bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic scores in post-endoscopic retrograde cholangiopancreatography acute pancreatitis: should we use all, some, or none?
Authors: Macedo Silva Vítor , Freitas Marta , Sousa Magalhães Rui , Cúrdia Gonçalves Tiago , Boal Carvalho Pedro , Rosa Bruno , Cotter José
Published: July 2022

Background/aims

Acute pancreatitis is the most commonly observed adverse event following endoscopic retrograde cholangiopancreatography (ERCP). Early risk stratification is crucial in the management of these patients, to reduce unfavorable outcomes. Multiple prognostic scores are already used in acute pancreatitis, regardless of its etiology. Scarce data is available for their use specifically on post-ERCP acute pancreatitis (PEP). We aimed to compare the accuracy of different prognostic scores at PEP diagnosis for the prediction of a moderate-to-severe course.

Methods

Cross-sectional study of consecutive ERCPs performed between 2010 and 2020. The final sample included patients with PEP, with the severity graded according to the Atlanta classification. For each patient, different prognostic scores were calculated. Each score’s accuracy for the prediction of a moderate-to-severe course was assessed by analysis of receiving-operating-characteristics (ROC) curves.

Results

From 2012 ERCPs, 102 (5.1%) were complicated by PEP. From these, 34 (1.7% of all ERCPs) were classified as moderate-to-severe. The scores with the best accuracy in predicting a moderate-to-severe course were the BISAP [ area under curve (AUC) = 0.92], Balthazar (AUC = 0.89) and Glasgow-Imrie (AUC = 0.88) scores, with very good to excellent acuities. APACHE II (AUC = 0.81), Marshall score (AUC = 0.81) and PANC3 score (AUC = 0.76) revealed good accuracies. Ranson’s criteria on admission (AUC = 0.70) and HAPS classification (AUC = 0.67) presented less accurate results. Optimal cutoffs for the top scoring classifications were BISAP ≥3 (sensitivity 88.3% and specificity 83.8%), Balthazar ≥2 (sensitivity 84.8% and specificity 85.3%) and Glasgow-Imrie ≥4 (sensitivity 81.0% and specificity 82.6%).

Conclusion

BISAP, Balthazar and Glasgow-Imrie classifications presented the best results for predicting moderate-to-severe PEP, and represent the most useful prognostic scores for risk stratification in this population.
Evaluating of the Quality of Hepatic Diffusion Weighted Imaging Using Multiband Imaging With Variable-Rate Selective Excitation
Authors: Yoshida Naofumi , Nakaura Takeshi , Morita Kosuke , Yoneyama Masami , Inoue Taihei , Tanoue Shota , Uetani Hiroyuki , Oda Seitaro , Nagayama Yasunori , Kidoh Masafumi , Hirai Toshinori
Published: July 2022

Objective

To assess the image quality of diffusion-weighted imaging (DWI) using multiband (MB) imaging with variable-rate selective excitation (VERSE) and compare it to conventional DWI.

Methods

We retrospectively evaluated hepatic DWI images of patients (n = 76) according to either the conventional method (SENSE, acceleration factor = 2) (n = 38) or fast scanning method (MB imaging with VERSE, acceleration factor = 2 × 2) (n = 38). We also conducted a volunteer study (n = 15) for those scanning methods. During quantitative analysis, the signal-to-noise ratio (SNR), apparent diffusion coefficient values, and contrast in the liver, spleen, and spinal cord were compared between the 2 groups. During qualitative analysis, all images were independently and blindly evaluated by 2 board-certified radiologists. The image contrast, noise, artifacts, and sharpness were assessed, and the performance of classification was measured using receiver operating characteristic curve analysis.

Results

In the retrospective study, the SNRs of the hepatic parenchyma and spinal cord between the 2 protocols were significantly different (liver, 8.9 [interquartile range {IQR}, 7.6–12.2] vs 13.0 [IQR, 10.0–16.7]; P < 0.001 and spinal cord, 6.0 [IQR, 4.7–9.4] vs 4.3 [IQR, 3.8–6.8]; P < 0.02). No significant differences between the 2 protocols in the other retrospective analyses were noted. In the receiver operating characteristic curve analysis, area under the curve was 0.49 (95% confidence intervals, 0.40–0.58).

Conclusion

Multiband VERSE reduced scan time and SNR of hepatic DWI; however, subjective image quality parameters were not significantly impacted.
The programmed death of fetal oocytes and the correlated surveillance mechanisms
Authors: Zhou Jia-Qi , Wang Wen-Ji , Xia Guo-Liang , Wang Chao
Published: July 2022

