bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of
Bacteroides thetaiotaomicron
bile acid-altering enzymes impacts bacterial fitness and the global metabolic transcriptome
Authors: McMillan Arthur S. , Foley Matthew H. , Perkins Caroline E. , Theriot Casey M.
Published: November 2023

Bacteroides thetaiotaomicron
(
B. theta
) is a Gram-negative gut bacterium that encodes enzymes that alter the bile acid pool in the gut. Primary bile acids are synthesized by the host liver and are modified by gut bacteria.
B. theta
encodes two bile salt hydrolases, as well as a hydroxysteroid dehydrogenase. We hypothesize that
B. theta
modifies the bile acid pool in the gut to provide a fitness advantage for itself. To investigate each gene’s role, different combinations of genes encoding bile acid-altering enzymes (
bshA
,
bshB
, and
hsdhA
) were knocked out by allelic exchange, including a triple KO. Bacterial growth and membrane integrity assays were done in the presence and absence of bile acids. To explore if
B. theta’s
response to nutrient limitation changes due to the presence of bile acid-altering enzymes, RNA sequencing (RNASeq) analysis of wild type (WT) and triple knockout (KO) strains in the presence and absence of bile acids was done. WT
B. theta
is more sensitive to deconjugated bile acids such as cholate, chenodeoxycholate (CDCA), and deoxycholate (DCA) compared with the triple KO. These deconjugated bile acids also decreased membrane integrity of both WT and triple KO. The presence of
bshB
is detrimental to growth in conjugated forms of CDCA and DCA. RNASeq analysis also showed that bile acid exposure impacts multiple metabolic pathways in
B. theta
, but DCA significantly increases expression of many genes in carbohydrate metabolism, specifically those in polysaccharide utilization loci or PULs, in nutrient-limited conditions. This study suggests that bile acids
B. theta
encounters in the gut may signal the bacterium to increase or decrease its utilization of carbohydrates. Further study looking at the interactions between bacteria, bile acids, and the host may inform rationally designed probiotics and diets to ameliorate inflammation and disease.

IMPORTANCE

Recent work on bile salt hydrolases (BSHs) in Gram-negative bacteria, such as Bacteroides, has primarily focused on how they can impact host physiology. However, the benefits bile acid metabolism confers to the bacterium that performs it are not well understood. In this study, we set out to define if and how
Bacteroides thetaiotaomicron
(
B. theta
) uses its BSHs and hydroxysteroid dehydrogenase to modify bile acids to provide a fitness advantage for itself
in vitro
and
in vivo
. Genes encoding bile acid-altering enzymes were able to impact how
B. theta
responds to nutrient limitation in the presence of bile acids, specifically carbohydrate metabolism, affecting many polysaccharide utilization loci. This suggests that
B. theta
may be able to shift its metabolism, specifically its ability to target different complex glycans including host mucin, when it comes into contact with specific bile acids in the gut.
Einstein Manifold of SO(p, 9 – p), Its Corresponding Parabolic Subgroup, and Invariant Differential Operators
Authors: Dobrev V. K.
Published: November 2023

In the present paper we continue the project of systematic explicit construction of invariant differential operators. On the example of the non-compact group$$SO(p,9 - p)$$(for$$p = 5,6$$) we give the classification multiplets of indecomposable elementary representations induced from suitable choice of parabolic subgroup$$MAN$$so that the factor-group$${G \mathord{\left/ {\vphantom {G M}} \right. \kern-0em} M}$$is an Einstein manifold. This classification includes the data for the relevant invariant differential operators.
A youth-centred approach to improving engagement in HIV services: human-centred design methods and outcomes in a research trial in Kisumu County, Kenya
Authors: Akama Eliud Omondi , Beres Laura K , Kulzer Jayne Lewis , Ontuga Gladys , Adhiambo Harriet , Bushuru Sarah , Nyagesoa Edwin , Osoro Joseph , Opondo Isaya , Sang Norton , Oketch Bertha , Nyanga James , Osongo Cirilus Ogollah , Nyandieka Evelyn , Ododa Evelyn , Omondi Eunice , Ochieng Felix , Owino Clinton , Odeny Thomas , Kwena Zachary Arochi , Eshun-Wilson Ingrid , Petersen Maya , Bukusi Elizabeth A , Geng Elvin H , Abuogi Lisa L
Published: November 2023

Introduction

Innovative interventions are needed to improve HIV outcomes among adolescents and young adults (AYAs) living with HIV. Engaging AYAs in intervention development could increase effectiveness and youth acceptance, yet research is limited. We applied human-centred design (HCD) to refine adherence-support interventions pretrial and assessed HCD workshop acceptability.

Methods

We applied an iterative, four-phased HCD process in Kenya that included: (1) systematic review of extant knowledge, (2) prioritisation of design challenges, (3) a co-creation workshop and (4) translation tables to pair insights with trial intervention adaptations. The co-creation workshop was co-led by youth facilitators employing participatory activities to inform intervention adaptations. Iterative data analysis included rapid thematic analysis of visualised workshop outputs and notes using affinity mapping and dialogue to identify key themes. We conducted a survey to assess workshop acceptability among participants.

