bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Social Factors Associated With Trajectories of HIV-Related Stigma and Everyday Discrimination Among Women Living With HIV in Vancouver, Canada: Longitudinal Cohort Findings
Authors: Logie Carmen H. , Shannon Kate , Braschel Melissa , Krüsi Andrea , Norris Candice , Zhu Haoxuan , Deering Kathleen
Published: October 2023

Introduction:

Women living with HIV (WLHIV) experience stigma rooted in social inequities. We examined associations between social factors (food insecurity, housing insecurity, violence, sexual minority identity, and substance use) and HIV-related stigma and Everyday Discrimination trajectories among WLHIV.

Methods:

This community-based open longitudinal cohort study with WLHIV living in and/or accessing HIV care in Metro Vancouver, Canada, plotted semiannual averages (2015–2019) of recent (past 6-month) HIV-related stigma and Everyday Discrimination. We examined distinct trajectories of HIV-related stigma and Everyday Discrimination using latent class growth analysis (LCGA) and baseline correlates of each trajectory using multinomial logistic regression.

Findings:

Among participants (HIV-related stigma sample: n = 197 participants with n = 985 observations; Everyday Discrimination sample: n = 203 participants with n = 1096 observations), LCGA identified 2 distinct HIV-related stigma and Everyday Discrimination trajectories: sustained low and consistently high. In multivariable analysis, concurrent food and housing insecurity (adjusted odds ratio [AOR]: 2.15, 95% confidence interval [CI] 1.12–4.12) and physical/sexual violence (AOR: 2.57, 95% CI: 1.22–5.42) were associated with higher odds of the consistently high (vs. sustained low) HIV-related stigma trajectory. Sexual minority identity (AOR: 2.84, 95% CI: 1.49–5.45), concurrent food and housing insecurity (AOR: 2.65, 95% CI: 1.38–5.08), and noninjection substance use (less than daily vs. none) (AOR: 2.04, 95% CI: 1.03–4.07) were associated with higher odds of the consistently high (vs. sustained low) Everyday Discrimination trajectory.

Conclusions:

Social inequities were associated with consistently high HIV-related stigma and Everyday Discrimination among WLHIV. Multilevel strategies can address violence, economic insecurity, intersecting stigma, and discrimination to optimize health and rights among WLHIV.
Association of Higher Intake of Plant-Based Foods and Protein With Slower Kidney Function Decline in Women With HIV
Authors: Banerjee Tanushree , Frongillo Edward A. , Turan Janet M. , Sheira Lila A. , Adedimeji Adebola , Wilson Tracey , Merenstein Daniel , Cohen Mardge , Adimora Adaora A. , Ofotokun Igho , Metsch Lisa , D'Souza Gypsyamber , Fischl Margaret A. , Fisher Molly C. , Tien Phyllis C. , Weiser Sheri D.
Published: October 2023

Background:

We investigated whether there exists an association between dietary acid load and kidney function decline in women living with HIV (WLWH) receiving antiretroviral therapy (ART).

Setting:

One thousand six hundred eight WLWH receiving ART in the WIHS cohort with available diet data and a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/minute/1.73 m2.

Methods:

A brief dietary instrument conducted from 2013 to 2016 under the Food Insecurity Sub-Study was used for assessing fruits and vegetables (FV) and protein intake. A mixed-effects model with random intercept and slope was used to estimate subjects' annual decline rate in eGFR and the association between FV intake and eGFR decline, adjusting for sociodemographics, serum albumin, comorbidities, time on ART, ART drugs, HIV markers, and baseline eGFR. We evaluated whether markers of inflammation mediated the effect of FV intake on decline in eGFR, using causal mediation analysis.

Results:

We found a dose–response relationship for the association of FV intake and eGFR decline, with lesser annual decline in eGFR in the middle and highest tertiles of FV intake. An increase of 5 servings of FV intake per day was associated with a lower annual eGFR decline (−1.18 [−1.43, −0.94]). On average, 39% of the association between higher FV intake and slower eGFR decline was explained by decreased levels of inflammation.

Conclusions:

Plant-rich diet was associated with slower decline in kidney function. Inflammation is a potential path through which diet may affect kidney function. The findings support an emerging body of literature on the potential benefits of plant-rich diets for prevention of chronic kidney disease.
Increasing Spiritual Beliefs are Associated With Lower HIV Incidence Among Black Men Who Have Sex With Men: Results From HPTN 061 Longitudinal Study
Authors: Ransome Yusuf , Taggart Tamara , Huang Amber Shu , Vermund Sten H. , Mayer Kenneth H. , Nunn Amy S.
Published: October 2023

Background:

There is a limited understanding about the impact of spiritual beliefs and activities on HIV seroconversion among black men who have sex with men (BMSM), which we investigate in this study.

Setting:

United States.

