bluuebunny/crossref_metadata_2025 huggingface dataset:
Emission of water soluble brown carbon from different combustion sources: optical properties and functional group characterisation
Authors: Hossen Md Al-amin , Roy Shatabdi , Zaman Shahid Uz , Salam Abdus
Published: July 2023

Brown carbon (BrC) has a large impact on the Earth’s radiative balance. This study examined BrC’s optical characteristics, chemical functional groups, and total organic carbon (TOC) in deposited particulate matter from combustion of biomass, fossil fuels, and mosquito coil. A UV–vis spectrophotometer was used to assess BrC’s optical properties, a TOC analyzer was used to quantify TOC, and attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR) was used to identify functional group. The light absorption properties (absorption coefficient (babs-BrC), mass absorption efficiency (MAE365), absorption angstrom exponent (AAE), and refractive index (kabs-BrC)) were determined. Among biomasses, wheat straw exhibited the greatest value of babs-BrC (27.26 × 103 ± 4.09 × 103 Mm−1) whereas maize straw had the lowest value of babs-BrC (7.38 × 103 ± 1.11 × 103 Mm−1). A higher light absorption coefficient at 365 nm suggested that chromophores contributed more to the process. AAE followed this sequence - mosquito coil (5.46 ± 0.82) > biomass (5.13 ± 1.45) > fossil fuels (2.85 ± 0.32). The highest value of MAE365 (0.99 ± 0.15 m2 gC−1) and kabs-BrC (0.028 ± 0.004) was obtained in wheat straw, whereas the lowest value of MAE365 (0.07 ± 0.011 m2 gC−1) and kabs-BrC (0.002) was identified in octane. Biomasses samples showed a strong peak at ∼850, ∼1368, ∼1370, ∼1306, and near 1640 cm−1, indicating that the major component of BrC was organic nitrate R-ONO2 which is responsible to increase the light absorption properties. It also contains complex heterocyclic aromatic ring compounds, carbonyl group (C=O), and nitrogen-containing groups such as −NO
2, C≡N. The projected substantial contribution of BrC to overall light absorption is one illustration of the probable climatic effect of biomasses and fossil fuel burning in Southeast Asian region.
Comparative analysis of gate-oxide engineering in charge plasma based nanowire transistor
Authors: Debnath Joyprokash , Sikder Md Ezazul Hoque , Singha Showmik
Published: July 2023

In this work, a hetero-gate-oxide charge plasma-based nanowire transistor (HGO-CPNWT) has been proposed, characterized, and a comparative analysis with the conventional charge plasma-based nanowire transistor (CCPNWT) and the Stack-Gate-Oxide CPNWT (SGO-CPNWT) has been investigated. The effects of stacking a high-κ gate oxide with a low-κ gate oxide beneath the gate and segmenting the gate oxide with a high-κ oxide at the source side and low-κ oxide at the drain side have been analyzed with the short channel effects (SCEs) parameters and radio-frequency (RF)/analog figure of merits. The HGO-CPNWT demonstrates enhanced performances in terms of Ion/Ioff of 1.66 × 108, subthreshold slope (SS) of 65.74 mV/decade, drain induced barrier lowering (DIBL) of 47.857 mV/V, peak transconductance (g
m
) of 3.43 × 10−5 S/μm, and peak cut-off frequency (f
t
) of 114 GHz. The simulation employs a comprehensive quantum transport model, and the comparative impacts of adjusting channel length (L
g
), nanowire radius (r), and gate oxide thickness (Tox) are studied.
A mixed-signal oscillatory neural network for scalable analog computations in phase domain
Authors: Delacour Corentin , Carapezzi Stefania , Boschetto Gabriele , Abernot Madeleine , Gil Thierry , Azemard Nadine , Todri-Sanial Aida
Published: July 2023

Digital electronics based on von Neumann’s architecture is reaching its limits to solve large-scale problems essentially due to the memory fetching. Instead, recent efforts to bring the memory near the computation have enabled highly parallel computations at low energy costs. Oscillatory neural network (ONN) is one example of in-memory analog computing paradigm consisting of coupled oscillating neurons. When implemented in hardware, ONNs naturally perform gradient descent of an energy landscape which makes them particularly suited for solving optimization problems. Although the ONN computational capability and its link with the Ising model are known for decades, implementing a large-scale ONN remains difficult. Beyond the oscillators’ variations, there are still design challenges such as having compact, programmable synapses and a modular architecture for solving large problem instances. In this paper, we propose a mixed-signal architecture named Saturated Kuramoto ONN (SKONN) that leverages both analog and digital domains for efficient ONN hardware implementation. SKONN computes in the analog phase domain while propagating the information digitally to facilitate scaling up the ONN size. SKONN’s separation between computation and propagation enhances the robustness and enables a feed-forward phase propagation that is showcased for the first time. Moreover, the SKONN architecture leads to unique binarizing dynamics that are particularly suitable for solving NP-hard combinatorial optimization problems such as finding the weighted Max-cut of a graph. We find that SKONN’s accuracy is as good as the Goemans–Williamson 0.878-approximation algorithm for Max-cut; whereas SKONN’s computation time only grows logarithmically. We report on Weighted Max-cut experiments using a 9-neuron SKONN proof-of-concept on a printed circuit board (PCB). Finally, we present a low-power 16-neuron SKONN integrated circuit and illustrate SKONN’s feed-forward ability while computing the XOR function.
A fast proximal gradient method and convergence analysis for dynamic mean field planning
Authors: Yu Jiajia , Lai Rongjie , Li Wuchen , Osher Stanley
Published: July 2023

