bluuebunny/crossref_metadata_2025 huggingface dataset:
Fourier-transform infrared spectroscopy for typing of vancomycin-resistant
Enterococcus faecium
: performance analysis and outbreak investigation
Authors: Scheier T. C. , Franz J. , Boumasmoud M. , Andreoni F. , Chakrakodi B. , Duvnjak B. , Egli A. , Zingg W. , Ramette A. , Wolfensberger A. , Kouyos R. D. , Brugger S. D.
Published: September 2023

Vancomycin-resistant Enterococci, mainly
Enterococcus faecium
(VREfm), are causing nosocomial infections and outbreaks. Bacterial typing methods are used to assist in outbreak investigations. Most of them, especially genotypic methods like multi-locus sequence typing (MLST), whole genome sequencing (WGS), or pulsed-field gel electrophoresis, are quite expensive and time-consuming. Fourier-transform infrared (FT-IR) spectroscopy assesses the biochemical composition of bacteria, such as carboxyl groups in polysaccharides. It is an affordable technique and has a faster turnaround time. Thus, the aim of this study was to evaluate FT-IR spectroscopy for VREfm outbreak investigations. Basic performance requirements like reproducibility and the effects of incubation time were assessed in distinct sample sets. After determining a FT-IR spectroscopy cut-off range, the clustering agreement between FT-IR and WGS within a retrospective (n: 92 isolates) and a prospective outbreak (n: 15 isolates) was investigated. For WGS an average nucleotide identity (ANI) cut-off score of 0.999 was used. Basic performance analysis showed reproducible results. Moreover, FT-IR spectroscopy readouts showed a high agreement with WGS-ANI analysis in clinical outbreak investigations (V-measure 0.772 for the retrospective and 1.000 for the prospective outbreak). FT-IR spectroscopy had a higher discriminatory power than MLST in the outbreak investigations. After determining cut-off values to achieve optimal resolution, FT-IR spectroscopy is a promising technique to assist in outbreak investigation as an affordable, easy-to-use tool with a turnaround time of less than one day.

IMPORTANCE

Vancomycin-resistant Enterococci, mainly
Enterococcus faecium
(VREfm), are a frequent cause of nosocomial outbreaks. Several bacterial typing methods are used to track transmissions and investigate outbreaks, whereby genome-based techniques are used as a gold standard. Current methods are either expensive, time-consuming, or both. Additionally, often, specifically trained staff needs to be available. This study provides insight into the use of Fourier-transform infrared (FT-IR) spectroscopy, an affordable, easy-to-use tool with a short turnaround time as a typing method for VREfm. By assessing clinical samples, this work demonstrates promising results for species discrimination and reproducibility. FT-IR spectrosopy shows a high level of agreement in the analysis of VREfm outbreaks in comparison with whole genome sequencing-based methods.
Assessing the transmission risk of red sea bream iridovirus (RSIV) in environmental water: insights from fish farms and experimental settings
Authors: Kawato Yasuhiko , Takada Yuzo , Mizuno Kaori , Harakawa Shogo , Yoshihara Yusaku , Nakagawa Yukihiro , Kurobe Tomofumi , Kawakami Hidemasa , Ito Takafumi
Published: September 2023

Aquatic animal viruses are considered to be transmitted via environmental water between fish farms. This study aimed to understand the actual transmission risk of red sea bream iridovirus (RSIV) through environmental water among fish farms. An environmental DNA (eDNA) method using iron-based flocculation coupled with large-pore filtration was used to monitor RSIV DNA copies in seawater from fish farms and from an experimental infection model. RSIV dispersion in seawater from a net pen where the disease outbreak occurred was visualized by the inverse distance weighting method using multiple-sampling data sets from a fish farm. The analysis demonstrated that the center of the net pen had a high viral load, and RSIV seemed to be quickly diluted by the tidal current. To evaluate the transmission risk of RSIV in environmental water, the red sea bream
Pagrus major
(approximately 10 g) was exposed to RSIV-contained seawater (10
3
, 10
4
, 10
5
, 10
6
, and 10
7
copies/L) for 3 days, which mimicked field exposure. A probit analysis of the challenge test indicated that the inferred infection rates of seawater containing 10
5.9
copies/L and 10
3.1
copies/L of RSIV were 50% and 0.0001%, respectively. In the surveillance for 3 years at 10 fixed points (
n
= 306), there were only seven samples in which the viral load exceeded 10
4
copies/L in seawater. These results suggest that the transmission of RSIV among fish farms via seawater is highly associated with the distance between the net pens, and the environmental water is not always an infection source for the transmission of RSIV between fish farms.

