bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical change during inter-hospital transfer for thrombectomy: Incidence, associated factors, and relationship with outcome
Authors: Seners Pierre , Ter Schiphorst Adrien , Wouters Anke , Yuen Nicole , Mlynash Michael , Arquizan Caroline , Heit Jeremy J , Kemp Stephanie , Christensen Soren , Sablot Denis , Wacongne Anne , Lalu Thibault , Costalat Vincent , Albers Gregory W , Lansberg Maarten G
Published: April 2024

Background:

Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome.

Methods:

We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately.

Results:

A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59–3.71; p < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37–0.98; p = 0.044).

Conclusion:

Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer.

Data access statement:

The data that support the findings of this study are available upon reasonable request.
A Pivotal Time and Place: University Place Attachment, Childhood Neighborhood Affordances, and Internalizing Symptoms in Emerging Adulthood
Authors: Tan Amber , Rice Marissa A. , Gonzalez Marlen Z.
Published: April 2024

People-place dynamics matter for well-being and for 69% of emerging adults in the US, the university is a pivotal place at a pivotal time. Research suggests that low childhood neighborhood affordances contribute to internalizing symptoms, but we know less about the impact of the university context. This study asked: how does university place attachment impact internalizing symptoms beyond the effects of childhood neighborhood affordances? Two-hundred and seventy-five university students self-reported on perceived childhood neighborhood affordances, university attachment, and current internalizing symptoms. Higher university attachment coincided with higher perceived neighborhood affordances and lower depression and social anxiety symptoms while controlling for demographic factors and parent-child relationship quality. Further, there was an indirect effect of neighborhood affordances via university attachment on social anxiety, but not depressive symptoms. Findings suggest that university place attachment contributes meaningfully to internalizing symptoms in emerging adulthood and that childhood neighborhood affordances may impact attachment to novel life-spaces.
Marginal Zone Lymphoma Manifesting as Macrophage Activation Syndrome: A Case Report
Authors: Ebrahimi Niloufar , Noor Sahibzadi Mahrukh , Kordasti Shahram , Akhtari Mojtaba , Norouzi Sayna , Vakhshoori Mehrbod , Abdipour Amir
Published: April 2024

Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis (HLH) when it occurs in the context of rheumatologic disorders. HLH is a rare and potentially life-threatening syndrome characterized by excessive immune system activation. It is mainly seen in children and can be genetic based or related to infections, malignancies, rheumatologic disorders, or immunodeficiency syndromes. MAS can present with nonspecific symptoms, leading to a delay in diagnosis. This report describes a case of a 64-year-old female with marginal zone lymphoma and systemic lupus erythematosus who presented with a purpuric rash and acute kidney injury. She underwent a kidney biopsy and was diagnosed with MAS. This case highlights the importance of promptly recognizing MAS’s symptoms and signs, allowing timely diagnosis and early therapeutic intervention. This potentially fatal condition tends to respond well to rapid treatment initiation with corticosteroids and to address the underlying condition.
The Impact of Miss Stitch on the Dimensional Properties and Stability of Double Weft Knitted Fabrics after Dry and Washing Relaxations
Authors: Bukhonka Nadiia P.
Published: April 2024

This study investigated the effect of the rib set-out repeat and single miss stitches on the structural properties and dimensional stability of double weft knitted fabrics compared with half Milano rib. Nine variations of double weft knitted fabrics were produced, each with a different number of inactive needles at the width repeat Rb. The fabrics were tested after 10 days of dry relaxation and five washings. The fabric’s structural repeat at the height Rh consisted of a combination of two courses, rib and plain (variant 1), and rib set-out and single with miss (float) stitch, with stitch repeats varying at the width Rb (for variants 2–10). The miss stitch was made on the technical back of the knitted fabrics, and the number of inactive needles during the production of the single and double stitches ranged from 1 to 3. The fabrics were manufactured using a 10-gauge flat bed-knitting machine from blended wool/PAN (60% wool, 40% PAN) 25×2tex×2 yarn. The results demonstrated that the width repeat of miss knit stitches Rb (different numbers of knit and miss loop stitches) plays a crucial role in determining the dimensional stability and structural properties of double knitted fabrics. The number of washing cycles did not significantly impact the structural properties (around ±5%). The research results demonstrated shrinkage in the length and width directions, specifically after the first two washing cycles. The rib set-out repeat and single miss stitches affect dimensional changes in both directions: an increase in the number of inactive needles increases shrinkage in the length and decreases shrinkage in the width direction. Overall, this study highlights the importance of the number and placement of miss stitches during the design process of double weft knitted fabrics, particularly when aiming to achieve specific structural and dimensional properties.
Auditing the Representation of Female Athletes in Sports Medicine Research: Fifth-Metatarsal Fractures
Authors: Klug Peter , Adams Jacob , Lents Gordon , Long Rachel , Herda Ashley , Vopat Bryan , Vopat Lisa
Published: April 2024