In this paper, we propose an efficient and flexible algorithm to solve dynamic mean-field planning problems based on an accelerated proximal gradient method. Besides an easy-to-implement gradient descent step in this algorithm, a crucial projection step becomes solving an elliptic equation whose solution can be obtained by conventional methods efficiently. By induction on iterations used in the algorithm, we theoretically show that the proposed discrete solution converges to the underlying continuous solution as the grid becomes finer. Furthermore, we generalize our algorithm to mean-field game problems and accelerate it using multilevel and multigrid strategies. We conduct comprehensive numerical experiments to confirm the convergence analysis of the proposed algorithm, to show its efficiency and mass preservation property by comparing it with state-of-the-art methods, and to illustrate its flexibility for handling various mean-field variational problems.
Clinician and System-Level Facilitators for Successful School-Based Telehealth Implementation during COVID-19: Guiding Factors to Help Embrace Changes in Service Delivery
Authors: Acri Mary , Layman Deborah , Grande Vincent , Cummings Anni , Goldstein Patricia , Wade Niasha , Manjunath Sanjana , Finnerty Molly
Published: July 2023

School-based mental health clinics are the ideal venue to provide mental health services for youth due to their accessibility and lack of stigma compared with other community treatment centers. There were challenges associated with the abrupt shift to remote education and clinic services caused by COVID-19, but some school-based mental health clinics excelled in their implementation of telehealth services. This study of New York schools found four main facilitators to implementing telehealth services among school-based mental health clinics: (1) strong collaborative relationships between the clinic and school setting, (2) active and responsive leadership, (3) provider experience in conducting telehealth, and (4) provider flexibility to accommodate the needs of children and families. Factors were identified at every level of the school-based mental health clinic and system that helped to facilitate exemplary telehealth service delivery and implementation.
Prezygotic reproductive barriers in precopulatory behavior of tidepool copepod species
Authors: Tsuboko-Ishii Satomi , Burton Ronald S
Published: July 2023

Complexity in prezygotic mating behavior can contribute to the emergence of sexual incompatibility and reproductive isolation. In this study, we performed behavioral tests with two tidepool copepod species of the genus Tigriopus to explore the possibility of precopulatory behavioral isolation. We found that interspecific mating attempts failed prior to genital contact, and that this failure occurred at different behavioral steps between reciprocal pairings. Our results suggest that prezygotic barriers may exist at multiple points of the behavioral process on both male and female sides, possibly due to interspecific differences in mate-recognition cues used at those “checkpoints.” While many copepod species are known to show unique precopulatory mate-guarding behavior, the potential contribution of prezygotic behavioral factors to their isolation is not widely recognized. The pattern of sequential mate-guarding behaviors may have allowed the diversification of precopulatory communication and contributed to the evolutionary diversity of the Tigriopus copepods.
A roadmap of haustorium morphogenesis in parasitic plants
Authors: Kirschner Gwendolyn K , Xiao Ting Ting , Jamil Muhammad , Al-Babili Salim , Lube Vinicius , Blilou Ikram
Published: July 2023

Parasitic plants invade their host through their invasive organ, the haustorium. This organ connects to the vasculature of the host roots and hijacks water and nutrients. Although parasitism has evolved independently in plants, haustoria formation follows a similar mechanism throughout different plant species, highlighting the developmental plasticity of plant tissues. Here, we compare three types of haustoria formed by the root and shoot in the plant parasites Striga and Cuscuta. We discuss mechanisms underlying the interactions with their hosts and how different approaches have contributed to major understanding of haustoria formation and host invasion. We also illustrate the role of auxin and cytokinin in controlling this process.
An integrated genomic approach identifies follistatin as a target of the p63-epidermal growth factor receptor oncogenic network in head and neck squamous cell carcinoma
Authors: Oyelakin Akinsola , Sosa Jennifer , Nayak Kasturi Bala , Glathar Alexandra , Gluck Christian , Sethi Isha , Tsompana Maria , Nowak Norma , Buck Michael , Romano Rose-Anne , Sinha Satrajit
Published: July 2023