Gamete production is essential for mammalian reproduction. In the ovaries, the primordial follicle, which is the basic reproductive unit, is formed either perinatally or during the second pregnancy stage in humans. However, some oocytes die before the establishment of the primordial follicle pool. Consequently, it is essential to uncover how the size of the primordial follicle pool is determined and how the programmed cell death of oocytes is performed under potential surveillance. According to recent studies, the fate of oocytes in the fetal ovary seems to be determined by different protective strategies through the timely control of apoptosis or autophagy. In this review, we discuss at least three oocyte-derived protective biomarkers, glycogen synthase kinase 3 beta, X-linked inhibitor of apoptosis, and Lysine-specific demethylase 1 (also known as KDM1A), responsible for surveilling the developmental quality of fetal oocytes to coordinate primordial follicle formation in the fetal ovary. This review contributes to a better understanding of the secrets of the female reproductive reserve under physiological conditions.
The imbalance of T-cell immunoglobulin and ITIM domain and CD226 on regulatory T cell in recurrent spontaneous abortion patients
Authors: Li Cui , Ying Chun-Mei , Duan Zhong-Liang
Published: July 2022

Objective:

To analyze the proportion of peripheral regulatory T cells (Tregs) and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain (TIGIT) and CD226 on Tregs in patients with recurrent spontaneous abortion (RSA).

Methods:

The proportion of CD3+CD4+CD25+Foxp3+ Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.

Results:

The proportion of Tregs in the RSA group (4.41% ± 1.54%) was significantly lower than that in the control group (5.27% ± 1.52%, P = 0.0374). Compared with the normal pregnant women, patients with RSA showed decreased TIGIT expression (54.75 ± 9.70% vs. 63.07 ± 12.48%, P = 0.0066) and increased CD226 expression on Tregs (25.59% ± 8.22% vs. 20.46% ± 6.97%, P = 0.0168). The ratio of CD226 to TIGIT in the RSA group (0.48 ± 0.19) was higher than that in the control group (0.34 ± 0.15, P = 0.0027). The proportion of TIGIT+CD226+ Tregs was significantly lower in patients with RSA (9.30% ± 4.95% vs. 13.43% ± 4.72%, P = 0.0020) than in the controls.

Conclusions:

Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.
A Novel Microbiome Signature in Gastric Cancer
Authors: Abate Miseker , Vos Elvira , Gonen Mithat , Janjigian Yelena Y. , Schattner Mark , Laszkowska Monika , Tang Laura , Maron Steven B. , Coit Daniel G. , Vardhana Santosh , Vanderbilt Chad , Strong Vivian E.
Published: July 2022

Objective:

The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC),Helicobacter pyloriis an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes.

Methods:

A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified.

Results:

Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts (P<0.05).Helicobacter,Lactobacillus,Streptococcus,Prevotella, andBacteroideswere significantly more enriched in GC samples when compared with nonmalignant tissue (P<0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes.

Conclusion:

Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy.
Determining the Ideal Intraoperative Resting Genital Hiatus Size—Balancing Surgical and Functional Outcomes
Authors: Chang Olivia H. , Yao Meng , Ferrando Cecile A. , Paraiso Marie Fidela R. , Propst Katie
Published: July 2022

Importance

The intraoperative resting genital hiatus (GH) size can be surgically modified but its relationship to prolapse recurrence is unclear.

Objectives

The objective of this study was to identify the optimal intraoperative resting GH size as it relates to prolapse recurrence and functional outcomes at 1 year.

Study Design

This prospective cohort study was conducted at 2 hospitals from 2019 to 2021. Intraoperative measurements of the resting GH, perineal body, and total vaginal length were collected. The composite primary outcome consisted of anatomic recurrence, subjective recurrence, and/or conservative or surgical retreatment at 1 year. Comparisons of anatomic, functional, and sexual outcomes were compared between patients stratified by the optimal intraoperative GH size identified by receiver operating characteristic curve analysis.

Results

Sixty-eight patients (median age of 63 years) underwent surgery, with 59 (86.8%) presenting for follow-up at 1 year. Based on the 13 patients (22%) with composite recurrence, receiver operating characteristic curve analysis demonstrated an intraoperative resting GH size of 3 cm, had 76.9% sensitivity (confidence interval [CI], 54–99.8%), and 34.8% specificity (CI, 21.0–48.5%) for composite recurrence at 1 year (area under curve = 0.61). Nineteen patients had an intraoperative GH less than 3 cm (32.2%) and 40 had a GH of 3 cm or greater (67.8%). The intraoperative resting GH size was significantly larger in patients with prolapse beyond the hymen at 1 year (4 cm [3.0, 4.0]) compared with those with prolapse at or proximal to the hymen (3.0 cm [2.5, 3.5], P = 0.009).

Conclusions

Intraoperative GH size may not reliably predict composite prolapse recurrence at 1 year, although there was an association between intraoperative resting GH size with prolapse beyond the hymen.
Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience
Authors: Greenhall George H.B. , Ushiro-Lumb Ines , Pavord Sue , Hunt Beverley J. , Sharma Hemant , Mehra Sanjay , Calder Francis , Kessaris Nicos , Kilbride Hannah , Jones Gareth , Motallebzadeh Reza , Arslan Zainab , Marks Stephen D. , Graetz Keith , Pettigrew Gavin J. , Torpey Nicholas , Watson Chris , Roy Debabrata , Casey John , Oniscu Gabriel C. , Currie Ian , Sutherland Andrew , Clancy Marc , Dor Frank , Willicombe Michelle , Sandhu Bynvant , Nath Jay , Weston Charles , van Dellen David , Roberts David J. , Madden Susanna , Ravanan Rommel , Forsythe John , Khurram Muhammad A. , Mohamed Ismail , Callaghan Chris J.
Published: July 2022

Background.