Results

Twenty-two participants engaged in the 4-day workshop. Co-creation activities yielded recommendations for improving planned interventions (eg, message frequency and content; strategies to engage hard-to-reach participants), critical principles to employ across interventions (eg, personalisation, AYA empowerment) and identification of unanticipated AYA HIV treatment priorities (eg, drug holidays, transition from adolescent to adult services). We revised intervention content, peer navigator training materials and study inclusion criteria in response to findings. The youth-led HCD workshop was highly acceptable to participants.

Conclusions

Research employing HCD among youth can improve interventions preimplementation through empathy, youth-led inquiry and real-time problem solving. Peer navigation may be most influential in improving retention when engagement with young people is based on mutual trust, respect, privacy and extends beyond HIV-specific support. Identifying opportunities for personalisation and adaptation within intervention delivery is important for AYAs. Patient engagement interventions that target young people should prioritise improved transition between youth and adult services, youth HIV status disclosure, AYA empowerment and healthcare worker responsiveness in interactions and episodic adherence interruptions.
Sponsorship bias in published pharmacoeconomic evaluations of national reimbursement negotiation drugs in China: a systematic review
Authors: He Zixuan , Huang Xianqin , Chen Dingyi , Wang Guoan , Zhu Yuezhen , Li Huangqianyu , Han Sheng , Shi Luwen , Guan Xiaodong
Published: November 2023

Background

China’s National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood.

Methods

We searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017–2020 NRDLs after successful negotiation. We categorised the study’s FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors’ disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2tests and conducted multivariate regression analysis.

Results

We identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p<0.01) and had a significantly higher proportion of resulting target drug economically dominated the comparison drug (p<0.05).

Conclusion

The study revealed that FCOI bias is common in published pharmacoeconomic evaluations conducted in Chinese settings and could significantly influence the study’s economical results and conclusions through various mechanisms. Multifaceted efforts are needed to improve transparency, comparability and reporting standardisation.
Treatment of overweight and obesity in general practice: a cluster randomised trial
Authors: Nilsen Morten Dag , Mdala Ibrahimu , Werner Erik L
Published: November 2023

Overweight and obesity are among the most serious health problems of our time.

A majority of patients with overweight and obesity will first get in touch with health services through primary care. This makes it crucial to develop strategies to enable physicians in primary care to help and treat patients with overweight and obesity. The physicians tend to avoid this subject. The main reason is reported to be lack of knowledge and education, and that they have nothing concrete to offer their patients.

We wanted to examine if a simple method with specific measures could be used in Norwegian general practice and achieve meaningful weight loss.

23 physicians and 210 patients participated in the study.

The physicians who participated were cluster randomised into either control group or intervention group. The physicians in the control group were told to follow their usual approach, while the physicians in the intervention group followed a fixed plan with specific diets given orally and in writing to the patients. The inclusion criteria for both groups were: body mass index (BMI)>30 kg/m2, or BMI>25 kg/m2with at least one weight-related condition. Weight was measured at the start, then after 1 year and finally after 2 years in both groups.

We found no significant weight loss in the control group. In the intervention group, there was a weight loss of at least 10% by 25.5% after the first year and 24.2% after the entire observation period. 53.5% of the patients lost at least 5% of their weight in the first year and nearly 45% after the entire observation period. We conclude that a simple tool with a specific diet and activity plan is feasible in general practice and may produce significant weight loss. Trial registration number:NCT03000062.
Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-β monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors
Authors: Bauer Todd M , Santoro Armando , Lin Chia-Chi , Garrido-Laguna Ignacio , Joerger Markus , Greil Richard , Spreafico Anna , Yau Thomas , Goebeler Maria-Elisabeth , Hütter-Krönke Marie Luise , Perotti Antonella , Juif Pierre-Eric , Lu Darlene , Barys Louise , Cremasco Viviana , Pelletier Marc , Evans Helen , Fabre Claire , Doi Toshikiko
Published: November 2023

Background

NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-β). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors.

Methods

Patients received NIS793 (0.3–1 mg/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab (NIS793 0.3–30 mg/kg Q3W and spartalizumab 300 mg Q3W or NIS793 20–30 mg/kg every 2 weeks [Q2W] and spartalizumab 400 mg every 4 weeks (Q4W)). In dose expansion, patients with non-small cell lung cancer (NSCLC) resistant to prior anti-programmed death ligand 1 or patients with microsatellite stable colorectal cancer (MSS-CRC) were treated at the recommended dose for expansion (RDE).

