bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of 12 426 SB2 candidates in the LAMOST-MRS, using a binary spectral model
Authors: Kovalev Mikhail , Zhou Zenghua , Chen Xuefei , Han Zhanwen
Published: October 2023

We use an updated method for the detection of double-lined spectroscopic binaries (SB2s) using Vsin i values from spectral fits. The method is applied to all spectra from Large sky Area Multi-Object fiber Spectroscopic Telescope Medium Resolution Survey. Using this method, we detect 12 426 SB2 candidates, where 4321 are already known and 8105 are new discoveries. We check their spectra manually to minimize possible false positives. We also detect several cases of contamination of the spectra by solar light. Additionally, for candidates with multiple observations, we compute mass ratios with systemic velocities and determine Keplerian orbits. We present an updated catalogue of all SB2 candidates together with additional information for some of them in separate data tables.
Mixed Methods Research in Criminology
Authors: Brent John , Kraska Peter , Skeen Jordan
Published: October 2023

Research methods provide the infrastructure and means to produce valid and reliable knowledge. These methods guide and structure the process through which scholars conceptualize, implement, conduct, analyze, and disseminate scholarly efforts. They help shed empirical light on motivations, individual behaviors, group- and community-level dynamics, complex social processes, and structural-level currents. To empirically capture this complexity, the field of criminal justice/criminology (and, more broadly, social sciences) has developed and established a diverse set of methodological tools. Historically, research efforts have used quantitative or qualitative methods, each informed by different philosophical assumptions, research designs, strategies, data collection techniques, forms of analysis, and pedagogical goals. A rigid adherence to mono-method practices has led to paradigm conflicts between quantitative and qualitative research. Each side posits that their approach to generating knowledge stem from different philosophical and epistemological roots. On the one hand, quantitative research emphasizes positivism, objectivity, deductive reasoning, precise quantification, value neutrality, and fact finding through empirical replication. On the other hand, qualitative research promotes interpretivism, subjectivity, inductive reasoning, empathy, socially constructed realities, and value-informed interpretations. The argument follows that, given such differences, quantitative and qualitative methods are incompatible and therefore should remain separate. Despite these exclusive boundaries the tendency to combine—or mix—methods has become more prominent. Methodological exclusivism has been labeled as unnecessary and inhibiting because it does not recognize the contributions made by each. Attempts at bridging this divide have led to more pragmatic approaches which combine quantitative and qualitative methods into a single study. Integration allows for complementary strengths to minimize weakness within each. At this point, many in the social sciences view “mixed methods” research as its own paradigm—marked by unique concepts, philosophical assumptions, research designs and typologies, integration strategies, methodological procedures, and pedagogical goals. The following provides a comprehensive review of this literature and approach by providing an annotated bibliography for each of these areas.
Amir Timur
Authors: Jackson Peter
Published: October 2023

Timur (Temür-i lang, “Temür the Lame” in Persian; hence the Europeanized form “Tamerlane”) was born in Kish (later Shahr-i Sabz), in Transoxiana, in c. 1328 as a member of the ruling family of the nomadic Turco-Mongol Barlas tribe in Transoxiana (now the southern part of Uzbekistan). Through a succession of alliances, in 1370 he effectively became ruler of the “Ulus Chaghadai,” the western part of the Central Asian territory bequeathed by Chinggis (Genghis) Khan to his second son and divided into two separate khanates since 1347–1348. As a commoner, Timur was debarred from sovereign rank. He governed in the name of a khan of Chinggisid descent and was styled simply Amir (or Great Amir) and also Güregen (“imperial son-in-law”) by virtue of his marriage to a Chinggisid princess, though later in life he appears to have claimed descent from one of Chinggis Khan’s ancestors. His principal residence was Samarkand, but he spent much of his life on campaign. His tireless military operations aimed at restoring the imperial Mongol order, which had lapsed since the mid-fourteenth century, and were directed against those who had usurped control in the Mongol dominions. Timur brought most of Iran, Iraq, and present-day Afghanistan under his authority, ravaged the lands of the Mongol Golden Horde in the southern Russian steppes, sacked Delhi, overran Syria, and defeated the Ottoman Sultan Bayezid at Ankara in 1402. At his death in 1405, he was poised to invade the Ming Empire in China, the only part of the formerly Mongol dominions that he had not attacked. Timur’s mixed reputation reflects the contradictions in his character that have long fascinated historians. His taste for the colossal found expression both in his appalling treatment of cities that refused to surrender and in the splendid buildings he left to posterity. Though probably illiterate, he spoke Persian as well as Turkish, evinced a strong interest in history, and enjoyed discussion with scholars. Albeit a Muslim who favored shaykhs and Sufis and whose campaigns against Christian Georgia and the Ming were portrayed as holy war, he devoted most of his energies to conflict with other Muslim potentates. His empire, founded on his personal authority, lacked strong institutional underpinnings, and his death inaugurated a conflict among his heirs, who were unable to preserve his empire in its entirety. Nevertheless, members of the Timurid dynasty ruled over Transoxiana until 1500 and eastern Iran until 1507, and in 1526 another descendant, Babur, founded the Mughal Empire in India.
Enzyme redesign and genetic code expansion
Authors: Opuu Vaitea , Simonson Thomas
Published: October 2023