Although numerous putative oncogenes have been associated with the etiology of head and neck squamous cell carcinoma (HNSCC), the mechanisms by which these oncogenes and their downstream targets mediate tumor progression have not been fully elucidated. We performed an integrative analysis to identify a crucial set of targets of the oncogenic transcription factor p63 that are common across multiple transcriptomic datasets obtained from HNSCC patients, and representative cell line models. Notably, our analysis revealed FST which encodes follistatin, a secreted glycoprotein that inhibits the transforming growth factor TGFβ/activin signaling pathways, to be a direct transcriptional target of p63. In addition, we found that FST expression is also driven by epidermal growth factor receptor EGFR signaling, thus mediating a functional link between the TGF-β and EGFR pathways. We show through loss- and gain-of-function studies that FST predominantly imparts a tumor-growth and migratory phenotype in HNSCC cells. Furthermore, analysis of single-cell RNA sequencing data from HNSCC patients unveiled cancer cells as the dominant source of FST within the tumor microenvironment and exposed a correlation between the expression of FST and its regulators with immune infiltrates. We propose FST as a prognostic biomarker for patient survival and a compelling candidate mediating the broad effects of p63 on the tumor and its associated microenvironment.
Access to High-Quality Hospice Care in a For-Profit World
Authors: Odejide Oreofe O , Aldridge Melissa D
Published: July 2023

Evidence supporting the relief of suffering and improved end-of-life care provided by hospice is in contrast with recent media reports of cases of poor-quality care driven by profit-motivated hospices. This commentary presents a brief history of hospice and potential solutions to address the current challenges affecting access to high-quality hospice care.
Multiplex Quantitative PCR Assay for Detection of Spinach and Lettuce Downy Mildews Using Spore Trapping
Authors: Clark Kelley J. , Anchieta Amy G. , Cavanaugh Keri , Martin Frank N. , Correll James C. , Montazar Aliasghar , Putman Alexander I. , Klosterman Steven J.
Published: July 2023

Downy mildews are major constraints on spinach and lettuce production globally. Disease management can be achieved with fungicides, but routine applications are costly and can lead to pathogen resistance. Detection of airborne spores could guide sustainable fungicide application, and, considering that spinach and lettuce are often grown in the same cycles, simultaneous detection of both pathogens is practical. Here, a multiplex hydrolysis probe quantitative PCR assay was designed using single copy mitochondrial DNA targets for spinach downy mildew ( Peronospora effusa) and lettuce downy mildew ( Bremia lactucae). To quantify P. effusa and B. lactucae sporangia, a standard curve was developed for each pathogen using the multiplex qPCR to amplify DNA obtained from known dilutions of sporangia. Analysis of these curves revealed a greater sensitivity for B. lactucae, indicating that the sporangia of B. lactucae may harbor more mitochondria than those of P. effusa, providing insight into the biology of these pathogens. The multiplex qPCR assay was partnered with two different spore trap types: a cyclone spore trap and an impaction spore trap. Results from air sampling revealed that the cyclone spore traps collect significantly more sporangia compared with impaction traps. Exposure of P. effusa sporangia to desiccation was performed to assess the environmental impact on the assay, and although detection levels were reduced, they were still apparent. This detection and quantification tool will be useful in efforts to improve the accuracy of downy mildew forecasting, which in return may reduce fungicide usage or improve its efficiency.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Care for the patient with low back pain
Authors: Kearns Gary A. , Day Mercedes , Moore Amy Karen , Munger Larry
Published: July 2023

Low back pain (LBP) continues to be one of the most common conditions leading patients to seek medical care globally. The NP is on the frontline, playing an integral role in caring for patients with LBP. Understanding the etiology of LBP is essential in the treatment.
Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors
Authors: Syal Arjun , Cozzi Francesca M. , Vazquez Sima , Spirollari Eris , Naftchi Alexandria F. , Das Ankita , Ng Christina , Akinleye OluwaToba , Gagliardi Thomas , Dominguez Jose F. , Wang Arthur , Kinon Merritt D.
Published: July 2023

Study Design:

This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks.

Objective:

This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs.

Summary of Background Data:

Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate.

Methods:

A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used.

Results:

A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies.

Conclusions:

After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted.

Level of Evidence:

Level 3.
Measuring the Impact of ICU Strain on Mortality, After-Hours Discharge, Discharge Delay, Interhospital Transfer, and Readmission in Australia With the Activity Index*
Authors: Pilcher David V. , Hensman Tamishta , Bihari Shailesh , Bailey Michael , McClure Jason , Nicholls Mark , Chavan Shaila , Secombe Paul , Rosenow Melissa , Huckson Sue , Litton Edward
Published: July 2023

OBJECTIVES:

ICU resource strain leads to adverse patient outcomes. Simple, well-validated measures of ICU strain are lacking. Our objective was to assess whether the “Activity index,” an indicator developed during the COVID-19 pandemic, was a valid measure of ICU strain.

DESIGN:

Retrospective national registry-based cohort study.

SETTING:

One hundred seventy-five public and private hospitals in Australia (June 2020 through March 2022).