Results

Sixty patients were treated in dose escalation, 11 with NIS793 monotherapy and 49 with NIS793 plus spartalizumab, and 60 patients were treated in dose expansion (MSS-CRC: n=40; NSCLC: n=20). No dose-limiting toxicities were observed. The RDE was established as NIS793 30 mg/kg (2100 mg) and spartalizumab 300 mg Q3W. Overall 54 (49.5%) patients experienced ≥1 treatment-related adverse event, most commonly rash (n=16; 13.3%), pruritus (n=10; 8.3%), and fatigue (n=9; 7.5%). Three partial responses were reported: one in renal cell carcinoma (NIS793 30 mg/kg Q2W plus spartalizumab 400 mg Q4W), and two in the MSS-CRC expansion cohort. Biomarker data showed evidence of target engagement through increased TGF-β/NIS793 complexes and depleted active TGF-β in peripheral blood. Gene expression analyses in tumor biopsies demonstrated decreased TGF-β target genes and signatures and increased immune signatures.

Conclusions

In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-β pathway inhibition.

Trial registration number

NCT02947165.
TP53/mTORC1-mediated bidirectional regulation of PD-L1 modulates immune evasion in hepatocellular carcinoma
Authors: Yu Jiongjie , Ling Sunbin , Hong Jiachen , Zhang Lincheng , Zhou Wei , Yin Lu , Xu Shengjun , Que Qingyang , Wu Yongfeng , Zhan Qifan , Bao Jiaqi , Xu Nan , Liu Yuchen , Chen Kangchen , Wei Xuyong , Liu Zhikun , Feng Tingting , Zhou Lin , Xie Haiyang , Wang Shuai , Liu Jimin , Zheng Shusen , Xu Xiao
Published: November 2023

Background

Immunotherapy has facilitated great breakthroughs in the treatment of hepatocellular carcinoma (HCC). However, the efficacy and response rate of immunotherapy are limited and vary among different patients with HCC. TP53 mutation substantially affects the expression of immune checkpoint molecules in multiple cancers. However, the regulatory relationship between programmed death ligand 1 (PD-L1) and TP53 is poorly studied in HCC. We aimed to elucidate the regulatory mechanism of PD-L1 in HCC with different TP53 statuses and to assess its role in modulating immune evasion in HCC.

Methods

HCC mouse models and cell lines with different TP53 statuses were constructed. PD-L1 levels were detected by PCR, western blotting and flow cytometry. RNA-seqencing, immunoprecipitation, chromatin immunoprecipitation and transmission electron microscopy were used to elucidate the regulatory mechanism in HCC with different TP53 status. HCC mouse models and patient with HCC samples were analyzed to demonstrate the preclinical and clinical significance of the findings.

Results

We report that loss of p53 promoted PD-L1 expression and reduced CD8+T-cell infiltration in patient with HCC samples and mouse models. Mammalian target of rapamycin (mTOR) pathway was activated in p53-loss-of-function HCC or after knocking down TP53. The transcription factor E2F1 was found to bind to the p53 protein in TP53 wild-type HCC cells, and inhibiting mammalian target of rapamycin complex 1 (mTORC1) disrupted this binding and enhanced E2F1 translocation to the nucleus, where it bound to the PD-L1 promoter and transcriptionally upregulated PD-L1. In p53-loss-of-function HCC cells, autophagosomes were activated after mTORC1 suppression, promoting the degradation of PD-L1 protein. The combination of mTOR inhibitor and anti-PD-L1 antibody enhanced CD8+T-cell infiltration and tumor suppression in TP53 wild-type HCC mouse models, but no benefit was observed in p53-loss-of-function HCC mouse models. In patients with TP53 wild-type HCC, PD-L1 levels were significantly higher in the high E2F1 group than in the low E2F1 group, and the low E2F1 level group had significantly superior survival.

Conclusion

We revealed the bidirectional regulatory mechanism of PD-L1 mediated by TP53/mTORC1 in HCC. The combination of mTOR inhibitor and anti-PD-L1 antibody could be a novel precise immunotherapy scheme for TP53 wild-type HCC.
Neuromuscular and cardiovascular phenotypes in paediatric titinopathies: a multisite retrospective study
Authors: Meyer Alayne P , Barnett Cara L , Myers Katherine , Siskind Carly E , Moscarello Tia , Logan Rachel , Roggenbuck Jennifer , Rich Kelly A
Published: November 2023

Background

Pathogenic variants inTTNcause a spectrum of autosomal dominant and recessive cardiovascular, skeletal muscle and cardioskeletal disease with symptom onset across the lifespan. The aim of this study was to characterise the genotypes and phenotypes in a cohort ofTTN+paediatric patients.

Methods

Retrospective chart review was performed at four academic medical centres. Patients with pathogenic or truncating variant(s) inTTNand paediatric-onset cardiovascular and/or neuromuscular disease were eligible.