IMPORTANCE

Our surveillance of viral loads for red sea bream iridovirus (RSIV) by monitoring environmental DNA in fish farms suggested that the viral loads in the seawater were low, except for the net pens where RSIV outbreaks occurred. Furthermore, our experimental infection model indicated that the infection risk of RSIV-contained seawater with less than 10
3
copies/L was extremely low. The limited risk of environmental water for transmission of RSIV gives an insight that RSIV could be partly transmitted between fish farms due to the movement of equipment and/or humans from the fish farm where the disease outbreaks. Since our data suggest that seawater can function as a potential wall to reduce the transmission of RSIV, biosecurity management, such as disinfection of equipment associated with fish farms could be effective, even in the semi-open system aquaculture that the environmental water can be freely transferred, to reduce the risk of RSIV outbreaks.
Taxonomic characterization of
Pseudomonas hygromyciniae
sp. nov., a novel species discovered from a commercially purchased antibiotic
Authors: Turner Timothy L. , Mitra Sumitra D. , Kochan Travis J. , Pincus Nathan B. , Lebrun-Corbin Marine , Cheung Bettina H. , Gatesy Samuel W. , Afzal Tania , Nozick Sophie H. , Ozer Egon A. , Hauser Alan R.
Published: September 2023

In an attempt to identify novel bacterial species, microbiologists have examined a wide range of environmental niches. We describe the serendipitous discovery of a novel gram-negative bacterial species from a different type of extreme niche: a purchased vial of antibiotic. The vial of antibiotic hygromycin B was found to be factory contaminated with a bacterial species, which we designate
Pseudomonas hygromyciniae
sp. nov. The proposed novel species belongs to the
P. fluorescens
complex and is most closely related to
P. brenneri
,
P. proteolytica
, and
P. fluorescens
. The type strain
Pseudomonas hygromyciniae
sp. nov.

strain SDM007
T

(SDM007
T
) harbors a novel 250 kb megaplasmid which confers resistance to hygromycin B and contains numerous other genes predicted to encode replication and conjugation machinery. SDM007
T
grows in hygromycin concentrations of up to 5 mg/mL but does not use the antibiotic as a carbon or nitrogen source. While unable to grow at 37°C ruling out its ability to infect humans, it grows and survives at temperatures between 4 and 30°C. SDM007
T
can infect plants, as demonstrated by the lettuce leaf model, and is highly virulent in the
Galleria mellonella
infection model but is unable to infect mammalian A549 cells. These findings indicate that commercially manufactured antibiotics represent another extreme environment that may support the growth of novel bacterial species.

IMPORTANCE

Physical and biological stresses in extreme environments may select for bacteria not found in conventional environments providing researchers with the opportunity to not only discover novel species but to uncover new enzymes, biomolecules, and biochemical pathways. This strategy has been successful in harsh niches such as hot springs, deep ocean trenches, and hypersaline brine pools. Bacteria belonging to the
Pseudomonas
species are often found to survive in these unusual environments, making them relevant to healthcare, food, and manufacturing industries. Their ability to survive in a variety of environments is mainly due to the high genotypic and phenotypic diversity displayed by this genus. In this study, we discovered a novel
Pseudomonas
sp. from a desiccated environment of a sealed antibiotic bottle that was considered sterile. A close genetic relationship with its phylogenetic neighbors reiterated the need to use not just DNA-based tools but also biochemical characteristics to accurately classify this organism.
Polymicrogyria in a patient after twin–twin transfusion syndrome
Authors: Karner Eva , Kasprian Gregor J , Farr Alex , Krampl-Bettelheim Elisabeth
Published: September 2023

This case report presents a patient with a monochorionic twin pregnancy, development of twin–twin transfusion-syndrome (TTTS) and polymicrogyria (PMG) of one fetus. Due to TTTS grade 3, fetoscopic laser ablation was performed at gestational week 16+1. Sonographic follow-up showed a cortical malformation of the right parietal lobe in the former donor, which was identified as PMG by MRI scans. We describe the course of the pregnancy, as well as the clinical, especially neurological, development of the child over 3 years. This case report documents the power of neuroplasticity, leading to comparably good neurological outcome in an extensive, likely acquired cortical malformation. Further, it emphasises the importance of a thorough prenatal imaging characterisation of malformations of cortical development for optimal prenatal counselling of these cases.
Relationship between daytime napping with the occurrence and development of diabetes: a systematic review and meta-analysis
Authors: Liu Mengdie , Liu Minhui , Wang Shuo , Sun Yumei , Zhou Fang , Sun Hongyu
Published: September 2023

Objective

To determine the relationship of napping with incident diabetes risk and glycaemic control in people with diabetes.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE (PubMed), EMBASE, Web of Science and the Cochrane Library were searched for studies published from database inception to 9 May 2023.

Eligibility criteria

Observational studies reporting the relationship of napping with diabetes or glycaemic control in patients with diabetes in adult populations were included.

Data extraction and synthesis

Two reviewers independently screened the literature, extracted data and assessed the quality of the included studies. The results were reported as ORs and 95% CIs, which were pooled by using fixed and random effects models, and subgroup analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation method was used to assess the quality of the evidence.

