bluuebunny/crossref_metadata_2025 huggingface dataset:
Turkey
Authors: Özgül Ceren
Published: December 2021

This chapter argues that the supposed binary of a secular state and popular Islam is inadequate as a tool of analysis if we are to understand how religion has become a prominent category of both privilege and exclusion in Turkish society. Specifically, it contends that successive Turkish governments have privileged Sunni Islam as national identity. To build this argument, the chapter follows two parallel threads. The first analyses the ethnic and religious homogenization of the national body with a particular emphasis on violence against non-Muslim and non-Sunni groups. The second shows how, within the larger historical context of modernization theory, Cold War politics, and the post-9/11 promotion of moderate Islam, successive Turkish governments worked towards maintaining Sunni Muslim privilege while continuously expanding the category of enemies of the Turkish nation.
Religion and Europe
Authors: Davie Grace , Leustean Lucian N.
Published: December 2021

This chapter introduces The Oxford Handbook of Religion and Europe: its rationale, timeline, geographical scope, approach, structure, and contents. The timeline—from Antiquity to the present day—is captured in a series of ‘portraits’ taken from European museums. The scope, methods, theories, and approaches are then outlined. No single theory or theoretical approach drives the volume as a whole, but particular attention is paid to the work of Max Weber, Jürgen Habermas, and David Martin. The structure (five parts) and contents (forty-five chapters and a statistical appendix) of the Handbook are carefully set out. A number of cross-cutting themes are then identified, including the role of religion in the circulation of knowledge and the tensions between Europe and its constituent states. The future is difficult to predict as Europe becomes not only more secular, but more religiously diverse.
Oxylipin signaling in salt-stressed soybean is modulated by ligand-dependent interaction of Class II acyl-CoA-binding proteins with lipoxygenase
Authors: Lung Shiu-Cheung , Lai Sze Han , Wang Haiyang , Zhang Xiuying , Liu Ailin , Guo Ze-Hua , Lam Hon-Ming , Chye Mee-Len
Published: December 2021

Plant lipoxygenases (LOXs) oxygenate linoleic and linolenic acids, creating hydroperoxy derivatives, and from these, jasmonates and other oxylipins are derived. Despite the importance of oxylipin signaling, its activation mechanism remains largely unknown. Here, we show that soybean ACYL-COA-BINDING PROTEIN3 (ACBP3) and ACBP4, two Class II acyl-CoA-binding proteins, suppressed activity of the vegetative LOX homolog VLXB by sequestering it at the endoplasmic reticulum. The ACBP4–VLXB interaction was facilitated by linoleoyl-CoA and linolenoyl-CoA, which competed with phosphatidic acid (PA) for ACBP4 binding. In salt-stressed roots, alternative splicing produced ACBP variants incapable of VLXB interaction. Overexpression of the variants enhanced LOX activity and salt tolerance in Arabidopsis and soybean hairy roots, whereas overexpressors of the native forms exhibited reciprocal phenotypes. Consistently, the differential alternative splicing pattern in two soybean genotypes coincided with their difference in salt-induced lipid peroxidation. Salt-treated soybean roots were enriched in C32:0-PA species that showed high affinity to Class II ACBPs. We conclude that PA signaling and alternative splicing suppress ligand-dependent interaction of Class II ACBPs with VLXB, thereby triggering lipid peroxidation during salt stress. Hence, our findings unveil a dual mechanism that initiates the onset of oxylipin signaling in the salinity response.
Effect of protein and glucogenic precursor supplementation on forage digestibility, serum metabolites, energy utilization, and rumen parameters in sheep
Authors: King Tasha M , Beard Joslyn K , Norman Mitch M , Wilson Hannah C , MacDonald James M , Mulliniks J Travis
Published: December 2021

Supplementation of glucogenic precursors in roughage diets may increase production responses due to improved efficiencies of nutrient utilization. Therefore, the objective of this study was to determine the effect of source of supplemental glucogenic potential (GP) on forage digestibility, serum metabolites, energy utilization, and rumen parameters of growing wethers consuming a roughage diet (8.8% crude protein, 71.4% ash-free neutral detergent fiber). Crossbred wethers (49.1 ± 4.7 kg initial BW; n = 16) were utilized in a 4 × 4 replicated Latin Square design with four periods of 21 d. Supplements were designed to supplement increasing amount of GP: 1) no supplementation (CON; 0 g), 2) 40 g of calcium propionate (CAP; 30 g of GP), 3) 70 g of blood meal + 100 g of feather meal (BF; 40 g of GP), or 4) combination of CAP and BF (COMBO; 70 g of GP). Total fecal and urine collection was conducted from days 13–17 to calculate digestibility estimates and urinary losses. An acetate tolerance test was administered on day 17 to determine the effect of GP on acetate clearance. Blood samples were collected on day 19 and were analyzed for serum concentrations of glucose, urea N (SUN), non-esterified fatty acids, and amino acids. Rumen fluid was collected on day 21 to determine supplementation effects on ruminal volatile fatty acid (VFA) and ammonia concentrations. Wethers receiving BF and COMBO supplementation had greatest (P ≤ 0.01) DM and OM total tract digestibility. Supplementation did not affect (P ≥ 0.37) NDF digestibility or digestible energy. Urinary nitrogen excretion was greatest (P = 0.02) for BF and COMBO. Circulating serum essential amino acid concentration was increased (P < 0.01) in BF and COMBO compared to CAP and CON. In addition, BF and COMBO had increased (P < 0.01) SUN concentrations compared to CAP and CON. Acetate half-life was not affected (P = 0.39) by supplementation strategy. However, area under the curve (AUC) for acetate was decreased (P = 0.04) with supplementation of BF and COMBO compared to CON-fed wethers. Ruminal propionate concentration was increased (P ≤ 0.01) for wethers fed CAP and COMBO supplementation, which resulted in decreased (P ≤ 0.01) A:P ratio. Overall, these results indicate that the increased propionate supply by providing propionate salts did not result in a protein sparing impact or increased N retention.
Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness
Authors: Schneider-Nachum Gily , Flynn Julia , Mavor David , Schiffer Celia A , Bolon Daniel N A
Published: December 2021

