bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of Mycophenolic Acid Exposure in Chinese Renal Transplant Patients by a Joint Deep Learning Model
Authors: Shao Kun , Jia Yichen , Lu Jiaqian , Zhang Wei , Chen Bing , Chen Dehua , An Huimin , Zhou Quan , Rong Ruiming , Zhu Tongyu , Zhou Peijun
Published: September 2022

Background:

To predict mycophenolic acid (MPA) exposure in renal transplant recipients using a deep learning model based on a convolutional neural network with bilateral long short-term memory and attention methods.

Methods:

A total of 172 Chinese renal transplant patients were enrolled in this study. The patients were divided into a training group (n = 138, Ruijin Hospital) and a validation group (n = 34, Zhongshan Hospital). Fourteen days after renal transplantation, rich blood samples were collected 0–12 hours after MPA administration. The plasma concentration of total MPA was measured using an enzyme-multiplied immunoassay technique. A limited sampling strategy based on a convolutional neural network–long short-term memory with attention (CALS) model for the prediction of the area under the concentration curve (AUC) of MPA was established. The established model was verified using the data from the validation group. The model performance was compared with that obtained from multiple linear regression (MLR) and maximum a posteriori (MAP) methods.

Results:

The MPA AUC0–12 of the training and validation groups was 54.28 ± 18.42 and 41.25 ± 14.53 µg·ml−1·h, respectively. MPA plasma concentration after 2 (C2), 6 (C6), and 8 (C8) hours of administration was the most significant factor for MPA AUC0–12. The predictive performance of AUC0–12 estimated using the CALS model of the validation group was better than the MLR and MAP methods in previous studies (r2 = 0.71, mean prediction error = 4.79, and mean absolute prediction error = 14.60).

Conclusions:

The CALS model established in this study was reliable for predicting MPA AUC0–12 in Chinese renal transplant patients administered mycophenolate mofetil and enteric-coated mycophenolic acid sodium and may have good generalization ability for application in other data sets.
Predictive Algorithm for Thiopurine-Induced Hepatotoxicity in Inflammatory Bowel Disease Patients
Authors: van Moorsel Sofia A. W. , Deben Debbie S. , Creemers Rob H. , Winkens Bjorn , Bus Paul , Pierik Marieke J. , Simsek Melek , de Boer Nanne K. H. , van Bodegraven Adriaan A. , Wong Dennis R.
Published: September 2022

Background:

Approximately 25% of patients with inflammatory bowel disease (IBD) discontinue azathioprine (AZA) or mercaptopurine (MP) therapy within 3 months of treatment initiation because of adverse drug reactions. Of these side-effects, about half are because of hepatotoxicity. The aim of this study was to validate and (subsequently) optimize a previously reported predictive algorithm for thiopurine-associated hepatotoxicity by increasing the number of patients with IBD benefitting from conventional thiopurine therapy.

Methods:

This multicenter observational study included consecutive thiopurine-naive patients with IBD who received AZA or MP treatment. The primary outcome was hepatotoxicity within 12 weeks. The patients with and without hepatotoxicity were compared. Four determinants, namely, age, sex, body mass index (BMI), and 6-methylmercaptopurine ribonucleotide concentrations 1 week after treatment initiation (T = 1) were used to validate and optimize 2 (1 dichotomous and 1 continuous) algorithms using multivariable logistic regression analysis.

Results:

Of 229 patients, 21 (9%) developed hepatotoxicity and 93% of the patients received MP with a median dose of 0.7 mg/kg (95% confidence interval 0.3–1.4 mg/kg). A difference in BMI was found between with and without hepatotoxicity groups (median 27.6 versus 24.2, P = 0.022). Specificities of 68% (Algorithm 1) and 77% (Algorithm 2) and sensitivities of 56% (Algorithm 1) and 50% (Algorithm 2) were obtained.

Conclusions:

Both algorithms demonstrated limited predictive accuracy for thiopurine-induced hepatotoxicity in the validation cohort. Relevant factors contributing to this outcome were changes in thiopurine prescription behavior over time, with more MP prescriptions at relatively lower dosages of MP.
Impact of a 12-minute educational video prior to initial consultation in a Mature Women’s Health and Menopause Clinic
Authors: Bouteaud Jeanne , Shaltout Ola , Christakis Marie K. , Murtaza Fahmeeda , Wolfman Wendy , Shirreff Lindsay
Published: September 2022

Objectives

Assess acceptability of a 12-minute educational video before menopause clinic consultation and evaluate its impact on knowledge and treatment certainty.

Methods

This was a pre-post intervention study among new patients with vasomotor symptoms (VMS) referred to a menopause clinic in Toronto, Canada. Participants completed electronic questionnaires before and after viewing a 12-minute online video covering menopause facts and VMS treatments. Participants’ demographic information and referring provider type were recorded. A 19-item true/false knowledge quiz and validated Decision Conflict Scale (DCS) were administered before and after viewing the video along with a validated Acceptability questionnaire after the video. Demographic information and acceptability were summarized descriptively and independent samples t tests compared knowledge and DCS total and subscores before and after viewing the education module. Multivariable analysis was used to identify factors associated with achieving treatment certainty.

