bluuebunny/crossref_metadata_2025 huggingface dataset:
Sis2 regulates yeast replicative lifespan in a dose-dependent manner
Authors: Ölmez Tolga T. , Moreno David F. , Liu Ping , Johnson Zane M. , McGinnis Madeline M. , Tu Benjamin P. , Hochstrasser Mark , Acar Murat
Published: November 2023

Application of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS); however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measure the RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type; while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion ofSIS2gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in thesis2Δbackground neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components insis2Δbackground. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.
Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue
Authors: Chang HaoRan , Esteves Ingrid M. , Neumann Adam R. , Mohajerani Majid H. , McNaughton Bruce L.
Published: November 2023

Episodic memories comprise diverse attributes of experience distributed across neocortical areas. The hippocampus is integral to rapidly binding these diffuse representations, as they occur, to be later reinstated. However, the nature of the information exchanged during this hippocampal-cortical dialogue remains poorly understood. A recent study has shown that the secondary motor cortex carries two types of representations: place cell-like activity, which were impaired by hippocampal lesions, and responses tied to visuo-tactile cues, which became more pronounced following hippocampal lesions. Using two-photon Ca2+ imaging to record neuronal activities in the secondary motor cortex of male Thy1-GCaMP6s mice, we assessed the cortical retrieval of spatial and non-spatial attributes from previous explorations in a virtual environment. We show that, following navigation, spontaneous resting state reactivations convey varying degrees of spatial (trajectory sequences) and non-spatial (visuo-tactile attributes) information, while reactivations of non-spatial attributes tend to precede reactivations of spatial representations surrounding hippocampal sharp-wave ripples.
Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study
Authors: Raineri Alessia , Radtke Thomas , Rueegg Sonja , Haile Sarah R. , Menges Dominik , Ballouz Tala , Ulyte Agne , Fehr Jan , Cornejo Daniel L. , Pantaleo Giuseppe , Pellaton Céline , Fenwick Craig , Puhan Milo A. , Kriemler Susi
Published: November 2023

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study “Ciao Corona”, we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3–98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717.
Sequential vaccinations with divergent H1N1 influenza virus strains induce multi-H1 clade neutralizing antibodies in swine
Authors: Van Reeth Kristien , Parys Anna , Gracia José Carlos Mancera , Trus Ivan , Chiers Koen , Meade Philip , Liu Sean , Palese Peter , Krammer Florian , Vandoorn Elien
Published: November 2023

Vaccines that protect against any H1N1 influenza A virus strain would be advantageous for use in pigs and humans. Here, we try to induce a pan-H1N1 antibody response in pigs by sequential vaccination with antigenically divergent H1N1 strains. Adjuvanted whole inactivated vaccines are given intramuscularly in various two- and three-dose regimens. Three doses of heterologous monovalent H1N1 vaccine result in seroprotective neutralizing antibodies against 71% of a diverse panel of human and swine H1 strains, detectable antibodies against 88% of strains, and sterile cross-clade immunity against two heterologous challenge strains. This strategy outperforms any two-dose regimen and is as good or better than giving three doses of matched trivalent vaccine. Neutralizing antibodies are H1-specific, and the second heterologous booster enhances reactivity with conserved epitopes in the HA head. We show that even the most traditional influenza vaccines can offer surprisingly broad protection if they are administered in an alternative way.
Modular interneuron circuits control motion sensitivity in the mouse retina
Authors: Jo Andrew , Deniz Sercan , Cherian Suraj , Xu Jian , Futagi Daiki , DeVries Steven H. , Zhu Yongling
Published: November 2023

Neural computations arise from highly precise connections between specific types of neurons. Retinal ganglion cells (RGCs) with similar stratification patterns are positioned to receive similar inputs but often display different response properties. In this study, we used intersectional mouse genetics to achieve single-cell type labeling and identified an object motion sensitive (OMS) AC type, COMS-AC(counter-OMS AC). Optogenetic stimulation revealed that COMS-AC makes glycinergic synapses with the OMS-insensitive HD2p-RGC, while chemogenetic inactivation showed that COMS-AC provides inhibitory control to HD2p-RGC during local motion. This local inhibition, combined with the inhibitory drive from TH2-AC during global motion, explains the OMS-insensitive feature of HD2p-RGC. In contrast, COMS-AC fails to make synapses with W3(UHD)-RGC, allowing it to exhibit OMS under the control of VGlut3-AC and TH2-AC. These findings reveal modular interneuron circuits that endow structurally similar RGC types with different responses and present a mechanism for redundancy-reduction in the retina to expand coding capacity.
A simeprevir-inducible molecular switch for the control of cell and gene therapies
Authors: Chin Stacey E. , Schindler Christina , Vinall Lisa , Dodd Roger B. , Bamber Lisa , Legg Sandrine , Sigurdardottir Anna , Rees D. Gareth , Malcolm Tim I. M. , Spratley Samantha J. , Granéli Cecilia , Sumner Jonathan , Tigue Natalie J.
Published: November 2023

Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components. Here we describe a CID module based on the orally available, approved, small molecule simeprevir and its target, the NS3/4A protease from hepatitis C virus. We demonstrate the utility of this CID module as a molecular switch to control biological processes such as gene expression and apoptosis in vitro, and show that the CID system can be used to rapidly induce apoptosis in tumor cells in a xenograft mouse model, leading to complete tumor regression.
scDREAMER for atlas-level integration of single-cell datasets using deep generative model paired with adversarial classifier
Authors: Shree Ajita , Pavan Musale Krushna , Zafar Hamim
Published: November 2023

Integration of heterogeneous single-cell sequencing datasets generated across multiple tissue locations, time, and conditions is essential for a comprehensive understanding of the cellular states and expression programs underlying complex biological systems. Here, we present scDREAMER (https://github.com/Zafar-Lab/scDREAMER), a data-integration framework that employs deep generative models and adversarial training for both unsupervised and supervised (scDREAMER-Sup) integration of multiple batches. Using six real benchmarking datasets, we demonstrate that scDREAMER can overcome critical challenges including skewed cell type distribution among batches, nested batch-effects, large number of batches and conservation of development trajectory across batches. Our experiments also show that scDREAMER and scDREAMER-Sup outperform state-of-the-art unsupervised and supervised integration methods respectively in batch-correction and conservation of biological variation. Using a 1 million cells dataset, we demonstrate that scDREAMER is scalable and can perform atlas-level cross-species (e.g., human and mouse) integration while being faster than other deep-learning-based methods.
The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii
Authors: Mitic Bernd M. , Troyer Christina , Lutz Lisa , Baumschabl Michael , Hann Stephan , Mattanovich Diethard
Published: November 2023

The current climatic change is predominantly driven by excessive anthropogenic CO2 emissions. As industrial bioprocesses primarily depend on food-competing organic feedstocks or fossil raw materials, CO2 co-assimilation or the use of CO2-derived methanol or formate as carbon sources are considered pathbreaking contributions to solving this global problem. The number of industrially-relevant microorganisms that can use these two carbon sources is limited, and even fewer can concurrently co-assimilate CO2. Here, we search for alternative native methanol and formate assimilation pathways that co-assimilate CO2 in the industrially-relevant methylotrophic yeast Komagataella phaffii (Pichia pastoris). Using 13C-tracer-based metabolomic techniques and metabolic engineering approaches, we discover and confirm a growth supporting pathway based on native enzymes that can perform all three assimilations: namely, the oxygen-tolerant reductive glycine pathway. This finding paves the way towards metabolic engineering of formate and CO2 utilisation to produce proteins, biomass, or chemicals in yeast.
Local H2 release remodels senescence microenvironment for improved repair of injured bone
Authors: Chen Shengqiang , Yu Yuanman , Xie Songqing , Liang Danna , Shi Wei , Chen Sizhen , Li Guanglin , Tang Wei , Liu Changsheng , He Qianjun
Published: November 2023

The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.
Discovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery
Authors: Tian Jinzhong , Deng Wangshuying , Zhang Ziwen , Xu Jiaqi , Yang Guiling , Zhao Guoping , Yang Sheng , Jiang Weihong , Gu Yang
Published: November 2023

Formic acid (FA) has emerged as a promising one-carbon feedstock for biorefinery. However, developing efficient microbial hosts for economically competitive FA utilization remains a grand challenge. Here, we discover that the bacterium Vibrio natriegens has exceptional FA tolerance and metabolic capacity natively. This bacterium is remodeled by rewiring the serine cycle and the TCA cycle, resulting in a non-native closed loop (S-TCA) which as a powerful metabolic sink, in combination with laboratory evolution, enables rapid emergence of synthetic strains with significantly improved FA-utilizing ability. Further introduction of a foreign indigoidine-forming pathway into the synthetic V. natriegens strain leads to the production of 29.0 g · L−1 indigoidine and consumption of 165.3 g · L−1 formate within 72 h, achieving a formate consumption rate of 2.3 g · L−1 · h−1. This work provides an important microbial chassis as well as design rules to develop industrially viable microorganisms for FA biorefinery.
Proton and molecular permeation through the basal plane of monolayer graphene oxide
Authors: Wu Z. F. , Sun P. Z. , Wahab O. J. , Tan Y. T. , Barry D. , Periyanagounder D. , Pillai P. B. , Dai Q. , Xiong W. Q. , Vega L. F. , Lulla K. , Yuan S. J. , Nair R. R. , Daviddi E. , Unwin P. R. , Geim A. K. , Lozada-Hidalgo M.
Published: November 2023