Enzyme design is an important application of computational protein design (CPD). It can benefit enormously from the additional chemistries provided by noncanonical amino acids (ncAAs). These can be incorporated into an ‘expanded’ genetic code, and introduced in vivo into target proteins. The key step for genetic code expansion is to engineer an aminoacyl-transfer RNA (tRNA) synthetase (aaRS) and an associated tRNA that handles the ncAA. Experimental directed evolution has been successfully used to engineer aaRSs and incorporate over 200 ncAAs into expanded codes. But directed evolution has severe limits, and is not yet applicable to noncanonical AA backbones. CPD can help address several of its limitations, and has begun to be applied to this problem. We review efforts to redesign aaRSs, studies that designed new proteins and functionalities with the help of ncAAs, and some of the method developments that have been used, such as adaptive landscape flattening Monte Carlo, which allows an enzyme to be redesigned with substrate or transition state binding as the design target.
Polyurethane scaffold-based 3D lung cancer model recapitulates in vivo tumor biological behavior for nanoparticulate drug screening
Authors: Sun Lu , Wang Xiaofei , He Yushui , Chen Boran , Shan Baoyin , Yang Jinlong , Wang Ruoran , Zeng Xihang , Li Jiehua , Tan Hong , Liang Ruichao
Published: October 2023

Lung cancer is the leading cause of cancer mortality worldwide. Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents, but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic. Thus, there is an urgent need to explore more reliable and effective in vitro lung cancer models. Here, we prepared a series of three-dimensional (3D) waterborne biodegradable polyurethane (WBPU) scaffolds as substrates to establish biomimetic tumor models in vitro. These 3D WBPU scaffolds were porous and could absorb large amounts of free water, facilitating the exchange of substances (nutrients and metabolic waste) and cell growth. The scaffolds at wet state could simulate the mechanics (elastic modulus ∼1.9 kPa) and morphology (porous structures) of lung tissue and exhibit good biocompatibility. A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds. Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial–mesenchymal transition-related genes, giving it a more moderate growth and adhesion pattern compared to 2D cells. In addition, WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor, including tumor stem cell markers, cell proliferation, apoptosis, invasion and tumor resistance proteins. Based on these features, we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs. Taken together, WBPU scaffold-based lung cancer model could better mimic the growth, microenvironment and drug response of tumor in vivo. This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.
Akkermansia muciniphila promotes testosterone‐mediated hair growth inhibition in mice
Authors: Lee Eunyoung , Kim Daedong , Seo Hyo‐Deok , Hahm Jeong‐Hoon , Seo Jae‐Gu , Lee Sang‐Nam , Kim Do‐Hak , Ahn Jiyun , Jung Chang Hwa
Published: October 2023

The beneficial effects of Akkermansia muciniphila (Akk) on gut health and inflammation reduction have been demonstrated; however, scientific evidence of hair growth enhancement by Akk has not been reported. Therefore, this study was undertaken to investigate the effect of Akk on improving testosterone‐mediated hair growth inhibition. Hair growth inhibition was induced through subcutaneous injection of testosterone into the shaved dorsal skin of C57BL/6 male mice. Live and pasteurized Akk were orally administered at a concentration of 1 × 108 colony‐forming unit. After 5 weeks, hair length and skin tissues were analyzed. The live and pasteurized Akk significantly stimulated hair growth, countering the inhibitory effect of testosterone compared to the testosterone‐alone group. Hematoxylin and eosin staining revealed a significant increase in hair follicle size in the Akk‐treated group. An increase in β‐catenin levels, which are associated with hair growth and cell cycle progression, was also observed. Moreover, the Akk‐treated group exhibited increased levels of fibroblast growth factors, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21. However, no significant difference was observed between the live and pasteurized Akk groups. These results underscore the potential of live and pasteurized Akk in improving testosterone‐mediated hair growth inhibition.
Decision-making in anesthesiology: will artificial intelligence make intraoperative care safer?
Authors: Duran Huong-Tram , Kingeter Meredith , Reale Carrie , Weinger Matthew B. , Salwei Megan E.
Published: October 2023

Purpose of review

This article explores the impact of recent applications of artificial intelligence on clinical anesthesiologists’ decision-making.

Recent findings

Naturalistic decision-making, a rich research field that aims to understand how cognitive work is accomplished in complex environments, provides insight into anesthesiologists’ decision processes. Due to the complexity of clinical work and limits of human decision-making (e.g. fatigue, distraction, and cognitive biases), attention on the role of artificial intelligence to support anesthesiologists’ decision-making has grown. Artificial intelligence, a computer's ability to perform human-like cognitive functions, is increasingly used in anesthesiology. Examples include aiding in the prediction of intraoperative hypotension and postoperative complications, as well as enhancing structure localization for regional and neuraxial anesthesia through artificial intelligence integration with ultrasound.

