bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informed interpretation of metagenomic data by StrainPhlAn enables strain retention analyses of the upper airway microbiome
Authors: Mostacci Nadja , Wüthrich Tsering Monika , Siegwald Léa , Kieser Silas , Steinberg Ruth , Sakwinska Olga , Latzin Philipp , Korten Insa , Hilty Markus 
Published: November 2023

ABSTRACT

Shotgun metagenomic sequencing has the potential to provide bacterial strain-level resolution which is of key importance to tackle a host of clinical questions. While bioinformatic tools that achieve strain-level resolution are available, thorough benchmarking is needed to validate their use for less investigated and low biomass microbiomes like those from the upper respiratory tract. We analyzed a previously published data set of longitudinally collected nasopharyngeal samples from Bangladeshi infants (Microbiota and Health study) and a novel data set of oropharyngeal samples from Swiss children with cystic fibrosis. Data from bacterial cultures were used for benchmarking the parameters of StrainPhlAn 3, a bioinformatic tool designed for strain-level resolution. In addition, StrainPhlAn 3 results were compared with metagenomic assemblies derived from StrainGE and newly derived whole-genome sequencing data. After optimizing the analytical parameters, we compared StrainPhlAn 3 results to culture gold standard methods and achieved sensitivity values of 87% (
Streptococcus pneumoniae
), 80% (
Moraxella catarrhalis
), 75% (
Haemophilus influenzae
), and 57% (
Staphylococcus aureus
) for 420 nasopharyngeal and 75% (
H. influenzae
) and 46% (
S. aureus
) for 260 oropharyngeal samples. Comparing the phylogenetic tree of the core genome of 50
S
.
aureus
isolates with a corresponding marker gene tree generated by StrainPhlAn 3 revealed a striking similarity in tree topology for all but three samples indicating adequate strain resolution. In conclusion, a comparison of StrainPhlAn 3 results to data from bacterial cultures revealed that strain-level tracking of the respiratory microbiome is feasible despite the high content of host DNA when parameters are carefully optimized to fit low biomass microbiomes.

IMPORTANCE
The usage of 16S rRNA gene sequencing has become the state-of-the-art method for the characterization of the microbiota in health and respiratory disease. The method is reliable for low biomass samples due to prior amplification of the 16S rRNA gene but has limitations as species and certainly strain identification is not possible. However, the usage of metagenomic tools for the analyses of microbiome data from low biomass samples is not straight forward, and careful optimization is needed. In this work, we show that by validating StrainPhlAn 3 results with the data from bacterial cultures, the strain-level tracking of the respiratory microbiome is feasible despite the high content of host DNA being present when parameters are carefully optimized to fit low biomass microbiomes. This work further proposes that strain retention analyses are feasible, at least for more abundant species. This will help to better understand the longitudinal dynamics of the upper respiratory microbiome during health and disease.
Taxonomic distribution of metabolic functions in bacteria associated with
Trichodesmium
consortia
Authors: Koedooder Coco , Zhang Futing , Wang Siyuan , Basu Subhajit , Haley Sheean T. , Tolic Nikola , Nicora Carrie D. , Glavina del Rio Tijana , Dyhrman Sonya T. , Gledhill Martha , Boiteau Rene M. , Rubin-Blum Maxim , Shaked Yeala 
Published: November 2023

ABSTRACT

The photosynthetic and diazotrophic cyanobacterium
Trichodesmium
is a key contributor to marine biogeochemical cycles in the subtropical-oligotrophic oceans.
Trichodesmium
form colonies that harbor a distinct microbial community in comparison to the surrounding seawater. The presence of their associated bacteria can expand
Trichodesmium
’s functional potential and is predicted to influence the cycling of carbon, nitrogen, phosphorus, and iron (C, N, P, and Fe). To link the bacteria associated with
Trichodesmium
to key functional traits and elucidate how community structure can influence nutrient cycling, we characterized Red Sea
Trichodesmium
colonies using metagenomics and metaproteomics. Colonies harbored bacteria that typically associate with algae and particles, such as the ubiquitous
Alteromonas macleodii,
but also lineages specific to
Trichodesmium
, such as members from the order Balneolales. The majority of associated bacteria were auxotrophic for different vitamins, indicating their dependency on vitamin production by
Trichodesmium
. The associated bacteria carry functional traits including siderophore biosynthesis, reduced phosphorus metabolism, and denitrification pathways. The analysis supports
Trichodesmium
as an active hotspot for C, N, P, Fe, and vitamin exchange. In turn,
Trichodesmium
may rely on associated bacteria to meet its high Fe demand as several lineages synthesize photolabile siderophores (e.g., vibrioferrin, rhizoferrin, petrobactin) which can enhance the bioavailability of particulate Fe to the entire consortium. Collectively, the results indicate that
Trichodesmium
colonies provide a structure where these interactions can take place. While further studies are required to clarify the exact nature of these interactions,
Trichodesmium
’s reliance on particle and algae-associated bacteria and the observed redundancy of key functional traits likely underpins the resilience of
Trichodesmium
within an ever-changing global environment.

