bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare Dedifferentiated Periosteal Chondrosarcoma with 11-Year Metastatic Relapse: A Case Report
Authors: Gasparro Matthew A. , Lee Linus , Vijayakumar Gayathri , Gusho Charles A. , Colman Matthew W. , Gitelis Steven , Miller Ira , Blank Alan T.
Published: May 2023

A 50-year-old man presented for evaluation of a periscapular mass. Biopsy suggested a low-grade chondrosarcoma; however, the resected specimen revealed a grade 2 chondrosarcoma with a low-grade dedifferentiated mesenchymal component. The mass multiply recurred as chondrosarcoma without a dedifferentiated component before the patient developed lung metastases of chondrosarcoma without a dedifferentiated component 11 years after the initial diagnosis and died of disease. This is one of the first reported cases of a dedifferentiated chondrosarcoma with low-grade dedifferentiated component. While overall prognosis may be better than in typical dedifferentiated chondrosarcoma, this tumor demonstrated numerous local recurrences as well as metastasis.
Position sensitive detector based non-contact vibration measurement with laser triangulation method utilizing Gabor Transform for noise reduction
Authors: Das Sampa , Khatri Shakilahemad , Saha Ardhendu
Published: May 2023

Measurement of vibration without having contact with the target is crucial for many applications. However, real time vibration signals are frequently mixed with various levels of dynamic noises. In this research, a non-contact type vibration measurement system based on laser triangulation method is proposed by using a PSD (Position sensitive detector) and here a single axis Brüel and Kjaer piezoelectric accelerometer is used to validate the experimental results. The primary goal of this measurement system is to develop a Gabor Transform based signal denoising technique, in order to eliminate noise from the real-time vibration data. Furthermore, PSD platform vibration, which might cause unanticipated inaccuracies in the detected vibration data, has also been eliminated by utilizing a self-vibration compensation approach using an ADXL-345 three-axis accelerometer. The self-vibration compensated vibration measurement technique has been designed using an NI (national instruments) cRIO (CompactRIO) 9074 real-time FPGA (field programmable gate array) based embedded controller. Consequently, a Gabor Transform and Expansion-based Signal Processing Technique is designed using NI cRIO-9074 real time platform to reduce external noise from the self-vibration compensated vibration data. It has been observed that the implementation of Gabor Transform has improved the performance of the system in term of enhancing the SNR (Signal-to-noise ratio).
Stability signatures for porous thermoelasticity with microtemperature and without temperature
Authors: Ramos AJA , Júnior DS Almeida , Aouadi M , Freitas MM , Barbosa RC
Published: May 2023

In this paper, we provide necessary and sufficient conditions for obtaining the stabilization properties for the one-dimensional Lord–Shulman thermoelastic theory with porosity subject to microtemperature but without temperature where the microtemperature conduction equations are governed by Cattaneo–Maxwell’s law. Based on recent results due to Bazarra et al., we introduce a stability number[Formula: see text] involving all coefficients of the system, and we prove that the exponential decay of the corresponding semigroup holds if and only if [Formula: see text]. Otherwise, we show that the system loses exponential stability and its solution decays polynomially with a rate equal to [Formula: see text].
Framingham risk score conventional risk factors are potent to predict all-cause mortality using machine learning algorithms: a population-based prospective cohort study over 40 years in China
Authors: Huang QianQian , Zeng TianShu , Zhang JiaoYue , Min Jie , Zheng Juan , Tian ShengHua , Huang Hantao , Liu XiaoHuan , Zhang Hao , Wang Ping , Hu Xiang , Chen LuLu
Published: May 2023

Predicting all-cause mortality using available or conveniently modifiable risk factors is potentially crucial in reducing deaths precisely and efficiently. Framingham risk score (FRS) is widely used in predicting cardiovascular diseases, and its conventional risk factors are closely pertinent to deaths. Machine learning is increasingly considered to improve the predicting performances by developing predictive models. We aimed to develop the all-cause mortality predictive models using five machine learning (ML) algorithms (decision trees, random forest, support vector machine (SVM), XgBoost, and logistic regression) and determine whether FRS conventional risk factors are sufficient for predicting all-cause mortality in individuals over 40 years. Our data were obtained from a 10-year population-based prospective cohort study in China, including 9143 individuals over 40 years in 2011, and 6879 individuals followed-up in 2021. The all-cause mortality prediction models were developed using five ML algorithms by introducing all features available (182 items) or FRS conventional risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the predictive models. The AUC and 95% confidence interval of the all-cause mortality prediction models developed by FRS conventional risk factors using five ML algorithms were 0.75 (0.726–0.772), 0.78 (0.755–0.799), 0.75 (0.731–0.777), 0.77 (0.747–0.792), and 0.78 (0.754–0.798), respectively, which is close to the AUC values of models established by all features (0.79 (0.769–0.812), 0.83 (0.807–0.848), 0.78 (0.753–0.798), 0.82 (0.796–0.838), and 0.85 (0.826–0.866), respectively). Therefore, we tentatively put forward that FRS conventional risk factors were potent to predict all-cause mortality using machine learning algorithms in the population over 40 years.
Learning From Recorded Lectures: Perceptions of Students With ADHD
Authors: Levenberg Ariella , Reesh Suzan Abu
Published: May 2023

