bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate score classification of hepatocellular carcinoma helps identify patients with tumors that respond to immune checkpoint blockade therapy
Authors: Jiang Kai , Zhu Lili , Huang Huizhen , Zheng Liu , Wang Zhuqing , Kang Xiaonan
Published: August 2023

Purpose

Hepatocellular carcinoma (HCC) responds poorly to immunotherapy, and the durable response rate is 10-20%. Here, we aim to characterize HCC classifications based on lactate genes to identify patients who may benefit from immunotherapy.

Methods

Lactate-related genes were applied for HCC classification in the current study, and lactate Cluster 1 (LC1) and lactate Cluster 2 (LC2) were defined. Differential genes from LC1 and LC2 helped define the following lactate phenotype clusters: lactate phenotype Cluster 1 (LPC1), lactate phenotype Cluster 2 (LPC2) and lactate phenotype Cluster 3 (LPC3). Based on the cluster annotation, the lactate score was defined and analyzed to evaluate the immunotherapy response.

Results

All the classified clusters were analyzed, and they showed different immune signatures. The survival rate of LPC3 was higher than that of LPC2 (LPC3 vs. LPC2, P = 0.027) and LPC1 (LPC3 vs. LPC1, P = 0.027). Then, the lactate score was annotated and confirmed to be effective in predicting responses to immune checkpoint blockade therapy.

Conclusion

In the current study, we developed a classification system for HCC and defined the lactate score, which was validated to be partially effective in estimating responses among tumor patients.
Soil organic carbon stock change following perennialization: a meta-analysis
Authors: Siddique Imran Ahammad , Grados Diego , Chen Ji , Lærke Poul Erik , Jørgensen Uffe
Published: August 2023

Perennial crops replacing annual crops are drawing global attention because they harbor potential for sustainable biomass production and climate change mitigation through soil carbon sequestration. At present, it remains unclear how long perennial crops can sequester carbon in the soil and how soil carbon stock dynamics are influenced by climate, soil, and plant properties across the globe. This study presents a meta-analysis synthesizing 51 publications (351 observations at 77 sites) distributed over different pedo-climatic conditions to scrutinize the effect of perennialization on organic carbon accumulation in soil compared with two annual benchmark systems (i.e., monoculture and crop rotation). Results showed that perennial crops significantly increased soil organic carbon stock by 16.6% and 23.1% at 0–30 cm depth compared with monoculture and crop rotation, respectively. Shortly after establishment (< 5 years), perennial crops revealed a negative impact on soil organic carbon stock; however, long duration (> 10 years) of perennialization had a significant positive effect on soil organic carbon stock by 30% and 36.4% at 0–30 cm depth compared with monoculture and crop rotation, respectively. Compared with both annual systems, perennial crops significantly increased soil organic carbon stock regardless of their functional photosynthetic types (C3, C4, or C3-C4 intermediates) and vegetation type (woody or herbaceous). Among other factors, pH had a significant impact on soil organic carbon; however, the effect of soil textures showed no significant impact, possibly due to a lack of observations from each textural class and mixed pedoclimatic effects. Results also showed that time effect of perennialization revealed a sigmoidal increase of soil organic carbon stock until about 20 years; thereafter, the soil carbon stocks advanced towards a steady-state level. In conclusion, perennial crops increased soil organic carbon stock compared with annual systems; however, the time since conversion from annual to perennial system decisively impacted soil organic carbon stock changes.
One Million Lives Saved Per Year: A Cost–Benefit Analysis of the Global Plan to End Tuberculosis, 2023–2030 and Beyond
Authors: Pretorius Carel , Arinaminpathy Nimalan , Mandal Sandip , Sahu Suvanand , Pai Madhukar , Mathiasson Roland , Wong Brad
Published: August 2023

This report presents a cost–benefit analysis of increased spending on tuberculosis (TB) using impacts and costs drawn from the Global Plan to End Tuberculosis, 2023–2030. The analysis indicates that the return on TB spending is substantial with a centrally estimated benefit–cost ratio (BCR) of 46, meaning every US$ 1 invested in TB yields US$ 46 in benefits. Alternative specifications using different baselines, interventions, cost profiles, and discount rates still yield robustly high BCRs, in the range of 28–84. This report also shows that TB investment would avert substantial mortality, estimated at 27.3 million averted deaths over the 28-year period between 2023 and 2050 inclusive: almost 1 million averted deaths per year on average. Accounting for all estimated direct and indirect costs, the cost per averted death is slightly over US$ 2000. Interventions to address TB represent exceptional value-for-money.
Designing foresights by communities: a new groundbreaker role for strategic design
Authors: Simonse Lianne , Simons Dasha , Skalska Zuzanna
Published: August 2023

