bluuebunny/crossref_metadata_2025 huggingface dataset:
Facilitators and barriers to implementing antimicrobial stewardship programs in public South African hospitals
Authors: Scheepers Lodewyk Nicolaas , Niesing Christina Maria , Bester Petra
Published: February 2023

Objective:

The South African National Department of Health released guidelines and recommendations for antimicrobial stewardship (AMS) programs to be established in public healthcare facilities. Their implementation remains challenged, especially in North West Province, where the public health system functions under severe strain. This research explored and interpreted the facilitators that strengthen and barriers that hinder the implementation of the national AMS program in public hospitals in North West Province.

Design:

A qualitative design and interpretive descriptive approach enabled insight into the realities of AMS program implementation.

Setting:

Public hospitals in North West Province, sampled through criterion sampling (n = 5).

Participants:

Purposive criterion sampling of healthcare practitioners (n = 30) actively participating in AMS programs in the 5 sampled public hospitals.

Method:

Qualitative, interpretive description with semi-structured individual interviews that were digitally recorded and transcribed. The ATLAS.ti version 8 software facilitated content analysis, followed by second-level analysis.

Results:

In total, 4 themes, 13 categories, and 25 subcategories emerged. We detected dissonance between government AMS ideals and the realities of AMS program implementation in public hospitals. A multilevel AMS leadership and governance vacuum exists in a dysfunctional health ecosystem in which AMS must operate. Healthcare practitioners agreed on the importance of AMS despite different understandings of AMS and ineffective multidisciplinary teams. Discipline-specific education and training are essential for all AMS participants.

Conclusions:

AMS is essential yet complex, and its contextualization and implementation are underestimated in public hospitals. Recommendations are focused on a supportive organizational culture, contextualized AMS program implementation plans, and changes in management.
The impact of strategic ventilation adjustments on stress responses in horses housed full-time in a vector-protected barn during the African horse sickness outbreak in Thailand
Authors: Poochipakorn Chanoknun , Joongpan Weena , Tongsangiam Pongphon , Phooseerit Areeya , Leelahapongsathon Kansuda , Chanda Metha
Published: February 2023

The severe outbreak of African horse sickness (AHS) in Thailand has forced horses to reside full-time inside barns that are covered by a small mesh net to prevent minuscule AHS insect vectors from gaining access. However, housing in the net-covered barn induces stress in horses, which compromises their welfare. Implementing strategic airflow adjustment while retaining the vector-protection characteristics has been proposed to help alleviate this problem. The present study aimed to investigate the effect of strategic ventilation adjustment on blood cortisol levels, heart rate and behaviour in horses in a vector-protected barn. Nine horses underwent two sequential stabling conditions: vector-protected barn housing and housing in a barn in which the air ventilation was explicitly adjusted. Heart rate was higher in the afternoon in horses housed in the barn without ventilation adjustment, whereas no change was observed in the barn with ventilation adjustment. The vector-protected housing increased the horses’ behavioural scores. Blood cortisol level declined over time, and an earlier decrease was detected at 1400h in the barn with ventilation adjustment. Although airflow adjustment did not appear to statistically alter the stress response in horses during housing in the vector-protected barn, an earlier decline in cortisol level alongside an unchanged heart rate in horses during the day may indicate the positive impact of ventilation adjustment within the vector-protected barn. With limited options to reduce stress or discomfort in horses, this strategic protocol could, at least in part, be applied to managing horses’ welfare during the AHS outbreak.
Welfare of extensively managed Swedish Gotland ponies
Authors: Viksten Sofie M , Hartmann Elke , Schneller Karin , Steen Margareta
Published: February 2023

It has been suggested that grazing horses could be used as a credible tool for landscape conservation which would, at the same time, improve horse welfare as opposed to conventional housing. A study was conducted between May 2014 and April 2015 on 12 one year old Gotland ponies managed extensively without supplementary feed. Monthly animal welfare assessments (n = 13) revealed welfare issues in most of the horses, i.e. low body condition score (BCS < 3/5), recurring poor skin condition in 11/12 horses and ocular discharge in 7/12 horses. At the end of the study, compared to the beginning, chafing and poor skin condition increased while coat condition improved. A correlation was found between a negative reaction (score > 0) in the human approach test and BCS < 3 and ocular discharge. Avoidance Distance test values were correlated with faecal parasite counts (> 350 eggs per gram [EPG]). These results indicate that the horses had acceptable welfare during late spring/summer (May–September) and that some horses required additional feed during winter. The animal welfare protocol proved to be an efficient tool for monitoring welfare. The results showed that factors important for extensive management are: daily monitoring; enclosures that provide sufficient feed; access to recovery enclosure; and habituation of horses to human approach.
A Prospective Post-disaster Longitudinal Follow-up Study of Emotional and Psychosocial Outcomes of the Oklahoma City Bombing Rescue and Recovery Workers During the First Quarter Century Afterward
Authors: North Carol S , McDonald Katy
Published: February 2023

Objective:

Little prospectively assessed post-disaster longitudinal research has been done on mental health (MH) outcomes of disaster rescue and recovery workers. This longitudinal prospective study, which is examining first responders to a terrorist bombing in Oklahoma City after nearly a quarter century, was conducted to investigate their long-term MH outcomes using full diagnostic assessments. This will most accurately inform planning for longitudinal MH care needs.

