bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic Profile of Mycobacterium tuberculosis-Specific CD4 T-Cell Responses in People With Advanced Human Immunodeficiency Virus Who Develop Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
Authors: Moseki Raymond M , Barber Daniel L , Du Bruyn Elsa , Shey Muki , Van der Plas Helen , Wilkinson Robert J , Meintjes Graeme , Riou Catherine
Published: October 2022

Background

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (Mtb)-specific CD4 T-cell phenotype and transcription factor profile associated with the development of TB-IRIS.

Methods

We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, activation, transcription factor profile, and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n = 25) and appropriate non-IRIS control patients (n = 18) using flow cytometry.

Results

In the murine model, CD4 T-cell expression of Eomesodermin (Eomes), but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ+CD4 T cells (P = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFNγ+CD4+ T cells showed higher expression of granzyme B in patients with TB-IRIS (P = .026).

Conclusions

Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis-specific IFNγ+CD4 T-cell responses in TB-IRIS patients are differentiated, highly activated, and potentially cytotoxic.
Bone Health and Denosumab Discontinuation in Oncology Populations
Authors: Cheung Yee-Ming Melody , Morgans Alicia , Hamnvik Ole-Petter Riksfjord
Published: October 2022

Managing bone health after denosumab cessation is a commonly encountered challenge. Although the “rebound phenomenon” is generally recognized by endocrinologists in the context of osteoporosis, it is not as widely understood in the context of bone metastases and cancer. This commentary reviews the evidence on the efficacy and safety of various bone health agents in mitigating the “rebound phenomenon” in cancer populations.
Changes in phytoplankton community structure over a century in relation to environmental factors
Authors: Lundsør Elisabeth , Eikrem Wenche , Stige Leif Christian , Engesmo Anette , Stadniczeñko Sandra Gran , Edvardsen Bente
Published: October 2022

Changes in phytoplankton abundance and biomass during the period 1933–2020 were examined by statistical modeling using data from the Inner Oslofjorden phytoplankton database. The phytoplankton abundances increased with eutrophication from 1930s to 1970s, but with the implementation of sewage cleaning measures and a resulting reduction in nutrient releases, the phytoplankton abundance has since then decreased significantly. The onset of the seasonal blooms has started progressively later during the last 15 years, especially the spring bloom. The delayed spring bloom co-occurred with increasing temperature in winter and spring. The diatom biomass decreased more than that of dinoflagellates and other microeukaryotes. The diatom genus Skeletonema dominated the spring bloom and was found to be the key taxa in explaining these changes in abundance and phenology. Extensive summer blooms of the coccolithophore Emiliania huxleyi, which has been characteristic for the inner Oslofjorden, has also gradually decreased during the last decades, along with reducing eutrophication. Dinoflagellates have not had the same reduction in abundance as the other groups. Despite an increasing proportion of dinoflagellates compared with other taxa, there are no clear indications of increased occurrence of toxic algal blooms in inner Oslofjorden. However, the introduction of new “toxin-producing” species may cause concern.
CGL160-mediated recruitment of the coupling factor CF1 is required for efficient thylakoid ATP synthase assembly, photosynthesis, and chloroplast development in Arabidopsis
Authors: Reiter Bennet , Rosenhammer Lea , Marino Giada , Geimer Stefan , Leister Dario , Rühle Thilo
Published: October 2022

Chloroplast ATP synthases consist of a membrane-spanning coupling factor (CFO) and a soluble coupling factor (CF1). It was previously demonstrated that CONSERVED ONLY IN THE GREEN LINEAGE160 (CGL160) promotes the formation of plant CFO and performs a similar function in the assembly of its c-ring to that of the distantly related bacterial Atp1/UncI protein. Here, we show that in Arabidopsis (Arabidopsis thaliana) the N-terminal portion of CGL160 (AtCGL160N) is required for late steps in CF1-CFO assembly. In plants that lacked AtCGL160N, CF1-CFO content, photosynthesis, and chloroplast development were impaired. Loss of AtCGL160N did not perturb c-ring formation, but led to a 10-fold increase in the numbers of stromal CF1 subcomplexes relative to that in the wild type. Co-immunoprecipitation and protein crosslinking assays revealed an association of AtCGL160 with CF1 subunits. Yeast two-hybrid assays localized the interaction to a stretch of AtCGL160N that binds to the DELSEED-containing CF1-β subdomain. Since Atp1 of Synechocystis (Synechocystis sp. PCC 6803) could functionally replace the membrane domain of AtCGL160 in Arabidopsis, we propose that CGL160 evolved from a cyanobacterial ancestor and acquired an additional function in the recruitment of a soluble CF1 subcomplex, which is critical for the modulation of CF1-CFO activity and photosynthesis.
Optimal Corporate Taxation Under Financial Frictions
Authors: Dávila Eduardo , Hébert Benjamin
Published: October 2022

