bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case report of a distal radius fracture treated with a dorsal spanning plate augmented with fragment specific fixation
Authors: Chen Andrew L , Hernandez Evan J , MacKay Brendan J 
Published: April 2024

Abstract
Dorsal spanning plates are frequently utilized to manage comminuted intra-articular distal radius fractures, but there is little literature on combining them with augmented fixation in complex cases. We present a 43-year-old man who fell 5 ft onto his outstretched right hand. On examination, there was gross swelling and tenderness of the right wrist with no neurovascular deficit. Radiographs confirmed a comminuted intra-articular displaced distal radius fracture. He was treated with a dorsal spanning plate fixation combined with radiostyloid and volar buttress plates. Follow-up at 2 months showcased intact hardware with good fracture healing. The dorsal spanning plate was removed 4 months after the procedure with radiographs demonstrating adequate alignment and healing without failure. The patient reported no complaints and minimal functional disability. We highlight a case of augmenting a dorsal spanning plate with fragment-specific plate fixation for a comminuted intra-articular displaced distal radius fracture.
The Patterns of Codon Usage between Chordates and Arthropods are Different but Co-evolving with Mutational Biases
Authors: Kotari Ioanna , Kosiol Carolin , Borges Rui 
Published: April 2024

Abstract
Different frequencies amongst codons that encode the same amino acid (i.e. synonymous codons) have been observed in multiple species. Studies focused on uncovering the forces that drive such codon usage showed that a combined effect of mutational biases and translational selection works to produce different frequencies of synonymous codons. However, only few have been able to measure and distinguish between these forces that may leave similar traces on the coding regions. Here, we have developed a codon model that allows the disentangling of mutation, selection on amino acids and synonymous codons, and GC-biased gene conversion (gBGC) which we employed on an extensive dataset of 415 chordates and 191 arthropods. We found that chordates need 15 more synonymous codon categories than arthropods to explain the empirical codon frequencies, which suggests that the extent of codon usage can vary greatly between animal phyla. Moreover, methylation at CpG sites seems to partially explain these patterns of codon usage in chordates but not in arthropods. Despite the differences between the two phyla, our findings demonstrate that in both, GC-rich codons are disfavored when mutations are GC-biased, and the opposite is true when mutations are AT-biased. This indicates that selection on the genomic coding regions might act primarily to stabilize its GC/AT content on a genome-wide level. Our study shows that the degree of synonymous codon usage varies considerably among animals, but is likely governed by a common underlying dynamic.
A case of eosinophilic granulomatosis with polyangiitis associated with diffuse alveolar haemorrhage: A case report and case-based review
Authors: Kawaguchi Rira , Usagawa Hirohisa , Miyawaki Yoshia , Oiwa Hiroshi 
Published: April 2024

ABSTRACT
A 76-year-old man with bronchial asthma was admitted for respiratory failure and bloody sputum. A significant drop in haemoglobin and multiple consolidations supported clinical diagnosis of diffuse alveolar haemorrhage (AH). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was positive and urinalysis suggested glomerulonephritis. Based on eosinophilia, sinusitis, peripheral nerve involvement, and leukocytoclastic vasculitis, he was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) associated with AH. Our case-based review suggested that male predominance (65%), high positivity for ANCA (88%), and a high frequency of renal involvement (45%) may be characteristic of AH in EGPA. Although AH is rare in EGPA, we should be aware of this life-threatening complication.
Multiple lymphadenopathies in eosinophilic granulomatosis with polyangiitis: Differentiating from IgG4-related lymphadenopathy
Authors: Kurashina Jun-ichi , Shimojima Yasuhiro , Kishida Dai , Ichikawa Takanori , Uehara Takeshi , Sekijima Yoshiki 
Published: April 2024

ABSTRACT
We report a case of eosinophilic granulomatosis with polyangiitis in a 75-year-old man who developed mononeuritis multiplex and purpura in the lower legs concomitantly presenting with lymphadenopathies. Biopsied lymph node tissue pathologically demonstrated fibrinoid necrotising vasculitis with perivascular eosinophil infiltration, resulting in eosinophilic granulomatosis with polyangiitis diagnosis. Additionally, abundant immunoglobulin (Ig) G4-positive plasma cell infiltration exhibiting &gt;70% IgG4/IgG ratio, without storiform pattern fibrosis and obliterative phlebitis, was observed in the biopsied lymph node. Clinical improvement was observed after corticosteroid therapy. IgG4-related lymphadenopathy has been defined as a distinct clinical category regardless of fulfilling IgG4-related disease classification criteria. However, some autoimmune diseases, including eosinophilic granulomatosis with polyangiitis, can develop lymphadenopathy pathologically similar to IgG4-related lymphadenopathy.
Molecular mechanism for target RNA recognition and cleavage of Cas13h
Authors: Chen Fugen , Zhang Chendi , Xue Jialin , Wang Feng , Li Zhuang 
Published: April 2024