Methods:

The HIV Prevention Trials Network Study 061 collected demographic and biomedical assessments among BMSM across 6 United States cities for longitudinal analysis. Spiritual beliefs and spiritual activities are constructed composite scales. Bivariate analyses among 894 who provided data at 12-month follow-up compared men who seroconverted to HIV between baseline and 6 months with those who remained uninfected with HIV at 12 months. Cox proportional hazard regression among 944 men tested spiritual beliefs and activities on the longitudinal risk of HIV seroconversion adjusting for age and any sexually transmitted infection (STI).

Results:

Among this sample, HIV incidence between baseline and 6 months was 1.69%, (95% confidence intervals [CI]: 1.04 to 2.77). Men who seroconverted to HIV were significantly younger than those who remained uninfected at the 12-month follow-up: (mean age 27, SD = 11 vs 37, SD = 12) and a higher proportion reported any STI (46.67% vs 11.39%, P < 0.01). A one-unit increase in spiritual beliefs was associated with lower hazard rate of seroconverting to HIV at follow-up [adjusted hazard ratio (aHR) = 0.37, 95% CI: = (0.16 to 0.87)]. Religious service attendance and spiritual activities were unrelated to seroconverting.

Conclusions:

Spirituality is important in the lives of BMSM. Biomedical and behavioral HIV prevention interventions should consider assessing spiritual beliefs in HIV care among BMSM.
Brief Report: Outcomes of Individuals Using HIV Postexposure Prophylaxis-In-Pocket (“PIP”) for Low-Frequency, High-Risk Exposures in Toronto, Canada
Authors: Billick Maxime J. , Fisher Karla N. , Myers Samantha , Tan Darrell H. S. , Bogoch Isaac I.
Published: October 2023

Background:

HIV postexposure prophylaxis-in-pocket (“PIP”) is a self-initiated, event-driven HIV prevention modality for individuals with a low frequency of HIV exposures.

Methods:

A cohort of 111 patients using PIP as their primary HIV prevention modality was longitudinally evaluated for PIP self-initiation, HIV and sexual transmitted infections, and switching to other HIV prevention modalities between February 2016 and December 2022.

Results:

A total of 111 patients had 178.7 cumulative patient-years of PIP use. PIP was self-initiated 69 times by 35 (31.5%) individuals, with 0 HIV seroconversions identified. Thirty four individuals (30.6%) transitioned from PIP to pre-exposure prophylaxis and 33 individuals (29.7%) switched from pre-exposure prophylaxis to PIP.

Conclusions:

PIP is a useful addition to other pharmacologic HIV prevention tools, and may help prevent infection in those with a lower frequency of unanticipated HIV exposures.
Laparoscopic Inguinal Hernia Repair for Female Patients: Experience from a High-volume Center in 20 years
Authors: Lu Jingfeng , Zhao Xuan , Yue Fei , Xue Pei , Feng Bo , Chen Qian , Li Jianwen
Published: October 2023

Background:

Although laparoscopic inguinal hernia repair (LIHR) is widely performed worldwide, few studies have focused on the procedure in female patients. This study investigated the characteristics and outcomes of female patients with inguinal hernias who underwent LIHR.

Materials and Methods:

This study retrospectively analyzed the data of 7380 patients with inguinal hernia admitted to the General Surgery Department of Ruijin Hospital and underwent LIHR from January 2001 to December 2020. The clinical characteristics, surgical outcomes, and complications were assessed.

Results:

In total, 572 female patients were enrolled in this study. The proportion of femoral hernias in female patients was higher in women than in male patients (17.4% vs. 0.3%, respectively). Mesothelial cysts of the round uterine ligament (MCURL) were noted in 74 patients. The mean age of patients with MCURL was lower than that of patients without MCURL (46.4 vs. 55.6, P=0.018). Seventy cases (93.3%) of MCURL were resected laparoscopically, and 5 cases were resected through an auxiliary small incision. The round ligament was cut off in 335 patients and preserved in 237. No significant differences were observed in the number of hospitalization days, recurrence rates, or complications between the transection and preservation groups. None of the cases were converted to laparotomy, and no recurrence was noted during follow-up.

Conclusion:

LIHR is safe and feasible in female patients. Treatment of femoral hernia, MCURL, and the round ligament of the uterus should be carefully considered during LIHR in female patients.
The role of perceived minority-group status in the conspiracy beliefs of factual majority groups
Authors: Gundersen Aleksander B. , van der Linden Sander , Piksa Michał , Morzy Mikołaj , Piasecki Jan , Ryguła Rafał , Gwiaździński Paweł , Noworyta Karolina , Kunst Jonas R.
Published: October 2023

Research suggests that minority-group members sometimes are more susceptible to misinformation. Two complementary studies examined the influence of perceived minority status on susceptibility to misinformation and conspiracy beliefs. In study 1 (
n
= 2140), the perception of belonging to a minority group, rather than factually belonging to it, was most consistently related with an increased susceptibility to COVID-19 misinformation across national samples from the USA, the UK, Germany and Poland. Specifically, perceiving that one belongs to a gender minority group particularly predicted susceptibility to misinformation when participants factually did not belong to it. In pre-registered study 2 (
n
= 1823), an experiment aiming to manipulate the minority perceptions of men failed to influence conspiracy beliefs in the predicted direction. However, pre-registered correlational analyses showed that men who view themselves as a gender minority were more prone to gender conspiracy beliefs and exhibited a heightened conspiracy mentality. This effect was correlationally mediated by increased feelings of system identity threat, collective narcissism, group relative deprivation and actively open-minded thinking. Especially, the perception of being a minority in terms of power and influence (as compared to numerically) was linked to these outcomes. We discuss limitations and practical implications for countering misinformation.
Economic inequality increases the number of hours worked and decreases work–life balance perceptions: longitudinal and experimental evidence
Authors: Filippi Silvia , Salvador Casara Bruno Gabriel , Pirrone Davide , Yerkes Mara , Suitner Caterina
Published: October 2023