This article studies the optimal design of corporate taxes when firms have private information about future investment opportunities and face financial constraints. A government whose goal is to efficiently raise a given amount of revenue from its corporate sector should attempt to tax unconstrained firms, which value resources inside the firm less than financially constrained firms. We show that a corporate payout tax (a tax on dividends and share repurchases) can both separate constrained and unconstrained firms and raise revenue and is therefore optimal. Our quantitative analysis implies that a revenue-neutral switch from profit taxation to payout taxation would increase the overall value of existing firms and new entrants by $7\%$. This switch could be implemented in the current US tax system by making retained earnings fully deductible.
Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis
Authors: Farooqui Naba , Mohan Arjunmohan , Isik Busra , Goksu Busra B , Thaler Roman , Zhu Xiang Yang , Krier James D , Saadiq Ishran M , Ferguson Christopher M , Jordan Kyra L , Tang Hui , Textor Stephen C , Hickson La Tonya J , van Wijnen Andre J , Eirin Alfonso , Lerman Lilach O , Herrmann Sandra M
Published: October 2022

Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.
Replacing Low-Risk Fungicides with High-Risk Fungicides for Control of Powdery Mildew in a Resistant and Susceptible Summer Squash Cultivar in New Jersey
Authors: Wyenandt Christian A. , Noto A. J. , Ward Daniel L.
Published: October 2022

From 2016 to 2018, six fungicide programs for the control of cucurbit powdery mildew ( Podosphaera xanthii) on a powdery mildew-resistant summer squash ‘Reward F1’ and powdery mildew-susceptible ‘Senator’ were evaluated with an emphasis on reducing the number of chlorothalonil applications. In all 3 years, cucurbit powdery control was greatest (based on lowest area under disease progress curve values) when fungicides with a high risk (HR) for resistance development and with different modes of action were applied in rotation all season or when HR fungicides were applied before and following the onset of disease development, rather than weekly following symptom observation in the susceptible and resistant cultivars. For a disease such as cucurbit powdery mildew, where there are multiple HR fungicides with different modes of action available and where their use could be limited to one or two applications per growing season, these fungicides might be suitable replacements for protectant fungicides in cucurbit crops that have stable genetic resistance to cucurbit powdery mildew.
An Overview of Streptomycin Resistance in Erwinia amylovora from Ohio Apple Orchards
Authors: Jimenez Madrid Alejandra M. , Ivey Melanie L. Lewis
Published: October 2022

Streptomycin is the primary method used to control apple blossom infections caused by Erwinia amylovora in the United States. Improper use of streptomycin can contribute to resistance development in E. amylovora and other epiphytic bacteria in the apple tree. Streptomycin-resistant E. amylovora strains have been reported in several apple production states in the United States; however, the prevalence and genetic basis of E. amylovora resistance in Ohio orchards is reported for the first time in this study. Although most strains isolated from Ohio were sensitive to streptomycin, 7.8% had a resistant phenotype with a minimum inhibitory concentration (MIC) of 500 or 2,500 µg/ml. Resistance was conferred by the linked strA-strB genes on the nonconjugative plasmid pEA29. Only one strain (MIC = 2,500 µg/ml) did not have the linked strA-strB genes or a mutation in codon 43 of rpsL. Epiphytic bacteria, including other species of Erwinia and species of Pantoea, with a resistant phenotype were also recovered from apple blossoms. Epiphytic isolates (44%) were resistant up to 500 µg/ml and 56% up to 2,500 µg/ml. The genetic basis for resistance of a subset of epiphytic bacteria (n = 54) was confirmed to be through the presence of the plasmid transmitted gene pair, strA/strB.
Integrative transcriptome analysis reveals TEKT2 and PIAS2 involvement in diabetic nephropathy
Authors: Li Yuanqing , Lin Hongchun , Shu Shuangshuang , Sun Yuxiang , Lai Weiyan , Chen Wenfang , Hu Zhaoyong , Peng Hui
Published: October 2022