With the outbreak of the Covid-19 pandemic, education systems worldwide, including higher education institutions, switched to remote learning in various modes, including recordings of lectures and lessons. Learning this way can be especially effective for students with Attention Deficit/Hyperactive Disorder (ADHD) who have difficulties maintaining organization, focus, and concentration. Hence, this qualitative study used semi-structured interviews to examine the perceptions of 12 students with ADHD that studied from recorded lectures from the perspective of the symptoms that define this disorder. Findings showed that learning from recordings of lectures gave students a sense of control over the learning in terms of pace, place, time, and convenience. The research contributes to understanding how to tailor accessible remote learning to students with ADHD.
Cat alpha-1-acid glycoprotein enzyme-linked immunosorbent assay: performance characteristics and reference intervals
Authors: Thalmeier Sabine , Güssow Arne , Häuser Mia K , Bauer Natali , Hazuchova Katarina
Published: May 2023

Objectives

The aim of this study was to evaluate performance of a feline-specific ELISA for the measurement of alpha-1-acid glycoprotein (AGP) and to establish a reference interval (RI).

Methods

Surplus serum samples with low (~200 µg/ml), medium (~450 µg/ml) and high (~745 and 930 µg/ml) AGP concentrations were used to assess the intra- and inter-assay coefficients of variation (CVs). The quality goal for bioanalytical method validation was a CV of <20%. Linearity was assessed by serial dilution of a sample with a high AGP concentration. Spike recovery was evaluated by mixing samples with low, medium and high AGP concentrations at different ratios. To establish the RI, residual serum samples from 51 healthy adult cats that were presented for health examinations or blood donation between August 2020 and June 2021 were included.

Results

The intra-assay CV was 8.5%, 4.3% and 4.0%, and the inter-assay CV was 18.8%, 15.5% and 11.5% for serum samples with low, medium and high AGP concentrations, respectively. Excellent linearity (R2 = 0.98) was demonstrated for AGP concentrations ranging between 251.6 and 954.4 µg/ml. Average recovery was 95.0–99.7%. The right-sided RI for AGP was 328 µg/ml (90% confidence interval 300–354). Age had a statistically significant impact (increasing values with older age, P = 0.0026), but sex did not ( P = 0.44), on AGP concentrations.

Conclusions and relevance

The ELISA was accurate and showed acceptable precision with the modification of dilution used in this study. AGP concentrations in this population appeared to increase with increasing age.
On the moral significance of military operations: A response to Hans-Herbert Kögler
Authors: King Anthony
Published: May 2023

Against pacifist calls for peace at any price in Ukraine, Hans-Herbert Kögler argues that the west has a moral obligation to support Ukraine in its war against Russia. Kögler’s argument is well-made. However, he does not mention the war at all. This may be an oversight because while moral principles may be universal, in practice, the context defines how morals are applied. Drawing on Clausewitz’s concept of the Trinity, this response seeks to develop Kögler’s moral argument by examining the practical, military implications of the war. It argues that because the war is heavily urbanised, the west’s moral commitment is likely to be very deep and long.
Covering inclusion: Frames, themes, and voice in news about LGBTI topics
Authors: Verhoeven Emma , Paulussen Steve , Dhoest Alexander
Published: May 2023

This article investigates how LGBTI topics are framed in the news and who is given a voice in this coverage by analysing the Dutch-speaking Belgian press. An inductive framing analysis and quantitative content analysis were applied on 1570 articles about LGBTI topics published in 2021 by 13 Dutch-language news outlets. Seven inclusive and two exclusionary frames were discerned. The study shows that primarily gay men serve as voices of the LGBTI community. The findings also indicate that articles are more likely to be framed inclusively when they cite LGBTI people or organisations. Building on the politics of voice and the concepts of valuable and inclusive journalism, this paper argues for journalists and academics to focus on voices that remain unheard in journalism.
Assembling a household in the Middle Nile Valley (Old Dongola, Sudan) in the 16th–17th centuries
Authors: Wyżgoł Maciej , Deptuła Agata
Published: May 2023

Old Dongola, with a history reaching back to the 5th century AD, was originally the capital of Makuria, one of the three medieval Nubian kingdoms. After the collapse of Makuria, its capital city saw migratory movements and political changes that resulted in the emergence of new power relations. In the 16th and 17th centuries, the city was the seat of a local ruler subordinate to the Funj Sultanate. New communities that emerged in this setting inhabited the city until the colonial era. This paper examines the ways in which Funj-period households, as fundamental social units in Old Dongola, were mutually constitutive with houses, engaging with their spatiality and materiality through social practices. The authors investigate domestic labour, which was an essential factor in the negotiation of social differences and identities within the household. Differences in building techniques are analysed to compare various ways in which dwellers engaged with houses and to assess their implications for social differentiation within the city.
Reaching Voters on Social Media: Planning Political Advertising on Snapchat
Authors: Tanusondjaja Arry , Michelon Aaron , Hartnett Nicole , Stocchi Lara
Published: May 2023