The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft.

Methods.

We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function.

Results.

There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m2. Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases.

Conclusions.

The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.
Yerbamate Tea Consumption: A Protective Factor in Parkinson Disease
Authors: Sáenz-Farret Michel , Salinas-Martínez Ana María , Zúñiga-Ramírez Carlos , Amorín-Costábile Ignacio , Maiola Ricardo , Mejía-Rojas Koni Katerin , Galeano Martha Sady , Velázquez Carolina , Ruiz Gabriela , Micheli Federico
Published: July 2022

Introduction

Little is known about the association between Yerbamate (YMT) tea consumption and Parkinson disease (PD). We determined whether there was an association between YMT tea consumption and PD.

Methods

We conducted a multicenter case-control study in 3 countries (Argentina, Paraguay, and Uruguay). We applied a structured questionnaire about YMT tea consumption history. The survey also included information about factors previously associated with a decreased and increased risk of PD, apart from medical and demographic factors. Odds ratios and 95% confidence intervals were calculated using multivariate unconditional binary logistic regression analysis.

Results

We included 215 cases and 219 controls. The mean age of the cases was 65.6 ± 10.5 years and that of controls was 63.1 ± 10.5 years (P < 0.02). Years of YMT tea consumption, number of liters drunk per day, and amount of YMT used for preparing the infusion were similar between cases and controls (P > 0.05), but not the number of times the YMT was added into the container (P = 0.003) and the YMT tea concentration per serving (P = 0.02). The multivariate analysis showed that YMT tea concentration per serving lowered the risk for PD, independent of potential confounders (odds ratio, 0.62; 95% confidence interval, 0.47–0.84).

Conclusions

This multicenter study highlights the association between an environmental factor, the YMT tea drinking, and PD. Although more evidence from longitudinal studies is needed, the results obtained here points toward a protective effect of the YMT tea concentration per serving on PD.
Inference and uncertainty quantification of stochastic gene expression via synthetic models
Authors: Öcal Kaan , Gutmann Michael U. , Sanguinetti Guido , Grima Ramon
Published: July 2022

Estimating uncertainty in model predictions is a central task in quantitative biology. Biological models at the single-cell level are intrinsically stochastic and nonlinear, creating formidable challenges for their statistical estimation which inevitably has to rely on approximations that trade accuracy for tractability. Despite intensive interest, a sweet spot in this trade-off has not been found yet. We propose a flexible procedure for uncertainty quantification in a wide class of reaction networks describing stochastic gene expression including those with feedback. The method is based on creating a tractable coarse-graining of the model that is learned from simulations, a
synthetic model
, to approximate the likelihood function. We demonstrate that synthetic models can substantially outperform state-of-the-art approaches on a number of non-trivial systems and datasets, yielding an accurate and computationally viable solution to uncertainty quantification in stochastic models of gene expression.
Ratiometric control of cell phenotypes in monostrain microbial consortia
Authors: Salzano Davide , Fiore Davide , di Bernardo Mario
Published: July 2022

We address the problem of regulating and keeping at a desired balance the relative numbers between cells exhibiting a different phenotype within a monostrain microbial consortium. We propose a strategy based on the use of external control inputs, assuming each cell in the community is endowed with a reversible, bistable memory mechanism. Specifically, we provide a general analytical framework to guide the design of external feedback control strategies aimed at balancing the ratio between cells whose memory is stabilized at either one of two equilibria associated with different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them
in silico
, implementing the memory element via a genetic toggle-switch. The proposed control framework may be used to allow long-term coexistence of different populations, with both industrial and biotechnological applications. As a representative example, we consider the realistic agent-based implementation of our control strategy to enable cooperative bioproduction of a dimer in a monostrain microbial consortium.
Madame Lavoisier and the others: women in Marie-Anne Paulze-Lavoisier's network (1771–1836)
Authors: Antonelli Francesca
Published: July 2022

Known as a translator and illustrator of chemical texts, Marie-Anne Paulze-Lavoisier (1758–1836) has been often represented as the associate of male
savants
and especially of her husband, the French chemist Antoine-Laurent Lavoisier. This article explores her biography from a different angle and focuses on her trajectories as a
secrétaire
; namely, someone whose main charge was to store and exchange information by means of writing. The article investigates the presence of women in Paulze-Lavoisier's network before and after Lavoisier's death in 1794. First, it shows that her work as a
secrétaire
combined a wide set of writing practices with domestic sociability. Then, it examines how other women contributed to her collaboration with Lavoisier. Finally, it analyses how these relationships changed in the post-revolutionary and Napoleonic era, when Paulze-Lavoisier's role as a
secrétaire
took on a new meaning.
Pareto optimality, economy–effectiveness trade-offs and ion channel degeneracy: improving population modelling for single neurons
Authors: Jedlicka Peter , Bird Alexander D. , Cuntz Hermann
Published: July 2022