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.
Mutual modulation of gut microbiota and the immune system in type 1 diabetes models
Authors: Rosell-Mases Estela , Santiago Alba , Corral-Pujol Marta , Yáñez Francisca , Varela Encarna , Egia-Mendikute Leire , Arpa Berta , Cosovanu Catalina , Panosa Anaïs , Serrano-Gómez Gerard , Mora Conchi , Verdaguer Joan , Manichanh Chaysavanh
Published: November 2023

The transgenic 116C-NOD mouse strain exhibits a prevalent Th17 phenotype, and reduced type 1 diabetes (T1D) compared to non-obese diabetic (NOD) mice. A cohousing experiment between both models revealed lower T1D incidence in NOD mice cohoused with 116C-NOD, associated with gut microbiota changes, reduced intestinal permeability, shifts in T and B cell subsets, and a transition from Th1 to Th17 responses. Distinct gut bacterial signatures were linked to T1D in each group. Using a RAG-2−/− genetic background, we found that T cell alterations promoted segmented filamentous bacteria proliferation in young NOD and 116C-NOD, as well as in immunodeficient NOD.RAG-2−/− and 116C-NOD.RAG-2−/− mice across all ages. Bifidobacterium colonization depended on lymphocytes and thrived in a non-diabetogenic environment. Additionally, 116C-NOD B cells in 116C-NOD.RAG-2−/− mice enriched the gut microbiota in Adlercreutzia and reduced intestinal permeability. Collectively, these results indicate reciprocal modulation between gut microbiota and the immune system in rodent T1D models.
A fully integrated, standalone stretchable device platform with in-sensor adaptive machine learning for rehabilitation
Authors: Xu Hongcheng , Zheng Weihao , Zhang Yang , Zhao Daqing , Wang Lu , Zhao Yunlong , Wang Weidong , Yuan Yangbo , Zhang Ji , Huo Zimin , Wang Yuejiao , Zhao Ningjuan , Qin Yuxin , Liu Ke , Xi Ruida , Chen Gang , Zhang Haiyan , Tang Chu , Yan Junyu , Ge Qi , Cheng Huanyu , Lu Yang , Gao Libo
Published: November 2023

Post-surgical treatments of the human throat often require continuous monitoring of diverse vital and muscle activities. However, wireless, continuous monitoring and analysis of these activities directly from the throat skin have not been developed. Here, we report the design and validation of a fully integrated standalone stretchable device platform that provides wireless measurements and machine learning-based analysis of diverse vibrations and muscle electrical activities from the throat. We demonstrate that the modified composite hydrogel with low contact impedance and reduced adhesion provides high-quality long-term monitoring of local muscle electrical signals. We show that the integrated triaxial broad-band accelerometer also measures large body movements and subtle physiological activities/vibrations. We find that the combined data processed by a 2D-like sequential feature extractor with fully connected neurons facilitates the classification of various motion/speech features at a high accuracy of over 90%, which adapts to the data with noise from motion artifacts or the data from new human subjects. The resulting standalone stretchable device with wireless monitoring and machine learning-based processing capabilities paves the way to design and apply wearable skin-interfaced systems for the remote monitoring and treatment evaluation of various diseases.
Alignment between initial state and mixer improves QAOA performance for constrained optimization
Authors: He Zichang , Shaydulin Ruslan , Chakrabarti Shouvanik , Herman Dylan , Li Changhao , Sun Yue , Pistoia Marco
Published: November 2023

Quantum alternating operator ansatz (QAOA) has a strong connection to the adiabatic algorithm, which it can approximate with sufficient depth. However, it is unclear to what extent the lessons from the adiabatic regime apply to QAOA as executed in practice with small to moderate depth. In this paper, we demonstrate that the intuition from the adiabatic algorithm applies to the task of choosing the QAOA initial state. Specifically, we observe that the best performance is obtained when the initial state of QAOA is set to be the ground state of the mixing Hamiltonian, as required by the adiabatic algorithm. We provide numerical evidence using the examples of constrained portfolio optimization problems with both low (p ≤ 3) and high (p = 100) QAOA depth. Additionally, we successfully apply QAOA with XY mixer to portfolio optimization on a trapped-ion quantum processor using 32 qubits and discuss our findings in near-term experiments.
A constraint on historic growth in global photosynthesis due to rising CO2
Authors: Keenan T. F. , Luo X. , Stocker B. D. , De Kauwe M. G. , Medlyn B. E. , Prentice I. C. , Smith N. G. , Terrer C. , Wang H. , Zhang Y. , Zhou S.
Published: November 2023