In order to humanize forecasting, communities have been proposed to activate and enlarge a collective ability of foresight. To better understand how communities relate to collective foresight abilities, this article untangles its critical modes, roles and social media involved. Based on a fine-grained analysis of 10 community practices, we uncovered the abilities of capturing, conceiving and designing foresights enacted in the distinct modes of creative, user and strategic communities. Discoveries included the novel abilities of conceiving foresights, a new groundbreaker role for strategic designers and specific activities of social media listening with regard to future interests. Grounded on the prime findings, we propose a framework with propositions that shape further theory development on community abilities of designing foresights. Further research directions are outlined.
Hasty Generalizations Are Pervasive in Experimental Philosophy: A Systematic Analysis
Authors: Peters Uwe , Lemeire Olivier
Published: August 2023

Scientists may sometimes generalize from their samples to broader populations when they have not yet sufficiently supported this generalization. Do such hasty generalizations also occur in experimental philosophy? To check, we analyzed 171 experimental philosophy studies published between 2017 and 2023. We found that most studies tested only Western populations but generalized beyond them without justification. There was also no evidence that studies with broader conclusions had larger, more diverse samples, but they nonetheless had higher citation impact. Our analyses reveal important methodological limitations of many experimental philosophy studies and suggest that philosophical training may not protect against hasty generalizations.
A plague of weasels and ticks: animal introduction, ecological disaster, and the balance of nature in Jamaica, 1870–1900
Authors: Holmes Matthew
Published: August 2023

Towards the end of the nineteenth century, British colonists in Jamaica became increasingly exasperated by the damage caused to their sugar plantations by rats. In 1872, a British planter attempted to solve this problem by introducing the small Indian mongoose (Urva auropunctata). The animals, however, turned on Jamaica's insectivorous birds and reptiles, leading to an explosion in the tick population. This paper situates the mongoose catastrophe as a closing chapter in the history of the nineteenth-century acclimatization movement. While foreign observers saw the introduction of the mongoose as a cautionary tale, caricaturing British Jamaica as overrun by a plague of weasels and ticks, British colonists, administrators and naturalists – identifying a gradual decline of both populations – argued that the ‘balance of nature’ would eventually reassert itself. As this paper argues, through this dubious claim they were attempting to retrospectively rationalize or justify the introductions and their disastrous aftermath. This strategy enabled them to gloss over the lasting ecological damage caused by the mongoose, and allowed its adherents to continue their uncritical support of both the Jamaican plantation economy and animal introductions in the British Empire.
Changes in affective control covary with changes in mental health difficulties following affective control training (AffeCT) in adolescents
Authors: Schweizer Susanne , Leung Jovita T. , Trender William , Kievit Rogier , Hampshire Adam , Blakemore Sarah-Jayne
Published: August 2023

Background

Everyday affective fluctuations are more extreme and more frequent in adolescence compared to any other time in development. Successful regulation of these affective experiences is important for good mental health and has been proposed to depend on affective control. The present study examined whether improving affective control through a computerised affective control training app (AffeCT) would benefit adolescent mental health.

Methods

One-hundred and ninety-nine participants (11–19 years) were assigned to complete 2 weeks of AffeCT or placebo training on an app. Affective control (i.e. affective inhibition, affective updating and affective shifting), mental health and emotion regulation were assessed at pre- and post-training. Mental health and emotion regulation were assessed again one month and one year later.

Results

Compared with the placebo group, the AffeCT group showed significantly greater improvements in affective control on the trained measure. AffeCT did not, relative to placebo, lead to better performance on untrained measures of affective control. Pre- to post-training change in affective control covaried with pre- to post-training change in mental health problems in the AffeCT but not the placebo group. These mental health benefits of AffeCT were only observed immediately following training and did not extend to 1 month or year post-training.

Conclusion

In conclusion, the study provides preliminary evidence that AffeCT may confer short-term preventative benefits for adolescent mental health.
Treated incidence of first episode psychosis in Sinop, Turkey: results of a 4-year admission-based study – SINOPsy
Authors: Binbay Tolga , Mollaahmetoğlu Özden Merve , Kırlı Umut , Arık Deniz , Alptekin Köksal
Published: August 2023

Background

The incidence of psychotic disorders varies in different geographic areas. As there has been no report from Turkey, this study aimed to provide the treated incidence rate of first-episode psychosis (FEP) in a defined area.

Methods

All individuals, aged 15–64 years, presenting with FEP (ICD-10 F20-29, F30-33) to mental health services in a defined catchment-area in Sinop which is located in the Black Sea region of the northern Turkey were recorded over a 4-year period (2009 to 2012). Incidence rates of psychotic disorders and their 95% confidence intervals (CIs) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex, and urbanicity.

Results

One hundred and fifteen FEP participants were identified during the 4 years. Crude incidence rates of all psychoses, schizophrenia, other psychotic disorders, and affective psychotic disorders were respectively 38.5 (95% CI 27.1–49.9), 10.7 (95% CI 6.6–14.8), 10.0 (95% CI 5.7–14.3) and 17.7 (95% CI 11.3–24.2) per 100 000 person-years. After age-sex standardisation the rates increased slightly. There were no gender differences in the incidence rates. IRR of any psychotic disorder was highest in the youngest age group (15–24 years) compared to the oldest age group (55–64 years), 7.9 (95% CI 2.8–30.5). In contrast with previous studies, the incidence rate of any psychotic disorder was not significantly increased in urban areas compared with rural areas.