Neurons encounter unavoidable evolutionary trade-offs between multiple tasks. They must consume as little energy as possible while effectively fulfilling their functions. Cells displaying the best performance for such multi-task trade-offs are said to be Pareto optimal, with their ion channel configurations underpinning their functionality. Ion channel degeneracy, however, implies that multiple ion channel configurations can lead to functionally similar behaviour. Therefore, instead of a single model, neuroscientists often use populations of models with distinct combinations of ionic conductances. This approach is called population (database or ensemble) modelling. It remains unclear, which ion channel parameters in the vast population of functional models are more likely to be found in the brain. Here we argue that Pareto optimality can serve as a guiding principle for addressing this issue by helping to identify the subpopulations of conductance-based models that perform best for the trade-off between economy and functionality. In this way, the high-dimensional parameter space of neuronal models might be reduced to geometrically simple low-dimensional manifolds, potentially explaining experimentally observed ion channel correlations. Conversely, Pareto inference might also help deduce neuronal functions from high-dimensional Patch-seq data. In summary, Pareto optimality is a promising framework for improving population modelling of neurons and their circuits.
Characterization and functional analysis of zinc trafficking in the human fungal pathogen
Candida parapsilosis
Authors: Takács Tamás , Németh Mihály Tibor , Bohner Flóra , Vágvölgyi Csaba , Jankovics Ferenc , Wilson Duncan , Gácser Attila
Published: July 2022

The zinc restriction and zinc toxicity are part of host defence, called nutritional immunity. The crucial role of zinc homeostasis in microbial survival within a host is established, but little is known about these processes in the opportunistic human fungal pathogen
Candida parapsilosis.
Our
in silico
predictions suggested the presence of at least six potential zinc transporters (ZnTs) in
C. parapsilosis
—orthologues of
ZRC1
,
ZRT3
and
ZRT101
—but an orthologue of
PRA1
zincophore was not found. In addition, we detected a species-specific gene expansion of the novel ZnT
ZRT2,
as we identified three orthologue genes in the genome of
C. parapsilosis
. Based on predictions, we created homozygous mutant strains of the potential ZnTs and characterized them. Despite the apparent gene expansion of
ZRT2
in
C. parapsilosis
, only
CpZRT21
was essential for growth in a zinc-depleted acidic environment, in addition we found that CpZrc1 is essential for zinc detoxification and also protects the fungi against the elimination of murine macrophages. Significantly, we demonstrated that
C. parapsilosis
forms zincosomes in a Zrc1-independent manner and zinc detoxification is mediated by the vacuolar importer CpZrc1. Our study defines the functions of
C. parapsilosis
ZnTs, including a species-specific survival and zinc detoxification system.
The effects of local homogeneity assumptions in metapopulation models of infectious disease
Authors: Zachreson Cameron , Chang Sheryl , Harding Nathan , Prokopenko Mikhail
Published: July 2022

Computational models of infectious disease can be broadly categorized into two types: individual-based (agent-based) or compartmental models. While there are clear conceptual distinctions between these methodologies, a fair comparison of the approaches is difficult to achieve. Here, we carry out such a comparison by building a set of compartmental metapopulation models from an agent-based representation of a real population. By adjusting the compartmental model to approximately match the dynamics of the agent-based model, we identify two key qualitative properties of the individual-based dynamics which are lost upon aggregation into metapopulations. These are (i) the local depletion of susceptibility to infection and (ii) decoupling of different regional groups due to correlation between commuting behaviours and contact rates. The first of these effects is a general consequence of aggregating small, closely connected groups (i.e. families) into larger homogeneous metapopulations. The second can be interpreted as a consequence of aggregating two distinct types of individuals: school children, who travel short distances but have many potentially infectious contacts, and adults, who travel further but tend to have fewer contacts capable of transmitting infection. Our results could be generalized to other types of correlations between the characteristics of individuals and the behaviours that distinguish them.
Spectral tuning of biotemplated ZnO photonic nanoarchitectures for photocatalytic applications
Authors: Piszter Gábor , Kertész Krisztián , Nagy Gergely , Baji Zsófia , Endre Horváth Zsolt , Bálint Zsolt , Sándor Pap József , Péter Biró László
Published: July 2022

The photocatalytic activity of a flat surface can be increased by micro- and nanostructuring the interface to increase the area of the contact surface between the photocatalyst and the solute, and moreover, to optimize charge carrier transfer. Further enhancement can be achieved by using photonic nanostructures, which exhibit photonic band gap (PBG). Structurally coloured butterfly wings offer a rich ‘library’ of PBGs in the visible spectral range which can be used as naturally tuned sample sets for biotemplating. We used conformal atomic layer deposition of ZnO on the wings of various butterfly species (
Arhopala asopia
,
Hypochrysops polycletus
,
Morpho sulkowskyi
,
Polyommatus icarus
) possessing structural colour extending from the near UV to the blue wavelength range, to test the effects arising from the nanostructured surfaces and from the presence of different types of PBGs. Aqueous solutions of rhodamine B were used to test the enhancement of photocatalytic activity that was found for all ZnO-coated butterfly wings. The best reaction rate of decomposing rhodamine B when illuminated with visible light was found in 15 nm ZnO coated
M. sulkowskyi
wing, the reflectance of which had the highest overlap with the absorption band of the dye and had the highest reflectance intensity.
Archaeological occurrences of terrestrial herpetofauna in the insular Caribbean: cultural and biological significance
Authors: Bochaton Corentin
Published: July 2022