Results

31 patients from 29 families were included. Seventeen patients had skeletal muscle disease, often with proximal weakness and joint contractures, with average symptom onset of 2.2 years. Creatine kinase levels were normal or mildly elevated; electrodiagnostic studies (9/11) and muscle biopsies (11/11) were myopathic. Variants were most commonly identified in the A-band (14/32) or I-band (13/32). Most variants were predicted to be frameshift truncating, nonsense or splice-site (25/32). Seventeen patients had cardiovascular disease (14 isolated cardiovascular, three cardioskeletal) with average symptom onset of 12.9 years. Twelve had dilated cardiomyopathy (four undergoing heart transplant), two presented with ventricular fibrillation arrest, one had restrictive cardiomyopathy and two had other types of arrhythmias. Variants commonly localised to the A-band (8/15) or I-band (6/15) and were predominately frameshift truncating, nonsense or splice-site (14/15).

Conclusion

Our cohort demonstrates the genotype–phenotype spectrum of paediatric-onset titinopathies identified in clinical practice and highlights the risk of life-threatening cardiovascular complications. We show the difficulties of obtaining a molecular diagnosis, particularly in neuromuscular patients, and bring awareness to the complexities of genetic counselling in this population.
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series
Authors: Colmegna Ines , Valerio Valeria , Amiable Nathalie , Useche Mariana , Rampakakis Emmanouil , Flamand Louis , Rollet-Labelle Emmanuelle , Bessette Louis , Fitzcharles Mary-Ann , Hazel Elizabeth , McCormack Deirdre , Michou Laëtitia , Panopalis Pantelis , Langlois Marc-André , Bernatsky Sasha , Fortin Paul R
Published: November 2023

Objective

To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.

Methods

We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.

Results

Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2–53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection.

Conclusion

In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.
Excess mortality following a first and subsequent osteoporotic fracture: a Danish nationwide register-based cohort study on the mediating effects of comorbidities
Authors: Christensen Emilie Rosenfeldt , Clausen Anne , Petersen Tanja Gram , Skjødt Michael Kriegbaum , Abrahamsen Bo , Möller Sören , Rubin Katrine Hass
Published: November 2023

Objectives

This study aimed to examine the risk of mortality following incident and subsequent osteoporotic fractures, the effect of different fracture type combinations, and the mediating role of postfracture morbidity in a Danish population.

Methods

We used the National Patient Registry to identify patients ≥60 years with incident major osteoporotic fracture of the hip, vertebrae, wrist or humerus between 2013 and 2018, and controls matched 1:10 on age and sex. Possible mediators were identified using International Classification of Diseases, 10th Revision codes registered in the 6 months following index fracture. HRs were estimated using Cox regression analyses with 95% CIs. The effect of possible mediators was estimated using mediation analyses.

Results

The study included 106 303 patients and 1 062 988 controls. Mortality following index fracture was highest in the month following hip fractures (HR 10.98 (95% CI 10.23 to 11.79) in women and HR 16.40 (95% CI 15.00 to 17.93) in men). Subsequent hip fractures resulted in the highest HRs for all fracture type combinations. In women, the highest HR was observed in patients with index wrist/subsequent hip fractures (HR 2.43 (95% CI 2.12 to 2.78)). In men, the highest HR was observed in patients with index humerus/subsequent hip fractures (HR 2.69 (95% CI 2.04 to 3.54)). Pneumonia mediated the largest proportion of mortality, but dehydration, urinary tract infection and sepsis were also important factors.

Conclusions

The highest mortality risk was found in the month immediately following both index and subsequent fracture. The combination of index and subsequent fractures at different skeletal sites had a substantial impact on the risk of mortality. Postfracture morbidities were found mediate the association.
Chilling alcohol on the computer: isothermal compressibility and the formation of hydrogen-bond clusters in liquid propan-1-ol
Authors: Baptista Luis A. , Sevilla Mauricio , Wagner Manfred , Kremer Kurt , Cortes-Huerto Robinson
Published: November 2023

Molecular dynamics simulations have been performed to compute the isothermal compressibility $$\kappa _T$$

κ
T

of liquid propan-1-ol in the temperature range $$200 \le T\le 300$$

200
≤
T
≤
300

K. A change in behaviour, from normal (high T) to anomalous (low T), has been identified for $$\kappa _T$$

κ
T

at $$210<T<230$$

210
<
T
<
230

K. The average number of hydrogen bonds (H–bond) per molecule turns to saturation in the same temperature interval, suggesting the formation of a relatively rigid network. Indeed, simulation results show a strong tendency to form H–bond clusters with distinct boundaries, with the average largest size and width of the size distribution growing upon decreasing temperature, in agreement with previous theoretical and experimental studies. These results also emphasise a connection between the behaviour of $$\kappa _T$$

κ
T

and the formation of nanometric structures.