To fully realize the benefits of artificial intelligence in anesthesiology, several important considerations must be addressed, including its usability and workflow integration, appropriate level of trust placed on artificial intelligence, its impact on decision-making, the potential de-skilling of practitioners, and issues of accountability. Further research is needed to enhance anesthesiologists’ clinical decision-making in collaboration with artificial intelligence.
Immune checkpoint inhibitors as adjuvant therapy in patients with completely resected nonsmall cell lung cancer
Authors: Pirker Robert
Published: October 2023

Purpose of review

The purpose of the review is to summarize the current status of immune checkpoint inhibitors as adjuvant therapy in patients with resected nonsmall cell lung cancer (NSCLC).

Recent findings

The IMpower010 phase 3 trial demonstrated improved disease-free survival and, in case of PD-L1 at least 50%, also improved overall survival for atezolizumab compared to best supportive care among patients with completely resected stage II-IIIA NSCLC. The PEARLS/KEYNOTE-091 trial showed increased disease-free survival for pembrolizumab among patients with stage IB-IIIA NSCLC. Trials with nivolumab and durvalumab are ongoing.

Atezolizumab or pembrolizumab have become options for adjuvant therapy in patients with completely resected NSCLC.
Hepatic steatosis after switching to integrase inhibitor-based regimens does not parallel short-term weight gain
Authors: Gonzalez-Serna Alejandro , Macías Juan , Rincon Pilar , Arriaza Maria Jose , Corma-Gomez Anais , Santos Marta , Fernandez-Fuertes Marta , Pineda Juan Antonio , Real Luis Miguel
Published: October 2023

We studied hepatic steatosis in people with HIV (PWH) who switched to an integrase inhibitor (INSTI)-based regimen. One hundred and fifty-four PWH were included. After 48 weeks, median (Q1–Q3) weight gain was 1.2 (−0.6 to 3.8) kg and median (Q1–Q3) controlled attenuation parameter (CAP) change was −4 (−33 to 27) dB/m. Weight gain was weakly correlated with CAP change [R
2 95% confidence interval (CI) = 0.144 (−0.014 to 0.296); P = 0.074)]. Changes in hepatic steatosis after switching to INSTI-based regimens do not seem to parallel weight gain after 1 year.
Physical and mental health of long-term users of HIV preexposure prophylaxis in Australia
Authors: Cornelisse Vincent J. , Murphy Dean , Lee Sue J. , Stoove Mark , Traeger Michael W. , Wright Edwina J. ,   for the X-PLORE Study Team
Published: October 2023

Introduction:

HIV preexposure prophylaxis (PrEP) is highly effective at preventing HIV. We aimed to assess mental and physical health among long-term PrEP users in Australia's X-PLORE cohort.

Methods:

In early 2021, 1485 X-PLORE participants were emailed a survey covering demographics, sexual practices, ongoing PrEP use, physical and psychological diagnoses received since commencing PrEP, substance use, and impacts of the COVID-19 pandemic. Current anxiety and depression were assessed using GAD-7 and PHQ-9 questionnaires.

Results:

Of 476 participants (completion rate 32.1%), 99.8% were cis-gender men. Median PrEP use duration was 48 months (2002 person-years), with 81.7% currently using PrEP. PrEP-related toxicity was uncommon: 2.9% reported bone fractures, 1.3% low bone density, and 4.0% reported kidney problems, largely not necessitating PrEP cessation. Most (92.0%) rated their health as ‘good’ to ‘excellent’, and 22.6% reported improved health since starting PrEP, often because of improved mental health. Only 6.2% reported deterioration in health since starting PrEP, largely unrelated to PrEP. The most common diagnoses were hypertension (9.9%), depression (13.2%) and anxiety (14.9%); 17% had PHQ-9 scores indicating current moderate-to-severe depression, which was associated with unemployment [adjusted odds ratio (aOR) 3.90], regular cannabis use (aOR 2.49), and having ceased PrEP (aOR 2.13).