SUBJECTS:

Two hundred seventy-seven thousand seven hundred thirty-seven adult ICU patients

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Data from the Australian and New Zealand Intensive Care Society Adult Patient Database were matched to the Critical Health Resources Information System. The mean daily Activity index of each ICU (census total of “patients with 1:1 nursing” + “invasive ventilation” + “renal replacement” + “extracorporeal membrane oxygenation” + “active COVID-19,” divided by total staffed ICU beds) during the patient’s stay in the ICU was calculated. Patients were categorized as being in the ICU during very quiet (Activity index < 0.1), quiet (0.1 to < 0.6), intermediate (0.6 to < 1.1), busy (1.1 to < 1.6), or very busy time-periods (≥ 1.6). The primary outcome was in-hospital mortality. Secondary outcomes included after-hours discharge from the ICU, readmission to the ICU, interhospital transfer to another ICU, and delay in discharge from the ICU. Median Activity index was 0.87 (interquartile range, 0.40–1.24). Nineteen thousand one hundred seventy-seven patients died (6.9%). In-hospital mortality ranged from 2.4% during very quiet to 10.9% during very busy time-periods. After adjusting for confounders, being in an ICU during time-periods with higher Activity indices, was associated with an increased risk of in-hospital mortality (odds ratio [OR], 1.49; 99% CI, 1.38–1.60), after-hours discharge (OR, 1.27; 99% CI, 1.21–1.34), readmission (OR, 1.18; 99% CI, 1.09–1.28), interhospital transfer (OR, 1.92; 99% CI, 1.72–2.15), and less delay in ICU discharge (OR, 0.58; 99% CI, 0.55–0.62): findings consistent with ICU strain.

CONCLUSIONS:

The Activity index is a simple and valid measure that identifies ICUs in which increasing strain leads to progressively worse patient outcomes.
Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis
Authors: Liu Kaixiong , Guo Qifu , Ding Ying , Luo Li , Huang Jianchai , Zhang Qijie
Published: July 2023

Background:

Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.

Methods:

Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3–V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.

Results:

The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella, Sphingomonas, Polaribacter_1, Lachnospiraceae_NK4A136_group, Klebsiella, and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; r
s = 0.349, P = 0.020 and r
s = 0.393, P = 0.008), while Prevotella-9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients (r
s = 0.304, P = 0.045, and r
s = 0.300, P = 0.048, respectively). Prevotella-1 was positively correlated with white blood cell counts (WBC, r
s = 0.347, P = 0.021), neutrophil percentage (Neu%, r
s = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, r
s = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, r
s = –0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% (r
s = –0.445, P = 0.003) and NLR (r
s = –0.436, P = 0.003), while positively associated with Lym% (r
s = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.

Conclusions:

ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.
Dysregulation of lipid metabolism in the pseudolobule promotes region-specific autophagy in hepatitis B liver cirrhosis
Authors: Pu Wenjun , Wang Xi , Zhong Xiaoni , Zhao Dong , Zeng Zhipeng , Cai Wanxia , Zhong Yafang , Huang Jianrong , Tang Donge , Dai Yong
Published: July 2023

Background:

Chronic hepatitis B (CHB) infection leads to liver cirrhosis (LC), the end stage of liver fibrosis. The precise diagnosis and effective therapy for hepatitis B cirrhosis are still lacking. It is highly necessary to elucidate the metabolic alteration, especially the spatial distribution of metabolites, in LC progression.

Methods:

In this study, LC-MS/MS together with an airflow-assisted ionization mass spectrometry imaging system was applied to analyze and compare the metabolites’ spatial distribution in healthy control (HC) and hepatitis B LC tissue samples. The liver samples were further divided into several subregions in HC and LC groups based on the anatomical characteristics and clinical features.

Results:

Both the LC-MS/MS and mass spectrometry imaging results indicated separated metabolite clusters between the HC and LC groups. The differential metabolites were mainly concentrated in lipid-like molecules and amino acids. The phosphatidylcholines (PCs), lysoPCs, several fatty acids, and amino acids reduced expression in the LC group with region specific. Acyl-CoA thioesterase 2 and choline/ethanolamine phosphotransferase 1, which regulate PC and fatty acid metabolism, were significantly decreased in the pseudolobule. Meanwhile, the increased expression of LC3B and p62 in the pseudolobule indicated the upregulation of autophagy.