Results

Forty studies were included in our review. Habitual napping was associated with an increased diabetes risk (OR 1.20, 95% CI 1.14 to 1.27) and poor glycaemic control in patients with diabetes (OR 2.05, 95% CI 1.55 to 2.73). Nap durations less than 30 min were unrelated to diabetes (OR 1.05, 95% CI 0.97 to 1.14). Nap durations of 30–60 min were associated with diabetes risk (OR 1.09, 95% CI 1.02 to 1.17), but there were differences in the subgroup analysis results. Nap durations of more than 60 min significantly increased the risk of diabetes (OR 1.31, 95% CI 1.20 to 1.44).

Conclusions

Napping is associated with increased diabetes risk and poor glycaemic control, and future research will need to confirm whether there are sex and regional differences. Nap durations of more than 60 min significantly increases the risk of diabetes, and the relationship between nap duration and glycaemic control in patients with diabetes needs to be further explored in the future.

PROSPERO registration number

CRD42021292103.
Effect of robotic-assisted gait training on gait and motor function in spinal cord injury: a protocol of a systematic review with meta-analysis
Authors: Wang Lei , Peng Jin-lin , Chen Ai-lian
Published: September 2023

Introduction

Robotic-assisted gait training (RAGT) has been reported to be effective in rehabilitating patients with spinal cord injury (SCI). However, studies on RAGT showed different results due to a varied number of samples. Thus, summarising studies based on robotic-related factors is critical for the accurate estimation of the effects of RAGT on SCI. This work aims to search for strong evidence showing that using RAGT is effective in treating SCI and analyse the deficiencies of current studies.

Methods and analysis

The following publication databases were electronically searched in December 2022 without restrictions on publication year: MEDLINE, Cochrane Library, Web of Science, Embase, PubMed, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure. Various combinations of keywords, including ‘motor disorders’, ‘robotics’, ‘robotic-assisted gait training’, ‘Spinal Cord Injuries’, ‘SCI’ and ‘gait analysis’ were used as search terms. All articles on randomised controlled trials (excluding retrospective trials) using RAGT to treat SCI that were published in English and Chinese and met the inclusion criteria were included. Outcomes included motor function, and gait parameters included those assessed by using the instrumented gait assessment, the Berg Balance Scale, the 10-m walk speed test, the 6-min walk endurance test, the functional ambulation category scale, the Walking index of SCI and the American Spinal Injury Association assessment scale. Research selection, data extraction and quality assessment were conducted independently by two reviewers to ensure that all relevant studies were free from personal bias. In addition, the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager V.5.3 software was used to produce deviation risk maps and perform paired meta-analyses.

Ethics and dissemination

Ethics approval is not required for systematic reviews and network meta-analyses. The results will be submitted to a peer-reviewed journal or presented at a conference.

PROSPERO registration number

CRD42022319555.
Multiple chemical sensitivity scoping review protocol: overview of research and MCS construct
Authors: Hempel Susanne , Danz Margie , Robinson Karen A , Bolshakova Maria , Rodriguez Jesus , Mears Alanna , Pham Cindy , Yagyu Sachi , Motala Aneesa , Tolentino Danica , Akbari Omid , Johnston Jill
Published: September 2023

Introduction

Multiple chemical sensitivity (MCS) has been characterised by reported adverse responses to environmental exposures of common chemical agents (eg, perfumes, paint, cleaning products and other inhaled or ingested agents) in low doses considered non-toxic for the general population. There is currently no consensus on whether MCS can be established as a distinct disorder.

Methods and analysis

The scoping review of the literature will be guided by five questions: How is MCS defined and which diagnostic criteria have been proposed? What methods are used to report prevalence and incidence estimates of MCS? What are the characteristics of the body of scientific evidence that addresses whether MCS is a distinct disorder or syndrome? What underlying mechanisms for MCS have been proposed in the scientific literature? Which treatment and management approaches for MCS have been evaluated in empirical research studies? We will conduct a comprehensive search in 14 research databases. Citation screening will be supported by machine learning algorithms. Two independent reviewers will assess eligibility of full-text publications against prespecified criteria. Data abstraction will support concise evidence tables. A formal consultation exercise will elicit input regarding the review results and presentation. The existing research evidence will be documented in a user-friendly visualisation in the format of an evidence map.

Ethics and dissemination

Determined to be exempt from review (UP-22-00516). Results will be disseminated through a journal manuscript and data will be publicly accessible through an online data repository.