Conclusions

The current study, the first of its kind from Turkey, indicates that the risk of schizophrenia and other psychotic disorders in a lowly urbanised area of Turkey is comparable to those reported in Western European cities.
THE GOVERNORS OF VENETIAN ITHACA
Authors: Nikias Kyriaco
Published: August 2023

The historiography of Venetian Greece has paid little attention to the colonial experience of Ithaca. While historians are served by extensive published documentary evidence for the administrations of the larger possessions in the region, the uncatalogued Venetian records at the state archive of Ithaca remain unstudied. The recent reopening of this archive has finally made it possible to survey its large Venetian collection and to provide an account of the role of the governors of Ithaca under Venetian rule. The seat of the governor was filled by Cephalonian nobles rather than by Venetian appointees in the manner of the larger Ionian islands. Here for the first time is presented a comprehensive list of Ithacan governors compiled from the Ithacan documents, together with further aid from research in the archives of Cephalonia and Venice. The account of the Ithacan governorship offered here aims to promote interest in the Ithacan archive of the Venetian administration and serve as a guide for future research into this neglected corner of the empire.
Management of Mass-Casualty Incidents in Nepal: A Qualitative Case Study of Three District Hospitals in Nepal
Authors: Singh Prinka , Lamine Hamdi , Sapkota Sujan , Bahattab Awsan , Eriksson Anneli
Published: August 2023

Introduction:

The frequency of disasters world-wide has significantly increased in recent years, leading to an increase in the number of mass-casualty incidents (MCIs). These MCIs can overwhelm health care systems, requiring hospitals to respond quickly and effectively, often with limited resources. While numerous studies have identified the challenges in managing MCIs and have emphasized the importance of hospital disaster preparedness, there is a research gap in the preparedness level and response capacities of district hospitals in Nepal.

Study Objective:

This study attempts to fill this gap by understanding the perception of hospital staff in managing MCIs in district hospitals of Nepal.

Methods:

A qualitative case study was conducted in three district hospitals in Nepal. Semi-structured interviews were conducted with the hospital personnel, using an interview guide. An inductive thematic analysis was carried out to understand their perception on the most recent MCI management.

Results:

Three themes emerged from the data analysis: enablers in MCI management, barriers in MCI management, and recommendations for the future. Use of multiple communication channels, mobilization of entire hospital teams, mobilization of police in crowd control, presence of disaster store, and pre-identified triage areas were the major enablers that facilitated successful MCI management. Nonetheless, the study also revealed challenges such as a lack of knowledge on MCI response among new staff, disruptions caused by media and visitors, and challenges in implementing triage.

Conclusion:

This study emphasized the importance of hospital disaster preparedness in managing MCIs and highlighted the significance of overcoming barriers and utilizing enablers for an efficient response. The findings of this study can provide the basis for the Ministry of Health and Population Nepal and district hospitals to plan initiatives for the effective management of MCIs in the future.
A munshi discussion on religion, and the Simla Akhbār, circa 1850
Authors: Ernst Carl
Published: August 2023

As a case study of the changing mentalities that emerged in colonial India, this article analyses a discussion that took place among several munshis (secretaries trained in Persian to run the affairs of princely states), and also provides a translation and edition of the text. The subject was a short polemical letter refuting the immortality of the soul, published around 1850 in the Simla Akhbār (Simla News). The main question entertained in this correspondence was not the merit of the sceptical argument, based in part on modern medical findings, but the potential public impact of dismissing a religious doctrine that sustains morality. Two of the participants in this conversation, Shivaprasad and Sital Singh, displayed the full range of changes that made the nineteenth century so extraordinary, and the way they responded illustrates some of the salient features and stages of this process, including the difficulty of foreseeing the elimination of much of the system for which munshis were trained.
In situ characterization of tamarind (Tamarindus indica L.) fruit and spotting sweet tamarind types in Palakkad gap of Kerala
Authors: Menon Jalaja S. , Asna A. C. , Menon Meera V. , Pooja A. , Gopinath Pratheesh P. , Singh A. K.
Published: August 2023

Kerala, a humid tropical southern state, is the third largest producer of Tamarind (Tamarindus indica L.) in India. This tree spice is an important livelihood option for the rural society, especially in Palakkad district which is the lead producer of tamarind in the state with a few accepted primitive cultivars, viz. ‘valanpuli’, ‘madhurapuli’ and ‘thenpuli’. A survey was conducted to identify the fruit variability and document the sweet tamarind types of Palakkad. This study revealed the variability and weight of 30 fruits was seen to be the most indicative variable of tamarind in Kerala. The pod length varied from 5.28 to 23.41 cm and fruit weight from 4.83 to 43.40 g. Hierarchical clustering on principal component analysis resulted in six clusters. The clusters I, IV and V represented collections with fruit weight more than 20 g. Box plot diagrams revealed the high real pulp value in sample KTJ 162 (9.57) and high fruit length in KTJ 44 (21.68 cm). Among 113 collections, 18 samples were collected as perceived sweet types based on local enquiry. In the scatter plot between total soluble solids and ratio between total soluble solids and total titrable acidity, two samples were spotted as sweet types with acidity below 8%. Further molecular characterization and systematic crop improvement programmes are required for conserving the eroding gene pool of tamarind in Kerala and to develop sweet types for commercial production.
Posttraumatische Belastungsstörung infolge eines Suizidversuchs
Authors: Lüke Ronja , Gerlach Alexander L. , Gysin-Maillart Anja , Lewitzka Ute , Teismann Tobias
Published: August 2023

