bluuebunny/crossref_metadata_2025 huggingface dataset:
The Utility of Weapons Reviews in Addressing Concerns Raised by Autonomous Weapon Systems
Authors: Copeland Damian , Liivoja Rain , Sanders Lauren
Published: November 2022

The obligation to legally review weapons, means and methods of warfare has been identified by the Group of Governmental Experts on Emerging Technologies in the Area of Lethal Autonomous Weapons Systems as one of its Guiding Principles. Despite calls to share practical measures and processes to undertake this review, national practice remains opaque and fragmented. This article describes the traditional weapons review process and explains why this process may need to be modified to adequately evaluate autonomous weapon systems (AWS). It uses three case studies of fictional AWS in various stages of development and acquisition to demonstrate how existing review processes can be adapted for the review of AWS. This article shows the utility of these reviews for ensuring compliance of AWS with existing legal requirements, thereby also demonstrating the suitability of existing law to regulate the use of this novel technology in warfare.
Monetary Policy in a World of Cryptocurrencies
Authors: Benigno Pierpaolo
Published: November 2022

Can currency competition affect central banks’ control of interest rates and prices? Yes, it can. In a two-currency world with competing cash (material or digital), the growth rate of the cryptocurrency sets an upper bound on the nominal interest rate and the attainable inflation rate, if the government currency is to retain its role as medium of exchange. In any case, the government has full control of the inflation rate. With an interest-bearing digital currency, equilibria in which government currency loses medium-of-exchange property are ruled out. This benefit comes at the cost of relinquishing control over the inflation rate.
Assessing Fungal Diversity and Abundance in the Black Soldier Fly and its Environment
Authors: Vitenberg Tzach , Opatovsky Itai
Published: November 2022

Detritivorous insects that flourish in decaying environments encounter microorganisms throughout their life cycle. However, it is not clear whether the microbial composition of the decaying environment affects the microbial composition of the insect gut, or whether the opposite is true, with the microorganisms that are adapted to the insect’s digestive system being dispersed by the insects to new habitats, thereby becoming more and more common in the environment. To test these questions the fungal composition of the black soldier fly (BSF) (Stratiomyidae; Hermetia illucens Linnaeus) larval gut and its surrounding decaying environment (household compost bins) were analyzed using amplicon sequencing. Constancy in the dominance of the genus Candida (Debaryomycetaceae) in most of the environments and larval guts was found. This finding may suggest a ‘core’ structure to the fungal community of the BSF. In locations where nutrient composition of the environment had higher fiber content, the Candida was not dominant and the most common fungi were the genus Gibberella (Nectriaceae) and the family Dipodascaceae. The later was dominant also in the larval gut and the former was replaced with Meyerozyma (Debaryomycetaceae), which may suggest a selection process by the insect’s gut. Little is known about the ecological interactions of insects with eukaryotic microorganisms, such as yeast-like fungi. As their metabolic complexity and ability is intense, they have the potential to dramatically affect the physiological condition of the insect.
Synchrotron emitting Komissarov torus with magnetic polarization around Kerr black holes
Authors: Velásquez-Cadavid J M , Lora-Clavijo Fabio D , Pimentel Oscar M , Arrieta-Villamizar J A
Published: November 2022

Magnetic fields in black hole accretion discs are associated with processes of mass accretion and energy amplification. The contribution of the magnetic field due to the magnetic polarization of the material induces effects on the physical properties of the medium that have repercussions on the radiation coming from the accretion discs. Hence, from observations, it could be possible to infer the ‘fingerprint’ left by the magnetic polarization of the material and establish the properties of the space–time itself. As the first step in this purpose, we use numerical simulations to systematically analyse the possible observable effects produced by the magnetic properties of an accretion disc around a Kerr black hole. We found that under the synchrotron radiation power-law model the effects of the magnetic polarization are negligible when the plasma is gas pressure-dominated. Nevertheless, as beta-plasma decreases, the emission becomes more intense for magnetic pressure-dominated discs. In particular, we found that paramagnetic discs emit the highest intensity value independent of the beta-plasma parameter in this regime. By contrast, the emitted flux decreases with the increase of beta-plasma due to the dependence of the magnetic field on the emission and absorption coefficients. Moreover, the disc morphology changes with the magnetic susceptibility: Paramagnetic discs are more compact than diamagnetic ones. This fact leads to diamagnetic discs emitting a greater flux because each photon has a more optical path to travel inside the disc.
TIMEDB: tumor immune micro-environment cell composition database with automatic analysis and interactive visualization
Authors: Wang Xueying , Chen Lingxi , Liu Wei , Zhang Yuanzheng , Liu Dawei , Zhou Chenxin , Shi Shuai , Dong Jiajie , Lai Zhengtao , Zhao Bingran , Zhang Wenjingyu , Cheng Haoyue , Li Shuaicheng
Published: November 2022