Registration details

The protocol is registered in Open Science Framework (osf.io/4a3wu).
Exploring HPV vaccine knowledge, attitudes, barriers and information sources among parents, health professionals and teachers in Kazakhstan: a mixed-methods study protocol
Authors: Kassymbekova Fatima , Zhetpisbayeva Indira , Tcoy Evgeniya , Dyussenov Rassul , Davletov Kairat , Rommel Alexander , Glushkova Natalya
Published: September 2023

Introduction

Human papillomavirus (HPV) is a prevalent sexually transmitted infection linked to certain types of malignant neoplasms, notably cervical cancer (CC). In Kazakhstan, a high prevalence of high oncogenic HPV types (HR-HPV) has been observed, and CC ranks as the second most common malignancy among women with a crude incidence rate of 18.3 cases per 100 000 women. The HPV vaccine, developed as the primary prevention measure against HPV infection, including the most prevalent HR-HPV, received approval from the WHO in 2009. In 2014, Kazakhstan initiated HPV vaccination as a pilot project in four sub-national regions; however, it was later in 2017 discontinued due to widespread parental refusal influenced by negative media reports. This study aims to examine knowledge, attitudes, information sources, barriers to HPV vaccination and factors associated with HPV vaccination hesitancy among different target groups in Kazakhstan prior to the HPV vaccine re-launch announced by the Ministry of Health.

Methods and analysis

This mixed-method-designed research comprises quantitative and qualitative components. Data on HPV awareness, attitudes towards HPV vaccination and sources of information will be collected through an online survey administered by parents and legal guardians, health professionals, and schoolteachers in the Republic of Kazakhstan between January 2023 and January 2024. Additionally, qualitative data on Kazakhstani parental beliefs and attitudes toward HPV vaccination will be collected through online focus group discussions.

Ethics and dissemination of results

The study has been approved by the local ethics committee at the Kazakhstan Medical University “Higher School of Public Health” (KMU “KSPH”) (No. 138 of 31.05.2021). The results will be reported in publications, at conferences among researchers and healthcare and school education professionals in Kazakhstan, and internationally.
Dynamic nomogram for predicting acute kidney injury in patients with community-acquired pneumonia
Authors: Chen Dawei , Zhao Jing , Ma Mengqing , Jiang Lingling , Tan Yan , Wan Xin
Published: September 2023

Introduction

Acute kidney injury (AKI) is a common complication in patients with community-acquired pneumonia (CAP) and negatively affects both short-term and long-term prognosis in patients with CAP. However, no study has been conducted on developing a clinical tool for predicting AKI in CAP patients. Therefore, this study aimed to develop a predictive tool based on a dynamic nomogram for AKI in CAP patients.

Methods

This retrospective study was conducted from January 2014 to May 2017, and data from adult inpatients with CAP at Nanjing First Hospital were analysed. Demographic data and clinical data were obtained. The least absolute shrinkage and selection operator (LASSO) regression model was used to select important variables, which were entered into logistic regression to construct the predictive model for AKI. A dynamic nomogram was based on the results of the logistic regression model. Calibration and discrimination were used to assess the performance of the dynamic nomogram. A decision curve analysis was used to assess clinical efficacy.

Results

A total of 2883 CAP patients were enrolled in this study. The median age was 76 years (IQR 63–84), and 61.3% were male. AKI developed in 827 (28.7%) patients. The LASSO regression analysis selected five important factors for AKI (albumin, acute respiratory failure, CURB-65 score, Cystatin C and white cell count), which were then entered into the logistic regression to construct the predictive model for AKI in CAP patients. The dynamic nomogram model showed good discrimination with an area under the receiver operating characteristics curve of 0.870 and good calibration with a Brier score of 0.129 and a calibration plot. The decision curve analysis showed that the dynamic nomogram prediction model had good clinical decision-making.

Conclusion

This easy-to-use dynamic nomogram may help physicians predict AKI in patients with CAP.
Consensus on acute behavioural disturbance in the UK: a multidisciplinary modified Delphi study to determine what it is and how it should be managed
Authors: Humphries Christopher , Kelly Anthony , Sadik Aws , Walker Alison , Smith Jason
Published: September 2023

Background

Acute behavioural disturbance (ABD) is a term used in law enforcement and healthcare, but there is a lack of clarity regarding its meaning. Common language should be used across staff groups to support the identification, prioritisation and delivery of care to this group of patients. The terminology currently used is inconsistent and confusing. This study aimed to reach a consensus on the criteria for identification and management of ABD, and to agree when other care pathways or guidelines might be more appropriately used.

Methods

A modified Delphi study with participation from stakeholder organisation representatives was conducted in January–April 2023 online. In round 1, statements were generated by participants in response to broad questions. Participants then rated their level of agreement with statements in subsequent rounds, with statements achieving a consensus removed for inclusion in the final derived consensus statement. Non-consensus statement responses were assessed for stability.

Results

Of 430 unique statements presented for rating, 266 achieved a consensus among 30 participants representing eight stakeholder organisations. A derived consensus statement was generated from these statements. The median group response to statements which failed to achieve a consensus was reliable (Krippendorff’s alpha=0·67).