Over the past decade, political advertising via social media has grown rapidly, spurred by microtargeting, which looks to deliver specific messages to tightly defined audiences. Microtargeting strategies have been claimed to be effective, but questions remain around their cost, when looking to optimise impressions for a given budget. We analyse 11,837 ads aired on Snapchat over a two-year period leading up to the 2020 presidential election in the United States, which differ in the number of targeting criteria applied. We compare the number of impressions and the spend per ad placement (measured in CPM), whilst also considering the length of advertising schedule. We find that using fewer targeting criteria and longer schedules increases impressions with comparable or lower spend than microtargeting. These findings are in line with those from traditional broadcast media, such as TV, highlighting the relevance of existing media scheduling knowledge from traditional platforms for political advertising on newer, digital media.
Understanding Genre as Atmospheric Assemblage: The Case of Videogames
Authors: Andiloro Andrea
Published: May 2023

This article advances an affect-based theorization of genre as atmospheric assemblage by applying such a framework to an analysis of videogame genre. The affective excess originating from the relations between the components of the assemblage is experienced by the player as a specific type of thinking-moving-feeling understood as a wholistic atmosphere. By looking at the cases of the soulsborne, rouguelike, and metroidvania genres, the article explains how an assemblage framework is useful to explain how players experience individual videogames as belonging to the same genre despite noticeable differences between them. On the other hand, a final example, that of the puzzle game, illustrates how minimal changes to the articulation of an assemblage enables quite different experiences for the players that may result in the establishment of a different genre. This article suggests that the atmospheric assemblage framework could be applied to other media forms, such as television and film.
Old Diagnostic Meets Newer Therapy; ECoG During LiTT
Authors: King-Stephens David
Published: May 2023

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Avant-Garde Endovascular Stent Graft Insertion in Dissected Ascending Thoracic Aortic Aneurysm
Authors: Álvarez Gómez José Lev , López de Victoria Orlando , Chévere Rivera Jaime Luis
Published: May 2023

Current guidelines and regulatory parameters for cardiothoracic surgery in the United States establish that open surgery is the first front line for treating ascending thoracic aortic aneurysms (ATAA). Despite advances in performing endovascular procedures in thoracic aortic aneurysms, there are no approved state-of-the-art techniques that allow endovascular procedures to be performed in ATAA. Thus, thoracic endovascular aortic repair (TEVAR) of the ascending aorta, as we will demonstrate, is a useful and effective technical opportunity for treating high-risk patients with type A dissections, intramural hematomas, and pseudoaneurysms. In this case, an 88-year-old female patient was consulted due to a preliminary diagnosed descending thoracic aortic aneurysm. As a result of uncertainty regarding the initial diagnosis, abdominal-pelvic and chest computed tomography scan tests contradicted the original conclusion and surprisingly yielded a different scenario; in fact, the patient had a dissected ATAA. Using the TEVAR procedure, the patient’s ATAA was treated with a thoracic GORE TAG endograft stent (W. L. Gore & Associates, Inc., Newark, DE, USA). Four weeks later, the aneurysm was completely thrombosed, and the stent-graft was properly in place.
Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support
Authors: Reid Elizabeth , Kamlin Omar F , Orsini Francesca , De Paoli Antonio G , Clark Howard W , Soll Roger F , Carlin John B , Davis Peter G , Dargaville Peter A
Published: May 2023

Background:

Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed.

Methods:

To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated.

Results:

From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm.

Conclusion:

Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.
Azygos anterior cerebral artery shield masquerading as an aneurysm
Authors: Andreev Alexander , Vranic Justin E , Doron Omer , Regenhardt Robert W , Patel Aman B
Published: May 2023

Here, we describe a case of a woman suspected to have an anterior cerebral artery (ACA) aneurysm that was ultimately found to have an azygous ACA shield. This benign entity highlights the importance of thorough investigation with cerebral digital subtraction angiography (DSA). This 73-year-old female initially presented with dyspnea and dizziness. CT angiogram of the head suggested an incidental 5 mm ACA aneurysm. Subsequent DSA demonstrated a Type I azygos ACA supplied by the left A1 segment. Also noted was a focal dilatation of the azygos trunk as it gave rise to the bilateral pericallosal and callosomarginal arteries. Three-dimensional visualization demonstrated a benign dilatation secondary to the four vessels branching; no aneurysm was noted. Incidence of aneurysms at the distal dividing point of an azygos ACA ranges from 13% to 71%. However, careful anatomical examination is imperative as findings may be a benign dilatation for which case intervention is not indicated.
Sequelae of Cryptococcal-Immune Reconstitution Inflammatory Syndrome in a Kidney Transplant Recipient: A Case Report
Authors: Lasry David , Cantarovich Marcelo , Sandal Shaifali
Published: May 2023

Rationale:

Cryptococcal-immune reconstitution inflammatory syndrome (C-IRIS) is a rare but recognized clinical entity in solid organ transplant recipients, though its clinical course and sequelae remain largely poorly described.