Theory predicts that rising CO2 increases global photosynthesis, a process known as CO2 fertilization, and that this is responsible for much of the current terrestrial carbon sink. The estimated magnitude of the historic CO2 fertilization, however, differs by an order of magnitude between long-term proxies, remote sensing-based estimates and terrestrial biosphere models. Here we constrain the likely historic effect of CO2 on global photosynthesis by combining terrestrial biosphere models, ecological optimality theory, remote sensing approaches and an emergent constraint based on global carbon budget estimates. Our analysis suggests that CO2 fertilization increased global annual terrestrial photosynthesis by 13.5 ± 3.5% or 15.9 ± 2.9 PgC (mean ± s.d.) between 1981 and 2020. Our results help resolve conflicting estimates of the historic sensitivity of global terrestrial photosynthesis to CO2 and highlight the large impact anthropogenic emissions have had on ecosystems worldwide.
Infants’ looking preferences for social versus non-social objects reflect genetic variation
Authors: Portugal Ana Maria , Viktorsson Charlotte , Taylor Mark J. , Mason Luke , Tammimies Kristiina , Ronald Angelica , Falck-Ytter Terje
Published: November 2023

To what extent do individual differences in infants’ early preference for faces versus non-facial objects reflect genetic and environmental factors? Here in a sample of 536 5-month-old same-sex twins, we assessed attention to faces using eye tracking in two ways: initial orienting to faces at the start of the trial (thought to reflect subcortical processing) and sustained face preference throughout the trial (thought to reflect emerging attention control). Twin model fitting suggested an influence of genetic and unique environmental effects, but there was no evidence for an effect of shared environment. The heritability of face orienting and preference were 0.19 (95% confidence interval (CI) 0.04 to 0.33) and 0.46 (95% CI 0.33 to 0.57), respectively. Face preference was associated positively with later parent-reported verbal competence (β = 0.14, 95% CI 0.03 to 0.25, P = 0.014, R2 = 0.018, N = 420). This study suggests that individual differences in young infants’ selection of perceptual input—social versus non-social—are heritable, providing a developmental perspective on gene–environment interplay occurring at the level of eye movements.
Effect of routine suction on lung aeration in critically ill neonates and young infants measured with electrical impedance tomography
Authors: Händel Claas , Becher Tobias , Miedema Martijn , Kallio Merja , Papadouri Thalia , Waldmann Andreas D. , Sophocleous Louiza , Karaoli Christina , Yerworth Rebecca , Bayford Richard , Rimensberger Peter C. , van Kaam Anton H. , Frerichs Inéz
Published: November 2023

Endotracheal suctioning is a widely used procedure to remove secretions from the airways of ventilated patients. Despite its prevalence, regional effects of this maneuver have seldom been studied. In this study, we explore its effects on regional lung aeration in neonates and young infants using electrical impedance tomography (EIT) as part of the large EU-funded multicenter observational study CRADL. 200 neonates and young infants in intensive care units were monitored with EIT for up to 72 h. EIT parameters were calculated to detect changes in ventilation distribution, ventilation inhomogeneity and ventilation quantity on a breath-by-breath level 5–10 min before and after suctioning. The intratidal change in aeration over time was investigated by means of regional expiratory time constants calculated from all respiratory cycles using an innovative procedure and visualized by 2D maps of the thoracic cross-section. 344 tracheal suctioning events from 51 patients could be analyzed. They showed no or very small changes of EIT parameters, with a dorsal shift of the center of ventilation by 0.5% of the chest diameter and a 7% decrease of tidal impedance variation after suctioning. Regional time constants did not change significantly. Routine suctioning led to EIT-detectable but merely small changes of the ventilation distribution in this study population. While still a measure requiring further study, the time constant maps may help clinicians interpret ventilation mechanics in specific cases.
Sliding principal component and dynamic reward reinforcement learning based IIoT attack detection
Authors: Ellappan Vijayan , Mahendran Anand , Subramanian Murali , Jotheeswaran Jeevanandam , Khadidos Adil O. , Khadidos Alaa O. , Selvarajan Shitharth
Published: November 2023

