bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediation effect of body mass index on the association between age at menopause and type 2 diabetes mellitus in postmenopausal Chinese women
Authors: Zhao Yijing , Wang Su , Yang Yu , Cao Wen , Chen Kun , Wang Kun
Published: January 2022

Objective:

This study aimed to examine the association between age at menopause and type 2 diabetes mellitus (T2DM), and whether this association is mediated by body mass index (BMI) in postmenopausal Chinese women.

Methods:

This cross-sectional study enrolled 4,279 postmenopausal women. Binary logistic regression was used to estimate the association between age at menopause and T2DM. A multiple linear regression model was used to evaluate the relationships between age at menopause and fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPBG), homeostasis model assessment for insulin resistance (HOMA)-IR, and HOMA of ß-cell function (HOMA-ß). Mediation analysis was performed to investigate whether these associations were mediated by BMI.

Results:

After full adjustment, women with a later age of menopause (>54 y) were more likely to have T2DM (odds ratio =1.401, 95% confidence interval [CI], 1.010-1.945; P 
= 0.044) than those in the reference group (4453 y). After multiple adjustments, each 1-year increase in the age at onset of menopause was associated with a 0.021 mmol/L increase in FPG (95% CI, 0.004-0.038; P 
= 0.014), 0.048 mmol/L increase in2hPBG (95% CI, 0.0060.090; P 
= 0.024), and 1.540 decrease in HOMA-ß (95% CI, —2.386 to —0.695; P 
< 0.001), but no changes in HOMA-IR. Later age of menopause was associated with overweight/general obesity (odds ratio = 1.416, 95% CI, 1.028-1.950; P 
= 0.015). BMI partially mediated the association between age at menopause and FPG and 2hPBG, and the proportion of the effect was 5.42% and 7.69%, respectively. Further, BMI suppressed the association between age at menopause and HOMA-ß, and the proportion of the suppressing effect was 9.54%.

Conclusions:

The later age of menopause was positively related to T2DM. BMI partially mediated the association between age at menopause and glucose status and suppressed the association between age at menopause and HOMA-ß. Prospective studies are warranted to confirm this association.
Prognostic value of arterial stiffness in menopausal women
Authors: Kim Minkwan , Kim Hack-Lyoung , Cho Yuna , Lim Woo-Hyun , Seo Jae-Bin , Kim Sang-Hyun , Zo Joo-Hee , Kim Myung-A
Published: January 2022

Objective:

Because menopausal women have an increased cardiovascular risk, risk stratification is very crucial in this population. This study aimed to verify the prognostic value of arterial stiffness in menopausal women.

Methods:

We retrospectively analyzed 2,917 menopausal women (age >55y) without overt cardiovascular disease who underwent brachial-ankle pulse wave velocity measurement. The primary endpoint was a composite of clinical events, including all-cause death, nonfatal myocardial infarction, coronary revascularization, and stroke, hereafter referred to as major adverse cardiovascular events. Propensity score matching and inverse probability-treatment weighting analysis were used to balance differences in baseline participant characteristics.

Results:

The mean participant age was 66.8 ± 7.7 years. During a median follow-up period of 4.0 (interquartile range of 1.9-6.3) years, the primary outcome was noted in 56 cases (1.9%). Pulse wave velocity was significantly higher in participants with the primary outcome than in those without (1,947 ± 388 vs 1,690 ± 348 cm/s; P 
< 0.001). For every 100 cm/s increase in pulse wave velocity, the hazard ratio for the primary endpoint increased by 1.15 times (95% confidence interval, 1.08-1.22; P 
< 0.001) in multivariable Cox regression analysis. A pulse wave velocity > 1,613 cm/s was associated with increased risk of the primary endpoint in the same multivariable analysis (hazard ratio, 3.06; 95% confidence interval, 1.40-6.68; P 
= 0.005). The results were consistent after propensity score matching and inverse probability-treatment weighting analysis.

Conclusions:

Elevated brachial-ankle pulse wave velocity was associated with the occurrence of major adverse cardiovascular events in menopausal women without cardiovascular disease and may represent a useful screening tool.
Myeloid Sarcoma of the Urinary Bladder Associated With t(8;21): Case Report and Review of the Literature
Authors: Suárez-Solís María Luisa , González Fernández Fernando Ataulfo , Barrera Ortega Jerónimo , Pérez Romero Natalia , García Roa María , Fernández Aceñero María Jesús , Durán Botia Freddy Fernando , Ortega Medina Luis
Published: January 2022

Myeloid sarcoma is a malignant neoplasm of myeloid lineage that occurs in extramedullary sites, frequently in patients with acute myeloid leukemia and other myeloproliferative and myelodysplastic syndromes. Myeloid sarcoma of the urinary bladder is exceptionally rare, and although the most common cytogenetic abnormality associated with this lesion is t(8;21)/RUNX-RUNX1T1, to the best of our knowledge, there are no previous reports of this in patients with bladder involvement. We report a case of a 30-year-old man with a urinary bladder mass, which was consistent with myeloid sarcoma with t(8;21). The importance of myeloid sarcoma of the bladder is that it could be misdiagnosed and must be differentiated from other poorly differentiated bladder tumors composed of round cells, mainly because it is a malignant neoplasm with a good response to treatment, which does not require surgery.
Soft Tissue Fibroblastic Reticular Cell Tumor With Whole-Exome Sequencing Findings: An Unexpected Presentation of Lynch Syndrome
Authors: Lopez Liurka V. , Marker Daniel F. , Bailey Nathanael , Liu Yen-Chun , McGough Richard L. , Singhi Aatur D. , John Ivy
Published: January 2022