Cell heterogeneity has impeded the accurate interpretation of the bulk transcriptome data from patients with diabetic nephropathy (DN). We performed an analysis by integrating bulk and single‐cell transcriptome datasets to uncover novel mechanisms leading to DN, especially in the podocytes. Microdissected glomeruli and tubules transcriptome datasets were selected from Gene Expression Omnibus (GEO). Then the consistency between datasets was evaluated. The analysis of the bulk dataset and single‐nucleus RNA dataset was integrated to reveal the cell type‐specific responses to DN. The candidate genes were validated in kidney tissues from DN patients and diabetic mice. We compared 4 glomerular and 4 tubular datasets and found considerable discrepancies among datasets regarding the deferentially expressed genes (DEGs), involved signaling pathways, and the hallmark enrichment profiles. Deconvolution of the bulk data revealed that the variations in cell‐type proportion contributed greatly to this discrepancy. The integrative analysis uncovered that the dysregulation of spermatogenesis‐related genes, including TEKT2 and PIAS2, was involved in the development of DN. Importantly, the mRNA level of TEKT2 was negatively correlated with the mRNA levels of NPHS1 (r = −.66, p < .0001) and NPHS2 (r = −.85, p < .0001) in human diabetic glomeruli. Immunostaining confirmed that the expression of TEKT2 and PIAS2 were up‐regulated in podocytes of DN patients and diabetic mice. Knocking down TEKT2 resisted high glucose‐induced cytoskeletal remodeling and down‐regulation of NPHS1 protein in the cultured podocyte. In conclusion, the integrative strategy can help us efficiently use the publicly available transcriptomics resources. Using this approach and combining it with classical research methods, we identified TEKT2 and PIAS2, two spermatogenesis‐related genes involved in the pathogenesis of DN. Furthermore, TEKT2 is involved in this pathogenesis by regulating the podocyte cytoskeleton.
Protective role for C3aR in experimental chronic pyelonephritis
Authors: Zhao Shu‐Juan , Wu Kun‐Yi , Min Xiao‐Yun , Wang Chun‐Xuan , Cao Bo , Ma Ning , Yang Xue‐Ling , Zhu Zhuo‐Ran , Fu Rong‐Guo , Zhou Wuding , Yang Ju‐Rong , Li Ke
Published: October 2022

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar−/−) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2‐C3ar−/−) mice exhibited a similar disease phenotype to global C3ar−/− mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar−/− mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.
Referred sensation location can be altered by a strong heterotopic nociceptive stimulus: implications for clinical pain conditions
Authors: Salis Benedetta , Svensson Peter , Exposto Fernando G.
Published: October 2022

Referred sensations (RS) are a common clinical phenomenon in patients with musculoskeletal pain; however, the underlying mechanisms of RS and implications for diagnosis and management are poorly understood. The location of referral seems to have a preferred site, but studies have suggested it can be redirected to a site of previous injury and pain. However, it is not known if the same phenomenon can occur for a much shorter-lasting painful stimulus in the trigeminal system. The aim of this study was to assess if RS location elicited with standardized palpation of the masseter muscle could be altered following a 10-minute painful infusion of hypertonic saline into the retromolar region. A total of 56 healthy participants participated in this cross-over study performed in 2 sessions separated by 1 hour. At each session, baseline and postinfusion assessments of masseter muscle mechanical sensitivity were performed using 2 different forces (0.5 kg and 2 kg). Between assessments, hypertonic saline (5%) or isotonic saline (control) were continuously infused into the retromolar region. Participants were asked to rate their mechanical sensitivity and any RS they experienced as well as to draw the location of the RS. No difference in mechanical sensitivity or RS frequency was seen after either infusion when compared with before infusion. However, the RS location was displaced on average 1.2 cm between the baseline and postinfusion assessments for the hypertonic saline infusion, which was significantly increased when compared with the isotonic saline infusion which was on average 0.4 cm. These novel findings indicate the potential to modify the location of RS in the trigeminal system following a relatively brief noxious input. Clinicians need to be aware of the possible rerouting of RS in patients with complex orofacial pain.
Consensus and guidelines on lipoprotein(a) – seeing the forest through the trees
Authors: Kronenberg Florian , Mora Samia , Stroes Erik S.G.
Published: October 2022

Purpose of the review

Over the past decade, lipoprotein(a) [Lp(a)] made it to several consensus and guideline documents. This review aims to summarize the literature which underlies the various recommendations and compares recent European and North American consensus and guideline documents of the recent 3–4 years.

Recent findings

Multiple large epidemiological and genetic studies have provided strong evidence for a causal association between Lp(a) concentrations and atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. There is a dose-dependent linear relationship between Lp(a) and ASCVD risk advocating to consider Lp(a) on a continuous scale rather than using thresholds. The best way to implement this in the clinic is by individualizing the Lp(a)-related risk using tools such as the ‘Lp(a) risk calculator’ (http://www.lpaclinicalguidance.com) that takes into account the Lp(a) level in the context of an individual's traditional risk factors and global risk for ASCVD. There is growing agreement across the guidelines regarding the clinical utility of measuring Lp(a) and more recent expert groups advocate for a general screening approach applied to all adults. As long as the cardiovascular outcomes trials for specific Lp(a)-lowering drugs are in progress, the current management of patients with high Lp(a) should focus on the comprehensive management of all other modifiable ASCVD risk factors which can be therapeutically addressed as per guideline recommendations.