Presenting Concerns of the Patient:

We present the case of a kidney transplant recipient who presented with headache and fever. A cerebrospinal fluid analysis was performed and found to be compatible with cryptococcal meningitis. After down titration of immunosuppression and antifungal initiation, the patient initially improved. Weeks later, they experienced a sudden deterioration in mental status, prompting admission to the intensive care unit (ICU).

Diagnosis:

This deterioration was attributed to C-IRIS, which developed following rapid de-escalation of immunosuppression in response to the diagnosis of cryptococcal meningitis.

Interventions:

The initial episode of C-IRIS responded well to high-dose steroids; however, maintenance immunosuppression was not increased.

Outcomes:

Within 2 months, the patient presented again to the hospital with a pulmonary infiltrate and multifocal ischemic strokes.

Novel Findings:

We argue this to be a case of relapsing multisystem C-IRIS, thus expanding the known spectrum of manifestations of C-IRIS in renal transplant recipients. We propose that following the diagnosis of C-IRIS, maintenance immunosuppression be escalated to avoid the risk of relapse and inflammatory-mediated organ dysfunction.
Functional Outcomes of Anterior-Based Muscle Sparing Approach Compared to Direct Lateral Approach for Total HIP Arthroplasty Following Acute Femoral Neck Fractures
Authors: Innocenti Matteo , Cozzi Lepri Andrea , Civinini Alessandro , Mondanelli Nicola , Matassi Fabrizio , Stimolo Davide , Cerciello Simone , Civinini Roberto
Published: May 2023

Introduction

Total hip arthroplasty (THA) performed for femoral neck fractures (FNFs) is becoming a more frequent treatment in the active elderly population. Since there is limited research available presenting clinical outcomes after THA using the anterior-based muscle sparing (ABMS) approach, the aim of this study was to compare this surgical approach to the direct lateral (DL) approach in patients treated by THA for FNFs.

Materials and Methods

We retrospectively reviewed the data prospectively collected as a part of our “Hip Fracture Unit” and included 163 patients who underwent THA from January 2016 to January 2019 for acute displaced FNFs.

Results

A total of 132 patients who completed a minimum 2-years follow up (69 in the ABMS group and 63 in DL group) were included. The ABMS group demonstrated significantly shorter time to reach milestone for hospital discharge (1.5 Days vs 2.1 days, P = .018), while no statistically significant differences were detected in peri-operative complications. At 3 months, the timed up and go test, the Harris Hip Score (HHS) and the Oxford ip Score (OHS) were significantly better ( P = .024, .032 and .034, respectively) in the ABMS group compared to the DL group. No differences were found in functional outcomes (HHS and OHS) nor in complication rate at 6, 12 and 24 months.

Discussion

This is one of the first studies to analyze functional results of THA performed for FNFs through an ABMS approach. Results are in line with those already present in the Literature.

Conclusion

ABMS approach allows earlier mobilization and better early functional outcomes, compared to DL approach, in patients undergoing THA for acute displaced FNF. No differences are found after 6 months in functional results and complications rate.
A Bibliometric Analysis of Takeover in Family Firms: Current Themes and Prospects
Authors: Dixit Jyoti , Singh Poonam , Soni Rashmi
Published: May 2023

This article highlights the crucial areas and recent dynamics of the takeover field in family firms and recommends avenues for further research. Employing a bibliometric examination, this study analyzes a sample of 63 studies from the Scopus database on acquisition involving family firms between 1997 and early 2021. The study also performed a systematic literature review of the most significant articles as revealed by the computation. We obtain the prominent authors based on citation analysis. We also find current themes and suggest future research avenues. Despite the worldwide prevalence of family firms, there is less study on the takeover of family firms. The results also show that most of the articles are based on the few most studied theories, such as agency theory, resource-based view and stewardship and stagnation perspective, and so on. The scant studies on the takeover of family firms center around acquisition decisions, determinants of acquisition, and acquisition outcomes, with relatively less attention on measuring non-economic goals, board structure, and generation of family members. Finally, the results indicate that very few studies have focused on cross-industry and cross-country to examine the effect of family ownership on takeover events.
Relationship of Altmetric Attention Score, Twitter Performance, and Dimensions Badge Value With Traditional Metrics in Top-Cited Anterior Cruciate Ligament Research Studies
Authors: Sezer Hasan Basri , Bohu Yoann , Hardy Alexandre , Lefevre Nicolas , Sezer Aysun
Published: May 2023

Background:

Alternative citation metrics—such as the Altmetric Attention Score (AAS), number of tweets (TN), and dimensions badge value (DBV)—are emerging as new options for assessing the value of scientific works.