Fibroblastic reticular cell tumor (FRCT) is an exceedingly rare tumor that is histologically reminiscent of follicular dendritic cell sarcoma or interdigitating dendritic cell sarcoma but lacks the immunophenotypic features of these tumors. This tumor is classically described in lymph nodes and spleen, with only 4 cases described in soft tissues. We report a case of FRCT presenting as a right thigh mass in a 67-year-old woman with no prior malignancies. Gross examination showed a 10.6-cm tan well-circumscribed intramuscular mass. Microscopic examination revealed a discohesive population of cells with indistinct pale cytoplasm and large irregular, atypical vesicular nuclei with variably prominent nucleoli in a collagenous background infiltrated by lymphocytes. The tumor cells were positive for smooth muscle actin, cytokeratins (in a dendritic pattern), and CD163, while negative for CD21, CD35, and CD23, supporting the diagnosis of FRCT. Whole-exome sequencing revealed 631 putative somatic mutations in the tumor (>10 mutations/Mb of sequence). Mutational signature analysis suggested DNA mismatch repair deficiency. Germline mutational analysis revealed a heterozygous pathogenic missense mutation of MLH1 (c.2246 T > C, p.Leu749Pro). Subsequent immunohistochemical analysis showed complete loss of MLH1 and PMS2 in tumor cells. To our knowledge, this is the first case of FRCT characterized by sequencing studies and found to be associated with Lynch syndrome (LS), expanding the spectrum of LS-associated neoplasms. This case demonstrates genetic hypermutation similar to that seen in the more common epithelial lesions arising in LS, and it highlights the potential for high-throughput genetic analysis to identify mismatch repair–deficient tumors of atypical histologies, which may have significant clinical implications in the era of immunotherapy.
Optimal Timing of Expander-to-Implant Exchange after Irradiation in Immediate Two-Stage Breast Reconstruction
Authors: Kim Ara , Bae Juyoung , Bang Sa-Ik , Pyon Jai-Kyong
Published: January 2022

Background:

Time intervals for expander-to-implant exchange from radiation therapy have been reported to reduce device failure. This study investigated the optimal timing of expander-to-implant exchange after irradiation in terms of short- and long-term outcomes.

Methods:

This retrospective review enrolled consecutive patients who underwent immediate two-stage breast reconstruction and radiation therapy to tissue expanders from 2010 to 2019. Receiver operating characteristic curves and the Youden index were used to estimate the optimal time from radiation therapy to implant placement in terms of 49-day (early) and 2-year (late) complications. Logistic regression analysis was performed to identify the risk factors for each complication.

Results:

Of the 1675 patients, 133 were included. The 49-day and 2-year complication rates were 8.3 percent and 29.7 percent, respectively. Capsular contracture was the most common 2-year complication. The Youden index indicated that implant placement at 131 days after radiation therapy was most effective in reducing the 49-day complications, but that the 2-year complication was less significant, with lower sensitivity and area under the curve. Modified radical mastectomy, expander fill volume at radiation therapy, and size of permanent implant increased the odds of 49-day complications; none of them was associated with the odds of 2-year complications.

Conclusions:

To reduce short-term complications, the best time point for permanent implant placement was 131 days after radiation therapy. However, there was no significant time interval for reducing long-term complications. Capsular contracture was an irreversible complication of radiation injury that was not modified by postirradiation variables including the time from irradiation or size of permanent implant.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
The Ever-Important Role of Ethics in Plastic Surgery Today
Authors: Teven Chad M. , Bluebond-Langner Rachel , Rohrich Rod J.
Published: January 2022

As the field of plastic surgery continues to advance, so too do the number and complexity of ethical challenges faced by plastic surgeons. There is a paucity of literature, however, focusing on ethics in plastic surgery. Therefore, the authors offer a timely special topic series discussing ethical issues relevant to the field of plastic surgery. The goals of this series are four-fold: (1) to increase awareness of both frequently and less commonly encountered ethical issues in plastic surgery, (2) to foster discussion and debate of relevant and significant ethical issues, (3) to facilitate clinical ethics education and scholarship in plastic surgery, and (4) to apply an understanding and analysis of ethical issues in a way that optimizes clinical decision-making and delivery of patient care. In this introductory article, the authors discuss the current state of medical ethics scholarship in plastic surgery and introduce the first of several topics that will be detailed in the series. Ultimately, the hope is that increased awareness of the ethical challenges faced by surgeons and patients will improve the practice of plastic surgery.
Subglandular-to-Subpectoral Conversion with Mastopexy: The Four-Step Approach
Authors: Ono Marcelo T. , Karner Bruno M.
Published: January 2022

Background:

Because of the multiplying number of patients undergoing breast augmentation, nonprimary augmentation mastopexy will be increasingly requested in the future; this operation represents an even more significant challenge than primary augmentation mastopexy. The authors describe a standardized approach for subglandular-to-subpectoral implant pocket conversion in mastopexy that provides a tight neopocket with inferolateral muscular support, which minimizes implant displacement complications and allows operative strategies to reduce the risk of bacterial load on implants.

