bluuebunny/crossref_metadata_2025 huggingface dataset:
Cataclysmic variables from Sloan Digital Sky Survey – V (2020–2023) identified using machine learning
Authors: Inight Keith , Gänsicke Boris T , Schwope Axel , Anderson Scott F , Breedt Elmé , Brownstein Joel R , Demasi Sebastian , Friedrich Susanne , Hermes J J , Long Knox S , Mulvany Timothy , Adamane Pallathadka Gautham , Salvato Mara , Scaringi Simone , Schreiber Matthias R , Stringfellow Guy S , Thorstensen John R , Tovmassian Gagik , Zakamska Nadia L
Published: November 2024

SDSS-V is carrying out a dedicated survey for white dwarfs, single and in binaries, and we report the analysis of the spectroscopy of 504 cataclysmic variables (CVs) and CV candidates obtained during the first 34 months of observations of SDSS-V. We developed a convolutional neural network (CNN) to aid with the identification of CV candidates among the over 2 million SDSS-V spectra obtained with the BOSS spectrograph. The CNN reduced the number of spectra that required visual inspection to $\simeq 2$ per cent of the total. We identified 776 CV spectra among the CNN-selected candidates, plus an additional 27 CV spectra that the CNN misclassified, but that were found serendipitously by human inspection of the data. Analysing the SDSS-V spectroscopy and ancillary data of the 504 CVs in our sample, we report 61 new CVs, spectroscopically confirm 248 and refute 13 published CV candidates, and we report 82 new or improved orbital periods. We discuss the completeness and possible selection biases of the machine learning methodology, as well as the effectiveness of targeting CV candidates within SDSS-V. Finally, we re-assess the space density of CVs, and find $1.2\times 10^{-5}\, \mathrm{pc^{-3}}$.
DRAMP 4.0: an open-access data repository dedicated to the clinical translation of antimicrobial peptides
Authors: Ma Tianyue , Liu Yanchao , Yu Bingxin , Sun Xin , Yao Huiyuan , Hao Chen , Li Jianhui , Nawaz Maryam , Jiang Xun , Lao Xingzhen , Zheng Heng
Published: November 2024

Antimicrobial peptides (AMPs) are potential candidates for treating multidrug-resistant bacterial infections, yet only a small number of them have progressed into clinical trials. The main challenges include the poor stability and hemolytic/cytotoxic properties of AMPs. Considering this, in the update of the Data Repository of Antimicrobial Peptides (DRAMP), a new annotation on serum and protease stability is added, and special efforts were made to update the hemolytic/cytotoxic information of AMPs. The DRAMP 4.0 currently holds 30 260 entries (8 001 newly added), consisting of 11 612 general entries, 17 886 patent entries, 96 clinical entries, 377 specific entries, 110 entries with stability data, and 179 expanded entries. A total of 2891 entries possess experimentally determined hemolytic activity information, while 2674 entries contain cytotoxicity data by experimental validation. The update also covers new annotations, statistics, categories, functions, and download links. DRAMP is available online at http://dramp.cpu-bioinfor.org/.
DDDR-18. TARGETTING GLIOBLASTOMA MULTIFORME USING A MULTIACTION ANTICANCER ANTI-INFLAMMATORY THERAPEUTIC STRATEGY
Authors: Fatima Shadma , Gamage Kasuni , Sajinovic Mila , Herman David , Scott Kieran F , de Souza Paul
Published: November 2024

