed viral size fraction metagenomes on 108 samples collected along a 2600 km transect across Australia, encompassing distinct climate conditions. A total of 14,531 viral operational taxonomic units were identified. Climate factors had a greater influence than edaphic and biotic factors on driving the alpha diversity of viral communities. The strongest relationship was observed between mean annual temperature and the diversity of viral communities. Moreover, climate factors, particularly aridity index, were the primary drivers of viral community structure. Overall, these findings underscore the pivotal role of climate factors in shaping viral communities and have implications for understanding how climate change influences soil viral ecology.
The Role of Alkyl Chains in the Thermoresponse of Supramolecular Network
Authors: Scherb Sebastian , Hinaut Antoine , Gu Yanwei , Vilhena J.G. , Pawlak Rémy , Song Yiming , Narita Akimitsu , Glatzel Thilo , Müllen Klaus , Meyer Ernst
Published: October 2024

Supramolecular materials provide a pathway for achieving precise, highly ordered structures while exhibiting remarkable response to external stimuli, a characteristic not commonly found in covalently bonded materials. The design of self‐assembled materials, where properties could be predicted/design from chemical nature of the individual building blocks, hinges upon our ability to relate macroscopic properties to individual building blocks – a feat which has thus far remained elusive. Here, a design approach is demonstrated to chemically engineer the thermal expansion coefficient of 2D supramolecular networks by over an order of magnitude (\boldmath 120 to \boldmath 1000 × 10−6 K−1). This systematic study provides a clear pathway on how to carefully design the thermal expansion coefficient of a 2D molecular assembly. Specifically, a linear relation has been identified between the length of decorating alkyl chains and the thermal expansion coefficient. Counter‐intuitively, the shorter the chains the larger is the thermal expansion coefficient. This precise control over thermo‐mechanical properties marks a significant leap forward in the de‐novo design of advanced 2D materials. The possibility to chemically engineer their thermo‐mechanical properties holds promise for innovations in sensors, actuators, and responsive materials across diverse fields.
Li–Sb Alloy Formation Strategy to Improve Interfacial Stability of All‐Solid‐State Lithium Batteries
Authors: Dandena Berhanu Degagsa , Su Wei‐Nien , Tsai Dah‐Shyang , Nikodimos Yosef , Taklu Bereket Woldegbreal , Bezabh Hailemariam Kassa , Desta Gidey Bahre , Yang Sheng‐Chiang , Lakshmanan Keseven , Sheu Hwo‐Shuenn , Wang Chia‐Hsin , Wu She‐Huang , Hwang Bing Joe
Published: October 2024

The solid electrolyte is anticipated to prevent lithium dendrite formation. However, preventing interface reactions and the development of undesirable lithium metal deposition during cycling are difficult and remain unresolved. Here, to comprehend these occurrences better, this study reports an alloy formation strategy for enhanced interface stability by incorporating antimony (Sb) in the lithium argyrodite solid electrolyte Li6PS5Cl (LPSC‐P) to form Li–Sb alloy. The Li–Sb alloy emergence at the anodic interface is crucial in facilitating uniform lithium deposition, resulting in excellent long‐term stability, and achieving the highest critical current density of 14.5 mA cm−2 (among the reported sulfide solid electrolytes) without lithium dendrite penetration. Furthermore, Li–Sb alloy formation maintain interfacial contact, even, after several plating and stripping. The Li–Sb alloy formation is confirmed by XRD, Raman, and XPS. The work demonstrates the prospect of utilizing alloy‐forming electrolytes for advanced solid‐state batteries.
The Influence of Yeast Inoculated on the Structural and Physicochemical Properties of Wheat Starch during Ganmianpi Fermentation
Authors: Luo Yueping , Qi Shanshan , Mu Tingting , He Yuanchen , Luo Min , Zhang Youe , Han Lin , He Caian , Wang Min
Published: October 2024

Ganmianpi is a traditional snack in China that has traditionally been produced through natural fermentation of wheat starch slurry. However, natural fermentation occurs spontaneously and lacks control, thereby an alternative yeast‐inoculated fermentation method is proposed for the industrialization of Ganmianpi production. This study aims to investigate the impact of yeast‐inoculated fermentation on the structural and physicochemical properties of wheat starch and elucidate the underlying mechanism. The findings reveal that yeast fermentation significantly affects the properties of wheat starch, varying with the fermentation time. Yeast‐inoculated fermentation leads to surface erosion of the starch granules and a significant reduction in amylose content, double helicity, gelatinization enthalpy, and relative crystallinity of wheat starch. Specially, yeast‐inoculated fermentation alters starch chain proportions, with a decrease in chain A and an increase in chains B1, B2, and B3. Ganmianpi produced from wheat starch exhibits decreased hardness, springiness, and chewiness, and sensory evaluation suggests an optimal fermentation time of 18 h for Ganmianpi production. Overall, this study provides valuable theoretical support for the industrial production of Ganmianpi and promotes the standardized production of fermented starch‐based foods.
Hypoxia‐Associated GPNMB+ Macrophages Promote Malignant Progression of Colorectal Cancer and Its Related Risk Signature Are Powerful Predictive Tool for the Treatment of Colorectal Cancer Patients
Authors: Zhang Junli , Hu Shangshang , Jin Xinxin , Zheng Yiwen , Yu Lianchen , Ma Junrao , Gu Biao , Wang Fen , Wu Wenjuan
Published: October 2024