Abstract
RNA-targeting type VI CRISPR-Cas effectors are widely used in RNA applications. Cas13h is a recently identified subtype of Cas13 ribonuclease, with strong RNA cleavage activity and robust in vivo RNA knockdown efficiency. However, little is known regarding its biochemical properties and working mechanisms. Biochemical characterization of Cas13h1 indicated that it lacks in vitro pre-crRNA processing activity and adopts a central seed. The cleavage activity of Cas13h1 is enhanced by a R(G/A) 5′-PFS, and inhibited by tag:anti-tag RNA pairing. We determined the structures of Cas13h1-crRNA binary complex at 3.1 Å and Cas13h1-crRNA-target RNA ternary complex at 3.0 Å. The ternary complex adopts an elongated architecture, and encodes a nucleotide-binding pocket within Helical-2 domain to recognize the guanosine at the 5′-end of the target RNA. Base pairing between crRNA guide and target RNA disrupts Cas13h1-guide interactions, leading to dramatic movement of HEPN domains. Upon target RNA engagement, Cas13h1 adopts a complicated activation mechanism, including separation of HEPN catalytic residues and destabilization of the active site loop and NTD domain, to get activated. Collectively, these insights expand our understanding into Cas13 effectors.
Implementation of an Automated Antibiotic Time-out at a Comprehensive Cancer Center
Authors: Tverdek Frank P , Aitken Samuel L , Mulanovich Victor E , Adachi Javier , Wu Cai , Cantu Sherry S , McDaneld Patrick M , Chemaly Roy F 
Published: April 2024

Abstract

Background
Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established.

Methods
An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed.

Results
Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: −0.89 days (95% confidence interval [CI], −1.38 to −.41); linezolid: −0.89 days (95% CI, −1.27 to −.52); meropenem: −0.97 days (95% CI, −1.39 to −.56); tigecycline: −1.41 days (95% CI, −2.19 to −.63); P &lt; .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (−43.49; 95% CI, −58.61 to −28.37; P &lt; .001), tigecycline (−35.47; 95% CI, −44.94 to −26.00; P &lt; .001), and daptomycin (−9.47; 95% CI, −15.25 to −3.68; P = .002).

Discussion
A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.
CDK9 inhibition activates innate immune response through viral mimicry
Authors: Yalala Shivani , Gondane Aishwarya , Poulose Ninu , Liang Jing , Mills Ian G. , Itkonen Harri M. 
Published: April 2024

AbstractCancer cells frequently exhibit hyperactivation of transcription, which can lead to increased sensitivity to compounds targeting the transcriptional kinases, in particular CDK9. However, mechanistic details of CDK9 inhibition‐induced cancer cell‐selective anti‐proliferative effects remain largely unknown. Here, we discover that CDK9 inhibition activates the innate immune response through viral mimicry in cancer cells. In MYC over‐expressing prostate cancer cells, CDK9 inhibition leads to the gross accumulation of mis‐spliced RNA. Double‐stranded RNA (dsRNA)‐activated kinase can recognize these mis‐spliced RNAs, and we show that the activity of this kinase is required for the CDK9 inhibitor‐induced anti‐proliferative effects. Using time‐resolved transcriptional profiling (SLAM‐seq), targeted proteomics, and ChIP‐seq, we show that, similar to viral infection, CDK9 inhibition significantly suppresses transcription of most genes but allows selective transcription and translation of cytokines related to the innate immune response. In particular, CDK9 inhibition activates NFκB‐driven cytokine signaling at the transcriptional and secretome levels. The transcriptional signature induced by CDK9 inhibition identifies prostate cancers with a high level of genome instability. We propose that it is possible to induce similar effects in patients using CDK9 inhibition, which, we show, causes DNA damage in vitro. In the future, it is important to establish whether CDK9 inhibitors can potentiate the effects of immunotherapy against late‐stage prostate cancer, a currently lethal disease.
An update on migraine
Authors: Hervias Teddy 
Published: April 2024