Investigating the relationships between protein function and fitness provides keys for understanding biochemical mechanisms that underly evolution. Mutations with partial fitness defects can delineate the threshold of biochemical function required for viability. We utilized a previous deep mutational scan of HIV-1 protease (PR) to identify variants with 15–45 per cent defects in replication and analysed the biochemical function of eight variants (L10M, L10S, V32C, V32I, A71V, A71S, Q92I, Q92N). We purified each variant and assessed the efficiency of peptide cleavage for three cut sites (MA-CA, TF-PR, and PR-RT) as well as gel-based analyses of processing of purified Gag. The cutting activity of at least one site was perturbed relative to WT protease for all variants, consistent with cutting activity being a primary determinant of fitness effects. We examined the correlation of fitness defects with cutting activity of different sites. MA-CA showed the weakest correlation (R2 = 0.02) with fitness, suggesting relatively weak coupling with viral replication. In contrast, cutting of the TF-PR site showed the strongest correlation with fitness (R2 = 0.53). Cutting at the TF-PR site creates a new PR protein with a free N-terminus that is critical for activity. Our findings indicate that increasing the pool of active PR is rate limiting for viral replication, making this an ideal step to target with inhibitors.
Skin Cancer Risk Perception and Tanning Bed Use: A Population-Based Survey to Identify Persons at Risk for Melanoma in Olmsted County, Minnesota
Authors: Barbosa Naiara S. , Yost Kathleen J. , Petterson Tanya M. , Mara Kristin C. , Brewer Jerry D.
Published: December 2021

BACKGROUND

Cutaneous melanoma is strongly associated with tanning bed use.

OBJECTIVE

To describe local residents' knowledge, attitudes, and behavior regarding skin cancer and tanning bed use and to estimate prevalence of high risk for melanoma.

MATERIALS AND METHODS

A survey was mailed to 886 local residents (549, aged 18–39 years; 337, aged ≥40 years). Logistic and linear regression and univariate and multivariable analysis were used to assess perceived risk and skin cancer knowledge.

RESULTS

The response rate was 21%; 55% of the younger group and 37% of the older group had used indoor tanning, and prevalence of high risk for melanoma according to a skin cancer risk calculator was 18% in the younger group and 33% in the older group. Individuals with high risk scores were more likely to correctly perceive that they were at high risk for skin cancer. Most participants with high risk scores and those who previously used tanning beds reported low likelihood of future indoor tanning.

CONCLUSION

Female sex, high risk score, and previous indoor tanning were associated with participants' views of higher skin cancer risk. No specific knowledge gaps were identified. Understanding community residents' attitudes about skin cancer and indoor tanning can help guide interventions.
Birth weight and the risk of overall breast cancer, premenopausal and postmenopausal breast cancer in adulthood: a dose-response meta-analysis of observational studies
Authors: Wang Kang , Ge Mingxiu , Liu Lulu , Lv Haihong , Wang Shujuan , Jia Fei , Sun Jinjun
Published: December 2021

Importance:

The effect of birth weight on breast cancer across different menopausal states remains unknown.

Objective:

The aim of this study was to systematically evaluate the association of birth weight with the risk of overall breast cancer (OBC) and premenopausal and postmenopausal breast cancer during adulthood. In parallel, the dose-response analyses were performed.

Evidence Review:

Relevant studies were systematically searched from the PubMed, Embase, and the Cochrane Library databases from the inception to May 25, 2021, without language restrictions. All the results were pooled according to risk ratios (RRs).

Findings:

In total, 21 cohort studies comprising 1,139,032 participants were included. An increase in the birth weight was not associated with the risk of OBC and premenopausal and postmenopausal breast cancer. Compared with women having normal weight at birth, those with a high birth weight are likely to have an increased risk of invasive breast cancer (RR: 1.19, 95% confidence intervals: 1.03-1.38; I2: 28.6%). The dose-response analyses showed that the risk of premenopausal breast cancer increased significantly in unknown singleton status with birth weight over 2850 g (RR: 1.14 [1.02-1.30]). Similarly, postmenopausal breast cancer risk was increased in singleton births with birth weight over 3750 g (RR: 1.21 [1.00-1.47]).