Colorectal cancer (CRC) is a highly malignant tumor with hypoxia being a crucial feature during its progression. This study utilized multiple independent CRC cohorts for bioinformatics analysis and in vitro experiments to investigate the role of hypoxia‐related subgroups in CRC. Machine learning was employed to construct risk features associated with this subgroup and further explore its therapeutic value in CRC. The study identified the GPNMB+ Macrophage (GPNMB+ Macr) subgroup as most relevant to hypoxia. GPNMB+ Macr showed significantly higher infiltration in tumor tissues compared to non‐tumor tissues, increasing with CRC stage. High infiltration of GPNMB+ Macr was associated with poor prognosis in terms of overall and recurrence‐free survival in CRC patients. GPNMB+ Macrophages exhibit M2‐like characteristics and have the ability to promote 5‐FU resistance, proliferation, and metastasis of CRC cells. The study developed the Hypoxia‐Related Macrophage Risk Score (HMRS), which not only served as an independent prognostic factor for CRC patients but also demonstrated robust prognostic performance compared to 84 previously published prognostic features. Patients with low HMRS were sensitive to fluorouracil, oxaliplatin (FOLFOX), and anti‐PD‐1 immunotherapy, while those with high HMRS showed resistance. Additionally, HMRS was identified as an independent prognostic factor in other digestive tract tumors (hepatocellular carcinoma, pancreatic cancer, esophageal cancer, and gastric cancer), indicating potential extrapolation to other tumor types. In conclusion, GPNMB+ Macr promotes the malignant progression of CRC, and HMRS serves as a powerful predictive tool for prognosis, chemotherapy, and immunotherapy in CRC patients, aiding in improving the quality of survival.
Attenuating susceptibility to ascites in cold‐stressed broiler chickens fed canola meal‐based diets by supplementing arginine or guanidinoacetic acid, either alone or in combination with phenylalanine
Authors: Delfani Negin , Daneshyar Mohsen , Farhoomand Parviz , Payvastegan Sina , Alijoo Younes Ali , Najafi Gholamreza
Published: October 2024

Objective

The purpose of this study was to determine the effects of dietary supplementation of arginine (ARG) or guanidinoacetic acid (GAA), with or without phenylalanine (PHE), on the ascites susceptibility in the cold‐stressed broilers fed canola meal (CM)‐based diet.

Method

A total of 450 one‐day‐old male broiler chicks were randomly allocated to 30 floor pens with 6 replications for each of the 5 treatments. The dietary treatments were as follows: CM‐based diet (control), CM‐based diet + 2.57 g/kg ARG, CM‐based diet + 1.8 g/kg GAA, CM‐based diet + 2.57 g/kg ARG + 1.5 g/kg PHE and CM‐based diet + 1.8 g/kg GAA + 1.5 g/kg PHE. The groups experienced cold stress induction starting at 32°C on day one, with gradual reductions to 15°C on days 21. The temperature was then held at 15°C for the remainder of the experiment.

Results

The supplements ARG + PHE and GAA + PHE resulted in improved feed conversion ratios (FCR) when compared to the control group. In comparison with the control group, supplementation of ARG and ARG + PHE decreased the ascites mortality by increasing the plasma nitric oxide level (NO), blood O2 partial pressure, blood O2 saturation (SO2), and decreasing the blood CO2 partial pressure (PCO2) and right ventricle to total ventricle (RV:TV) ratio. Supplementation of GAA and GAA + PHE also declined ascites mortality by reducing blood PCO2 while increasing blood SO2 and plasma NO levels. Although plasma corticosterone level and RV:TV ratio were similar between the GAA and control groups, adding GAA + PHE significantly reduced both compared to the control group.

Conclusion

In summary, supplementing cold‐stressed broiler chicken diets with 2.57 g/kg ARG may alleviate hypertension. Additionally, 1.8 g/kg GAA proves to be an effective substitute for dietary ARG in low‐ARG diets, alleviating adverse effects from cold stress. Proper PHE formulation, at 1.5 g/kg in this study, is crucial when using ARG and GAA supplements.
First molecular diagnosis of the human pathogen Rickettsia raoultii and other spotted fever group rickettsiae in Sudanese ixodid ticks from domestic ruminants
Authors: Eisawi Nagwa , Ahmed Jabbar , Bakheit Mohammed A. , Hassan Dina A. , Hussien Mohammed O. , El Hussein Abdel Rahim M.
Published: October 2024

Background

Rickettsial infections are often neglected and poorly recognized by physicians in many tropical and subtropical regions. Despite a number of recent reports describing rickettsial diseases in new locations and the discovery of new rickettsiae, medical science and research have largely neglected the diagnosis and antimicrobial treatment of rickettsial infections in subtropical and tropical areas; thus, much remains to be discovered. This study aimed to detect and characterize spotted fever group (SFG) rickettsiae in ixodid ticks infesting domestic ruminants in Khartoum State.