ABSTRACT
Migraine headache is a common and potentially debilitating disorder often treated by physician associates/assistants (PAs) and other providers. With the recent advances in new drugs and device technology for the treatment of migraine, the American Headache Society has released a consensus statement on both preventive and acute strategies for clinical practice. The US FDA has recently approved various types of medications and devices for the treatment and prevention of migraine attacks including several calcitonin gene-related peptide (CGRP) receptor inhibitors, a selective serotonin receptor agonist (SSRA), noninvasive vagus nerve stimulation (nVNS), external trigeminal nerve stimulation (e-TNS), and external concurrent occipital and trigeminal neurostimulation (eCOT-NS), among other pharmacologic and nonpharmacologic options. This article provides a review of migraine prevention and acute treatment protocol, highlighting new approaches to both.
Axial spondyloarthritis guidelines – aiming for maximum impact
Authors: Choufani Mathieu , Kay Jonathan , Ermann Joerg 
Published: April 2024

Purpose of review
This review discusses international clinical practice guidelines (CPGs) for axial spondyloarthritis (axSpA) focusing on methodology, guideline quality, and implementation.

Recent findings
The Assessment of SpondyloArthritis International Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) and Pan-American League of Associations for Rheumatology (PANLAR) recently published axSpA CPGs and updates of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Asia-Pacific League of Associations for Rheumatology (APLAR) CPGs are expected. GRADE has emerged as the dominant framework for CPG development and has been used by three of the four international axSpA guidelines. Notable differences exist among these guidelines in the way that the recommendations are presented. Two of the four acknowledge the need for implementation strategies, but little detail about this is provided. The few studies that have evaluated the implementation of axSpA CPGs have identified poor adherence to recommendations on physical therapy/exercise and disease activity monitoring. Implementation science has identified many barriers and facilitators affecting guideline uptake, including those related to healthcare professionals and to the guidelines themselves. Creation of a tailored implementation plan simultaneously with the CPG is recommended.

Summary
While methodological rigor in the creation of evidence-based recommendations is the focus of CPG development, recommendations must be presented in a user-friendly format that makes them easy to apply. ‘Living guidelines’ could facilitate keeping content up to date. Implementation is critical for the success of a CPG and should be emphasized in future axSpA guideline updates. Further research is needed to better understand the factors impacting the successful implementation of axSpA CPGs.
Treatment With Topical Ivermectin 1% Once a Month to Control Demodex Blepharitis
Authors: Rivera Salazar Jorge , Lara Peñaranda Jesús , González del Valle Fernando , Gálvez Martínez Javier , Valdés González José Juan , Olalla Gallardo José María , Juárez Tosina Rocío , Calzas Durán José Manuel , Arias Ángel , Tejera-Muñoz Antonio 
Published: April 2024

Purpose:
The study aimed to assess the effectiveness of a monthly application of topical 1% ivermectin cream, for 3 months, to the eyelids and eyelids margin, accompanied by gentle squeezing of meibomian glands and microexfoliation to the base of eyelashes, in the management of Demodex blepharitis.

Methods:
Thirty-eight patients diagnosed with Demodex blepharitis based on the presence of sleeves at the base of the eyelashes, telangiectasias, and signs of local inflammation with at least 4 Demodex mites observed at the lash roots were enrolled. Treatment involved applying 1% ivermectin topical cream using an eyelash brush in circular motion, gradually moving toward the eyelid margin. The procedure was repeated several times over 10 min by applying more cream. Each patient was evaluated before each treatment and 1 month after completion of the 3-month period.

Results:
Significant improvements in symptoms and signs were observed, with the disappearance of cylindrical sleeves on the base of the eyelashes, telangiectasias, signs of inflammation, and a significant decrease in night itching. The Schirmer test showed no changes, while the tear breakup time test exhibited slight yet statistically significant enhancement. No adverse events were reported during the study.

Conclusions:
The results of this investigation establish that Demodex blepharitis can be effectively managed by the application of 1% ivermectin cream once a month over a three-month period. This treatment approach, in conjunction with the gentle squeezing of meibomian glands and eyelid margin microexfoliation to the base of the eyelashes, resulted in the disappearance of objective indicators, such as cylindrical sleeves and telangiectasia, along with a significant reduction in nocturnal itching.
Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice
Authors: De Rudder Maxime , Manco Rita , Coubeau Laurent , Fontaine Alix , Bertrand Claude , Leclercq Isabelle A. , Dili Alexandra 
Published: April 2024

Background and Aims:
Surgical resection remains the gold standard for liver tumor treatment, yet the emergence of postoperative liver failure, known as the small-for-size syndrome (SFSS), poses a significant challenge. The activation of hypoxia sensors in an SFSS liver remnant initiated early angiogenesis, improving the vascular architecture, safeguarding against liver failure, and reducing mortality. The study aimed to elucidate vascular remodeling mechanisms in SFSS and their impact on hepatocyte function and subsequent liver failure.