Conclusions:

Hepatitis B LC induced region-specific autophagy by increasing the expression of LC3B and p62 in the pseudolobule and by dysregulation of unsaturated fatty acids, amino acids, and PC metabolism. The mass spectrometry imaging system provided additional metabolites’ spatial information, which can promote biomarker screening technology and support the exploration of novel mechanisms in LC.
“But I didn’t drink!”: What to do with discordant phosphatidylethanol results
Authors: Winder Gerald Scott , Clifton Erin G. , Denysenko Lex , DiChiara Alex M. , Hathaway David , Perumalswami Ponni V. , Shenoy Akhil , Suzuki Joji , Tareen Kinza , Mellinger Jessica L. , Fernandez Anne C.
Published: July 2023

Liver transplantation (LT) teams must be adept at detecting, evaluating, and treating patients’ alcohol use, given its prominence among psychological and behavioral phenomena which cause and contribute to liver diseases. Phosphatidylethanol (PEth) is a highly useful alcohol biomarker increasingly recommended for routine use in hepatology and LT. PEth is unique among alcohol biomarkers because of its wide detection window, high sensitivity and specificity, and the correlation of its numerical value with different patterns of alcohol use. Alongside myriad clinical opportunities in hepatology and LT, PEth also confers numerous challenges: little guidance exists about its clinical use; fearing loss of LT access and the reactions of their clinicians and families, candidates and recipients are incentivized to conceal their alcohol use; and liver clinicians report lack of expertise diagnosing and treating substance-related challenges. Discordance between patient self-reported alcohol use and toxicology is yet another common and particularly difficult circumstance. This article discusses the general toxicological properties of PEth; explores possible scenarios of concordance and discordance among PEth results, patient history, and self-reported drinking; and provides detailed clinical communication strategies to explore discordance with liver patients, a key aspect of its use.
Estimation of Time Since Death Using Biochemical Markers in Synovial Fluid
Authors: V Poovaragavan , Vidua Raghvendra Kumar , Kumar Ashok , P Ponmani , Keche Atul S. , Sahoo Niranjan , Agarwal Puneet K.
Published: July 2023

In the field of forensic medicine, estimating time since death plays an important role in helping the investigative organizations unravel the mystery of crime. Presently, many less reliable subjective parameters are being used to measure it, necessitating the need to have more specific and objective parameters. This cross-sectional comparative study was conducted at the Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Bhopal, India on 60 deceased bodies to determine the correlation between known time since death and biochemical parameters in the synovial fluid specifically sodium, potassium, lactate, and total proteins, analyzed using random access fully automated chemical analyzer (Beckman Coulter Au680) followed by estimation of correlation using Spearman correlation test.

All the biochemical parameters that were tested in the synovial fluid except for sodium showed a significant correlation. The potassium and lactate showed a significant positive correlation (P < 0.001), and on the contrary, the total protein level showed a significant negative correlation with time since death (P < 0.001). This study shows usefulness of these markers in estimating the time since death. The smaller sample size and the unavailability of the results of effect of cold storage on these parameters necessitate the need of further similar studies to uncover the real practical application.
Behavioural susceptibility theory: the role of appetite in genetic susceptibility to obesity in early life
Authors: Llewellyn C. H. , Kininmonth A. R. , Herle M. , Nas Z. , Smith A. D. , Carnell S. , Fildes A.
Published: July 2023

Excess weight gained during the early years and, in particular, rapid weight gain in the first 2 years of life, are a major risk factors for adult obesity. The growing consensus is that childhood obesity develops from a complex interaction between genetic susceptibility and exposure to an ‘obesogenic’ environment. Behavioural susceptibility theory (BST) was developed to explain the nature of this gene–environment interaction, and why the ‘obesogenic’ environment does not affect all children equally. It hypothesizes that inherited variation in appetite, which is present from birth, determines why some infants and children overeat, and others do not, in response to environmental opportunity. That is, those who inherit genetic variants promoting an avid appetite are vulnerable to overeating and developing obesity, while those who are genetically predisposed to have a smaller appetite and lower interest in food are protected from obesity—or even at risk of being underweight. We review the breadth of research to-date that has contributed to the evidence base for BST, focusing on early life, and discuss implications and future directions for research and theory.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Physiological protection against weight gain: evidence from overfeeding studies and future directions
Authors: Lund Jens , Clemmensen Christoffer
Published: July 2023

Body weight is under physiological regulation. When body fat mass decreases, a series of responses are triggered to promote weight regain by increasing food intake and decreasing energy expenditure. Analogous, in response to experimental overfeeding, excessive weight gain is counteracted by a reduction in food intake and possibly by an increase in energy expenditure. While low blood leptin and other hormones defend against weight loss, the signals that oppose overfeeding-induced fat mass expansion are still unknown. In this article, we discuss insights gained from overfeeding interventions in humans and intragastric overfeeding studies in rodents. We summarize the knowledge on the relative contributions of energy intake, energy expenditure and energy excretion to the physiological defence against overfeeding-induced weight gain. Furthermore, we explore literature supporting the existence of unidentified endocrine and non-endocrine pathways that defend against weight gain. Finally, we discuss the physiological drivers of constitutional thinness and suggest that overfeeding of individuals with constitutional thinness represents a gateway to understand the physiology of weight gain resistance in humans. Experimental overfeeding, combined with modern multi-omics techniques, has the potential to unveil the long-sought signalling pathways that protect against weight gain. Discovering these mechanisms could give rise to new treatments for obesity.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Characterization of Multidrug Resistant serogroup 19 Streptococcus pneumoniae isolated from the healthy children below five years of age in Indonesia
Authors: Salsabila Korrie , Winarti Yayah , Paramaiswari Wisiva Tofriska , Tafroji Wisnu , Putri Hanifah Fajri Maharani , Daningrat Wa Ode Dwi , Wulandari I Gusti Ayu Inten , Soebandrio Amin , Safari Dodi
Published: July 2023