Methods:

The authors’ technique proposes the following: (1) modified subpectoral pocket, with muscular inferolateral support for the implant; (2) independent approaches to the submuscular pocket and subglandular (preexisting) pocket; and (3) preestablished four-step surgical sequence. The authors collected data from their private practices for 46 patients who underwent the technique from March of 2017 to April of 2020. Patient perception about aesthetic outcomes, photographs from multiple postoperative follow-ups, and surgical complications/reoperation rates were analyzed.

Results:

Overall results were positive; 89.1 percent of patients reported satisfaction with their aesthetic outcomes. No major complications occurred. The total revision rate was 15.2 percent, but only 2.1 percent in the last year, as the learning curve progressed.

Conclusions:

Secondary augmentation mastopexy is a complicated procedure. The four-step sequence approach is one reliable option for subglandular-to-subpectoral pocket conversion, once it produced high levels of patient satisfaction while producing low complication rates. Other surgeons’ experiences with the technique and further studies are necessary to validate these findings.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Rapid urine-based screening tests increase the yield of same-day tuberculosis diagnoses among patients living with advanced HIV disease
Authors: Wake Rachel M. , Govender Nelesh P. , Omar Shaheed V. , Ismail Farzana , Tiemessen Caroline T. , Harrison Thomas S. , Jarvis Joseph N.
Published: January 2022

Objective:

Investigation of the diagnostic yield of urine-based tuberculosis (TB) screening in patients with advanced HIV disease.

Design:

A cross-sectional screening study

Setting:

HIV outpatient clinics and wards at two hospitals in Johannesburg, South Africa, between June 2015 and October 2017.

Participants:

Two hundred and one patients living with advanced HIV disease (CD4+ T-lymphocytes <100 cells/μl) attending healthcare facilities following cryptococcal antigen (CrAg) screening.

Intervention:

Screening for TB using sputum for microscopy, culture, and Xpert MTB/Rif and urine for lipoarabinomannan (LAM) and Xpert Ultra.

Main outcome measures:

Proportion of positive results using each testing modality, sensitivity, and specificity of urine-based testing compared with culture, and survival outcomes during 6 months follow up.

Results:

Urine was obtained from 177 of 181 (98%) participants and sputum from 91 (50%). Urine-based screening increased same-day diagnostic yield from 7 (4%) to 31 (17%). A positive urine test with either LAM or Xpert Ultra had 100% sensitivity (95% confidence interval, 59–100%) for detecting culture-positive TB at any site. Patients with newly diagnosed TB on urine-based screening were initiated on treatment and did not have excess mortality compared with the remainder of the cohort.

Conclusion:

Urine is an easily obtainable sample with utility for detecting TB in patients with advanced HIV disease. Combining urine and sputum-based screening in this population facilitates additional same-day TB diagnoses and early treatment initiation, potentially reducing the risk of TB-related mortality. Urine-based as well as sputum-based screening for TB should be integrated with CrAg screening in patients living with advanced HIV disease.
Prophylactic Central Neck Lymph Node Dissection in Low-risk Thyroid Carcinoma Patients Does Not Decrease the Incidence of Locoregional Recurrence
Authors: Sanabria Alvaro , Betancourt-Agüero Carlos , Sánchez-Delgado Juan G. , García-Lozano Carlos
Published: January 2022

Objective:

To evaluate the effectiveness of T + prophylactic CND (T+CND) compared to T alone on locoregional recurrence in patients with PTC.

Summary background data:

Few RCTs have assessed the risks and benefits of prophylactic CND in patients with PTC. Most recommendations are still based on meta-analyses that include observational studies, which are prone to selection bias.

Methods:

We included RCTs involving adult patients with clinically negative neck (cN0) PTC that compared T versus T+CND. The main outcomes assessed were structural and biochemical recurrence and complications. For methodological quality assessment, we used the Revised Cochrane risk-of-bias tool for randomized trials instrument, and for robustness, we used the fragility index.

Results:

Five RCTs with 763 patients were included (354 in the T group and 409 in the T+CND group). Most studies were classified as having a low risk of bias. Publication bias was not found. Structural recurrence occurred in 11/409 (2.7%) patients in the T+CND group and 9/354 (2.5%) patients in the T group, with a risk difference (RD) =0% [95% confidence interval (CI) –2% to 2%]. For biochemical recurrence, the RD was 0% (95% CI –5% to 4%). The number needed to treat was 500. The rate of permanent hypoparathyroidism was higher in the T+CND group than in the T group [RD 3% (95% CI 0%–6%)].

Conclusions:

We did not find a beneficial effect of prophylactic CND associated with T on locoregional or biochemical recurrence but did confirm a higher risk of permanent hypoparathyroidism associated with this procedure.
Impact of N-Acetyl-Cysteine on Ischemic Stumps Following Major Lower Extremity Amputation
Authors: Lee Jin Vivian , Engel Connor , Tay Shirli , DeSilva Gayan , Desai Kshitij , Cashin John , Semenkovich Clay F. , Zayed Mohamed A.
Published: January 2022

Objective:

To evaluate the impact of N-acetyl-cysteine (NAC) on amputation stump perfusion and healing in patients with critical limb-threatening ischemia (CLTI).