Conclusions

There is a consensus across stakeholder organisations that ABD is not a separate entity to agitation, and guidance should instead be altered to address the full range of presentations of agitation. While the features of concern in this severely agitated group of patients can be described, the advice for recognition may vary depending on staff group. Criteria for recognition are provided and potential new terminology is described.
A simulated search for the singlet vector-like bottom quark decaying into tW at high energy pp colliders
Authors: Han Jinzhong , Shang Liangliang , Yang Bingfang
Published: September 2023

In a framework of simplified model, we perform a simulated search for the singlet vector-like bottom quark B decaying into tW with t hadronic decay and W leptonic decay at the 14 TeV high-luminosity LHC (HL-LHC), 27 TeV high energy LHC (HE-LHC) and 100 TeV Future Circular Hadron Collider (FCC-hh). In this work, we focus on the case that the B only couples with the third generation quarks of the Standard Model. We make a detailed detector simulations of the signal and backgrounds and obtain the $$2\sigma $$

2
σ

exclusion limit and $$5\sigma $$

5
σ

discovery prospects. Our results show that the upcoming HL-LHC can exclude (discover) the $$m_B$$

m
B

to 2100 (1900) GeV for a typical coupling strength $$g^{*}=0.2$$

g

∗

=
0.2

. For the HE-LHC (FCC-hh), this exclusion capability on the B quark mass can be expanded to more than 3000 (5000) GeV.
A new type of supercontinuum generation in hexagonal lattice C6H6-core PCF with broadband and low-power pump
Authors: Tran Bao Tran Le , Van Lanh Chu
Published: September 2023

Most of the spectral bandwidths of previous publications are still limited by high input powers making them economically less than ideal. By using a benzene core (C6H6) photonic crystal fiber (PCF) as a new supercontinuum (SC) light source, it is possible to achieve a very large spectral broadening with hundreds of times lower peak power. Due to the change in the diameter of air holes in the first ring near the core, near-zero flattened dispersion, high nonlinearity and small attenuation can be achieved for spectral broadening. The structural geometries of two C6H6-PCFs are optimized to generate wide SC at low input energy. The SC spectrum produced in 1[Formula: see text]cm long of all dispersion fiber extends from a part of visible light to the near-infrared range at 1.3[Formula: see text][Formula: see text]m wavelength and a small pulse energy of 18[Formula: see text]pJ (or 450[Formula: see text]W of electrical input). The second PCF shows wide soliton-induced SC from 0.8 to 4.2[Formula: see text][Formula: see text]m with 71[Formula: see text]pJ pulse energy (or input power approximately 790[Formula: see text]W) at 1.5[Formula: see text][Formula: see text]m wavelength within a fiber of 12[Formula: see text]cm. The proposed structures have the potential to become a new class of microstructured optical fibers for low-cost, broad-spectrum SC generation.
NUMERICAL APPROXIMATION AND ANALYSIS OF EPIDEMIC MODEL WITH CONSTANT PROPORTIONAL CAPUTO OPERATOR
Authors: XU CHANGJIN , FARMAN MUHAMMAD , LIU ZIXIN , PANG YICHENG
Published: September 2023

The social life, economic issues, and health issues resulting from various diseases will be impacted by the use of the epidemiological model to address the negative effects of drinking in society. The paper aims to investigate a nonlinear drinking epidemic fractional SHTR model in the sense of a Constant Proportional Caputo (CPC) operator. For the CPC operator, a stability study of the fractional order model and the presence of a solution have been made. A nonlinear system of the suggested system has an approximative solution provided by the Laplace Adomian Decomposition technique. A convergence analysis of the system is also treated to show the effect and efficiency of the scheme. Additionally, we offer some numerical outcomes to demonstrate the efficiency of this operator. A comparative study for different values of [Formula: see text] shows that these methods are effective for giving better results in fractional order as compared to classical order derivatives.
User Experience of Digital Voice Assistant: Conceptualization and Measurement
Authors: Chen Qian , Gong Yeming , Lu Yaobin
Published: September 2023

With the development of digital virtual assistants (DVA), academics and practitioners have increased attention to the DVA user experience. However, the measurement scale of DVA user experience is still under-researched, which may hinder further empirical study on human-DVA interaction. This study rigorously developed dimensions and associated scales of the DVA user experience. We employed a mixed-method approach that integrated qualitative and quantitative methods. This study first developed multilevel dimensions of DVA user experience based on consumers’ online reviews (n = 21,314), then adopted the ten-step method to develop the associate measurement scale with reliability and validity by collecting and examining three data sets (pretest: n = 368, refinement and validation: n = 585, cross-validation: n = 567). This study fills the gap of a lack of research on the classification and measurement of DVA user experience and provides a reference for practitioners in developing DVA and continuously improving the DVA user experience.
Tailor
: Altering Skip Connections for Resource-Efficient Inference
Authors: Weng Olivia , Marcano Gabriel , Loncar Vladimir , Khodamoradi Alireza , G Abarajithan , Sheybani Nojan , Meza Andres , Koushanfar Farinaz , Denolf Kristof , Duarte Javier Mauricio , Kastner Ryan
Published: September 2023