Conclusions and Relevance:

High weight at birth might be not significantly associated with the risk of OBC, premenopausal and postmenopausal breast cancer and ER+ and ER− breast cancer but is positively associated with the risk of invasive breast cancer, regardless of parity. Furthermore, with an increase in birth weight, the risk of postmenopausal breast cancer is likely to increase in the singleton births, whereas the risk of premenopausal breast cancer is likely to increase in unknown singleton status.
Monckeberg's arteriosclerosis: a case report of chronic endometritis presenting as postmenopausal bleeding
Authors: Mercer Victoria J. , Naseemuddin Ather , Webb Amanda
Published: December 2021

Objective:

Chronic endometritis is rarely reported in the postmenopausal population. Here, we describe a case of chronic endometritis in a patient who had undergone premature menopause that was later found to have Monckeberg arteriosclerosis (MocA) of the uterine vessels.

Methods:

A review of the literature revealed a single report of MocA affecting the uterine vessels and no reports in a patient who had undergone premature menopause. A case of a 69-year-old presenting with postmenopausal bleeding and having the diagnosis of chronic endometritis is described.

Results:

Following definitive management with hysterectomy, final histopathology showed MocA of the uterine vessels.

Conclusions:

The lack of reviews of chronic endometritis in postmenopausal women reveals a gap in the literature. Further studies are necessary to review MocA and decreased uterine perfusion in the context of a possible predisposition to chronic endometrial infection and/or inflammation.
Prevention and Management of Donor-transmitted Cancer After Liver Transplantation: Guidelines From the ILTS-SETH Consensus Conference
Authors: Domínguez-Gil Beatriz , Moench Kerstin , Watson Christopher , Serrano M. Trinidad , Hibi Taizo , Asencio José M. , Van Rosmalen Marieke , Detry Olivier , Heimbach Julie , Durand François
Published: December 2021

As with any other intervention in health, liver transplantation (LT) entails a variety of risks, including donor-transmitted cancers (DTCs). At present, 2%–4% of used deceased organ donors are known to have a current or past history of malignancy. The frequency of DTCs is consistently reported at 3–6 cases per 10 000 solid organ transplants, with a similar frequency in the LT setting. A majority of DTCs are occult cancers unknown in the donor at the time of transplantation. Most DTCs are diagnosed within 2 y after LT and are associated with a 51% probability of survival at 2 y following diagnosis. The probability of death is greatest for DTCs that have already metastasized at the time of diagnosis. The International Liver Transplantation Society-Sociedad Española de Trasplante Hepático working group on DTC has provided guidance on how to minimize the occurrence of DTCs while avoiding the unnecessary loss of livers for transplantation both in deceased and living donor LT. The group endorses the Council of Europe classification of risk of transmission of cancer from donor to recipient (minimal, low to intermediate, high, and unacceptable), classifies a range of malignancies in the liver donor into these 4 categories, and recommends when to consider LT, mindful of the risk of DTCs, and the clinical condition of patients on the waiting list. We further provide recommendations to professionals who identify DTC events, stressing the need to immediately alert all stakeholders concerned, so a coordinated investigation and management can be initiated; decisions on retransplantation should be made on a case-by-case basis with a multidisciplinary approach.
Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age
Authors: Ahn JiYoon B. , Bae Sunjae , Schnitzler Mark , Hess Gregory P. , Lentine Krista L. , Segev Dorry L. , McAdams-DeMarco Mara A.
Published: December 2021

Background.

Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age.

Methods.

Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010–2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18–29, 30–54, and ≥55 y).

Results.

Of 12 488, 28.3% recipients received ESW. The incidence rate for PTD was 13 per 100 person-y and lower among recipients who received ESW (11 per 100 person-y in ESW; 14 per 100 person-y in CSM). Overall, ESW was associated with lower risk of PTD compared with CSM (adjusted hazard ratio [aHR] = 0.720.790.86), but the risk differed by recipient age (P
interaction = 0.09 for comparison between recipients aged 18–29 and those aged 30–54; P
interaction = 0.01 for comparison between recipients aged 18–29 and those aged ≥55). ESW was associated with lower risk of PTD among recipients aged ≥55 (aHR = 0.620.710.81) and those aged 30–54 (aHR = 0.730.830.95), but not among recipients aged 18–29 (aHR = 0.811.181.72). Although recipients who received ESW had a higher risk of acute rejection across the age groups (adjusted odds ratio = 1.011.171.34), recipients with no PTD had a lower risk of mortality (aHR = 0.580.660.74).

Conclusions.

The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.
Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients
Authors: Reza Nosheen , De Feria Alejandro , Wang Teresa , Chowns Jessica L. , Hoffman-Andrews Lily , Kim Jessica , Hornsby Nicole , Marzolf Amy , Atluri Pavan , Herrmann Howard C. , Owens Anjali Tiku
Published: December 2021

Background.

Hypertrophic cardiomyopathy (HCM) in pediatric solid organ transplant recipients has been reported in association with use of calcineurin inhibitors. However, data on the incidence and prevalence of HCM in adult posttransplant patients are limited. We sought to describe the clinical characteristics of solid organ transplant recipients who were diagnosed with HCM from 2011 to 2021 at a single center.

Methods.