Methods:

Longitudinal follow-up interviews of 124 rescue and recovery workers, from an original volunteer sample of 181 volunteer workers, were completed 3 years after the bombing, and reassessed 23 years after using consistent research methods. Structured diagnostic interviews were conducted at both assessments, but these were limited to posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) with additional questions about alcohol use, problems, and major psychosocial problems of life at follow up.

Results:

Initially, the rescue and recovery workers had a lower prevalence of post-disaster PTSD and MDD than directly exposed survivors. They also showed higher rates of PTSD than MDD. However, over time, PTSD increased a little while MDD increased 4-fold though fewer than 50% of the cases were remitted.

Conclusion:

Low remission and increasing MDD provide incentives for surveillance and availability of treatment for decades after disaster, regardless of whether they were pre-existing conditions or disaster related.
How spanwise travelling transversal surface waves change the near-wall flow
Authors: Mäteling Esther , Albers Marian , Schröder Wolfgang
Published: February 2023

The alteration of the near-wall flow field of a turbulent boundary layer flow subjected to spanwise travelling transversal surface waves at a friction Reynolds number

$Re_\tau \approx 1525$

is investigated. The results of a spatial noise-assisted multivariate empirical mode decomposition reveal that this flow control method periodically induces near-wall large-scale bursts while simultaneously lowering the energetic content of small-scale features. The increasing occurrence of intense large-scale ejections in the near-wall region is of particular importance for reducing the wall-shear stress since these ejections balance large-scale sweeps originating from the outer layer. Thus, they corrupt the outer-layer impact on the near-wall dynamics and, consequently, the overall fluctuation intensity at the wall is attenuated. This disturbed top-down momentum exchange is highlighted by an inner–outer interaction analysis, which further reveals an increased bottom-up communication provoked by the large-scale ejections. Moreover, it is shown that the periodic secondary flow field induced by the actuation interferes with the quasi-streamwise vortices in the near-wall region. The velocity gradients of the secondary flow field deform the vortices’ cross-section into an elliptic shape, which yields an unstable vortex state resulting in vortex disintegration. In combination with the effect of the large-scale ejections, the reduced number of quasi-streamwise vortices compared with the undisturbed boundary layer flow results in a decreased wall-normal momentum exchange and the widening and weakening of near-wall streaks. This yields a reduced fluctuation intensity in the near-wall region that lowers the overall wall-shear stress level.
COMPLETENESS OF THE GÖDEL–LÖB PROVABILITY LOGIC FOR THE FILTER SEQUENCE OF NORMAL MEASURES
Authors: GOLSHANI MOHAMMAD , ZOGHIFARD REIHANE
Published: February 2023

Assuming the existence of suitable large cardinals, we show it is consistent that the Provability logic
$\mathbf {GL}$
is complete with respect to the filter sequence of normal measures. This result answers a question of Andreas Blass from 1990 and a related question of Beklemishev and Joosten.
How can deep time perspectives contribute to tackling contemporary One Health challenges, improving understanding and disease mitigation?
Authors: Bendrey Robin , Fournié Guillaume
Published: February 2023

The One Health concept explicitly acknowledges that the well-being of humans, animals and environments are linked. These relationships are complex and dynamic, evolving through time. Temporal perspectives also frame biological evolution and contextualise changes in our knowledge base and disease mitigation measures.
Evaluating the outcomes of children undergoing lacrimal surgery for congenital nasolacrimal duct obstruction with the aim of developing a patient pathway for children presenting to a tertiary paedatric service with epiphora
Authors: Sooby P , Wynne D
Published: February 2023

Objective

Nasolacrimal duct obstruction is the most common cause of epiphora in children. Management has classically focused on probing and syringing followed by stent insertion and dacryocystorhinostomy either externally or endonasally. This study aimed to assess the effectiveness and safety of these procedures.

Methods

This was a retrospective analysis of the outcomes of all patients under the age of 16 who have undergone a surgical lacrimal intervention for nasolacrimal duct obstruction under general anaesthetic over a 10-year period. Outcomes included success rates and complications.

Results

A total of 432 patients were identified. Primary probe and syringing had a success rate of 83 per cent. Primary endonasal dacryocystorhinostomy had a success rate of 71 per cent, and revision surgery had a success rate of 82 per cent.