Methods

Polymerase chain reaction targeting both genes that encode for citrate synthase (gltA) and outer membrane protein (ompA) was performed for the presence of SFG rickettsia followed by sequence and phylogenetic analysis.

Results

Of the 202 ticks examined for the presence of SFG rickettsia, gltA gene was detected in 4 samples (2%). Furthermore, gltA‐positive samples were used to amplify the ompA gene, in which only two samples yielded positive results. Sequence and phylogenetic analysis of the positive samples revealed four different species of SFG rickettsiae: Rickettsia aeschlimannii, Rickettsia rhipicephali, Rickettsia massiliae and Rickettsia raoultii.

Conclusions

These results indicated the presence of SFG rickettsia in Sudanese ticks. This also indicates that humans have an opportunity to acquire these infections. It is important to keep in mind the need for careful consideration of rickettsial infections in individuals with a fever of unknown origin.
Evaluation of thiol/disulphide and oxidant–antioxidant status of dairy cows in periparturient and post‐partum period
Authors: Balkan Burcu Menekse , Meral Ogunc , Cetintav Bekir , Ozkurt Guzin , Balkan Ali Burak , Sel Tevhide
Published: October 2024

Background

Thiol/disulphide homeostasis (TDH) has a critical role in many cellular activities such as antioxidant protection. Alterations of oxidative stress in the transition period play an important role in development of some diseases and disorders in dairy cows.

Objectives

The purpose of this study is to assess the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total thiol, native thiol, disulphide and lipid profile in Simmental and Montofon dairy cows (aged 2–3) before and after calving.

Methods

Blood samples were collected 233–280 days of pregnancy and the 30 days of post‐partum. Serum total thiol, native thiol and disulphide levels were determined as well as TAS, TOS and paraoxonase‐1 (PON‐1) levels were measured using colorimetric assays. Triglycerides (TG), total cholesterol, HDL cholesterol and LDL cholesterol levels were measured with an automatic analyser.

Results

Total thiol (p = 0.038) and disulphide (p = 0.015) levels were higher after calving compare to pregnancy in Montofon. TAS was found lower (p < 0.001), and OSI was higher in both breeds (Montofon p = 0.012, Simmental p = 0.028) after calving than in pregnancy. When compared between pregnancy and after calving levels in the same breed, HDL was found to be higher after calving (p < 0.001) and TG was lower after calving (p = 0.020) in Montofon. PON (p = 0.090), HDL (p < 0.001) and cholesterol levels were found higher (p < 0.001) and TG level was lower (p < 0.001) after calving in Simmental.

Conclusions

According to our results, we observed different responses between two breeds before and after calving. There are few studies about TDH in animal research, and this is the first study in the literature that evaluates the TDH along with oxidative stress and lipid profiles in dairy cows in the periparturient and post‐partum period.
Effects of dietary digestible lysine levels in breeding Japanese quails on productive and reproductive performance, egg quality, blood metabolites and immune responses
Authors: Omary Mohammad Amin , Zarghi Heydar , Hassanabadi Ahmad
Published: October 2024

Background

The vegetable‐based diet alone does not provide the lysine (Lys) needed to maximize poultry productive performance.

Objectives

This experiment aimed to evaluate the effects of dietary digestible Lys (dLys) level on productive and reproductive performance, egg quality, blood metabolites and immune responses in breeding Japanese quails (Coturnix japonica).

Methods

The experiment was conducted in a completely randomized design with 6 treatments, 5 replicates and 15 (12 females and 3 meals) 10‐week‐old breeding Japanese quails each. A basal diet was formulated to meet nutritional requirements of breeding quails except dLys. The basal diet was supplemented with graded (+0.82 g/kg) levels of l‐Lys‐HCl, corresponding to dietary dLys levels of 0.690%, 0.755%, 0.820%, 0.885%, 0.950% and 1.015%. The experiment lasted for 12 weeks, which was divided into 3‐4‐week periods.

Results

Significant differences were observed for egg production (EP), egg mass (EM) and feed efficiency (FE) in response to increasing dietary dLys concentration with quadratic trends. The highest traits were observed in the birds fed with a diet containing 0.885% dLys. However, feed intake, egg quality, reproductive performance, blood metabolites and immune responses against sheep red blood cell inoculation were not significantly affected by increasing dietary dLys concentrations. The dLys requirements during 11–14, 15–18, 19–22 and 11–22 (overall) weeks of age for optimal EP, EM and FE, based on the quadratic broken‐line regression analysis, were estimated 272, 265, 250 and 266; 293, 285, 264 and 279; and 303, 294, 281 and 293 mg/bird/day, respectively.