Deep neural networks use skip connections to improve training convergence. However, these skip connections are costly in hardware, requiring extra buffers and increasing on- and off-chip memory utilization and bandwidth requirements. In this article, we show that skip connections can be optimized for hardware when tackled with a hardware-software codesign approach. We argue that while a network’s skip connections are needed for the network to learn, they can later be removed or shortened to provide a more hardware-efficient implementation with minimal to no accuracy loss. We introduce
Tailor
, a codesign tool whose hardware-aware training algorithm gradually removes or shortens a fully trained network’s skip connections to lower the hardware cost.
Tailor
improves resource utilization by up to 34% for block random access memories (BRAMs), 13% for flip-flops (FFs), and 16% for look-up tables (LUTs) for on-chip, dataflow-style architectures.
Tailor
increases performance by 30% and reduces memory bandwidth by 45% for a two-dimensional processing element array architecture.
Cross-modality Neuroimage Synthesis: A Survey
Authors: Xie Guoyang , Huang Yawen , Wang Jinbao , Lyu Jiayi , Zheng Feng , Zheng Yefeng , Jin Yaochu
Published: September 2023

Multi-modality imaging improves disease diagnosis and reveals distinct deviations in tissues with anatomical properties. The existence of completely aligned and paired multi-modality neuroimaging data has proved its effectiveness in brain research. However, collecting fully aligned and paired data is expensive or even impractical, since it faces many difficulties, including high cost, long acquisition time, image corruption, and privacy issues. An alternative solution is to explore unsupervised or weakly supervised learning methods to synthesize the absent neuroimaging data. In this article, we provide a comprehensive review of cross-modality synthesis for neuroimages, from the perspectives of weakly supervised and unsupervised settings, loss functions, evaluation metrics, imaging modalities, datasets, and downstream applications based on synthesis. We begin by highlighting several opening challenges for cross-modality neuroimage synthesis. Then, we discuss representative architectures of cross-modality synthesis methods under different supervisions. This is followed by a stepwise in-depth analysis to evaluate how cross-modality neuroimage synthesis improves the performance of its downstream tasks. Finally, we summarize the existing research findings and point out future research directions. All resources are available at https://github.com/M-3LAB/awesome-multimodal-brain-image-systhesis.
The Size of Clausal Complements
Authors: Wurmbrand Susanne
Published: September 2023

Drawing mainly—but not exclusively—on data from Germanic, this article compares syntactic, morphological, and semantic approaches to size differences of complement clauses. Focusing on two phenomena that have been related to clause size reduction and truncation—Exceptional Case Marking (ECM) and restructuring—it is shown that their distribution is radically different and that clause size cannot be the main factor regulating both of these phenomena. This article provides a solution to this conflicting state of affairs and lays out an approach that builds on a fine-grained CP structure, including both syntactic and semantic categories, a reduced structure for infinitives, and a syntax–meaning mapping that predicts different minimal clause sizes for different semantic types of complements. Based on the distribution of ECM in Germanic, a tentative ECM hierarchy is suggested that follows implicational containment relations of an expanded CP.
Emerging Therapies in Hypothyroidism
Authors: Bianco Antonio C.
Published: September 2023

Levothyroxine (LT4) is effective for most patients with hypothyroidism. However, a minority of the patients remain symptomatic despite the normalization of serum thyrotropin levels. Randomized clinical trials including all types of patients with hypothyroidism revealed that combination levothyroxine and liothyronine (LT4+LT3) therapy is safe and is the preferred choice of patients versus LT4 alone. Many patients who do not fully benefit from LT4 experience improved quality of life and cognition after switching to LT4+LT3. For these patients, new slow-release LT3 formulations that provide stable serum T3 levels are being tested. In addition, progress in regenerative technology has led to the development of human thyroid organoids that restore euthyroidism after being transplanted into hypothyroid mice. Finally, there is a new understanding that, under certain conditions, T3 signaling may be compromised in a tissue-specific fashion while systemic thyroid function is preserved. This is seen, for example, in patients with metabolic (dysfunction)-associated fatty liver disease, for whom liver-selective T3-like molecules have been utilized successfully in clinical trials.
Antibody and B Cell Responses to SARS-CoV-2 Infection and Vaccination: The End of the Beginning
Authors: Röltgen Katharina , Boyd Scott D.
Published: September 2023

As the COVID-19 pandemic has evolved during the past years, interactions between human immune systems, rapidly mutating and selected SARS-CoV-2 viral variants, and effective vaccines have complicated the landscape of individual immunological histories. Here, we review some key findings for antibody and B cell–mediated immunity, including responses to the highly mutated omicron variants; immunological imprinting and other impacts of successive viral antigenic variant exposures on antibody and B cell memory; responses in secondary lymphoid and mucosal tissues and non-neutralizing antibody-mediated immunity; responses in populations vulnerable to severe disease such as those with cancer, immunodeficiencies, and other comorbidities, as well as populations showing apparent resistance to severe disease such as many African populations; and evidence of antibody involvement in postacute sequelae of infection or long COVID. Despite the initial phase of the pandemic ending, human populations will continue to face challenges presented by this unpredictable virus.
Genetics and Pathogenesis of Dystonia
Authors: Thomsen Mirja , Lange Lara M. , Zech Michael , Lohmann Katja
Published: September 2023

Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or intermittent muscle contractions. A number of groundbreaking genetic and molecular insights have recently been gained. While they enable genetic testing and counseling, their translation into new therapies is still limited. However, we are beginning to understand shared pathophysiological pathways and molecular mechanisms. It has become clear that dystonia results from a dysfunctional network involving the basal ganglia, cerebellum, thalamus, and cortex. On the molecular level, more than a handful of, often intertwined, pathways have been linked to pathogenic variants in dystonia genes, including gene transcription during neurodevelopment (e.g., KMT2B, THAP1), calcium homeostasis (e.g., ANO3, HPCA), striatal dopamine signaling (e.g., GNAL), endoplasmic reticulum stress response (e.g., EIF2AK2, PRKRA, TOR1A), autophagy (e.g., VPS16), and others. Thus, different forms of dystonia can be molecularly grouped, which may facilitate treatment development in the future.
Artificial Intelligence for Drug Discovery: Are We There Yet?
Authors: Hasselgren Catrin , Oprea Tudor I.
Published: September 2023

Drug discovery is adapting to novel technologies such as data science, informatics, and artificial intelligence (AI) to accelerate effective treatment development while reducing costs and animal experiments. AI is transforming drug discovery, as indicated by increasing interest from investors, industrial and academic scientists, and legislators. Successful drug discovery requires optimizing properties related to pharmacodynamics, pharmacokinetics, and clinical outcomes. This review discusses the use of AI in the three pillars of drug discovery: diseases, targets, and therapeutic modalities, with a focus on small-molecule drugs. AI technologies, such as generative chemistry, machine learning, and multiproperty optimization, have enabled several compounds to enter clinical trials. The scientific community must carefully vet known information to address the reproducibility crisis. The full potential of AI in drug discovery can only be realized with sufficient ground truth and appropriate human intervention at later pipeline stages.
Sexual Incentive Motivation and Sexual Behavior: The Role of Consent
Authors: Ågmo Anders , Laan Ellen
Published: September 2023

The generalized social concern with sexual harassment and nonconsensual sex makes it imperative to incorporate notions of consent in any analysis of human sexual interactions. Such interactions follow an ordered sequence of events, starting with the perception of a sexual incentive, followed by an approach to it, genital interaction, and eventually orgasm. Consent from the partner is needed at every stage. At some points in this chain of events, the individuals involved make cognitive evaluations of the context and predictions of the likelihood for obtaining consent for proceeding to the next phase. Processes such as communication of consent or lack thereof, sexual decision making, and interpretation of cues emitted by the partner are decisive. Increased sexual motivation may influence these processes. However, available data make it possible to ascertain that enhanced motivation has no, or at most minor, effects, thereby invalidating the old assumption that heightened sexual motivation leads to impaired control.
Prokaryotic voltage-gated sodium channels are more effective than endogenous Nav1.5 channels in rescuing cardiac action potential conduction: an in silico study
Authors: Needs Daniel , Wu Tianyu , Nguyen Hung X. , Henriquez Craig S. , Bursac Nenad
Published: September 2023

Slow action potential conduction is a common cause of various cardiac arrhythmias; yet, current pharmacotherapies cannot augment cardiac conduction. This in silico study compared the efficacy of recently proposed antiarrhythmic gene therapy approaches that increase peak sodium current in cardiomyocytes. When compared with the augmentation of endogenous sodium current, expression of slower-inactivating bacterial sodium channels was superior in preventing conduction block and arrhythmia induction. These results further the promise of antiarrhythmic gene therapies targeting sodium channels.
Synthesis of Nanoporous Biochar from Rice Husk for Adsorption of Methylene Blue
Authors: Dang Dan , Mei Lei , Yan Gaimeng , Liu Wenju
Published: September 2023

In this study, rice husk charcoal prepared with KOH and KOH-NaOH as activators were investigated as adsorbents for the removal of methylene blue from aqueous solutions in order to improve the utilisation of rice husk. Firstly, the rice husk carbon was morphologically and chemically characterised using scanning electron microscopy, specific surface area analyser, and infrared spectroscopy. Secondly, the effects of the alkali-carbon ratio, pyrolysis temperature, and pyrolysis time on the activation of KOH alone and combined activation of KOH-NaOH were investigated. The results showed that the adsorption capacity of the activated biochar was 359.7 mg/g (higher than that of 315.4 mg/g when KOH alone was activated) under the same adsorption conditions when KOH-NaOH was coactivated. Finally, combined with the characterization results and data analysis, it can be seen that the rice husk carbon obtained by KOH-NaOH composite activation is predominantly microporous with a more uniform pore size distribution, making it an economical and efficient adsorbent for the removal of methylene blue from aqueous solutions.
Generalized Ordered Intuitionistic Fuzzy C‐Means Clustering Algorithm Based on PROMETHEE and Intuitionistic Fuzzy C‐Means
Authors: Bashir Muhammad Adnan , Rashid Tabasam , Bashir Muhammad Salman
Published: September 2023