Conclusion:

Among long-term PrEP users, of which over 80% were currently using PrEP, self-reported PrEP toxicity was uncommon. With almost one in five PrEP users categorized as having depression, and with higher risk among those having ceased PrEP, we recommend routine screening for depression and anxiety in PrEP users and corresponding follow-up of patients no longer attending for PrEP.
MULTIPLE MACHINE LEARNING METHODS AND COMPARATIVE TRANSCRIPTOMICS IDENTIFY PIVOTAL GENES FOR ISCHEMIA-REPERFUSION INJURY IN HUMAN DONOR TISSUE UNDERGOING ORTHOTOPIC LIVER TRANSPLANTATION
Authors: Chen Chengxin , Wang Qiang , Yang Zhe , Zuo Shi , Cao Kun , Li Haiyang
Published: October 2023

Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication affecting patient prognosis during the period after orthotopic liver transplantation (OLT). Although an increasing number of scientists have investigated the molecular biology of ischemia-reperfusion injury (IRI) during OLT in animal and cellular models in recent years, studies using comprehensive and high-quality sequencing results from human specimens to screen for key molecules are still lacking. Aims: The objective of this study is to explore the molecular biological pathways and key molecules associated with HIRI during OLT through RNA sequencing and related bioinformatics analysis techniques. Methods: The study was done by performing mRNA sequencing on liver tissue samples obtained from 15 cases of in situ liver transplantation patients who experienced ischemia and reperfusion injury within 1 year at Guizhou Medical University, and combined with bioinformatics analysis and machine learning methods, we identified the genes and transcription factors that are closely associated with IRI during in situ liver transplantation surgery. Results: There were 877 differentially expressed genes (DEGs) identified in the included liver samples, of which 817 DEGs were upregulated and 60 were downregulated. Functional enrichment analysis revealed significant enrichment of immune-related terms, such as inflammation, defense responses, responses to cytokines, immune system processes, and cellular activation. In addition, core gene enrichment analysis after cytoHubba screening suggested that liver reperfusion injury might be associated with translation-related elements as a pathway together with protein translation processes. Machine learning with the weighted correlation network analysis screening method identified PTGS2, IRF1, and CDKN1A as key genes in the reperfusion injury process. Conclusions: This study demonstrated that the pathways and genomes whose expression is altered throughout the reperfusion process might be critical for the progression of HIRI during OLT.
BACTERIAL EXTRACELLULAR VESICLES IN THE REGULATION OF INFLAMMATORY RESPONSE AND HOST-MICROBE INTERACTIONS
Authors: Liu Benjamin D. , Akbar Rubab , Oliverio Anna , Thapa Kajol , Wang Xiaohong , Fan Guo-Chang
Published: October 2023

Extracellular vesicles (EVs) are a new revelation in cross-kingdom communication, with increasing evidence showing the diverse roles of bacterial EVs (BEVs) in mammalian cells and host-microbe interactions. Bacterial EVs include outer membrane vesicles released by gram-negative bacteria and membrane vesicles generated from gram-positive bacteria. Recently, BEVs have drawn attention for their potential as biomarkers and therapeutic tools because they are nano-sized and can deliver bacterial cargo into host cells. Importantly, exposure to BEVs significantly affects various physiological and pathological responses in mammalian cells. Herein, we provide a comprehensive overview of the various effects of BEVs on host cells (i.e., immune cells, endothelial cells, and epithelial cells) and inflammatory/infectious diseases. First, the biogenesis and purification methods of BEVs are summarized. Next, the mechanisms and pathways identified by BEVs that stimulate either proinflammatory or anti-inflammatory responses are highlighted. In addition, we discuss the mechanisms by which BEVs regulate host-microbe interactions and their effects on the immune system. Finally, this review focuses on the contribution of BEVs to the pathogenesis of sepsis/septic shock and their therapeutic potential for the treatment of sepsis.
Clinical Value of Syndecan-1 Levels in Trauma Brain Injury: A Meta-Analysis
Authors: Xie Wei-Wei , Ding Ya-Jun , Bhandari Suwas , Li Hui , Chen Hua-Sen , Jin Sheng-Wei , Weng Hai-Xu , Hao Yu
Published: October 2023

Background

Traumatic brain injury (TBI) is a head trauma, usually associated with death and endothelial glycocalyx damage. Syndecan-1 (SDC-1)—a biomarker of glycocalyx degradation—has rarely been reported in meta-analyses to determine the clinical prognostic value in TBI patients.

Methods

We looked into PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 01, 1990, to May 1, 2023, to identify eligible studies. A meta-analysis was conducted using RevMan 5.4 and Stata 16.0 with the search terms “SDC-1” and “traumatic brain injury”.

Results

The present study included five studies with a total of 640 enrolled patients were included. SDC-1 concentrations were higher in the Iso-trauma TBI group than in the non-TBI group [standardized mean difference (SMD) = 0.52; 95% CI: 0.03 – 1.00; P = 0.04]. Subgroup analysis revealed statistical significance when comparing the SDC-1 level of multi-trauma TBI (TBI + other injuries) group with the Iso-trauma TBI group (SMD = 0.74; 95% CI: 0.42–1.05; P < 0.001), and the SDC-1 level of the TBI coagulopathy (+) group (TBI with early coagulopathy) with the TBI coagulopathy (-) group (SMD =1.75; 95% CI:0.41–3.10; P = 0.01). Iso-trauma TBI patients with higher SDC-1 level were at a higher risk of 30-day in-hospital mortality [odds ratio (OR) =3.32; 95% CI: 1.67–6.60; P = 0.0006].