Glioblastoma multiforme (GBM) represents a significant challenge in adult brain tumor management, characterized by its aggressive nature and poor prognosis despite multimodal therapies. Current standard chemotherapy, Temozolomide (TMZ), offers limited survival benefits. In a recent breakthrough, the cyclic peptide cyclo-((2-Nal)-Leu-Ser-(2-Nal)-Arg) acetate (c2), initially developed for prostate cancer, demonstrates remarkable promise against GBM. By selectively inhibiting the inflammatory phospholipase enzyme sPLA2IIA, c2 significantly impedes GBM cell proliferation, surpassing TMZ efficacy in multiple resistant cell lines. Moreover, c2 exhibits potential to inhibit tumor growth and metastasis, confirmed in 3D tumoroid and wound healing assays. Mechanistic insights reveal modulation of crucial cellular pathways, including viral entry, cytoskeletal structure, and signaling cascades. Preclinical investigations demonstrate c2’s ability to penetrate the blood-brain barrier and attenuate tumor progression markers. At multiple levels, c2 is shown to target inhibition of ERBB2 and EGFR signalling and also have impacts on HIF1-NF-kB axis. This study proposes c2 as a potent anti-GBM candidate, warranting evaluations for its pharmacological profile, safety, and efficacy. With its potential to address the urgent need for effective GBM therapies, c2 holds promise as a significant advancement in GBM treatment, offering hope for improved patient outcomes.
Multiomic analyses reveal new targets of polycomb repressor complex 2 in Schwann lineage cells and malignant peripheral nerve sheath tumors
Authors: Bhunia Minu M , Stehn Christopher M , Jubenville Tyler A , Novacek Ethan L , Larsson Alex T , Madala Mahathi , Suppiah Suganth , Velez-Reyes Germán L , Williams Kyle B , Sokolowski Mark , Williams Rory L , Finnerty Samuel J , Temiz Nuri A , Caride Ariel , Bhagwate Aditya V , Nagaraj Nagaswaroop K , Lee Jeong-Heon , Ordog Tamas , Zadeh Gelareh , Largaespada David A
Published: November 2024

Background

Malignant peripheral nerve sheath tumors (MPNSTs) can arise from atypical neurofibromas (ANF). Loss of the polycomb repressor complex 2 (PRC2) is a common event. Previous studies on PRC2-regulated genes in MPNST used genetic add-back experiments in highly aneuploid MPNST cell lines which may miss PRC2-regulated genes in NF1-mutant ANF-like precursor cells. A set of PRC2-regulated genes in human Schwann cells (SCs) has not been defined. We hypothesized that PRC2 loss has direct and indirect effects on gene expression resulting in MPNST, so we sought to identify PRC2-regulated genes in immortalized human Schwann cells (iHSCs).

Methods

We engineered NF1-deficient iHSCs with loss of function SUZ12 or EED mutations. RNA sequencing revealed 1327 differentially expressed genes to define PRC2-regulated genes. To investigate MPNST pathogenesis, we compared genes in iHSCs to consistent gene expression differences between ANF and MPNSTs. Chromatin immunoprecipitation sequencing was used to further define targets. Methylome and proteomic analyses were performed to further identify enriched pathways.

Results

We identified potential PRC2-regulated drivers of MPNST progression. Pathway analysis indicates many upregulated cancer-related pathways. We found transcriptional evidence for activated Notch and Sonic Hedgehog (SHH) signaling in PRC2-deficient iHSCs. Functional studies confirm that Notch signaling is active in MPNST cell lines, patient-derived xenografts, and transient cell models of PRC2 deficiency. A combination of MEK and γ-secretase inhibition shows synergy in MPNST cell lines.

Conclusions

We identified PRC2-regulated genes and potential drivers of MPNSTs. Our findings support the Notch pathway as a druggable target in MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches.
Associations between employees’ alcohol consumption, insomnia and HR management strength
Authors: Dao-Tran T-H , Townsend K , Loudoun R , Wilkinson A , Seib C
Published: November 2024

Background

Understanding of hazardous alcohol drinking and insomnia among Australian ambulance personnel is limited. Australian ambulance organizations have strengthened their organizational human resource management (HRM) to promote their employees’ healthy lifestyles, health and well-being.

Aims

To describe the prevalence of hazardous alcohol consumption and insomnia among Australian ambulance personnel and to explore their associations with the organizational HRM strength.

Methods

This cross-sectional study was conducted on 492 ambulance personnel randomly selected from three Australian states. The Alcohol Use Disorders tool, The Insomnia Severity Index and the Perceived HRM System Strength instrument measured alcohol consumption, insomnia and HRM strength. Descriptive analyses, bivariate association analyses and general linear models were used for data analysis.

Results

Twenty per cent of Australian ambulance personnel consumed alcohol at a hazardous level and 68% experienced clinically significant insomnia. There was no significant association between organizational HRM strength and ambulance personnel’s hazardous alcohol consumption. There was a significant association between organizational HRM strength (consensus) and ambulance personnel’s insomnia experience.