Background:

Female representation within athletics has increased as a result of Title IX, rising popularity, demand for equal compensation, and greater participation in multiple sports. Despite this, gender disparities in sports medicine research are apparent. This project serves to review the literature available on fifth-metatarsal fractures and assess the representation of female athletes in current literature.

Methods:

We used a standardized protocol to audit the representation of female athletes in sports science and sports medicine research for fifth-metatarsal fractures. Primary factors included population, athletic caliber, menstrual status, research theme, sample of males and females, journal impact factor, and Altmetric score.

Results:

Thirty articles met the inclusion criteria. A total of 472 fifth-metatarsal fractures were identified, with 373 of 472 fractures (79%) occurring in males and 99 of 472 (21%) in females. The majority of studies (18/30, 60%) were mixed cohort, followed by 10 male only (33.33%), 1 female only (3.33%), and 1 male vs female (3.33%). Out of 831 total patients in the 18 mixed-cohort studies, 605 of 831 patients (72.8%) were male and 226 of 831 patients (27%) were female. All 18 mixed-sex cohorts investigated health outcomes. Male-only studies evaluated health outcomes and performance metrics. No studies investigated female performance. The one female-only study investigated health outcomes and was the only study to account for menstrual status. There was a single metatarsal fracture in this study population.

Conclusion:

Females are underrepresented in research regarding sports science and sports medicine research for fifth-metatarsal fractures. Research focused on female-only fifth-metatarsal fracture studies exploring the potential impact of female sex–specific factors such as menstrual status in study design are needed.
“How I Do It: Endoscopic Management of Weight Regain After Roux-en-Y Gastric Bypass (With Video)”
Authors: Deng John , Montecino Ronald Blanco , Ellis Daniel J. , Tavakkoli Anna
Published: April 2024

Transoral outlet reduction (TORe) is an endoscopic intervention for patients who have weight recurrence, dumping syndrome, or post-prandial hypoglycemia following Roux-en-Y gastric bypass (RYGB). TORe offers a minimally invasive alternative to surgical revision, which is often associated with high morbidity rates. This paper will detail the approach to TORe in regard to patient selection, endoscopic technique, and post-TORe outcomes.
The prevalence and demographic associations of headache in the adult population of Benin: a cross-sectional population-based study
Authors: Adoukonou Thierry , Agbetou Mendinatou , Dettin Eric , Kossi Oyene , Husøy Andreas , Thomas Hallie , Houinato Dismand , Steiner Timothy J
Published: April 2024

Background

The Global Burden of Disease (GBD) study is increasingly well informed with regard to headache disorders, but sub-Saharan Africa (SSA) remains one of the large regions of the world with limited data directly derived from population-based studies. The Global Campaign against Headache has conducted three studies in this region: Ethiopia in the east, Zambia in the south and Cameroon in Central SSA. Here we report a similar study in Benin, the first from West SSA.

Methods

We used the same methods and questionnaire, applying cluster-randomized sampling in three regions of the country, randomly selecting households in each region, visiting these unannounced and randomly selecting one adult member (aged 18–65 years) of each household. The HARDSHIP structured questionnaire, translated into Central African French, was administered face-to-face by trained interviewers. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria.

