bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Bile Acid Composition Changes Following Faecal Microbiota Transplantation for Clostridioides difficile Infection in Children With and Without Underlying Inflammatory Bowel Disease
Authors: Chen Lea Ann , Oliva-Hemker Maria , Radin Arielle , Weidner Melissa , O’Laughlin Brynn D , Sears Cynthia L , Javitt Norman B , Hourigan Suchitra K
Published: March 2023

Background and Aims

Faecal microbiota transplant [FMT] is effective in treating recurrent Clostridioides difficile infection [CDI] and restores gut microbiota composition. This is unlikely to account for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease [IBD].

Methods

Eight children received FMT; five had underlying IBD. Primary and secondary faecal bile acids were measured by liquid chromatography–mass spectrometry in recipients [pre-FMT and longitudinally post-FMT for up to 6 months] and donors.

Results

Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. Whereas gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalisation of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels.

Conclusions

The differences in bile acid profiles compared with gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts, with longitudinal sampling to understand the mechanisms of FMT effectiveness.
Direct oral anticoagulants versus vitamin K antagonists in the first 3 months after bioprosthetic valve replacement: a systematic review and meta-analysis
Authors: Eikelboom Rachel , Whitlock Richard P , Muzaffar Raveen , Lopes Renato D , Siegal Deborah , Schulman Sam , Belley-Côté Emilie P
Published: March 2023

OBJECTIVES

We conducted a systematic review and meta-analysis of randomized controlled trials comparing direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in the first 90 days after bioprosthetic valve implantation.

METHODS

We systematically searched Embase, Medline and CENTRAL. We screened titles, abstracts and full texts, extracted data and assessed the risk of bias in duplicate. We pooled data using the Mantel–Haenzel method and random effects modelling. We conducted subgroup analyses based on the type of valve (transcatheter versus surgical) and timing of initiation of anticoagulation (<7 vs >7 days after valve implantation). We assessed the certainty of evidence using the Grading of Recommendations, Assessments, Development and Evaluation approach.

RESULTS

We included 4 studies of 2284 patients with a median follow-up of 12 months. Two studies examined transcatheter valves (1877/2284 = 83%) and 2 examined surgical valves (407/2284 = 17%). We found no statistically significant differences between DOACs and VKAs with regard to thrombosis, bleeding, death or subclinical valve thrombosis. However, there was a subgroup trend towards more bleeding with DOACs when initiated within 7 days of valve implantation.

CONCLUSIONS

In the existing randomized literature on DOACs versus VKAs in the first 90 days after bioprosthetic valve implantation, there appears to be no difference with regard to thrombosis, bleeding or death. Interpretation of the data is limited by small numbers of events and wide confidence intervals. Future studies should focus on surgical valves and should include long-term follow-up to assess any potential impact of randomized therapy on valve durability.
Autograft reoperations after the Ross procedure
Authors: Abeln Karen B , Ehrlich Tristan , Souko Idriss , Brenner Friederike , Schäfers Hans-Joachim
Published: March 2023

OBJECTIVES

After a Ross procedure, autograft failure can occur. At reoperation, repair of the autograft preserves the advantages of the Ross procedure. The aim of this retrospective study was to assess mid-term results after reoperation of a failed autograft.

METHODS

Between 1997 and 2022, 30 consecutive patients (83% male; age 41 ± 11 years) underwent autograft reintervention between 60 days and 24 years (median 10 years) after a Ross procedure. The initial technique varied, full-root replacement (n = 25) being the most frequent. The indication for reoperation was isolated autograft regurgitation (n = 7), root dilatation (>43 mm) with (n = 17) or without (n = 2) autograft regurgitation, mixed dysfunction (n = 2) and endocarditis (n = 2). In 4 instances, the valve was replaced by valve (n = 1) or combined valve and root replacement (n = 3). Valve-sparing procedures consisted of isolated valve repair (n = 7) or root replacement (n = 19), and tubular aortic replacement. Cusp repair was performed in all but 2. Mean follow-up was 5.4 ± 6 years (35 days to 24 years).

RESULTS

Mean cross-clamp and perfusion times were 74 ± 26 and 132 ± 64 min. There were 2 perioperative deaths (7%; both valve replacement) and 2 patients died late (32 days to 1.2 years postoperatively). Freedom from cardiac death at 10 years was 96% after valve repair and 50% after replacement. Two patients required reoperation (1.68 and 16 years) following repair. One underwent valve replacement for cusp perforation, the other, root remodelling for dilatation. Freedom from autograft reintervention at 15 years was 95%.