IMPORTANCE

Colonies of the cyanobacteria
Trichodesmium
act as a biological hotspot for the usage and recycling of key resources such as C, N, P, and Fe within an otherwise oligotrophic environment. While
Trichodesmium
colonies are known to interact and support a unique community of algae and particle-associated microbes, our understanding of the taxa that populate these colonies and the gene functions they encode is still limited. Characterizing the taxa and adaptive strategies that influence consortium physiology and its concomitant biogeochemistry is critical in a future ocean predicted to have increasingly resource-depleted regions.
Occupational health hazards of bidi workers and their families in India: a scoping review
Authors: Tyagi Jyoti , Beri Deepti , Ingale Samiksha , Sinha Praveen , Bhaumik Soumyadeep 
Published: November 2023

BackgroundBidi workers and their families are exposed to harmful substances during bidi rolling, thereby jeopardising their health. We aimed to assess existing evidence on health conditions of bidi workers and their families in India.MethodsWe searched nine databases and relevant websites, and conducted citation screening to identify primary studies assessing occupational health hazards of bidi workers and their families. Two authors independently conducted screening and data extraction. We synthesised the findings narratively in a structured fashion.ResultsWe found 3842 studies, out of which 95 studies met our eligibility criteria. High prevalence of disease conditions across all organ systems of the body was reported in bidi workers. Studies on female bidi workers showed decreased fertility (n=2), increased frequency of miscarriages (n=1) and higher risk of cervical cancer (n=1). Pregnant bidi workers were at an increased risk of anaemia and pregnancy-induced hypertension (n=2), higher frequency of neonatal deaths (n=1), stillbirths (n=1) and premature births (n=1) in comparison with non-bidi workers. Babies born to bidi workers reported low birth weight (n=5). Evidence from cohort studies suggests causal nature of the exposure to the disease condition.ConclusionOur review shows that bidi rolling leads to numerous occupational health hazards in bidi workers and their family members. It is essential to provide alternative livelihoods, and safe and protective working environment, and cover bidi workers under various social security provisions to alleviate the deleterious effect of bidi making at home. It is also important to shift bidi making away from home and strengthen existing regulations and promulgation of new provisions, including India’s Occupational Safety, Health, and Working Conditions Code 2020.
Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow
Authors: Faizy Tobias D , Winkelmeier Laurens , Mlynash Michael , Broocks Gabriel , Heitkamp Christian , Thaler Christian , van Horn Noel , Seners Pierre , Kniep Helge , Stracke Paul , Zelenak Kamil , Lansberg Maarten G , Albers Gregory W , Wintermark Max , Fiehler Jens , Heit Jeremy J 
Published: November 2023

Background
We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy.

Methods
This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC− (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes.

Results
538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC− profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC− (β 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (β 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence.

Conclusion
A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.
Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting
Authors: Palmer Andrew J , Zhao Ting , Taylor Bruce V , van der Mei Ingrid , Campbell Julie A 
Published: November 2023

BackgroundIncreasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting.MethodsA five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed.ResultsFrom societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=−$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=−$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios.ConclusionsMS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.
Association of low-dose ionising radiation with site-specific solid cancers: Chinese medical X-ray workers cohort study, 1950–1995
Authors: Gu Yeqing , Wang Jinhan , Wang Yan , Xu Chang , Liu Yang , Du Liqing , Wang Qin , Ji Kaihua , He Ningning , Zhang Manman , Song Huijuan , Niu Kaijun , Liu Qiang 
Published: November 2023