Results

Seventy-one participants completed pre- and postintervention questionnaires. Mean age was 51.4 ± 6.0 years and most were White (58/71, 81.7%), had a university degree (24/71, 63.3%) and household income >$90,000 (53/71, 74.6%). After the video, there was significant increase in knowledge score (12.7 ± 2.1 vs. 16.9 ± 1.8, P < 0.001) and decrease in all DCS scores (total and five subscores) compared with preintervention scores (P < 0.001). Acceptability was high with 62/71 (87.3%) respondents indicating the tool was useful. Findings were independent of level of education, household income, and referring physician type.

Conclusion

In a study of predominantly university-educated White women, a 12-minute education module on menopause and VMS treatment was acceptable, there was improved knowledge and decision certainty about VMS treatment.
Radiation-induced Cell Death and Its Mechanisms
Authors: Jiao Yunfei , Cao Fangyu , Liu Hu
Published: September 2022

With rapid technical advances, ionizing radiation has been put into wider application in ordinary living, with the worst cytological effect on the human body being cell death. Moreover, according to the Nomenclature Committee on Cell Death, the method of radiation-induced cell death, usually classified as interphase and proliferative death, undergoes more detailed classifications oriented by its molecular mechanism. Elaborating its mode and molecular mechanism is crucial for the protection and treatment of radiation injury, as well as the radiotherapy and recovery of tumors. Varying with the changes of the radiation dose and the environment, the diverse targets and pathways of ionizing radiation result in various cell deaths. This review focuses on classifications of radiation-induced cell death and its molecular mechanism. We also examine the main characteristics of ionizing radiation-induced cell death. The modes of radiation-induced cell death can be classified as apoptosis, necrosis, autophagy-dependent cell death, pyroptosis, ferroptosis, immunogenic cell death, and non-lethal processes. Once the dose is high enough, radiation effects mostly appear as destructiveness (“destructiveness” is used to describe a situation in which cells do not have the opportunity to undergo a routine death process, in which case high-dose radiation works like a physical attack). This breaks up or even shatters cells, making it difficult to find responses of the cell itself. Due to diversities concerning cell phenotypes, phases of cell cycle, radiation dose, and even cellular subregions, various methods of cell death occur, which are difficult to identify and classify. Additionally, the existence of common initial activation and signaling molecules among all kinds of cell deaths, as well as sophisticated crossways in cellular molecules, makes it more laborious to distinguish and classify various cell deaths.
Monitoring Length of Stay of Acute Myocardial Infarction Patients: A Times Series Analysis Using Statistical Process Control
Authors: Pakdil Fatma , Beazoglou Hannah
Published: September 2022

Goal:

Given that length of stay (LOS) of acute myocardial infarction (AMI) patients has a significant impact on the utilization of hospital resources and the health status of communities, this study focused on how best to monitor LOS of AMI patients admitted to U.S. hospitals by employing statistical process control (SPC).

Methods:

Data were abstracted from the Healthcare Cost and Utilization Project Nationwide Readmissions Database between 2010 and 2016. A total of 1,491 patients were examined in the study. Patients who were admitted to nonfederal government (public) hospitals in metropolitan areas of at least 1 million residents with the primary diagnosis of AMI were abstracted. They were excluded if they developed AMI secondary to an interventional procedure or surgery, died during their index hospitalization, and were admitted and discharged on the same day. Patients were also excluded if they were discharged to short-term hospitals, nursing facilities, intermediate care facilities, home healthcare, or against medical advice. Individual moving range (I-MR) charts were used to monitor LOS of individual AMI patients in each subgroup from 2010 to 2016.

Principal Findings:

The results showed I-MR charts could be used to indicate statistically out-of-control signals on LOS. Specifically, I-MR charts showed that LOS decreased between 2010 and 2016. LOS appeared to be longer at teaching hospitals compared to nonteaching hospitals and varied by gender. Female patients appeared to stay longer than male patients in the hospitals.

Practical Applications:

The application of SPC and control charts can facilitate improved decision-making in healthcare organizations. This study shows the value of integrating control charts in administrative and medical decision-making processes. It may also help healthcare providers and managers achieve higher quality and lower cost of care.
The Role of the Leader in Fostering Employee Resilient Behaviors
Authors: Caniëls Marjolein C.J. , Stynen Dave
Published: September 2022

Objective

This study aims to uncover the relationship between leadership behaviors (servant and resilient), leaders’ psychological capital, and employee resilient behaviors over time, and we assess whether employee resilient behaviors and employee psychological capital mediate this relationship.

Methods

Based on dyadic 3-wave data collected from 111 unique leader-follower pairs, we use time-lagged path analysis to test our hypotheses.

Results

Servant leadership and leaders’ psychological capital may strengthen employees’ psychological capital, which in turn may foster resilient behaviors in employees over time. Resilient leadership was, however, negatively related to employee psychological capital on the short term but positively related to employee resilient behaviors over a 6-week time window.

Conclusions

Enacting servant leadership and resilient behavior and through their psychological capital leaders can foster resilient behaviors in employees.
Environmental Factors at the Periconceptional Period and the Occurrence of Cleft Lip and Palate in a Midwest Brazil Population
Authors: Silvestre Carla Meliso R. , Silva Ageo M. C. , Ferreira da Silva Renata Cristina Giroto , Bittencourt Walkiria S. , Borba Alexandre Meireles , Fernandes Vander , da Silva Cristhiane A. L.
Published: September 2022

Objective

To investigate the association between periconceptional environmental exposures and the occurrence of cleft lips and palates.