CONCLUSIONS

Autograft reoperations after the Ross procedure can be performed as valve-sparing operations in the majority of cases. With valve-sparing, long-term survival and freedom from reoperation are excellent.
Utopian Spaces and Dystopian Subjects in Ray Loriga’s Urban Fiction
Authors: Almanza-Gálvez Carla
Published: March 2023

This article examines the interplay between socio-spatial environments, social control mechanisms and alienated subjectivities in the urban fiction of Spanish author Ray Loriga. It analyses how the search for an urban utopia intertwines in Loriga’s work with an attention to processes of commodification, consumerism and social control. These represented processes are read, in turn, as driving the dystopian production of dehumanized, objectified individual subjects. Focusing principally on the futuristic cities of Loriga’s 1999 novel Tokio ya no nos quiere, the discussion also draws on relevant elements of two subsequent works – El hombre que inventó Manhattan (2004) and Rendición (2017).
Regulation of the hypertonic stress response by the 3′ mRNA cleavage and polyadenylation complex
Authors: Urso Sarel J , Sathaseevan Anson , Brent Derry W , Lamitina Todd
Published: March 2023

Maintenance of osmotic homeostasis is one of the most aggressively defended homeostatic set points in physiology. One major mechanism of osmotic homeostasis involves the upregulation of proteins that catalyze the accumulation of solutes called organic osmolytes. To better understand how osmolyte accumulation proteins are regulated, we conducted a forward genetic screen in Caenorhabditis elegans for mutants with no induction of osmolyte biosynthesis gene expression (Nio mutants). The nio-3 mutant encoded a missense mutation in cpf-2/CstF64, while the nio-7 mutant encoded a missense mutation in symk-1/Symplekin. Both cpf-2 and symk-1 are nuclear components of the highly conserved 3′ mRNA cleavage and polyadenylation complex. cpf-2 and symk-1 block the hypertonic induction of gpdh-1 and other osmotically induced mRNAs, suggesting they act at the transcriptional level. We generated a functional auxin-inducible degron (AID) allele for symk-1 and found that acute, post-developmental degradation in the intestine and hypodermis was sufficient to cause the Nio phenotype. symk-1 and cpf-2 exhibit genetic interactions that strongly suggest they function through alterations in 3′ mRNA cleavage and/or alternative polyadenylation. Consistent with this hypothesis, we find that inhibition of several other components of the mRNA cleavage complex also cause a Nio phenotype. cpf-2 and symk-1 specifically affect the osmotic stress response since heat shock-induced upregulation of a hsp-16.2::GFP reporter is normal in these mutants. Our data suggest a model in which alternative polyadenylation of 1 or more mRNAs is essential to regulate the hypertonic stress response.
JC Polyomavirus Modifies the Expression of Human microRNAs in Progressive Multifocal Leukoencephalopathy Brain
Authors: Honkimaa Anni , Suppula Joni , Tynninen Olli , Saarela Mika , Liimatainen Hanna , Laine Pia , Auvinen Petri , Auvinen Eeva
Published: March 2023

Progressive multifocal leukoencephalopathy (PML) is a severe neurological condition caused by reactivation of JC polyomavirus (JCPyV) in immunosuppression. Asymptomatic JCPyV persists in peripheral tissues. Upon reactivation, neurotropic rearrangements may emerge, and the virus gains access to the brain. To assess the mechanisms of PML pathogenesis, brain tissue material from PML patients was collected for small RNA sequencing. Upregulation of 8 microRNAs (miRNAs) in PML brain was validated using quantitative microRNA polymerase chain reaction (PCR). Bioinformatics tools were utilized to identify major associations of the upregulated miRNAs: neuroinflammation and blood-brain barrier disruption. The results indicate involvement of human miRNA regulation in PML pathogenesis.
Bridging the Gap in a Changing World: New Opportunities and Challenges for Engaging Practitioners and the Public
Authors: Tama Jordan , Barma Naazneen H , Durbin Brent , Goldgeier James , Jentleson Bruce W
Published: March 2023

In recent years, an array of initiatives has sought to bridge widely recognized gaps separating international studies scholars from policymakers and the public. While such gaps persist, changes in society, the media, and academia have altered the context for scholars seeking to make their research known to public and policy communities. On the one hand, the emergence on the public agenda of new policy concerns, proliferation of public-facing outlets seeking to feature scholarly expertise, and growing attention to diversity and inclusion have reduced some of the barriers to gap-bridging work. On the other hand, tenure and promotion standards continue to place limited weight on public engagement, political attacks on experts have raised new barriers to bridging, and social media often serve as sites of discrimination and harassment. We take stock of these shifts and use a scenario exercise to consider how the landscape for bridging the gap might evolve further in the years ahead. Focusing on potential changes in research funding models and the relationship between international studies scholarship and geopolitics, we highlight new bridging opportunities and challenges that may emerge over the next decade.
(Mis)Led by an Outsider: Abusive Supervision, Disengagement, and Silence in Politicized Bureaucracies
Authors: Story Joana , Lotta Gabriela , Tavares Gustavo M
Published: March 2023