Graphic Abstract
Update on the Ivory-billed Woodpecker (Campephilus principalis) Scandal
Authors: Collins Michael D.
Published: November 2023

The Ivory-billed Woodpecker (Campephilus principalis) is an elusive bird that has repeatedly been feared extinct only to be rediscovered during the past hundred years. The most recent rediscovery, which took place in Arkansas, was announced in an article that was featured on the cover of Science in 2005. Despite published reports of sightings in Florida and Louisiana in the years that followed, the issue became controversial when nobody managed to obtain a clear photo and critics attacked relatively weak video evidence that was presented in the original article. The issue began to develop into a science scandal when the critics used specious arguments to delay the publication of the strongest evidence, which consists of three videos that were obtained during encounters with birds that were identified in the field as Ivory-billed Woodpeckers and that show field marks, body proportions, flights, and other behaviors that are consistent with that species but no other species of the region. The scandal culminated in a decision by the U.S. Fish & Wildlife Service to declare the species extinct in 2021, which was made without addressing the strongest evidence. An update is given here on recent developments. The decision to declare the species extinct was based on a five-year review of evidence for persistence. During an interview, it came to light that the person who performed the review was unaware of basic facts about the strongest evidence. Evidence that was obtained at another site in Louisiana [Latta et al., “Multiple lines of evidence suggest the persistence of the Ivory-billed Woodpecker (Campephilus principalis) in Louisiana,” Ecology and Evolution (2023)] is discussed and compared with the strongest evidence. Videos obtained with a drone on a sunny day often show white markings that do not correspond to actual field marks. It is demonstrated that a video that was purported to show an Ivory-billed Woodpecker on the basis of apparent white markings is apparently a Pileated Woodpecker (Dryocopus pileatus). The bird in that video appears to have black trailing edges on the dorsal surfaces of the wings, which are consistent with the Pileated Woodpecker, not the Ivory-billed Woodpecker. The wingbeat frequency and an upward swooping landing also seem to be consistent with the Pileated Woodpecker but are not consistent with historical accounts of the Ivory-billed Woodpecker or flights appearing in videos that contain the strongest evidence.
Petrophysical characteristics of igneous rocks in the Outboard Browse Basin, North West Shelf of Australia: implications for predicting igneous sequences prior to exploration drilling
Authors: Tsutsui Kosuke , Holford Simon , Schofield Nick , Bunch Mark , King Rosalind , McClay Ken
Published: November 2023

The Browse Basin is one of Australia's major hydrocarbon provinces, where significant discoveries have been made in recent decades including the Ichthys and Prelude fields, which accounted for ∼15% of the cumulative Australian liquified natural gas (LNG) production in 2019–20. This rift basin hosts extensive Mesozoic intrusive and extrusive igneous rocks, having been identified from both well and seismic data, and which are recognized as one of the key challenges for exploration and production activities in this region. Their impact on petroleum exploration is demonstrated by the number of wells which encountered unpredicted or thicker than expected igneous rock units both within and adjacent to target sections. This study therefore aims to document the reasons of such unexpectedness, and to develop capability to predict the occurrence of igneous rock units prior to drilling in the Browse Basin and other rift settings that contain igneous rocks. Multiple case studies of uncommercial exploration wells are developed by integrating petrophysical and seismic reflection data, focusing in particular along the outboard part of the basin where igneous rocks are most prevalent. Our study highlights the importance of understanding petrophysical, spatial and chemical heterogeneities of igneous rocks in basins to explain their emplacement and distribution, and thereby predict their occurrence prior to exploration and development activities.
DEEPFAKER: A Unified Evaluation Platform for Facial Deepfake and Detection Models
Authors: Wang Li , Meng Xiangtao , Li Dan , Zhang Xuhong , Ji Shouling , Guo Shanqing
Published: November 2023

Deepfake data contains realistically manipulated faces—its abuses pose a huge threat to the security and privacy-critical applications. Intensive research from academia and industry has produced many deepfake/detection models, leading to a constant race of attack and defense. However, due to the lack of a unified evaluation platform, many critical questions on this subject remain largely unexplored. How is the anti-detection ability of the existing deepfake models? How generalizable are existing detection models against different deepfake samples? How effective are the detection APIs provided by the cloud-based vendors? How evasive and transferable are adversarial deepfakes in the lab and real-world environment? How do various factors impact the performance of deepfake and detection models?

To bridge the gap, we design and implement
DEEPFAKER

1

a unified and comprehensive deepfake detection evaluation platform. Specifically,
DEEPFAKER
has integrated 10 state-of-the-art deepfake methods and 9 representative detection methods, while providing a user-friendly interface and modular design that allows for easy integration of new methods. Leveraging
DEEPFAKER
, we conduct a large-scale empirical study of facial deepfake/detection models and draw a set of key findings: (i) the detection methods have poor generalization on samples generated by different deepfake methods; (ii) there is no significant correlation between anti-detection ability and visual quality of deepfake samples; (iii) the current detection APIs have poor detection performance and adversarial deepfakes can achieve about 70% attack success rate on all cloud-based vendors, calling for an urgent need to deploy effective and robust detection APIs; (iv) the detection methods in the lab are more robust against transfer attacks than the detection APIs in the real-world environment; and (v) deepfake videos may not always be more difficult to detect after video compression. We envision that
DEEPFAKER
will benefit future research on facial deepfake and detection.
Inferring Human Intent and Predicting Human Action in Human–Robot Collaboration
Authors: Hoffman Guy , Bhattacharjee Tapomayukh , Nikolaidis Stefanos
Published: November 2023