Background:

Patients with CLTI are at increased risk of poor amputation site healing leading to increased procedure-associated morbidity.

Methods:

In a pilot, double-blind, placebo-controlled, randomized controlled trial, patients with CLTI undergoing major elective lower extremity amputation were randomized 1:1 to intravenous NAC (1200 mg twice-daily) or placebo for up to 5 days postoperatively. Primary outcomes were change in stump perfusion at postoperative day 3 (POD3) and POD5, and healing at POD30. Stumps were serially evaluated for wound healing, and tissue perfusion was evaluated using noninvasive laser-assisted fluorescent angiography.

Results:

Thirty-three patients were randomized to NAC (n = 16) or placebo (n = 17). Thirty-one patients were eligible for intent-to-treat analysis (NAC14; placebo17). Twenty patients (NAC7; placebo13) had amputation stump perfusion defects at POD0 and were considered high-risk for poor healing. Intent-to-treat analysis revealed no significant differences between treatment groups. Subgroup analysis of high-risk patients revealed differences in stump perfusion defect size (NAC–0.53-fold, placebo +0.71–fold; 95% confidence interval -2.11 to–0.35; P < 0.05) and healing (NAC [100%], placebo [46%]; P < 0.01) between study treatments.

Conclusions:

Postoperative NAC administration may improve amputation stump perfusion and healing in patients with CLTI and tissue perfusion defects at the time of amputation. Intraoperative laser-assisted fluorescent angiogra-phy may help surgeons identify high-risk patients with stump perfusion defects and provide early adjunctive interventions. Future studies can further explore the therapeutic benefits of NAC in the healing and perfusion of other surgical operative sites in high-risk individuals.

Trial Registration:

clinicaltrials.gov, Identifier: NCT03253328.
Genetic and lipidomic analyses suggest that Nostoc punctiforme, a plant-symbiotic cyanobacterium, does not produce sphingolipids
Authors: Belton Samuel , Lamari Nadia , Jermiin Lars S. , Mariscal Vicente , Flores Enrique , McCabe Paul F. , Ng Carl K. Y.
Published: January 2022

Sphingolipids, a class of amino-alcohol-based lipids, are well characterized in eukaryotes and in some anaerobic bacteria. However, the only sphingolipids so far identified in cyanobacteria are two ceramides (i.e., an acetylsphingomyelin and a cerebroside), both based on unbranched, long-chain base (LCB) sphingolipids in Scytonema julianum and

Moorea producens

, respectively. The first step in de novo sphingolipid biosynthesis is the condensation of l-serine with palmitoyl-CoA to produce 3-keto-diyhydrosphingosine (KDS). This reaction is catalyzed by serine palmitoyltransferase (SPT), which belongs to a small family of pyridoxal phosphate-dependent α-oxoamine synthase (AOS) enzymes. Based on sequence similarity to molecularly characterized bacterial SPT peptides, we identified a putative SPT (Npun_R3567) from the model nitrogen-fixing, plant-symbiotic cyanobacterium,

Nostoc punctiforme

strain PCC 73102 (ATCC 29133). Gene expression analysis revealed that Npun_R3567 is induced during late-stage diazotrophic growth in

N. punctiforme

. However, Npun_R3567 could not produce the SPT reaction product, 3-keto-diyhydrosphingosine (KDS), when heterologously expressed in

Escherichia coli

. This agreed with a sphingolipidomic analysis of

N. punctiforme

cells, which revealed that no LCBs or ceramides were present. To gain a better understanding of Npun_R3567, we inferred the phylogenetic position of Npun_R3567 relative to other bacterial AOS peptides. Rather than clustering with other bacterial SPTs, Npun_R3567 and the other cyanobacterial BioF homologues formed a separate, monophyletic group. Given that

N. punctiforme

does not appear to possess any other gene encoding an AOS enzyme, it is altogether unlikely that

N. punctiforme

is capable of synthesizing sphingolipids. In the context of cross-kingdom symbiosis signalling in which sphingolipids are emerging as important regulators, it appears unlikely that sphingolipids from

N. punctiforme

play a regulatory role during its symbiotic association with plants.
Lysobacter terrestris sp. nov., isolated from soil
Authors: Woo Chae Yung , Kim Jaisoo
Published: January 2022

A yellow-pigmented, non-motile, Gram-stain-negative, rod-shaped bacterium, designated II4T was obtained from soil sampled at Seongnam, Gyeonggi-do, Republic of Korea. Cells were strictly aerobic, grew optimally at 20–28 °C and hydrolysed casein. A phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain II4T formed a lineage within the family

Xanthomonadaceae

and clustered as members of the genus

Lysobacter

. The closest members were

Lysobacter terrae

THG-A13T (97.88 % sequence similarity),

Lysobacter niabensis

GH34-4T (97.82 %),

Lysobacter oryzae

YC6269T (97.74%),

Lysobacter yangpyeongensis

GH19-3T (97.53 %) and

Lysobacter enzymogenes

ATCC 29487T (96.18 %). The principal respiratory quinone was Q-8 and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The predominant cellular fatty acids were summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1
 ω9c) and iso-C15 : 0 and iso-C16 : 0. The DNA G+C content was 68.2 mol%. The average nucleotide identity and in silico DNA–DNA hybridization relatedness values between strain II4T and its closely related genus members with possible full genome sequences were ≤79.6 and 23.7 %, respectively. Based on genomic, chemotaxonomic, phenotypic and phylogenetic data, strain II4T represents novel species in the genus