Conclusions

The dLys requirements vary depending on the EP phase and the trait being optimized. The estimated dLys requirement for FE was higher than those for EP and EM. During the peak stage of the first laying cycle, the dietary dLys level of 0.932% and a daily intake of 303 mg dLys/bird are sufficient for optimal performance.
Apache is a neuronal player in autophagy required for retrograde axonal transport of autophagosomes
Authors: Parisi Barbara , Esposito Alessandro , Castroflorio Enrico , Bramini Mattia , Pepe Sara , Marte Antonella , Guarnieri Fabrizia C. , Valtorta Flavia , Baldelli Pietro , Benfenati Fabio , Fassio Anna , Giovedì Silvia
Published: October 2024

Neurons are dependent on efficient quality control mechanisms to maintain cellular homeostasis and function due to their polarization and long-life span. Autophagy is a lysosomal degradative pathway that provides nutrients during starvation and recycles damaged and/or aged proteins and organelles. In neurons, autophagosomes constitutively form in distal axons and at synapses and are trafficked retrogradely to the cell soma to fuse with lysosomes for cargo degradation. How the neuronal autophagy pathway is organized and controlled remains poorly understood. Several presynaptic endocytic proteins have been shown to regulate both synaptic vesicle recycling and autophagy. Here, by combining electron, fluorescence, and live imaging microscopy with biochemical analysis, we show that the neuron-specific protein APache, a presynaptic AP-2 interactor, functions in neurons as an important player in the autophagy process, regulating the retrograde transport of autophagosomes. We found that APache colocalizes and co-traffics with autophagosomes in primary cortical neurons and that induction of autophagy by mTOR inhibition increases LC3 and APache protein levels at synaptic boutons. APache silencing causes a blockade of autophagic flux preventing the clearance of p62/SQSTM1, leading to a severe accumulation of autophagosomes and amphisomes at synaptic terminals and along neurites due to defective retrograde transport of TrkB-containing signaling amphisomes along the axons. Together, our data identify APache as a regulator of the autophagic cycle, potentially in cooperation with AP-2, and hypothesize that its dysfunctions contribute to the early synaptic impairments in neurodegenerative conditions associated with impaired autophagy.
Alternated cross-laminated timber (aCLT) panels: development and mechanical characterization
Authors: Santos P. , Cardoso L. , Dias A. M. P. G.
Published: October 2024

A novel type of wood-based panel for structural applications is presented. Such panel named as alternated cross-laminated timber (aCLT) is based on the cross-laminated timber (CLT) panel concept but with a modified internal architecture, in which the cross-layers are replaced by hybrid layers composed of the traditional cross-lamellas alternated with in-line lamellas—as in glued laminated timber (GLT). Such modification aims to improve stiffness and strength in the main direction of the panel in comparison to the traditional CLT concept. To study the referred panel concept and its behavior, a series of panel stripes specimens (beams) of the new panel concept, as well as of CLT and GLT, were produced with 3 and 5 layers. An experimental campaign was performed to determine: (i) the Young`s modulus of the lamellas; (ii) the shear modulus and strength of the cross/hybrid layers of the panels and; (iii) the force vs. deflection of the beams in bending for the determination of bending and shear stiffness and strength. The data obtained in (i) and (ii) was inputted into a developed finite element (FE) model and the results from (iii) were used to validate the models. The FE model was later used to compare the performance of CLT and aCLT of equivalent thickness for a practical case. The results revealed a slight reduction in deflection (between 2 and 11%) and normal stress (1–7%) and a more substantial reduction in shear stress (between 28 and 94%) against the CLT solutions.
Should sports professionals consider their adversary’s strategy? A case study of match play in golf
Authors: Wajge Nishad , Stauffer Gautier
Published: October 2024

This study explores strategic considerations in professional golf’s Match Play format. Leveraging Professional Golfers’ Association Tour data, we investigate the impact of factoring in an adversary’s strategy. Our findings suggest that while slight strategy adjustments can be advantageous in specific scenarios, the overall benefit of considering an opponent’s strategy remains modest. This confirms the common wisdom in golf, reinforcing the recommendation to adhere to optimal stroke-play strategies due to challenges in obtaining precise opponent statistics. The methodology employed here is generic and could offer valuable insights into whether opponents’ performances should also be considered in other two-player or team sports, such as tennis, darts, soccer, volleyball, etc. We hope that this research will pave the way for new avenues of study in these areas.
Inverse demand tracking in transportation networks
Authors: Göttlich Simone , Mehlitz Patrick , Schillinger Thomas
Published: October 2024

This paper deals with the reconstruction of the desired demand in an optimal control problem, stated over a tree-shaped transportation network which is governed by a linear hyperbolic conservation law. As desired demands typically undergo fluctuations due to seasonality or unexpected events making short-term adjustments necessary, such an approach can exemplary be used for forecasting from past data. We suggest to model this problem as a so-called inverse optimal control problem, i.e., a hierarchical optimization problem whose inner problem is the optimal control problem and whose outer problem is the reconstruction problem. In order to guarantee the existence of solutions in the function space framework, the hyperbolic conservation law is interpreted in weak sense allowing for control functions in Lebesgue spaces. For the computational treatment of the model, we transfer the hierarchical problem into a nonsmooth single-level one by plugging the uniquely determined solution of the inner optimal control problem into the outer reconstruction problem before applying techniques from nonsmooth optimization. Some numerical experiments are presented to visualize various features of the model including different types of noise in the demand and strategies of how to observe the network in order to obtain good reconstructions of the desired demand.
On the non-uniqueness of linear Markov perfect equilibria in linear-quadratic differential games: a geometric approach
Authors: Eigruber Markus , Wirl Franz
Published: October 2024