Conclusion

Endonasal dacryocystorhinostomy is an effective and safe technique for the treatment of epiphora, and this study has provided a suggested protocol for management of patients presenting with epiphora.
Challenging deficit frameworks in research on heritage language bilingualism
Authors: Higby Eve , Gámez Evelyn , Holguín Mendoza Claudia
Published: February 2023

Recent years have seen an increased interest in the study of heritage language bilinguals. However, much of the research on heritage bilingualism is fraught with deficit framing. In this article, we demonstrate how many of the assumptions that underlie this growing field of research and the way that heritage speakers are positioned as research subjects reveal ideologies that center and value monolingualism and whiteness. We problematize a number of ways in which these ideologies commonly show up in the frameworks and methodologies used in psycholinguistics to study this population. We advocate for frameworks such as usage-based linguistics and multicompetence that center the multidimensional experiences of bilinguals and embrace nuance and complexity. We call on the research community to examine their research designs and theories to dismantle the systems that maintain heritage bilingualism at the margins of bilingualism research.
A metaphorical advantage for bilingual children? Understanding figurative meaning by L2 and L3 EFL learners
Authors: ALIPOUR Javad , RANJBAR Maryam
Published: February 2023

This study compared school-aged monolingual and bilingual English-as-a-foreign-language (EFL) learners in terms of understanding metaphors on recall, multiple-choice, and reasoning tasks. It also examined the relationship between cognitive capacity and understanding metaphors on different measures. A hundred and thirty Persian–Turkish early bilinguals and 122 monolingual Persian-speaking EFL learners took three different tests of metaphor comprehension and the Figural Intersections Test, a test of cognitive capacity. Bilinguals outperformed monolinguals in terms of cognitive capacity and understanding metaphors on two of the tasks, though with a small effect size. Furthermore, there was a significant positive relationship between cognitive capacity and the scores on the multiple-choice and reasoning tests, but not the recall test. Results suggest that bilingual L3 learners have an edge in understanding metaphors, reflecting a cognitive advantage.
Bringing the Party Back into the Community: Restructuring Grassroots Governance in Shenzhen
Authors: Cai Changkun , Liu Ying , Jiang Weiqi
Published: February 2023

While burgeoning research on China's state–society relations has paid attention to the Party, little is known about how the Party interacts with diverse actors and involves itself at the grassroots level in a specific region. This article delineates Party-advancement strategies at the community level in Shenzhen since 2013. To reclaim its leading role at the grassroots level, the Party opted for “Party–government disaggregation” by framing community governance as a Party-building affair, separating the government's affairs from those of the Party and “kicking” the government out of the community. Under the rubric of “reshaping Party–mass relations,” the Party penetrated deep into the community by innovating a “centre-periphery” organizational system, absorbing community elites in a top-down way and using a “service delivery taking the lead” method in a reciprocal exchange. In the end, the Party-governance structure, in which Party–mass relations are at the core, was reframed in the communities.
‘The dialogue between a cat and a mouse’ inMahābhārata12.136 and narratives about spiritual liberation (mokṣa) in Ancient Indian literature
Authors: Negribs Valters
Published: February 2023

‘The dialogue between a cat and a mouse’ (Mārjāramūṣakasaṃvāda) is an animal fable used in theMahābhāratato provide instruction in statecraft (nīti). This article argues that theMahābhārataversion of this tale must be based on an earlier soteriological allegory about a brahmin who provides spiritual liberation to a king in exchange for protection. TheMārjāramūṣakasaṃvādaabounds in terms and phrases that, in addition to their everyday meanings, have a technical or typical usage in the ascetic traditions of Ancient India. Moreover, the conversation between the cat and the mouse resembles that between a teacher and a disciple, rather than a discussion of a possible alliance between two kings. The hunter of theMārjāramūṣakasaṃvādacan be identified with the Buddhist Māra. To support the plausibility of this soteriological reading, the article includes a discussion of Buddhistjātakas with a similar plot.
‘The Whole Nature of the Child’: Children and Youth at the Lambeth Conferences
Authors: García Emily J.
Published: February 2023

This article examines the ways the Lambeth Conference resolutions discuss children and youth. It is a contribution to the work of identifying historical Anglican theological perspectives on children. Opening with a brief definition and review of theologies of childhood, it then presents chronologically (1857–1998) and briefly analyzes the resolutions which name ‘children’ or ‘youth’; it closes with an analysis of how the Lambeth resolutions map onto three basic claims shared by the reviewed theologies of childhood.
Rapid 21st Century Weakening of the Agulhas Current in a Warming Climate
Authors: Zhang Ruize , Sun Shantong , Chen Zhaohui , Yang Haiyuan , Wu Lixin
Published: February 2023