Lysobacter

, for which the name Lyobacter terrestris sp. nov. is proposed. The type strain is II4T (=KACC 21196T=NBRC 113956T).
Evidence against Zika virus infection of pets and peri-domestic animals in Latin America and Africa
Authors: Oliveira-Filho Edmilson F. de , Carneiro Ianei O. , Fischer Carlo , Kühne Arne , Postigo-Hidalgo Ignacio , Ribas Jorge R. L. , Schumann Peggy , Nowak Kathrin , Gogarten Jan F. , de Lamballerie Xavier , Dantas-Torres Filipe , Netto Eduardo Martins , Franke Carlos Roberto , Couacy-Hymann Emmanuel , Leendertz Fabian H. , Drexler Jan Felix
Published: January 2022

Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013–2018 in Brazil and 2006–2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire (n=259) and Brazil (n=1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8–60.1) in West African chimpanzees (Pan troglodytes verus) and 11.1% (1/9, 95% CI, 0.3–48.3) in king colobus (Colobus polycomos). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.
Distribution, organization and expression of genes concerned with anaerobic lactate utilization in human intestinal bacteria
Authors: Sheridan Paul O. , Louis Petra , Tsompanidou Eleni , Shaw Sophie , Harmsen Hermie J. , Duncan Sylvia H. , Flint Harry J. , Walker Alan W.
Published: January 2022

Lactate accumulation in the human gut is linked to a range of deleterious health impacts. However, lactate is consumed and converted to the beneficial short-chain fatty acids butyrate and propionate by indigenous lactate-utilizing bacteria. To better understand the underlying genetic basis for lactate utilization, transcriptomic analyses were performed for two prominent lactate-utilizing species from the human gut,

Anaerobutyricum soehngenii

and

Coprococcus catus

, during growth on lactate, hexose sugar or hexose plus lactate. In

A. soehngenii

L2-7 six genes of the lactate utilization (lct) cluster, including NAD-independent d-lactate dehydrogenase (d-iLDH), were co-ordinately upregulated during growth on equimolar d- and l-lactate (dl-lactate). Upregulated genes included an acyl-CoA dehydrogenase related to butyryl-CoA dehydrogenase, which may play a role in transferring reducing equivalents between reduction of crotonyl-CoA and oxidation of lactate. Genes upregulated in

C. catus

GD/7 included a six-gene cluster (lap) encoding propionyl CoA-transferase, a putative lactoyl-CoA epimerase, lactoyl-CoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. A d-iLDH homologue in

C. catus

is encoded by a separate, partial lct, gene cluster, but not upregulated on lactate. While

C. catus

converts three mols of dl-lactate via the acrylate pathway to two mols propionate and one mol acetate, some of the acetate can be re-used with additional lactate to produce butyrate. A key regulatory difference is that while glucose partially repressed lct cluster expression in

A. soehngenii

, there was no repression of lactate-utilization genes by fructose in the non-glucose utilizer

C. catus

. This suggests that these species could occupy different ecological niches for lactate utilization in the gut, which may be important factors to consider when developing lactate-utilizing bacteria as novel candidate probiotics.
3D Capsule Networks for Brain Image Segmentation
Authors: Avesta Arman , Hui Yongfeng , Aboian Mariam , Duncan James , Krumholz Harlan M. , Aneja Sanjay
Published: January 2022

Background and Purpose

Current auto-segmentation models of brain structures, UNets and nnUNets, have limitations, including the inability to segment images that are not represented during training and lack of computational efficiency. 3D capsule networks (CapsNets) have the potential to address these limitations.

Methods

We used 3430 brain MRIs, acquired in a multi-institutional study, to train and validate our models. We compared our CapsNet with standard alternatives, UNets and nnUNets, based on segmentation efficacy (Dice scores), segmentation performance when the image is not well-represented in the training data, performance when the training data are limited, and computational efficiency including required memory and computational speed.

Results

The CapsNet segmented the third ventricle, thalamus, and hippocampus with Dice scores of 95%, 94%, and 92%, respectively, which were within 1% of the Dice scores of UNets and nnUNets. The CapsNet significantly outperformed UNets in segmenting images that are not well-represented in the training data, with Dice scores 30% higher. The computational memory required for the CapsNet is less than a tenth of the memory required for UNets or nnUNets. The CapsNet is also more than 25% faster to train compared with UNet and nnUNet.