Methods

This case-control study analyzed 150 mothers of children with cleft lips and palates living in the same city as 250 mothers whose children did not present with this malformation (controls). Environmental exposure data were gathered through a questionnaire (Latin American Collaborative Study of Congenital Malformations methodology).

Results

Multivariate analysis revealed that monthly income below minimum wage, having another malformed child, other diseases in the first gestational trimester (urinary infection), use of pesticides in home gardens, and pesticide use in farms close to the home were risk factors associated with the malformation, whereas taking vitamins was a protective factor.

Conclusion

Maternal and paternal exposure to pesticides is associated with cleft lip and palate in Mato Grosso State, Brazil.
Perceived Adequacy of Infection Control Practices and Symptoms of Anxiety Among In-Person Elementary School Educators in Ontario
Authors: Smith Peter M. , Oudyk John , Cedillo Leonor , Inouye Kimiko , Potter Guy , Mustard Cameron
Published: September 2022

Objective

The aim of this study was to examine the association between the perceived adequacy of infection control practices (ICPs) and symptoms of anxiety among educators in Ontario, Canada.

Methods

Data from 4947 educators were collected in December 2020. Modified Poisson models assessed the association between adequacy of ICPs and moderate or severe anxiety symptoms, adjusting for a range of covariates.

Results

Approximately 60% of respondents reported moderate or severe anxiety symptoms. Two-thirds (66.5%) of the sample had less than half of their ICP needs met. Respondents with less than half their ICP needs met were more than three times more likely to have moderate or severe anxiety, compared with respondents with their ICP needs met.

Conclusion

Findings highlight the importance of adequate administrative and engineering controls in schools, not only to minimize risk of infection, but also for educator's mental health.
Workplace Infection Control Measures and Perceived Organizational Support During the COVID-19 Pandemic in Japan
Authors: Mori Takahiro , Nagata Tomohisa , Ando Hajime , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsugaki Ryutaro , Fujino Yoshihisa , Mori Koji ,   and for the CORoNaWork project
Published: September 2022

Objective

We investigated whether workplace infection control measures during the COVID-19 pandemic could increase perceived organizational support (POS).

Methods

This prospective cohort study was conducted in Japan from December 2020 to December 2021 using a questionnaire survey. There were 18,560 respondents at follow-up; we investigated 4971 who rated low POS at baseline. The participants were asked a single question about POS and nine about workplace infection control measures. We determined the odds ratios (ORs) of high POS at follow-up using multilevel logistic regression analysis.

Results

The groups of 5 to 6 (OR = 1.29, 95% confidence interval = 1.05–1.57,P= 0.014) and 7 to 9 workplace infection control measures (OR = 1.54, 95% confidence interval, 1.28–1.85,P< 0.001) had significantly higher ORs than the group with 0 to 2 measures.

Conclusions

Health support for employees through workplace infection control measures can increase POS.
Novel Use of Botulinum Toxin in Long-Standing Adductor-Related Groin Pain: A Case Series
Authors: Creuzé Alexandre , Fok-Cheong Thomas , Weir Adam , Bordes Philippe , Reboul Gilles , Glize Bertrand , de Seze Mathieu
Published: September 2022

Background:

Adductor-related groin pain (ARGP) is the most common groin injury in athletes. If conservative treatment fails, then adductor tenotomy to relieve tension can be considered. The use of botulinum toxin A (BoNT-A) has shown good results in other musculoskeletal pathologies.

Objective:

Assess the effectiveness of BoNT-A injections in ARGP in cases where usual treatment has failed.

Design:

Retrospective cohort study.

Setting:

Orthopedic Medicine and Rehabilitation Unit, University of Bordeaux.

Participants:

Fifty patients treated by BoNT-A injection in ARGP after failure of medical and/or surgical treatment were included in this study.

Interventions:

One or several adductor muscles were injected with BoNT-A, according to clinical evaluation using ultrasound and electrical stimulation guidance. Patients were followed up at 1, 3, 6, and 12 months.

Main Outcome Measures:

The primary assessment criterion was the improvement of Hip and Groin Outcome Score subscales at day 30. Secondary outcomes included pain intensity and impact on sport, work, and quality of life (QoL), the Blazina scale, and side effects.

Results:

All the first 50 injected patients (45 male and 5 female patients) were included. A significant improvement was noted regarding the majority of Hip and Groin Outcome Score subscales at day 30 (P < 0.05). Pain intensity and its impacts were both significantly reduced (P < 0.001): less sport and professional disability and lower impact on QoL. Severity of symptoms assessed by the Blazina scale was significantly reduced (P < 0.001). The improvements remained significant until 1-year postinjection.