International institutions' attention to work–life balance (WLB) demonstrates the global breadth of this issue. Yet the scientific community has thus far paid little attention to its structural underpinnings and to the interplay between these macro-level underpinnings and individual psychological factors. We examine the contextual role of economic inequality at the national level as a significant factor influencing working time and WLB perceptions using multiple empirical strategies. In the first set of studies (1a and 1b), we compared countries with different levels of inequality (Study 1a with 37 countries, Study 1b with longitudinal data from 34 countries,N= 254) and found increased working time and reduced WLB in highly unequal countries. In a pilot study (N= 81) and in the pre-registered Studies 2 (N= 338) and 3 (N= 499) we corroborated this evidence with an experimentally induced inequality perception, reporting an indirect effect of inequality on WLB (Studies 2 and 3) and working time (Study 3) through status anxiety and competitiveness. In Study 2, we manipulated socio-economic class in addition to economic inequality, showing that the detrimental effect of inequality on WLB is especially marked for participants assigned to a low-class condition. This research contributes to an integrated understanding of the impact of economic inequality and socio-economic class in shaping WLB and provides useful insights for organizations to develop context-specific policies to improve employees’ WLB that take both individual and structural factors into account.
In fission yeast, 65 non-essential mitochondrial proteins related to respiration and stress become essential in low-glucose conditions
Authors: Mori Ayaka , Uehara Lisa , Toyoda Yusuke , Masuda Fumie , Soejima Saeko , Saitoh Shigeaki , Yanagida Mitsuhiro
Published: October 2023

Mitochondria perform critical functions, including respiration, ATP production, small molecule metabolism, and anti-oxidation, and they are involved in a number of human diseases. While the mitochondrial genome contains a small number of protein-coding genes, the vast majority of mitochondrial proteins are encoded by nuclear genes. In fission yeast
Schizosaccharomyces pombe
, we screened 457 deletion (
del
) mutants deficient in nuclear-encoded mitochondrial proteins, searching for those that fail to form colonies in culture medium containing low glucose (0.03–0.1%; low-glucose sensitive,
lgs
), but that proliferate in regular 2–3% glucose medium. Sixty-five (14%) of the 457 deletion mutants displayed the
lgs
phenotype. Thirty-three of them are defective either in dehydrogenases, subunits of respiratory complexes, the citric acid cycle, or in one of the nine steps of the CoQ10 biosynthetic pathway. The remaining 32
lgs
mutants do not seem to be directly related to respiration. Fifteen are implicated in translation, and six encode transporters. The remaining 11 function in anti-oxidation, amino acid synthesis, repair of DNA damage, microtubule cytoskeleton, intracellular mitochondrial distribution or unknown functions. These 32 diverse
lgs
genes collectively maintain mitochondrial functions under low (1/20–1/60× normal) glucose concentrations. Interestingly, 30 of them have homologues associated with human diseases.
Social networks and voter turnout
Authors: Kernell Georgia , Lamberson P. J.
Published: October 2023

This paper develops a model of voter turnout that embeds Riker and Ordeshook’s (1968
Am. Pol. Sci. Rev.
62
, 25–42 (
doi:10.2307/1953324
)) calculus of voting into the context of a social network. In the model, an individual’s expressive benefits to voting depend on the behaviour of their social contacts. We show that there may be multiple equilibria and analyse how these equilibria depend on the structure of the network. We discuss six empirical implications of the model for turnout, some of which suggest novel answers to longstanding puzzles in the turnout literature, such as: why are higher income individuals more likely to vote even in cases when registration costs are low? Why is turnout so difficult to predict? Why does lowering registration costs disproportionately increase turnout among high-income voters? And why do we observe inertia in turnout across elections?
Managing ecological thresholds of a risky commons
Authors: Sarkar Sukanta
Published: October 2023

Common resources are often overexploited and appear subject to critical transitions from one stable state to another antagonistic state. Many times resulting in tragedy of the commons (TOC)—exploitation of shared resources for personal gain/payoffs, leading to worse outcomes or extinction. An adequate response would be strategic interaction, such as inspection and punishment by institutions to avoid TOC. This strategic interaction is often coupled with dynamically changing common resources. However, effect of strategic interaction in complex, coupled socio-ecological systems is less studied. Here, we develop replicator equations using evolving games in which strategy and common resources co-evolve. We consider the shared commons as fish dynamics governed by the intrinsic growth rate, predation and harvesting. The joint dynamics exhibit an oscillatory TOC, revealing that institutions need to pay special attention to intrinsic growth rate and nonlinear interaction. Our research shows that the co-evolving system exhibits a broader range of dynamics when predation is present compared to the disengaged fishery system. We conclude that the usefulness, chances and challenges of modelling co-evolutionary games to create sustainable systems merit further research.
Mechanical loading due to muscle movement regulates establishment of the collagen network in the developing murine skeleton
Authors: Ahmed Saima , Rogers Andrew V. , Nowlan Niamh C.
Published: October 2023