Approach and results:
Mice underwent extended partial hepatectomy to induce SFSS, with a subset exposed to hypoxia immediately after surgery. Hypoxia bolstered posthepatectomy survival rates. The early proliferation of liver sinusoidal cells, coupled with recruitment of putative endothelial progenitor cells, increased vascular density, improved lobular perfusion, and limited hemorrhagic events in the regenerating liver under hypoxia. Administration of granulocyte colony-stimulating factor in hepatectomized mice mimicked the effects of hypoxia on vascular remodeling and endothelial progenitor cell recruitment but failed to rescue survival. Compared to normoxia, hypoxia favored hepatocyte function over proliferation, promoting functional preservation in the regenerating remnant. Injection of Adeno-associated virus serotype 8-thyroxine-binding globulin-hepatocyte nuclear factor 4 alpha virus for hepatocyte-specific overexpression of hepatocyte nuclear factor 4 alpha, the master regulator of hepatocyte function, enforced functionality in proliferating hepatocytes but did not rescue survival. The combination of hepatocyte nuclear factor 4 alpha overexpression and granulocyte colony-stimulating factor treatment rescued survival after SFSS-setting hepatectomy.

Conclusions:
In summary, SFSS arises from an imbalance and desynchronized interplay between functional regeneration and vascular restructuring. To improve survival following SFSS hepatectomy, it is essential to adopt a 2-pronged strategy aimed at preserving the function of proliferating parenchymal cells and simultaneously attenuating vascular damage.
Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension
Authors: Wang Ji-Guang , Topouchian Jirar , Bricout-Hennel Stéphanie , Mu Jianjun , Chen Lianglong , Li Ping , He Shenghu , Luo Suxin , Jiang Weihong , Jiang Yinong , Sun Yuemin , Zhang Yuqing , Asmar Roland 
Published: April 2024

Background:
In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals.

Methods:
This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM).

Results:
A total of 532 patients were randomized: Per/Ind/Aml (n = 262) and Per/Ind + Aml (n = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: −14.99 ± 14.46 mmHg Per/Ind/Aml versus −14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed (P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated.

Conclusions:
Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.
Brief Report: HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Initiating Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate: A Subanalysis of ALLIANCE Data
Authors: D'Antoni Michelle L. , Andreatta Kristen , Chang Silvia , Cox Stephanie , Hindman Jason T. , Avihingsanon Anchalee , Martin Hal , VanderVeen Laurie A. , Callebaut Christian 
Published: April 2024

Background:
In the phase 3 ALLIANCE study, both bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) achieved high rates of HIV-1 RNA suppression through week 96 in adults with HIV-1 and hepatitis B virus initiating treatment (NCT03547908). In this study, we quantify preexisting HIV-1 resistance, evaluate its effect on HIV-1 virologic suppression, and describe postbaseline HIV-1 resistance through week 96.

Methods:
Preexisting HIV-1 resistance was assessed by historical and/or screening genotyping. HIV-1 RNA suppression to <50 copies (c)/mL at week 96 was assessed by the preexisting resistance category. Postbaseline resistance was assessed in participants with HIV-1 RNA ≥200 c/mL through week 96.

Results:
Primary nucleoside/nucleotide reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor resistance substitutions were present at baseline in 4 (1.7%), 19 (7.9%), and 5 (2.1%) of 241 participants, respectively. Virologic suppression rates were high, irrespective of preexisting primary resistance substitutions, including M184I. Six participants (3 per group) had confirmed HIV-1 RNA ≥200 c/mL and did not resuppress to <50 c/mL while on study drugs; none of the 5 with postbaseline resistance data had treatment-emergent primary resistance substitutions. One participant on DTG + F/TDF with multiple virologic failures and documented nonadherence by pill count had treatment-emergent K70E and M184V/I, and subsequently resuppressed.

Conclusion:
In people with HIV-1 and hepatitis B virus treated with first-line B/F/TAF or DTG + F/TDF, preexisting HIV-1 resistance was uncommon and did not affect virologic suppression. No treatment-emergent HIV-1 resistance occurred with B/F/TAF, further supporting the high barrier to resistance of this regimen.