The Internet of Things (IoT) involves the gathering of all those devices that connect to the Internet with the purpose of collecting and sharing data. The application of IoT in the different sectors, including health, industry has also picked up the threads to augment over the past few years. The IoT and, by integrity, the IIoT, are found to be highly susceptible to different types of threats and attacks owing to the networks nature that in turn leads to even poor outcomes (i.e., increasing error rate). Hence, it is critical to design attack detection systems that can provide the security of IIoT networks. To overcome this research work of IIoT attack detection in large amount of evolutions is failed to determine the certain attacks resulting in a minimum detection performance, reinforcement learning-based attack detection method called sliding principal component and dynamic reward reinforcement learning (SPC–DRRL) for detecting various IIoT network attacks is introduced. In the first stage of this research methodology, preprocessing of raw TON_IoT dataset is performed by employing min–max normalization scaling function to obtain normalized values with same scale. Next, with the processed sample data as output, to extract data from multi-sources (i.e., different service profiles from the dataset), a robust log likelihood sliding principal component-based feature extraction algorithm is applied with an arbitrary size sliding window to extract computationally-efficient features. Finally, dynamic reward reinforcement learning-based IIoT attack detection model is presented to control the error rate involved in the design. Here, with the design of dynamic reward function and introducing incident repository that not only generates the reward function in an arbitrary fashion but also stores the action results in the incident repository for the next training, therefore reducing the attack detection error rate. Moreover, an IIoT attack detection system based on SPC–DRRL is constructed. Finally, we verify the algorithm on the ToN_IoT dataset of University of New South Wales Australia. The experimental results show that the IIoT attack detection time and overhead along with the error rate are reduced considerably with higher accuracy than that of traditional reinforcement learning methods.
NAxtra magnetic nanoparticles for low-cost, efficient isolation of mammalian DNA and RNA
Authors: Starheim Eirin Johannessen , Ravlo Erlend , Schjølberg Jørn-Ove , Solvang Vanessa , Wang Wei , Scrimgeour Nathan Robert , Manaf Adeel , Erlandsen Sten Even , Aas Per Arne , Hagen Lars , de Sousa Mirta Mittelstedt Leal , Bjørås Magnar
Published: November 2023

A cost-effective, viral nucleic acid (NA) isolation kit based on NAxtra magnetic nanoparticles was developed at the Norwegian University of Science and Technology in response to the shortage of commercial kits for isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA during the coronavirus disease 2019 (COVID-19) pandemic. This method showed comparable sensitivity to available kits at significantly reduced cost, making its application for other biological sources an intriguing prospect. Thus, based on this low-cost nucleic acid extraction technology, we developed a simple, low- and high-throughput, efficient method for isolation of high-integrity total NA, DNA and RNA from mammalian cell lines (monolayer) and organoids (3D-cultures). The extracted NA are compatible with downstream applications including (RT-)qPCR and next-generation sequencing. When automated, NA isolation can be performed in 14 min for up to 96 samples, yielding similar quantities to available kits.
Early detection of brain metastases and appropriate local therapy followed by systemic chemotherapy may improve the prognosis of gastric cancer
Authors: Ishizuka Yasunobu , Omori Takeshi , Shinno Naoki , Yamamoto Masaaki , Hara Hisashi , Otsuka Tomoyuki , Nishio Minako , Nishida Naohiro , Fujisawa Fumie , Sugimoto Naotoshi , Yagi Toshinari , Goto Masahiro , Nishikawa Hiroki , Kudo Toshihiro
Published: November 2023

Brain metastases develop in 0.5–0.7% of patients with gastric/gastroesophageal junction (G/GEJ) cancer. Although rare, brain metastasis is often identified when the patient is already symptomatic; hence prognosis is poor. Given the therapeutic developments for G/GEJ cancer, overall survival is prolonged, thereby the incidence of brain metastases is predicted to increase. We retrospectively surveyed the rate of brain metastasis among 1257 patients diagnosed with G/GEJ cancer who received chemotherapy between January 2011 and April 2021. We investigated the time of onset of brain metastasis, treatments administered, and impact of the metastasis on the overall treatment course and prognosis. Of the 741 patients included in the analysis, brain metastasis was confirmed in 16 (2.2%). The median survival time (MST) from G/GEJ cancer diagnosis was 14.9 months in patients with brain metastasis detected during the treatment period, and the MST from the diagnosis of brain metastasis was 2.8 months. Patients who received chemotherapy exhibited prolonged survival compared with those who did not (12.4 months vs 1.0 months, p < 0.001). Our findings suggest that the early detection of brain metastases and local therapy for poor responders to chemotherapy enable the continuation of chemotherapy and prolong survival.
Tuberculosis testing patterns in South Africa to identify groups that would benefit from increased investigation
Authors: Shapiro Anne N. , Scott Lesley , Moultrie Harry , Jacobson Karen R. , Bor Jacob , Fofana Abdou M. , Dor Graeme , Ndjeka Norbert O. , da Silva Pedro , Mlisana Koleka , Jenkins Helen E. , Stevens Wendy S.
Published: November 2023