Deciphering the cell-type composition in the tumor immune microenvironment (TIME) can significantly increase the efficacy of cancer treatment and improve the prognosis of cancer. Such a task has benefited from microarrays and RNA sequencing technologies, which have been widely adopted in cancer studies, resulting in extensive expression profiles with clinical phenotypes across multiple cancers. Current state-of-the-art tools can infer cell-type composition from bulk expression profiles, providing the possibility of investigating the inter-heterogeneity and intra-heterogeneity of TIME across cancer types. Much can be gained from these tools in conjunction with a well-curated database of TIME cell-type composition data, accompanied by the corresponding clinical information. However, currently available databases fall short in data volume, multi-platform dataset integration, and tool integration. In this work, we introduce TIMEDB (https://timedb.deepomics.org), an online database for human tumor immune microenvironment cell-type composition estimated from bulk expression profiles. TIMEDB stores manually curated expression profiles, cell-type composition profiles, and the corresponding clinical information of a total of 39,706 samples from 546 datasets across 43 cancer types. TIMEDB comes readily equipped with online tools for automatic analysis and interactive visualization, and aims to serve the community as a convenient tool for investigating the human tumor microenvironment.
MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters
Authors: Terlouw Barbara R , Blin Kai , Navarro-Muñoz Jorge C , Avalon Nicole E , Chevrette Marc G , Egbert Susan , Lee Sanghoon , Meijer David , Recchia Michael J J , Reitz Zachary L , van Santen Jeffrey A , Selem-Mojica Nelly , Tørring Thomas , Zaroubi Liana , Alanjary Mohammad , Aleti Gajender , Aguilar César , Al-Salihi Suhad A A , Augustijn Hannah E , Avelar-Rivas J Abraham , Avitia-Domínguez Luis A , Barona-Gómez Francisco , Bernaldo-Agüero Jordan , Bielinski Vincent A , Biermann Friederike , Booth Thomas J , Carrion Bravo Victor J , Castelo-Branco Raquel , Chagas Fernanda O , Cruz-Morales Pablo , Du Chao , Duncan Katherine R , Gavriilidou Athina , Gayrard Damien , Gutiérrez-García Karina , Haslinger Kristina , Helfrich Eric J N , van der Hooft Justin J J , Jati Afif P , Kalkreuter Edward , Kalyvas Nikolaos , Kang Kyo Bin , Kautsar Satria , Kim Wonyong , Kunjapur Aditya M , Li Yong-Xin , Lin Geng-Min , Loureiro Catarina , Louwen Joris J R , Louwen Nico L L , Lund George , Parra Jonathan , Philmus Benjamin , Pourmohsenin Bita , Pronk Lotte J U , Rego Adriana , Rex Devasahayam Arokia Balaya , Robinson Serina , Rosas-Becerra L Rodrigo , Roxborough Eve T , Schorn Michelle A , Scobie Darren J , Singh Kumar Saurabh , Sokolova Nika , Tang Xiaoyu , Udwary Daniel , Vigneshwari Aruna , Vind Kristiina , Vromans Sophie P J M , Waschulin Valentin , Williams Sam E , Winter Jaclyn M , Witte Thomas E , Xie Huali , Yang Dong , Yu Jingwei , Zdouc Mitja , Zhong Zheng , Collemare Jérôme , Linington Roger G , Weber Tilmann , Medema Marnix H
Published: November 2022

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.
In-situ composite microstructure formation of immiscible alloy solidified in space
Authors: Zhao Jiuzhou , Sun Hao , Zhang Lili , Jiang Hongxiang , Yang Linjie , He Jie
Published: November 2022

The immiscible alloy Ti-Co-Gd is solidified in space by using the Electrostatic Levitation Device on board the Chinese Space Station. A sample with in-situ composite structure is obtained. The microstructure formation and gravity effect are discussed.
Bird signs can be important for ecocultural conservation by highlighting key information networks in people–bird communities
Authors: Wyndham Felice S , Park Karen E
Published: November 2022