Conclusions:

BoNT-A is promising as a new treatment for ARGP but should be fully assessed in a randomized controlled trial.
Morphologic and Molecular Heterogeneity of Cervical Neuroendocrine Neoplasia
Authors: Ordulu Zehra , Mino-Kenudson Mari , Young Robert H. , Van de Vijver Koen , Zannoni Gian Franco , Félix Ana , Burandt Eike , Wong Adele , Nardi Valentina , Oliva Esther
Published: September 2022

Neuroendocrine neoplasms (NENs) of the cervix are rare aggressive tumors associated with poor prognosis and only limited treatment options. Although there is some literature on molecular underpinnings of cervical small cell neuroendocrine carcinomas (SCNECs), detailed morphologic and associated molecular characteristics of cervical NENs remains to be elucidated. Herein, 14 NENs (SCNEC: 6, large cell neuroendocrine carcinoma [LCNEC]: 6, neuroendocrine tumor [NET]: 2), including 5 admixed with human papillomavirus (HPV)-associated adenocarcinoma (carcinoma admixed with neuroendocrine carcinoma) were analyzed. All except 3 SCNECs were HPV16/18 positive. TP53 (3) and/or RB1 (4) alterations (3 concurrent) were only seen in SCNECs (4/6) and were enriched in the HPV16/18-negative tumors. The other most common molecular changes in neuroendocrine carcinomas (NECs) overlapping with those reported in the literature for cervical carcinomas involved PI3K/MAPK pathway (4) and MYC (4) and were seen in both SCNECs and LCNECs. In contrast, the 2 NETs lacked any significant alterations. Two LCNECs admixed with adenocarcinoma had enough material to sequence separately each component. In both pathogenic alterations were shared between the 2 components, including ERBB2 amplification in one and an MSH6 mutation with MYC amplification in the other. Overall, these findings suggest that cervical HPV-associated NETs are genomically silent and high-grade NECs (regardless of small or large cell morphology) share molecular pathways with common cervical carcinomas as it has been reported in the endometrium and are different from NECs at other sites. Molecular analysis of these highly malignant neoplasms might inform the clinical management for potential therapeutic targets.
Characterizing Asbestos Hazard Emergency Response Act (AHERA) Compliance in New Jersey: 2008-2017
Authors: Lefkowitz Daniel , Fontus Helga , Vermeychuk James , Centifonti Gary , McGreevy Katharine
Published: September 2022

Context:

The Asbestos Hazard Emergency Response Act (AHERA) became a law in 1986, and the US Environmental Protection Agency (USEPA) was mandated to promulgate rules to regulate the inspection, management, and abatement of asbestos-containing building materials (ACBM) in schools. This study describes 10 years (2008-2017) of AHERA compliance site inspection data conducted by the New Jersey Department of Health (NJDOH).

Objectives:

To establish the level to which inspected NJ schools comply with AHERA regulations, to characterize compliance deficiencies including those that may lead to increased asbestos exposure risk to students and school employees, and to determine whether age, type, and geographic location of school impacted the likelihood of noncompliance.

Design:

Information collected during 456 unique inspections between 2008 and 2017 was analyzed.

Setting and Participants:

Inspections were conducted at public and private schools in New Jersey. These included elementary, middle, and high schools, as well as charter and vocational/technical schools.

Main Outcome Measures:

Descriptive statistics and multiple logistic regression modeling of 3 factors, school type, geographical region, and school age.

Results:

NJDOH inspectors found damage to friable ACBM in 50% (n = 229) of the schools and fiber release episodes in 27% of inspections (n = 121). The case of schools failing to attach warning labels on or immediately adjacent to ACBM was the most frequently noted compliance deficiency over the 10-year period. The modeling output showed that compliance was associated with the type of school and geographical region.

Conclusions:

Inspected schools during the 10-year period were in serious noncompliance with AHERA regulations. This included deficiencies that demonstrate a potential exposure to asbestos such as missing ACBM in management plans, damaged ACBM, lack of protection of short-term workers and custodial staff, and the identification of fiber release episodes. Modeling results of specific school characteristics can help direct limited resources to mitigate potential asbestos exposures.
Synthetic CT in Musculoskeletal Disorders
Authors: Lombardi Alecio F. , Ma Ya-Jun , Jang Hyungseok , Jerban Saeed , Du Jiang , Chang Eric Y. , Chung Christine B.
Published: September 2022

Repeated computed tomography (CT) examinations increase patients' ionizing radiation exposure and health costs, making an alternative method desirable. Cortical and trabecular bone, however, have short T2 relaxation times, causing low signal intensity on conventional magnetic resonance (MR) sequences. Different techniques are available to create a “CT-like” contrast of bone, such as ultrashort echo time, zero echo time, gradient-echo, and susceptibility-weighted image MR sequences, and artificial intelligence. This systematic review summarizes the essential technical background and developments of ultrashort echo time, zero echo time, gradient-echo, susceptibility-weighted image MR imaging sequences and artificial intelligence; presents studies on research and clinical applications of “CT-like” MR imaging; and describes their main advantages and limitations. We also discuss future opportunities in research, which patients would benefit the most, the most appropriate situations for using the technique, and the potential to replace CT in the clinical workflow.
Masculinizer-induced dosage compensation is achieved by transcriptional downregulation of both copies of Z-linked genes in the silkworm,
Bombyx mori
Authors: Tomihara Kenta , Kawamoto Munetaka , Suzuki Yutaka , Katsuma Susumu , Kiuchi Takashi
Published: September 2022