Mechanical loading is critical for collagen network maintenance and remodelling in adult skeletal tissues, but the role of loading in collagen network formation during development is poorly understood. We test the hypothesis that mechanical loading is necessary for the onset and maturation of spatial localization and structure of collagens in prenatal cartilage and bone, using
in vivo
and
in vitro
mouse models of altered loading. The majority of collagens studied was aberrant in structure or localization, or both, when skeletal muscle was absent
in vivo
. Using
in vitro
bioreactor culture system, we demonstrate that mechanical loading directly modulates the spatial localization and structure of collagens II and X. Furthermore, we show that mechanical loading
in vitro
rescues aspects of the development of collagens II and X from the effects of fetal immobility. In conclusion, our findings show that mechanical loading is a critical determinant of collagen network establishment during prenatal skeletal development.
Pre-existing visual preference for white dot patterns in estrildid finches: a comparative study of a multi-species experiment
Authors: Mizuno Ayumi , Soma Masayo
Published: October 2023

The diverse characteristics of animal signal designs can be explained by the sensory bias hypothesis, which suggests that natural selection shapes sensory bias and preferences associated with signal design. Traditionally, this hypothesis has focused on female sensory biases and male sexual traits. However, considering shared sensory systems between males and females in non-sexual contexts, existing sensory bias possibly contributes to the evolution of shared social and sexual traits. Our previous studies on the family Estrildidae supported this idea. An evolutionary relationship probably existed between diet and white dot plumage, and a species of estrildid finches showed a visual preference for white dot patterns. To investigate this further, we examined hunger-related visual preferences using phylogenetic comparative methods and behavioural experiments. Specifically, we compared the gazing responses of 12 species of estrildids to monochromatic printed white dot and stripe patterns, considering their phylogenetic relationships. The results support our idea that the common estrildid ancestor had a hunger-related visual preference for white dot patterns. Subject species generally preferred white dots to stripes. Furthermore, males and females showed a similar preference towards dots. Our findings provide insights into the role of sensory bias in the evolution of mutual ornamentation.
Stream function solutions for some contact line boundary conditions: Navier slip, super slip and the generalized Navier boundary condition
Authors: Kulkarni Yash , Fullana Tomas , Zaleski Stephane
Published: October 2023

The stream function solution for the inner region Stokes flow, for a locally plane moving fluid interface near the triple point, is derived considering three different boundary conditions: the Navier slip boundary condition (NBC), the super-slip boundary condition and the generalized Navier boundary condition (GNBC). The NBC, incorporating a slip length parameter

λ

, is a well-known method for regularization in the context of the three-phase dynamic contact line problem. It is demonstrated that the velocity field solution under this boundary condition maintains a

C
0

continuity at the contact line, resulting in a logarithmic divergence of the pressure at the contact line. By contrast, the super-slip boundary condition establishes a proportional relationship between the wall velocity and the normal derivative of the shear stress, leading to a

C
1

velocity field. Furthermore, the GNBC, which introduces an uncompensated Young stress to drive the contact line, yields a

C
2

velocity field. The dominant terms are explicitly derived, and the analytical approach presented here can be extended to other bi-harmonic problems as well.
Epidemiology and characterization of Providencia stuartii isolated from hospitalized patients in southern Brazil: a possible emerging pathogen
Authors: Guidone Gustavo Henrique Migliorini , Cardozo Jennifer Germiniani , Silva Luana Carvalho , Sanches Matheus Silva , Galhardi Ligia Carla Faccin , Kobayashi Renata Katsuko Takayama , Vespero Eliana Carolina , Rocha Sergio Paulo Dejato
Published: October 2023

This study aimed to characterize the virulence factors and antimicrobial resistance of

Providencia stuartii

, an opportunistic pathogen that causes human infections. We examined 45 isolates of

P. stuartii

both genotypically and phenotypically by studying their adherence to HeLa cells, biofilm formation, cytotoxicity and antimicrobial resistance, and analysed their genomes for putative virulence and resistance genes. This study found that most isolates possessed multiple virulence genes, including fimA, mrkA, fptA, iutA, ireA and hlyA, and were cytotoxic to Vero cells. All the isolates were resistant to amoxicillin plus clavulanic acid, levofloxacin and sulfamethoxazole plus trimethoprim, and most were resistant to ceftriaxone and cefepime. All isolates harboured extended-spectrum beta-lactamase coding genes such as bla
CTX-M-2 and 23/45(51.11 %) of them also harboured bla
CTX-M-9. The gene KPC-2 (carbapenemase) was detected in 8/45(17.77 %) isolates. This study also found clonality among the isolates, indicating the possible spread of the pathogen among patients at the hospital. These results have significant clinical and epidemiological implications and emphasize the importance of a continued understanding of the virulence and antimicrobial resistance of this pathogen for the prevention and treatment of future infections.
Contrasting genes conferring short- and long-term biofilm adaptation in Listeria
Authors: Monteith William , Pascoe Ben , Mourkas Evangelos , Clark Jack , Hakim Maliha , Hitchings Matthew D. , McCarthy Noel , Yahara Koji , Asakura Hiroshi , Sheppard Samuel K.
Published: October 2023