Results

From 2,550 households with eligible members, we recruited 2,400 participants (participating proportion 94.1%). Headache ever was reported by almost all (95.2%), this being the lifetime prevalence. Headache in the last year was reported by 74.9%. Age-, gender- and habitation-adjusted estimates of 1-year prevalence were 72.9% for all headache, 21.2% for migraine (including definite and probable), 43.1% for TTH (also including definite and probable), 4.5% for probable medication-overuse (pMOH) and 3.1% for other headache on ≥ 15 days/month. One-day (point) prevalence of headache was 14.8% according to reported headache on the day preceding interview.

Conclusions

Overall, these findings are evidence that headache disorders are very common in Benin, a low-income country. The prevalence of pMOH, well above the estimated global mean of 1–2%, is evidence that poverty is not a bar to medication overuse. The findings are very much the same as those in a similar study in its near neighbour, Cameroon. With regard to migraine, they are reasonably in accord with two of three earlier studies in selected Beninese populations, which did not take account of probable migraine. This study adds to the hitherto limited knowledge of headache in SSA.
DPPA3 facilitates genome-wide DNA demethylation in mouse primordial germ cells
Authors: Toriyama Keisuke , Au Yeung Wan Kin , Inoue Azusa , Kurimoto Kazuki , Yabuta Yukihiro , Saitou Mitinori , Nakamura Toshinobu , Nakano Toru , Sasaki Hiroyuki
Published: April 2024

Background

Genome-wide DNA demethylation occurs in mammalian primordial germ cells (PGCs) as part of the epigenetic reprogramming important for gametogenesis and resetting the epigenetic information for totipotency. Dppa3 (also known as Stella or Pgc7) is highly expressed in mouse PGCs and oocytes and encodes a factor essential for female fertility. It prevents excessive DNA methylation in oocytes and ensures proper gene expression in preimplantation embryos: however, its role in PGCs is largely unexplored. In the present study, we investigated whether or not DPPA3 has an impact on CG methylation/demethylation in mouse PGCs.

Results

We show that DPPA3 plays a role in genome-wide demethylation in PGCs even before sex differentiation. Dppa3 knockout female PGCs show aberrant hypermethylation, most predominantly at H3K9me3-marked retrotransposons, which persists up to the fully-grown oocyte stage. DPPA3 works downstream of PRDM14, a master regulator of epigenetic reprogramming in embryonic stem cells and PGCs, and independently of TET1, an enzyme that hydroxylates 5-methylcytosine.

Conclusions

The results suggest that DPPA3 facilitates DNA demethylation through a replication-coupled passive mechanism in PGCs. Our study identifies DPPA3 as a novel epigenetic reprogramming factor in mouse PGCs.
The massive 340 megabase genome of Anisogramma anomala, a biotrophic ascomycete that causes eastern filbert blight of hazelnut
Authors: Cohen Alanna B. , Cai Guohong , Price Dana C. , Molnar Thomas J. , Zhang Ning , Hillman Bradley I.
Published: April 2024

Background

The ascomycete fungus Anisogramma anomala causes Eastern Filbert Blight (EFB) on hazelnut (Corylus spp.) trees. It is a minor disease on its native host, the American hazelnut (C. americana), but is highly destructive on the commercially important European hazelnut (C. avellana). In North America, EFB has historically limited commercial production of hazelnut to west of the Rocky Mountains. A. anomala is an obligately biotrophic fungus that has not been grown in continuous culture, rendering its study challenging. There is a 15-month latency before symptoms appear on infected hazelnut trees, and only a sexual reproductive stage has been observed. Here we report the sequencing, annotation, and characterization of its genome.

Results

The genome of A. anomala was assembled into 108 scaffolds totaling 342,498,352 nt with a GC content of 34.46%. Scaffold N50 was 33.3 Mb and L50 was 5. Nineteen scaffolds with lengths over 1 Mb constituted 99% of the assembly. Telomere sequences were identified on both ends of two scaffolds and on one end of another 10 scaffolds. Flow cytometry estimated the genome size of A. anomala at 370 Mb. The genome exhibits two-speed evolution, with 93% of the assembly as AT-rich regions (32.9% GC) and the other 7% as GC-rich (57.1% GC). The AT-rich regions consist predominantly of repeats with low gene content, while 90% of predicted protein coding genes were identified in GC-rich regions. Copia-like retrotransposons accounted for more than half of the genome. Evidence of repeat-induced point mutation (RIP) was identified throughout the AT-rich regions, and two copies of the rid gene and one of dim-2, the key genes in the RIP mutation pathway, were identified in the genome. Consistent with its homothallic sexual reproduction cycle, both MAT1-1 and MAT1-2 idiomorphs were found. We identified a large suite of genes likely involved in pathogenicity, including 614 carbohydrate active enzymes, 762 secreted proteins and 165 effectors.