Conclusions

Hazardous alcohol consumption and insomnia were concerns among Australian ambulance personnel. Even though strengthening the HRM system might reduce their experience of insomnia, simply strengthening the HRM system could not reduce their hazardous alcohol consumption.
Wood hardness drives nest-site selection in woodpeckers of the humid Chaco
Authors: Di Sallo Facundo G , Cockle Kristina L
Published: November 2024

Avian excavators (woodpeckers and other species) select nest sites based on the characteristics of the nest patch, nest tree, and substrate. These characteristics could increase foraging opportunities or reduce the risk of predation, but there is also a potentially important role for wood hardness in restricting nest-site selection, a role that has been little explored and is expected to vary among species according to their ability to excavate. We examined patterns of nest-site selection in 8 woodpecker species in the humid Chaco of South America, where the dominant trees have extremely hard wood. We hypothesized that (1) wood hardness is the main factor driving the selection of excavation sites, and (2) interspecific variation in body size and foraging behavior (traits frequently related to excavation ability) explain interspecific variation in the wood hardness of excavated nest substrates. From 2016 to 2019 in well-preserved forests of the Argentine Chaco, we compared nesting cavities excavated in wood (cases; n = 42) vs. potential wood substrates without cavities (matched controls) and made 187 focal observations of foraging woodpeckers. Woodpeckers selected nesting substrates with softer heartwood than potential substrates, regardless of any other characteristics of the tree or nest patch. Wood hardness around nest cavities increased with body size and the prevalence of chiseling during foraging, traits that were positively correlated. Woodpeckers often excavated in Prosopis spp. (Algarrobos) but rarely in Schinopsis balansae (Quebracho), a tree with exceptionally hard internal wood, in which cavity adopters frequently nest in non-excavated cavities. Wood hardness is critical to assessing the role of woodpeckers as cavity facilitators, understanding the costs and benefits of excavation, and interpreting excavation patterns across species and forests globally.
Defective flux and splicing abnormality restoration of stellar spectra in LAMOST based on deep learning
Authors: Wu Minglei , Bu Yude
Published: November 2024

Sky surveys such as the Large Sky Area Multi-Object Fibre Spectroscopic Telescope can capture numerous spectra. However, many factors in astronomical observations, such as observation conditions and instrumental effects, can degrade spectrum quality, resulting in defective fluxes and splicing abnormality. These factors significantly reduce the precision of scientific information extracted from such spectra. In the past, these flux values were considered unreliable and their utilization was low. Thus, it is crucial to develop and utilize spectra restoration algorithms to improve spectra quality and enable further scientific exploration. Unfortunately, few research has been done on these low-quality spectra. In this paper, we propose a novel spectrum restoration algorithm, which is called the Anomaly Spectra Restoration Generative Adversarial Nets (Anomaly_GANs) based on Generative Adversarial Networks (GANs). The experiment shows that the performance of Anomaly_GANs is better than those of other methods concerning spectrum restoration. Therefore, our method can serve as an effective approach for spectrum restoration, providing a suitable replacement for previous methods.
Efficacy and safety assessment of probiotic Bacillus coagulans (Heyndrickxia coagulans) BCP92 for treatment of diarrhea
Authors: Shaikh Sohel S , Patel Snehal , Malik Anis , Kumar S Aakash
Published: November 2024

Objective: Probiotics offer a potentially new therapeutic approach for the treatment of diarrhea. This study aimed to determine the anti-diarrheal activity of Bacillus coagulans BCP92 (MTCC 25460) and its safety assessment (acute and sub-acute toxicity studies) in animal models and cell lines. Methods: The antidiarrheal activity was studied in mice using a castor oil-induced diarrhea model. In the acute toxicity study, the rats were orally fed 2000 mg/kg (4 × 1011 CFU/g) of B. coagulans BCP92 (MTCC 25460) as a single dose, and for sub-acute toxicity study rats received 250, 500, and 1,000 mg/kg/day for 28 days. At the end of the treatment, body weight, organ weight, food intake, biochemical parameters, hematological parameters, and histopathology were studied. B. coagulans BCP92 is effective against diarrhea by reducing the onset of diarrhea (latency), frequency of defecation, total fecal weight, and percentage of defecation. In-vitro MTT assay was performed on Vero cell lines. Results: In-vitro MTT assay showed a cytoprotective effect. In acute toxicity study, 2000 mg/kg dose did not cause any alteration in clinical signs, morbidity, or mortality. The findings of the subacute toxicity study showed no alterations in physical appearance and behavioral patterns. Moreover, no significant variations were found in organ weights and hematological and biochemical parameters of the treated groups in the control group. Furthermore, no visible histological changes were observed in the heart, lung, liver, and kidney of the high-dose treatment groups. Conclusion: Thus, the results of the present study conclude that B. coagulans BCP92 is safe for human use in the treatment of diarrhea.
Chronic inhalation exposure to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) alters cardiac collagen in Wistar rats
Authors: Mariano Larissa Ferreira Rós , Mariano Thaoan Bruno , Floriano Rafael Stuani , Gomes Mariana Janini , Engel Letícia Estevam , Nai Gisele Albonguetti , Pacagnelli Francis Lopes
Published: November 2024