Patients who had undergone solid organ transplant and exhibited left ventricular hypertrophy with left ventricular wall thickness ≥13 mm on transthoracic echocardiography were included. Clinical history, pedigree analysis, clinical genetic testing, transthoracic echocardiography, cardiac magnetic resonance imaging, treatment, and follow-up testing results were collected. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges and compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. A 2-sided P < 0.05 was considered statistically significant.

Results.

Three lung, 5 kidney, and 4 liver transplant recipients from 12 different families were included. Seven patients (58%) did not carry a preexisting diagnosis of hypertension, and none had a history of aortic or subaortic stenosis. A majority of patients exhibited asymmetric septal hypertrophy (67%; medial septal thickness versus left ventricular posterior wall thickness 17 versus 13 mm; P < 0.001) and dynamic left ventricular outflow tract (LVOT) obstruction (58%). All patients were managed long term with calcineurin inhibitors. Clinical genetic testing in 6 patients identified 2 with disease-causing variants in 2 sarcomere genes, myosin binding protein-C and myosin heavy chain 7. Four patients (33%) underwent successful septal reduction therapy for treatment of symptomatic LVOT obstruction.

Conclusions.

Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients, and genetic testing can identify individuals with sarcomeric HCM. Medical management and septal reduction therapies are treatment options for severe symptomatic disease.
Shewanella nanhaiensis sp. nov., a marine bacterium isolated from sediment of South China Sea, and emended descriptions of Shewanella woodyi, Shewanella hanedai and Shewanella canadensis
Authors: Cao Wen-Rui , Li Xue , Sun Yuan-Yuan , Jiang Ming-Yu , Xu Xiao-Dong , Li Ying-Jie
Published: December 2021

A Gram-stain-negative, motile, facultative anaerobic and rod-shaped bacterium, designated strain NR704-98T, was isolated from marine sediment of the northern South China Sea. Cells were positive for oxidase and catalase activity. Growth was observed at 4–30 °C (optimum 20–25 °C), at pH 6–9 (pH 7) and with 0.5–7 % NaCl (2 %). The 16S rRNA gene-based phylogenetic analysis revealed that the nearest phylogenetic neighbours of strain NR704-98T were

Shewanella woodyi

MS32T (97.9 %),

Shewanella hanedai

281T (97.1 %),

Shewanella sediminis

HAW-EB3T (96.8 %) and

Shewanella canadensis

HAW-EB2T (96.7 %). Based on the results of phylogenomic analysis, the average nucleotide identity and the digital DNA–DNA hybridization values between strain NR704-98T and the previously mentioned type strains of species of the genus

Shewanella

were in the range of 74.9–93.1 % and 20.6–51.4 %, respectively. The respiratory quinones were Q-7 and Q-8. The predominant fatty acids (>10 %) of strain NR704-98T were C16 : 0, summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c) and iso-C15 : 0. Phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminophospholipids and five unidentified lipids were detected in strain NR704-98T. Based on the phylogenetic and phenotypic characteristics, strain NR704-98T is considered to represent a novel species of the genus

Shewanella

, for which the name Shewanella nanhaiensis sp. nov. is proposed. The type strain is NR704-98T (=KCTC 82799T=MCCC 1K06091T).
Secondary metabolite biosynthetic diversity in Arctic Ocean metagenomes
Authors: Rego Adriana , Fernandez-Guerra Antonio , Duarte Pedro , Assmy Philipp , Leão Pedro N. , Magalhães Catarina
Published: December 2021

Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are mega enzymes responsible for the biosynthesis of a large fraction of natural products (NPs). Molecular markers for biosynthetic genes, such as the ketosynthase (KS) domain of PKSs, have been used to assess the diversity and distribution of biosynthetic genes in complex microbial communities. More recently, metagenomic studies have complemented and enhanced this approach by allowing the recovery of complete biosynthetic gene clusters (BGCs) from environmental DNA. In this study, the distribution and diversity of biosynthetic genes and clusters from Arctic Ocean samples (NICE-2015 expedition), was assessed using PCR-based strategies coupled with high-throughput sequencing and metagenomic analysis. In total, 149 KS domain OTU sequences were recovered, 36 % of which could not be assigned to any known BGC. In addition, 74 bacterial metagenome-assembled genomes were recovered, from which 179 BGCs were extracted. A network analysis identified potential new NP families, including non-ribosomal peptides and polyketides. Complete or near-complete BGCs were recovered, which will enable future heterologous expression efforts to uncover the respective NPs. Our study represents the first report of biosynthetic diversity assessed for Arctic Ocean metagenomes and highlights the potential of Arctic Ocean planktonic microbiomes for the discovery of novel secondary metabolites. The strategy employed in this study will enable future bioprospection, by identifying promising samples for bacterial isolation efforts, while providing also full-length BGCs for heterologous expression.
Applications of geospatial analyses in health research among homeless people: A systematic scoping review of available evidence
Authors: Ahasan Rakibul , Alam Md Shaharier , Chakraborty Torit , Asger Ali S M , Alam Tunazzina Binte , Islam Tania , Hossain Md Mahbub
Published: December 2021

Background

The coronavirus pandemic visualized the inequality in the community living standards and how housing is a fundamental requirement to ensure a livable environment. However, even before the pandemic, unequal housing access resulted in more than 150 million homeless people worldwide, and more than 22 million new people were added to this inventory for climate-related issues. This homeless population has a counterproductive effect on the social, psychological integration efforts by the community and exposure to other severe health-related issues.