Listeria monocytogenes

is an opportunistic food-borne bacterium that is capable of infecting humans with high rates of hospitalization and mortality. Natural populations are genotypically and phenotypically variable, with some lineages being responsible for most human infections. The success of

L. monocytogenes

is linked to its capacity to persist on food and in the environment. Biofilms are an important feature that allow these bacteria to persist and infect humans, so understanding the genetic basis of biofilm formation is key to understanding transmission. We sought to investigate the biofilm-forming ability of

L. monocytogenes

by identifying genetic variation that underlies biofilm formation in natural populations using genome-wide association studies (GWAS). Changes in gene expression of specific strains during biofilm formation were then investigated using RNA sequencing (RNA-seq). Genetic variation associated with enhanced biofilm formation was identified in 273 genes by GWAS and differential expression in 220 genes by RNA-seq. Statistical analyses show that the number of overlapping genes flagged by either type of experiment is less than expected by random sampling. This novel finding is consistent with an evolutionary scenario where rapid adaptation is driven by variation in gene expression of pioneer genes, and this is followed by slower adaptation driven by nucleotide changes within the core genome.
PD-L1 Restrains the PD-1hiNrp1loTGFβ+Treg to block IL6+Neutrophil tumor infiltration to Suppress Inflammation-driven Colorectal Cancer
Authors: Poschel Dakota B. , Klement John D. , Merting Alyssa D. , Lu Chunwan , Zhao Yang , Yang Dafeng , Xiao Wei , Zhu Huabin , Rajeshwari Ponnala , Toscano Michael , Jones Kimya , Madwani Kiran , Barrett Amanda , Bollag Roni J. , Fallon Padraic G. , Shi Huidong , Liu Kebin
Published: October 2023

PD-L1 functions as a suppressor of T cell activation and colonic inflammation. The consequence of and mechanism underlying these opposite functions of PD-L1 in colorectal cancer remains unknown. We report that globalCd274deletion promotes inflammation-driven colorectal tumorigenesis. 16S rRNA and shotgun metagenomic sequencing revealed that loss of host PD-L1 leads to expansion of gutLigilactobacillus murinusand activation of the AhR pathway in tumor-bearing mice. scRNA-seq analysis revealed that PD-L1 regulates PD-189Nrp11215Treg, IL6+neutrophils, and B cells in colorectal tumor. Treg expresses high level of TGFβ to recruit IL6+neutrophils. IL6 inhibits activation of B and T cells. IL6 blockade or B cell activation via CD40 agonist increases CTL activation and suppresses colon tumor growth in vivo. Our findings determine that PD-L1 functions as a tumor suppressor in the context of inflammation-driven colorectal cancer and the PD-L1/L. murius/PD-189Nrp11215TGFβ+Treg/IL6+neutrophils pathway controls host cancer immunosurveillance and colorectal tumorigenesis.

Key points

Global deletion ofCd274promotes inflammation-driven colorectal tumorigenesis.

Loss of PD-L1 increases gutL. murinusand activates AhR pathway in colorectal tumor.

PD-1hiTGFβ+Nrp1loTreg recruits IL6+neutrophils to inhibit B and T cell function in colorectal tumor.

L. murinusand tryptophan metabolites connect PD-L1 and colorectal tumor immunosurveillance.

Graphic summary
Evidence of spatial regime shifts: contrasting spatial dynamics of three Atlantic cod (Gadusmorhua) populations in the North Sea
Authors: Cecapolli Enrico , Romagnoni Giovanni , Blöcker Alexandra M. , Möllmann Christian , Sguotti Camilla
Published: October 2023

Recent scientific assessments have started to consider the presence of multiple populations of Atlantic cod (Gadus morhua) in the North Sea due to genetic evidence. The Atlantic cod stock as a whole has experienced a regime shift in the North Sea and is now considered to be in a persistent depleted state. Here we investigated if the regime shift detected for North Sea cod manifested differently across areas (South, North-West and Viking (North-East)), revealing different dynamics and recovery potential for the corresponding populations. Methods from change point analyses to stochastic cusp models were applied to detect the regime shifts. We found that cod in the Southern North Sea has undergone a regime shift and is now in a persistent depleted state. The Viking population is in a low state but with high resilience, making its dynamics more predictable and thus easier to manage. Finally, the north-western population did not show signs of a regime shift and is in a high biomass level. Several abiotic and biotic drivers (e.g. fishing, warming) contribute to these differences. Our study provides useful information for the restructuring of management units of cod in the North Sea and highlights the importance of looking at regime shifts spatially.
Structural and modelling insights into the dynamic association between the transcription factor and DNA
Authors: Jin Fang. , Xu Ke.
Published: October 2023