The ways people think, feel, speak about, and act in and with environments are inextricably intertwined with the well-being of other living things, including birds. We report on the kinds of messages contained in 598 examples of locally-defined signs from 498 bird taxa from 169 sources and 123 ethnolinguistic groups. Using Peirce’s three sign forms: symbolic, iconic, and indexical, we analyze one aspect of human–bird interactions: that of reading bird sign for ecological and social interpretations. Understanding ecological semiotic nuance is important for translating between local, regional, and global science, and for respecting autonomous processes of local people attributing value or lack thereof to birds and their habitats. Over one-third of the signs in our sample (216; 36%) were specifically described as omens of some kind, commonly of death, illness, or something “bad”. Three modes of message delivery account for the majority of the data: predicting (60%), bringing (15%; including news, rain, luck), and indicating (15%; including seasonal change, fruit ripening, animals). Reading birds to predict weather (especially rain) was common, as was listening to and interpreting birds’ alarm calls warning of snakes or predators, and knowing that a certain bird indicates the presence of certain other animals, or of a water source. We collected 51 examples of warblish, the imitation or translation of bird sounds into non-onomatopoeic words. We argue for the amplification of ecocultural conservation (attending to histories of human–nonhuman relationships in place) to channel resources and land control to local and Indigenous managers who are immersed in relevant bird–people information networks. We discuss the importance of (1) reduction of uncertainty in local and hyper-local environments, (2) biocultural provocations in which birds fulfill important roles in human society, and (3) informational connectivity and locally-defined interspecies ethical relationships as key elements for inclusive and effective ecocultural bird conservation.
Vasoactive inotropic score as a predictor of mortality in neonatal septic shock
Authors: Demirhan Salih , Topcuoglu Sevilay , Karadag Nilgun , Ozalkaya Elif , Karatekin Guner
Published: November 2022

Background

Although many improvements in neonatal care have been achieved, mortality rates for sepsis and septic shock in newborns are still high. The vasoactive inotropic score (VIS) was designed and studied to predict mortality in different settings. There are currently no data on the predictive ability of the VIS for mortality in newborn patients with septic shock.

Methods

Patients with late-onset neonatal sepsis who required inotropes because of fluid-refractory septic shock during the study period were included in the study. Four distinct VIS values were calculated for each septic shock episode after inotropic treatment had begun, that is, at the initiation of inotropic treatment and at 24 and 48 h after inotropic treatment had begun, and the highest VIS (VISmax) at any time after initiation of inotropic agents.

Results

The 98 episodes studied were divided into two groups according to the outcomes of their sepsis episodes as survivors (n = 39) or nonsurvivors (n = 59). The areas under the curve of the VIS values for the prediction of mortality were the VISmax (0.819, p < 0.001), followed by the VIS48 (0.802, p < 0.001), VIS24 (0.762, p = 0.001) and VIS0 (0.699, p = 0.015). Patients with a VISmax of greater than 20 had significantly higher odds of mortality (p < 0.001, β = 14.7, 95% confidence interval [4.7–45.9]).

Conclusion

We found that the VISmax was an easy-to-use and helpful tool for predicting a poor outcome in neonatal sepsis. Physicians should be aware that the prognosis is poor for any newborn with a VIS of 20 or greater at any point after the onset of sepsis.
Increase of Bacterial Leaf Streak in Hard Red Spring Wheat in North Dakota and Yield Loss Considerations
Authors: Friskop Andrew , Green Andrew , Ransom Joel , Liu Zhaohui , Knodel Janet , Hansen Bryan , Halvorson Jessica , Lux LeAnn
Published: November 2022

Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has increased in both prevalence and severity in the major hard red spring wheat (HRSW)-producing state North Dakota. The disease is readily observed after flag leaf emergence and can quickly lead to defoliation and severe yield loss. The objectives of this research were to document the prevalence and incidence of BLS in North Dakota and provide estimations of yield and economic losses. Trained field scouts determined the incidence and prevalence of BLS in ND on HRSW plants between Feekes growth stage (FGS) 8 and FGS 11.2 from 2015 to 2021, and data were used to determine BLS-affected hectares. Yield data in combination with BLS ratings were obtained from HRSW performance trials to estimate the impact of BLS on yield. The combination of variety identity, hectarage data, BLS-affected hectarage estimates, and yield loss estimates was used to estimate economic losses from BLS in 2019 and 2020. Our data suggest that BLS-affected hectares ranged from 747 to 141,680 between 2015 and 2021. Yield loss was observed at multiple HRSW performance trial locations, with estimated yield losses as high as 60% on susceptible varieties. The amount of BLS-affected hectares was the highest in 2019 and 2020, and direct economic losses for North Dakota HRSW producers were estimated to be as high as $4.7 and $8.0 million, respectively. These data highlight the importance of BLS in HRSW and the need to procure resources for breeding efforts and grower education on management of BLS.
USPSTF colorectal cancer screening update 2021
Authors: Klimkiewicz Pawel
Published: November 2022