The evolution of dosage compensation produces similar expression of sex-linked and autosomal genes in the heterogametic sex. The silkworm (
Bombyx mori
), a lepidopteran insect, has a female heterogametic WZ sex determination system. A Z-linked gene,
Masculinizer
(
Masc
), is the primary determinant of maleness and dosage compensation in
B. mori
. However, it remains unknown whether one of the two Z chromosomes is inactivated or both Z chromosomes are suppressed in
B. mori
males. Hence, we performed transcriptome analysis using hybrids between two
B. mori
strains and analysed allele-specific expression to distinguish these alternatives. Our analysis revealed that genes on both the maternal and paternal Z chromosomes are transcriptionally upregulated in
Masc
knocked down males. We therefore conclude that both Z chromosomes are transcriptionally downregulated in
B. mori
males, similar to the system in
Caenorhabditis elegans
.
Andrew James Thomson. 31 July 1940—2 March 2021
Authors: Armstrong Fraser A. , Grinter Roger , Johnson Michael K. , Le Brun Nick E. , Wilson Michael T.
Published: September 2022

Andrew Thomson developed and exploited optical and magnetic resonance spectroscopy to address unresolved questions in biological inorganic chemistry, in a career that spanned more than 50 years. Despite his important role in the discovery of cisplatin as a young scientist, he went on to pursue a different direction. Leading original and creative investigations into the nature of metal-containing sites in proteins, he exploited the way that these centres, responsible for the activities of their host proteins, absorbed light and interacted with magnetic fields in very characteristic ways. He was devoted to ensuring the success of science at the newly-founded University of East Anglia (UEA), where he began his pioneering work on magnetic circular dichroism spectroscopy in 1967. Throughout the following decades he painstakingly supervised many young scientists and collaborated enthusiastically with established figures across the world—unravelling numerous complex properties underpinning the catalytic and sensory activity of transition metals in biology, including their reactions with oxygen, iron, sulfur and the oxides of nitrogen. Realizing the importance of broadening the appeal of chemistry in society, he established pharmacy at UEA, went on to become the first dean of the Science Faculty and helped to plan the Norwich Research Park. His selfless effort in these endeavours was recognized by the award of an OBE for services to higher education in 2008.
The valence-dominance model applies to body perception
Authors: Tzschaschel Eva , Brooks Kevin R. , Stephen Ian D.
Published: September 2022

First impressions of a person, including social judgements, are often based on appearance. The widely accepted valence-dominance model of face perception (Oosterhof and Todorov 2008
Proc. Natl Acad. Sci. USA
105
, 11 087–11 092 (
doi:10.1073/pnas.0805664105
)) posits that social judgements of faces fall along two orthogonal dimensions: trustworthiness (valence) and dominance. The current study aimed to establish the principal components of social judgements based on the perception of bodies, hypothesizing that these would follow the same dimensions as face perception. Stimuli were black and white photographs showing bodies dressed in grey clothing, standing in their natural posture, in left profile. Raters (
N
= 237) judged the stimuli on the 14 traits used in Oosterhof and Todorov's original study (Oosterhof and Todorov 2008
Proc. Natl Acad. Sci. USA
105
, 11 087–11 092 (
doi:10.1073/pnas.0805664105
)). Data were analysed using principal component analysis (PCA), as in the original study, with an additional exploratory factor analysis (EFA) using oblique rotation. While PCA produced a third dimension in line with several replications of the original study, results from the EFA produced two dimensions, representing trustworthiness and dominance, providing support for the hypothesis that social perceptions of bodies can be summarized using the valence-dominance model. These two factors could represent universal perceptions we have about people. Future research could explore social judgements of humans based on other stimuli, such as voices or body odour, to evaluate whether the trustworthiness and dominance dimensions are consistent across modalities.
Echiuran Hox genes provide new insights into the correspondence between Hox subcluster organization and collinearity pattern
Authors: Wei Maokai , Qin Zhenkui , Kong Dexu , Liu Danwen , Zheng Qiaojun , Bai Shumiao , Zhang Zhifeng , Ma Yubin
Published: September 2022

In many bilaterians, Hox genes are generally clustered along the chromosomes and expressed in spatial and temporal order. In vertebrates, the expression of Hox genes follows a whole-cluster spatio-temporal collinearity (WSTC) pattern, whereas in some invertebrates the expression of Hox genes exhibits a subcluster-level spatio-temporal collinearity pattern. In bilaterians, the diversity of collinearity patterns and the cause of collinearity differences in Hox gene expression remain poorly understood. Here, we investigate genomic organization and expression pattern of Hox genes in the echiuran worm
Urechis unicinctus
(Annelida, Echiura).
Urechis unicinctus
has a split cluster with four subclusters divided by non-Hox genes: first subcluster (
Hox1
and
Hox2
), second subcluster (
Hox3
), third subcluster (
Hox4
,
Hox5
,
Lox5
,
Antp
and
Lox4
), fourth subcluster (
Lox2
and
Post2
). The expression of
U. unicinctus
Hox genes shows a subcluster-based whole-cluster spatio-temporal collinearity (S-WSTC) pattern: the anterior-most genes in each subcluster are activated in a spatially and temporally colinear manner (reminiscent of WSTC), with the subsequent genes in each subcluster then being very similar to their respective anterior-most subcluster gene. Combining genomic organization and expression profiles of Hox genes in different invertebrate lineages, we propose that the spatio-temporal collinearity of invertebrate Hox is subcluster-based.
Evolutionary allometry and ecological correlates of fang length evolution in vipers
Authors: Holding Matthew L. , Trevine Vivian C. , Zinenko Oleksandr , Strickland Jason L. , Rautsaw Rhett M. , Mason Andrew J. , Hogan Michael P. , Parkinson Christopher L. , Grazziotin Felipe G. , Santana Sharlene E. , Davis Mark A. , Rokyta Darin R.
Published: September 2022