Zusammenfassung: Hintergrund: Erste Studien legen nahe, dass ein selbstdurchgeführter Suizidversuch überraschend häufig eine PTBS-Symptomatik verursachen könnte. Die berichteten Prävalenzangaben der Studien variieren jedoch erheblich. Methode: In der vorliegenden Online-Studie wurden N = 50 Suizidversuchsüberlebenden zu suizidversuchsbezogenen PTBS-Symptomen und gegenwärtigen Suizidgedanken befragt. Zur Falldefinition diente eine modifizierte Version der Posttraumatischen Checkliste für DSM-5 (PCL-5) entweder auf Basis eines Cut-off Wertes oder auf Syndrom-Basis. Ergebnisse: In Abhängigkeit von der Falldefinition wurden 52 % ( n = 26) bzw. 42 % ( n = 21) der Teilnehmenden als Personen identifiziert, welche potenziell die Diagnosekriterien einer PTBS infolge eines eigenen Suizidversuchs erfüllten. Teilnehmende mit suizidversuchsbezogener PTBS-Symptomatik berichteten teilweise über mehr gegenwärtige Suizidgedanken. Schlussfolgerung: Die Ergebnisse legen nahe, dass Personen nach einem selbstdurchgeführten Suizidversuch eine PTBS-Symptomatik entwickeln. Aufgrund der Relevanz dieser Ergebnisse für eine wirksame Behandlung von Suizidversuchsüberlebenden sind weitere Studien an größeren deutschen Stichproben und unter Nutzung klinischer Interviews zu empfehlen.
Numerical Simulations of Metallic Ion Density Perturbations in Sporadic E Layers Caused by Gravity Waves
Authors: Qiu Lihui , Yamazaki Yosuke , Yu Tao , Becker Erich , Miyoshi Yasunobu , Qi Yifan , Siddiqui Tarique A. , Stolle Claudia , Feng Wuhu , Plane John M. C. , Liang Yu , Liu Huixin
Published: August 2023

Tidal signatures in sporadic E (Es) layer have been confirmed by observations and simulations. However, the effect of gravity waves (GWs) on the Es layer formation process has not yet been fully understood. In this paper, the modulation of Es layers by GWs is examined through numerical simulations, in which a physics‐based model of Es layer is forced by neutral winds from the High Altitude Mechanistic General Circulation Model that can resolve GWs with horizontal wavelengths longer than 156 km (λh > 156 km). Comparison of the simulation results with and without the GWs (1,350 km > λh > 156 km) forcing reveals that the inclusion of GWs leads to short‐period (1.2–3 hr) density perturbations in Es layers, which are also seen in ground‐based ionosonde observations. At a given time, the metallic ion density at altitudes between 120 and 150 km can either increase (by up to ∼+600%) or reduce (by up to −90%) in response to GW forcing. The relative density perturbations are smaller (by up to 60%) between 90 and 120 km altitude. It is also found that the GW effect on the metallic ion density relates to the longitude, which is mostly explained by the geographical distribution of GWs activity in the mesosphere and lower thermosphere region. The longitudinal variation of the background geomagnetic field plays only a secondary role.
Calibration and Validation for the Surface Biology and Geology (SBG) Mission Concept: Recommendations for a Multi‐Sensor System for Imaging Spectroscopy and Thermal Imagery
Authors: Turpie Kevin R. , Casey Kimberly A. , Crawford Christopher J. , Guild Liane S. , Kieffer Hugh , Lin Guoqing (Gary) , Kokaly Raymond , Shrestha Alok K. , Anderson Cody , Ramaseri Chandra Shankar N. , Green Robert , Hook Simon , Lukashin Constantine , Thome Kurt
Published: August 2023