Although the possibility of multiple nonlinear equilibria in linear-quadratic differential games is extensively discussed, the literature on models with multiple linear Markov perfect equilibria (LMPEs) is scarce. Indeed, almost all papers confined to a single state (the vast majority of the application of differential games to economic problems) find a unique LMPE. This paper explains this finding and derives conditions for multiplicity based on the analysis of the phase plane in the state and the derivative of the value function. The resulting condition is applied to derive additional pathways different from the (two) known ones. All these examples, more precisely, their underlying pathways or the resulting outcomes, contradict usual assumptions in economic models. However, by extending the state space, we provide an economic setting (learning by doing) that gives rise to multiple LMPEs.
Determination of double bond positions in unsaturated fatty acids by pre-column derivatization with dimethyl and dipyridyl disulfide followed by LC-SWATH-MS analysis
Authors: Olfert Matthias , Knappe Cornelius , Sievers-Engler Adrian , Masberg Benedikt , Lämmerhofer Michael
Published: October 2024

Comprehensive in-depth structural characterization of free mono-unsaturated and polyunsaturated fatty acids often requires the determination of carbon-carbon double bond positions due to their impact on physiological properties and relevance in biological samples or during impurity profiling of pharmaceuticals. In this research, we report on the evaluation of disulfides as suitable derivatization reagents for the determination of carbon-carbon double bond positions of unsaturated free fatty acids by UHPLC-ESI-QTOF-MS/MS analysis and SWATH (sequential windowed acquisition of all theoretical mass spectra) acquisition. Iodine-catalyzed derivatization of C = C double bonds with dimethyl disulfide (DMDS) enabled detection of characteristic carboxy-terminal MS2 fragments for various fatty acids in ESI negative mode. The determination of double bond positions of fatty acids with up to three double bonds, the transfer of the method to plasma samples, and its limitations have been shown. To achieve charge-switching for positive ion mode MS-detection, derivatization with 2,2′-dipyridyldisulfide (DPDS) was investigated. It enabled detection of both corresponding characteristic omega-end- and carboxy-end-fragments for fatty acids with up to two double bonds in positive ion mode. It provides a straightforward strategy for designing MRM transitions for targeted LC–MS/MS assays. Both derivatization techniques represent a simple and inexpensive way for the determination of double bond positions in fatty acids with low number of double bonds. No adaptation of MS hardware is required and the specific isotopic pattern of resulting sulfur-containing products provides additional structural confirmation. This reaction scheme opens up the avenue of structural tuning of disulfide reagents beyond DMDS and DPDS using reagents like cystine and analogs to achieve enhanced performance and sensitivity.

Graphical Abstract
An electrochemical proximity assay (ECPA) for antibody detection incorporating flexible spacers for improved performance
Authors: Kurian Amanda S. N. , Mazumder Mainul Islam , Gurukandure Asanka , Easley Christopher J.
Published: October 2024

A clever approach for biosensing is to leverage the concept of the proximity effect, where analyte binding to probes can be coupled to a second, controlled binding event such as short DNA strands. This analyte-dependent effect has been exploited in various sensors with optical or electrochemical readouts. Electrochemical proximity assays (ECPA) are more amenable to miniaturization and adaptation to the point-of-care, yet ECPA has been generally targeted toward protein sensing with antibody-oligonucleotide probes. Antibodies themselves are also important as biomarkers, since they are produced in bodily fluids in response to various diseases or infections, often in low amounts. In this work, by using antigen-DNA conjugates, we targeted an ECPA method for antibody sensing and showed that the assay performance can be greatly enhanced using flexible spacers in the DNA conjugates. After adding flexible polyethylene glycol (PEG) spacers at two distinct positions, the spacers ultimately increased the antibody-dependent current by a factor of 4.0 without significant background increases, similar to our recent work using thermofluorimetric analysis (TFA). The optimized ECPA was applied to anti-digoxigenin antibody quantification at concentrations ranging over two orders of magnitude, from the limit of detection of 300 pM up to 50 nM. The assay was functional in 90% human serum, where increased ionic strength was used to counteract double-layer repulsion effects at the electrode. This flexible-probe ECPA methodology should be useful for sensing other antibodies in the future with high sensitivity, and the mechanism for signal improvement with probe flexibility may be applicable to other DNA-based electrochemical sensor platforms.