Conclusions

This study reveals the genomic structure, composition, and putative gene function of the important pathogen A. anomala. It provides insight into the molecular basis of the pathogen’s life cycle and a solid foundation for studying EFB.
Single-cell profiling reveals transcriptome dynamics during bovine oocyte growth
Authors: Latorraca Lais Barbosa , Galvão António , Rabaglino Maria Belen , D’Augero Julieta Maria , Kelsey Gavin , Fair Trudee
Published: April 2024

Background

Mammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first signs of transcription activation in the oocyte are observed in the secondary follicle, later than during mouse and human oogenesis. While many studies have generated extensive datasets characterizing gene expression in bovine oocytes, they are mostly limited to the analysis of fully grown and matured oocytes. The aim of the present study was to apply single-cell RNA sequencing to interrogate the transcriptome of the growing bovine oocyte from the secondary follicle stage through to the mid-antral follicle stage.

Results

Single-cell RNA-seq libraries were generated from oocytes of known diameters (< 60 to > 120 μm), and datasets were binned into non-overlapping size groups for downstream analysis. Combining the results of weighted gene co-expression network and Trendy analyses, and differently expressed genes (DEGs) between size groups, we identified a decrease in oxidative phosphorylation and an increase in maternal -genes and transcription regulators across the bovine oocyte growth phase. In addition, around 5,000 genes did not change in expression, revealing a cohort of stable genes. An interesting switch in gene expression profile was noted in oocytes greater than 100 μm in diameter, when the expression of genes related to cytoplasmic activities was replaced by genes related to nuclear activities (e.g., chromosome segregation). The highest number of DEGs were detected in the comparison of oocytes 100–109 versus 110–119 μm in diameter, revealing a profound change in the molecular profile of oocytes at the end of their growth phase.

Conclusions

The current study provides a unique dataset of the key genes and pathways characteristic of each stage of oocyte development, contributing an important resource for a greater understanding of bovine oogenesis.
Metabolome and transcriptome analyses reveal changes of rapeseed in response to ABA signal during early seedling development
Authors: Chen Yaqian , Wu Jinfeng , Ma Changrui , Zhang Dawei , Zhou Dinggang , Zhang Jihong , Yan Mingli
Published: April 2024

Seed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.
The Egyptian wheat cultivar Gemmeiza-12 is a source of resistance against the fungus Zymoseptoria tritici
Authors: Qutb Abdelrahman M , Cambon Florence , McDonald Megan C , Saintenac Cyrille , Kettles Graeme J
Published: April 2024

Background

Wheat is one of the world’s most important cereal crops. However, the fungal pathogen Zymoseptoria tritici can cause disease epidemics, leading to reduced yields. With climate change and development of new agricultural areas with suitable environments, Z. tritici may advance into geographical areas previously unaffected by this pathogen. It is currently unknown how Egyptian wheat will perform in the face of this incoming threat. This project aimed to assess the resistance of Egyptian wheat germplasm to Z. tritici, to identify cultivars with high levels of resistance and characterise the mechanism(s) of resistance present in these cultivars.