Methods

We systematically identified and reviewed 24 articles which met all three requirements we set forth-i. samples include homeless people, ii. focused on public health-related issues among the same group of people, and iii. used geospatial analysis tools and techniques in conducting the research.

Result

Our review findings indicated a major disparity in the geographic distribution of the case study locations-all the articles are from six (6) countries-USA (n = 16), Canada (n = 3), UK (n = 2), and one study each from Brazil, Ireland, and South Africa. Majority of the studies used spatial analysis tools to identify the hotspots, clustering and spatial patterns of patient location and distribution. ArcGIS is the most frequently used GIS application, however, studies also used other statistical applications with spatial analysis capabilities. These studies reported relationship between the location of homeless shelters and substance use, discarded needles, different infectious and non-infectious disease clusters.

Conclusion

Although, most studies were restricted in analyzing and visualizing the trends, patterns, and disease clusters, geospatial analyses techniques can be used to assess health problems such as disease distributions and associated factors across communities. Moreover, health and services and accessibility concerns could be well addressed by integrating spatial analysis into homelessness-related research. This may facilitate policymaking for health-issues among the homeless people and address health inequities in this vulnerable population.
Reduced Odds of SARS-CoV-2 Reinfection after Vaccination among New York City Adults, June–August 2021
Authors: Levin-Rector Alison , Firestein Lauren , McGibbon Emily , Sell Jessica , Lim Sungwoo , Lee Ellen H. , Weiss Don , Geevarughese Anita , Zucker Jane R. , Greene Sharon K.
Published: December 2021

Background

Belief in immunity from prior infection and concern that vaccines might not protect against new variants are contributors to vaccine hesitancy. We assessed effectiveness of full and partial COVID-19 vaccination against reinfection when Delta was the predominant variant in New York City.

Methods

We conducted a case-control study in which case-patients with reinfection during June 15– August 31, 2021 and control subjects with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Conditional logistic regression was used to calculate matched odds ratios (mOR) and 95% confidence intervals (CI).

Results

Of 349,598 adult residents who tested positive for SARS-CoV-2 infection in 2020, did not test positive again >90 days after initial positive test through June 15, 2021, and did not die before June 15, 2021, 1,067 were reinfected during June 15–August 31, 2021. Of 1,048 with complete matching criteria data, 499 (47.6%) were known to be symptomatic for COVID-19-like-illness, and 75 (7.2%) were hospitalized. Unvaccinated individuals, compared with fully vaccinated individuals, had elevated odds of reinfection (mOR, 2.23; 95% CI, 1.90, 2.61), of symptomatic reinfection (mOR, 2.17; 95% CI, 1.72, 2.74), and of reinfection with hospitalization (mOR, 2.59; 95% CI, 1.43, 4.69). Partially versus fully vaccinated individuals had 1.58 (95% CI: 1.22, 2.06) times the odds of reinfection. All three vaccines authorized or approved for use in the U.S. were similarly effective.

Conclusion

Among adults with previous SARS-CoV-2 infection, vaccination reduced odds of reinfections when the Delta variant predominated.
Neural networks for classification and image generation of aging in genetic syndromes
Authors: Duong Dat , Hu Ping , Tekendo-Ngongang Cedrik , Hanchard Suzanna Ledgister , Liu Simon , Solomon Benjamin D. , Waikel Rebekah L.
Published: December 2021

In medical genetics, one application of neural networks is the diagnosis of genetic diseases based on images of patient faces. While these applications have been validated in the literature with primarily pediatric subjects, it is not known whether these applications can accurately diagnose patients across a lifespan. We aimed to extend previous works to determine whether age plays a factor in facial diagnosis, as well as to explore other factors that may contribute to the overall diagnosis accuracy. To investigate this, we chose two relatively common conditions, Williams syndrome and 22q11.2 deletion syndrome. We built a neural network classifier trained on images of affected and unaffected individuals of different ages. Our classifier outperformed clinical geneticists at recognizing face images of these two conditions within each of the age groups (the performance varied between the age groups): (1) under 2 years old, (2) 2-9 years old, (3) 10-19 years old, (4) 20-34 years old, and (5) ≥35 years old. The overall accuracy improvement by our classifier over the clinical geneticists was 15.5% and 22.7% for Williams syndrome and 22q11.2 deletion syndrome, respectively. Additionally, comparison of saliency maps revealed that key facial features learned by the neural network differed slightly with respect to age. Finally, joint training real images with multiple different types of fake images created by a generative adversarial network showed up to 3.25% accuracy gain in classification accuracy.
Neutralizing Antibody Activity Against SARS-CoV-2 Variants in Gestational Age-Matched Mother-Infant Dyads
Authors: Matsui Yusuke , Li Lin , Prahl Mary , Cassidy Arianna G. , Ozarslan Nida , Golan Yarden , Gonzalez Veronica J. , Lin Christine Y. , Jigmeddagva Unurzul , Chidboy Megan A. , Montano Mauricio , Taha Taha Y. , Khalid Mir M. , Sreekumar Bharath , Hayashi Jennifer M. , Chen Pei-Yi , Kumar G. Renuka , Warrier Lakshmi , Wu Alan H.B. , Song Dongli , Jegatheesan Priya , Rai Daljeet S. , Govindaswami Balaji , Needens Jordan , Rincon Monica , Myatt Leslie , Asiodu Ifeyinwa V. , Flaherman Valerie J. , Afshar Yalda , Jacoby Vanessa L. , Murtha Amy P. , Robinson Joshua F. , Ott Melanie , Greene Warner C. , Gaw Stephanie L.
Published: December 2021