The National Health Laboratory Service (NHLS) collects all public health laboratory test results in South Africa, providing a cohort from which to identify groups, by age, sex, HIV, and viral suppression status, that would benefit from increased tuberculosis (TB) testing. Using NHLS data (2012–2016), we assessed levels and trends over time in TB diagnostic tests performed (count and per capita) and TB test positivity. Estimates were stratified by HIV status, viral suppression, age, sex, and province. We used logistic regression to estimate the odds of testing positive for TB by viral suppression status. Nineteen million TB diagnostic tests were conducted during period 2012–2016. Testing per capita was lower among PLHIV with viral suppression than those with unsuppressed HIV (0.08 vs 0.32) but lowest among people without HIV (0.03). Test positivity was highest among young adults (aged 15–35 years), males of all age groups, and people with unsuppressed HIV. Test positivity was higher for males without laboratory evidence of HIV than those with HIV viral suppression, despite similar individual odds of TB. Our results are an important national baseline characterizing who received TB testing in South Africa. People without evidence of HIV, young adults, and males would benefit from increased TB screening given their lower testing rates and higher test positivity. These high-test positivity groups can be used to guide future expansions of TB screening.
A novel ensemble approach for estimating the competency of bank telemarketing
Authors: Guo Wei , Yao Yao , Liu Lihua , Shen Tong
Published: November 2023

Having a reliable understanding of bank telemarketing performance is of great importance in the modern world of economy. Recently, machine learning models have obtained high attention for this purpose. In order to introduce and evaluate cutting-edge models, this study develops sophisticated hybrid models for estimating the success rate of bank telemarketing. A large free dataset is used which lists the clients’ information of a Portuguese bank. The data are analyzed by four artificial neural networks (ANNs) trained by metaheuristic algorithms, namely electromagnetic field optimization (EFO), future search algorithm (FSA), harmony search algorithm (HSA), and social ski-driver (SSD). The models predict the subscription of clients for a long-term deposit by evaluating nineteen conditioning parameters. The results first indicated the high potential of all four models in analyzing and predicting the subscription pattern, thereby, revealing the competency of neuro-metaheuristic hybrids. However, comparatively speaking, the EFO yielded the most reliable approximation with an area under the curve (AUC) around 0.80. FSA-ANN emerged as the second-accurate model followed by the SSD and HSA with respective AUCs of 0.7714, 0.7663, and 0.7160. Moreover, the superiority of the EFO-ANN is confirmed against several conventional models from the previous literature, and finally, it is introduced as an effective model to be practically used by banking institutions for predicting the likelihood of deposit subscriptions.
Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view
Authors: Żyła Adriana , Martel Anne , Jurczak Przemysław , Moliński Augustyn , Szymańska Aneta , Kozak Maciej
Published: November 2023

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and various types of amyloidosis, are incurable; therefore, understanding the mechanisms of amyloid decomposition is crucial to develop an effective drug against them for future therapies. It has been reported that one out of three people over the age of 85 are suffering from dementia as a comorbidity to AD. Amyloid beta (Aβ), the hallmark of AD, transforms structurally from monomers into β-stranded aggregates (fibrils) via multiple oligomeric states. Astrocytes in the central nervous system secrete the human cystatin C protein (HCC) in response to various proteases and cytokines. The codeposition of Aβ and HCC in the brains of patients with AD led to the hypothesis that cystatin C is implicated in the disease process. In this study, we investigate the intermolecular interactions between different atomic structures of fibrils formed by Aβ peptides and HCC to understand the pathological aggregation of these polypeptides into neurotoxic oligomers and then amyloid plaques. To characterize the interactions between Aβ and HCC, we used a complementary approach based on the combination of small-angle neutron scattering analysis, atomic force microscopy and computational modelling, allowing the exploration of the structures of multicomponent protein complexes. We report here an optimized protocol to study that interaction. The results show a dependency of the sequence length of the Aβ peptide on the ability of the associated HCC to disaggregate it.
Functional connectivity of the human face network exhibits right hemispheric lateralization from infancy to adulthood
Authors: Lesinger Keren , Rosenthal Gideon , Pierce Karen , Courchesne Eric , Dinstein Ilan , Avidan Galia
Published: November 2023

Adults typically exhibit right hemispheric dominance in the processing of faces. In this cross-sectional study, we investigated age-dependent changes in face processing lateralization from infancy to adulthood (1–48 years old; N = 194). We co-registered anatomical and resting state functional Magnetic Resonance Imaging (fMRI) scans of toddlers, children, adolescents, and adults into a common space and examined functional connectivity across the face, as well as place, and object-selective regions identified in adults. As expected, functional connectivity between core face-selective regions was stronger in the right compared to the left hemisphere in adults. Most importantly, the same lateralization was evident in all other age groups (infants, children, adolescents) and appeared only in face-selective regions, and not in place or object-selective regions. These findings suggest that the physiological development of face-selective brain areas may differ from that of object and place-selective areas. Specifically, the functional connectivity of the core-face selective regions exhibits rightward lateralization from infancy, years before these areas develop mature face-selective responses.
Numerical modelling approach for estimation of a yield zone in the face of a deep longwall panel
Authors: Islavath Sreenivasa Rao
Published: November 2023