BackgroundThe dose–response relationship between cancers and protracted low-dose rate exposure to ionising radiation is still uncertain. This study aims to estimate quantified relationships between low-dose radiation exposures and site-specific solid cancers among Chinese medical X-ray workers.MethodsThis cohort study included 27 011 individuals who were employed at major hospitals in 24 provinces in China from 1950 to 1980 and had been exposed to X-ray equipment, and a control group of 25 782 physicians who were not exposed to X-ray equipment. Person-years of follow-up were calculated from the year of employment to the date of the first diagnosis of cancer or the end of follow-up, whichever occurred first. All cancers were obtained from medical records during 1950–1995. This study used Poisson regression models to estimate the excess relative risk (ERR) and excess absolute risk (EAR) for incidence of site-specific solid cancers associated with cumulative dose.Results1643 solid cancers were developed, the most common being lung, liver and stomach cancer. Among X-ray workers, the average cumulative colon dose was 0.084 Gy. We found a positive relationship between cumulative organ-specific dose and liver (ERR/Gy=1.48; 95% CI 0.40 to 2.83), oesophagus (ERR/Gy=18.1; 95% CI 6.25 to 39.1), thyroid (ERR/Gy=2.96; 95% CI 0.44 to 8.18) and non-melanoma skin cancers (ERR/Gy=7.96; 95% CI 2.13 to 23.12). We found no significant relationship between cumulative organ-specific doses and other cancers. Moreover, the results showed a statistically significant EAR for liver, stomach, breast cancer (female), thyroid and non-melanoma skin cancers.ConclusionsThese findings provided more useful insights into the risks of site-specific cancers from protracted low-dose rate exposure to ionising radiation.
The impact of post-cutoff bend curvature on channel kinematics in meandering rivers: an example from the Trinity River, Texas, USA
Authors: Speed Cole M. , Sylvester Zoltán , Morris Paul D. , Mohrig David 
Published: November 2023

Abstract
Neck and chute cutoffs along meandering rivers are near-instantaneous morphodynamic perturbations that drive modification of planform channel geometry and kinematics at the cutoff site and in adjacent bends. Despite their ubiquity, quantitative and predictive linkages between post-cutoff planform bend geometry and subsequent bend kinematics remain limited. Here, using a 37-year record of Landsat-derived river channel centrelines from a meandering reach of the Trinity River in Texas (USA) and a newly developed directed graph-based approach for high-resolution channel tracking, we identify a linkage between post-cutoff bend curvature and the magnitude, spatial extent, and temporal duration of cutoff influence on local and non-local channel bend kinematics. We further explore this relationship using a kinematic model of meandering applied to synthetically generated river reaches and the Landsat-derived Trinity River centrelines. While the model captures the observed linkages between post-cutoff bend curvature and resultant bend kinematics, it underpredicts the magnitude of cutoff influence observed in the real centreline data – particularly at the cutoff site – by up to one order of magnitude. Our results provide a promising advance in the characterization and prediction of the spatiotemporal impact of cutoffs on local and non-local post-cutoff channel bend kinematics.
Topic Modeling based Text Classification Regarding Islamophobia using Word Embedding and Transformers Techniques
Authors: Saeed Ammar , Khan Hikmat Ullah , Shankar Achyut , Imran Talha , Khan Danish , Kamran Muhammad , Khan Muhammad Attique 
Published: November 2023

Islamophobia is a rising area of concern in the current era where Muslims face discrimination and receive negative perspectives towards their religion, Islam. Islamophobia is a type of racism that is being practiced by individuals, groups, and organizations worldwide. Moreover, the ease of access to social media platforms and their augmented usage has also contributed to spreading hate speech, false information, and negative opinions about Islam. In this research study, we focused to detect Islamophobic textual content shared on various social media platforms. We explored the state-of-the-art techniques being followed in text data mining and Natural Language Processing (NLP). Topic modelling algorithm Latent Dirichlet Allocation is used to find top topics. Then, word embedding approaches such as Word2Vec and Global Vectors for word representation (GloVe) are used as feature extraction techniques. For text classification, we utilized modern text analysis techniques of transformers-based Deep Learning algorithms named Bidirectional Encoders Representation from Transformers (BERT) and Generative Pre-Trained Transformer (GPT). For results comparison, we conducted an extensive empirical analysis of Machine Learning algorithms and Deep Learning using conventional textual features such as the Term Frequency-Inverse Document Frequency, N-gram, and Bag of words (BoW). The empirical based results evaluated using standard performance evaluation measures show that the proposed approach effectively detects the textual content related to Islamophobia.
In the corpus of the study under Machine Learning models Support Vector Machine (SVM) performed best with an F1 score of 91%. The Transformer based core NLP models and the Deep Learning model Convolutional Neural Network (CNN) when combined with GloVe performed best among all the techniques except SVM with BoW. GPT, SVM when combined with BoW and BERT yielded the best F1 score of 92%, 92% and 91.9% respectively, while CNN performed slightly poor with an F1 score of 91%.
Optimal Model Partitioning with Low-Overhead Profiling on the PIM-based Platform for Deep Learning Inference
Authors: Kim Seok Young , Lee Jaewook , Paik Yoonah , Kim Chang Hyun , Lee Won Jun , Kim Seon Wook 
Published: November 2023