Traits for prey acquisition form the phenotypic interface of predator–prey interactions. In venomous predators, morphological variation in venom delivery apparatus like fangs and stingers may be optimized for dispatching prey. Here, we determine how a single dimension of venom injection systems evolves in response to variation in the size, climatic conditions and dietary ecology of viperid snakes. We measured fang length in more than 1900 museum specimens representing 199 viper species (55% of recognized species). We find both phylogenetic signal and within-clade variation in relative fang length across vipers suggesting both general taxonomic trends and potential adaptive divergence in fang length. We recover positive evolutionary allometry and little static allometry in fang length. Proportionally longer fangs have evolved in larger species, which may facilitate venom injection in more voluminous prey. Finally, we leverage climatic and diet data to assess the global correlates of fang length. We find that models of fang length evolution are improved through the inclusion of both temperature and diet, particularly the extent to which diets are mammal-heavy diets. These findings demonstrate how adaptive variation can emerge among components of complex prey capture systems.
Whole Genome Sequencing Based Characterization of Streptomyces sp. 6(4): focus on natural products
Authors: Borba Marcela Proença , Witusk João Paulo , Cunha Débora Marchesan , de Lima-Morales Daiana , Martins Andreza Francisco , Van Der Sand Sueli
Published: September 2022

We have sequenced the whole genome of Streptomyces sp. 6(4) isolated from tomato roots that presents antifungal activity against phytopathogenic fungi, mainly against Bipolaris sorokiniana . The genome has almost 7 Mb and 3,368 hypothetical proteins that were analyzed and characterized in Uniprot with emphasize in biological compounds. MLST analysis were performed in effort to characterize and identify this isolate, resulting in a new ST, classified as ST64. Phenetic and phylogenetic trees were constructed to investigate Streptomyces sp. 6(4) evolution and sequence similarity, and the isolate is a strain closer to Streptomyces prasinus and Streptomyces viridosporus . It is known that Streptomyces genera comprises a huge metabolism capacity with the presence of cryptic genes. These genes are usually present in clusters who are responsible for production of a high diversity of natural products, mainly antibiotics. In addition, 6(4) showed 11 biosynthetic gene cluster through antiSMASH, including 3 clusters PKS and NRPS type.
Diagnosis and successful treatment of unusual presentation of Urogenital tuberculosis.
Authors: Bala Kiran , Xess Ashit , Das Rojaleen , Singla Neeta , Seth Amlesh , Singh Urvashi B
Published: September 2022

Extra-pulmonary tuberculosis (EPTB) is known to cause for 8%-24% of all tuberculosis (TB) cases in the world.[1] The commonest extra-pulmonary sites to be affected in EPTB are lymph nodes and pleura, other sites being urogenital system, central nervous system, eye, cutaneous tissue and skeletal system. GUTB is insidious in onset and manifests most commonly as infertility sometimes present with chronic pelvic pain, dysmenorrhoea, bladder dysfunction and renal failure. We are discussing two case reports of GUTB, first one was an isolated case of tuberculous epididymo-orchitis in a 20 year old male and second a 29 year old male with TB involving the kidney along with genital organs. The cases were unique because of the atypical presentation and delayed effective treatment (in one case), despite the best diagnostic approach used.
Zwartia hollandica gen. nov., sp. nov., Jezberella montanilacus gen. nov., sp. nov. and Sheuella amnicola gen. nov., comb. nov., representing the environmental GKS98 (betIII) cluster
Authors: Hahn Martin W. , Pitt Alexandra , Schmidt Johanna , Koll Ulrike , Wolf Jacqueline , Whitman William B. , Bodelier Paul L. E. , Neumann-Schaal Meina
Published: September 2022

We present two strains affiliated with the GKS98 cluster. This phylogenetically defined cluster is representing abundant, mainly uncultured freshwater bacteria, which were observed by many cultivation-independent studies on the diversity of bacteria in various freshwater lakes and streams. Bacteria affiliated with the GKS98 cluster were detected by cultivation-independent methods in freshwater systems located in Europe, Asia, Africa and the Americas. The two strains, LF4-65T (=CCUG 56422T=DSM 107630T) and MWH-P2sevCIIIbT (=CCUG 56420T=DSM 107629T), are aerobic chemoorganotrophs, both with genome sizes of 3.2 Mbp and G+C values of 52.4 and 51.0 mol%, respectively. Phylogenomic analyses based on concatenated amino acid sequences of 120 proteins suggest an affiliation of the two strains with the family

Alcaligenaceae

and revealed

Orrella amnicola

and

Orrella marina

(=

Algicoccus marinus

) as being the closest related, previously described species. However, the calculated phylogenomic trees clearly suggest that the current genus

Orrella

represents a polyphyletic taxon. Based on the branching order in the phylogenomic trees, as well as the revealed phylogenetic distances and chemotaxonomic traits, we propose to establish the new genus Zwartia gen. nov. and the new species Z. hollandica sp. nov. to harbour strain LF4-65T and the new genus Jezberella gen. nov. and the new species J. montanilacus sp. nov. to harbour strain MWH-P2sevCIIIbT. Furthermore, we propose the reclassification of the species