Researchers in human–robot collaboration have extensively studied methods for inferring human intentions and predicting their actions, as this is an important precursor for robots to provide useful assistance. We review contemporary methods for intention inference and human activity prediction. Our survey finds that intentions and goals are often inferred via Bayesian posterior estimation and Markov decision processes that model internal human states as unobserved variables or represent both agents in a shared probabilistic framework. An alternative approach is to use neural networks and other supervised learning approaches to directly map observable outcomes to intentions and to make predictions about future human activity based on past observations. That said, due to the complexity of human intentions, existing work usually reasons about limited domains, makes unrealistic simplifications about intentions, and is mostly constrained to short-term predictions. This state of the art provides opportunity for future research that could include more nuanced models of intents, reason over longer horizons, and account for the human tendency to adapt.
Common Method Bias: It's Bad, It's Complex, It's Widespread, and It's Not Easy to Fix
Authors: Podsakoff Philip M. , Podsakoff Nathan P. , Williams Larry J. , Huang Chengquan , Yang Junhui
Published: November 2023

Despite recognition of the harmful effects of common method bias (CMB), its causes, consequences, and remedies are still not well understood. Therefore, the purpose of this article is to review our current knowledge of CMB and provide recommendations on how to control it. We organize our review into five main sections. First, we explain the harmful effects of CMB (why it is bad). Second, we discuss the complexity caused by the fact that there are multiple sources of CMB, several of which are likely to be present in any study. Third, we present evidence that the conditions under which CMB is likely to occur are relatively widespread, and fourth, we explain why CMB is not easy to fix. Finally, we identify several avenues for future research.
Manifold Learning: What, How, and Why
Authors: Meilă Marina , Zhang Hanyu
Published: November 2023

Manifold learning (ML), also known as nonlinear dimension reduction, is a set of methods to find the low-dimensional structure of data. Dimension reduction for large, high-dimensional data is not merely a way to reduce the data; the new representations and descriptors obtained by ML reveal the geometric shape of high-dimensional point clouds and allow one to visualize, denoise, and interpret them. This review presents the underlying principles of ML, its representative methods, and their statistical foundations, all from a practicing statistician's perspective. It describes the trade-offs and what theory tells us about the parameter and algorithmic choices we make in order to obtain reliable conclusions.
Effects of Hydrophobic Treatment on Performance and Water Management of Titanium Felt GDLs in PEMFCs
Authors: Moydien Hassan , Levecque Pieter , Susac Darija
Published: November 2023

This work follows our recent study of titanium fibre felts applied as a cathode gas diffusion layer (GDL) in a proton exchange membrane fuel cell. Here, an in-house hydrophobic treatment of PTFE (0−20 wt%) is applied to these felts and the effects on cell performance, gas diffusion, and water transport are studied with comparison to conventional commercial carbon GDLs. The titanium fibre felt with a low PTFE loading of 5 wt% consistently outperformed the untreated substrate and all carbon GDLs tested across all six sets of operating conditions. This loading is shown to improve flooding resistance due to the increased hydrophobicity while not majorly reducing porosity, gas permeability, or ohmic resistance. The low loading also maintains a fraction of hydrophilic pathways within the substrate which has been shown to contribute to improved liquid water transport under wetter operating conditions. An increase in PTFE loading to 10 wt% and higher results in reduced porosity and permeability, and saturation of the internal structure of the substrate with PTFE resulting in poorer performance. Finally, the full range of treated and untreated felts are shown to exhibit a good balance between water retention, water rejection, and hydrophobicity based on oxygen transport resistance.
Functional hypothalamic amenorrhea: gut microbiota composition and the effects of exogenous estrogen administration
Authors: Notaristefano Giovanna , Ponziani Francesca Romana , Ranalli Monia , Diterlizzi Alice , Policriti Martina Asia , Stella Leonardo , Del Zompo Fabio , Fianchi Francesca , Picca Anna , Petito Valentina , Del Chierico Federica , Scanu Matteo , Toto Francesca , Putignani Lorenza , Marzetti Emanuele , Ferrarese Daniele , Mele Maria Cristina , Merola Annamaria , Tropea Anna , Gasbarrini Antonio , Scambia Giovanni , Lanzone Antonio , Apa Rosanna
Published: November 2023

Our study marks the first comprehensive analysis of gut microbiota composition in FHA and the impact of HRT on it, along with biochemical, anthropometric, and psychometric aspects. Our results indicate distinct gut microbiota composition in patients with FHA compared with healthy individuals. Importantly, HRT prompts a transition toward a more beneficial gut microbiota profile and reduced inflammation. This study validates the concept of FHA as a multifaceted disorder interlinked with dysbiosis, particularly involving the gut-brain axis.
Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression
Authors: He Hongjuan , Ji Xiaoyan , Cao Lihua , Wang Zhenzhen , Wang Xiaoyu , Li Xiu-Min , Miao Mingsan
Published: November 2023