Although the importance of the archaeological record for addressing questions of biodiversity is gaining ground, its relevance for describing past faunal communities is still under-exploited, particularly for the most under-documented areas and species. Among the most poorly documented taxa are reptiles and amphibians, which are rarely studied in detail in the archaeological record, even in tropical areas where most of these species occur today. Here I evaluate the archaeological and paleontological significance of reptiles and amphibians from the Indigenous archaeological record of the insular Caribbean. Quantitative (bone counts) and qualitative (taxonomic identification) analyses allow researchers to discuss the role of herpetofauna in the subsistence strategies of Indigenous populations as well as their interest for assessing past insular biodiversity. This overview sheds light on both the poor representation of herpetofaunal taxa in Caribbean archaeological deposits and trends in the potential exploitation of reptiles and amphibians by Indigenous populations. In terms of paleoecology, the presented results reveal strong regional differences in the quality and density of data as well as the inadequacy of available archaeofaunal data for addressing questions of past biodiversity.
A synchronous spectrofluorometric technique for simultaneous detection of alfuzosin and tadalafil: applied to tablets and spiked biological samples
Authors: Elama Heba Samir , shalan Shereen M. , El-Shabrawy Yasser , Eid Manal I. , Zeid Abdallah M.
Published: July 2022

A facile, accurate, eco-friendly and sensitive spectrofluorometric method was evolved to assay alfuzosin hydrochloride (AFH) and tadalafil (TDF) in different matrices. Such a co-administered combination is clinically used for the treatment of lower urinary tract symptoms. Both compounds are characterized by their native fluorescence spectra upon excitation at specific wavelengths. Their characteristic fluorescence spectra were used for sensitive assay of the studied analytes in tablets and human biological samples. The assay principle is based on first-order synchronous spectrofluorometric scan using Δλ= 60 nm in which AFH peaks were recorded at 366 nm. Meanwhile, TDF measurements were recorded at 293 nm in the same scans without overlap with AFH spectra. Recent analytical chemistry trends were implemented to lessen occupational and environmental perils, using ethanol as a diluting solvent for method optimization and application. Linearity ranges were 5.0–90.0 and 10.0–100.0 ng ml−1for AFH and TDF, respectively in their raw materials with average % recoveries of 100.44% and 99.73% in raw materials, 100.15% and 100.20% in spiked plasma, and 97.14% and 99.99% in spiked urine. The proposed method was successfully applied to Prostetrol and Starkoprex commercial tablets with no interference with common tablet additives.
The earliest known brood care in insects
Authors: Fu Yanzhe , Cai Chenyang , Chen Pingping , Huang Diying
Published: July 2022

Brood care enhances offspring fitness and survival by providing protection or feeding through parents (commonly by females). It has evolved independently multiple times in animals, e.g. mammals, birds, dinosaurs and arthropods, especially various lineages of insects, and has significant implications for understanding the emergence of sociality of insects. However, few fossil insects document such an ephemeral behaviour directly. New exceptional fossils of the water boatman
Karataviella popovi
from the Middle–Late Jurassic Daohugou biota (
ca
163.5 Ma, northeastern China), with adult females bearing clutches of eggs on their left mesotibia, provide a unique brooding strategy (asymmetric egg-carrying behaviour) unknown in all extinct and extant insects. Our discovery represents the earliest direct evidence of brood care among insects, pushing back by more than 38 million years, indicating that relevant adaptations associated with maternal investment of insects can be traced back to at least the Middle–Late Jurassic, and highlighting the existence of diverse brooding strategies in Mesozoic insects. In addition, our discovery reveals that a specialized trawl-like filter-capture apparatus of
K
.
popovi
probably represents pre-adaptions originally used for trapping coeval anostracan (fairy shrimp) eggs for food.
Underwater visibility constrains the foraging behaviour of a diving pelagic seabird
Authors: Darby J. , Clairbaux M. , Bennison A. , Quinn J. L. , Jessopp M. J.
Published: July 2022