The US Preventive Services Task Force recently expanded its colorectal cancer screening recommendations to start screening adults with average risk profile at age 45. In the face of rising healthcare costs, limited medical resources, and in order to facilitate shared decision-making conversations, primary care clinicians should have a thorough understanding of the evidence supporting this new screening guideline.
Diagnosis and Management of Cuffitis: A Systematic Review
Authors: Hembree Amy E. , Scherl Ellen
Published: November 2022

BACKGROUND:

In patients with ulcerative colitis or familial adenomatous polyposis who develop neoplasia or fail medical therapy and require colectomy, restorative proctocolectomy with IPAA is often indicated. Although often well tolerated, IPAA can be complicated by cuffitis or inflammation of the remaining rectal cuff. Although much has been published on this subject, there is no clear and comprehensive synthesis of the literature regarding cuffitis.

METHODS:

Our systematic literature review analyzes 34 articles to assess the frequency, cause, pathogenesis, diagnosis, classification, complications, and treatment of cuffitis.

RESULTS:

Cuffitis occurs in an estimated 10.2% to 30.1% of pouch patients. Purported risk factors include rectal cuff length >2 cm, pouch-rectal anastomosis, stapled anastomosis, J-pouch configuration, 2- or 3-stage IPAA, preoperative Clostridium difficile infection, toxic megacolon, fulminant colitis, preoperative biologic use, medically refractory disease, immunomodulator/steroids use within 3 months of surgery, extraintestinal manifestations of IBD, and BMI <18.5 kg/m2 at the time of colectomy. Adverse consequences associated with cuffitis include decreased quality-of-life scores, increased risk for pouchitis, pouch failure, pouch excision, and pouch neoplasia.

CONCLUSIONS:

Given the similarities between pouchitis and cuffitis, diagnosis and treatment of cuffitis should proceed according to the International Ileal Pouch Consortium guidelines. This review found that the majority of the current literature fails to distinguish between classic cuffitis (a form of reminant ulcerative proctitis) and nonclassic cuffitis (resulting from other causes). Further work is needed to distinguish the unique risk factors and endoscopic characteristics associated with each subtype, and further randomized clinical trials should be conducted to strengthen the evidence for treatment options.
Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome
Authors: van Meenen David M.P. , Algera Anna Geke , Schuijt Michiel T.U. , Simonis Fabienne D. , van der Hoeven Sophia M. , Neto Ary Serpa , Abreu Marcelo Gama de , Pelosi Paolo , Paulus Frederique , Schultz Marcus J.
Published: November 2022

BACKGROUND

The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain.

OBJECTIVE

To investigate the association of mechanical power with mortality in ICU patients without ARDS.

DESIGN

This was an individual patient data analysis that uses the data of three multicentre randomised trials.

SETTING

This study was performed in academic and nonacademic ICUs in the Netherlands.

PATIENTS

One thousand nine hundred and sixty-two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women.

MAIN OUTCOME MEASURES

The primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital.

RESULTS

At day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure (P < 0.001), tidal volume (P < 0.001), respiratory rate (P < 0.001) and maximum airway pressure (P = 0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component.

CONCLUSION

In ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580.
Mitigating the Spread of COVID-19
Authors: Myroniuk Tyler W. , Lewis Kaleea R. , Hermsen Joan M. , Schatz Enid
Published: November 2022

Racially minoritized groups have disproportionately borne the impacts of the COVID-19 pandemic in America. We draw on Public Health Critical Race Praxis to investigate racial differences in college students' attitudes about mitigation efforts to limit the spread of COVID-19 and concerns about one's own and others' actions in these efforts. We used survey data from a random sample of Midwestern undergraduates (n = 620) who participated in a fall 2020 COVID-19 study; chi-square tests and logistic regression modeling were employed. Students of color were more likely than white students to report mitigation strategies as not sufficiently restrictive and that communities ought to prioritize limiting the spread of COVID-19. Students of color were also more likely to be concerned that the actions of others were spreading COVID-19. Universities need to continuously ask how their policies and practices acknowledge the broader racial context and seek the perspectives of diverse students.
Performance of Paralympic Powerlifting Records Holders
Authors: Lopes-Silva João Paulo , Franchini Emerson , Kons Rafael
Published: November 2022

Objective

This study was conducted to investigate the performance difference for current World (Junior and Senior) and Paralympic (Senior) record holders according to origin of impairment (acquired or congenital), level of competition, and sex and to describe the performance progression of Paralympic Powerlifting records holders.