The Agulhas Current (AC) is a critical component of the global ocean circulation. Climate models consistently project the AC to decline in the 21st century. Previous studies typically attributed the weakening of AC to changes in Indian Ocean wind and/or a decline of the Indonesian Throughflow (ITF) transport. However, our analysis suggests that changes in local surface wind and ITF can only explain a portion of the model‐simulated AC changes. Using a hierarchy of models, we show that the decline of the Atlantic Meridional Overturning Circulation (AMOC) strength in a warming climate could also contribute substantially to the AC weakening. Following a weakening of the AMOC, the baroclinic structure of the AC is also modified such that the AC is shoaled to a shallower depth, communicated between basins via Kelvin waves. Our results highlight the importance of remote processes in future western boundary current changes.
Can Clay Mimic the High Reflectivity of Briny Water Below the Martian SPLD?
Authors: Cosciotti Barbara , Mattei Elisabetta , Brin Alessandro , Lauro Sebastian Emanuel , Stillman David E. , Cunje Alister , Hickson Dylan , Caprarelli Graziella , Pettinelli Elena
Published: February 2023

It has recently been suggested that clay minerals, which are widespread on the Martian surface, could be the possible source of the basal bright reflections detected by MARSIS at Ultimi Scopuli, instead of briny water. This hypothesis is based on dielectric measurements on a wet Ca‐Montorillonite (STx‐1b) sample conducted at 230 K, which reported permittivity values (apparent permittivity of 39 at 4 MHz) compatible with the median value of 33 retrieved by MARSIS 4 MHz data inversion in the high reflectivity area. These experimental results are, however, incompatible with well‐established dielectric theory and with laboratory measurements on clays, at MARSIS frequency and Martian temperatures, reported in the literature. Here, we replicate the experiment using a setup to precisely control the rate of cooling/warming and the temperature inside and outside the clay sample. We found that the rate of cooling, the position of the temperature sensor and, consequently, the thermal equilibrium between the sample and the sensor play a fundamental role in the reliability of the measurements. Our results indicate that even for a large water content in the clay sample, at 230 K and 4 MHz, the apparent permittivity is only 8.4, dropping to 4.1 at 200 K, ruling out clays as a possible source of the bright reflections detected by MARSIS at the base of the SPLD.
The association between patterns of early respiratory disease and diastolic dysfunction in preterm infants
Authors: de Waal Koert , Crendal Edward , Poon Amy Chin-Yu , Latheef Mariyam Shaya , Sachawars Elias , MacDougall Thomas , Phad Nilkant
Published: February 2023

Background

This study aims to determine the association between clinical patterns of early respiratory disease and diastolic dysfunction in preterm infants.

Methods

Preterm infants <29 weeks’ gestation underwent cardiac ultrasounds around day 7 and 14–21. Respiratory dysfunction patterns were classified as stable (ST), respiratory deterioration (RD) or early persistent respiratory dysfunction (EPRD) according to oxygen need. Diastolic dysfunction was diagnosed using a multi-parameter approach including left atrial strain (LASR) to help differentiate between cardiac or pulmonary pathophysiology.

Results

98 infants (mean 27 weeks) were included. The prevalence of ST, RD and EPRD was 53%, 21% and 26% respectively. Diastolic dysfunction was more prevalent in the RD and EPRD groups with patent ductus arteriosus and significant growth restriction as risk factors. Not all infants with a PDA developed diastolic dysfunction. LASR was lower in the EPDR group.

Conclusion

Respiratory dysfunction patterns are associated with diastolic dysfunction in preterm infants.
Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value
Authors: Franken André , Kraemer Annika , Sicking Alicia , Watolla Meike , Rivandi Mahdi , Yang Liwen , Warfsmann Jens , Polzer Bernhard M. , Friedl Thomas W. P. , Meier-Stiegen Franziska , Stoecklein Nikolas H. , Dayan Davut , Riethdorf Sabine , Mueller Volkmar , Pantel Klaus , Koch André , Hartkopf Andreas D. , Krawczyk Natalia , Ruckhaeberle Eugen , Niederacher Dieter , Fehm Tanja , Neubauer Hans
Published: February 2023

Background

Circulating tumour cells (CTCs) are mainly enriched based on the epithelial cell adhesion molecule (EpCAM). Although it was shown that an EpCAM low-expressing CTC fraction is not captured by such approaches, knowledge about its prognostic and predictive relevance and its relation to EpCAM-positive CTCs is lacking.

Methods

We developed an immunomagnetic assay to enrich CTCs from metastatic breast cancer patients EpCAM independently using antibodies against Trop-2 and CD-49f and characterised their EpCAM expression. DNA of single EpCAM high expressing and low expressing CTCs was analyzed regarding chromosomal aberrations and predictive mutations. Additionally, we compared CTC-enrichment on the CellSearch system using this antibody mix and the EpCAM based enrichment.

Results

Both antibodies acted synergistically in capturing CTCs. Patients with EpCAM high-expressing CTCs had a worse overall and progression-free survival. EpCAM high- and low-expressing CTCs presented similar chromosomal aberrations and mutations indicating a close evolutionary relationship. A sequential enrichment of CTCs from the EpCAM-depleted fraction yielded a population of CTCs not captured EpCAM dependently but harbouring predictive information.