Purpose:

To analyze the AAS of highly cited articles on the anterior cruciate ligament (ACL) and to assess the relationship between alternative and traditional metrics such as journal rankings and article citation performance.

Study Design:

Cross-sectional study.

Methods:

A search was conducted using the Web of Science Core Collection of databases with “anterior cruciate ligament” as the search term. Full-text articles published between 2011 and 2021 were reviewed, and the top 100 cited articles were determined. The articles were analyzed by publication year, study design, research topic, journal impact factor, journal h-index, number of total citations (TC), recent citations (RC) (ie, citations in the latest 2 years), and average citation per year (ACY), as well as AAS, TN, and DBV.

Results:

For articles in the top 100 list, the median TC was 160 (interquartile range [IQR], 117-561) and the median AAS was 24.50 (IQR, 1-730). A higher AAS score was achieved by articles on return to sports and anterolateral ligament ( P < .05). The AAS and TN were significantly and positively correlated with the RC ( r = 0.459 and P = .001; r = 0.438 and P = .001, respectively) and ACY ( r = 0.363 and P = .001; r = 0.393 and P = .001, respectively).

Conclusion:

Alternative metrics were linked to traditional metrics but were not a direct representation of bibliometrics. The AAS was not correlated with TC numbers in the ACL research. Higher AAS and Twitter popularity of an article were related to receiving high-volume RC performance. The DBV represented a stronger correlation with traditional metrics than the AAS.
The nonlinear relationships between built environment features and urban street vitality: A data-driven exploration
Authors: Han Yun , Qin Chunpeng , Xiao Longzhu , Ye Yu
Published: May 2023

The relationship between the built environment and urban street vitality, as a key issue of contemporary urban design, has been discussed over decades. However, most existing studies relying on linear regression models do not reveal the complicated impacts of built environment features and often neglect their threshold effects. As a response, this study applies the gradient boosting decision tree (GBDT) model with a large amount of new urban data to explore the in-depth understanding of urban street vitality. Based on the street samples from 12 Chinese cities, a series of morphological, functional, and human-scale features were analyzed together with socioeconomic indicators as control variables. The street vitality is measured by street activity intensity computed from billions of location-based service records. The results show that the nonlinear model brings an overall improvement in resolution. Specifically, compared with the functional and human-scale features, the morphological characteristics, especially the street intersection density, average block size, and building density, are dominant contributors to street vitality. It is also worth noting that most built-up environment features obtain the threshold effects on street vitality, which means there is a turning point where the effect of features changes. The interaction between built environment characteristic variables is common and can be divided into two typical types. Insights achieved in this study help to indicate an effective interval of built environment characteristics on vitality, which was missed in previous studies, and thus contribute to more precise urban design practices. Moreover, by clarifying the interaction influence mechanism, this study emphasizes the need for the planner to exploit synergies between variables through optimal combinations while avoiding their antagonistic effects.
Use of Sodium-Glucose Cotransporter-2 Inhibitor for Diabetes Management in Patients Following Kidney Transplantation
Authors: Crannage Erica F. , Nguyen Katherine L. , Ellebrecht Morgan D. , Challen Laura M. , Crannage Andrew J.
Published: May 2023

Objective: To evaluate data sources pertaining to the safety and efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitor use for diabetes management in patients following kidney transplantation. Data Sources: A literature search was conducted through PubMed (1966-January 2023), EMBASE (1973-January 2023), and clinicaltrials.gov databases using the search terms kidney transplantation, diabetes mellitus, and SGLT2 inhibitor or empagliflozin, dapagliflozin, and canagliflozin. Study Selection and Data Extraction: Studies evaluating human kidney transplant recipients (KTR) receiving SGLT2 inhibitors treatment and published in the English language were included. Eight case series or retrospective analyses, 4 prospective observational studies, and 1 randomized controlled trial were identified. Data Synthesis: Available literature provides evidence that the addition of SGLT2 inhibitors may provide modest benefits on glycemic control, body weight, and serum uric acid levels in certain KTR. Various studies and case reports found that incidence of urinary tract infections was low, but still present. Overall, there are limited data on mortality and graft survival; however, one study reported a benefit of SGLT2 inhibitor use in KTR relative to these outcomes. Conclusions: The current literature evaluated demonstrates that there may be benefit to the addition of SGLT2 inhibitors for diabetes management in select KTR. However, the limited evidence within a large diverse population and extended duration of treatment makes it difficult to definitively identify the true efficacy and safety of SGLT2 inhibitor use in this population.
Genetic events associated with venetoclax resistance in CLL identified by whole-exome sequencing of patient samples
Authors: Khalsa Jasneet Kaur , Cha Justin , Utro Filippo , Naeem Aishath , Murali Ishwarya , Kuang Yanan , Vasquez Kevin , Li Liang , Tyekucheva Svitlana , Fernandes Stacey M. , Veronese Lauren , Guieze Romain , Sasi Binu Kandathilparambil , Wang Zixu , Machado John-Hanson , Bai Harrison , Alasfour Maryam , Rhrissorrakrai Kahn , Levovitz Chaya , Danysh Brian P. , Slowik Kara , Jacobs Raquel A. , Davids Matthew S. , Paweletz Cloud P. , Leshchiner Ignaty , Parida Laxmi , Getz Gad , Brown Jennifer R.
Published: May 2023