Employing loyal external appointees has been identified as a key strategy used by incumbents to gain control over the state bureaucracy. This phenomenon is known as politicization and has been associated with democratic backsliding. Frequently, career civil servants perceive these appointees as illegitimate outsiders, leaders whose main objective is to ensure political compliance rather than advance the organization’s mission. In this study, we explore how civil servants interpret the presence of outside leaders in their organizations in the context of politicization and how this influences their job attitudes and behaviors. We use a mixed methods exploratory sequential design to examine a recent case of politicization in environmental agencies in Brazil. First, we interviewed 25 civil servants who reported an environment of abuse, fear, disengagement, and alienation due to the actions of outside leaders. We identified silence (both defensive and acquiescent) as a key outcome of this process. We extended and confirmed these findings with a quantitative study using a new sample of 255 civil servants. This second study allowed us to test the relationship between the variables identified in the qualitative analysis. Our combined findings indicate that politicization may reduce the effectiveness and capability of public agencies not only because some external appointees lack competence or a commitment the organization’s mission (as suggested by previous studies), but also because their behaviors and decisions can have a significant negative impact on civil servants’ job attitudes and behaviors.
Clinical Educators’ Teaching Approaches and Attributes in Laboratory Medicine
Authors: Phillips Heather L , Jator Eleanor K , Latchem Shelley R , Catalano Timothy A
Published: March 2023

The quality of clinical experiences for students in health care professions relies heavily on clinical educators. Hence the quest to be informed on qualities that make great clinical educators in medical laboratory professions as well as teaching methods. A 48-question survey was developed, validated, and distributed to laboratory professionals in the American Society for Clinical Pathology database. Four questions pertaining to teaching and evaluation as well as clinical educators’ attributes were evaluated in the study. Responses were analyzed using the Statistical Package for the Social Sciences. Descriptive statistics were performed with the P value set at .05. The results revealed that communication and motivation to teach were most valued among clinical educators and empathy was the least valued attribute. Educators reported on different approaches to teaching and evaluating students. Clinical educators could benefit from training that highlights these attributes and teaching methods for great clinical experiences both for educators and students.
DNA supercoiling-induced shapes alter minicircle hydrodynamic properties
Authors: Waszkiewicz Radost , Ranasinghe Maduni , Fogg Jonathan M , Catanese Daniel J , Ekiel-Jeżewska Maria L , Lisicki Maciej , Demeler Borries , Zechiedrich Lynn , Szymczak Piotr
Published: March 2023

DNA in cells is organized in negatively supercoiled loops. The resulting torsional and bending strain allows DNA to adopt a surprisingly wide variety of 3-D shapes. This interplay between negative supercoiling, looping, and shape influences how DNA is stored, replicated, transcribed, repaired, and likely every other aspect of DNA activity. To understand the consequences of negative supercoiling and curvature on the hydrodynamic properties of DNA, we submitted 336 bp and 672 bp DNA minicircles to analytical ultracentrifugation (AUC). We found that the diffusion coefficient, sedimentation coefficient, and the DNA hydrodynamic radius strongly depended on circularity, loop length, and degree of negative supercoiling. Because AUC cannot ascertain shape beyond degree of non-globularity, we applied linear elasticity theory to predict DNA shapes, and combined these with hydrodynamic calculations to interpret the AUC data, with reasonable agreement between theory and experiment. These complementary approaches, together with earlier electron cryotomography data, provide a framework for understanding and predicting the effects of supercoiling on the shape and hydrodynamic properties of DNA.
A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA
Authors: Cadoni Enrico , De Paepe Lessandro , Colpaert Gertjan , Tack Ruben , Waegeman Dries , Manicardi Alex , Madder Annemieke
Published: March 2023

The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions.
Rethinking Screening Intensity in Terms of Reducing Prevalence or Increasing Selection Pressure for the Emergence of Resistant Gonorrhea: A Modeling Study of Men Who Have Sex With Men in Belgium
Authors: Tsoumanis Achilleas , Van Dijck Christophe , Hens Niel , Kenyon Chris
Published: March 2023

Background

Neisseria gonorrhoeae (NG) has developed antimicrobial resistance (AMR) to multiple classes of antibiotics. While treatment of symptomatic NG in groups, such as men who have sex with men (MSM), is crucial, screening programs targeting asymptomatic NG cases may contribute to excessive antibiotic exposure of the population and thus to the emergence of gonococcal AMR. Our primary aim was to assess if intense screening could promote AMR in NG.

Methods

We built a network-based model of NG transmission dynamics among MSM in Belgium to estimate the prevalence of NG in the population and the risk of AMR. The model simulates daily transmission of NG among 3 anatomical sites in a population of 10 000 MSM, grouped as low risk or high risk, over 10 years. The effect of group-wise variation in treatment efficacy levels and screening intensities on NG prevalence and cumulative risk of AMR emergence was evaluated.

Results

Increasing screening intensity in the low-risk MSM had little effect on NG prevalence. An inverse correlation between screening intensity in the high-risk group and both NG prevalence and the risk for azithromycin resistance was observed, irrespective of the screening intensity in the low-risk group. High-risk MSM were at higher risk for azithromycin-resistant NG in all screening intensity and treatment efficacy scenarios, compared to low-risk MSM.