Conclusions

Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumour surrogate material—although they may be prognostically less relevant than EpCAM high-expressing CTCs—and have particular benefit if no CTCs are detected using EpCAM-dependent technologies.
Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?
Authors: Lord Simon R. , Harris Adrian L.
Published: February 2023

Over the past 15 years, there has been great interest in the potential to repurpose the diabetes drug, metformin, as a cancer treatment. However, despite considerable efforts being made to investigate its efficacy in a number of large randomised clinical trials in different tumour types, results have been disappointing to date. This perspective article summarises how interest initially developed in the oncological potential of metformin and the diverse clinical programme of work to date including our contribution to establishing the intra-tumoral pharmacodynamic effects of metformin in the clinic. We also discuss the lessons that can be learnt from this experience and whether a further clinical investigation of metformin in cancer is warranted.
Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis
Authors: Niu Shudong , Cheng Kaixin , Jia Longzhong , Liang Jing , Mu Lu , Wang Yibo , Yang Xuebing , Yang Chen , Zhang Yan , Wang Chao , Huang Lijun , Wang Huarong , Zhang Shuang , Zhang Hua
Published: February 2023

Ovarian granulosa cell tumors (GCTs) originate from granulosa cells (GCs) and represent the most common sex cord-stromal tumor in humans. However, the developmental regulations and molecular mechanisms underlying their etiology are largely unknown. In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo. Together, our study has revealed an immune evasion mechanism via CD24/CD47 upregulation to GCT formation, shedding light on the future potential clinical therapies for GCTs.
High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq
Authors: Liu Yang , DiStasio Marcello , Su Graham , Asashima Hiromitsu , Enninful Archibald , Qin Xiaoyu , Deng Yanxiang , Nam Jungmin , Gao Fu , Bordignon Pino , Cassano Marco , Tomayko Mary , Xu Mina , Halene Stephanie , Craft Joseph E. , Hafler David , Fan Rong
Published: February 2023

In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site.
Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis
Authors: Hendriks Delilah , Brouwers Jos F. , Hamer Karien , Geurts Maarten H. , Luciana Léa , Massalini Simone , López-Iglesias Carmen , Peters Peter J. , Rodríguez-Colman Maria J. , Chuva de Sousa Lopes Susana , Artegiani Benedetta , Clevers Hans
Published: February 2023

The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity of human-relevant models for target discovery and compound screening. Here we use human fetal hepatocyte organoids to model the first stage of NAFLD, steatosis, representing three different triggers: free fatty acid loading, interindividual genetic variability (PNPLA3 I148M) and monogenic lipid disorders (APOB and MTTP mutations). Screening of drug candidates revealed compounds effective at resolving steatosis. Mechanistic evaluation of effective drugs uncovered repression of de novo lipogenesis as the convergent molecular pathway. We present FatTracer, a CRISPR screening platform to identify steatosis modulators and putative targets using APOB−/− and MTTP−/− organoids. From a screen targeting 35 genes implicated in lipid metabolism and/or NAFLD risk, FADS2 (fatty acid desaturase 2) emerged as an important determinant of hepatic steatosis. Enhancement of FADS2 expression increases polyunsaturated fatty acid abundancy which, in turn, reduces de novo lipogenesis. These organoid models facilitate study of steatosis etiology and drug targets.
Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4
Authors: Blanco-Míguez Aitor , Beghini Francesco , Cumbo Fabio , McIver Lauren J. , Thompson Kelsey N. , Zolfo Moreno , Manghi Paolo , Dubois Leonard , Huang Kun D. , Thomas Andrew Maltez , Nickols William A. , Piccinno Gianmarco , Piperni Elisa , Punčochář Michal , Valles-Colomer Mireia , Tett Adrian , Giordano Francesca , Davies Richard , Wolf Jonathan , Berry Sarah E. , Spector Tim D. , Franzosa Eric A. , Pasolli Edoardo , Asnicar Francesco , Huttenhower Curtis , Segata Nicola
Published: February 2023

Metagenomic assembly enables new organism discovery from microbial communities, but it can only capture few abundant organisms from most metagenomes. Here we present MetaPhlAn 4, which integrates information from metagenome assemblies and microbial isolate genomes for more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01 M prokaryotic reference and metagenome-assembled genomes, we define unique marker genes for 26,970 species-level genome bins, 4,992 of them taxonomically unidentified at the species level. MetaPhlAn 4 explains ~20% more reads in most international human gut microbiomes and >40% in less-characterized environments such as the rumen microbiome and proves more accurate than available alternatives on synthetic evaluations while also reliably quantifying organisms with no cultured isolates. Application of the method to >24,500 metagenomes highlights previously undetected species to be strong biomarkers for host conditions and lifestyles in human and mouse microbiomes and shows that even previously uncharacterized species can be genetically profiled at the resolution of single microbial strains.
Network expansion of genetic associations defines a pleiotropy map of human cell biology
Authors: Barrio-Hernandez Inigo , Schwartzentruber Jeremy , Shrivastava Anjali , del-Toro Noemi , Gonzalez Asier , Zhang Qian , Mountjoy Edward , Suveges Daniel , Ochoa David , Ghoussaini Maya , Bradley Glyn , Hermjakob Henning , Orchard Sandra , Dunham Ian , Anderson Carl A. , Porras Pablo , Beltrao Pedro
Published: February 2023