Understanding the sensory ecology of species is vital if we are to predict how they will function in a changing environment. Visual cues are fundamentally important for many predators when detecting and capturing prey. However, many marine areas have become more turbid through processes influenced by climate change, potentially affecting the ability of marine predators to detect prey. We performed the first study that directly relates a pelagic seabird species's foraging behaviour to oceanic turbidity. We collected biologging data from 79 foraging trips and 5472 dives of a visually dependent, pursuit-diving seabird, the Manx shearwater (Puffinus puffinus). Foraging behaviour was modelled against environmental variables affecting underwater visibility, including water turbidity, cloud cover and solar angle. Shearwaters were more likely to initiate area-restricted search and foraging dives in clearer waters. Underwater visibility also strongly predicted dive rate and depth, suggesting that fine-scale prey capture was constrained by the detectability of prey underwater. Our novel use of dynamic descriptors of underwater visibility suggests that visual cues are vital for underwater foraging. Our data indicate that climate change could negatively impact seabird populations by making prey more difficult to detect, compounded by the widely reported effects of reduced prey populations.
Disruption of flour beetle microbiota limits experimentally evolved immune priming response, but not pathogen resistance
Authors: Prakash Arun , Agashe Deepa , Khan Imroze
Published: July 2022

Host-associated microbiota play a fundamental role in the training and induction of different forms of immunity, including inducible as well as constitutive components. However, direct experiments analysing the relative importance of microbiota during evolution of different immune functions are missing. We addressed this gap by using experimentally evolved lines of Tribolium castaneum that either produced inducible immune memory-like responses (immune priming) or constitutively expressed basal resistance (without priming), as mutually exclusive strategies against Bacillus thuringiensis infection. We disrupted the microbial communities in these evolved lines and estimated the impact on the beetle’s ability to mount a priming response vs basal resistance. Populations that had evolved immune priming lost the ability to mount a priming response upon microbiota disruption. Microbiota manipulation also caused a drastic reduction in their reproductive output and post-infection longevity. In contrast, in pathogen-resistant beetles, microbiota manipulation did not affect post-infection survival or reproduction. The divergent evolution of immune responses across beetle lineages was thus associated with divergent reliance on the microbiome. Whether the latter is a direct outcome of differential pathogen exposure during selection or reflects evolved immune functions remains unclear. We hope that our results will motivate further experiments to understand the mechanistic basis of these complex evolutionary associations between microbiota, host immune strategies, and fitness outcomes.
Paternal transmission of behavioural and metabolic traits induced by postnatal stress to the 5thgeneration in mice
Authors: Boscardin Chiara , Manuella Francesca , Mansuy Isabelle M
Published: July 2022

Life experiences and environmental conditions in childhood can change the physiology and behaviour of exposed individuals and in some cases, of their offspring. In rodent models, stress/trauma, poor diet and endocrine disruptors in a parent have been shown to cause phenotypes in the direct progeny, suggesting intergenerational inheritance. A few models also examined transmission to further offspring and suggested transgenerational inheritance, but such multi-generations inheritance is not well characterized. Our previous work in a mouse model of early postnatal stress showed that behaviour and metabolism are altered in the offspring of exposed males up to the 4thgeneration in the patriline and up to the 2ndgeneration in the matriline. The present study examined if in the patriline, symptoms can be transmitted beyond the 4thgeneration. Analyses of the 5thand 6thgeneration of mice revealed that altered risk-taking and glucose regulation caused by postnatal stress are still manifested in the 5thgeneration but are attenuated in the 6thgeneration. Some of the symptoms are expressed in both males and females, but some are sex-dependent and sometimes opposite. These results indicate that postnatal trauma can affect behaviour and metabolism over many generations, suggesting epigenetic mechanisms of transmission.
Efficient Human Germ Cell Specification from Stem Cells via Combinatorial Expression of Transcription Factors
Authors: Kramme Christian , Smela Merrick Pierson , Wolf Bennett , Fortuna Patrick R. , Brixi Garyk , Palepu Kalyan , Dong Edward , Adams Jessica , Bhat Suhaas , Koseki Sabrina , Tysinger Emma , Stan Teodora , Kohman Richie E. , Liu Songlei , Kobayashi Mutsumi , Shioda Toshi , Church George M. , Chatterjee Pranam
Published: July 2022

Germ cells are the vehicle of human reproduction, arising early in embryonic development and developing throughout adult life until menopause onset in women. Primordial germ cells are the common precursors of germline cells in both sexes, undergoing sexual specification into oogonia or gonocytes which further develop into oocytes or spermatocytes during development. Methods for recapitulation of primordial germ cell and oogonia formation have been developed extensively in recent decades, but fundamental technical limitations in their methodologies, throughput, and yield limit their utilization. Recently, transcription factor (TF)-based methods for human primordial germ cell-like cell (hPGCLC) formation, mouse meiotic entry, and mouse oocyte maturation have demonstrated the feasibility of gene overexpression screening in identifying potent regulators of germ cell development. Here we screened 47 folliculogenesis-regulating TFs for their role in hPGCLC and oogonia formation, identifying DLX5, HHEX, and FIGLA whose individual overexpression enhances hPGCLC formation from hiPSCs. Additionally, we identify a set of three TFs, ZNF281, LHX8, and SOHLH1, whose combinatorial overexpression drives direct oogonia-like formation from hiPSCs in a four-day, feeder-free monolayer culture condition with additional feeder-free culture capabilities post-isolation. We characterize these TF-based germ cells via gene and protein expression analyses, and demonstrate their broad similarity to in vivo germ cells. Together, these results identify novel regulators of human germ cell development and establish new TF-based tools for human in vitro oogenesis research.
Transcriptome Variant Analysis of Noise Susceptibility in C57BL/6J Mice
Authors: Wang Siyue , Cai Jing , Kong Ligang , Xu Lei , Fan Zhaoming , Wang Haibo
Published: July 2022

Background

Susceptibility to noise varies dramatically between mice of the same genetic background; however, the underlying molecular mechanism remains unknown.