Orrella amnicola

in the new genus Sheuella gen. nov. The new genera Zwartia, Jezberella and Sheuella together represent taxonomically the GKS98 cluster.
Scaling rules for pandemics: Estimating infected fraction from identified cases for the SARS-Cov-2 Pandemic
Authors: Ma Mingyang , Zsolway Mary , Tarafder Ayush , Doniach Sebastian , Bhanot Gyan
Published: September 2022

Using a modified form of the SIR model, we show that, under general conditions, all pandemics exhibit certain scaling rules. Using only daily data for symptomatic, confirmed cases, these scaling rules can be used to estimate: (i) reff, the effective pandemic R-parameter; (ii) ftot, the fraction ofexposedindividuals that were infected (symptomatic and asymptomatic); (iii) Leff,the effective latency, the average number of days an infected individual is able to infect others in the pool of susceptible individuals; and (iv) α, the probability of infection per contact between infected and susceptible individuals. We validate the scaling rules using an example and then apply our method to estimate reff, ftot, Leffand α for the first phase of the SARS-Cov-2, Covid-19 pandemic for several countries where there was a well separated first peak in identified infected daily cases after the outbreak of the pandemic in early 2020. Our results are general and can be applied to any pandemic.
Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity
Authors: Amano Tomokazu , Yu Hong , Amano Misa , Leyder Erica , Badiola Maria , Ray Priyanka , Kim Jiyoung , Ko Akihiro C. , Achour Achouak , Weng Nan-ping , Kochba Efrat , Levin Yotam , Ko Minoru S.H.
Published: September 2022

Intradermal delivery of self-replicating RNA (srRNA) is a promising vaccine platform. Considering that human skin temperature is around 33°C, lower than core body temperature of 37°C, we have developed an srRNA that functions optimally at skin temperature and is inactivated at or above 37°C as a safety switch. This temperature-controllable srRNA (c-srRNA), when tested as an intradermal vaccine against SARS-CoV-2, functions when injected naked without lipid nanoparticles. Unlike most currently available vaccines, c-srRNA vaccines predominantly elicit cellular immunity with little or no antibody production. Interestingly, c-srRNA-vaccinated mice produced antigen-specific antibodies upon subsequent stimulation with antigen protein. Antigen-specific antibodies were also produced when B-cell stimulation using antigen protein was followed by c-srRNA booster vaccination. Using c-srRNA, we have designed a pan-coronavirus booster vaccine that incorporates both spike receptor binding domains as viral surface proteins and evolutionarily conserved nucleoproteins as viral non-surface proteins, from both SARS-CoV-2 and MERS-CoV. It can thereby potentially immunize against SARS-CoV-2, SARS-CoV, MERS-CoV, and their variants. c-srRNA may provide a route to activate cellular immunity against a wide variety of pathogens.
Leveraging the p53 signaling pathway as a radio-sensitization strategy in endometrial cancer
Authors: Vargas Roberto , Petty Aaron , Yard Brian , Durmaz Arda , Lin-Rahardja Kristi , Reizes Ofer , Debernardo Robert , Scott Jacob
Published: September 2022

Endometrial cancer (EC) is the most common type of gynecologic malignancy in the United States, with over 66, 200 new cases expected in 2023. The number of mortalities per year now approximate that of ovarian cancer. Despite our ability to identify different biologic clusters of EC, we have yet to understand the functional impact of key genomic alterations associated with discrepant prognoses and exploit this knowledge for therapeutic benefit. Given this, we set out to determine how alterations in p53 signaling, as conferred myTP53mutations, impact radiotherapy response in EC. We also explored if manipulation of this signaling pathway could be utilized as a radio-sensitization strategy in EC. Our work demonstrates that p53 signaling plays a significant role in radiotherapy response for EC and that leveraging this genomic data may allow us to exploit this pathway as a viable radiotherapeutic target in a significant number of EC cases.
Genomic analysis reveals HDAC1 regulates clinically relevant transcriptional programs in pancreatic cancer
Authors: Wright Carter A. , Gordon Emily R. , Cooper Sara J.
Published: September 2022

Novel strategies are needed to combat multidrug resistance in pancreatic ductal adenocarcinoma (PDAC). We applied genomic approaches to understand mechanisms of resistance in order to better inform treatment and precision medicine. Altered function of chromatin remodeling complexes contribute to chemoresistance. Our study generates and analyzes genomic and biochemical data from PDAC cells overexpressingHDAC1, a histone deacetylase involved in several chromatin remodeling complexes. We characterized the impact of overexpression on drug response, gene expression, HDAC1 binding, and chromatin structure using RNA-sequencing and ChIP-sequencing for HDAC1 and H3K27 acetylation. Integrative genomic analysis shows thatHDAC1overexpression promotes activation of key resistance pathways including epithelial to mesenchymal transition, cell cycle, and apoptosis through global chromatin remodeling. Target genes are similarly altered in patient tissues and show correlation with patient survival. We also demonstrate that direct targets of HDAC1 that also show altered chromatin are enriched near genes associated with altered GTPase activity. HDAC1 target genes identified usingin vitromethods and observed in patient tissues were used to develop a clinically relevant nine-transcript signature associated with patient prognosis. Integration of multiple genomic and biochemical data types enables understanding of multidrug resistance and tumorigenesis in PDAC, a disease in desperate need of novel treatment strategies.
A report card methodology to showcase progress towards threatened species recovery
Authors: Ward Michelle , Rout Tracy , Stewart Romola , Possingham Hugh P. , McDonald-Madden Eve , Clark Thomas G. , Kindler Gareth S. , Valentine Leonie , Macmillan Ellen , Watson James E.M.
Published: September 2022