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there is limited data comparing vaccine versus infection-induced nAb to COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines were matched with 30 naturally infected women by gestational age of exposure. Neutralization activity against the five SARS-CoV-2 Spike sequences was measured by a SARS-CoV-2 pseudotyped Spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared to wild type or Alpha variant Spike, these nAbs were less effective against the Kappa, Delta, and Mu Spike variants. Vaccination during the third trimester induced higher nAb levels at delivery than infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared to infection during the first trimester. The transfer ratio (cord nAb level/maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicit effective nAbs with differing neutralization kinetics that is impacted by gestational time of exposure. Vaccine induced neutralizing activity was reduced against the Delta, Mu, and Kappa variants.

Graphic abstract
SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification
Authors: Zhang Zichen , Bae Ye Eun , Bradley Jonathan R. , Wu Lang , Wu Chong
Published: December 2021

Genes with moderate to low expression heritability may explain a large proportion of complex trait heritability, but these genes are insufficiently captured in transcriptome-wide association studies (TWAS) partly due to the relatively small available reference datasets for developing expression genetic prediction models to capture the moderate to low genetically regulated components of gene expression. Here, we introduce a new method, Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction model accuracy and the power of TWAS by using a large expression quantitative trait loci (eQTL) summary-level dataset. We applied SUMMIT to the eQTL summary-level data provided by the eQTLGen consortium, which involve 31,684 blood samples from 37 cohorts. Through simulation studies and analyses of GWAS summary statistics for 24 complex traits, we show that SUMMIT substantially improves the accuracy of expression prediction in blood, successfully builds expression prediction models for genes with low expression heritability, and achieves higher statistical power than several benchmark methods. In the end, we conducted a case study of COVID-19 severity with SUMMIT and identified 11 likely causal genes associated with COVID-19 severity.
The minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers
Authors: Doggett Karen , Morgan Kimberly J , Mieruszynski Stephen , Williams Benjamin B , Olthof Anouk M , Garnham Alexandra L , Milevskiy Michael J G , Whitehead Lachlan , Coates Janine , Buchert Michael , O’Donoghue Robert JJ , Hall Thomas E , Gong Zhiyuan , Putoczki Tracy L , Ernst Matthias , Sutherland Kate D , Kanadia Rahul N , Heath Joan K
Published: December 2021

Minor splicing is a second splicing system required for the correct expression of ∼700 human minor intron-containing genes (MIGs). Many MIGs are expressed in vigorously proliferating cells and are frequently dysregulated in cancer includingBRAF, ERK, JNKandp38. Minor splicing is carried out by the minor spliceosome which comprises several unique components, including a 65kDa protein encoded byRNPC3. We show thatRnpc3heterozygosity reduces tumour burden in a broad spectrum ofin vivocancer settings, without harming normal tissues. Using the collective power of zebrafish, mouse and human cancer models, we reveal a sequence of events connectingRnpc3deficiency and impaired splicing of MIGs to DNA damage and activation of a Tp53-dependent transcriptional program that restricts tumour burden by inducing cell cycle arrest and apoptosis. Interrogation of human liver and lung cancer transcriptomes curated in TCGA revealed that the expression of many of the genes encoding protein components of the minor spliceosome is upregulated in these cancers. This is accompanied by upregulation of the expression of MIGs that are enriched in cell cycle and DNA damage pathways. These findings suggest that cancer cells can invoke mechanisms to increase the efficiency of minor splicing to support their high proliferation rates. Finally, Kaplan Meier survival analysis shows that highly expressed MIGs are frequently associated with poor patient survival. Taken together, these results indicate that the minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers.
No evidence of paralogous loci or new bona fide microRNAs in telomere to telomere (T2T) genomic data
Authors: Patil Arun H. , Halushka Marc K. , Fromm Bastian
Published: December 2021

The telomere to telomere (T2T) genome project discovered and mapped ∼240 million additional base pairs of primarily telomeric and centromeric reads. Much of this sequence was comprised of satellite sequences and large segmental duplications. We evaluated the extent to which human bona fide microRNAs (miRNAs) may be found in additional paralogous genomic loci or if previously undescribed microRNAs are present in these newly sequenced regions of the human genome. New genomic regions of the T2T project spanning ∼240 million bp of sequence were obtained and evaluated by blastn for the human miRNAs contained in MirGeneDB2.0 (N=556) and miRBase (N = 1917) along with all species of MirGeneDB2.0 miRNAs (N=10,899). Additionally, bowtie was used to compare unmapped reads from >4,000 primary cell samples to the new T2T sequence. Based on sequence and structure, no bona fide miRNAs were identified. Ninety-seven miRNAs of questionable authenticity (frequently known repeat elements) were identified from the miRBase dataset across the newly described regions of the human genome. These 97 represent only 51 miRNA families due to paralogy of highly similar miRNAs such as 24 members of the hsa-mir-548 family. Altogether, this data strongly supports our having identified widely expressed bona fide miRNAs in the human genome and move us further toward the completion of human miRNA discovery.
Using ultraconserved elements to reconstruct the termite tree of life
Authors: Hellemans Simon , Wang Menglin , Hasegawa Nonno , Šobotník Jan , Scheffrahn Rudolf H. , Bourguignon Thomas
Published: December 2021