Methods

C57BL/6J (B6) mice of the same sex, age, and strain were exposed to noise of the same intensity and duration, and the auditory brainstem response (ABR) threshold was determined 48 h later. Some mice had significant hearing loss, while some did not; the ABR threshold measured in these two groups of mice was significantly different. The cochlea of the two groups of mice was dissected, and RNA sequencing and analysis were performed. Differentially expressed genes (DEGs) between the two groups were selected, Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed, and protein–protein interaction network maps were listed.

Results

This study showed that noise exposure of the same intensity and duration caused different degrees of hearing loss in C57BL/6J (B6) mice. This was the result of the up-regulation or down-regulation of many genes, such as Nop2, Bysl, Rrp9, Spsb1, Fbxl20, and Fbxo31. Changes in the transcriptome of these genes may affect cochlear susceptibility to noise.

Conclusion

The DEGs identified in this experiment may provide more insight into protocols for gene therapy in the clinical practice of hearing loss.
Contexts enhance ratings of craving and psychophysiological responses of cue-reactivity in tobacco use disorder
Authors: Vollstädt-Klein Sabine , Nees Frauke , Wieland Alfred , Karl Damian , Diener Carsten , Smolka Michael N. , Flor Herta
Published: July 2022

Introduction

Confrontation with smoking-related cues can provoke craving and relapse, even after long periods of abstinence. The context of these cues might be important for the elicitation of craving. In this study we examined the effects of social, physical and consumptive contexts on cue-reactivity in smokers using ratings and physiological measures.

Method

A total of 22 smokers (12 male, 10 female) with tobacco use disorder (TUD) assessed using a cue-reactivity picture perception paradigm in a laboratory setting. Pictures of smoking in different physical and social contexts and of different phases of the smoking ritual were used. Ratings of cigarette craving, valence and arousal as well as startle reflex modulation, skin conductance responses and heart rate were assessed.

Results

We observed an increased startle modulation in the bar versus control context and a stronger heart rate deceleration in the social versus neutral context. Social smoking induced more craving than neutral context, and cues from the beginning of the smoking ritual induced more craving than in the terminal phase. Social smoking context was rated as more arousing than neutral context, and cigarettes of the terminal phase of the smoking ritual were rated as least pleasant.

Conclusions

The results indicate that physical, social and consumptive contexts differentially affect cue-reactivity in TUD.

Implications

Cues in contexts lead to more pronounced indicators of craving than cues alone. Thus, contexts should be included in both, the assessment and treatment of TUD.
Mechanisms contributing to differential genetic risks for TREM2 R47H and R62H variants in Alzheimer’s Disease
Authors: Fancy Nurun , Willumsen Nanet , Tsartsalis Stergios , Khozoie Combiz , McGarry Aisling , Muirhead Robert C , Schneegans Eleonore , Davey Karen , Chau Vicky MN , Smith Amy M , Scotton William , Hardy John , Huh Dann , Matthews Paul M , Jackson Johanna S
Published: July 2022

Coding variants in the microglial TREM2 ectodomain differentially (R47H> R62H) increase the risk of Alzheimer’s disease (AD). To define mechanisms responsible, we characterised neuropathology and transcriptomic responses in heterozygotes for these TREM2 variant alleles (TREM2var) and for common allele homozygotes (CV) in non-diseased and AD brain cortical tissue from 58 donors. Increased neurodegeneration in the TREM2var AD cortex was associated with genotype-dependent reductions in expression of Disease Associated Microglia (DAM) genes and increased expression of complement and Type I and II interferon pathways in microglia, phagocytosis and amyloid binding pathways and Disease Associated Astrocyte (DAA) genes in astrocytes, and growth factor, ubiquitination and apoptotic pathways in neurons. The microglial phenotypes and secondary differences in tissue β-amyloid deposition and in astrocyte and neuronal responses describe a variably partial loss of TREM2 function with variant alleles (R47H>R62H) relative to CV and suggest mechanisms that could account for differences in genetic risks conferred.
Application of Atraumatic Care Philosophy to Children in Hospitals a Literature Review
Authors: Ilmiasih Reni , Ningsih Nurul Syafitri
Published: July 2022

Background

Hospitalization for children has an impact on physical and psychological problems for children and parents. Many interventions can be done to reduce stressors for children or parents in nursing using the philosophy of atraumatic care, but there are not many articles that provide specific identification in the realm of the philosophy of atraumatic care. This study aims to determine the Evidence-Based Practice Nursing (EBPN) atraumatic care carried out by nurses in hospitals.