The primary objective of the National Aeronautics and Space Administration (NASA) Surface Biology and Geology (SBG) mission is to measure biological, physical, chemical, and mineralogical features of the Earth's surface, realizing a key conceptual component of the envisioned NASA Earth System Observatory (ESO). SBG is planned to launch as a two‐platform mission in the late 2020s, the first of the ESO satellites. Targeted science and applications objectives based on observations of the Earth's SBG helped to define the mission architecture and instrument capabilities for the SBG mission concept. These objectives further drove the need for enabling change detection and trending of surface biological and geological features. These needs implied fundamental calibration goals to achieve the necessary science data quality characteristics. To meet those goals, calibration and validation pre‐launch and on‐orbit methods formed a basis of the calibration and validation concept, including the combined use of on‐board references, vicarious techniques, and routine lunar imaging. International collaboration with space agencies in other countries, an important feature of the recommended SBG mission architecture, uncovered and emphasized the need for inter‐calibration techniques that underscored the importance of collaborative instrument characterization data sharing and the use of common calibration references that are International System of Units (SI) traceable in pre‐launch and post‐launch on orbit calibration mission phases. International collaboration through the use of terrestrial and aquatic networks on six continents for vicarious calibration and validation activities will further assure necessary science data quality while in orbit.
Mitochondria-associated programmed cell death as a therapeutic target for age-related disease
Authors: Nguyen Thanh T. , Wei Shibo , Nguyen Thu Ha , Jo Yunju , Zhang Yan , Park Wonyoung , Gariani Karim , Oh Chang-Myung , Kim Hyeon Ho , Ha Ki-Tae , Park Kyu Sang , Park Raekil , Lee In-Kyu , Shong Minho , Houtkooper Riekelt H. , Ryu Dongryeol
Published: August 2023

Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse cell death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed cell death. Thus, dysfunctional cellular pathways eventually lead or contribute to various age-related diseases, such as neurodegenerative, cardiovascular and metabolic diseases. Thus, mitochondrion-associated programmed cell death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli and that maintain cellular homeostasis via mitohormesis, the mitochondrial unfolded protein response, and mitophagy. The review also presents details on various forms of mitochondria-associated programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and paraptosis, and highlights their involvement in age-related disease pathogenesis, collectively suggesting therapeutic directions for further research.
Diversity and complexity of cell death: a historical review
Authors: Park Wonyoung , Wei Shibo , Kim Bo-Sung , Kim Bosung , Bae Sung-Jin , Chae Young Chan , Ryu Dongryeol , Ha Ki-Tae
Published: August 2023

Death is the inevitable fate of all living organisms, whether at the individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome of nonfunctioning cells, as inflammation was inevitably triggered in response to damage. However, experimental evidence accumulated over the past few decades has revealed different types of cell death that are genetically programmed to eliminate unnecessary or severely damaged cells that may damage surrounding tissues. Several types of cell death, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, and erebosis, have been discovered and advanced our understanding of cell death and its complexity. In this review, we provide a historical overview of the discovery and characterization of different forms of cell death and highlight their diversity and complexity. We also briefly discuss the regulatory mechanisms underlying each type of cell death and the implications of cell death in various physiological and pathological contexts. This review provides a comprehensive understanding of different mechanisms of cell death that can be leveraged to develop novel therapeutic strategies for various diseases.
N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer
Authors: Yun Rebecca , Hong Eunji , Kim Junil , Park Bora , Kim Staci Jakyong , Lee Bona , Song Yong Sang , Kim Seong-Jin , Park Sujin , Kang Jin Muk
Published: August 2023

KIAA1324 is a transmembrane protein largely reported as a tumor suppressor and favorable prognosis marker in various cancers, including gastric cancer. In this study, we report the role of N-linked glycosylation in KIAA1324 as a functional post-translational modification (PTM). Loss of N-linked glycosylation eliminated the potential of KIAA1324 to suppress cancer cell proliferation and migration. Furthermore, we demonstrated that KIAA1324 undergoes fucosylation, a modification of the N-glycan mediated by fucosyltransferase, and inhibition of fucosylation also significantly suppressed KIAA1324-induced cell growth inhibition and apoptosis of gastric cancer cells. In addition, KIAA1324-mediated apoptosis and tumor regression were inhibited by the loss of N-linked glycosylation. RNA sequencing (RNAseq) analysis revealed that genes most relevant to the apoptosis and cell cycle arrest pathways were modulated by KIAA1324 with the N-linked glycosylation, and Gene Regulatory Network (GRN) analysis suggested novel targets of KIAA1324 for anti-tumor effects in the transcription level. The N-linked glycosylation blockade decreased protein stability through rapid proteasomal degradation. The non-glycosylated mutant also showed altered localization and lost apoptotic activity that inhibits the interaction between GRP78 and caspase 7. These data demonstrate that N-linked glycosylation of KIAA1324 is essential for the suppressive role of KIAA1324 protein in gastric cancer progression and indicates that KIAA1324 may have anti-tumor effects by targeting cancer-related genes with N-linked glycosylation. In conclusion, our study suggests the PTM of KIAA1324 including N-linked glycosylation and fucosylation is a necessary factor to consider for cancer prognosis and therapy improvement.
Accurate haplotype construction and detection of selection signatures enabled by high quality pig genome sequences
Authors: Tong Xinkai , Chen Dong , Hu Jianchao , Lin Shiyao , Ling Ziqi , Ai Huashui , Zhang Zhiyan , Huang Lusheng
Published: August 2023