Conclusion

This meta-analysis suggests that SDC-1 could be a biomarker of endotheliopathy and coagulopathy in TBI, as it was increased in iso-trauma TBI patients and was higher in multi-trauma TBI patients. There is a need for additional research into the use of syndecan-1 as a prognostic biomarker in TBI, especially in iso-trauma TBI patients.
Primary central nervous system vasculitis and headache: Ten themes
Authors: Younger David S.
Published: October 2023

Purpose of review

The primary central nervous system (CNS) vasculitides refers to clinicopathologic disorders that share the histopathology of inflammation of cerebral or spinal blood vessels. Unrecognized and therefore untreated, vasculitis of the CNS results in irreversible injury and disability making these disorders of paramount importance to clinicians.

Recent findings

Headache is an important clue to vasculitic involvement of CNS vessels. CNS vasculitis can be primary, in which only intracranial or spinal vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. The suspicion of vasculitis based on the history, clinical examination, and laboratory studies warrants prompt evaluation and treatment to prevent cerebral ischemia or infarction.

Primary CNS vasculitides can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. As in its systemic counterparts, clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by anticipated medication adverse effects.
Sensitivity to the role of an animated agent from observed interactions in newborn chicks (
Gallus gallus
)
Authors: De Roni P. , Geraci A. , Simion F. , Regolin L.
Published: October 2023

Few month old human infants are able to detect the social roles of artificial agents and consistently choose the object behaving as ‘approacher’ rather than ‘repulser’. This preference has been considered evidence of a pre-linguistic and pre-cultural origin of the social mind. Similar preferences have not been described in other species, though comparative data could help clarify the nature of this phenomenon and its evolutionary origin. In this study, we investigated sensitivity to the social role of an artificial agent in domestic chicks. Birds offer an excellent model to study the evolutionary roots of cognitive abilities, since they separated from mammals over 300 Ma. Moreover, the investigation of newly hatched chicks allows control for previous experience. After being exposed to computer-presented animations depicting an interaction among two agents, chicks underwent a free choice test among those same objects. While no initial evidence of a clear preference emerged from the planned analysis, chicks in the experimental condition showed a preference for the ‘approacher’ when controlling for side bias, mirroring human infants behaviour. This suggests the existence of an early ability to discriminate agents from their interactions, independent from any social experience
Adult neurogenesis does not explain the extensive post-eclosion growth ofHeliconiusmushroom bodies
Authors: Alcalde Anton Amaia , Young Fletcher J. , Melo-Flórez Lina , Couto Antoine , Cross Stephen , McMillan W. Owen , Montgomery Stephen H.
Published: October 2023

Among butterflies,Heliconiushave a unique behavioural profile, being the sole genus to actively feed on pollen.Heliconiuslearn the location of pollen resources, and have enhanced visual memories and expanded mushroom bodies, an insect learning and memory centre, relative to related genera. These structures also show extensive post-eclosion growth and developmental sensitivity to environmental conditions. However, whether this reflects plasticity in neurite growth, or an extension of neurogenesis into the adult stage, is unknown. Adult neurogenesis has been described in some Lepidoptera, and could provide one route to the increased neuron number observed inHeliconius.Here, we compare volumetric changes in the mushroom bodies of freshly eclosed and agedHeliconius eratoandDryas iulia, and estimate the number of intrinsic mushroom body neurons using a new and validated automated method to count nuclei. Despite extensive volumetric variation associated with age, our data show that neuron number is remarkably constant in both species, suggesting a lack of adult neurogenesis in the mushroom bodies. We support this conclusion with assays of mitotic cells, which reveal very low levels of post-eclosion cell division. Our analyses provide an insight into the evolution of neural plasticity, and can serve as a basis for continued exploration of the potential mechanisms behind brain development and maturation.
Assessment of help value affects reciprocation in Norway rats
Authors: Enghelhardt Sacha C. , Paulsson Niklas I. , Taborsky Michael
Published: October 2023

Wild-type Norway rats reciprocate help received in a well-replicated experimental food-giving task, but the criteria to appraise the received help's value are unclear. We tested whether quality or quantity of received help is more important when deciding to return help, and whether partner familiarity and own current need affect this evaluation. We experimentally varied recipients of help's hunger state, and familiar or unfamiliar partners provided either higher caloric food (enhanced quantity; carrots) or food higher in protein and fat (enhanced quality; cheese). Reciprocation of received help was our criterion for the rats' value assessment. Familiarity, food type and hunger state interacted and affected help returned by rats. Rats returned less help to familiar partners than to unfamiliar partners. With unfamiliar partners, rats returned more help to partners that had donated preferred food (cheese) than to partners that had donated less preferred food (carrots), and they returned help earlier if they were satiated and had received cheese. With familiar partners, food-deprived rats that had received cheese returned more help than satiated rats that had received carrots. Our results suggest that Norway rats assess the received help's value based on its quality, their current need and partner familiarity before reciprocating received help.
Bacillus dicomae sp. nov., a new member of the Bacillus cereus group isolated from medicinal plant Dicoma anomala
Authors: Makuwa Sephokoane Cindy , Motadi Lesetja Raymond , Choene Mpho , Liu Yang , Serepa-Dlamini Mahloro Hope
Published: October 2023