Introduction: 2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most used in the world and exposure to herbicides can affect animals and humans, causing toxic effects that include cardiotoxicity. This is the first study to evaluate cardiac remodeling after experimental simulation of environmental exposure by chronic inhalation (6 months) to the herbicide 2,4-D. Methods: Thirty male Wistar rats were exposed to two different concentrations of the 2,4-D formulation (low – 187.17 mg/m3; and high – 467.93 mg/m3) and the control group exposed to nebulization of chloride solution 0.9% sodium. Inhalation exposure lasted 6 months. Mice hearts were collected for histology. Results: There was a difference between exposure concentrations in relation to the increase in cardiac collagen (P < 0.0001). In mice exposed to a low dose of 2,4-D and a decrease in the fractal dimension of cardiac collagen in the high dose of 2, 4-D (P = 0.010). Discussion: This study shows that chronic inhalation exposure to 2,4-D induces cardiotoxicity in rats, characterized by extracellular matrix reorganization and changes in collagen levels, highlighting the impact of the exposure route on cardiac outcomes. Conclusion: There was no difference in relation to anatomical parameters, cardiomyocyte area, collagen types I and III and analysis of arteriole thickness. Chronic exposure at different doses to the 2,4D herbicide had the potential to cause damage to cardiac remodeling by altering cardiac collagen in rats.
The novel immune landscape of immune‐checkpoint blockade in EBV‐associated malignancies
Authors: Zhang Feng , Li Wenjing , Zheng Xinglong , Ren Yinlong , Li Lijun , Yin Haiyan
Published: November 2024

The Epstein–Barr virus (EBV) is a ubiquitous gamma‐herpesvirus and a class 1 carcinogen that is closely associated with a series of malignant lymphomas and epithelial cell carcinomas. Although these EBV‐related cancers may exhibit different features in clinical symptoms and anatomical sites, they all have a characteristic immune‐suppressed tumor immune microenvironment (TIME) that is tightly correlated with an abundance of tumor‐infiltrating lymphocytes (TILs) that primarily result from the EBV infection. Overwhelming evidence indicates that an upregulation of immune‐checkpoint molecules is a powerful strategy employed by the EBV to escape immune surveillance. While previous studies have mainly focused on the therapeutic effects of PD‐1 and CTLA‐4 blockades in treating EBV‐associated tumors, several novel inhibitory receptors (e.g., CD47, LAG‐3, TIM‐3, VISTA, and DDR1) have recently been identified as potential targets for treating EBV‐associated malignancies (EBVaMs). This review retrospectively summarizes the biological mechanisms used for immune checkpoint evasion in EBV‐associated tumors. Its purpose is to update our current knowledge concerning the underlying mechanisms by which an immune checkpoint blockade triggers host antitumor immunity against EBVaMs. Additionally, this review may help investigators to more fully understand the correlation between EBV infection and tumor development and subsequently develop novel therapeutic strategies.
Biochemical, biophysical, and structural investigations of two mutants (C154Y and R312H) of the human Kir2.1 channel involved in the Andersen‐Tawil syndrome
Authors: Zuniga Dania , Zoumpoulakis Andreas , Veloso Rafael F. , Peverini Laurie , Shi Sophie , Pozza Alexandre , Kugler Valérie , Bonneté Françoise , Bouceba Tahar , Wagner Renaud , Corringer Pierre‐Jean , Fernandes Carlos A. H. , Vénien‐Bryan Catherine
Published: November 2024