Although BCL2 mutations are reported as later occurring events leading to venetoclax resistance, many other mechanisms of progression have been reported though remain poorly understood. Here, we analyze longitudinal tumor samples from 11 patients with disease progression while receiving venetoclax to characterize the clonal evolution of resistance. All patients tested showed increased in vitro resistance to venetoclax at the posttreatment time point. We found the previously described acquired BCL2-G101V mutation in only 4 of 11 patients, with 2 patients showing a very low variant allele fraction (0.03%-4.68%). Whole-exome sequencing revealed acquired loss(8p) in 4 of 11 patients, of which 2 patients also had gain (1q21.2-21.3) in the same cells affecting the MCL1 gene. In vitro experiments showed that CLL cells from the 4 patients with loss(8p) were more resistant to venetoclax than cells from those without it, with the cells from 2 patients also carrying gain (1q21.2-21.3) showing increased sensitivity to MCL1 inhibition. Progression samples with gain (1q21.2-21.3) were more susceptible to the combination of MCL1 inhibitor and venetoclax. Differential gene expression analysis comparing bulk RNA sequencing data from pretreatment and progression time points of all patients showed upregulation of proliferation, B-cell receptor (BCR), and NF-κB gene sets including MAPK genes. Cells from progression time points demonstrated upregulation of surface immunoglobulin M and higher pERK levels compared with those from the preprogression time point, suggesting an upregulation of BCR signaling that activates the MAPK pathway. Overall, our data suggest several mechanisms of acquired resistance to venetoclax in CLL that could pave the way for rationally designed combination treatments for patients with venetoclax-resistant CLL.
A non-canonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML
Authors: Bamezai Shiva , Pulikkottil Alex Jose , Yadav Tribhuwan , Naidu Vegi Mahalakshmi , Mueller Julia , Mark Jasmin , Mandal Tamoghna , Feder Kristin Anja , Lehle Susann , Song Chenlin , Rosler Reinhild , Wiese Sebastian , Hoell Jessica I , Kloetgen Andreas , Karsan Aly , Kumari Ankita , Wojenski Luke , Sinha Amit U , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Donato Elisa , Trumpp Andreas , Kruse Elisabeth , Hamperl Stephan , Zou Lee , Rawat Vijay P. S. , Buske Christian
Published: May 2023

RNA-binding proteins (RBPs) form a large and diverse class of factors many members of which are overexpressed in hematological malignancies. RBPs participate in various processes of mRNA metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in acute myeloid leukemia patients and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells. In AML cells, PIWIL4 binds to a small number of known piwi-interacting RNA. It instead largely interacts with mRNA annotated to protein-coding genic regions and enhancers that are enriched for genes associated with cancer and human myeloid progenitor gene signatures. PIWIL4 depletion in AML cells downregulates human myeloid progenitor signature and LSC-associated genes and upregulates DNA damage signalling. We demonstrate that PIWIL4 is an R-loop resolving enzyme that prevents R-loop accumulation on a subset of AML and LSC-associated genes, and maintains their expression. It also prevents DNA damage, replication stress, and activation of the ATR pathway in AML cells. PIWIL4 depletion potentiates sensitivity to pharmacological inhibition of the ATR pathway and creates a pharmacologically actionable dependency in AML cells.
Fetal Factors Disrupt Placental and Maternal Iron Homeostasis in Murine β-Thalassemia
Authors: Yu Yang , Woloshun Regina R , Lee Jennifer K , Ebea Pearl Onuwa , Zhu Sean , Nemeth Elizabeta , Garrick Laura , Garrick Michael , Collins James F.
Published: May 2023