A Gram-stain-positive, endospore-forming endophytic bacterial strain designated MHSD28T was isolated from surface-sterilized leaves of Dicoma anomala collected from Eisleben, Botlokwa, Limpopo Province, South Africa. The phenotypic and phylogenetic characteristics of strain MHSD28T were consistent with those of members within the

Bacillus cereus

group. Comparative analysis between this strain and its relatives confirmed that it belongs to this group and forms a monophyletic branch. The digital DNA–DNA hybridization values between strain MHSD28T and its relatives were lower than the 70 % threshold for species delineation. To further determine its phylogenetic position, multi-locus sequence analysis (MLSA) based on five concatenated housekeeping gene (gyrB, atpD, DnaK, rpoB and rpoD) sequences, phenotypic analysis, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) biotyper identification, fatty acid and polar lipid profile analyses were carried out. Phenotypic characterization, MLSA, whole genome sequence based analyses and MALDI-TOF results placed strain MHSD28T within the

B. cereus

group. The major fatty acids were iso-C15 : 0 and summed feature 3 and the main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The respiratory quinone was menaquinone-7. The cell-wall peptidoglycan structure included meso-diaminopimelic acid. Considering the above results, strain MHSD28T represents a novel species of the

B. cereus

group, for which the name Bacillus dicomae sp. nov. is proposed. The type strain is MHSD28T (=BD 2262T=LMG 32287T=CECT 30671T).
A SLiM-dependent conformational change in baculovirus IE1 controls its focus formation ability
Authors: Nagamine Toshihiro , Sako Yasushi
Published: October 2023

The baculovirus IE1 gene encodes a multifunctional protein that is essential for both DNA replication and RNA transcription of the virus. Prior to viral DNA replication, IE1 promotes early gene transcription when localized in hr-dependent foci. During viral DNA replication, the IE1 foci expand and fuse to generate the virogenic stroma (VS) with IE1 found in the VS reticulum. To explore the IE1 structural features essential for this coordinated localization, we constructed various IE1 mutants based on three putative domains (N, I, and C). We determined that a BDI motif located in the intrinsic disorder region (IDR) between the N and I domains acts as a nuclear localization signal, whereas BDII and HLH in the C domain are required for VS localization in infected cells or for chromosomal association in uninfected mitotic cells. Deletion of the SLiM (short linear motif) located in the I domain restrains both nuclear- and VS localization. Intra-molecular fluorescence resonance energy transfer (FRET) probes of IE1 mutants revealed a conformational change of the I-C two-domain fragment during infection, which was inhibited by aphidicolin, suggesting that IE1 undergoes a stage-dependent conformational change. Further, homo-dimerization of the I domain and stage-dependent conformational changes require an intact SLiM. Mutational analysis of SLiM revealed that VS localization and chromosomal association were retained following S291A and S291E substitutions, but hr-dependent focus formation differed between the two mutations. These results suggest that coordinated IE1 localization is controlled by SLiM-dependent conformational changes that are potentially switched by the phosphorylation state of the SLiM.
Federated Learning-Driven Collaborative Diagnostic System for Metastatic Breast Cancer
Authors: Gao William , Wang Dayong , Huang Yi
Published: October 2023

Metastatic breast cancer is one of the leading causes of cancer mortality. While there has been progress in developing deep learning-driven diagnostic system for metastatic breast cancer based on histopathological images, it faces a major challenge in real-world application, i.e., how to improve generalizability of the diagnostic models for diverse patient populations and variations in sample and image processing across different geographic regions. Multi-institutional collaborative learning, which trains a single model using data from multiple institutions, can address the challenges of data inadequacy, lack of data diversity, and data quality. However, the current practice of direct medical data transfer among institutions faces increasing restrictions including patient privacy, intellectual property, data ownership and legal obligations. To enable multi-institutional collaborative learning for cancer diagnosis, we developed a federated learning-driven collaborative diagnostic system for metastatic breast cancer. This system preserves patient privacy by decoupling model training from the need for direct medical data transfer between institutions. Further, this study has demonstrated that the federate learning-driven system can improve diagnostic model accuracy and generalizability by leveraging information derived from diverse data sources across multiple institutions. This study has also shown that this collaborative diagnostic system has a strong potential of improving local diagnosis performance on lower quality images at a resource constrained institution. Our research indicated that federated learning-driven diagnostic system is a feasible and robust framework for multi-institutional collaborative development of diagnostic models for metastatic breast cancer. In addition to the benefits of improving diagnostic model generalizability for diverse patient populations, the collaborative diagnostic system presents a new opportunity to enable under-resourced healthcare institutions to leverage external data resources to improve local diagnosis performance while preserving patient privacy.
Hypertension control and its relationship with cognitive impairment among adults aged 45 to 80 in China
Authors: Li Xin , wu Qian , Chen Xing , Tang Yanmin , Fei Beini , zhao Qi , Ding Jing , Wang Xin
Published: October 2023