Since the contribution of high Lp(a) concentrations to global ASCVD risk has been underestimated in the past, a clear recommendation to measure Lp(a) at least once in a person's lifetime is imperative. Recent expert consensus recommendations provide clinicians with direction on how to manage the excess risk associated with elevated Lp(a) concentration by comprehensive and individualized management of modifiable ASCVD risk factors while awaiting the results of clinical trials of Lp(a) targeted therapies.
Can 18F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy?
Authors: Cheriyalinkal Parambil Badira , Shah Sneha , Prasad Maya , Vora Tushar , Laskar Siddhartha , Khanna Nehal , Qureshi Sajid , Ramadwar Mukta , Kembhavi Seema , Sankaran Hari , Rangarajan Venkatesh , Thakur Sonali , Chinnaswamy Girish
Published: October 2022

Background:

Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS.

Materials and Methods:

Children 15 years old or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors.

Results:

Sixty-three children were eligible (Group III-55, Group IV-8). 18F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) (P=0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) (P=0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) (P=0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) (P=0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) (P=0.011)].

Conclusions:

Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.
No Difference in Mortality and Outcomes After Addition of a Nearby Pediatric Trauma Center
Authors: Naaseh Ariana , Grigorian Areg , Lekawa Michael , Dolich Matthew , Schubl Sebastian , Joe Victor , Nahmias Jeffry
Published: October 2022

Objectives

Previous studies demonstrate that higher volume pediatric trauma centers (PTCs) offer improved outcomes. This study evaluated pediatric trauma volume and outcomes at an existing level I (L-I) adult and level II (L-II) PTC after the addition of a new children's hospital L-II PTC within a 2-mile radius, hypothesizing no difference in mortality and complications.

Methods

A retrospective review of patients aged 14 years or younger presenting to a single adult L-I and L-II PTC was performed. Patients from 2015–2016 (PRE) were compared with patients from 2018–2019 (POST) for mortality and complications using bivariate analyses.

Results

Compared with the PRE cohort, there were less patients in the POST cohort (277 vs 373). Patients in the POST cohort had higher rates of insurance coverage (91.3% vs 78.8%, P < 0.001), self-transportation (7.2% vs 2.7%, P < 0.01), and hospital admission (72.6% and 46.1%, P < 0.001). There was no difference in all complications and mortality (all P > 0.05) between the 2 cohorts.

Conclusions

After opening a second L-II PTC within a 2-mile radius, there was an increase in the rate of admissions and self-transportation to the preexisting L-II PTC. Despite a nearly 26% decrease in pediatric trauma volume, there was no difference in length of stay, hospital complications, or mortality.
Incidence and risk factors for suicide, death due to substance use, and violent/accidental death in people with HIV
Authors: Tusch Erich S. , Ryom Lene , Fursa Olga , Peters Lars , Østergaard Lars , Florence Eric , Edwards Simon , Hoffmann Christian , Sambatakou Helen , Reiss Peter , Shahar Eduardo , Reikvam Dag Henrik , Schmied Brigitte , Paduta Dzmitry , Yakovlev Alexei , Szlávik János , Ranin Jovan , Zilmer Kai , Uždaviniene Vilma , Pelchen-Matthews Annegret , Mocroft Amanda , Reekie Joanne
Published: October 2022

Objective:

Deaths due to suicide, substance use and violence/accident may reflect similar risk factors and overlap in their classification. This study aimed to investigate incidence and risk factors of mortality among people with HIV (PWH) due to these three related causes.

Design:

Prospectively collected data from PWH at least 18 years old and under active follow-up in the EuroSIDA study from 2007 to 2019 were analysed.

Methods:

Cause-specific Cox regression analysis was used to assess risk factors.

Results:

A total of 17 881 participants were included, comprising 149 327 person-years of follow-up (PYFU). Forty participants died by suicide {incidence rate [IR] [95% confidence interval (CI)]: 0.3/1000 PYFU (0.2, 0.4)} 93 from substance use [IR (95% CI): 0.6/1000 PYFU (0.5, 0.8)], and 57 by violence/accident [IR (95% CI): 0.4/1000 PYFU (0.3, 0.5)]. An AIDS diagnosis within the last 12 months was associated with nine-fold increased risk of suicide vs. no history of AIDS [adjusted hazard ratio (aHR): 9.06; 95% CI: 2.07, 39.7]. Male gender was associated with double the risk of violent/accidental death (aHR: 2.28; 95% CI: 1.09, 4.78). PWH in Eastern Europe and those who acquired HIV by injection drug use (IDU) demonstrated a greater risk of death due to substance use or violence/accident.