Conclusions

Our results suggest that intensive screening in the low-risk population has little impact on prevalence but may increase the probability of AMR emerging. In contrast, intensive screening in the high-risk population reduces both the prevalence of NG and macrolide resistance.
Successful treatment of Hidradenitis Suppurativa with tofacitinib: two cases and a review of the literature
Authors: Sadeghzadeh Bazargan Afsaneh , Pashaei Arezoo , Goodarzi Azadeh
Published: March 2023

Hidradenitis Suppurativa (HS) is a major public health challenge affecting people globally, which is painful and the hard lumps under the skin are prone to infection. We aimed to investigate whether tofacitinib can help people with HS in a safe and effective way. In this study, we report two cases diagnosed with HS. Tofacitinib was used as a part of the treatment plan. The first patient received 5 mg of tofacitinib twice daily, 36 weeks, and the second one for 24 weeks. Clinical outcomes are described. The efficacy of tofacitinib in HS was confirmed in our study. The clinical characteristics of the patients improved after receiving tofacitinib. Lesions discharge significantly reduced, particularly in the axillary area. Tofacitinib may be useful as an adjuvant therapy when used in combination with other treatments. Further research in this area is required to improve our understanding of treatment with tofacitinib at HS.
A case in which immunohistochemistry was useful in the diagnosis of gastric metastasis of invasive lobular carcinoma
Authors: Jinushi Ryuhei , Sato Ryo , Kawasaki Tomonori , Ryozawa Shomei
Published: March 2023

Metastatic breast cancer can spread to the bone, brain, liver and lung. However, metastasis to the stomach is rare. Gastric metastasis mostly presents within 10 years from the diagnosis of the primary breast cancer. We present a rare case of gastric metastasis occurring 20 years after mastectomy, diagnosed through immunohistochemistry.
A necrotic primary central nervous system lymphoma in immunocompetent patient with MYC and BCL6 rearrangements (double-hit lymphoma): a case report
Authors: Khalil Nabil C N , Iwaiwi Bashaer Imad , Hammad Shurooq , Jobran Afnan W M , Itkaidek Saeed , Lahham Elias Edward
Published: March 2023

Primary Central Nervous System Lymphoma (PCNSL) is a rare, aggressive extranodal non-Hodgkin lymphoma. It is critical to get a diagnosis and start therapy as soon as possible to improve clinical results. Despite a new medicinal strategy that has increased survivability, the survival rate is still quite low. This report presents a new case of PCNSL that appears in an immunocompetent patient with two different rare genetic rearrangements and a necrotic histological appearance.
Twelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis
Authors: Meza Luis , Zengin Zeynep , Salgia Sabrina , Malhotra Jasnoor , Karczewska Ewa , Dorff Tanya , Tripathi Abhishek , Ely Jennifer , Kelley Erin , Mead Heather , Hsu JoAnn , Dizman Nazli , Salgia Nicholas , Chawla Neal , Chehrazi-Raffle Alex , Muddasani Ramya , Govindarajan Ameish , Rock Adam , Liu Sandy , Salgia Ravi , Trent Jeffrey , Altin John , Pal Sumanta K
Published: March 2023

Background

Vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had a transformative impact on morbidity and mortality. However, the long-term impact of vaccination on patients with genitourinary cancers is currently unknown.

Materials and Methods

This study aimed to assess seroconversion rates in patients with genitourinary cancers receiving COVID-19 vaccination. Patients with prostate cancer, renal cell carcinoma, or urothelial cancer who had not been vaccinated for COVID-19 were included. Blood samples were obtained at baseline and after 2, 6, and 12 months of one dose of an FDA-approved COVID-19 vaccine. Antibody titer analysis was performed using the SCoV-2 Detect IgG ELISA assay, and the results were reported as immune status ratio (ISR). A paired t-test was used for comparison of ISR values between timepoints. In addition, T-cell receptor (TCR) sequencing was performed to assess for differences in TCR repertoire 2 months after vaccination.

Results

Out of 133 patients enrolled, 98 baseline blood samples were collected. At 2-, 6-, and 12-month time points 98, 70, and 50 samples were collected, respectively. Median age was 67 (IQR, 62-75), with the majority of patients diagnosed with prostate (55.1%) or renal cell carcinoma (41.8%). Compared to baseline (0.24 [95% CI, 0.19-0.31]) a significant increase in the geometric mean ISR values was observed at the 2-month timepoint (5.59 [4.76-6.55]) (P < .001). However, at the 6-month timepoint, a significant decrease in the ISR values was observed (4.66 [95% CI, 4.04-5.38]; P < .0001). Notably, at the 12-month timepoint, the addition of a booster dose resulted in an absolute increase in the ISR values compared to those who did not receive a booster dose (P = .04).

Conclusions

Only a minority of patients with genitourinary cancers did not ultimately achieve satisfactory seroconversion after receiving commercial COVID-19 vaccination. Cancer type or treatment rendered did not appear to affect the immune response mounted after vaccination.
Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy
Authors: Burke John M , Liu Nicholas , Yu Kristina S , Fanale Michelle A , Surinach Andy , Flores Carlos , Lisano Julie , Phillips Tycel
Published: March 2023

Background

Since Food and Drug Administration approval of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A + CHP) as initial therapy for previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL), there has been limited research on real-world patient characteristics, treatment patterns, and clinical outcomes.