This cross-sectional study aimed to investigate the control of hypertension and its association with cognitive impairment in Chinese adults aged 45-80 years. Using cross-sectional surveys conducted in Shanghai and Guizhou from 2019-2021, 9,688 eligible subjects were eventually included. After analyzing the data using statistical methods such as unconditional logistic regression and restricted cubic splines (RCS), we found that severe blood pressure was positively associated with the risk of cognitive impairment. There was no significant association between mild/moderate BP and the risk of cognitive impairment. Moreover, diastolic blood pressure was significantly positively correlated with cognitive impairment. The restricted cubic spline modelresults showed that the associations with cognitive impairment seem to be U-shaped for SBP and linear for DBP. In conclusion, this study shows that uncontrolled hypertension is an independent risk factor for cognitive impairment and that the risk of cognitive impairment increases as diastolic blood pressures continues to rise.
In vitrophenotypic susceptibility of HIV-1 non-group M to CCR5 inhibitor (Maraviroc): TROPI-CO study
Authors: Gracias Ségolène , El Yaalaoui Ikrame , Visseaux Benoît , Charpentier Charlotte , Descamps Diane , Martin Charlène , Lermechain Fanny , Plantier Jean-Christophe , Alessandri-Gradt Elodie
Published: October 2023

The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from group O, N and P to the CCR5 co-receptor antagonist, Maraviroc (MVC) was investigated among a large panel of 45 clinical strains, representative of the genetic diversity. The results were compared to reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC was observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC with median and mean IC50values at 1.23 and 1.33 nM respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the 2 remaining HIV-1/O strains exhibited a lower susceptibility (IC50at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the 2 HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50values.

Our study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5 or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles.
Cryptic diversity and signatures of domestication in the Black Soldier Fly (Hermetia illucens)
Authors: Generalovic Tomas N. , Sandrock Christoph , Roberts Benjamin J. , Meier Joana I. , Hauser Martin , Warren Ian A. , Pipan Miha , Durbin Richard , Jiggins Chris D.
Published: October 2023

The black soldier fly (Hermetia illucens) is the prime species in the developing global industry of insects as food and feed, but the genetic basis of its domestication has not been studied. We obtained whole genome sequences for 54 individuals from both wild and captive populations. We identified two genetic lineages at least 3 million years divergent, revealing cryptic diversity within the species complex. Our study indicates that the most common populations used for commercial and academic applications are primarily derived from just one of these divergent lineages, originating from a wild North American progenitor. Despite insect farming practices only reaching mass production scale over the past two decades, we find that captive populations show strong genome-wide signatures of domestication. Selective sweeps are found in multiple independently domesticated populations but are not seen in wild populations and suggest five major domestication loci located on chromosomes two, four and five. These regions contain development, behaviour, reproduction, metabolism and immunity genes. Populations experiencing independent domestication events, in the early stages of domestication, also show evidence of convergent genome evolution with repeated signatures of domestication in these same regions. Some limited evidence of gene flow between divergent lineages was observed, as well as evidence of hybridisation from domesticated populations into the wild. Our study reveals the genetic basis of ongoing domestication and provides a genomic platform for breeding and genetic surveillance in this novel agricultural species.
The Sun within: active processes from two-temperature models
Authors: Khodabandehlou Faezeh , Maes Christian
Published: October 2023

We propose an embedding of standard active particle models in terms of two-temperature processes. One temperature refers to an ambient thermal bath, and the other temperature effectively describes “hot spots,”i.e., systems with few degrees of freedom showing important population homogenization or even inversion of energy levels as a result of activation. As a result, the effective Carnot efficiency would get much higher than for our standard macroscopic thermal engines, making connection with the recent conundrum of hot mitochondria. Moreover, that setup allows to quantitatively specify the resulting nonequilibrium driving, useful in particular for bringing the notion of heat into play, and making easy contact with thermodynamic features. Finally, we observe that the shape transition in the steady low-temperature behavior of run-and-tumble particles (with the interesting emergence of edge states at high persistence) is stable and occurs for all temperature differences, including close-to-equilibrium.
Air pollution from biomass burning disrupts early adolescent cortical microarchitecture development
Authors: Bottenhorn Katherine L. , Sukumaran Kirthana , Cardenas-Iniguez Carlos , Habre Rima , Schwartz Joel , Chen Jiu-Chiuan , Herting Megan M.
Published: October 2023