Conclusion

We developed and validated a CapsNet that is effective in segmenting brain images, can segment images that are not well-represented in the training data, and are computationally efficient compared with alternatives.
Pan-cancer analysis reveals the prognostic potential of THAP9/THAP9-AS1 Sense-Antisense gene pair in human cancer
Authors: Rashmi Richa , Majumdar Sharmistha
Published: January 2022

Human THAP9 is a domesticated transposon homologous to the Drosophila P-element transposase (DmTNP). However, the exact functional role of THAP9 is unknown. THAP9-AS1 (THAP9-anti sense1) is a lncRNA involved in various cancers. Together they are arranged head-to-head on opposite DNA strands forming a sense and anti-sense gene pair. No studies have analyzed THAP9 and THAP9-AS1 from a pan-cancer perspective. First, we analyzed the bidirectional promoter region between THAP9 and THAP9-AS1 for core promoter elements and CPG Islands. Moreover, we analyzed the expression, prognosis, and biological function of the two genes across different types of tumors included in The Cancer Genome Atlas and GTEx datasets. The results showed that the expression of both genes varies in different tumors. Expression of the THAP9 and THAP9-AS1 gene pair was observed to be strongly correlated with prognosis in patients with tumors; higher expression of the two genes was usually linked to poor overall and disease-free survival. Therefore, they may serve as a potential biomarker of clinical tumor prognosis. Further, we performed gene coexpression analysis using WGCNA followed by differential gene correlation analysis (DGCA) across 22 cancers to study which genes share the expression pattern THAP9 and THAP9-AS1 and if their interacting partners change in various conditions. Gene ontology & KEGG pathway analysis of genes coexpressed with the two genes identified gene enrichment related to DNA binding and Herpes simplex virus 1 infection.
Mutations of SARS-CoV-2 variants of concern escaping Spike-specific T cells
Authors: Le Bert Nina , Tan Anthony , Kunasegaran Kamini , Chia Adeline , Tan Nicole , Chen Qi , Hang Shou Kit , Qui Martin DC , Chan Bianca SW , Low Jenny GH , Young Barnaby , Ng Kee Chong , Chan Derrick Wei Shih , Lye David Chien , Bertoletti Antonio
Published: January 2022

The amino acid (AA) mutations that characterise the different variants of concern (VOCs), which replaced the ancestral SARS-CoV-2 Wuhan-Hu-1 isolate worldwide, provide biological advantages such as increased infectivity and partial escape from humoral immunity. Here we analysed the impact of these mutations on vaccination- and infection-induced Spike-specific T cells. We confirmed that, in the majority of infected or vaccinated individuals, different mutations present in a single VOC (Delta) or a combined mosaic of more than 30 AA substitutions and deletions found in Alpha, Beta, Gamma, Delta and Omicron VOCs cause modest alteration in the global Spike-specific T cell response. However, distinct numerically dominant Spike-specific CD4 and CD8 T cells preferentially targeted regions affected by AA mutations and do not recognise the mutated peptides. Importantly, some of these mutations, such as N501Y (present in Alpha, Beta, Gamma, and Omicron) and L452R (present in Delta), known to provide biological advantage to SARS-CoV-2 in terms of infectivity also abolished CD8 T cell recognition.

Taken together, our data show that while global mRNA vaccine- and infection-induced Spike-specific T cells largely tolerate the diverse mutations present in VOCs, single Spike-specific T cells might contribute to the natural selection of SARS-CoV-2 variants.
Safety and Efficacy of Navigational Bronchoscopy with Archimedes Virtual Bronchoscopic Platform in Patients with Advanced Pulmonary Disease
Authors: Verga Steven R. , Marron Robert , Criner Gerard J. , Veselis Clinton , Dass Chandra , Zhao Hauqing
Published: January 2022

Background

Patients with advanced lung disease who present with suspicious pulmonary nodules (SPNs) undergoing transthoracic needle aspiration pose a diagnostic challenge given risk for complications. Virtual bronchoscopic navigation (VBN) is an alternative means to biopsy patients.

Study Design

The study was a retrospective chart review of all patients who underwent VBN with the Archimedes platform. Demographic information, radiographic evidence of parenchymal lung disease and pulmonary function testing were gathered. Peri-procedure complications and clinical data on biopsy results were gathered to assist in determining both adequate tissue sample (defined if adequate specimen was obtained as per pathology/cytology report) and diagnostic yield (defined as if after further testing/CT imaging from 1 year post-procedure the diagnosis did not change). Univariate analysis was performed to determine the impact of clinical factors on diagnostic yield.

Results

Ninety-six patients with 110 nodules underwent VBN. Eight-eight patients (92%) had radiographic emphysema with 56% having moderate to severe. Fourteen patients (17%) had radiographic ILD. Adequate tissue sample at time of VBN was 93%. Overall diagnostic yield in 80 patients (excluding 16 patients who were initially benign/non-diagnostic that were lost to follow-up) was 72%. Overall complication rate was 7% with 1-pneumothorax (1%), 3-significant bleeding and 3-hospitalized for respiratory failure.

Conclusion

In our cohort of patients the diagnostic yield and complication rate were comparable to other studies where there were fewer patients with advanced lung disease. This data suggests that VBN-guided bronchoscopic biopsy of SPNs is a viable diagnostic option with an acceptable safety profile.
Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India
Authors: Malhotra Sumit , Kalaivani Mani , Lodha Rakesh , Bakhshi Sameer , Mathur Vijay Prakash , Gupta Pooja , Kedia Saurabh , Sankar Jeeva , Kumar Parmeshwar , Kumar Arvind , Ahuja Vineet , Sinha Subrata , Guleria Randeep
Published: January 2022

Background

Delta variant transmission resulted in surge of SARS CoV-2 cases in New Delhi, India during the early half of year 2021. Health Care Workers (HCWs) received vaccines on priority for prevention of infection. Real life effectiveness of BBV152 vaccine against severe disease including hospitalization and death was not known.