Methods

We retrospectively analyzed claims of patients with PTCL treated with frontline A + CHP or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) using the Symphony Health Solutions database. Adults with International Classification of Diseases-9/10 PTCL diagnosis codes who initiated A + CHP or CHOP between November 2018 and July 2021 were included. A 1:1 propensity score matching analysis was performed that adjusted for potential confounders between groups.

Results

A total of 1344 patients were included (A + CHP, n = 749; CHOP, n = 595). Before matching, 61% were men; median age at index was 62 (A + CHP) and 69 (CHOP) years. The most common A + CHP-treated PTCL subtypes were systemic anaplastic large cell lymphoma (sALCL; 51%), PTCL-not otherwise specified (NOS; 30%), and angioimmunoblastic T-cell lymphoma (AITL; 12%); the most common CHOP-treated subtypes were PTCL-NOS (51%) and AITL (19%). After matching, similar proportions of patients treated with A + CHP and CHOP received granulocyte colony-stimulating factor (89% vs. 86%, P = .3). Fewer patients treated with A + CHP received subsequent therapy than CHOP overall (20% vs. 30%, P < .001) and specifically with the sALCL subtype (15% vs. 28%, P = .025).

Conclusions

Characteristics and management of this real-world PTCL population who were older and had a higher comorbidity burden than that in the ECHELON-2 trial demonstrate the importance of retrospective studies when assessing the impact of new regimens on clinical practice.
Synergistic action of the Arabidopsis spliceosome components PRP39a and SmD1b in promoting posttranscriptional transgene silencing
Authors: Bazin Jérémie , Elvira-Matelot Emilie , Blein Thomas , Jauvion Vincent , Bouteiller Nathalie , Cao Jun , Crespi Martin D , Vaucheret Hervé
Published: March 2023

Besides regulating splicing, the conserved spliceosome component SmD1 (Small nuclear ribonucleoprotein D1)b promotes posttranscriptional silencing of sense transgenes (S-PTGS [post-transcriptional genesilencing]). Here, we show that the conserved spliceosome component PRP39 (Pre-mRNA-processing factor 39)a also plays a role in S-PTGS in Arabidopsis thaliana. However, PRP39a and SmD1b actions appear distinct in both splicing and S-PTGS. Indeed, RNAseq-based analysis of expression level and alternative splicing in prp39a and smd1b mutants identified different sets of deregulated transcripts and noncoding RNAs. Moreover, double mutant analyses involving prp39a or smd1b and RNA quality control (RQC) mutants revealed distinct genetic interactions for SmD1b and PRP39a with nuclear RQC machineries, suggesting nonredundant roles in the RQC/PTGS interplay. Supporting this hypothesis, a prp39a smd1b double mutant exhibited enhanced suppression of S-PTGS compared to the single mutants. Because the prp39a and smd1b mutants (i) showed no major changes in the expression of PTGS or RQC components or in small RNA production and (ii) do not alter PTGS triggered by inverted-repeat transgenes directly producing dsRNA (IR-PTGS), PRP39a, and SmD1b appear to synergistically promote a step specific to S-PTGS. We propose that, independently from their specific roles in splicing, PRP39a and SmD1b limit 3′-to-5′ and/or 5′-to-3′ degradation of transgene-derived aberrant RNAs in the nucleus, thus favoring the export of aberrant RNAs to the cytoplasm where their conversion into double-stranded RNA (dsRNA) initiates S-PTGS.
Chlamydomonas mutants lacking chloroplast TRIOSE PHOSPHATE TRANSPORTER3 are metabolically compromised and light sensitive
Authors: Huang Weichao , Krishnan Anagha , Plett Anastasija , Meagher Michelle , Linka Nicole , Wang Yongsheng , Ren Bijie , Findinier Justin , Redekop Petra , Fakhimi Neda , Kim Rick G , Karns Devin A , Boyle Nanette , Posewitz Matthew C , Grossman Arthur R
Published: March 2023

Modulation of photoassimilate export from the chloroplast is essential for controlling the distribution of fixed carbon in the cell and maintaining optimum photosynthetic rates. In this study, we identified chloroplast TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR 2 (CreTPT2) and CreTPT3 in the green alga Chlamydomonas (Chlamydomonas reinhardtii), which exhibit similar substrate specificities but whose encoding genes are differentially expressed over the diurnal cycle. We focused mostly on CreTPT3 because of its high level of expression and the severe phenotype exhibited by tpt3 relative to tpt2 mutants. Null mutants for CreTPT3 had a pleiotropic phenotype that affected growth, photosynthetic activities, metabolite profiles, carbon partitioning, and organelle-specific accumulation of H2O2. These analyses demonstrated that CreTPT3 is a dominant conduit on the chloroplast envelope for the transport of photoassimilates. In addition, CreTPT3 can serve as a safety valve that moves excess reductant out of the chloroplast and appears to be essential for preventing cells from experiencing oxidative stress and accumulating reactive oxygen species, even under low/moderate light intensities. Finally, our studies indicate subfunctionalization of the TRIOSE PHOSPHATE/PHOSPHATE TRANSLOCATOR (CreTPT) transporters and suggest that there are differences in managing the export of photoassimilates from the chloroplasts of Chlamydomonas and vascular plants.
Polarized Politics: Protest Against COVID-19 Containment Policies in the USA
Authors: Pfaff Katharina Gabriela , Plümper Thomas , Neumayer Eric
Published: March 2023