Pregnancy rates in β-thalassemia are increasing, but the risk of complications is higher; thus, better understanding of maternal and fetal iron homeostasis in this disorder is needed. HbbTh3/+ (Th3/+) mice model human β-thalassemia. Both the murine and human diseases are characterized by low hepcidin, high iron absorption and tissue iron overload, with concurrent anemia. We hypothesized that disordered iron metabolism in pregnant Th3/+ mice would negatively impact their unborn offspring. The experimental design included these groups: WT dams carrying WT fetuses (WT1); WT dams carrying WT and Th3/+ fetuses (WT2); Th3/+ dams carrying WT and Th3/+ fetuses (Th3/+); and age-matched, non-pregnant adult females. Serum hepcidin was low, and mobilization of splenic and hepatic storage iron was enhanced in all three groups of experimental dams. Intestinal 59Fe absorption was lower in Th3/+ dams (as compared to WT1/2 dams), but splenic 59Fe uptake was higher. Th3/+ dams had hyperferremia, which led to fetal and placenta iron loading, fetal growth restriction and placentomegaly. Notably, Th3/+ dams loaded Th3/+ and WT fetuses, with the latter situation more closely mirroring human circumstances when thalassemic mothers have relatively unaffected (thalassemia trait) offspring. Iron-related oxidative stress, and hypoxia, likely explains impaired fetal growth; enhanced placental erythropoiesis is a probable cause of placental enlargement. Moreover, high fetal liver iron transactivated Hamp; fetal hepcidin downregulated placental FPN expression, limiting placental iron flux and thus mitigating fetal iron loading. Whether gestational iron loading occurs in human thalassemic pregnancy, when blood transfusion can further elevate serum iron, is worth consideration.
iTRAQ-based comparative proteomics reveal an enhancing role of PRDX6 in the freezability of Mediterranean buffalo sperm
Authors: Luo Xi , Liang Mingming , Huang Shihai , Xue Qingsong , Ren Xuan , Li Yanfang , Wang Jinli , Shi Deshun , Li Xiangping
Published: May 2023

Background

Semen cryopreservation is a critical tool for breed improvement and preservation of biodiversity. However, instability of sperm freezability affects its application. The Mediterranean buffalo is one of the river-type buffaloes with the capacity for high milk production. Until now, there is no specific cryopreservation system for Mediterranean buffalo, which influences the promotion of excellent cultivars. To improve the semen freezing extender used in cryopreservation of Mediterranean buffalo, different protein datasets relating to freezability sperm were analyzed by iTRAQ-based proteomics. This study will be beneficial for further understanding the sperm freezability mechanism and developing new cryopreservation strategy for buffalo semen.

Results

2652 quantified proteins were identified, including 248 significantly differentially expressed proteins (DEP). Gene Ontology (GO) analysis indicated that many these were mitochondrial proteins, enriched in the molecular function of phospholipase A2 activity and enzyme binding, and biological processes of regulation of protein kinase A signaling and motile cilium assembly. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 17 significant pathways, including oxidative phosphorylation (OXPHOS). Furthermore, 7 DEPs were verified using parallel reaction monitoring or western blot, which confirmed the accuracy of the iTRAQ data. Peroxiredoxin 6 (PRDX6), which expressed 1.72-fold higher in good freezability ejaculate (GFE) compared to poor freezability ejaculate (PFE) sperms, was selected to explore the function in sperm freezability by adding recombinant PRDX6 protein into the semen freezing extender. The results showed that the motility, mitochondrial function and in vitro fertilization capacity of frozen-thawed sperm were significantly increased, while the oxidation level was significantly decreased when 0.1 mg/L PRDX6 was added compared with blank control.

Conclusions

Above results revealed the metabolic pattern of freezability of Mediterranean buffalo sperms was negatively associated with OXPHOS, and PRDX6 had protective effect on cryo-damage of frozen-thawed sperms.
Transcriptomic profiling of near-isogenic lines reveals candidate genes for a significant locus conferring metribuzin resistance in wheat
Authors: Bhattarai Rudra , Liu Hui , Siddique Kadambot H.M. , Yan Guijun
Published: May 2023

Background

Weeds reduce wheat yields in dryland farming systems. Herbicides such as metribuzin are commonly used to control weeds. However, wheat has a narrow safety margin against metribuzin. Standing crops such as wheat with weeds in the same field can also be killed by the same dose of metribuzin. Therefore, it is important to identify metribuzin resistance genes and understand the resistance mechanism in wheat for sustainable crop production. A previous study identified a significant metribuzin resistance wheat QTL,Qsns.uwa.4 A.2, explaining 69% of the phenotypic variance for metribuzin resistance.

Results

Two NIL pairs with the most contrasting performance in the metribuzin treatment and different in genetic backgrounds were compared using RNA sequence analysis, identifying nine candidate genes underlyingQsns.uwa.4 A.2responsible for metribuzin resistance. Quantitative RT-qPCR further validated the candidate genes, withTraesCS4A03G1099000(nitrate excretion transporter),TraesCS4A03G1181300(aspartyl protease), andTraesCS4A03G0741300(glycine-rich proteins) identified as key factors for metribuzin resistance.

Conclusion

Identified markers and key candidate genes can be used for selecting metribuzin resistance in wheat.
Barriers to access to antiretroviral therapy by people living with HIV in an indonesian remote district during the COVID-19 pandemic: a qualitative study
Authors: Fauk Nelsensius Klau , Gesesew Hailay Abrha , Seran Alfonsa Liquory , Ward Paul Russell
Published: May 2023

Background

Coronavirus disease (COVID-19) pandemic has a significant influence on the access to healthcare services. This study aimed to understand the views and experiences of people living with HIV (PLHIV) about barriers to their access to antiretroviral therapy (ART) service in Belu district, Indonesia, during the COVID-19 pandemic.