Inwardly rectifying potassium (Kir) channels play a pivotal role in physiology by establishing, maintaining, and regulating the resting membrane potential of the cells, particularly contributing to the cellular repolarization of many excitable cells. Dysfunction in Kir2.1 channels is implicated in several chronic and debilitating human diseases for which there are currently no effective treatments. Specifically, Kir2.1‐R312H and Kir2.1‐C154Y mutations are associated with Andersen‐Tawil syndrome (ATS) in humans. We have investigated the impact of these two mutants in the trafficking of the channel to the cell membrane and function in Xenopus laevis oocytes. Despite both mutations being trafficked to the cell membrane at different extents and capable of binding PIP2 (phosphatidylinositol‐4,5‐bisphosphate), the main modulator for channel activity, they resulted in defective channels that do not display K+ current, albeit through different molecular mechanisms. Coexpression studies showed that R312H and C154Y are expressed and associated with the WT subunits. While WT subunits could rescue R312H dysfunction, the presence of a unique C154Y subunit disrupts the function of the entire complex, which is a typical feature of mutations with a dominant‐negative effect. Molecular dynamics simulations showed that Kir2.1‐C154Y mutation induces a loss in the structural plasticity of the selectivity filter, impairing the K+ flow. In addition, the cryo‐EM structure of the Kir2.1‐R312H mutant has been reconstructed. This study identified the molecular mechanisms by which two ATS‐causing mutations impact Kir2.1 channel function and provide valuable insights that can guide potential strategies for the development of future therapeutic interventions for ATS.
Percutaneous Screw Fixation for the Management of Delayed Unions in Pediatric Lateral Humeral Condylar Fractures
Authors: Chang Eric , Gajewski Christopher , Thompson Rachel M. , Silva Mauricio
Published: November 2024

Background:

The use of in situ screw fixation for the treatment of pediatric lateral humeral condyle (LCH) delayed unions has recently been reported. While attractive, the currently available literature consists of small retrospective studies with mixed results. As such, the present study aims to describe the outcome of a group of children with delayed unions of LCH fractures treated with in situ fixation using a single, percutaneously placed cannulated screw in compression.

Methods:

A retrospective review of all pediatric patients (below 18 y) with lateral condyle fractures of the humerus treated surgically for delayed union between 2013 and 2023 at a single, tertiary referral center was completed. Clinical and radiologic variables related to the initial injury and delayed union were abstracted from the medical record, as were surgical variables. Radiographs were evaluated for union postoperatively; time to union was determined by the senior authors. Descriptive statistics were used to summarize demographic and outcome variables.

Results:

A total of 12 consecutive patients met the inclusion criteria. The mean age at the time of initial injury was 5.6 years; subjects were followed for a mean of 3.0 years following initial presentation. All were treated with a single, percutaneously placed screw in compression at a mean of 10.5 months after the original injury. Radiographic union was achieved in 11 (91.7%) patients. At the latest follow-up, all patients were pain free and demonstrated a functional arc of motion without evidence of avascular necrosis. A total of 2 patients required revision for loss of fixation. In one patient, a persistent lucent line was observed, and 1 patient was found to have a cubitus valgus deformity, both of which were not clinically relevant.

Conclusions:

Our results suggest that with the use of proper technique (a 4.5 cannulated screw inserted through the metaphyseal portion of the lateral condyle fragment, engaging the most medial/distal aspect of the humeral shaft), radiographic union and clinical healing can be achieved in the majority of patients. Percutaneous screw fixation should be considered as an option for cases of noninfected pediatric lateral condyle delayed unions.

Level of Evidence:

Level IV—evidence therapeutic studies
Safety of the contrast enhancement agent sulfur hexafluoride in ultrasound: Analysis of the Federal Drug Administration Adverse Event Reporting System database
Authors: Walker Courtney N. , Andrews Michael B. , Adler Douglas G.
Published: November 2024

Background and Objectives

Sulfur hexafluoride is an inert gas that creates microbubbles to enhance diagnostic accuracy in a variety of ultrasound (US) studies and is widely used in EUS. We analyzed the reported adverse events (AEs) of the US contrast agent, sulfur hexafluoride, extensively used during EUS procedures using a US national database.

Methods

From December 2008 to January 2024, AEs reported in the Federal Drug Administration Adverse Event Reporting System database for sulfur hexafluoride were examined.

Results

There were 1069 individual reports analyzed. Reports were excluded if they contained drugs other than sulfur hexafluoride. Echocardiogram (70.9%) was the common diagnostic study in which sulfur hexafluoride was administered. The most common AE reported was anaphylactic reaction (n = 179, 16.7%), followed by hypotension (n = 162, 15.2%), cardiac arrest (n = 161, 15.1%), and dyspnea (n = 159, 14.9%). The most common gastrointestinal AE was nausea (n = 135, 12.6%). Severity of AEs ranged from nonserious to death. Death associated with sulfur hexafluoride use was reported in 58 patients (5.4% of AE reports).