Interacting proteins tend to have similar functions, influencing the same organismal traits. Interaction networks can be used to expand the list of candidate trait-associated genes from genome-wide association studies. Here, we performed network-based expansion of trait-associated genes for 1,002 human traits showing that this recovers known disease genes or drug targets. The similarity of network expansion scores identifies groups of traits likely to share an underlying genetic and biological process. We identified 73 pleiotropic gene modules linked to multiple traits, enriched in genes involved in processes such as protein ubiquitination and RNA processing. In contrast to gene deletion studies, pleiotropy as defined here captures specifically multicellular-related processes. We show examples of modules linked to human diseases enriched in genes with known pathogenic variants that can be used to map targets of approved drugs for repurposing. Finally, we illustrate the use of network expansion scores to study genes at inflammatory bowel disease genome-wide association study loci, and implicate inflammatory bowel disease-relevant genes with strong functional and genetic support.
CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions
Authors: Liu Pu-Ste , Chen Yi-Ting , Li Xiaoyun , Hsueh Pei-Chun , Tzeng Sheue-Fen , Chen Hsi , Shi Pei-Zhu , Xie Xin , Parik Sweta , Planque Mélanie , Fendt Sarah-Maria , Ho Ping-Chih
Published: February 2023

Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD+/NADH ratio via glutamine-to-lactate conversion. Genetic ablation of important metabolic enzymes involved in CD40-mediated metabolic reprogramming abolishes agonistic anti-CD40-induced antitumor responses and reeducation of tumor-associated macrophages. Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments.
Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial
Authors: Mellinghoff Ingo K. , Lu Min , Wen Patrick Y. , Taylor Jennie W. , Maher Elizabeth A. , Arrillaga-Romany Isabel , Peters Katherine B. , Ellingson Benjamin M. , Rosenblum Marc K. , Chun Saewon , Le Kha , Tassinari Ania , Choe Sung , Toubouti Youssef , Schoenfeld Steven , Pandya Shuchi S. , Hassan Islam , Steelman Lori , Clarke Jennifer L. , Cloughesy Timothy F.
Published: February 2023

Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDHglioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration ofd-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1–97.6) and 91.1% (95% CrI, 72.0–97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of ‘proneural’ and ‘stemness’ gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDHLGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.
The shape parameters of coal and gangue particles derived from 3D scanning
Authors: Yang Daolong , Tang Jinjing , Hu Ningning , Xia Youtao , Yu Yanting , Huang Qianqian
Published: February 2023

The irregular shape of mineral particles directly affects the angle of repose, bulk density and flow-properties, and the interaction behaviour between the particles and a contact surface. This paper presents a dataset of spatial data and shape parameters collected from 37 gangue particles and 135 anthracite coal particles, which come from the Shangzhuang Coal Mine. The particle surface models were obtained by a Wiiboox white light raster 3D scanner and Reeyee software. To obtain the scanning surface, each particle was scanned 8 times in different axial rotation directions. The final scanning model was obtained by stacking two scanning surfaces, and the shape parameters, such as length ratio, flatness ratio, and Zingg index, were obtained. This dataset is particularly useful for researchers and engineers who want to investigate the shape of coal and gangue particles or who want to test or benchmark measurement methods concerning the three-dimensional morphology of particles.
Numerical simulation on energy transfer enhancement of a Williamson ferrofluid subjected to thermal radiation and a magnetic field using hybrid ultrafine particles
Authors: Swalmeh Mohammed Z. , Alwawi Firas A. , Kausar Muhammad Salman , Ibrahim Mohd Asrul Hery , Hamarsheh Abdulkareem Saleh , Sulaiman Ibrahim Mohammed , Awwal Aliyu Muhammed , Pakkaranang Nuttapol , Panyanak Bancha
Published: February 2023

In this numerical investigation, completely developed laminar convective heat transfer characteristics of a Williamson hybrid ferronanofluid over a cylindrical surface are reported. This new model in 2D is engaged to examine the effects of the magnetic field, thermal radiation factor, volume fraction of ultrafine particles, and Weissenberg number with the help of the Keller box method. The numerical calculations are implemented at a magnetic parameter range of 0.4 to 0.8, volume fraction range of 0.0 to 0.1, and a Weissenberg number range of 0.1 to 0.8. The numerical outcomes concluded that the velocity increases when the thermal radiation parameter and the volume fraction of a nanoparticle are increased, but inverse impacts are obtained for the magnetic parameter and the Weissenberg number. The rate of energy transport increases with increasing thermal radiation and volume fraction, while it declines with increasing the magnetic parameter and Weissenberg number. The drag force shows a positive relationship with the thermal radiation parameter and has an opposite relationship with the Weissenberg number and the magnetic parameter. Furthermore, even when the magnetic field, thermal radiation, volume fraction, and Weissenberg number are all present, the heat transfer rate of Williamson hybrid ferronanofluid is greater than that of mono Williamson ferronanofluid.
Independence and upper extremity functioning after spinal cord injury: a cross-sectional study
Authors: Lili Lamprini , Sunnerhagen Katharina S. , Rekand Tiina , Alt Murphy Margit
Published: February 2023