High-quality whole-genome resequencing in large-scale pig populations with pedigree structure and multiple breeds would enable accurate construction of haplotype and robust selection-signature detection. Here, we sequence 740 pigs, combine with 149 of our previously published resequencing data, retrieve 207 resequencing datasets, and form a panel of worldwide distributed wild boars, aboriginal and highly selected pigs with pedigree structures, amounting to 1096 genomes from 43 breeds. Combining with their haplotype-informative reads and pedigree structure, we accurately construct a panel of 1874 haploid genomes with 41,964,356 genetic variants. We further demonstrate its valuable applications in GWAS by identifying five novel loci for intramuscular fat content, and in genomic selection by increasing the accuracy of estimated breeding value by 36.7%. In evolutionary selection, we detect MUC13 gene under a long-term balancing selection, as well as NPR3 gene under positive selection for pig stature. Our study provides abundant genomic variations for robust selection-signature detection and accurate haplotypes for deciphering complex traits in pigs.
Cryopreservation and revival of Hawaiian stony corals using isochoric vitrification
Authors: Powell-Palm Matthew J. , Henley E. Michael , Consiglio Anthony N. , Lager Claire , Chang Brooke , Perry Riley , Fitzgerald Kendall , Daly Jonathan , Rubinsky Boris , Hagedorn Mary
Published: August 2023

Corals are under siege by both local and global threats, creating a worldwide reef crisis. Cryopreservation is an important intervention measure and a vital component of the modern coral conservation toolkit, but preservation techniques are currently limited to sensitive reproductive materials that can only be obtained a few nights per year during spawning. Here, we report the successful cryopreservation and revival of cm-scale coral fragments via mL-scale isochoric vitrification. We demonstrate coral viability at 24 h post-thaw using a calibrated oxygen-uptake respirometry technique, and further show that the method can be applied in a passive, electronics-free configuration. Finally, we detail a complete prototype coral cryopreservation pipeline, which provides a platform for essential next steps in modulating post-thaw stress and initiating long-term growth. These findings pave the way towards an approach that can be rapidly deployed around the world to secure the biological genetic diversity of our vanishing coral reefs.
Click-electrochemistry for the rapid labeling of virus, bacteria and cell surfaces
Authors: Depienne Sébastien , Bouzelha Mohammed , Courtois Emmanuelle , Pavageau Karine , Lalys Pierre-Alban , Marchand Maia , Alvarez-Dorta Dimitri , Nedellec Steven , Marín-Fernández Laura , Grandjean Cyrille , Boujtita Mohammed , Deniaud David , Mével Mathieu , Gouin Sébastien G.
Published: August 2023

Methods for direct covalent ligation of microorganism surfaces remain poorly reported, and mostly based on metabolic engineering for bacteria and cells functionalization. While effective, a faster method avoiding the bio-incorporation step would be highly complementary. Here, we used N-methylluminol (NML), a fully tyrosine-selective protein anchoring group after one-electron oxidation, to label the surface of viruses, living bacteria and cells. The functionalization was performed electrochemically and in situ by applying an electric potential to aqueous buffered solutions of tagged NML containing the viruses, bacteria or cells. The broad applicability of the click-electrochemistry method was explored on recombinant adeno-associated viruses (rAAV2), Escherichia coli (Gram-) and Staphyloccocus epidermidis (Gram + ) bacterial strains, and HEK293 and HeLa eukaryotic cell lines. Surface electro-conjugation was achieved in minutes to yield functionalized rAAV2 that conserved both structural integrity and infectivity properties, and living bacteria and cell lines that were still alive and able to divide.
A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus
Authors: Spisak Sandor , Tisza Viktoria , Nuzzo Pier Vitale , Seo Ji-Heui , Pataki Balint , Ribli Dezso , Sztupinszki Zsofia , Bell Connor , Rohanizadegan Mersedeh , Stillman David R. , Alaiwi Sarah Abou , Bartels Alan H. , Papp Marton , Shetty Anamay , Abbasi Forough , Lin Xianzhi , Lawrenson Kate , Gayther Simon A. , Pomerantz Mark , Baca Sylvan , Solymosi Norbert , Csabai Istvan , Szallasi Zoltan , Gusev Alexander , Freedman Matthew L.
Published: August 2023

To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNLPs) may also confer disease risk. Multiple reports have shown that the 5p15.33 prostate cancer risk region is a particularly strong expression quantitative trait locus (eQTL) for Iroquois Homeobox 4 (IRX4) transcripts. Here, we demonstrate using epigenome and genome editing that a biallelic (21 and 47 base pairs (bp)) MNLP is the causal variant regulating IRX4 transcript levels. In LNCaP prostate cancer cells (homozygous for the 21 bp short allele), a single copy knock-in of the 47 bp long allele potently alters the chromatin state, enabling de novo functional binding of the androgen receptor (AR) associated with increased chromatin accessibility, Histone 3 lysine 27 acetylation (H3K27ac), and ~3-fold upregulation of IRX4 expression. We further show that an MNLP is amongst the strongest candidate susceptibility variants at two additional prostate cancer risk loci. We estimated that at least 5% of prostate cancer risk loci could be explained by functional non-SNP causal variants, which may have broader implications for other cancers GWAS. More generally, our results underscore the importance of investigating other classes of inherited variation as causal mediators of human traits.
Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis
Authors: Zhang Shu , Fang Wen , Zhou Siqi , Zhu Dongming , Chen Ruidong , Gao Xin , Li Zhuojin , Fu Yao , Zhang Yixuan , Yang Fa , Zhao Jing , Wu Hao , Wang Pin , Shen Yonghua , Shen Shanshan , Xu Guifang , Wang Lei , Yan Chao , Zou Xiaoping , Chen Dijun , Lv Ying
Published: August 2023