The phylogenetic history of termites has been investigated using mitochondrial genomes and transcriptomes. However, both sets of markers have specific limitations. Mitochondrial genomes represent a single genetic marker likely to yield phylogenetic trees presenting incongruences with species trees, and transcriptomes can only be obtained from well-preserved samples. In contrast, ultraconserved elements (UCEs) include a great many independent markers that can be retrieved from poorly preserved samples. Here, we designed termite-specific baits targeting 50,616 UCE loci. We tested our UCE bait set on 42 samples of termites and three samples of Cryptocercus, for which we generated low-coverage highly-fragmented genome assemblies and successfully extracted in silico between 3,426 to 42,860 non-duplicated UCEs per sample. Our maximum likelihood phylogenetic tree, reconstructed using the 5,934 UCE loci retrieved from upward of 75% of samples, was congruent with transcriptome-based phylogenies, demonstrating that our UCE bait set is reliable and phylogenetically informative. Combined with non-destructive DNA extraction protocols, our UCE bait set provides the tool needed to carry out a global taxonomic revision of termites based on poorly preserved specimens such as old museum samples. The Termite UCE database is maintained at: https://github.com/oist/TER-UCE-DB/.
Exploring selection bias in COVID-19 research: Simulations and prospective analyses of two UK cohort studies
Authors: Millard Louise AC , Fernández-Sanlés Alba , Carter Alice R , Hughes Rachael , Tilling Kate , Morris Tim P , Major-Smith Daniel , Griffith Gareth J , Clayton Gemma L , Kawabata Emily , Smith George Davey , Lawlor Deborah A , Borges Maria Carolina
Published: December 2021

Background

Non-random selection into analytic subsamples could introduce selection bias in observational studies of SARS-CoV-2 infection and COVID-19 severity (e.g. including only those have had a COVID-19 PCR test). We explored the potential presence and impact of selection in such studies using data from self-report questionnaires and national registries.

Methods

Using pre-pandemic data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (mean age=27.6 (standard deviation [SD]=0.5); 49% female) and UK Biobank (UKB) (mean age=56 (SD=8.1); 55% female) with data on SARS-CoV-2 infection and death-with-COVID-19 (UKB only), we investigated predictors of selection into COVID-19 analytic subsamples. We then conducted empirical analyses and simulations to explore the potential presence, direction, and magnitude of bias due to selection when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19.

Results

In both ALSPAC and UKB a broad range of characteristics related to selection, sometimes in opposite directions. For example, more educated participants were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB. We found bias in many simulated scenarios. For example, in one scenario based on UKB, we observed an expected odds ratio of 2.56 compared to a simulated true odds ratio of 3, per standard deviation higher BMI.

Conclusion

Analyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depends on the outcome definition, the true effect of the risk factor, and the assumed selection mechanism.

Key messages

Observational studies assessing the association of risk factors with SARS-CoV-2 infection and COVID-19 severity may be biased due to non-random selection into the analytic sample.

Researchers should carefully consider the extent that their results may be biased due to selection, and conduct sensitivity analyses and simulations to explore the robustness of their results. We provide code for these analyses that is applicable beyond COVID-19 research.
Functional brain network and trail making test changes after major surgery and delirium
Authors: van Montfort Simone JT , Ditzel Fienke L , Kant Ilse MJ , Aarts Ellen , Vernooij Lisette M , Spies Claudia D , Hendrikse Jeroen , Slooter Arjen JC , van Dellen Edwin
Published: December 2021

Background

Delirium is a frequent complication of elective surgery in elderly patients, associated with an increased risk of long-term cognitive impairment and dementia. Disturbances in the functional brain network were previously reported during delirium. We hypothesized persisting alterations in functional brain networks three months after elective surgery in patients with postoperative delirium, and hypothesized that postoperative brain connectivity changes (irrespective of delirium) are related to cognitive decline.

Methods

Elderly patients (N=554) undergoing elective surgery underwent clinical assessments (including Trail Making Test B (TMT-B) and resting-state functional magnetic resonance imaging (rs-fMRI) before and three months after surgery. Delirium was assessed on the first seven postoperative days. After strict motion correction, rs-fMRI connectivity strength and network characteristics were calculated in 246 patients (130 patients underwent scans at both timepoints), of whom 38 (16%) developed postoperative delirium.

Results

Rs-fMRI functional connectivity strength increased after surgery in the total study population (β=0.006, 95%CI=0.000–0.012, p=0.021), but decreased after postoperative delirium (β=-0.014, 95%CI=0.000–0.012, p=0.026). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium. Patients who decreased in functional connectivity strength declined in TMT-B scores compared to the group that did not (β=11.04, 95%CI=0.85-21.2, p=0.034).