Design

This retrospective cohort study involving 60 current world (20 Junior and 20 Senior) and Paralympic (20 Senior) Para powerlifting record holders with 15 males congenital impairment and 14 acquired impairment, while 18 females were acquired impairment and 9 congenital impairments.

Results

The origin of impairment did not influence the absolute and relative load of male and female recordists. However, for males, acquired athletes were older and heavier when compared with congenital athletes, but without differences for females. The absolute load of Junior World recordists was lower in relation to Senior World and Paralympic recordists independently of the sex. Congenital athletes more often reached the world record in the Junior category, while the acquired athletes were the ones who obtained most of the records in senior categories.

Conclusions

Our results show that origin of impairment did not influence the absolute and relative load of current World (Junior and Senior) and Paralympic (Senior) recordists.
Vaporized Nicotine (E-Cigarette) and Tobacco Smoking Among People With HIV: Use Patterns and Associations With Depression and Panic Symptoms
Authors: Hahn Andrew W. , Ruderman Stephanie A. , Nance Robin M. , Whitney Bridget W. , Eltonsy Sherif , Haidar Lara , Delaney Joseph A. C. , Drumright Lydia N. , Ma Jimmy , Mayer Kenneth H. , 'Cleirigh Conall O. , Napravnik Sonia , Eron Joseph J. , Christopoulos Katerina , Bamford Laura , Cachay Edward , Jacobson Jeffrey M. , Willig Amanda , Cropsey Karen , Chander Geetanjali , Crane Heidi M. , Fredericksen Rob J.
Published: November 2022

Background:

Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH.

Methods:

We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with the frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic symptoms. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics.

Results:

Among 7431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, to be White, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared with never CC use [95% confidence interval (95% CI): 5.5 to 11.5 days/month] or current CC use (95% CI: 6.6 to 10.5 days/month). Depression (relative risk: 1.20 [95% CI: 1.02 to 1.42]) and panic disorder (1.71 [95% CI: 1.43 to 2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN and 16% for CC).

Conclusion:

Our study elucidated demographic associations with VN use among PWH, revealed the overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research.
Phylogeography of the pallid ground squirrel (Spermophilus pallidicaudaSatunin, 1903) as a consequence of Holocene changes in the Mongolian steppe ecosystems
Authors: Kapustina Svetlana , Adiya Yansanjav , Lyapunova Elena , Brandler Oleg
Published: November 2022

The influence of Quaternary climatic changes is a source of intraspecific genetic heterogeneity of faunal components of Asian steppe and semi-desert ecosystems. The pallid ground squirrelSpermophilus pallidicaudais a typical representative of Inner Asian Marmotini, the intraspecific structure of which remained unstudied to date. We studied for the first time the genetic structure of the pallid ground squirrel based on cytochromeband control region of mitochondrial DNA variability. We generated ecological niche models to estimate the current and past habitat suitability forS. pallidicauda. Our results revealed two phyletic lineages dividing this species into western and eastern population groups. According to our proposed reconstruction of the history ofS. pallidicaudadistribution, the divergence of the detected phyla may have resulted from the formation of the ecological barrier that separated the western and eastern parts of the range in the early Holocene. The hypothesis of the origin and life history ofS. pallidicaudais given.
Results of a phase Ib study of SB-121, an investigational probiotic formulation, in participants with autism spectrum disorder
Authors: Schmitt Lauren M. , Smith Elizabeth G. , Pedapati Ernest V. , Horn Paul , Will Meredith , Lamy Martine , Barber Lillian , Trebley Joe , Meyer Kevin , Heiman Mark , West Korbin H.J. , Hughes Phoevos , Ahuja Sanjeev , Erickson Craig A.
Published: November 2022

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. While aripiprazole and risperidone are indicated for use in autistic youth with interfering irritability, there are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination ofL. reuteri, Sephadex®(dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients.
Characterization of molecular heterogeneity of colorectal cancer among Bangladeshi population by targeted next generation sequencing
Authors: Kamruzzaman Mohammad , Rahman Aura , Karmakar Aparna R , Alam A B M Khurshid , Kader Kazi Monzur , Jamal A B M , Hossain Maqsud
Published: November 2022

Background

Since the Sanger sequencing procedure was invented, scientists all over the world have been working to improve and further develop this cutting-edge technology. Next-generation sequencing (NGS) is a game-changing advancement and the ability to profile genetic changes in cancer in great detail has been made possible by recent advances in sequencing technology.

Several studies produced high-quality data in terms of mutation identification, particularly in the areas of actionable or rarely mutated genes, epigenetics, and transcriptomics. The goal of this project is to look at genetic heterogeneity in Bangladeshi colorectal cancer patients so that cost-effective precision medicine can be developed applied in Bangladesh.