Protest against containment policies in U.S. states is fueled by two drivers: the stringency of containment policies and the partisan control over the governorship and legislatures in each state. In our analysis of the period from March 2020 to March 2022, we find more protest events in states fully controlled by Democrats than in Republican controlled states both in a sample consisting of all states and a balanced sample in which we constrain observations to those red and blue states with on average similarly stringent containment policies. Protest was therefore politicized, and we find that partisanship exerts a roughly equal substantive effect on the number of protest events as the stringency of containment policies. If we assume no direct effect of partisanship on protest but allow for causal heterogeneity along partisan lines in the effect of containment policies, we find that the same increase in the stringency of policies evokes a stronger protest response in blue states than in red states.
In your face: a comparative field experiment on racial discrimination in Europe
Authors: Polavieja Javier G , Lancee Bram , Ramos María , Veit Susanne , Yemane Ruta
Published: March 2023

We present the first large-scale comparative field experiment on appearance-based racial discrimination in hiring conducted in Europe. Using a harmonized methodology, we sent fictitious résumés to real vacancies in Germany, the Netherlands and Spain, randomly varying applicants’ ethnic ancestry (signaled foremost by name) and applicants’ racial appearance (signaled by photographs). Applicants are young-adult country nationals born to parents from over 40 different countries of ancestry (N = 12 783). We examine average differences in callback across four phenotypic groups and four regions of ancestry and present the first cross-country comparable estimates of appearance-based racial discrimination reported in the field-experimental literature. We find that applicants’ phenotype has a significant and independent effect on employers’ responses in Germany and the Netherlands, whereas in Spain we only find evidence of hiring discrimination for particular combinations of phenotype and ancestry, which suggests a less direct and more complex effect of phenotype in this country. Implications are discussed.
The usefulness of the exercise stress test to predict outcome in patients with chronic Chagas disease: a longitudinal cohort study
Authors: Grassi Luciano Vaccari , Neto Augusto Cardinalli , Nogueira Paulo Roberto , Silva Elissandro de Freitas , Bestetti Reinaldo Bulgareli
Published: March 2023

Background

Risk stratification is paramount for treatment of patients with chronic Chagas disease (CCD). The exercise stress test (EST) may be useful in the risk stratification of patients with this condition, but few studies have been performed in patients with CCD.

Methods

This was a longitudinal, retrospective cohort study. A total of 339 patients followed at our institution from January 2000 to December 2010 were screened. A total of 76 (22%) patients underwent the EST. The Cox proportional hazards model was used to identify independent predictors of all-cause mortality.

Results

Sixty-five (85%) patients were alive and 11 (14%) patients died by the study's close. In the univariate analysis, decreased systolic blood pressure (BP) at the peak of exercise and the double product were associated with all-cause mortality. However, in the multivariate analysis, only systolic BP at the peak of exercise was independently associated with all-cause mortality [hazard ratio 0.97 (95% confidence interval 0.94 to 0.99), p=0.02].

Conclusion

Systolic BP at the peak of EST is an independent predictor of mortality in patients with CCD.
Characteristics of Leaf Spot Disease Caused by Didymella Species and the Influence of Infection on Tea Quality
Authors: Deng Xinyi , Yang Juan , Wan Yuhe , Han Yuxin , Tong Huarong , Chen Yingjuan
Published: March 2023

Leaf spots are the most damaging and common foliar diseases of tea and are caused by several species of fungi. During 2018 to 2020, leaf spot diseases showing different symptoms (large and small spots) were observed in commercial tea plantations in Guizhou and Sichuan provinces of China. The pathogen causing the two different sized leaf spots was identified as the same species ( Didymella segeticola) based on morphological characteristics, pathogenicity, and multilocus phylogenetic analysis using the combined ITS, TUB, LSU, and RPB2 gene regions. Microbial diversity analysis of lesion tissues from small spots on naturally infected tea leaves further confirmed Didymella to be present as the main pathogen. Results of sensory evaluation and quality-related metabolite analysis of tea shoots infected with the small leaf spot symptom indicated that D. segeticola negatively affected the quality and flavor of tea by changing the composition and content of caffeine, catechins, and amino acids. In addition, the significantly reduced amino acid derivatives in tea are confirmed to be positively associated with the enhanced bitter taste. The results improve our understanding of the pathogenicity of Didymella species and the influence of Didymella on the host plant, Camellia sinensis.
Are Final Residency Milestones Correlated With Early Fellowship Performance in Pediatrics?
Authors: Reed Suzanne , Mink Richard , Stanek Joseph , Tyrrell Laura , Li Su-Ting T.
Published: March 2023

Purpose

Milestones have been used to assess trainees across graduate medical education programs and reflect a developmental continuum from novice to expert. This study examined whether residency milestones are correlated with initial fellowship milestone performance in pediatrics.