Conclusions:

The association between a recent diagnosis of AIDS and suicide highlights a critical period for intervention. HIV infection acquired through IDU demonstrated an expected relationship with death due to substance use and violent/accidental deaths. Increased risk of death due to substance use and violence/accident in Eastern Europe demands investigation into specific differences that may drive that association.
VEXAS Syndrome—A Review of Pathophysiology, Presentation, and Prognosis
Authors: Koster Matthew J. , Samec Matthew J. , Warrington Kenneth J.
Published: October 2022

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic mutations in the UBA1 gene resulting in refractory autoinflammatory features, frequently accompanied by cytopenias. Although the prevalence of this syndrome is yet unknown, understanding the clinical phenotype can assist clinicians in prompt recognition of cases among patients with glucocorticoid-responsive but immunosuppressive-resistant inflammatory symptoms. The pathophysiology, clinical presentation, diagnostic methods, treatment, and prognosis of VEXAS are herein reviewed.
High Infertility Rates and Pregnancy Complications in Female Physicians Indicate a Need for Culture Change
Authors: Lai Krista , Garvey Erin M. , Velazco Cristine S. , Gill Manrit , Weidler Erica M. , van Leeuwen Kathleen , Kim Eugene S. , Rangel Erika L. , Grimsby Gwen M.
Published: October 2022

Objective:

This survey study aims to determine the prevalence of pregnancy complications and infertility in female physicians in comparison to the general population. Risk factors, workplace environment, and education are also examined.

Background:

Physicians undertake long training and have stressful work environments during optimal childbearing years. While growing literature indicates increased rates of pregnancy complications and infertility in female surgeons, the prevalence in female physicians of all specialties is unknown.

Methods:

An anonymous, voluntary survey was distributed to female physicians via private physician social media groups. It queried pregnancy demographics and complications, infertility diagnosis and treatment, workplace environment, and prior education on these topics. Results were compared with general population data, between medical and surgical subspecialties, and between physicians who were and were not educated on the risks of delaying pregnancy.

Results:

A total of 4533 female physicians completed the survey. Compared with the general population, female physicians were older at first pregnancy, more often underwent infertility evaluation and treatment, and had higher rates of miscarriage and preterm birth. During training, only 8% of those surveyed received education on the risks of delaying pregnancy. Those who were educated were significantly less likely to experience miscarriage or seek infertility evaluation or treatment. Compared with physicians in nonsurgical specialties, surgeons had fewer children, were older at first pregnancy, had more preterm births and fetal growth problems, and were more likely to be discouraged from starting a family during training and practice.

Conclusions:

Female physicians, particularly surgeons, have a significantly greater incidence of miscarriage, infertility, and pregnancy complications compared with the general population. The culture of medicine and surgery must continue to evolve to better support women with family planning during their training and careers.
The Experiences of Motherhood in Female Surgeons
Authors: Mavedatnia Dorsa , Ardestani Shakiba , Zahabi Sarah , Neocleous Penelope , Madou Edward , Dzioba Agnieszka , Strychowsky Julie E. , Graham M. Elise
Published: October 2022

Objective:

The objective of this study is to systematically synthesize the existing literature on the experiences of motherhood in female surgeons both during surgical training and as staff physicians, to identify knowledge gaps, and to provide recommendations for institutional changes to better support pregnant female surgeons.

Background:

There are disproportionately fewer medical students pursuing surgical specialties, as surgery is often seen as incompatible with childbearing and pregnancy. However, no review has summarized the published literature on the collective experiences of female surgeons in navigating motherhood.

Methods:

Four databases were searched and 1106 abstracts were identified. Forty-two studies were included and a thematic analysis was performed.

Results:

Four themes were identified: path toward motherhood (n=18), realities of motherhood (n=25), medical culture and its impact on career and family life (n=24), and institutional reproductive wellness policies (n=21). Female surgeons are more likely to delay motherhood until after training and have high rates of assisted reproductive technology use. Pregnancy during surgical training is associated with negative perception from peers, pregnancy complications, and scheduling challenges. Maternity leave policies and breastfeeding and childcare facilities are variable and often inadequate. Many female surgeons would agree that greater institutional support would help support women in both their roles as mothers and as surgeons.

Conclusions:

Both female residents and staff surgeons experience significant and unique barriers before, during, and after motherhood that impact their personal and professional lives. Understanding the unique challenges that mothers face when pursuing surgical specialties is critical to achieving gender equity.
Relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex in hypoxic-ischemic brain injury: a pilot study
Authors: Jang Sung Ho , Choi Eun Bi
Published: October 2022