In the Longwall mining method, the coal face is being supported with two-legged or four-legged shield supports which improve better roof control between the face and canopy tip. The development of load on the face increases with the face retreating rate or the increase of the overhung length behind the shield support and as a result, the coal face tends to yield/fail. The yield/failure zone in the face extends depending on intensity of developed load due to the depth of mining, panel size, height of excavation and geometry of the overhung. The broken coal from the yielded face may fall on the shearer, armoured flexible conveyor (AFC), shield supports or may hit the deployed manpower in the face and causes the face stoppage which in turn results in to the loss of the project. It is therefore, a study is conducted to understand the face yield/failure behaviour considering various geo-mining conditions based on input parameters such as main roof thickness, overhung length, and material type and setting load. This paper develops a unique statistical model to predict the yield/failure zone in the longwall face. For this purpose, a total of fifty-four (54) three-dimensional finite element models in ANSYS software are developed and analyzed considering Drucker-Prager failure criterion.
Distribution characteristics of circulating B cell subpopulations in patients with chronic kidney disease
Authors: Chen Xuya , Guo Haoyang , Jin Danxia , Lu Yan , Zhang Longyi
Published: November 2023

This study compared the levels of circulating B cell subpopulations in patients with different stages of chronic kidney disease (CKD), investigated the effects of haemodialysis (HD) on the B cell-related immune spectrum in patients with end-stage renal disease, and evaluated the link between renal function and immune homeostasis. Overall, 197 patients with CKD (158 non-dialysis patients with CKD stages I–V and 39 end-stage patients undergoing maintenance HD) and 77 healthy controls were included. Compared to healthy controls, patients with CKD stages I–II showed no significant differences except for the proportion of transitional B cells; patients with CKD stage V showed a significant decrease in the proportions of transitional B cells and CD5+ B cells and a significant increase in double-negative (DN) B cells. Compared with early-stage patients with CKD, the absolute count of various B cell subpopulations in advanced-stage patients with CKD showed a significant decrease. The distribution of circulating B cell subpopulations in patients with CKD was significantly altered and was associated with CKD progression. Furthermore, the proportion of DN B cells and CD5+ B cells was inconsistent pre- and post-HD. This in-depth study of the immune status of patients with CKD may have important clinical value.
Insights into orbital morphological features and fracture patterns in medial and inferior wall fracture: a retrospective cohort study
Authors: Yang Junjie , Du Yali , Zhen Zhengyun , Wang Shuang , Zhao Sumei , Zhao Guang , Shi Bingjie
Published: November 2023

This study investigated the orbital morphological features that lead to fractures at different sites by comparing patients with isolated inferior wall fracture (IWF) to patients with isolated medial wall fracture (MWF). This study analyzed the orbital morphologic characteristics of all orbital fracture patients who underwent orbital computed tomography (CT) scans between January 2017 and October 2022. On CT scans, the bony structures of the orbit were measured. We investigated the bilateral symmetry of orbital. In addition, orbital morphological differences were compared between patients with fractures of the medial wall and those with fractures of the inferior wall. A total of 135 patients with orbital fractures were included in the study. Of these, 91 were isolated MWFs and 44 were isolated IWF. We confirmed the symmetry of bilateral orbits and measured the orbit of the uninjured side. No differences were found between the MWF group and the IWF group in terms of ocular prominence, horizontal orbital diameter, orbital rim angle, sagittal orbital depth, sagittal orbital depth, and angle of inferior wall inclination. The distance between the infraorbital nerve (ION) entry point and the orbital rim was significantly smaller in the inferior lateral wall fracture group than in the MWF group (11.87 ± 2.54 vs 14.90 ± 4.64, P < 0.001), and the percentage of type 1 ION was significantly lower in the IWF group than in the MWF group (40.9% vs 65.9%, P = 0.012). We demonstrated the symmetry of bilateral orbits and found that when the point where the ION enters the infraorbital canal is near the orbital rim, patients are more prone to suffering a fracture of the inferior wall after orbital trauma. It is less likely for patients with type 1 ION to suffer an IWF following an orbital fracture.
The arousal effect of sugammadex reversal of neuromuscular blockade differs with anesthetic depth in propofol-remifentanil anesthesia: a randomized controlled trial
Authors: Kim Jeayoun , Kim Jie Ae , Jang Jae Ni , Yang Mikyung , Ahn Hyun Joo , Choi Jiwon , Jo Sungwoo
Published: November 2023