The problem of ordered clustering in the context of decision‐making with multiple criteria has garnered significant interest from researchers in the field of management science and operational research. In real‐world scenarios, the datasets often exhibit imprecision or uncertainty, which can lead to suboptimal ordered‐clustering outcomes. However, the intuitionistic fuzzy c‐means (IFCM) clustering algorithm enhances the accuracy and effectiveness of decision‐making processes by effectively handling uncertain dataset information for clustering. Therefore, we propose a new clustering algorithm, called the generalized ordered intuitionistic fuzzy c‐means (G‐OIFCM), based on PROMETHEE and the IFCM clustering algorithm. Different from the classical IFCM clustering algorithm, we use positive flow (φ+(si) ∈ [0,  1]) and negative flow (φ−(si) ∈ [0,  1]) of PROMETHEE to generate ordered clusters within the intuitionistic environment. We define a new objective function based on the positive and negative flow of the PROMETHEE and IFCM clustering algorithm, whose properties are mathematically justified in terms of convergence and optimization. The performance of the proposed algorithm is evaluated using two different real‐world datasets to assess both the ordered clustering and the quality of partitioning. To demonstrate the effectiveness of G‐OIFCM, a comparison is conducted with three other algorithms: fuzzy c‐means (FCM), ordered fuzzy c‐means (OFCM), and an adaptive generalized intuitionistic fuzzy c‐means (G‐IFCM). The results demonstrate the effectiveness of G‐OIFCM in enhancing optimal ordered clustering and utility when dealing with uncertainty in datasets.
Data from Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous KIT/PDGFRA Mutations in the Phase III INVICTUS Study
Authors: Bauer Sebastian , Heinrich Michael C. , George Suzanne , Zalcberg John R. , Serrano César , Gelderblom Hans , Jones Robin L. , Attia Steven , D'Amato Gina , Chi Ping , Reichardt Peter , Meade Julie , Su Ying , Ruiz-Soto Rodrigo , Blay Jean-Yves , von Mehren Margaret , Schöffski Patrick
Published: September 2023

AbstractPurpose:
Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in KIT/PDGFRA and are initially responsive to tyrosine kinase inhibitors (TKI). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase III INVICTUS study (NCT03353753) characterizing the genomic heterogeneity of tumors from patients with advanced GIST and evaluating ripretinib efficacy across KIT/PDGFRA mutation subgroups.
Patients and Methods:
Tumor tissue and liquid biopsy samples that captured circulating tumor DNA were collected prior to study enrollment and sequenced using next-generation sequencing. Subgroups were determined by KIT/PDGFRA mutations and correlation of clinical outcomes and KIT/PDGFRA mutational status was assessed.
Results:
Overall, 129 patients enrolled (ripretinib 150 mg once daily, n = 85; placebo, n = 44). The most common primary mutation subgroup detected by combined tissue and liquid biopsies were in KIT exon 11 (ripretinib, 61.2%; placebo, 77.3%) and KIT exon 9 (ripretinib, 18.8%; placebo, 15.9%). Patients receiving ripretinib demonstrated progression-free survival (PFS) benefit versus placebo regardless of mutation status (HR 0.16) and in all assessed subgroups in Kaplan–Meier PFS analysis (exon 11, P < 0.0001; exon 9, P = 0.0023; exon 13, P < 0.0001; exon 17, P < 0.0001). Among patients with wild-type KIT/PDGFRA by tumor tissue, PFS ranged from 2 to 23 months for ripretinib versus 0.9 to 10.1 months for placebo.
Conclusions:
Ripretinib provided clinically meaningful activity across mutation subgroups in patients with advanced GIST, demonstrating that ripretinib inhibits a broad range of KIT/PDGFRA mutations in patients with advanced GIST who were previously treated with three or more TKIs.
Supplementary Data from Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer
Authors: Brasky Theodore M. , Newton Alison M. , Conroy Sara , Adib Anita , Adley Neema C. , Strassels Scott A. , Hays John L. , Cooper Ziva D. , Wagener Theodore L. , Stevens Erin , Plascak Jesse J. , Krok-Schoen Jessica L.
Published: September 2023

Research Questionnaire
Data from Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer
Authors: Brasky Theodore M. , Newton Alison M. , Conroy Sara , Adib Anita , Adley Neema C. , Strassels Scott A. , Hays John L. , Cooper Ziva D. , Wagener Theodore L. , Stevens Erin , Plascak Jesse J. , Krok-Schoen Jessica L.
Published: September 2023

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population.

Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use.

Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6–7.0) days/week, 2.0 (1.0–3.0) times per use/day, and for 3 years (0.8–30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use.

This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations.
Significance:
Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.