The DNA recognition mechanisms by transcription factor (TF) was a significant scientific issue in the gene transcription and regulation. Multiple research technology including the experimental and modelling method has been introduced into the study of this aspect. In this article bioinformatic, protein modelling and dynamic simulation method was employed to display the overview of the dynamic binding between TF and DNA. Physical properties of positional change and freedom of atoms in addition with the volume exchange and the interaction analysis revealed the flexible binding sites of this element. The association of TF increased its stability with dynamic conformational change. The different levels of resistance to the thermal fluctuations of the residues and the nucleotides in the binding site stabilize the overall structure of the complex and initiated the open of the double helix that indicated the molecular mechanisms of the recognition and regulation of the elements.
How motivational interviewing shifts food choices and craving-related brain responses to healthier options
Authors: Rodrigues Belina , Khalid Iraj , Frileux Solene , Flament Benjamin , Yoldas Zeynep , Rampanana Martine , Aubertin Hippolyte , Oppert Jean-Michel , Poitou Christine , Rotge Jean-Yves , Fossati Philippe , Koban Leonie , Schmidt Liane
Published: October 2023

Changing one's habits is challenging. Motivational interviewing (MI) has been proposed as a communication-based approach to overcome this challenge. Here, we tested how change and sustain talk suggestions, elicited by MI, influenced value-based dietary decision-making and responses of a recently developed neurobiological craving signature (NCS) in healthy female adults. We found that following change talk, compared to sustain talk, participants' food choices and activity in the ventromedial prefrontal cortex were more driven by the healthiness and less by the tastiness of food. These findings were paralleled by lower NCS responses to tasty food after change compared to sustain talk. Further, following change talk, participants' body mass indices moderated the NCS decoding of healthy and tasty food choices. These results show that MI can shift value-based decision-making and reduce craving-related brain marker responses to highly palatable food items. The findings contribute to a better understanding of behavioral change toward healthier eating.
PEPSI: Polarity measurements from spatial proteomics imaging suggest immune cell engagement
Authors: Wu Eric , Wu Zhenqin , Mayer Aaron T. , Trevino Alexandro E. , Zou James
Published: October 2023

Subcellular protein localization is important for understanding functional states of cells, but measuring and quantifying this information can be difficult and typically requires high-resolution microscopy. In this work, we develop a metric to define surface protein polarity from immunofluorescence (IF) imaging data and use it to identify distinct immune cell states within tumor microenvironments. We apply this metric to characterize over two million cells across 600 patient samples and find that cells identified as having polar expression exhibit characteristics relating to tumor-immune cell engagement. Additionally, we show that incorporating these polarity-defined cell subtypes improves the performance of deep learning models trained to predict patient survival outcomes. This method provides a first look at using subcellular protein expression patterns to phenotype immune cell functional states with applications to precision medicine.
A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy
Authors: Nebuloni Federico , Do Quyen B. , Cook Peter R. , Walsh Edmond J. , Wade-Martins Richard
Published: October 2023

In our brains, different neurons make appropriate connections; however, there remain fewin vitromodels of such circuits. We use an open microfluidic approach to build and study neuronal circuitsin vitroin ways that fit easily into existing bio-medical workflows. Dumbbell-shaped circuits are built in minutes in standard Petri dishes; the aqueous phase is confined by fluid walls – interfaces between cell-growth medium and an immiscible fluorocarbon, FC40. Conditions are established that ensure post-mitotic neurons derived from human induced pluripotent stem cells (iPSCs) plated in one chamber of a dumbbell remain where deposited. After seeding cortical neurons on one side, axons grow through the connecting conduit to ramify amongst striatal neurons on the other – an arrangement mimicking unidirectional cortico-striatal connectivity. We also develop a moderate-throughput non-contact axotomy assay. Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks, and screening drugs for their effects on connectivity.
An Automated and Robust Tool for Musculoskeletal and Finite Element Modeling of the Knee Joint
Authors: Esrafilian Amir , Chandra Shekhar S. , Gatti Anthony A. , Nissi Mikko , Mustonen Anne-Mari , Säisänen Laura , Reijonen Jusa , Nieminen Petteri , Julkunen Petro , Töyräs Juha , Saxby David J. , Lloyd David G. , Korhonen Rami K.
Published: October 2023

Objective

To develop and assess an automatic and robust knee musculoskeletal finite element (MSK-FE) modeling pipeline.

Methods

Magnetic resonance images (MRI) were used to train nnU-Net networks for auto-segmentation of knee bones (femur, tibia, patella, and fibula), cartilages (femur, tibia, and patella), menisci, and major knee ligaments. Two different MRI sequences were used to broaden applicability. Next, we created MSK-FE models of an unseen dataset using two MSK-FE modeling pipelines: template-based and auto-meshing. MSK models had personalized knee geometries with multi-degree-of-freedom elastic foundation contacts. FE models used fibril-reinforced poroviscoelastic swelling material models for cartilages and menisci.