Method

This retrospective cohort study used descriptive statistics to assess milestone scores from pediatric fellows who began fellowship training between July 2017 and July 2020. Milestone scores were obtained at the end of residency (R), middle of the first fellowship year (F1), and end of the first fellowship year (F2).

Results

Data represent 3,592 unique trainees. High composite R scores, much lower F1 scores, and slightly higher F2 scores were found over time for all pediatric subspecialities. R scores were positively correlated with F1 scores (Spearman ρ = 0.12, P < .001) and F2 scores (Spearman ρ = 0.15, P < .001). Although scores are negligibly different when trainees graduate from residency, there were differences in F1 and F2 scores among fellows in different specialties. Those who trained at the same institution for residency and fellowship had higher composite milestone F1 and F2 scores compared with those who trained at different institutions (P < .001). The strongest associations were between R and F2 scores for the professionalism and communication milestones, although associations were still relatively weak overall (rs = 0.13–0.20).

Conclusions

This study found high R scores and low F1 and F2 scores across all shared milestones, with weak association of scores within competencies, indicating that milestones are context dependent. Although professionalism and communication milestones had a higher correlation compared with the other competencies, the association was still weak. Residency milestones may be useful for individualized education in early fellowship, but fellowship programs should be cautious about overreliance on R scores due to the weak correlation with F1 and F2 scores.
Training for Adaptive Expertise: Why, What, and How
Authors: Branzetti Jeremy , Hopson Laura R. , Gisondi Michael A. , Regan Linda
Published: March 2023

Background

Routine expertise is the efficient use of mastered skills at a high level of competency in familiar situations.

Problem

Novel case variation and continuous scientific advances preclude reliance on routine expertise alone.

Solution

Medical training programs must prepare learners to solve unfamiliar problems by cultivating adaptive expertise. Adaptive expertise is the ability to transfer existing knowledge to innovate a solution for an unfamiliar problem.
Proximal Junction Failure in Spine Surgery: Integrating Geometrical and Biomechanical Global Descriptors Improves GAP Score-Based Assessment
Authors: Rasouligandomani Morteza , del Arco Alex , Pellisé Ferran , González Ballester Miguel A. , Galbusera Fabio , Noailly Jérôme
Published: March 2023

Study Design.

Retrospective observational study.

Objective.

Biomechanical and geometrical descriptors are used to improve global alignment and proportion (GAP) prediction accuracy to detect proximal junctional failure (PJF).

Summary of Background Data.

PJF is probably the most important complication after sagittal imbalance surgery. The GAP score has been introduced as an effective predictor for PJF, but it fails in certain situations. In this study, 112 patient records were gathered (57 PJF; 55 controls) with biomechanical and geometrical descriptors measured to stratify control and failure cases.

Patients and Methods.

Biplanar EOS radiographs were used to build 3-dimensional full-spine models and determine spinopelvic sagittal parameters. The bending moment (BM) was calculated as the upper body mass times, the effective distance to the body center of mass at the adjacent upper instrumented vertebra +1. Other geometrical descriptors such as full balance index (FBI), spino-sacral angle (SSA), C7 plumb line/sacrofemoral distance ratio (C7/SFD ratio), T1-pelvic angle (TPA), and cervical inclination angle (CIA) were also evaluated. The respective abilities of the GAP, FBI, SSA, C7/SFD, TPA, CIA, body weight, body mass index, and BM to discriminate PJF cases were analyzed through receiver operating characteristic curves and corresponding areas under the curve (AUC).

Results.

GAP (AUC = 0.8816) and FBI (AUC = 0.8933) were able to discriminate PJF cases but the highest discrimination power (AUC = 0.9371) was achieved with BM at upper instrumented vertebra + 1. Parameter cutoff analyses provided quantitative thresholds to characterize the control and failure groups and led to improved PJF discrimination, with GAP and BM being the most important contributors. SSA (AUC = 0.2857), C7/SFD (AUC = 0.3143), TPA (AUC = 0.5714), CIA (AUC = 0.4571), body weight (AUC = 0.6319), and body mass index (AUC = 0.7716) did not adequately predict PJF.

Conclusion.

BM reflects the quantitative biomechanical effect of external loads and can improve GAP accuracy. Sagittal alignments and mechanical integrated scores could be used to better prognosticate the risk of PJF.
Why Are Some Intervertebral Discs More Prone to Degeneration?
Authors: Cheung Samuel Tin Yan , Cheung Prudence Wing Hang , Cheung Jason Pui Yin
Published: March 2023

Study Design.

Prospective observational study.

Objective.

To determine the prevalence of isolated thoracic degeneration on magnetic resonance imaging (MRI), demographic factors and imaging features, as well as the patient-reported quality of life outcomes associated with this condition.

Summary of Background Data.

Thoracic intervertebral discs are least susceptible to disc degeneration (DD) and may represent a manifestation of “dysgeneration.” These discs may never be hydrated from the beginning and seem hypointense on MRI.

Patients and Methods.