Upper extremity functioning is important for achieving independence in activities of daily living (ADL). A better understanding of relationships between different aspects of independence in ADL after spinal cord injury (SCI) and upper extremity functioning is required to guide rehabilitation practices. To determine which aspects of independence in ADL are correlated with upper extremity functioning in individuals with cervical or thoracic SCI. A total of 25 adults (mean age 58.4 years, 72% men) with established cervical or thoracic SCI were recruited. Independence in ADL was assessed by Spinal Cord Independence Measure (SCIM-III) and upper extremity functioning by kinematic measures (movement time, smoothness, and wrist angle during drinking task), grip strength, Upper Extremity Motor and Sensory Score, Box and Block Test (BBT), Action Research Arm Test (ARAT), and Upper Extremity Basic Data Set (ISCI-Hand and ISCI-Shoulder). Spearman correlation coefficients were used for data analyses. The SCIM-self-care subscale, particularly the feeding and dressing items, correlated moderately (r ≥ 0.5) with movement time and smoothness, grip strength, ARAT, BBT, and ISCI-Hand. The SCIM-respiration/sphincter subscale and the SCIM-mobility showed very low and low correlations with upper extremity assessments. However, at item level, respiration and bed/wheelchair mobility showed moderate correlations. Independence in self-care as domain and feeding/dressing, respiration and bed/wheelchair mobility as separate items were dependent on upper extremity functioning in individuals with cervical or thoracic SCI. Movement time and smoothness along with BBT, grip strength, ARAT, and ISCI-Hand can be used as indicators of independence in ADL. These findings can provide guidance to clinical practice in selection of upper extremity assessments in the context for ADL in individuals with SCI.
Estimation of rocks’ failure parameters from drilling data by using artificial neural network
Authors: Siddig Osama , Ibrahim Ahmed Farid , Elkatatny Salaheldin
Published: February 2023

Comprehensive and precise knowledge about rocks' mechanical properties facilitate the drilling performance optimization, and hydraulic fracturing design and reduces the risk of wellbore-related problems. This paper is concerned with the failure parameters, namely, cohesion and friction angle which are conventionally estimated using Mohr's cycles that are drawn using compressional tests on rock samples. The availability, continuity and representability, and cost of acquiring those samples are major concerns. The objective of this paper is to investigate an alternative technique to estimate these parameters from the drilling data. In this work, more than 2200 data points were used to develop and test the correlations built by the artificial neural network. Each data point comprises the failure parameters and five drilling records that are available instantaneously in drilling rigs such as rate of penetration, weight on bit, and torque. The data were grouped into three datasets, training, testing, and validation with a corresponding percentage of 60/20/20, the former two sets were utilized in the models' building while the last one was hidden as a final check afterward. The models were optimized and evaluated using the correlation coefficient (R) and average absolute percentage error (AAPE). In general, the two models yielded good fits with the actual values. The friction angle model yielded R values around 0.86 and AAPE values around 4% for the three datasets. While the model for cohesion resulted in R values around 0.89 and APPE values around 6%. The equation and the parameters of those models are reported in the paper. These results show the ability of in-situ and instantaneous rock mechanical properties estimation with good reliability and at no additional costs.
Assessing brain state and anesthesia level with two-photon calcium signals
Authors: Tort-Colet Núria , Resta Francesco , Montagni Elena , Pavone Francesco , Allegra Mascaro Anna Letizia , Destexhe Alain
Published: February 2023

Brain states, such as wake, sleep, or different depths of anesthesia are usually assessed using electrophysiological techniques, such as the local field potential (LFP) or the electroencephalogram (EEG), which are ideal signals for detecting activity patterns such as asynchronous or oscillatory activities. However, it is technically challenging to have these types of measures during calcium imaging recordings such as two-photon or wide-field techniques. Here, using simultaneous two-photon and LFP measurements, we demonstrate that despite the slower dynamics of the calcium signal, there is a high correlation between the LFP and two-photon signals taken from the neuropil outside neuronal somata. Moreover, we find the calcium signal to be systematically delayed from the LFP signal, and we use a model to show that the delay between the two signals is due to the physical distance between the recording sites. These results suggest that calcium signals alone can be used to detect activity patterns such as slow oscillations and ultimately assess the brain state and level of anesthesia.
Development of a chub mackerel with less-aggressive fry stage by genome editing of arginine vasotocin receptor V1a2
Authors: Ohga Hirofumi , Shibata Koki , Sakanoue Ryo , Ogawa Takuma , Kitano Hajime , Kai Satoshi , Ohta Kohei , Nagano Naoki , Nagasako Tomoya , Uchida Seiichi , Sakuma Tetsushi , Yamamoto Takashi , Kim Sangwan , Tashiro Kosuke , Kuhara Satoru , Gen Koichiro , Fujiwara Atushi , Kazeto Yukinori , Kobayashi Takanori , Matsuyama Michiya
Published: February 2023