Objective. Dysregulation of epithelial-mesenchymal transition (EMT) in the airway epithelium is associated with airway remodeling and the progression of pulmonary fibrosis. Many treatments have been shown to inhibit airway remodeling and pulmonary fibrosis progression in asthma and chronic obstructive pulmonary disease (COPD) by regulating EMT and have few side effects. This review aimed to describe the development of airway remodeling through the EMT pathway, as well as the potential therapeutic targets in these pathways. Furthermore, this study aimed to review the current research on drugs to treat airway remodeling and their effects on the EMT pathway. Findings. The dysregulation of EMT was associated with airway remodeling in various respiratory diseases. The cytokines released during inflammation may induce EMT and subsequent airway remodeling. Various drugs, including herbal formulations, specific herbal compounds, cytokines, amino acid or protein inhibitors, microRNAs, and vitamins, may suppress airway remodeling by inhibiting EMT-related pathways.
Limit Directions of Julia Sets of Entire Functions and Complex Differential Equations
Authors: Qin Zhigao , Long Jianren , Xiang Xuxu
Published: November 2023

The limiting directions of Julia sets of infinite order entire functions are studied by combining the theory of complex dynamic system and the theory of complex differential equations, in which the lower bound of the measure of limiting direction of Julia set of entire solutions of complex differential equations is obtained.
The Clinical and Cellular Impact of RBMS2 on the Progression and Prognosis of Kidney Renal Clear Cell Carcinoma
Authors: Gao Zhixiang , Fan Shouren
Published: November 2023

This research delves into the implications of the RNA binding motif, single stranded interacting protein 2 (RBMS2)—a gene associated with tumor-suppressing functions—in the context of kidney renal clear cell carcinoma (ccRCC). Through meticulous exploration of online databases, we have identified a negative association between RBMS2 expression and adverse clinico-pathological features, such as advanced TNM stage. Furthermore, our findings indicate that RBMS2 acts as a prognostic predictor for clinical outcomes in ccRCC, evidenced by both univariate and multivariate analyses. Cellular assays have corroborated these findings, revealing that an overexpression of RBMS2 curtails ccRCC cell proliferation and migration. Additionally, our research has unearthed links between RBMS2 and immune infiltration within the ccRCC tumor microenvironment. Collectively, our results underscore the tumor-inhibiting role of RBMS2 in ccRCC and spotlight its potential as a prognostic marker and therapeutic intervention target.
Characterization of Cost-Saving Monofacial PERC Module under Field Conditions in South Korea
Authors: Hwang Sungho , Lee Hae-seok
Published: November 2023

The photovoltaic (PV) industry is constantly striving to increase module power output while decreasing costs. Importantly, the performance and reliability of cost-saving products should be evaluated before being launched into the PV market to avoid any unnecessary side effects. This study investigated the performance of a monofacial module employing a cost-saving bifacial cell installed at a carport in South Korea. The bifacial cell reduces costs, compared to monofacial cell, by using a lower quantity of aluminum paste on its rear; consequently, it has become a popular product in the PV industry. The monofacial module employing the bifacial cell showed an improved voltage temperature coefficient and low-light performance over monofacial cell-based module. Our field data highlight three conclusions from the bifacial cell-based module; it showed (1) different voltage temperature coefficients with better performance at lower temperatures, (2) better low-light performance owing to high series resistance, and (3) high current owing to its bifaciality. Notably, under high irradiance and temperature conditions, the bifacial cell performed worse than the monofacial cell. We concluded that this type of cell may perform well under northern European climatic conditions, though further investigation is required to optimize cell performance under various weather conditions.
Religious Practices and Its Impacts on a Sustainable Urban Environment in Nigeria: The Way Forward
Authors: Ogunbode Timothy Oyebamiji , Oyekan Funke Elizabeth
Published: November 2023

A sustainable and serene environment is a prerequisite and a driver of human productivity in space and time. The quality of a human environment, however, is under threat always partly as a result of various human cultural activities such as festivities and religious practices. This work specifically investigated various ways religious activities have impacted the urban environment in two cities in the southwestern part of Nigeria together as a case study. Data for the work were generated through the administration of 250 copies of the structured questionnaire, out of which 232 were completed and retrieved. The data were subjected to data adequacy tests (i.e., Kaiser–Meyer–Olkin (KMO) and Bartlett’s test of sphericity (BTS)). The test showed 67.6% at a significance level of