Graphical Abstract
Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas
Authors: Silver Luke W. , McLennan Elspeth A. , Beaman Julian , da Silva Karen Burke , Timms Peter , Hogg Carolyn J. , Belov Katherine
Published: October 2024

Conservation genomics can greatly improve conservation outcomes of threatened populations, including those impacted by disease. Understanding diversity within immune gene families, including the major histocompatibility complex (MHC) and toll-like receptors (TLR), is important due to the role they play in disease resilience and susceptibility. With recent advancements in sequencing technologies and bioinformatic tools, the cost of generating high-quality sequence data has significantly decreased and made it possible to investigate diversity across entire gene families in large numbers of individuals compared to investigating only a few genes or a few populations previously. Here, we use the koala as a case study for investigating functional diversity across populations. We utilised previous target enrichment data and 438 whole genomes to firstly, determine the level of sequencing depth required to investigate MHC diversity and, secondly, determine the current level of diversity in MHC genes in koala populations. We determined for low complexity, conserved genes such as TLR genes 10 × sequencing depth is sufficient to reliably genotype more than 90% of variants, whereas for complex genes such as the MHC greater than 20 × and preferably 30 × sequencing depth is required. We used whole genome data to identify 270 biallelic SNPs across 24 MHC genes as well as copy number variation (CNV) within class I and class II genes and conduct supertype analysis. Overall, we have provided a bioinformatic workflow for investigating variation in a complex immune gene family from whole genome sequencing data and determined current levels of diversity within koala MHC genes.
Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome
Authors: Huls Gerwin , Chitu Dana A. , Tick Lidwine , Boersma Rinske , Breems Dimitri , Herbers Alexandra , Klein Saskia K. , de Jonge Suzan , Westerweel Peter E. , Cruijsen Marjan , Hoogendoorn Mels , Cuijpers Marlous , Deeren Dries , Bailly Benjamin , Visser Otto , van Rhenen Anna , Posthuma Eduard F. M. , Valk Peter J. M. , Cloos Jacqueline , Ammatuna Emanuele , Refos Jeannine M. , Fakkert R. , Löwenberg Bob , Ossenkoppele Gert J.
Published: October 2024

The treatment of older patients with acute myeloid leukemia (AML) considered unfit for receiving intensive chemotherapy is challenging. Based on the hypothesis that addition of the broad tyrosine kinase inhibitor (TKI) midostaurin could improve the response to hypomethylating agents, irrespective of FLT3 gene mutational status, we conducted a randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to a 10-day schedule of decitabine in unfit (i.e. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≥ 3) AML and higher risk myelodysplasia (MDS) patients (HOVON155 trial). In total, 140 eligible patients were randomly (1:1) assigned to treatment with 10-days of decitabine alone (N = 70) or combined with midostaurin (50 mg bid;starting the day following the last dose of decitabine), (N = 70). Addition of midostaurin was well tolerated and the number of AEs was comparable for both treatment arms. Early death rates (< 30 days) were similar as well (10%). In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.
Cryptofaunal communities are influenced by benthic cover and fish abundance in a large Caribbean coral reef system
Authors: Armenteros Maickel , Díaz-Delgado Yarima , Marzo-Pérez Diana , Pérez-García José A. , Hernández-Fernández Leslie , González de Zayas Roberto , Navarro-Martínez Zenaida M. , Apprill Amy
Published: October 2024

Small-sized invertebrates inhabiting hard substrates in coral reefs (a.k.a. cryptofauna) contribute substantially to reef biodiversity, but their patterns of distribution and ecological controls are poorly understood. Here, we characterized the cryptofauna community and explored “bottom-up” and “top-down” controls by benthic cover and fish abundance, respectively. We sampled the cryptofauna inhabiting the reef terrace from 13 sites along 200 km in Jardines de la Reina (Cuba), a well-preserved and protected area in the Caribbean. We counted 23,959 invertebrates of 14 higher taxa, being the most abundant Copepoda (54%), Nematoda (21%), Mollusca (7%), Ostracoda (5%), Polychaeta (5%), and Amphipoda (3%). Richness, abundance, and community structure varied across the reefs without any geographical gradient of distribution. One-third of the variance occurred at site scale (~ 10 km), and half occurred at quadrat scale (~ 1 m). Algal cover promoted cryptofauna richness and abundance likely providing substrate and food, while live coral cover negatively influenced nematode abundances, potentially due to coral defenses. Relationships between cryptofauna and reef fishes were also present, with invertivores and herbivores negatively affecting cryptofauna abundance likely due to direct or indirect predation pressures. This research highlights the important roles of bottom-up and top-down controls, by algal/coral cover and fishes, respectively, on cryptofauna and in extension to coral reef biodiversity. Current threats by climate change are expected to alter these controls on cryptofauna resulting in changes to diversity, trophodynamics and energy flows of coral reefs.
National centralization of Hirschsprung’s disease in Sweden: a comparison of postoperative outcome
Authors: Söderström Linnea , Graneli Christina , Rossi Daniel , Hagelsteen Kristine , Gunnarsdottir Anna , Oddsberg Jenny , Svensson Pär-Johan , Borg Helena , Bräutigam Matilda , Gustafson Elisabet , Löf Granström Anna , Stenström Pernilla , Wester Tomas
Published: October 2024

Background

In Sweden, surgical treatment of Hirschsprung’s disease (HSCR) was centralized from four to two pediatric surgery centers 1st of July 2018. In adults, centralization of surgical care for complex or rare diseases seems to improve quality of care. There is little evidence supporting centralization of pediatric surgical care. The aim of this study was to assess surgical management and postoperative outcome in HSCR patients following centralization of care.