Methods

The mutational characteristics of 24 colorectal tumor samples from Bangladeshi patients were investigated using targeted next generation sequencing to explore the association of mutations with clinical aspects. A total of 50 genes were sequenced with an average target depth of 675X.

Results

The left-sided tumors had higher mutation frequencies in TP53, APC, and ATM, while the right-sided tumors had higher mutation frequencies in EZH2, HNF1A, HRAS, and PIK3CA. Almost all of the samples in this study had a mutation in FGFR3. Deleterious mutations in the APC gene (94%) provided a selective advantage to the nascent intestinal tumor cell via constitutional stimulation of the Wnt signal transduction pathway and chromosomal instability. CDKN2A nonsynonymous mutations were found in almost all patient samples, with the exception of one. In a different patient with three unique mutations, 17 samples (71%) had a mutation in SMAD4 located in exon5 (p.P223N) synonymous and nonsynonymous mutations (two in NGRI04, and one in NGRI10). Several genes, including ATM, CDH1, ERBB4, and FBXW7, have been identified as being significantly affected by TNM stages.

Except for a few key colorectal cancer genes, a comparison of mutational characteristics with subjects from other countries’ independent data re vealed that the identified mutational characteristics are largely Bangladesh-specific.

Conclusion

In Bangladesh, precision medicine development and use in colorectal cancer are poorly addressed. The pilot study will serve as a starting point for genomics research into colon cancer in poor-resource settings like Bangladesh. The relationship between metastasis and genomic markers will aid in the identification of prospective intervention markers and the development of therapeutic options at the individual level, resulting in the development of precision medicine.
Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Authors: Potts Martin , Fletcher-Etherington Alice , Nightingale Katie , Mescia Federica , Bergamaschi Laura , Calero-Nieto Fernando J. , Antrobus Robin , Williamson James ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Kingston Nathalie , Göttgens Berthold , Bradley John R , Lehner Paul J , Matheson Nicholas J , Smith Kenneth G.C. , Wills Mark R , Lyons Paul A , Weekes Michael P
Published: November 2022

Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+and CD16+CEACAM1/6/8+mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.
The CANDID Study: impact of COVID-19 on critical care nurses and organisational outcomes: implications for the delivery of critical care services. A questionnaire study before and during the pandemic
Authors: McCallum Louise , Rattray Janice , Pollard Beth , Miller Jordan , Hull Alastair , Ramsay Pam , Salisbury Lisa , Scott Teresa , Cole Stephen , Dixon Diane
Published: November 2022

Objective

To use a model of occupational stress to quantify and explain the impact of working in critical care during the Covid-19 pandemic on critical care nurses and organisational outcomes.

Participants

Critical care nurses (CCNs) who worked in the UK NHS between January to November 2021 (n=461).

Methods

A self-reported survey measured the components of the Job-Demand Reward model of occupational stress. Job-demands, job-resources, health impairment (mental health (GHQ-12), burnout (MBI), PTSD symptoms (PCL-5)), work engagement and six organisational outcomes (commitment, job satisfaction, changing jobs, certainty about the future, quality of care, patient safety) were measured. Data were compared to baseline data (n=557) collected between April to October 2018. Regression analyses identified predictors of health impairment, work engagement and organisational outcomes.

Findings

Compared to 2018, CCNs were at elevated risk of probable psychological distress (GHQ-12, OR 6.03 [95% C.I. 4.75 to 7.95]; burnout emotional exhaustion, OR 4.02 [3.07 to 5.26]; burnout depersonalisation, OR 3.18 [1.99 to 5.07]; burnout accomplishment, OR 1.53 [1.18 to 1.97]). A third of CCNs reported probable PTSD. Job demands predicted psychological distress and job demands increased during the pandemic. Resources reduced the negative impact of job demands on psychological distress, but this moderating effect of resources was not observed at higher levels of demand. CCNs were less engaged in their work. Job and personal resources predicted work engagement and were reduced during the pandemic. All six organisational outcomes were impaired. Lack of resources, especially reduced learning opportunities, lack of focus on staff wellbeing, and reduced focus on quality predicted worse organisational outcomes.