p

 < 0.001 The results showed that 52.6% were of secondary school level, 52.2 were of Christian faith, and 61.6% were also of the male gender who were mostly in the age category of 46 to 65 years. The factor analysis identified 11 out of 23 variables as significant ones which explained 72.052% of the ways religious activities have negatively impacted the urban environment. Of the 11 variables, the first six alone offered 45.248%, namely, (i) contribution to climate change, (ii) night worships, (iii) noise pollution caused, (iv) use of the public address system, (v) quest for expansion, and (vi) religious uses of natural resources, especially water. In view of this, it is recommended that efforts should be made to check the extracted variables for a sustainable serene environment. However, there is a need to put in place relevant legislation/policies to control the activities of various religious bodies and mechanisms to enlighten religious practitioners on practices that will not jeopardize a serene urban environment. Further studies in other places to affirm or otherwise the findings here are suggested.
Spatial Variation Law of Blasting Vibration in Layered Strata under Blasting Excavation of Subway Tunnel
Authors: Zhang Zhen , Zhou Chuanbo , Jiang Nan , Yao Yingkang
Published: November 2023

Blasting vibration generated from blasting excavation of subway tunnel may endanger the adjacent structures buried in strata. To guarantee their safety and stability, it is crucial to understand the spatial variation law of blasting vibration in strata. In this paper, the blasting excavation of the large cross-sectional tunnel of Wuhan Metro Line 8 is studied. Three-dimensional finite element simulation is performed using the dynamic finite element program LS-DYNA, and its validity is verified by the field monitoring data. The spatial variation law of blasting vibration in layered strata is investigated through analyzed the distribution characteristic of blasting vibration in three directions, including the direction along the axis of the large cross-sectional tunnel, the direction perpendicular to the axis of the large cross-sectional tunnel, and the direction along the depth. A prediction model for blasting vibration velocity, which considers the impact of elevation differences, is established through dimensional analysis, enabling the prediction of blasting-induced vibrations at various depths in the layered strata.
Antimicrobial Resistance in Poultry Farming: A Look Back at Environmental Escherichia coli Isolated from Poultry Farms during the Growing and Resting Periods
Authors: Thongratsakul Sukanya , Amavisit Patamabhorn , Poolkhet Chaithep
Published: November 2023

During the production cycle of poultry farms, pathogens may remain in the next cycle of rearing young chickens. This study was conducted at three industrial chicken farms (A, B, and C) in central Thailand. Results showed that the percentages of E. coli during the resting period in farms A, B, and C were 28.6, 53.8, and 7.8, respectively, and those during the growing period were 45, 68.8, and 75. The most common resistant patterns during the resting period in all farms were AML‐AMP‐SXT and AML‐AMP‐DO‐SXT, and those during the growing period were AML‐AMP and AML‐AMP‐SXT. The locations of blaTEM‐positive E. coli isolates from the inside houses (inside buildings) of all farms included cloacal swabs, floors, water nipples, pan feeders, and husks, whereas that from the outside environment included boots, wastewater, soil, and water from cooling pads and tanks. Our results indicate that the percentage of antimicrobial resistance (AMR) and its pattern depend on the husbandry period and the strictness of biosecurity. Moreover, our findings derived from samples gathered from broiler farms between 2013 and 2015 align with those of the current studies, highlighting persistent trends in E. coli resistance to various antimicrobial agents. Therefore, enhancing biosecurity measures throughout both the resting and growing periods is crucial, with a specific focus on managing raw materials, bedding, breeding equipment, and staff hygiene to reduce the transmission of antimicrobial resistance in poultry farms.
Potential for Cure by Stage across the Cancer Spectrum in the United States
Authors: Hubbell Earl , Clarke Christina A. , Smedby Karin E. , Adami Hans-Olov , Chang Ellen T.
Published: November 2023

Background:

Cure fraction—the proportion of persons considered cured of cancer after long-term follow-up—reflects the total impact of cancer control strategies, including screening, without lead-time bias. Previous studies have not reported stage-stratified cure fraction across the spectrum of cancer types.

Methods:

Using a mixture cure model, we estimated cure fraction across stages for 21 cancer types and additional subtypes. Cause-specific survival for 2.4 million incident cancers came from 17 US Surveillance, Epidemiology, and End Results registries for adults 40 to 84 years at diagnosis in 2006 to 2015, followed through 2020.

Results:

Across cancer types, a substantial cure fraction was evident at early stages, followed by either a sharp drop from stages III to IV or a steady decline from stages I to IV. For example, estimated cure fractions for colorectal cancer at stages I, II, III, and IV were 62% (95% confidence interval: 59%–66%), 61% (58%–65%), 58% (57%–59%), and 7% (7%–7%), respectively. Corresponding estimates for gallbladder cancer were 50% (46%–54%), 24% (22%–27%), 22% (19%–25%), and 2% (2%–3%). Differences in 5-year cause-specific survival between early-stage and stage IV cancers were highly correlated with between-stage differences in cure fraction, indicating that survival gaps by stage are persistent and not due to lead-time bias.

Conclusions:

A considerable fraction of cancer is amenable to cure at early stages, but not after metastasis.

Impact:

These results emphasize the potential for early detection of numerous cancers, including those with no current screening modalities, to reduce cancer death.