Results

Volumes of knee bones, cartilages, and menisci did not significantly differ (p>0.05) across MRI sequences. MSK models estimated secondary knee kinematics during passive knee flexion tests consistent within vivoand simulation-based values from the literature. Between the template-based and auto-meshing FE models, estimated cartilage mechanics often differed significantly (p<0.05), though differences were <15% (considering peaks during walking), i.e., <1.5 MPa for maximum principal stress, <1 percentage point for collagen fibril strain, and <3 percentage points for maximum shear strain.

Conclusion

The template-based modeling provided a more rapid and robust tool than the auto-meshing approach, while the estimated knee biomechanics were comparable. Nonetheless, the auto-meshing approach might provide more accurate estimates in subjects with distinct knee irregularities, e.g., cartilage lesions.

Significance

The MSK-FE modeling tool provides a rapid, easy-to-use, and robust approach to investigating task- and person-specific mechanical responses of the knee cartilage and menisci, holding significant promise, e.g., in personalized rehabilitation planning.
MADAME: a user-friendly bioinformatic tool for data and metadata retrieval in microbiome research
Authors: Fumagalli Sara , Soletta Giulia , Agostinetto Giulia , Striani Manuel , Labra Massimo , Casiraghi Maurizio , Bruno Antonia
Published: October 2023

Microbiome research advancements have provided countless insights. Despite the massive amount of data currently stored in public repositories, these resources remain vastly underutilized due to the intricacy of data and metadata retrieval from these databases. However, leveraging data-driven approaches is crucial for microbiome research progress by overcoming variations between studies and identifying generalizable trends.

We designed the open-access and user-friendly bioinformatic tool MADAME (MetADAta MicrobiomE) to streamline the data and metadata retrieval process. MADAME addresses the challenges posed by the public repositories’ current limitations, allowing users to retrieve publications associated with the accession codes of interest. Additionally, MADAME allows users to visually explore retrieved results through the generation of a comprehensive report with plots and statistics. These unique features of MADAME let users maximize their time and resources, enabling them to assess metadata suitability before pursuing data download. To showcase its diverse functionalities, we recreate several scenarios to meet the diverse requirements that researchers may have.
Epigenome erosion in Alzheimer’s disease brain cells and induced neurons
Authors: Wang Bang-An , Jones Jeffrey R. , Zhou Jingtian , Tian Wei , Wu Yue , Wang Wenliang , Berube Peter , Bartlett Anna , Castanon Rosa , Nery Joseph R. , Chen Huaming , Kenworthy Mia , Altshul Jordan , Valadon Cynthia , Wang Yichen , Kang Austin , Goodman Ryan , Liem Michelle , Claffey Naomi , O’Connor Caz , Metcalf Jeffrey , Luo Chongyuan , Gage Fred H. , Ecker Joseph R.
Published: October 2023

Late-onset Alzheimer’s disease (LOAD) is typically sporadic, correlated only to advanced age, and has no clear genetic risk factors. The sporadic nature of LOAD presents a challenge to understanding its pathogenesis and mechanisms. Here, we comprehensively investigated the epigenome of LOAD primary entorhinal cortex brain tissues via single-cell multi-omics technologies, simultaneously capturing DNA methylation and 3D chromatin conformation. We identified AD-specific DNA methylation signatures and found they interact with bivalent promoters of AD differentially expressed genes. In addition, we discovered global chromosomal epigenome erosion of 3D genome structure within and across brain cell types. Furthermore, to evaluate whether these age- and disease-dependent molecular signatures could be detected in thein vitrocellular models, we derived induced neurons (iNs) converted directly from AD patients’ fibroblasts and found a set of conserved methylation signatures and shared molecular processes. We developed a machine-learning algorithm to identify robust and consistent methylation signatures of LOADin vivoprimary brain tissues andin vitrofibroblast-derived iNs. The results recapitulate the age- and disease-related epigenetic features in iNs and highlight the power of epigenome and chromatin conformation for identifying molecular mechanisms of neuronal aging and generating biomarkers for LOAD.

HIGHLIGHT

AD-specific DNA methylation signatures are identified in entorhinal cortex brain cell types

The AD differentially expressed genes linked with differentially methylated regions via loop interactions are enriched in a bivalent chromatin state

Chromosomal epigenome erosion of 3D genome structures occurs in LOAD brain cell types.

Shared and reliable methylation signatures are observed in bothin vitrocellular iN models and primary brain tissues.