Conclusions

The NHS needs to prioritise the welfare of CCNs, implement workplace change/planning, and support them to recover from the pandemic. The NHS is struggling to retain CCNs and, unless staff welfare is improved, quality of care and patient safety will likely decline.
The genomic footprint of social stratification in admixing American populations
Authors: Mas-Sandoval Alex , Mathieson Sara , Fumagalli Matteo
Published: November 2022

Cultural and socioeconomic differences stratify human societies and shape their genetic structure beyond the sole effect of geography. Despite mating being limited by the permeability of sociocultural stratification, most demographic models in population genetics often assume random mating. Taking advantage of the correlation between sociocultural stratification and the proportion of genetic ancestry in admixed populations, we sought to infer the former process in the Americas. To this aim, we define a mating model where the individual proportions of the genome inherited from Native American, European and sub-Saharan African ancestral populations constrain the mating probabilities through ancestry-related assortative mating and sex bias parameters. We simulate a wide range of admixture scenarios under this model. Then, we train a deep neural network and retrieve good performance in predicting mating parameters from genomic data. Our results show how population stratification shaped by racial and gender hierarchies have constrained the admixture processes in the Americas since the European colonisation and the subsequent Atlantic slave trade.
Maximizing the reliability and the number of species assignments in metabarcoding studies
Authors: Bourret Audrey , Nozères Claude , Parent Eric , Parent Geneviève J.
Published: November 2022

The use of environmental DNA (eDNA) for biodiversity assessments has increased rapidly over the last decade. However, the reliability of taxonomic assignments in metabarcoding studies is variable, and affected by the reference databases and the assignment methods used. Species level assignments are usually considered as reliable using regional libraries but unreliable using public repositories. In this study, we aimed to test this assumption for metazoan species detected in the Gulf of St. Lawrence, in the Northwest Atlantic. We first created a regional library with COI barcode sequences including a reliability ranking system for species assignments. We then estimated the accuracy of the public repository NCBI-nt for species assignments using sequences from the regional library, and contrasted assigned species and their reliability using NCBI-nt or the regional library with a metabarcoding dataset and popular assignment methods. With NCBI-nt and sequences from the regional library, Blast-LCA was the most accurate method for species assignments but the proportions of accurate species assignments were higher with Blast-TopHit (>80 % overall taxa, between 70 and 90 % amongst taxonomic groups). With the metabarcoding dataset, the reliability of species assignments was greater using the GSL-rl compared to NCBI-nt. However, we also observed that the total number of reliable species assignments could be maximized using both GSL-rl and NCBI-nt, and their optimal assignment methods, which differed. The use of a two-step approach in species assignments, using a regional library and a public repository, could improve the reliability and the number of detected species in metabarcoding studies.
Therapy-induced senescence upregulates antigen presentation machinery and triggers anti-tumor immunity in Acute Myeloid Leukemia
Authors: Gilioli Diego , Fusco Simona , Tavella Teresa , Giannetti Kety , Conti Anastasia , Santoro Antonella , Carsana Edoardo , Beretta Stefano , Schönlein Martin , Gambacorta Valentina , Aletti Federico Mario , Carrabba Matteo Giovanni , Bonini Chiara , Ciceri Fabio , Merelli Ivan , Vago Luca , Schmitt Clemens , Di Micco Raffaella
Published: November 2022

Acute myeloid leukemia (AML) is an aggressive hematological malignancy often curable only by using intensive chemotherapy. Nonetheless, resistance/early relapses are frequent, underscoring the need to investigate the molecular events occurring shortly after chemotherapy. Therapy-induced senescence (TIS) is a fail-safe tumor suppressive mechanism that may elicit immune-mediated responses contributing to senescent cell clearance. Yet, TIS functional role in AML eradication and immune surveillance early post-chemotherapy remains ill-defined. By combining transcriptional and cellular-based evaluation of senescence markers in AML patient samples, we found upregulation of senescence-associated genes and interferon gene categories with concomitant induction of HLA class I and class II molecules, pointing to a causal link between TIS and leukemia immunogenicity. Consistently, senescence-competent AML samples activated autologous CD4+and CD8+T cells and improved leukemia recognition by both T-cell subsets. Lastly, the anti-leukemic activity of Immune Checkpoint Blockades (ICBs) was enhanced upon senescence engagement in AML. Altogether, our results identify senescence as a potent immune-related anti-leukemic mechanism that may rapidly translate into innovative senescence-based strategies to prevent AML relapse.