This pilot study investigated the relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex (mPFC SNC) in patients with hypoxic-ischemic brain injury (HI-BI), using diffusion tensor tractography (DTT). Twenty-three patients with HI-BI were recruited into the study based on predefined inclusion criteria. Their consciousness levels were evaluated using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R). Using DTT, the mPFC SNC was reconstructed for each patient. The average of the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and voxel number (VN) for the mPFC SNC in both hemispheres were determined. The GCS score showed moderate positive correlations with the FA value and VN of the mPFC SNC [(FA) r = 0.439; (VN) r = 0.466; P < 0.05], and a strong negative correlation with ADC value (r = −0.531; P < 0.05). The CRS-R score had a strong positive and negative correlation with the FA and ADC values of the mPFC SNC, respectively, [(FA) r = 0.540; (ADC) r = −0.614; P < 0.05] and a moderate positive correlation with the VN of the mPFC SNC (r = 0.488; P < 0.05). We found that the severity of the injury to the mPFC SNC was closely related to the consciousness level. Our results suggest that the mPFC SNC appears to be a neural correlate for the control of consciousness in patients with HI-BI. Based on these results, we believe that the mPFC could be a target area for noninvasive neurostimulation therapies for patients with impaired consciousness following HI-BI.
Impact of transcranial alternating current stimulation on working memory and selective attention in athletes with attention deficit hyperactivity disorder: randomized controlled trial
Authors: Amouzadeh Fereshteh , sheikh Mahmood
Published: October 2022

Objective

The current study aimed to investigate the impact of transcranial alternating current stimulation (tACS) on working memory and selective attention in athletes with attention deficit hyperactivity disorder (ADHD).

Methods

In total 45 athletes with attention deficit hyperactivity disorder were randomly divided into three equal groups (sham, control and experimental groups). All participants in the sham and experimental groups received stimulations on the F3 and SO with a current of (10 HZ) 1 mA for 15 min over 10 sessions (P ≤ 0.05), and after 10 sessions, each group was retested. After 2 weeks, a follow-up test was performed according to the post-test using the Stroop test and N-BACK- (working memory test) to test statistical hypotheses (P ≤ 0.05).

Results

The results of repeated measures analysis of variance revealed that applying tACS proved effective in improving the working memory and selective attention of ADHD athletes.

Conclusions

The study’s findings indicated that the protocol of applying tACS 1 MA with 10 HZ improved the working memory and selective attention of ADHD athletes.
The brain responses to the gating opening mechanism on perceptual and conceptual mismatches in the 1-back matching task
Authors: Yuan Shangqing , Sun Tie , Xiao Feng
Published: October 2022

Objective

Although working memory performance is predicted by the gating mechanism, which is part of attentional control, the attentional control effect on domain-specific matching processes in the 1-back task, is lack of neural evidence.

Method

This study adopted event-related potential (ERP) technique, and employed both perceptual and conceptual matching conditions in a digital 1-back task, requiring to judge whether the current number was perceptually or quantitatively identical to the prior one. Three types of number pairs were adopted: shape/value match (S + V +, e.g., ‘3 3’ or ‘三 三’), shape mismatch/value match (S − V + , e.g., ‘3 三’ or ‘五 5’) and shape/value mismatch (S − V − , e.g., ‘3 5’ or ‘五 三’).

Main results

The ERP results showed that both S − V + and S − V − elicited similar larger P2 amplitudes and longer N2 and P3 latencies than S + V + in both conditions, reflecting the gate opening for perceptual input. Moreover, a task-relevance effect on P3 amplitudes was observed, with a deflection for S − V − in the conceptual matching condition and for S − V + and S − V − in the perceptual matching condition, suggesting that the gating opening mechanism enabled the retrieval of relevant information.

Conclusion

Hence, the matching effect on P3 supported the gating opening mechanism on the matching subprocess underlying the N-back task.
Analyzing Impact of Multimorbidity on Long-Term Outcomes after Emergency General Surgery: A Retrospective Observational Cohort Study
Authors: Rosen Claire B , Roberts Sanford E , Wirtalla Chris J , Ramadan Omar I , Keele Luke J , Kaufman Elinore J , Halpern Scott D , Kelz Rachel R
Published: October 2022

BACKGROUND:

Little is known about the impact of multimorbidity on long-term outcomes for older emergency general surgery patients.

STUDY DESIGN:

Medicare beneficiaries, age 65 and older, who underwent operative management of an emergency general surgery condition were identified using Centers for Medicare & Medicaid claims data. Patients were classified as multimorbid based on the presence of a Qualifying Comorbidity Set (a specific combination of comorbid conditions known to be associated with increased risk of in-hospital mortality in the general surgery setting) and compared with those without multimorbidity. Risk-adjusted outcomes through 180 days after discharge from index hospitalization were calculated using linear and logistic regressions.