Method

This research uses the literature study method. The Literature Study stages include problem identification, searching data in 4 databases, namely Pubmed (370 Journals), Proquest (295 Journals), Clinical Key (751 Journals), and Science Direct (573 Journals) with a total of 1,989 journals after that through the screening method, assessment of study quality using the JBI Critical Appraisal Tool which resulted in the final results with 18 journals, after that through data extraction and data analysis methods.

Results

From 18 intervention journals to prevent physical and psychological stress, including the use of Virtual Reality (VR), and the use of buzzy and interactive play. Intervention impact separation with the presence of parents and involvement in care. Interventions related to the impact of the foreign environment are by modifying the nurse’s uniform and car orientation of the care environment. Intervention in improving treatment control with PRISM-P and Progressive Muscle Relaxation (PMR) with Guided Imagery (GI).

Conclusion

All interventions that are included in the 4 philosophies of atraumatic care, show the results of the effectiveness of the intervention on each principle of atraumatic care. This can be applied to patients, especially children and the elderly according to their condition.
Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation
Authors: Ren Xuefeng , Nguyen Thanh N. , Lam Wai Kit , Buffalo Cosmo Z. , Lazarou Michael , Yokom Adam Lee , Hurley James H.
Published: July 2022

The assembly of the autophagy initiation machinery nucleates autophagosome biogenesis, including in the PINK1- and Parkin-dependent mitophagy pathway implicated in Parkinson’s disease. The structural interaction between the sole transmembrane autophagy protein, ATG9A, and components of the ULK1 complex is one of the major missing links needed to complete a structural map of autophagy initiation. We determined the 2.4 Å x-ray crystallographic structure of the ternary structure of ATG9A C-terminal tail bound to the ATG13:ATG101 HORMA dimer, which is part of the ULK1 complex. We term the interacting portion of the extreme C-terminal part of the ATG9A tail the “HORMA dimer interacting region” (HDIR). This structure shows that the HDIR binds to the HORMA domain of ATG101 by β-sheet complementation such that the ATG9A tail resides in a deep cleft at the ATG13:ATG101 interface. Disruption of this complex in cells impairs damage induced PINK1/Parkin mitophagy mediated by the cargo receptor NDP52.
Accurate protein stability predictions from homology models
Authors: Valanciute Audrone , Nygaard Lasse , Zschach Henrike , Jepsen Michael Maglegaard , Lindorff-Larsen Kresten , Stein Amelie
Published: July 2022

Calculating changes in protein stability (ΔΔG) has been shown to be central for predicting the consequences of single amino acid substitutions in protein engineering as well as interpretation of genomic variants for disease risk. Structure-based calculations are considered most accurate, however the tools used to calculate ΔΔGs have been developed on experimentally resolved structures. Extending those calculations to homology models based on related proteins would greatly extend their applicability as large parts of e.g. the human proteome are not structurally resolved. In this study we aim to investigate the accuracy of ΔΔG values predicted on homology models compared to crystal structures. Specifically, we identified four proteins with a large number of experimentally tested ΔΔGs and templates for homology modeling across a broad range of sequence identities, and selected three methods for ΔΔG calculations to test. We find that ΔΔG-values predicted from homology models compare equally well to experimental ΔΔGs as those predicted on experimentally established crystal structures, as long as the sequence identity of the model template to the target protein is at least 40%. In particular, the Rosettacartesian_ddgprotocol is robust against the small perturbations in the structure which homology modeling introduces. In an independent assessment, we observe a similar trend when using ΔΔGs to categorize variants as low or wild-type-like abundance. Overall, our results show that stability calculations performed on homology models can substitute for those on crystal structures with acceptable accuracy as long as the model is built on a template with sequence identity of at least 40% to the target protein.
A glycine zipper motif governs translocation of type VI secretion toxic effectors across the cytoplasmic membrane of target cells
Authors: Ali Jemal , Yu Manda , Sung Li-Kang , Cheung Yee-Wai , Lai Erh-Min
Published: July 2022

Type VI secretion systems (T6SSs) can deliver diverse toxic effectors into eukaryotic and bacterial cells. Although much is known about the regulation and assembly of T6SS, the translocation mechanism of effectors into the periplasm and/or cytoplasm of target cells remains elusive. Here we use theAgrobacterium tumefaciensDNase effector Tde1 to unravel the mechanism of translocation from attacker to prey. We demonstrate that Tde1 binds to its adaptor Tap1 through the N-terminus, which harbours continuous copies of GxxxG motifs resembling the glycine zipper structure found in proteins involved in the membrane channel formation. Amino acid substitutions on G39xxxG43motif does not affect Tde1-Tap1 interaction and secretion but abolish its membrane permeability and translocation of its fluorescent fusion protein into prey cells. The data suggest that G39xxxG43governs the delivery of Tde1 into target cells by permeabilizing the cytoplasmic membrane. Considering the widespread presence of GxxxG motifs in bacterial effectors and pore-forming toxins, we propose that glycine zipper mediated permeabilization is a conserved mechanism used by bacterial effectors for translocation across target cell membranes.