A population-based MRI study of 2007 volunteers was conducted. Each disc from C2/3 to L5/S1 was measured by Pfirrmann and Schneiderman grading. Disc herniation, Schmorl node (SN), high-intensity zones (HIZ), and Modic changes were studied. DD was defined by Pfirrmann 4 or 5. patient-reported quality of life scores, including a 36-item short-form questionnaire and visual analog scale for low back pain, were recorded. Subjects were divided into “isolated thoracic degeneration” (only thoracic segment) and “tandem thoracic degeneration” (thoracic with other segments). The association between imaging findings and isolated thoracic degeneration was determined using multivariate logistic regression.

Results.

The mean age of the subjects was 50.0 ± 0.5 and 61.4% were females (n = 1232). Isolated thoracic degeneration was identified in 2.3% of the cohort. Factors associated with isolated thoracic degeneration included lower age, C6/7 HIZ, T8/9 HIZ, and T8/9 SN. Factors associated with tandem thoracic degeneration included L4/5 posterior bulging. The thoracic and lumbar tandem degeneration group demonstrated higher bodily pain, despite a lower visual analog scale, and a higher physical component score of the 36-item short form.

Conclusions.

Isolated thoracic degeneration demonstrated an earlier age of onset, mostly involving the mid-thoracic region (T5/6–T8/9), and in association with findings such as SN. Subjects with tandem thoracolumbar degeneration had less severe lumbar DD and low back pain as compared with those with isolated lumbar degeneration. This paints the picture of “dysgeneration” occurring in the thoracic and lumbar spine.

Level of Evidence.

1.
Reoperation Rates Due to ASD following Primary 1-2 level MIS vs. Open TLIF
Authors: Galetta Matthew S. , Lorentz Nathan A. , Lan Rae , Chan Calvin , Zabat Michelle A. , Raman Tina , Protopsaltis Themistocles S. , Fischer Charla R.
Published: March 2023

Study Design.

Retrospective analysis of prospectively collected data

Objective.

To investigate the effect of the approach of the TLIF (open vs. MIS) on reoperation rates due to ASD at 2 – 4 year follow up

Summary of Background Data.

Adjacent segment degeneration (ASDeg) is a complication of lumbar fusion surgery which may progress to adjacent segment disease (ASD) and cause debilitating postoperative pain potentially requiring additional operative management for relief. Minimally invasive (MIS) transforaminal lumbar interbody fusion surgery (TLIF) has been introduced to minimize this complication but the impact on ASD incidence is unclear.

Methods.

For a cohort of patients undergoing 1- or 2-level primary TLIF between 2013 and 2019, patient demographics and follow-up outcomes were collected and compared between patients who underwent open versus MIS TLIF using Mann Whitney U test, Fischer’s exact test, and binary logistic regression.

Results.

238 patients met inclusion criteria. There was a significant difference in revision rates due to ASD between MIS and open TLIFs at 2 (5.8% vs. 15.4%, P=0.021) and 3 (8% vs. 23.2%, P=0.03) year follow up, with open TLIFs demonstrating significantly higher revision rates. Surgical approach was the only independent predictor of reoperation rates at both 2 and 3 year follow ups (2-year P=0.009; 3-year P=0.011).

Conclusion.

Open TLIF was found to have a significantly higher rate of reoperation due to ASD compared to the MIS approach. Additionally, surgical approach (MIS vs. Open) appears to be an independent predictor of reoperation rates.
Creating 2 Unique Platelet-rich Plasma Products From a Single Batch of Whole Blood With a Single Processing Kit
Authors: Baria Michael R. , DiBartola Alex C. , Woods Karen , Valentas Lok , Vasileff W. Kelton , Durgam Sushmitha
Published: March 2023

Introduction:

Platelet-rich plasma (PRP) is effective for knee osteoarthritis (OA) and certain tendinopathies. Current recommendations support the use of leukocyte-poor PRP for OA and leukocyte-rich PRP for tendinopathy. If a patient presents with both OA and tendinopathy, very few systems can create multiple PRP products in the same treatment session. The Angel device processes multiple cycles to produce different PRP products.

Methods:

Ten healthy volunteers donated 156 mL whole blood (WB) that was mixed with 24 mL of anticoagulant citrate dextrose solution, solution A. The first PRP was produced by processing 120 mL at the 0% hematocrit setting and the second PRP was created by processing the remaining 60 mL at the 15% hematocrit setting. WB and PRP underwent complete blood counts and growth-factor analysis.

Results:

Ten patients donated WB for processing. The 0% setting yielded 3.7 ± 0.15 mL PRP, whereas the 15% setting produced 4.7 ± 0.33 mL. The 0% and 15% settings both concentrated platelets significantly more than WB (1101.5 ± 281.7 K/uL and 1357.8 ± 363.7 vs 184.3 ± 39.1 K/uL, P = 0.000). The 0% setting reduced total leukocytes, but this was not statistically significant. The 15% setting concentrated total leukocytes to 24 ± 8.72 K/uL, which was significantly higher than WB (P = 0.000). Neutrophil concentration was significantly reduced in the 0% PRP compared with 15% (0.032 ± .02 vs 6.75 ± 5.76 K/uL, P = 0.000).

Discussion:

Two unique PRP products were created from the same batch of WB using a single commercial kit by processing aliquots at different settings.