Results

Eighteen Egyptian wheat cultivars were screened against two Z. tritici model isolates and exhibited a wide spectrum of responses. This ranged from resistance to complete susceptibility to one or both isolates tested. The most highly resistant cultivars from the initial screen were then tested under two environmental conditions against modern UK field isolates. Disease levels under UK-like conditions were higher, however, symptom development on the cultivar Gemmeiza-12 was noticeably slower than on other Egyptian wheats. The robustness of the resistance shown by Gemmeiza-12 was confirmed in experiments mimicking Egyptian environmental conditions, where degree of Z. tritici infection was lower. The Kompetitive allele-specific PCR (KASP) diagnostic assay suggested the presence of an Stb6 resistant allele in several Egyptian wheats including Gemmeiza-12. Infection assays using the IPO323 WT and IPO323ΔAvrStb6 mutant confirmed the presence of Stb6 in several Egyptian cultivars including Gemmeiza-12. Confocal fluorescence microscopy demonstrated that growth of the IPO323 strain is blocked at the point of stomatal penetration on Gemmeiza-12, consistent with previous reports of Stb gene mediated resistance. In addition to this R-gene mediated resistance, IPO323 spores showed lower adherence to leaves of Gemmeiza-12 compared to UK wheat varieties, suggesting other aspects of leaf physiology may also contribute to the resistance phenotype of this cultivar.

Conclusion

These results indicate that Gemmeiza-12 will be useful in future breeding programs where improved resistance to Z. tritici is a priority.
Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery
Authors: Luo Jing-chao , Luo Ming-hao , Zhang Yi-jie , Liu Wen-jun , Ma Guo-guang , Hou Jun-yi , Su Ying , Hao Guang-wei , Tu Guo-wei , Luo Zhe
Published: April 2024

Background

Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

Methods

Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified.

Results

Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling.

Conclusion

In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.
Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review
Authors: Kim Yoon-Ju , Lee Seong-Wook , Kim Mee-Seon , Kim Yong-Jin , Choi Ji-Young , Cho Jang-Hee , Kim Chan-Duck , Kim Yong-Lim , Yun Woo-Sung , Huh Seung , Lim Jeong-Hoon , Park Sun-Hee
Published: April 2024

Background

Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT.

Case presentation

A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL.

Conclusions

These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.
Prediction of the Ki-67 expression level in head and neck squamous cell carcinoma with machine learning-based multiparametric MRI radiomics: a multicenter study
Authors: Chen Weiyue , Lin Guihan , Chen Yongjun , Cheng Feng , Li Xia , Ding Jiayi , Zhong Yi , Kong Chunli , Chen Minjiang , Xia Shuiwei , Lu Chenying , Ji Jiansong
Published: April 2024

Background

This study aimed to develop and validate a machine learning (ML)-based fusion model to preoperatively predict Ki-67 expression levels in patients with head and neck squamous cell carcinoma (HNSCC) using multiparametric magnetic resonance imaging (MRI).

Methods

A total of 351 patients with pathologically proven HNSCC from two medical centers were retrospectively enrolled in the study and divided into training (n = 196), internal validation (n = 84), and external validation (n = 71) cohorts. Radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images and screened. Seven ML classifiers, including k-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forest (RF), linear discriminant analysis (LDA), naive Bayes (NB), and eXtreme Gradient Boosting (XGBoost) were trained. The best classifier was used to calculate radiomics (Rad)-scores and combine clinical factors to construct a fusion model. Performance was evaluated based on calibration, discrimination, reclassification, and clinical utility.

Results

Thirteen features combining multiparametric MRI were finally selected. The SVM classifier showed the best performance, with the highest average area under the curve (AUC) of 0.851 in the validation cohorts. The fusion model incorporating SVM-based Rad-scores with clinical T stage and MR-reported lymph node status achieved encouraging predictive performance in the training (AUC = 0.916), internal validation (AUC = 0.903), and external validation (AUC = 0.885) cohorts. Furthermore, the fusion model showed better clinical benefit and higher classification accuracy than the clinical model.

Conclusions

The ML-based fusion model based on multiparametric MRI exhibited promise for predicting Ki-67 expression levels in HNSCC patients, which might be helpful for prognosis evaluation and clinical decision-making.
Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study
Authors: Mennecier Bertrand , Khalifa Jonathan , Descourt Renaud , Greillier Laurent , Naltet Charles , Falchero Lionel
Published: April 2024

Background

We designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice.

Methods

A 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers.

Results

In ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2–7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI.