Sugammadex reverses neuromuscular blockade by encapsulating steroidal neuromuscular blockers; therefore, it does not pharmacologically affect sedation levels. However, some clinicians avoid using it because of sudden unwanted acting out or patient arousal. Previous studies suggested sugammadex-induced awakening, but frontal muscle contraction after sugammadex administration compromised reliability of results obtained from EEG-based anesthesia depth monitoring tools like bispectral index (BIS). We hypothesized that sugammadex would affect patients’ arousal depending on their baseline levels of sedation. We evaluated arousal signs after sugammadex administration with BIS between 25 − 35 and 45 − 55 under steady-state propofol-remifentanil anesthesia at the end of a surgery (n = 33 in each group). After sugammadex administration, twelve patients with a BIS of 45 − 55 showed clinical signs of awakening but none with a BIS of 25 − 35 (36.4% vs. 0%, P = 0.001). The distribution of the modified observer’s assessment of alertness/sedation scale scores was also significantly different between the two groups (P < 0.001). Changes in the BIS were significantly greater in the BIS 45 − 55 than in the 25 − 35 group (median difference, 7; 95% CI 2 − 19, P = 0.002). Arousal after sugammadex was affected by patient sedation levels, and clinical signs of awakening appeared only in those with BIS 45 − 55. Unwanted arousal of the patient should be considered when using sugammadex under shallow anesthesia.

Clinical trial registry number: Clinical Trial Registry of Korea (https://cris.nih.go.kr; Principal investigator: Jieae Kim; Registration number: KCT0006248; Date of first registration: 11/06/2021).
High-altitude and low-altitude adapted chicken gut-microbes have different functional diversity
Authors: Bhagat Neha Rani , Chauhan Priyanka , Verma Pratibha , Mishra Aradhana , Bharti Vijay K.
Published: November 2023

Recently, there has been considerable interest in the functions of gut microbiota in broiler chickens in relation to their use as feed additives. However, the gut-microbiota of chickens reared at different altitudes are not well documented for their potential role in adapting to prevailing conditions and functional changes. In this context, the present study investigates the functional diversity of gut-microbes in high-altitude (HACh) and low-altitude adapted chickens (LACh), assessing their substrate utilization profile through Biolog Ecoplates technology. This will help in the identification of potential microbes or their synthesized metabolites, which could be beneficial for the host or industrial applications. Results revealed that among the 31 different types of studied substrates, only polymers, carbohydrates, carboxylic acids, and amine-based substrates utilization varied significantly (p < 0.05) among the chickens reared at two different altitudes where gut-microbes of LACh utilized a broad range of substrates than the HACh. Further, diversity indices (Shannon and MacIntosh) analysis in LACh samples showed significant (p < 0.05) higher richness and evenness of microbes as compared to the HACh samples. However, no significant difference was observed in the Simpson diversity index in gut microbes of lowversus high-altitude chickens. In addition, the Principal Component Analysis elucidated variation in substrate preferences of gut-microbes, where 13 and 8 carbon substrates were found to constitute PC1 and PC2, respectively, where γ-aminobutyric acid, d-glucosaminic acid, i-erythritol and tween 40 were the most relevant substrates that had a major effect on PC1, however, alpha-ketobutyric acid and glycyl-l-glutamic acid affected PC2. Hence, this study concludes that the gut-microbes of high and low-altitudes adapted chickens use different carbon substrates so that they could play a vital role in the health and immunity of an animal host based on their geographical location. Consequently, this study substantiates the difference in the substrate utilization and functional diversity of the microbial flora in chickens reared at high and low altitudes due to altitudinal changes.
Scleral remodeling in early adulthood: the role of FGF-2
Authors: Qin Yingyan , Liu Taixiang , Zhang Zhaotian , Xing Shuwen , Gong Li , Ni Yao
Published: November 2023

Emmetropization, a natural process of ocular elongation, is closely associated with scleral remodeling. The Fibroblast growth factor-2 (FGF-2) was reported involved in scleral remodeling in myopia models. Herein, we aimed to investigate the role of scleral fibroblast-to-myofibroblast differentiation and FGF-2 in scleral remodeling during maturation. Our findings revealed that the posterior scleral fibroblasts (SFs) from mature guinea pigs exhibit increased stiffness compared to those from young guinea pigs. Moreover, mature SFs displayed decreased cell proliferation but increased levels of α-SMA, matrix metalloproteinase 2 (MMP2), and collagen 1, when compared to young SFs. Additionally, the mRNA expression of scleral Fgf-2, Fgf receptor 1 (Fgfr1), Fgfr2, Fgfr3, and Fgfr4 was increased in mature SFs. Notably, exogenous FGF-2 showed increased cell proliferation and led to decreased expression of α-SMA, MMP2, and collagen 1 in mature SFs. Overall, our findings highlight the influence of maturation on SFs from posterior scleral shells, resulting in increased stiffness and the manifestation of fibroblast-to-myofibroblast differentiation during development. Exogenous FGF-2 increased cell proliferation and reversed the age-related fibroblast-to-myofibroblast differentiation, suggesting a potential role of FGF-2 in regulating scleral remodeling.