RESULTS:

Of 174,891 included patients, 45.5% were identified as multimorbid. Multimorbid patients had higher rates of mortality during index hospitalization (5.9% vs 0.7%, odds ratio [OR] 3.05, p < 0.001) and through 6 months (17.1% vs 3.4%, OR 2.33, p < 0.001) after discharge. Multimorbid patients experienced higher rates of readmission at 1 month (22.9% vs 11.4%, OR 1.48, p < 0.001) and 6 months (38.2% vs 21.2%, OR 1.48, p < 0.001) after discharge, lower rates of discharge to home (42.5% vs 74.2%, OR 0.52, p < 0.001), higher rates of discharge to rehabilitation/nursing facility (28.3% vs 11.3%, OR 1.62, p < 0.001), greater than double the use of home oxygen, walker, wheelchair, bedside commode, and hospital bed (p < 0.001), longer length of index hospitalization (1.33 additional in-patient days, p < 0.001), and higher costs through 6 months ($5,162 additional, p < 0.001).

CONCLUSIONS:

Older, multimorbid patients experience worse outcomes, including survival and independent function, after emergency general surgery than nonmultimorbid patients through 6 months after discharge from index hospitalization. This information is important for setting recovery expectations for high-risk patients to improve shared decision-making.
Developmental and mechanical roles of Reichert's membrane in mouse embryos
Authors: Matsuo Isao , Kimura-Yoshida Chiharu , Ueda Yoko
Published: October 2022

Embryonic development and growth in placental mammals proceeds
in utero
with the support of exchanges of gases, nutrients and waste products between maternal tissues and offspring. Murine embryos are surrounded by several extraembryonic membranes, parietal and visceral yolk sacs, and amnion in the uterus. Notably, the parietal yolk sac is the most outer membrane, consists of three layers, trophoblasts and parietal endoderm (PaE) cells, and is separated by a thick basal lamina termed Reichert's membrane (RM). RM is composed of extracellular matrix (ECM) initially formed as the basement membrane of the trophectoderm of pre-implanted embryos and followed by the heavy deposition of ECM mainly produced in PaE cells of post-implanted embryos. In addition to the physiological roles of RM, such as gas and nutrient exchange, it also plays a crucial role in cushioning and dispersing intrauterine pressures exerted on embryos for normal egg-cylinder morphogenesis. Mechanistically, such intrauterine pressures generated by uterine smooth muscle contractions appear to be involved in the elongation of the egg-cylinder shape, along with primary axis formation, as an important biomechanical element
in utero
. This review focuses on our current views of the roles of RM in properly buffering intrauterine mechanical forces for mouse egg-cylinder morphogenesis.

This article is part of the theme issue ‘Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom’.
Stay on the road: from germ cell specification to gonadal colonization in mammals
Authors: Roelen Bernard A. J. , Chuva de Sousa Lopes Susana M.
Published: October 2022

The founder cells of the gametes are primordial germ cells (PGCs). In mammals, PGCs are specified early during embryonic development, at the boundary between embryonic and extraembryonic tissue, long before their later residences, the gonads, have developed. Despite the differences in form and behaviour when differentiated into oocytes or sperm cells, in the period between specification and gonadal colonization, male and female PGCs are morphologically indistinct and largely regulated by similar mechanisms. Here, we compare different modes and mechanisms that lead to the formation of PGCs, putting in context protocols that are in place to differentiate both human and mouse pluripotent stem cells into PGC-like cells. In addition, we review important aspects of the migration of PGCs to the gonadal ridges, where they undergo further sex-specific differentiation. Defects in migration need to be effectively corrected, as misplaced PGCs can become tumorigenic. Concluding, a combination of
in vivo
studies and the development of adequate innovative
in vitro
models, ensuring both robustness and standardization, are providing us with the tools for a greater understanding of the first steps of gametogenesis and to develop disease models to study the origin of germ cell tumours.

This article is part of the theme issue ‘Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom’.
Mesothelial fusion mediates chorioallantoic membrane formation
Authors: Nagai Hiroki , Tanoue Yuki , Nakamura Tomonori , Chan Christopher J. J. , Yamada Shigehito , Saitou Mitinori , Fukuda Takaichi , Sheng Guojun
Published: October 2022