Conclusions

There is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.
Enhancing indicator condition–guided HIV testing in Taiwan: a nationwide case–control study from 2009 to 2015
Authors: Lee Chun-Yuan , Lin Yi-Pei , Lin Chun-Yu , Lu Po-Liang , Liang Fu-Wen
Published: April 2024

Background

Although indicator condition (IC)-guided HIV testing (IC-HIVT) is effective at facilitating timely HIV diagnosis, research on IC categories and the related HIV risk in Taiwan is limited. To improve the adoption and spread of IC-HIVT in Taiwan, this study compared the IC categories of people living with HIV (PLWH) and non-HIV controls and investigated delays in the diagnosis of HIV infection.

Methods

This nationwide, retrospective, 1:10-matched case–control study analyzed data from the Notifiable Diseases Surveillance System and National Health Insurance Research Database to evaluate 42 ICs for the 5-year period preceding a matched HIV diagnostic date from 2009 to 2015. The ICs were divided into category 1 ICs (AIDS-defining opportunistic illnesses [AOIs]), category 2 ICs (diseases associated with impaired immunity or malignancy but not AOIs), category 3 ICs (ICs associated with sexual behaviors), and category 4 ICs (mononucleosis or mononucleosis-like syndrome). Logistic regression was used to evaluate the HIV risk associated with each IC category (at the overall and annual levels) before the index date. Wilcoxon rank-sum test was performed to assess changes in diagnostic delays following an incident IC category by HIV transmission routes.

Results

Fourteen thousand three hundred forty-seven PLWH were matched with 143,470 non-HIV controls. The prevalence results for all ICs and category 1–4 ICs were, respectively, 42.59%, 11.16%, 15.68%, 26.48%, and 0.97% among PLWH and 8.73%, 1.05%, 4.53%, 3.69%, and 0.02% among non-HIV controls (all P < 0.001). Each IC category posed a significantly higher risk of HIV infection overall and annually. The median (interquartile range) potential delay in HIV diagnosis was 15 (7–44), 324.5 (36–947), 234 (13–976), and 74 (33–476) days for category 1–4 ICs, respectively. Except for category 1 for men who have sex with men, these values remained stable across 2009–2015, regardless of the HIV transmission route.

Conclusions

Given the ongoing HIV diagnostic delay, IC-HIVT should be upgraded and adapted to each IC category to enhance early HIV diagnosis.
The impact of preoperative nutritional status on postoperative outcomes: an insight from Geriatric Nutritional Risk Index in elderly pancreaticoduodenectomy patients
Authors: Hou Teng-Yuan , Lin Yu-Hung , Liu Yueh-Wei , Liu Yu-Yin , Li Wei-Feng , Kuo Ming-Chun , Huang Szu-Wei , Yeh Cheng-Hsi , Lin Yu-Cheng , Yin Shih-Min
Published: April 2024

Background

Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD.

Materials and Methods

This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS).

Results

Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002).

Conclusions

Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.
Impact of treatment with orthodontic aligners on the oral health-related quality of life
Authors: Souza Gabriela Luiza Nunes , de Campos França Esdras , de Araújo Lombardi Marcelo , da Costa Giselle Cabral , da Rocha Najara Barbosa , Abreu Lucas Guimarães
Published: April 2024

Background

There is an increasing interest in information on the effects of orthodontic aligners on the oral health-related quality of life (OHRQoL) of people.

Aim

To compare the impact of orthodontic aligners versus conventional fixed appliances on OHRQoL, using a validated tool and controlling for sociodemographic and clinical variables.

Method

Sixty-one individuals participated in this study. Group 1 (G1) consisted of 33 individuals under treatment with orthodontic aligners and Group 2 (G2) comprised 28 individuals under treatment with conventional fixed appliances. OHRQoL was evaluated with the Oral Health Impact Profile (OHIP-14) in which 14 items are distributed across seven dimensions: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. The higher the score, the more negative is the perception of the individual regarding his/her OHRQoL. Descriptive statistics, Mann-Whitney test, and Poisson regression were performed. Effect Size (ES) and Minimal Clinically Important Difference (MCID) were also determined.