Recently Processing-in-Memory (PIM) has become a promising solution to achieve energy-efficient computation in data-intensive applications by placing computation near or inside the memory. In most Deep Learning (DL) frameworks, a user manually partitions a model’s computational graph (CG) onto the computing devices by considering the devices’ capability and the data transfer. The Deep Neural Network (DNN) models become increasingly complex for improving accuracy; thus, it is exceptionally challenging to partition the execution to achieve the best performance, especially on a PIM-based platform requiring frequent offloading of large amounts of data.
This article proposes two novel algorithms for DL inference to resolve the challenge: low-overhead profiling and optimal model partitioning. First, we reconstruct CG by considering the devices’ capability to represent all the possible scheduling paths. Second, we develop a profiling algorithm to find the required minimum profiling paths to measure all the node and edge costs of the reconstructed CG. Finally, we devise the model partitioning algorithm to get the optimal minimum execution time using the dynamic programming technique with the profiled data. We evaluated our work by executing the BERT, RoBERTa, and GPT-2 models on the ARM multicores with the PIM-modeled FPGA platform with various sequence lengths. For three computing devices in the platform, i.e., CPU serial/parallel and PIM executions, we could find all the costs only in four profile runs, three for node costs and one for edge costs. Also, our model partitioning algorithm achieved the highest performance in all the experiments over the execution with manually assigned device priority and the state-of-the-art greedy approach.
Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations
Authors: Varkaris Andreas , Fece de la Cruz Ferran , Martin Elizabeth E. , Norden Bryanna L. , Chevalier Nicholas , Kehlmann Allison M. , Leshchiner Ignaty , Barnes Haley , Ehnstrom Sara , Stavridi Anastasia-Maria , Yuan Xin , Kim Janice S. , Ellis Haley , Papatheodoridi Alkistis , Gunaydin Hakan , Danysh Brian P. , Parida Laxmi , Sanidas Ioannis , Ji Yongli , Lau Kayao , Wulf Gerburg M. , Bardia Aditya , Spring Laura M. , Isakoff Steven J. , Lennerz Jochen K. , Del Vecchio Kathryn , Pierce Levi , Pazolli Ermira , Getz Gad , Corcoran Ryan B. , Juric Dejan 
Published: November 2023

Abstract

PIK3CA mutations occur in ∼8% of cancers, including ∼40% of HR-positive breast cancers, where the PI3K-alpha (PI3Kα)-selective inhibitor alpelisib is FDA approved in combination with fulvestrant. Although prior studies have identified resistance mechanisms, such as PTEN loss, clinically acquired resistance to PI3Kα inhibitors remains poorly understood. Through serial liquid biopsies and rapid autopsies in 39 patients with advanced breast cancer developing acquired resistance to PI3Kα inhibitors, we observe that 50% of patients acquire genomic alterations within the PI3K pathway, including PTEN loss and activating AKT1 mutations. Notably, although secondary PIK3CA mutations were previously reported to increase sensitivity to PI3Kα inhibitors, we identified emergent secondary resistance mutations in PIK3CA that alter the inhibitor binding pocket. Some mutations had differential effects on PI3Kα-selective versus pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Kα-inhibitor RLY-2608. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers.

Significance:
In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Kα inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Kα inhibitor.
See related commentary by Gong and Vanhaesebroeck, p. 204 .
See related article by Varkaris et al., p. 240 .
This article is featured in Selected Articles from This Issue, p. 201