Conclusions

Anaphylactic reaction was the most common AE reported with sulfur hexafluoride use, and severe AEs including death may be more common than prior large, retrospective, observational studies to date have suggested.
Serum autotaxin positively associates with hypertension in postmenopausal women: a single center study in China
Authors: Zhang Jie , Wang Jiayi , Zhou Xuefeng , Chen Shurong , Li Yu , Ke Yini , Li Youming , Yu Chaohui , Chen Yi
Published: November 2024

Aim:

Autotaxin is an adipokine involved in metabolic disorders. The aim of the current study was to evaluate serum autotaxin levels in hypertensive postmenopausal women and establish a relationship between autotaxin and other comorbidities in this special group.

Methods:

This single-center study included postmenopausal women who received annual health examinations at the First Affiliated Hospital, College of Medicine, Zhejiang University in Zhejiang, China. The metabolic and demographic characteristics of the subjects, including age, sex, height, weight, blood pressure, and biochemical indices, were collected. The serum autotaxin level was measured via ELISA. The Kolmogorov-Smirnov test, Student's t test, Mann–Whitney U test, χ
2 test, receiver operating characteristic (ROC) curve analysis, Spearman correlation analysis and multivariate logistic regression analysis were adopted for statistical analysis.

Results:

This pilot observational study included 25 hypertensive postmenopausal women and 25 age-matched normotensive controls. Hypertensive patients presented significant metabolic disturbances with greater comorbidities such as nonalcoholic fatty liver disease, obesity, overweight, diabetes, hypertriglyceridemia and hyperuricemia (P < 0.05), impaired renal health with higher uric acid levels (P < 0.001), and slightly elevated creatinine levels (P = 0.156) with lower estimated glomerular filtration rates (eGFRs) (P = 0.195). The serum autotaxin level was markedly greater in the hypertensive group (239.0±59.6 ng/ml vs. 192.7 ± 49.0 ng/ml; P < 0.01) and was positively associated with systolic blood pressure; diastolic blood pressure; and alanine transaminase, triglycerides (TG), creatinine, and uric acid levels and inversely associated with the eGFR (P < 0.05) among postmenopausal women. Serum autotaxin levels positively predicted hypertension, with an AU-ROC of 0.750 [95% confidence interval (CI): 0.613–0.888] and a Youden index of 0.480 at a cutoff of 225 ng/ml. In the multivariate logistic regression analysis, after adjustment for demographic and metabolic parameters (including age, BMI, ALT, TB, uric acid, FBG, TG, LDL and creatinine), autotaxin (ATX) remained independently positively correlated with the risk of hypertension [odds ratio: 1.016, 95% CI 1.001–1.031; P < 0.05).

Conclusions:

Among postmenopausal women, the serum autotaxin level is significantly elevated in the hypertensive group compared with age-matched normotensive controls. ATX is related to multiple metabolic disorders and renal health, suggesting that autotaxin has potential as a multiorgan therapeutic target for cardiovascular-metabolic-renal disorders.
Predictive Factors in Asymptomatic Bacteriuria Treatment
Authors: Yazdi Mona T. , Mahatanan Rattanaporn , Ho Caroline , Rovelsky Suzette
Published: November 2024

Background

Asymptomatic bacteriuria (ASB) can often be inappropriately treated with antibiotics. The primary objective was to identify factors associated with antibiotic treatment of ASB. The secondary objective was to identify the prevalence of ASB treatment at our institution before and after Infectious Diseases Society of America (IDSA) updated Clinical Practice Guidelines for the Management of Asymptomatic Bacteriuria in 2019.
1

Methods

This is a retrospective chart review of adults admitted to a rural Veterans Affairs Hospital in White River Junction, Vermont, with culture confirmed bacteriuria. Those who did not meet National Healthcare Safety Network criteria for diagnosis of urinary tract infection were classified as having ASB.

Results

The prevalence of ASB treatment was 58% (n = 61/106). Patients older than 80 years had 3.73 increased odds of receiving antibiotics for ASB (adjusted odds ratio 3.73, 95% confidence interval 1.43–9.71 P < 0.01). Leukocytes >5/hpf on urinalysis (adjusted odds ratio 4.45, confidence interval 1.19–16.57, P = 0.03) was significantly associated with antibiotic treatment in ASB. There was no significant difference between ASB treatment before 2019 versus after 2019.