STATEMENT OF SIGNIFICANCE

Our findings uncover a novel link between senescence induction and leukemia immune recognition by T cells via upregulation of antigen presentation machinery components, providing the basis for conceptually novel senescence-based targeted immunotherapeutic regimens for AML patients.
Transcriptional analysis in bacteriophage Fc02 ofPseudomonas aeruginosarevealed two overlapping genes with exclusion activity
Authors: Ramírez-Sánchez Irais , Magos-Castro Marco , Guarneros Gabriel
Published: November 2022

Little is known about the gene expression program during transition from lysogenic to lytic cycles of temperate bacteriophages inPseudomonas aeruginosa. To investigate this issue, we developed a thermo-sensitive repressor mutant in a lysogen and analyzed the phage transcriptional program by strand-specific RNA-Seq before and after thermo-induction. As expected, the repressor gene located on the phage DNA forward strand, is transcribed in the lysogen at the permissive temperature of 30°C. Upstream the promoter gene, we noticed the presence of two overlapped ORFs apparently in the same transcript, one ORF is a gene that encodes a protein of 7.9 kDa mediating exclusion of various super-infecting phages. The other ORF, placed in an alternate reading frame, with a possible AUG initiation codon at 25 n downstream the AUG of the first gene, is expected to encode a 20.7 kDa polypeptide of yet unknown function. Upon lifting repression at 40°C, starts transcription of an operon, involved in the lytic cycle from a promoter on the reverse phage DNA strand. The first gene in the operon is a homolog of the antirepresorner, a common gene in the lysis-lysogeny regulation region of other phages. Interestingly, the next gene afterneris gene10 that on the reverse strand, overlaps the overlapped geneolg1on the forward strand. Curiously, gene 10 expression also shows superinfection exclusion. Strand-specific RNA-Seq also has uncover the transcription succession of gene modules expressed during the phage lytic stage.
Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine
Authors: Zou Jing , Kurhade Chaitanya , Patel Sohil , Kitchin Nicholas , Tompkins Kristin , Cutler Mark , Cooper David , Yang Qi , Cai Hui , Muik Alexander , Zhang Ying , Lee Dung-Yang , Sahin Ugur , Anderson Annaliesa S. , Gruber William C. , Xie Xuping , Swanson Kena A. , Shi Pei-Yong
Published: November 2022

The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4thdose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4thdose of monovalent BNT162b2 vaccine induced a 3.0×, 2.9×, 2.3×, 2.1×, 1.8×, and 1.5× geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8×, 13.0×, 11.1×, 6.7×, 8.7×, and 4.8× GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4×, 3.0×, 2.5×, 2.0×, 1.5×, and 1.3× GMFRs, respectively; the bivalent vaccine induced 9.9×, 26.4×, 22.2×, 8.4×, 12.6×, and 4.7× GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.
Sleep deprivation detected by voice analysis
Authors: Thoret Etienne , Andrillon Thomas , Gauriau Caroline , Léger Damien , Pressnitzer Daniel
Published: November 2022

Sleep deprivation has an ever-increasing impact on individuals and societies. Yet, to date, there is no quick and objective test for sleep deprivation. Here, we used automated acoustic analyses of the voice to detect sleep deprivation. Building on current machine-learning approaches, we focused on interpretability by introducing two novel ideas: the use of a fully generic auditory representation as input feature space, combined with an interpretation technique based on reverse correlation. The auditory representation consisted of a spectro-temporal modulation analysis derived from neurophysiology. The interpretation method aimed to reveal the regions of the auditory representation that supported the classifiers’ decisions. Results showed that generic auditory features could be used to detect sleep deprivation successfully, with an accuracy comparable to state-of-the-art speech features. Furthermore, the interpretation revealed two distinct effects of sleep deprivation on the voice: a change in prosody and a change in timbre. Importantly, the relative balance of the two effects varied widely across individuals, even though the amount of sleep deprivation was controlled, thus confirming the need to characterize sleep deprivation at the individual level. Moreover, while the prosody factor correlated with subjective sleepiness reports, the timbre factor did not, consistent with the presence of both explicit and implicit consequences of sleep deprivation. Overall, the findings show that individual effects of sleep deprivation may be observed in vocal biomarkers. Future investigations correlating such markers with objective physiological measures of sleep deprivation could enable “sleep stethoscopes” for the cost-effective diagnosis of the individual effects of sleep deprivation.

Author summary

Sleep deprivation has an ever-increasing impact on individuals and societies, from accidents to chronic conditions costing billions to health systems. Yet, to date, there is no quick and objective test for sleep deprivation. We show that sleep deprivation can be detected at the individual level with voice recordings. Importantly, we focused on interpretability, which allowed us to identify two independent effects of sleep deprivation on the voice: a change in prosody and a change in timbre. The results also revealed a striking variability in individual reactions to the same deprivation, further confirming the need to consider the effects of sleep deprivation at the individual level. Vocal markers could be correlated to specific underlying physiological factors in future studies, outlining possible cost-effective and non-invasive “sleep stethoscopes”.