Results

Participants’ mean age was 30.69 years. Individuals in G1 had a significantly lower score for physical pain and the total score of OHIP-14 compared to individuals in G2 (p < 0.05). The ES was large (ES = 0.74) for physical pain and moderate (ES = 0.46) for the total score. The ES was moderate for physical disability (ES = 0.50). The difference between groups for physical pain (1.30) and for physical disability (0.90) was greater than the MCID (0.87 and 0.88, respectively). Poisson regression showed that G2 individuals showed a score for physical pain 1.39 times higher than those of G1 in the adjusted model (OR = 1.39, [1.03–1.89], p = 0.031).

Conclusion

Those under treatment with orthodontic aligners have a more positive perception of OHRQoL compared to those wearing fixed appliances.
Epigallocatechin-3-Gallate attenuates lipopolysacharide-induced pneumonia via modification of inflammation, oxidative stress, apoptosis, and autophagy
Authors: Shen Meili , You Yuting , Xu Chengna , Chen Zhixu
Published: April 2024

Background

Pneumonia, the acute inflammation of lung tissue, is multi-factorial in etiology. Hence, continuous studies are conducted to determine the mechanisms involved in the progression of the disease and subsequently suggest effective treatment. The present study attempted to evaluate the effects of Epigallocatechin-3-Gallate (EGCG), an herbal antioxidant, on inflammation, oxidative stress, apoptosis, and autophagy in a rat pneumonia model.

Methods

Forty male Wistar rats, 5 months old and 250–290 g were divided into four groups including control, EGCG, experimental pneumonia (i/p LPS injection, 1 mg/kg), and experimental pneumonia treated with EGCG (i/p, 15 mg/kg, 1 h before and 3 h after LPS instillation). Total cell number in the bronchoalveolar lavage fluid, inflammation (TNF-a, Il-6, IL-1β, and NO), oxidative stress (Nrf2, HO-1, SOD, CAT, GSH, GPX, MDA, and TAC), apoptosis (BCL-2, BAX, CASP-3 and CASP-9), and autophagy (mTOR, LC3, BECN1) were evaluated.

Results

The findings demonstrated that EGCG suppresses the LPS-induced activation of inflammatory pathways by a significant reduction of inflammatory markers (p-value < 0.001). In addition, the upregulation of BCL-2 and downregulation of BAX and caspases revealed that EGCG suppressed LPS-induced apoptosis. Furthermore, ECGC suppressed oxidative injury while promoting autophagy in rats with pneumonia (p-value < 0.05).

Conclusion

The current study revealed that EGCG could suppress inflammation, oxidative stress, apoptosis, and promote autophagy in experimental pneumonia models of rats suggesting promising therapeutical properties of this compound to be used in pneumonia management.
Evaluation of Lippia scaberrima Sond. and Aspalathus linearis (Burm.f.) R. Dahlgren extracts on human CYP enzymes and gold nanoparticle synthesis: implications for drug metabolism and cytotoxicity
Authors: Kok Anna-Mari , Juvonen Risto , Pasanen Markku , Mandiwana Vusani , Kalombo Michel Lonji , Ray Suprakas Sinha , Rikhotso-Mbungela Rirhandzu , Lall Namrita
Published: April 2024

Background

Metabolism is an important component of the kinetic characteristics of herbal constituents, and it often determines the internal dose and concentration of these effective constituents at the target site. The metabolic profile of plant extracts and pure compounds need to be determined for any possible herb-drug metabolic interactions that might occur.

Methods

Various concentrations of the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with fermented and unfermented Aspalathus linearis extract were used to determine the inhibitory potential on placental, microsomal and recombinant human hepatic Cytochrome P450 enzymes. Furthermore, the study investigated the synthesis and characterization of gold nanoparticles from the ethanolic extract of Lippia scaberrima as a lead sample. Confirmation and characterization of the synthesized gold nanoparticles were conducted through various methods. Additionally, the cytotoxic properties of the ethanolic extract of Lippia scaberrima were compared with the gold nanoparticles synthesized from Lippia scaberrima using gum arabic as a capping agent.