Genome editing is a technology that can remarkably accelerate crop and animal breeding via artificial induction of desired traits with high accuracy. This study aimed to develop a chub mackerel variety with reduced aggression using an experimental system that enables efficient egg collection and genome editing. Sexual maturation and control of spawning season and time were technologically facilitated by controlling the photoperiod and water temperature of the rearing tank. In addition, appropriate low-temperature treatment conditions for delaying cleavage, shape of the glass capillary, and injection site were examined in detail in order to develop an efficient and robust microinjection system for the study. An arginine vasotocin receptor V1a2 (V1a2) knockout (KO) strain of chub mackerel was developed in order to reduce the frequency of cannibalistic behavior at the fry stage. Video data analysis using bioimage informatics quantified the frequency of aggressive behavior, indicating a significant 46% reduction (P = 0.0229) in the frequency of cannibalistic behavior than in wild type. Furthermore, in the V1a2 KO strain, the frequency of collisions with the wall and oxygen consumption also decreased. Overall, the manageable and calm phenotype reported here can potentially contribute to the development of a stable and sustainable marine product.
The tumor biological significance of RNF43 and LRP1B in gastric cancer is complex and context-dependent
Authors: Holm Bente , Barsuhn Stephan , Behrens Hans-Michael , Krüger Sandra , Röcken Christoph
Published: February 2023

Gastric cancer (GC) is the fifth most common cancer in the world with a poor prognosis. Both RNF43 and LRP1B function as tumor suppressors in the Wnt signaling pathway and have been described to be frequently mutated in GC. In this study of a large and well characterized cohort of 446 GCs we explored the significance of expression of RNF43 and LRP1B and their correlations with clinicopathological patient characteristics. Immunostaining of whole mount tissue sections was documented with the histoscore. Dichotomized at the median, we separated the cohort into a low/negative and a high/positive group of RNF43 and LRP1B expression, respectively. Apart from the entire cohort, we also examined the intestinal and diffuse type GCs separately. Regarding the entire cohort, the expression of RNF43 and LRP1B correlated significantly with the Lauren phenotype and with each other. Interestingly, differences were noted regarding RNF43 between the intestinal and diffuse type GCs. Survival analysis of the intestinal type GCs showed that RNF43 low/negative GCs tended to have a better outcome compared with RNF43 high/positive GCs [24.5 months overall survival (OS) and 25.0 months tumor-specific survival (TSS) vs. 14.1 months OS and 17.9 months TSS, respectively]. To the contrary, diffuse type GCs with RNF43 low/negative had a worse outcome compared with RNF43 high/positive GCs (12.9 months OS and 18.2 months TSS vs. 17.1 months OS and 21.5 months TSS, respectively). On multivariate analysis, RNF43 low/negative versus high/positive was an independent prognosticator of survival in diffuse type GC (hazard ratio 2.393 for OS and 2.398 for TSS). These data support the contention that the expression and biological effect of RNF43 and LRP1B in GC is context-dependent.
Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review
Authors: Nguyen Thu Hang , Nguyen Hung Anh , Tran Thi Y-Van , Hoang Tran Donna , Cao Hung , Chu Duc Trinh , Bui Tung Thanh , Do Quang Loc
Published: February 2023

This review focuses on the theoretical concepts, electrode engineering, data analytics, and biomedical applications of electric and electrochemical microfluidic platforms, and highlights future directions for development.
Morphology dependent light-induced photoluminescence enhancement of CsPbBr3 microcrystals
Authors: Ye Xin , Li Cuicui , Jiang Jinke , Zheng Xiaoxin , Han Quangxiang , Lin Qinglian , Liu Yang , Tao Xutang
Published: February 2023

High luminescent CsPbBr3 cube and prism microcrystals were grown by microspacing in-air sublimation, based on which morphology dependence of the light-induced photoluminescence enhancement was comprehensively investigated.
Stable and microporous covalent organic frameworks via weak interactions for gas uptake
Authors: Wang Zhitao , Li Xiu-Mei , Li Hui
Published: February 2023

Here, we reported two stable and micro-porous covalent organic frameworks for gas uptake.
Photo-oxidation reaction of tert-butyl chloride with OH radicals and Cl atoms in the troposphere and its implications
Authors: Joy Fredy , Rajakumar Balla
Published: February 2023

Temperature-dependent kinetics of the photo-oxidation of tert-butyl chloride with OH radicals and Cl atoms were investigated to determine their impact in the troposphere. The kinetics were determined both experimentally and computationally.