In amniotic vertebrates (birds, reptiles and mammals), an extraembryonic structure called the chorioallantoic membrane (CAM) functions as respiratory organ for embryonic development. The CAM is derived from fusion between two pre-existing membranes, the allantois, a hindgut diverticulum and a reservoir for metabolic waste, and the chorion which marks the embryo's external boundary. Modified CAM in eutherian mammals, including humans, gives rise to chorioallantoic placenta. Despite its importance, little is known about cellular and molecular mechanisms mediating CAM formation and maturation. In this work, using the avian model, we focused on the early phase of CAM morphogenesis when the allantois and chorion meet and initiate fusion. We report here that chicken chorioallantoic fusion takes place when the allantois reaches the size of 2.5–3.0 mm in diameter and in about 6 hours between E3.75 and E4. Electron microscopy and immunofluorescence analyses suggested that before fusion, in both the allantois and chorion, an epithelial-shaped mesothelial layer is present, which dissolves after fusion, presumably by undergoing epithelial–mesenchymal transition. The fusion process
per se
, however, is independent of allantoic growth, circulation, or its connection to the developing mesonephros. Mesoderm cells derived from the allantois and chorion can intermingle post-fusion, and chorionic ectoderm cells exhibit a specialized sub-apical intercellular interface, possibly to facilitate infiltration of allantois-derived vascular progenitors into the chorionic ectoderm territory for optimal oxygen transport. Finally, we investigated chorioallantoic fusion-like process in primates, with limited numbers of archived human and fresh macaque samples. We summarize the similarities and differences of CAM formation among different amniote groups and propose that mesothelial epithelial–mesenchymal transition mediates chorioallantoic fusion in most amniotic vertebrates. Further study is needed to clarify tissue morphogenesis leading to chorioallantoic fusion in primates. Elucidating molecular mechanisms regulating mesothelial integrity and epithelial-mesenchymal transition will also help understand mesothelial diseases in the adult, including mesothelioma, ovarian cancer and fibrosis.

This article is part of the theme issue ‘Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom’.
Acuticoccus kalidii sp. nov., a 1-aminocyclopropane-1-carboxylate (ACC) deaminase-producing endophyte from a root of Kalidium cuspidatum
Authors: Tian Jing , Xu Lian , Zhang Xu , Sun Ji-Quan
Published: October 2022

A 1-aminocyclopropane-1-carboxylate (ACC) deaminase-producing, Gram-stain-negative, strictly aerobic, non-motile, yellow-reddish, oval-shaped bacterial strain, designated M5D2P5T, was isolated from a root of Kalidium cuspidatum, in Tumd Right Banner, Inner Mongolia, PR China. M5D2P5T grew at 10–40 °C (optimum 30–35 °C), pH 5.0–10.0 (optimum pH 8.0) and with 0–7% NaCl (optimum 3.0 %). The strain was positive for catalase and oxidase. The phylogenetic trees based on 16S rRNA gene sequences indicated that M5D2P5T clustered with

Acuticoccus yangtzensis

JL1095T, and shared 98.0, 97.3, 97.2, 96.9 and less than 96.9 % 16S rRNA gene similarities to

A. yangtzensis

JL1095T,

Acuticoccus mangrovi

B2012T,

Acuticoccus sediminis

PTG4-2T,

Acuticoccus kandeliae

J103T, and all the other type strains, respectively. However, the phylogenomic tree showed it clustered with

A. kandeliae

J103T. M5D2P5T contained Q-10 as the major respiratory quinone, as well as two minor respiratory quinones, Q-7 and Q-8. Its major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified phospholipid, an unidentified glycolipid, and four unidentified lipids. The genomic DNA G+C content was 66.5 %. The digital DNA–DNA hybridization score and the average nucleotide identity based on blast values of M5D2P5T to

A. yangtzensis

JL1095T,

A. kandeliae

J103T,

A. mangrovi

B2012T, and

A. sediminis

PTG4-2T, were 20.8, 23.7, 20.7, and 21.5 %, and 73.3, 79.5, 74.4, and 73.7 %, respectively. The phylogenetic and phenotypic characteristics allowed the discrimination of M5D2P5T from its phylogenetic relatives. The novel species Acuticoccus kalidii sp. nov. is therefore proposed, and the type strain is M5D2P5T (=CGMCC 1.19149T=KCTC 92132T).
A wide foodomics approach coupled with metagenomics elucidates the environmental signature of Protected Geographical Indication potatoes
Authors: Boutsika Anastasia , Michailidis Michail , Ganopoulou Maria , Dalakouras Athanasios , Skodra Christina , Xanthopoulou Aliki , Stamatakis George , Samiotaki Martina , Tanou Georgia , Moysiadis Theodoros , Angelis Lefteris , Bazakos Christos , Molassiotis Athanassios , Nianiou-Obeidat Irini , Mellidou Ifigeneia , Ganopoulos Ioannis
Published: October 2022

The term “terroir” has been widely employed to link differential geographic phenotypes with sensorial signatures of agricultural food products, influenced by agricultural practices, soil type and climate. Nowadays, the Geographical Indications labeling has been developed to safeguard the quality of plant-derived food that is linked to a certain terroir and is generally considered as an indication of superior organoleptic properties and phytochemical profile. As the dynamics of agroecosystems are highly intricate, consisting of tangled networks of interactions between plants, microorganisms, and the surrounding environment, the recognition of the key molecular components of terroir fingerprinting remains a great challenge to protect both the origin and the safety of food commodities. Furthermore, the contribution of microbiome as a potential driver of the terroir signature has been underestimated until recently. Herein, we present a first comprehensive view of the multi-omic landscape related to transcriptome, proteome, epigenome, and metagenome of the popular Protected Geographical Indication potatoes of Naxos.