Results

All the samples showed varying levels of CYP inhibition. The most potent inhibition took place for CYP2C19 and CYP1B1 with 50% inhibitory concentration (IC50) values of less than 0.05 µg/L for the essential oil tested and IC50-values between 0.05 µg/L-1 µg/L for all the other combinations and extracts tested, respectively. For both CYP1A2 and CYP2D6 the IC50-values for the essential oil, the extracts and combinations were found in the range of 1 – 10 µg/L. The majority of the IC50 values found were higher than 10 µg/L and, therefore, were found to have no inhibition against the CYP enzymes tested.

Conclusion

Therefore, the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with Aspalathus linearis do not possess any clinically significant CYP interaction potential and may be further investigated for their adjuvant potential for use in the tuberculosis treatment regimen. Furthermore, it was shown that the cytotoxic potential of the Lippia scaberrima gold nanoparticles was reduced by twofold when compared to the ethanolic extract of Lippia scaberrima.
Physicians’ views on the role of relatives in euthanasia and physician-assisted suicide decision-making: a mixed-methods study among physicians in the Netherlands
Authors: Renckens Sophie C. , Onwuteaka-Philipsen Bregje D. , van der Heide Agnes , Pasman H. Roeline
Published: April 2024

Background

Relatives have no formal position in the practice of euthanasia and physician-assisted suicide (EAS) according to Dutch legislation. However, research shows that physicians often involve relatives in EAS decision-making. It remains unclear why physicians do (not) want to involve relatives. Therefore, we examined how many physicians in the Netherlands involve relatives in EAS decision-making and explored reasons for (not) involving relatives and what involvement entails.

Methods

In a mixed-methods study, 746 physicians (33% response rate) completed a questionnaire, and 20 were interviewed. The questionnaire included two statements on relatives’ involvement in EAS decision-making. Descriptive statistics were used, and multivariable logistic regression analyses to explore characteristics associated with involving relatives. In subsequent interviews, we explored physicians’ views on involving relatives in EAS decision-making. Interviews were thematically analysed.

Results

The majority of physicians want to know relatives’ opinions about an EAS request (80%); a smaller group also takes these opinions into account in EAS decision-making (35%). Physicians who had ever received an explicit EAS request were more likely to want to know opinions and clinical specialists and elderly care physicians were more likely to take these opinions into account. In interviews, physicians mentioned several reasons for involving relatives: e.g. to give relatives space and help them in their acceptance, to tailor support, to be able to perform EAS in harmony, and to mediate in case of conflicting views. Furthermore, physicians explained that relatives’ opinions can influence the decision-making process but cannot be a decisive factor. If relatives oppose the EAS request, physicians find the process more difficult and try to mediate between patients and relatives by investigating relatives’ objections and providing appropriate information. Reasons for not taking relatives’ opinions into account include not wanting to undermine patient autonomy and protecting relatives from a potential burdensome decision.

Conclusions

Although physicians know that relatives have no formal role, involving relatives in EAS decision-making is common practice in the Netherlands. Physicians consider this important as relatives need to continue with their lives and may need bereavement support. Additionally, physicians want to perform EAS in harmony with everyone involved. However, relatives’ opinions are not decisive.
Bacterial accumulation in intestinal folds induced by physical and biological factors
Authors: Yang Jinyou , Isaka Toma , Kikuchi Kenji , Numayama-Tsuruta Keiko , Ishikawa Takuji
Published: April 2024

Background

The gut microbiota, vital for host health, influences metabolism, immune function, and development. Understanding the dynamic processes of bacterial accumulation within the gut is crucial, as it is closely related to immune responses, antibiotic resistance, and colorectal cancer. We investigated Escherichia coli behavior and distribution in zebrafish larval intestines, focusing on the gut microenvironment.

Results

We discovered that E. coli spread was considerably suppressed within the intestinal folds, leading to a strong physical accumulation in the folds. Moreover, a higher concentration of E. coli on the dorsal side than on the ventral side was observed. Our in vitro microfluidic experiments and theoretical analysis revealed that the overall distribution of E. coli in the intestines was established by a combination of physical factor and bacterial taxis.

Conclusions

Our findings provide valuable insight into how the intestinal microenvironment affects bacterial motility and accumulation, enhancing our understanding of the behavioral and ecological dynamics of the intestinal microbiota.