Objective

To estimate effectiveness of BBV152 vaccine among HCWs against SARS CoV-2 infection, hospitalization or death

Design

Observational study

Setting

a multi -speciality tertiary care public funded hospital in New Delhi, India.

Participants

12,237 HCWs

Interventions

BBV152 vaccine (Covaxin, Bharat Biotech limited, Hyderabad, India); whole virion inactivated vaccine; two doses four weeks apart

Measurements

vaccine effectiveness after receipt of two doses of BBV152 protecting against any SARS CoV-2 infection, symptomatic infections or hospitalizations or deaths, and hospitalizations or deaths.

Results

The mean age of HCWs was 36(±11) years, 66% were men and 16% had comorbidity. After adjusting for potential covariates viz age, sex, health worker type category, body mass index, and comorbidity, the vaccine effectiveness (95% Confidence Interval) in fully vaccinated HCWs and ≥14 days elapsed after the receipt of second dose was 44% (37 to 51, p<0.001) against symptomatic infection, hospitalization or death due to SARS CoV-2, and 61% (37 to 76, p<0.001) against hospitalization or death, respectively.

Conclusions

BBV152 vaccine with complete two doses offer a modest response to SARS CoV-2 infection in real life situations against a backdrop of high delta variant community transmission. Efforts in maximizing receipt of full vaccines should be invested for HCWs, who are at higher occupational risk for infection.
Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion
Authors: Hu Shiling , Wang Nan , Chen Shaohong , Ding Qiang , Wang Cheng , Ma Weina , Zhang Xinghai , Wu Yan , Lv Yanni , Xue Zhuoyin , Bai Haoyun , Ge Shuai , He Huaizhen , Lu Wen , Zhang Tao , Ding Yuanyuan , Liu Rui , Han Shengli , Zhan Yingzhuan , Zhan Guanqun , Guo Zengjun , Zhang Yongjing , Lu Jiayu , Gao Jiapan , Jia Qianqian , Wang Yuejin , Wang Hongliang , Lu Shemin , Zhang Huajun , He Langchong
Published: January 2022

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein’s autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.
A robust and fast two-sample test of equal correlations with an application to differential co-expression
Authors: He Liang , Philipp Ian , Webster Stephanie , Kulminski Alexander M.
Published: January 2022

A robust and fast two-sample test for equal Pearson correlation coefficients (PCCs) is important in solving many biological problems, including, e.g., analysis of differential co-expression. However, few existing methods for this test can achieve robustness against deviation from normal distributions, accuracy under small sample sizes, and computational efficiency simultaneously. Here, we propose such a method for testing DIfferential COrrelation using a Saddlepoint Approximation of the Residual bootstrap (DICOSAR). To achieve robustness, accuracy, and efficiency, DICOSAR combines the ideas underlying the pooled residual bootstrap, the signed root of a likelihood ratio statistic, and a multivariate saddlepoint approximation. Through a comprehensive simulation study and a real data analysis of gene co-expression, we demonstrate that DICOSAR is accurate and robust in controlling the type I error rate for detecting differential correlation and provides a faster alternative to the permutation method. We further show that it can also be used for testing differential correlation matrices. These results suggest that DICOSAR provides an analytical approach to facilitate rapid testing for the equality of PCCs in a large-scale analysis.
Marine invertebrate diversity and distribution; the evidence of human activities in Rommel Bay
Authors: Ibrahim Marwa Abd El-Aziz M. , Zidan Islam Mohammad
Published: January 2022

The current note hypothesised that human/tourism beach activities in Rommel Bay, Marsa Matrouh, Egypt (31°21’39.9”N 27°15’12.3”E) affected the marine invertebrates in this area. The note resulted some new findings of arthropod, molluscan, and seagrasses species diversity and distribution. The hypothesised study concluded that human/tourism beach activities did not eliminate the invertebrate communities, but these animals have shifted and moved themselves to escape away from noise and pollution. Further investigations should be taken into consideration about aquatic insects, mites, crustaceans, seagrasses, and molluscans diversity and distribution, to figure out the actual structures and interactions between these animals within the Rommel Bay ecosystem, besides what are the stresses they have, and what are the consequences.
Chondroitin sulfates enhances the barrier function of basement membrane assembled by heparan sulfates
Authors: Tao Chenqi , Makrides Neoklis , Wu Yihua , Brooks Steven E , Esko Jeffrey D. , Zhang Xin
Published: January 2022

Glycosaminoglycans (GAGs) are ubiquitously expressed polysaccharides attached to proteoglycans, but their functions in the retina are poorly understood. Here we generated conditional knockouts of biosynthetic enzymes for heparan sulfate (HS) and chondroitin sulfate (CS) in retinal progenitor cells. We showed that ablation of HS polymerase Ext1 did not affect initial progression of retinal angiogenesis, but it disrupted the pruning of blood vessels and establishment of arterioles and venules. In the absence of retinal HS, blood vessels were also vulnerable to high oxygen tension in early postnatal stages, which can be rescued by exogenous VEGF, consistent with the role of retinal HS in the fine-tuning of VEGF signaling. Furthermore, we observed that the retinal inner limiting membrane (ILM) was disrupted by deletion of Ext1 in a timing specific manner, suggesting that retinal HS is required for the assembly but not the maintenance of the ILM. Lastly, we showed that further deletion of C4st1, a CS sulfation enzyme, did not affect the assembly of the ILM, but aggravated the ILM permeability when combined with Ext1 deletion. These results demonstrated an important role of CS and HS in establishing the barrier function of basement membrane.
Global success in oyster reef restoration despite ongoing recovery debt
Authors: Hemraj Deevesh A. , Bishop Melanie J. , Hancock Boze , Minuti Jay J. , Thurstan Ruth H. , Zu Ermgassen Philine S.E. , Russell Bayden D.
Published: January 2022