Among the conservation community, it is well known that Earth’s mass species extinction crisis is getting worse. Yet, an often neglected problem is the need for effectively communicating the species extinction crisis to diverse audiences in ways that catalyse immediate action. Here we generated a streamlined threatened species recovery report card methodology, which combined two input indicators including planning and funding, one output indicator capturing habitat protection, and one outcome indicator which highlights threatened species trajectories, to provide simple scores for all Australian threatened species. We show that just 41 (2.3%) of species achieved an A grade for the input indicator (i.e., recovery plans and federal funding), 240 (13.3%) achieved a C grade, and 1,521 (84.4%) achieved an F. Five hundred and twenty nine (29.3%) species achieved an A for the output indicator (i.e, habitat protection), 130 (7.2%) achieved a B, 158 (8.8%) achieved a C, 189 (10.5%) achieved a D, 212 (11.8%) achieved an E, and 584 (32.4%) achieved a F. While five (0.3%) species achieved an A for the output indicator (i.e., threat status improvement), every other species (99.7%) achieved an F. We provide a method to combine scores to test how individual jurisdictions are tracking and show that Australia is achieving an F for the input and outcome indicators, and a D for the output indicator. While the threatened species recovery report card highlighted a clear failure in many federal environmental legislation responsibilities, it provides a baseline from which different governments can track policy progress and outlines clear direction for immediate improvement including developing adequate recovery plans, funding the actions in the recovery plans, protecting habitat from further destruction, verifying recovery through monitoring and evaluation of species trajectories, and supporting transparency and collaboration on the execution on the plans through an improved data infrastructure. Without an immediate step change in how Australia communicates and faces its species crisis, we will leave a tragic legacy of extinction and fail our obligations to future generations of Australians, and the international community.
High-risk microbial signatures are associated with severe parasitemia in controlledPlasmodiuminfections of both humans and rhesus macaques
Authors: Gustin Andrew T. , Broedlow Courtney A. , Hager Kevin , Coronado Ernesto , Wangari Solomon , Iwayama Naoto , Ahrens Chul Y. , Garrison William D. , Guerriero Kathryn A. , De Paris Kristina , Gale Michael , Klatt Nichole R. , Kublin James G. , Manuzak Jennifer A.
Published: September 2022

While functions of the gastrointestinal (GI) microbiome include maintenance of immune homeostasis and protection against infectious disease, its role in determining disease severity duringPlasmodiuminfection has been limited to mouse models and observational human cohorts. Here, we performed controlledPlasmodiuminfection in both humans and rhesus macaques (RMs) to experimentally determine the impact of GI microbiome composition on disease progression. Through analysis of serially collected microbiome samples, we identified a high-risk microbial signature that strongly associated with increased risk of developing severe parasitemia in human participants. Importantly, we identified a parallel phenomenon in RMs. The combined weight of this evidence demonstrates that pre-infection GI microbiome composition is highly indicative ofP. falciparumdisease risk. Moreover, our observation thatP. fragile-microbiome dynamics in RMs closely mirrorsP. falciparum-microbiome interactions in humans strongly supports the use of this model in pre-clinical investigations of novel microbiome-targeting approaches to reduce malaria burden.
Quantitative physiology and proteome adaptations of Bifidobacterium breve NRBB57 at near-zero growth rates
Authors: Camargo Angela Rocio Ortiz , van Mastrigt Oscar , Bongers Roger S. , Ben- Amor Kaouther , Knol Jan , Abee Tjakko , Smid Eddy J.
Published: September 2022

In natural environments, nutrients are usually scarce causing microorganisms to grow slow while staying metabolically active. These natural conditions can be simulated using retentostat cultivations. The present study describes the physiological and proteome adaptations of the probiotic Bifidobacterium breve NRBB57 from high (0.4 h−1) to near-zero growth rates. Lactose-limited retentostat cultivations were carried out for 21 days in which the bacterial growth rate progressively reduced to 0.00092 h−1, leading to a 3.4-fold reduction of the maintenance energy requirement. Lactose was mainly converted into acetate, formate and ethanol at high growth rates while in the retentostat lactate production increased. Interestingly, the consumption of several amino acids (serine, aspartic acid and glutamine/arginine) and glycerol increased over time in the retentostat. Morphological changes and viable but non-culturable cells were also observed in the retentostat. Proteomes were compared for all growth rates, revealing a down-regulation of ribosomal proteins at near-zero growth rates and an up-regulation of proteins involved in the catabolism of alternative energy sources. Finally, we observed induction of the stringent response and stress defence systems. Retentostat cultivations were proven useful to study the physiology of B. breve, mimicking the nutrient scarcity of its complex habitat, the human gut.

IMPORTANCE

In natural environments, nutrients are usually scarce causing microorganisms to grow slow while staying metabolically active. In this study we used retentostat cultivation to investigate how the probiotic Bifidobacterium breve adapts its physiology and proteome under severe nutrient limitation resulting in near-zero growth rates (<0.001 h−1). We showed that the nutrient limitation induced a multifaceted response including stress defence and stringent response, metabolic shifts and the activation of novel alternative energy producing pathways.