Machine learning models identify robust and reliable methylation loci as AD biomarkers across cell types.
Neural activity ramps in frontal cortex signal extended motivation during learning
Authors: Regalado Josue M. , Asensio Ariadna Corredera , Haunold Theresa , Toader Andrew C. , Li Yan Ran , Neal Lauren A. , Rajasethupathy Priya
Published: October 2023

Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC) -to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.
High-density recording reveals sparse clusters (but not columns) for shape and texture encoding in macaque V4
Authors: Namima Tomoyuki , Kempkes Erin , Zamarashkina Polina , Owen Natalia , Pasupathy Anitha
Published: October 2023

Macaque area V4 includes neurons that exhibit exquisite selectivity for visual form and surface texture, but their functional organization across laminae is unknown. We used high-density Neuropixels probes in two awake monkeys to characterize shape and texture tuning of dozens of neurons simultaneously across layers. We found sporadic clusters of neurons that exhibit similar tuning for shape and texture: ∼20% exhibited similar tuning with their neighbors. Importantly, these clusters were confined to a few layers, seldom ‘columnar’ in structure. This was the case even when neurons were strongly driven, and exhibited robust contrast invariance for shape and texture tuning. We conclude that functional organization in area V4 is not columnar for shape and texture stimulus features and in general organization maybe at a coarse scale (e.g. encoding of 2D vs 3D shape) rather than at a fine scale in terms of similarity in tuning for specific features (as in the orientation columns in V1). We speculate that this may be a direct consequence of the great diversity of inputs integrated by V4 neurons to build variegated tuning manifolds in a high-dimensional space.

Significance Statement

In primary visual cortex of the macaque monkey, studies have demonstrated columnar functional organization, i.e. shared tuning across layers for stimulus orientation, spatial frequency, ocular dominance, etc. In mid and higher level visual form processing stages, where neurons exhibit high-dimensional tuning, functional organization has been harder to evaluate. Here, leveraging the use of the high-density Neuropixels probes to record simultaneously from dozens of neurons across cortical layers, we demonstrate that functional organization is not columnar for shape and texture tuning in area V4, a midlevel stage critical for form processing. Our results contribute to the debate about the functional significance of cortical columns providing support to the idea that they emerge due to one-to-many representational expansion.
NCOR1+/CD4+ T cells in tertiary lymphoid organs suppresses tumor growth and predicts favourable prognosis in pancreatic ductal adenocarcinoma
Authors: Dong Tiangeng , Yi Tuo , Gong Yuda , Gao Weidong , Zhang Bo , Sheng Weizhong
Published: October 2023

CD4+ T cells have critical roles in anti-tumour immunity and its differentiation is known to be regulated by the nuclear receptor co-repressor 1 (NCOR1). Previous studies suggested that high CD4+ T cells are associated with a favourable prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of NCOR1 in PDAC is still missing. In this study, the pathological impact of NCOR1 and CD4 has been analysed by multiplex immunohistochemistry in 100 PADC patients. NCOR1 expression in tertiary lymphoid organs is positively associated with the good prognosis of PDAC patients, while its expression in tumour tissue is not. Furthermore, the presence of NCOR1+/CD4+ T cells in tertiary lymphoid organs predicts a favourable prognosis in PDAC. Mechanistically, upregulation of NCOR1 expression in CD4+ T cells increases the release of TNF-α, which induces the apoptosis of the tumor cellsin vitro. Together, our data highlighted the tumour suppressive role of NCOR1+/CD4+ T cells in PDAC.
PhenoID, a language model normalizer of physical examinations from genetics clinical notes
Authors: Weissenbacher Davy , Rawal Siddharth , Zhao Xinwei , Priestley Jessica R. C. , Szigety Katherine M. , Schmidt Sarah F. , Higgins Mary J. , Magge Arjun , O’Connor Karen , Gonzalez-Hernandez Graciela , Campbell Ian M.
Published: October 2023

Abstract

Background

Phenotypes identified during dysmorphology physical examinations are critical to genetic diagnosis and nearly universally documented as free-text in the electronic health record (EHR). Variation in how phenotypes are recorded in free-text makes large-scale computational analysis extremely challenging. Existing natural language processing (NLP) approaches to address phenotype extraction are trained largely on the biomedical literature or on case vignettes rather than actual EHR data.

Methods

We implemented a tailored system at the Children’s Hospital of Philadelpia that allows clinicians to document dysmorphology physical exam findings. From the underlying data, we manually annotated a corpus of 3136 organ system observations using the Human Phenotype Ontology (HPO). We provide this corpus publicly. We trained a transformer based NLP system to identify HPO terms from exam observations. The pipeline includes an extractor, which identifies tokens in the sentence expected to contain an HPO term, and a normalizer, which uses those tokens together with the original observation to determine the specific term mentioned.

Findings

We find that our labeler and normalizer NLP pipeline, which we call PhenoID, achieves state-of-the-art performance for the dysmorphology physical exam phenotype extraction task. PhenoID’s performance on the test set was 0.717, compared to the nearest baseline system (Pheno-Tagger) performance of 0.633. An analysis of our system’s normalization errors shows possible imperfections in the HPO terminology itself but also reveals a lack of semantic understanding by our transformer models.

Interpretation

Transformers-based NLP models are a promising approach to genetic phenotype extraction and, with recent development of larger pre-trained causal language models, may improve semantic understanding in the future. We believe our results also have direct applicability to more general extraction of medical signs and symptoms.

Funding

US National Institutes of Health