Habitat destruction and biodiversity loss from exploitation of ecosystems have led to increased restoration and conservation efforts worldwide. Disturbed ecosystems accumulate a recovery debt – the accumulated loss of ecosystem services - and quantifying this debt presents a valuable tool to develop better ecosystem restoration practices. Here, we quantified the ongoing recovery debt following structural restoration of oyster habitats, one of the most degraded marine ecosystems worldwide. We found that whilst restoration initiates a rapid increase in biodiversity and abundance of 2- to 5-fold relative to unrestored habitat, recovery rate decreases substantially within a few years post-restoration and accumulated global recovery debt persists at >35% per annum. Therefore, while efficient restoration methods will produce enhanced recovery success and minimise recovery debt, potential future coastal development should be weighed up against not just the instantaneous damage to ecosystem functions and services but also the potential for generational loss of services and long-term recovery.
Reversal of obesogenic feeding and hypometabolism by a bifurcating GABAergic neural circuit
Authors: Han Yong , He Yang , Harris Lauren , Xu Yong , Wu Qi
Published: January 2022

Diet-induced obesity is characterized by unsatiated consumption of energy-dense diets and impaired metabolism, whereby anti-obesity effect of the high-level of circulating leptin is unknowingly blunted. Emerging evidence suggests that the leptin receptor (LepR) signaling system, residing within the agouti-related protein (AgRP) neurons of the hypothalamus, critically contributes to obesogenic feeding, nutrient partitioning, and energy metabolism. However, the neural circuit mechanism underlying the leptin-dependent control of obesogenic feeding and energy balance remains largely elusive. Here, we show that two distinct subgroups of LepR-expressing AgRP neurons send non-collateral, GABAergic projections to the dorsomedial hypothalamic nucleus (DMH) and to the medial part of the medial preoptic nucleus (MPO) for the differential control of metabolic homeostasis and obesogenic feeding, respectively. We found that the AgRPLepR-DMH neural circuit plays a significant role in leptin-dependent control of metabolic homeostasis through the α3-containing GABAA receptor signaling on the melanocortin 4 receptor neurons within the DMH (MC4RDMH). In contrast, the AgRPLepR-MPO neural circuit elicits dominant effects on the appetitive response to high-fat diet through the α2-containing GABAA receptors on the MC4RMPO neurons. Consistent with these behavioral results, the post-synaptic GABAA neurons located within the DMH and MPO displayed differentiated firing responses under various feeding and nutrient conditions. Our results demonstrate that these novel GABAergic neural circuits exert differentiated control of metabolic hemostasis and obesogenic feeding via distinct post-synaptic targets of leptin-responsive AgRP neurons. The findings of two genetically and anatomically distinct GABAA receptor signaling pathways within the DMH and MPO would undoubtedly accelerate the development of targeted, individualized, anti-obesity therapy.
USH2A gene mutations in rabbits lead to progressive retinal degeneration and hearing loss
Authors: Nguyen Van Phuc , Song Jun , Prieskorn Diane , Li Yanxiu , Dolan David , Xu Jie , Zhang Jifeng , Jayasundera K Thiran , Raphael Yehoash , Chen Y. Eugene , Paulus Yannis M. , Yang Dongshan
Published: January 2022

Mutations in USH2A gene are responsible for the greatest proportion of hearing and vision loss among individuals with Usher Syndrome (USH) and for autosomal recessive non-syndromic retinitis pigmentosa. Mutations on USH2A exon 13 account for more than 35% of the disease causing USH2A variants including the most prevalence point mutation, c.2299delG, a frameshift mutation. The lack of a clinically relevant animal model has been a bottleneck for the development of therapeutics for USH2A related vision loss. Using CRSPR/Cas9 technology, this study establishes a rabbit line carrying an USH2A frameshift mutation on exon12 (equivalent to human USH2A Exon 13) as a novel mammalian animal model of USH2A. The bi-allelic mutant rabbits exhibit hyper reflective signals in FAF indicating RPE damage and OCT changes indicating photoreceptor degeneration as early as 4 months of age. ERG signals of both rod and cone function were reduced in the USH2A mutant rabbits starting from 7 months old and further decreased at 15-22 months old, indicating progressive retinal photoreceptor degeneration, which is further confirmed by retinal histopathology examination. ABR examination showed moderate to server hearing loss in the USH2A mutant rabbits. These results indicated that disruption of USH2A gene in rabbits is sufficient to induce hearing loss and progressive photoreceptor degeneration. To our knowledge, this is the first mammalian animal model of USH2 which closely recapitulates the phenotype of retinitis pigmentosa in human patients. This study supports the use of rabbits as a clinically relevant animal model to understand the pathogenesis and to develop novel therapeutics for Usher Syndrome.