We investigated the resistance genes, pilus islet, biofilm formation ability, and sequence types of multidrug-resistant Streptococcus pneumoniae (MDRSP) isolated from the healthy children below 5 years of age in Indonesia. In all, 104 archived MDRSP isolates were screened for the presence of antibiotic resistance genes and  the rrgC  (pilus islet 1) and pitB (pilus islet 2) genes. Multilocus sequence typing and  biofilm formation was determined by DNA sequencing and the ability of cells to adhere to the walls respectively. Results have shown that the mefA, ermB, and tetM genes were found in 93%, 52%, and 100% of MDRSP isolates respectively. The insertion of arginine, proline, and Ile-100-Leu were the most common mutations in the folA and folP genes. Pilus islet 1 and type 2 were discovered in 93% and 82% of MDRSP isolates respectively. The MDRSP isolates showed no biofilm formation ability (64%) and  the most of sequence type was ST1464. This finding can be used to provide further considerations in implementing and monitoring pneumococcal vaccination in Indonesia.
TREATMENT OUTCOME AND ITS PREDICTORS AMONG DIABETIC PATIENTS ATTENDING AT SELECTED HOSPITALS OF SOUTHERN ETHIOPIA
Authors: Gebre Bereket Beyene , Hoyiso Dawit , Woldu Kinfe
Published: July 2023

Background

Diabetes is one of the most serious health crises of the twenty-first century, with the World Health Organization (WHO) estimating that hyperglycemia is the third leading cause of early death globally, following high blood pressure and cigarette use. It is an important cause of blindness, kidney failure, lower limb amputation and other long-term consequences that impact significantly on quality of life. People get sick, die, and health care costs go up as a result.

Objectives

Diabetes mellitus treatment outcome and determinants in patients undergoing diabetes treatments in selected hospitals in southern Ethiopia, 2021.

Methods

A source population included all diabetic patients who attended chosen hospitals in southern Ethiopia. A cross-sectional study with an institutional focus was conducted in a few hospitals in southern Ethiopia. A pre-tested questionnaire was used to collect information about the patient. Following data cleaning and error checking, the data was loaded into Epi-data to eliminate errors before being exported to SPSS for analysis. The descriptive data were presented using tables and graphics. The result variable was evaluated using a logistic regression model to uncover predictors once the underlying assumptions of the regression analysis were verified. All independent variables with p0.25 were considered for multivariate analysis. The level of significance was then set at p0.05, and the final model was AOR with 95% CL.

Result

277 (65.6%) of the whole sample had positive treatment outcomes. The existence of complication AOR 95%CI; 0.425 (0.217,.832), and elevated fasting blood glucose AOR 95%CI; 0.080 (0.034, 0.188) were revealed to be independent predictors. Given the low size of treatment outcome, providing health information regarding sticking to prescribed medicine and monitoring fasting blood glucose level will result in a positive clinical outcome.
Machine learning illuminates how diet influences the evolution of yeast galactose metabolism
Authors: Harrison Marie-Claire , Ubbelohde Emily J. , LaBella Abigail L. , Opulente Dana A. , Wolters John F. , Zhou Xiaofan , Shen Xing-Xing , Groenewald Marizeth , Hittinger Chris Todd , Rokas Antonis
Published: July 2023

How genomic differences contribute to phenotypic differences across species is a major question in biology. The recently characterized genomes, isolation environments, and qualitative patterns of growth on 122 sources and conditions of 1,154 strains from 1,049 fungal species (nearly all known) in the subphylum Saccharomycotina provide a powerful, yet complex, dataset for addressing this question. In recent years, machine learning has been successfully used in diverse analyses of biological big data. Using a random forest classification algorithm trained on these genomic, metabolic, and/or environmental data, we predicted growth on several carbon sources and conditions with high accuracy from presence/absence patterns of genes and of growth in other conditions. Known structural genes involved in assimilation of these sources were important features contributing to prediction accuracy, whereas isolation environmental data were poor predictors. By further examining growth on galactose, we found that it can be predicted with high accuracy from either genomic (92.6%) or growth data in 120 other conditions (83.3%) but not from isolation environment data (65.7%). When we combined genomic and growth data, we noted that prediction accuracy was even higher (93.4%) and that, after theGALactose utilization genes, the most important feature for predicting growth on galactose was growth on galactitol. These data raised the hypothesis that several species in two orders, Serinales and Pichiales (containingCandida aurisand the genusOgataea, respectively), have an alternative galactose utilization pathway because they lack theGALgenes. Growth and biochemical assays of several of these species confirmed that they utilize galactose through an oxidoreductive D-galactose pathway, rather than the canonicalGALpathway. We conclude that machine learning is a powerful tool for investigating the evolution of the yeast genotype-phenotype map and that it can help uncover novel biology, even in well-studied traits.
Distinct disease-modifying therapies are associated with different blood immune cell profiles in people with relapsing-remitting multiple sclerosis
Authors: Canto-Gomes João , Boleixa Daniela , Teixeira Catarina , da Silva Ana Martins , González-Suárez Inés , Cerqueira João , Correia-Neves Margarida , Nobrega Claudia
Published: July 2023