Conclusions

Delirium was associated with decreased functional connectivity strength three months after the syndrome was clinically resolved, which implies that delirium has lasting impact on brain networks. Decreased connectivity strength was associated with statistically significant (but not necessarily clinically relevant) cognitive deterioration after major surgery, which was not specifically related to delirium.

Summary statement

Delirium was associated with decreased resting-state fMRI functional connectivity strength three months after the syndrome was clinically resolved. Irrespective of delirium, decreased connectivity strength after major surgery was associated with a statistically significant cognitive deterioration.
Increased risk of fungal infection detection in women using menstrual cups vs. tampons: a cross-sectional study
Authors: Tessandier Nicolas , Uysal Ilkay Başak , Elie Baptiste , Selinger Christian , Bernat Claire , Boué Vanina , Grasset Sophie , Groc Soraya , Kamiya Tsukushi , Rahmoun Massilva , Reyné Bastien , Bender Noemi , Bonneau Marine , Graf Christelle , Tribout Vincent , Foulongne Vincent , Ravel Jacques , Waterboer Tim , Hirtz Christophe , Bravo Ignacio G , Reynes Jacques , Segondy Michel , Murall Carmen Lia , Boulle Nathalie , Alizon Samuel
Published: December 2021

Objective

To determine if the use of menstrual cups rather than tampons is associated with more or less health risk.

Design

Analysing biological, demographic, and behavioural data in a cohort of women who reported using mostly tampons (n = 81) or menstrual cups (n = 22).

Setting

A cross-sectional analysis using the inclusion data of a single centre longitudinal study.

Population

149 women from 18 to 25 years old living in the area of Montpellier (France) who reported having at least one new sexual partner over the last year.

Methods

Statistical modelling (mainly binomial regression models and factor analyses of mixed data).

Main Outcome Measures

Self-reported data from questionnaires (fungal infection, urinary tract infection, stress level) and biological data (HPV screening, vaginal microbiota profiling, circulating antibodies titration, and local cytokine concentrations).

Results

We identify an increased risk of reporting fungal infections for women using menstrual cups over tampons. We do not detect significant differences in terms of vaginal microbiota composition or local cytokines expression profile but find that women fall into two different clusters in a factor analysis of mixed data depending on the type of menstrual product they use more (cups or tampons).

Conclusions

These results point to potential health risks in the use of menstrual cups and differences in local vaginal environments. In-depth studies are needed to better understand potential associations between menstrual product use and women’s health.

Funding

European Research Council (EVOLPROOF, grant 648963)

Ethics

The PAPCLEAR study ClinicalTrials.gov identifier is NCT02946346.

Tweetable abstract

A cross-sectional study finds a significant association between menstrual cup use and fungal infection risk.
Cerebrospinal fluid formation is controlled by membrane transporters to modulate intracranial pressure
Authors: Oernbo Eva K. , Steffensen Annette B. , Khamesi Pooya Razzaghi , Toft-Bertelsen Trine L. , Barbuskaite Dagne , Vilhardt Frederik , Gerkau Niklas J. , Tritsaris Katerina , Simonsen Anja H. , Lolansen Sara D. , Andreassen Søren N. , Hasselbalch Steen G. , Zeuthen Thomas , Rose Christine R. , Kurtcuoglu Vartan , MacAulay Nanna
Published: December 2021

Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge. Nevertheless, the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP. Here, we employed experimental rats to demonstrate low osmotic water permeability of the choroid plexus, lack of an osmotic gradient across this tissue, and robust CSF secretion against osmotic gradients. Together, these results illustrate that CSF secretion occurs independently of conventional osmosis, which challenges the existing assumption that CSF production is driven entirely by bulk osmotic forces across the CSF-secreting choroid plexus. Instead, we reveal that the choroidal Na+/K+/Cl− cotransporter NKCC1, Na+/HCO3− cotransporter NBCe2, and Na+/K+-ATPase are actively involved in CSF production and propose a molecular mode of water transport supporting CSF production in this secretory tissue. Further, we demonstrate that inhibition of NKCC1 directly reduces the ICP, illustrating that altered CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP.
Generation of bright autobioluminescent bacteria by chromosomal integration of the improved lux operon ilux2
Authors: Gregor Carola
Published: December 2021

The bacterial bioluminescence system enables light production in living cells without an external luciferin. Due to its relatively low levels of light emission, many applications of bioluminescence imaging would benefit from an increase in brightness of this system. In this report a new approach of mutagenesis and screening of the involved proteins is described that is based on the identification of mutants with improved properties under rate-limiting reaction conditions. Multiple rounds of screening in Escherichia coli resulted in the operon ilux2 that contains 26 new mutations in the fatty acid reductase complex which provides the aldehyde substrate for the bioluminescence reaction. Chromosomal integration of ilux2 yielded an autonomously bioluminescent E. coli strain with 7-fold increased brightness compared to the previously described ilux operon. The ilux2 strain produces sufficient signal for the robust detection of individual cells and enables highly sensitive long-term imaging of bacterial propagation without a selection marker.