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.
Janus nanoparticles targeting extracellular polymeric substance achieve flexible elimination of drug-resistant biofilms
Authors: Liu Zhiwen , Guo Kangli , Yan Liemei , Zhang Kai , Wang Ying , Ding Xiaokang , Zhao Nana , Xu Fu-Jian
Published: August 2023

Safe and efficient antibacterial materials are urgently needed to combat drug-resistant bacteria and biofilm-associated infections. The rational design of nanoparticles for flexible elimination of biofilms remains challenging. Herein, we propose the fabrication of Janus-structured nanoparticles targeting extracellular polymeric substance to achieve dispersion or near-infrared (NIR) light-activated photothermal elimination of drug-resistant biofilms, respectively. Asymmetrical Janus-structured dextran-bismuth selenide (Dex-BSe) nanoparticles are fabricated to exploit synergistic effects of both components. Interestingly, Janus Dex-BSe nanoparticles realize enhanced dispersal of biofilms over time. Alternatively, taking advantage of the preferential accumulation of nanoparticles at infection sites, the self-propelled active motion induced by the unique Janus structure enhances photothermal killing effect. The flexible application of Janus Dex-BSe nanoparticles for biofilm removal or NIR-triggered eradication in vivo is demonstrated by Staphylococcus aureus-infected mouse excisional wound model and abscess model, respectively. The developed Janus nanoplatform holds great promise for the efficient elimination of drug-resistant biofilms in diverse antibacterial scenarios.
Reef-building corals farm and feed on their photosynthetic symbionts
Authors: Wiedenmann Jörg , D’Angelo Cecilia , Mardones M. Loreto , Moore Shona , Benkwitt Cassandra E. , Graham Nicholas A. J. , Hambach Bastian , Wilson Paul A. , Vanstone James , Eyal Gal , Ben-Zvi Or , Loya Yossi , Genin Amatzia
Published: August 2023

Coral reefs are highly diverse ecosystems that thrive in nutrient-poor waters, a phenomenon frequently referred to as the Darwin paradox1. The energy demand of coral animal hosts can often be fully met by the excess production of carbon-rich photosynthates by their algal symbionts2,3. However, the understanding of mechanisms that enable corals to acquire the vital nutrients nitrogen and phosphorus from their symbionts is incomplete4–9. Here we show, through a series of long-term experiments, that the uptake of dissolved inorganic nitrogen and phosphorus by the symbionts alone is sufficient to sustain rapid coral growth. Next, considering the nitrogen and phosphorus budgets of host and symbionts, we identify that these nutrients are gathered through symbiont ‘farming’ and are translocated to the host by digestion of excess symbiont cells. Finally, we use a large-scale natural experiment in which seabirds fertilize some reefs but not others, to show that the efficient utilization of dissolved inorganic nutrients by symbiotic corals established in our laboratory experiments has the potential to enhance coral growth in the wild at the ecosystem level. Feeding on symbionts enables coral animals to tap into an important nutrient pool and helps to explain the evolutionary and ecological success of symbiotic corals in nutrient-limited waters.
Generation of time-synchronized two-color X-ray free-electron laser pulses using phase shifters
Authors: Cho Myung-Hoon , Kang Teyoun , Yang Haeryong , Kim Gyujin , Kwon Seong-Hoon , Moon Kook-Jin , Nam Inhyuk , Min Chang-Ki , Heo Hoon , Kim Changbum , Kang Heung-Sik , Shim Chi Hyun
Published: August 2023

To optimize the intensity of X-ray free-electron lasers (XFELs), phase shifters, oriented in phase with the phases of the XFEL pulse and electron beam, are typically installed at undulator lines. Although a π-offset between the phases (i.e., an “out-of-phase” configuration) can suppress the XFEL intensity at resonant frequencies, it can also generate a side-band spectrum, which results in a two-color XFEL pulse; the dynamics of such a pulse can be described using the spontaneous radiation or low gain theory. This attributes of this two-color XFEL pulse can be amplified (log-scale amplification) through an undulator line with out-of-phase phase shifters. In this study, the features of two-color XFEL pulses were evaluated through theory, simulations and experiments performed at Pohang Accelerator Laboratory X-ray Free Electron Laser. The XFEL gain slope and energy separation between the two-color spectral peaks were consistent through theoretical expectation, and the results of simulation and experiment. The experimentally determined two-color XFEL pulse energy was 250 μJ at a photon energy of 12.38 keV with a separation of 60 eV.
Effects of 13C isotope-labeled allelochemicals on the growth of the invasive plant Alternanthera philoxeroides
Authors: Hua Zexun , Xie Qingsong , Li Yue , He Mengying , Wang Yan , Wu Hongmiao , Zhang Zhen
Published: August 2023