Disease modifying therapies (DMTs) used for treating people with relapsing-remitting multiple sclerosis (pwRRMS) target the immune system by different mechanisms of action. However, there is a lack of a comprehensive comparison of their effects on the immune system. Herein, we evaluated the numbers of circulating B cells, CD4+and CD8+T cells, regulatory T cells (Tregs), natural killer (NK) cells and NKT cells, and their subsets, in pwRRMS who were treatment-naïve or treated with different DMTs. Compared to treatment-naïve pwRRMS, common and divergent effects on immune system cells were observed on pwRRMS treated with different DMTs, with no consistent pattern across all therapies in any of the cell populations analysed. PwRRMS treated with fingolimod, dimethyl fumarate (DMF), or alemtuzumab have reduced numbers of CD4+and CD8+T cells, as well as Treg subsets, with fingolimod causing the most pronounced decrease in T cell subsets. In contrast, teriflunomide and interferon (IFN) β have minimal impact on T cells, and natalizumab marginally increases the number of memory T cells in the blood. The effect of DMTs on the B cell, NKT and NK cell subsets is highly variable with alemtuzumab inducing a strong increase in the number of the most immature NK cells and its subsets. This study highlights the absence of a consistent pattern of the impact of various DMTs on immune system cells, with variations in both direction and magnitude of effect thus reenforcing the notion that distinct immune cell subsets are potential players in MS pathophysiology and/or DMT efficacy.
Statistical mechanics of phenotypic eco-evolution: from adaptive dynamics to complex diversification
Authors: Sireci Matteo , Muñoz Miguel A.
Published: July 2023

The ecological and evolutionary dynamics of large sets of individuals can be theoretically addressed using ideas and tools from statistical mechanics. This strategy has been addressed in the literature, both in the context of population genetics –whose focus is of genes or “genotypes”— and in adaptive dynamics, putting the emphasis on traits or “phenotypes”. Following this tradition, here we construct a framework allowing us to derive “macroscopic” evolutionary equations from a rather general “microscopic” stochastic dynamics representing the fundamental processes of reproduction, mutation and selection in a large community of individuals, each one characterized by its phenotypic features. Importantly, in our setup, ecological and evolutionary timescales are intertwined, which makes it particularly suitable to describe microbial communities, a timely topic of utmost relevance. Our framework leads to a probabilistic description of the distribution of individuals in phenotypic space —even in the case of arbitrarily large populations— as encoded in what we call “generalized Crow-Kimura equation” or “generalized replicator-mutator equation”. We discuss the limits in which such an equation reduces to the (deterministic) theory of “adaptive dynamics” (i.e. the standard approach to evolutionary dynamics in phenotypic space. Moreover, we emphasize the aspects of the theory that are beyond the reach of standard adaptive dynamics. In particular, by working out, as a guiding example, a simple model of a growing and competing population, we show that the resulting probability distribution can exhibit “dynamical phase transitions” changing from unimodal to bimodal —by means of an evolutionary branching— or to multimodal, in a cascade of evolutionary branching events. Furthermore, our formalism allows us to rationalize these cascades of transitions using the parsimonious approach of Landau’s theory of phase transitions. Finally, we extend the theory to account for finite populations and illustrate the possible consequences of the resulting stochastic or “demographic” effects. Altogether the present framework extends and/or complements existing approaches to evolutionary/adaptive dynamics and paves the way to more systematic studies of e.g. microbial communities as well as to future developments including theoretical analyses of the evolutionary process from the general perspective of non-equilibrium statistical mechanics.
Targeting pioneer transcription factor Ascl1 to promote optic nerve regeneration
Authors: Dong Bryan C , Luo Ximei , Qi Cheng , Qian Jiang , Qian Cheng , Zhou Feng-Quan
Published: July 2023