Methods

This study retrospectively analyzed data of patients with HSCR that had undergone pull-through at a pediatric surgery center in Sweden from 1st of July 2013 to 30th of June 2023. Patients managed from 1st of July 2013 to 30th of June 2018 (before centralization) were compared with patients managed from 1st of July 2018 to 30th of June 2023 (after centralization) regarding surgical treatment, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through as well as complications classified according to Clavien–Madadi up to 30 days after pull-through.

Results

In the 5-year period prior to centralization, 114 individuals from 4 treating centers were included and compared to 83 patients from 2 treating centers in the second period. There was no difference regarding age at pull-through or proportion of patients with a stoma prior to pull-through. An increase of laparoscopically assisted endorectal pull-through (8.8% to 39.8%) was observed (p < 0.001). No significant differences were seen in postoperative hospital stay, unplanned procedures under general anesthesia, or readmissions up to 90 days after pull-through. There was no difference in severe complications (Clavien–Madadi ≥ 3); however, HAEC treated with antibiotics increased following centralization (10.5–24.1%; p = 0.018).

Conclusion

Centralization of care for HSCR does not seem to delay time to pull-through nor reduce severe complications, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through. The increased HAEC rate may be due to increased awareness of mild HAEC.

Level of evidence: Level III.
Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy
Authors: Moser Tobias , Gruber Joachim , Mylonaki Eirini , Böhm Vincent , Schwarzenhofer Daniel , Tröscher Anna R. , Lenzenweger Eva , Krehan Ingomar , Söllradl Eva , Leitinger Markus , Helbok Raimund , Trinka Eugen , von Oertzen Tim J. , Wagner Judith N.
Published: October 2024

Background

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.

Methods

A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits.

Results

Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433–3274) indicated favorable outcomes in both groups.

Conclusion

This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.
The work–recovery cycle of kidney strain and inflammation in sugarcane workers following repeat heat exposure at work and at home
Authors: Lucas Rebekah A. I. , Hansson Erik , Skinner Bethany D. , Arias-Monge Esteban , Wesseling Catharina , Ekström Ulf , Weiss Ilana , Castellón Zoey E. , Poveda Scarlette , Cerda-Granados Fatima I. , Martinez-Cuadra William Jose , Glaser Jason , Wegman David H. , Jakobsson Kristina
Published: October 2024

Purpose

To examine heat exposure at work and home and the work–recovery cycle and temporal variation of kidney strain, muscle injury and inflammation biomarkers in sugarcane workers.

Methods

20 male sugarcane workers (age: 33 ± 7 years) with a workplace Rest.Shade.Hydration (RSH) intervention were observed over 4 days, at the end (18 h post-shift recovery) and beginning of a work week (42 h post-shift recovery). Measures included work intensity (heart rate), gastro-intestinal temperature, estimated body core temperature (using heart rate), fluid consumption, pre- and post-work blood and urine samples, physical activity (accelerometery) away from work, plus ambient heat exposure at work and home.

Results

On workdays, workers awakened at approx. 02:40 after 5 h sleep in ~ 30 °C. Across work shifts, daily average WBGT ranged from 26 to 29 °C (cooler than normal) and average workload intensity ranged from 55 to 58%HRmax. Workers reported consuming ~ 8 L of water and ~ 4 × 300 mL bags of electrolyte fluid each day. Serum creatinine, cystatin C and creatine phosphokinase markedly increased post-work and decreased during recovery; serum potassium did the opposite (all p < 0.01). Biomarker concentration changes were similar between recovery periods (18 h vs. 42 h; all p > 0.27). C-reactive protein was the highest at the end of the work week (p = 0.01).

Conclusion

Despite RSH intervention, cross-shift kidney strain was marked (recovering overnight) and systemic inflammation increased over the work week. Thus, biomonitoring of kidney function in occupational populations should be performed before a work shift at any point in the work week. This is essential knowledge for field studies and surveillance.
Neuromuscular characteristics of eccentric, concentric and isometric contractions of the knee extensors
Authors: Ruas Cassio V. , Taylor Janet L. , Latella Christopher , Haff G. Gregory , Nosaka Kazunori
Published: October 2024

Purpose

We compared voluntary drive and corticospinal responses during eccentric (ECC), isometric (ISOM) and concentric (CON) muscle contractions to shed light on neurophysiological mechanisms underpinning the lower voluntary drive in a greater force production in ECC than other contractions.

Methods

Sixteen participants (20–33 years) performed ISOM and isokinetic (30°/s) CON and ECC knee extensor contractions (110°–40° knee flexion) in which electromyographic activity (EMG) was recorded from vastus lateralis. Voluntary activation (VA) was measured during ISOM, CON and ECC maximal voluntary contractions (MVCs). Transcranial magnetic stimulation elicited motor-evoked potentials (MEPs) and corticospinal silent periods (CSP) during MVCs and submaximal (30%) contractions, and short-interval intracortical inhibition (SICI) in submaximal contractions.