Exposure to outdoor particulate matter (PM2.5) represents a ubiquitous threat to human health, and particularly the neurotoxic effects of PM2.5from multiple sources may disrupt neurodevelopment. Studies addressing neurodevelopmental implications of PM exposure have been limited by small, geographically limited samples and largely focus either on macroscale cortical morphology or postmortem histological staining and total PM mass. Here, we leverage residentially assigned exposure to six, data-driven sources of PM2.5and neuroimaging data from the longitudinal Adolescent Brain Cognitive Development Study (ABCD Study®), collected from 21 different recruitment sites across the United States. To contribute an interpretable and actionable assessment of the role of air pollution in the developing brain, we identified alterations in cortical microstructure development associated with exposure to specific sources of PM2.5using multivariate, partial least squares analyses. Specifically, average annual exposure (i.e., at ages 8-10 years) to PM2.5from biomass burning was related to differences in neurite development across the cortex between 9 and 13 years of age.

Graphical Abstract
Unraveling the Impact of Therapeutic Drug Monitoring via Machine Learning
Authors: Ates H. Ceren , Alshanawani Abdallah , Hagel Stefan , Cotta Menino O , Roberts Jason A , Dincer Can , Ates Cihan
Published: October 2023

Clinical studies investigating the benefits of beta-lactam therapeutic drug monitoring (TDM) among critically ill patients have been hindered by small patient group, variability between studies, patient heterogeneity and inadequate use of TDM. Accordingly, definitive conclusions regarding the efficacy of TDM have remained elusive. To address these challenges, we propose an innovative approach that leverages data-driven methods to unveil the concealed connections between therapy effectiveness and patient data. Our findings reveal that machine learning algorithms can identify informative features that distinguish between healthy and sick states. These hold promise as potential markers for disease classification and severity stratification, as well as offering a continuous and data-driven “multidimensional” SOFA score. The implementation of TDM-guided therapy was associated with improved recovery rates particularly during the critical 72 hours after sepsis onset. Providing the first-ever quantification of the impact of TDM, our approach has the potential to revolutionize the way TDM applied in critical care.
Increased Risks of Large-Artery Atherosclerosis and Brainstem Stroke in Patients With Nasopharyngeal Carcinoma
Authors: Lin Chin-Yang , Lin Cheng-Li , Liang Ji-An , Wang Yao-Ching , Lin Ying-Chun , Liao Chih-Ying , Lin Ting-Chun
Published: October 2023

Background

Information about the characteristics of stroke is crucial for improved screening, prevention, and treatment. The pattern of ischemic stroke in patients with nasopharyngeal carcinoma (NPC) is not well understood. The objective of this study is to investigate the etiology of ischemic stroke and the affected vascular territories in patients with NPC.

Methods

The Taiwan National Health Insurance Research Database and the Taiwan Stroke Registry were combined to identify the following 2 cohorts: patients with NPC having a subsequent stroke (NPC cohort) and patients without NPC having a stroke (non-NPC cohort). Data pertaining to the period from 2006 to 2018 were analyzed. The TOAST (Trial of ORG 10 172 in Acute Stroke Treatment) subtype of ischemic stroke and the affected vascular territories were analyzed and compared between the 2 cohorts.

Results

The NPC cohort comprised 277 patients, whereas the non-NPC cohort comprised 125 024 patients. The most common TOAST subtype of ischemic stroke was large-artery atherosclerosis (LAA) in the NPC cohort and small-vessel occlusion in the non-NPC cohort. The prevalence of LAA was considerably higher in the NPC cohort (41.9%) than in the non-NPC cohort (28.3%). The analysis of the affected vascular territories revealed that the incidence of brainstem stroke was significantly higher in the NPC cohort (25.4%) than in the non-NPC cohort (14.5%).

Conclusions

Patients with NPC tend to have increased risks of LAA and brainstem ischemic stroke. Physicians should consider sparing the vertebral and basilar arteries during definitive radiotherapy for NPC. Long-term follow-up for patients with NPC may include brain magnetic resonance imaging. This study may guide radiation oncologists in clinical decision-making.
Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry
Authors: Engelbrecht Eric , Rodriguez Oscar L. , Shields Kaitlyn , Schultze Steven , Tieri David , Jana Uddalok , Yaari Gur , Lees William , Smith Melissa L. , Watson Corey T.
Published: October 2023

Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of IG loci has hindered effective use of standard high- throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we leverage long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n=36), representing the first comprehensive description of IGK haplotype variation at population-scale. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and a common novel ∼24.7 Kbp structural variant harboring a functional IGKV gene. Among 47 functional IGKV genes, we identify 141 alleles, 64 (45.4%) of which were not previously curated. We report inter-population differences in allele frequencies for 14 of the IGKV genes, including alleles unique to specific populations within this dataset. Finally, we identify haplotypes carrying signatures of gene conversion that associate with enrichment of SNVs in the IGK distal region. These data provide a critical resource of curated genomic reference information from diverse ancestries, laying a foundation for advancing our understanding of population-level genetic variation in the IGK locus.