The secondary metabolites of indigenous plants have significant allelopathic inhibitory effects on the growth and development of invasive alien plants. Methyl palmitate (MP) and methyl linolenate (ML) were used as exogenous allelopathic substances. The research investigated the differences of inhibitory effects of MP and ML on the growth of seedlings of Alternantheraphiloxeroides, and calculated their morphological characteristics, biomass, physiological indicators and the response index (RI). The synthetical allelopathic index (SE) of 1 mmol/L MP was the smallest (− 0.26) and the allelopathic inhibition was the strongest; therefore, it was selected as a 13C-labeled allelochemical. The distribution of 1 mmol/L MP in different parts of A.philoxeroides and the correlation between the biomass ratios of roots, stems and leaves and the 13C content were studied by 13C stable isotope tracing experiments. Atom percent excess (APE) between roots, stems and leaves of A.philoxeroides treated with 1 mmol/L MP were significantly different in terms of magnitude, with leaves (0.17%) > roots (0.12%) > stems (0.07%). The root, stem and leaf biomass ratios of invasive weeds had great significant positive correlation with 13C content (p < 0.01, R2 between 0.96 and 0.99). This current research provides a new idea and method for the control of A.philoxeroides, but large-scale popularization remains to be studied.
Non cancer causes of death after gallbladder cancer diagnosis: a population-based analysis
Authors: Xia Yang , Lu Shuangshuang , Huo Chunyan , Fan Li , Lin Min , Huang Jin
Published: August 2023

Mortality from non cancer causes in patients with gallbladder cancer (GBC) still unclear. This study evaluated the causes and risk factors of non cancer death during different follow-up periods after GBC diagnosis. Non cancer causes of death for GBC patients diagnosed between 2000 and 2017 in Surveillance, Epidemiology and End Results database were analyzed and standardized mortality rates (SMR) for each non cancer death were calculated. Predictors for non cancer death were identified through multivariate competing risk analysis. A total 11,927 GBC patients were identified for further analysis, 9393 died during follow up. The largest proportion of non cancer deaths occurred > 3 years after diagnosis (39.4%). Most common non cancer cause were cardiovascular disease (43.3%), followed by other cause of death (34.4%) and infectious diseases (8.6%). Compared with US general population, GBC patients has higher risk of death from disease of heart (SMR, 1.58; 95%CI, 1.41–1.75), septicemia (SMR,3.21; 95%CI, 2.27–4.40), diabetes mellitus (SMR,1.97; 95%CI, 1.43–2.63), alone with other causes. Non cancer causes accounted for a significant proportion of deaths during the follow-up period after GBC diagnosis. The risk of non cancer death is higher in GBC patients than in the general population. Our study provides comprehensive assessment of death from non cancer cause in GBC patients, which has important implications for health management in GBC patients.
Association between physical demands, skin temperature and wellbeing status in elite football players
Authors: Majano Carlos , Garcia-Unanue Jorge , Fernández-Cuevas Ismael , Escamilla-Galindo Víctor , Alonso-Callejo Antonio , Sanchez-Sanchez Javier , Gallardo Leonor , Felipe Jose Luis
Published: August 2023

The demanding nature of elite football requires players to be closely monitored to ensure optimal performance and minimize injury risk. This study aimed to evaluate the relationship between physical demands, skin temperature, and well-being status in 30 elite football players over a 12-week competitive period. Thermography assessments, weekly Well-being questionnaires, and daily training and match load recordings were used to gather data. Results indicated that along the microcycles there was a decrease in high-intensity accelerations and decelerations distance completed, while maintaining other high-intensity actions. Furthermore, it was found that high-intensity movements contribute to the generation of thermal asymmetries in the thighs; the adductor thermal asymmetry showed a positive relationship with stress and muscle soreness, the knee thermal asymmetry had a positive relationship with fatigue and a negative relationship with rest and quality of rest, and finally the hamstrings muscles exhibited significant differences between the thermal asymmetry groups, with the high asymmetry completing less high intensity actions than the low asymmetry group. In conclusion, this study highlights the interconnections between physical demands, skin temperature, and well-being in elite football players and provides valuable insights for coaches and trainers in their efforts to optimize performance and health.
Chemical features and machine learning assisted predictions of protein-ligand short hydrogen bonds
Authors: Zhou Shengmin , Liu Yuanhao , Wang Sijian , Wang Lu
Published: August 2023

There are continuous efforts to elucidate the structure and biological functions of short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms reside more than 0.3 Å closer than the sum of their van der Waals radii. In this work, we evaluate 1070 atomic-resolution protein structures and characterize the common chemical features of SHBs formed between the side chains of amino acids and small molecule ligands. We then develop a machine learning assisted prediction of protein-ligand SHBs (MAPSHB-Ligand) model and reveal that the types of amino acids and ligand functional groups as well as the sequence of neighboring residues are essential factors that determine the class of protein-ligand hydrogen bonds. The MAPSHB-Ligand model and its implementation on our web server enable the effective identification of protein-ligand SHBs in proteins, which will facilitate the design of biomolecules and ligands that exploit these close contacts for enhanced functions.