In adult mammalian central nervous system (CNS) neurons, axon regeneration after injury remains limited due to unfavorable gene regulatory programs. Factors enabling comprehensive epigenetic and transcriptional transitions, for instance, pivotal transcription factors that mediate neurogenesis and morphogenesis may be sufficient to promote CNS axon regeneration. Based on the analyses of multiple public whole-genome RNA and chromatin accessibility sequencing dataset of mouse retina development, as well as previous functional studies on the regeneration-capable dorsal root ganglion neurons, we hypothesize that the overexpression of pioneer transcription factor Achaete-Scute homolog 1 (Ascl1) would promote axon regeneration in the adult mammalian CNS neurons. We employed the optic nerve crush in mice, a common model for studying CNS axon regeneration, neuron survival and glaucoma, to investigate the effect of Ascl1 overexpression on the post-injury optic nerve regeneration. We found that Ascl1 could sufficiently promote regenerated axons past the crush site and significantly preserve the survival of retinal ganglion cells. Mechanistically, we revealed that effects of Ascl1 was mediated by known pro-regeneration factor Sox11 but not others. Together, our study established an effective workflow combined with the integrated computational inference and experimental validation for discovering functionally important target for promoting CNS neuron axon regeneration and survival.
The potential ofPseudomonas fluorescensSBW25 to produce viscosin enhances wheat root colonization and shapes root-associated microbial communities in a plant genotype dependent manner in soil systems
Authors: Guan Ying , Bak Frederik , Hennessy Rosanna Catherine , Herms Courtney Horn , Elberg Christine Lorenzen , Dresbøll Dorte Bodin , Winding Anne , Sapkota Rumakanta , Nicolaisen Mette Haubjerg
Published: July 2023

Microorganisms interact with plant roots through colonization of the root surface i.e. the rhizoplane or the surrounding soil i.e. the rhizosphere. Beneficial rhizosphere bacteria such asPseudomonasspp. can promote plant growth and protect against pathogens by producing a range of bioactive compounds, including specialized metabolites like cyclic lipopeptides (CLPs) known for their biosurfactant and antimicrobial activities. However, the role of CLPs in natural soil systems during bacteria-plant interactions is underexplored. Here,Pseudomonas fluorescensSBW25, producing the CLP viscosin, was used to study the impact of viscosin on bacterial root colonization and microbiome assembly in two cultivars of winter wheat (Heerup and Sheriff). We inoculated germinated wheat seeds with SBW25 wild-type or a viscosin-deficient mutant, and grew the plants in agricultural soil. After two weeks, enhanced root colonization of SBW25 wild-type compared to the viscosin-deficient mutant was observed, while no differences were observed between wheat cultivars. In contrast, the impact on root-associated microbial community structure was plant genotype specific, and SBW25 wild-type specifically reduced the relative abundance of an unclassified oomycete andPhytophthorain Sheriff and Heerup, respectively. This study provides new insights into the natural role of viscosin and specifically highlights the importance of viscosin in wheat root colonization under natural soil conditions and in shaping the root microbial communities associated with different wheat cultivars. Further, it pinpoints the significance of microbial microdiversity, plant genotype and microbe-microbe interactions when studying colonization of plant roots.
Identifying risk genes for embryo aneuploidy using ultra-low coverage whole-genome sequencing
Authors: Sun Siqi , Aboelenain Mansour , Ariad Daniel , Haywood Mary E. , Wageman Charles R. , Duke Marlena , Bag Aishee , Viotti Manuel , Katz-Jaffe Mandy , McCoy Rajiv C. , Schindler Karen , Xing Jinchuan
Published: July 2023

Background

Aneuploidy, the state of a cell containing extra or missing chromosomes, frequently arises during human meiosis and is the primary cause of early miscarriage and maternal age-related in vitro fertilization (IVF) failure. IVF patients exhibit significant variability in aneuploidy rates, although the exact genetic causes of the variability in aneuploid egg production remain unclear. Preimplantation genetic testing for aneuploidy (PGT-A) using ultra-low coverage whole-genome sequencing (ulc-WGS) is a standard test for identifying and selecting IVF-derived embryos with a normal chromosome complement. The wealth of embryo aneuploidy data and ulc-WGS data from PGT-A has potential for discovering variants in paternal genomes that are associated with aneuploidy risk in their embryos.

Methods

Using ulc-WGS data from ∼10,000 PGT-A biopsies, we imputed genotype likelihoods of genetic variants in parental genomes. We then used the imputed variants and aneuploidy calls from the embryos to perform a genome-wide association study of aneuploidy incidence. Finally, we carried out functional evaluation of the identified candidate gene in a mouse oocyte system.

Results

We identified one locus on chromosome 3 that is significantly associated with maternal meiotic aneuploidy risk. One candidate gene,CCDC66,encompassed by this locus, is involved in chromosome segregation during meiosis. Using mouse oocytes, we showed that CCDC66 regulates meiotic progression and chromosome segregation fidelity, especially in older mice.

Conclusions

Our work extended the research utility of PGT-A ulc-WGS data by allowing robust association testing and improved the understanding of the genetic contribution to maternal meiotic aneuploidy risk. Importantly, we introduce a generalizable method that can be leveraged for similar association studies using ulc-WGS data.