Results

MVC torque was greater (P < 0.01) during ECC (302.6 ± 90.0 Nm) than ISOM (269.8 ± 81.5 Nm) and CON (235.4 ± 78.6 Nm), but VA was lower (P < 0.01) for ECC (68.4 ± 14.9%) than ISOM (78.3 ± 13.1%) and CON (80.7 ± 15.4%). In addition, EMG/torque was lower (P < 0.02) for ECC (1.9 ± 1.1 μV.Nm−1) than ISOM (2.2 ± 1.2 μV.Nm−1) and CON (2.7 ± 1.6 μV.Nm−1), CSP was shorter (p < 0.04) for ECC (0.097 ± 0.03 s) than ISOM (0.109 ± 0.02 s) and CON (0.109 ± 0.03 s), and MEP amplitude was lower (P < 0.01) for ECC (3.46 ± 1.67 mV) than ISOM (4.21 ± 2.33 mV) and CON (4.01 ± 2.06 mV). Similar results were found for EMG/torque and CSP during 30% contractions, but MEP and SICI showed no differences among contractions (p > 0.05).

Conclusions

The lower voluntary drive indicated by reduced VA during ECC may be partly explained by lower corticospinal excitability, while the shorter CSP may reflect extra muscle spindle excitation of the motoneurons from vastus lateralis muscle lengthening.
GLP-1 receptor agonists are a transformative prehabilitation tool for weight loss in obese patients undergoing elective hernia repair
Authors: Spurzem Graham J. , Broderick Ryan C. , Ruiz-Cota Patricia , Hollandsworth Hannah M. , Sandler Bryan J. , Horgan Santiago , Grunvald Eduardo , Jacobsen Garth R.
Published: October 2024

Background

Obesity is an independent risk factor for complications after abdominal hernia repair. Glucagon-like-peptide-1 (GLP-1) receptor agonists are gaining popularity as pharmacologic weight loss adjuncts and may help patients reach weight loss goals for surgery. We examine our early experience utilizing GLP-1 agonists versus lifestyle modifications alone to achieve weight loss in patients before elective hernia repair.

Methods

This single-center, retrospective review identified obese patients who underwent elective hernia repair from 2014 to 2023. Patients were asked to achieve a BMI ≤ 33 kg/m2 before surgery. Patients who lost weight with GLP-1 therapy in addition to lifestyle changes were compared to a control cohort that achieved similar preoperative weight loss without GLP-1 therapy. Primary outcome was mean time from GLP-1 agonist initiation and initial surgery clinic visit to surgery. Secondary outcomes were 30-day morbidity, mortality, and reoperation rates, and hernia recurrence.

Results

Forty-six patients with ventral/incisional, flank, umbilical, parastomal, inguinal, and hiatal hernias were identified (GLP-1 N = 24, control N = 22). 81.8% (N = 18) of controls had a ventral/incisional hernia, compared to 45.8% (N = 11) of GLP-1 patients (p = 0.03). Mean BMI at GLP-1 agonist initiation was similar to mean BMI at initial clinic visit for controls (38.1 ± 4.9 vs 38.2 ± 2.7 kg/m2, p = 0.66). Preoperative mean percentage total weight loss (14.9 ± 7.5 vs 12.4 ± 6.9 kg, p = 0.39) and mean BMI reduction (6.0 ± 3.8 vs 4.9 ± 2.3 kg/m2, p = 0.43) were similar between groups. The mean time from GLP-1 agonist initiation to surgery was significantly shorter than initial clinic visit to surgery for controls (6.3 ± 4.0 vs 14.7 ± 17.6 months, p = 0.03). There was no statistically significant difference in time from initial clinic visit to surgery between groups (7.6 ± 4.4 vs 14.7 ± 17.6 months, p = 0.06). There was no significant difference in 30-day morbidity between groups (8.3 vs 27.3%, p = 0.13).

Conclusion

GLP-1 agonists accelerate preoperative weight loss for obese hernia patients without negatively impacting postoperative outcomes.
Multi-hierarchical surrogate learning for explicit structural dynamical systems using graph convolutional neural networks
Authors: Kneifl Jonas , Fehr Jörg , Brunton Steven L. , Kutz J. Nathan
Published: October 2024

Highly nonlinear dynamic finite element simulations using explicit time integration are particularly valuable tools for structural analysis in fields like automotive, aerospace, and civil engineering, or in the study of injury biomechanics. However, such state-of-the-art simulation models demand significant computational resources. Conventional data-driven surrogate modeling approaches address this by evolving the dynamics on low-dimensional embeddings, yet the majority of them operate directly on high-resolution data obtained from numerical discretizations, making them costly and unsuitable for adaptive resolutions or for handling information flow over large spatial distances. We therefore propose a multi-hierarchical framework for the structured creation of a series of surrogate models at different resolutions. Macroscale features are captured on coarse surrogates, while microscale effects are resolved on finer ones, while leveraging transfer learning to pass information between scales. The objective of this study is to develop efficient surrogates for a kart frame model in a frontal impact scenario. To achieve this, its mesh is simplified to obtain multi-resolution representations of the kart. Subsequently, a graph-convolutional neural network-based surrogate learns parameter-dependent low-dimensional latent dynamics on the coarsest representation. Following surrogates are trained on residuals using finer resolutions, allowing for multiple surrogates with varying hardware requirements and increasing accuracy.