Methods

This qualitative inquiry employed in-depth interviews to collect data from 21 participants who were recruited using a snowball sampling technique. Data analysis was guided by a thematic framework analysis.

Results

The findings showed that fear of contracting COVID-19 was a barrier that impeded participants’ access to ART service. Such fear was influenced by their awareness of their vulnerability to the infection, the possibility of unavoidable physical contact in public transport during a travelling to HIV clinic and the widespread COVID-19 infection in healthcare facilities. Lockdowns, COVID-19 restrictions and lack of information about the provision of ART service during the pandemic were also barriers that impeded their access to the service. Other barriers included the mandatory regulation for travellers to provide their COVID-19 vaccine certificate, financial difficulty, and long-distance travel to the HIV clinic.

Conclusions

The findings indicate the need for dissemination of information about the provision of ART service during the pandemic and the benefits of COVID-19 vaccination for the health of PLHIV. The findings also indicate the need for new strategies to bring ART service closer to PLHIV during the pandemic such as a community-based delivery system. Future large-scale studies exploring views and experiences of PLHIV about barriers to their access to ART service during the COVID-19 pandemic and new intervention strategies are recommended.
Epidemiological characteristics of New Delhi Metallo-β-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University
Authors: Zhao Mengsi , He Jing , Zhang Ran , Feng Junhua , Deng Yanli , Zhang Jinyan
Published: May 2023

The epidemiological characteristics of New Delhi Metallo-β-Lactamase-Producing (NDM) Enterobacteriaceae were analyzed to provide theoretical support for clarifying the distribution characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the hospital environment and early identification of susceptible patients. From January 2017 to December 2021,42 strains of NDM-producing Enterobacteriaceae were gathered from the Fourth Hospital of Hebei Medical University, primarily Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. The micro broth dilution method combined with the Kirby-Bauer method was used to determine the minimal inhibitory concentrations (MICs) of antibiotics. The carbapenem phenotype was detected by the modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM). Carbapenem genotypes were detected by colloidal gold immunochromatography and real-time fluorescence PCR. The results of antimicrobial susceptibility testing showed that all NDM-producing Enterobacteriaceae were multiple antibiotic resistant, but the sensitivity rate to amikacin was high. Invasive surgery prior to culture, the use of excessive amounts of different antibiotics, the use of glucocorticoids, and ICU hospitalization were clinical characteristics of NDM-producing Enterobacteriaceae infection. Molecular typing of NDM-producing Escherichia coli and Klebsiella pneumoniae was carried out by Multilocus Sequence Typing (MLST), and the phylogenetic trees were constructed. Eight sequence types (STs) and two NDM variants were detected in 11 strains of Klebsiella pneumoniae, primarily ST17, and NDM-1. A total of 8 STs and 4 NDM variants were detected in 16 strains of Escherichia coli, mainly ST410, ST167, and NDM-5. For high-risk patients who have CRE infection, CRE screening should be done as soon as feasible to adopt prompt and efficient intervention measures to prevent outbreaks in the hospital.
Atypical haemolytic uremic syndrome with refractory multiorgan involvement and heterozygous CFHR1/CFHR3 gene deletion
Authors: Diep Jason , Potter Daniela , Mai Jun , Hsu Danny
Published: May 2023

Background

We present this challenging case report of Atypical Haemolytic Uremic Syndrome (aHUS) presenting with multi-organ involvement in a patient and heterozygous CFHR1/CFHR3 gene variant, which was refractory to initial eculizumab therapy.

Case presentation

A forty-three year old female presented with aHUS and had heterozygous disease-associated deletions in the complement genes CFHR1/CFHR3. She had progressive kidney failure and severe extra-renal manifestations including cardiomyopathy and haemorrhagic cystitis; as well as pulmonary, gastrointestinal and neurological involvement. The initial kidney biopsy revealed thrombotic microangiopathy (TMA) changes involving all glomeruli. Clinical improvement was initially seen during eculizumab initiation with suppressed CH50 level, but a new rhinovirus/enterovirus upper respiratory tract infection triggered further severe multi-organ disease activity. The extra-renal manifestations stabilised, then ultimately improved after a period of eculizumab dose intensification. However, the impact on dose intensification on this improvement is unclear. Despite the extra-renal clinical improvement, she ultimately progressed to end-stage kidney disease (ESKD), commencing peritoneal dialysis for three years before undergoing a successful uncomplicated cadaveric kidney transplant without prophylactic eculizumab. Two years after transplant, she has excellent transplant graft function without any further disease recurrence.

Conclusions

This case highlights the concept of extra-renal manifestations in aHUS initially resistant to eculizumab, which potentially responded to dose intensification. Whilst organ injuries are potentially reversible with timely targeted treatment, it appears that the kidneys are most vulnerable to injury.