Conclusions

Predictors of clinicians treating ASB with antibiotics were most significant in patients older than 80 years and those with leukocytes >5/hpf on urinalysis. The 2019 IDSA guidance on avoiding antibiotic treatment for ASB was not well adopted to clinical practice for hospitalized patients at our institution.
Bloodstream Infections in Childhood Acute Myeloid Leukemia and Machine Learning Models: A Single-institutional Analysis
Authors: Chappell Taylor L. , Pflaster Ellen G. , Namata Resty , Bell Jometa , Miller Lane H. , Pomputius William F. , Boutilier Justin J. , Messinger Yoav H.
Published: November 2024

Childhood acute myeloid leukemia (AML) requires intensive chemotherapy, which may result in life-threatening bloodstream infections (BSIs). This study evaluated whether machine learning (ML) could predict BSI using electronic medical records. All children treated for AML at Children’s Minnesota between 2005 and 2019 were included. Patients with Down syndrome AML or acute promyelocytic leukemia were excluded. Standard statistics analyzed predictors of BSI, and ML models were trained to predict BSI. Of 95 AML patients, 54.7% had BSI. Of 480 admissions, 19% included BSI. No deaths were related to BSI, and survival of non-Whites was significantly inferior to White patients. Logistic regression revealed that higher cytarabine doses increased the risk of BSI, with an odds ratio (OR) of 1.110 (P < 0.05). Prophylactic levofloxacin-vancomycin reduced the risk of BSI, with OR of 0.495 (P < 0.05). The best-performing ML model was regularized logistic regression with an area under the curve (AUC) of 0.748, improved specificity by 37.5% compared with neutropenia, and 2.6% compared with fever. In conclusion, BSI risk was increased by cytarabine and reduced by levofloxacin-vancomycin prophylaxis. ML predicted BSI with improvement over fever or neutropenia. In clinical practice, ML may offer flexibility by controlling sensitivity and specificity by adjusting BSI diagnosis thresholds.
Hazardous alcohol consumption is associated with an increased occurrence of falls among people with HIV in the PROSPER-HIV Study
Authors: dos Santos Andre P. , Willig Amanda L. , Ruderman Stephanie A. , Oliveira Vitor H.F. , Horvat Davey Christine , Buford Thomas W. , Long Dustin M. , Gripshover Barbara , Katundu Mari , Cleveland John D. , Crane Heidi M. , Fleming Julia , Burkholder Greer , Saag Michael S. , Webel Allison R.
Published: November 2024

Objective:

Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH.

Methods:

The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, nonhazardous, and hazardous drinking. Data collection included demographics, medical history [i.e. comorbidities, treated hypertension, estimated glomerular filtration rate (eGFR)], alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson's correlation and Poisson regression models to estimate fall prevalence ratios, adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR).

Results:

The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percentage were classified as nondrinking, 50% nonhazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls [prevalence ratio: 2.12, 95% confidence interval (CI) 1.11–4.03] and recurrent falls (prevalence ratio 3.54, 95% CI 1.21–10.3) among hazardous drinking compared with nonhazardous drinking, even after adjusting for confounders. The prevalence ratios for falls per daily intake in grams was not statistically significant.

Conclusion:

There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C but not when accessing recall of alcohol consumption in grams.
Clinical Results of Percutaneous Transhepatic Biliary Drainage With Different Hepatic Access and Methods in the Treatment of Obstructive Jaundice
Authors: Şahan Mehmet Hamdi , Akşamoğlu Melih
Published: November 2024

Background:

Percutaneous transhepatic biliary drainage (PTBD) is a common procedure for biliary obstruction jaundice caused by biliary tract obstruction. PTBD can be performed using external or external-internal methods, by the right or left lobe approach. However, differences in both the method used and the hepatic approach may affect success rates and complications. Therefore, this study aimed to examine the outcomes and complications of PTBD and compare them according to different methods and hepatic approaches.

Methods:

Patients who underwent PTBD procedures in our interventional radiology department due to benign or malignant pathologies between March 2021 and March 2024 were included in the study. The diagnoses of the patients, and total and direct bilirubin values before and after the procedure were recorded. The clinical results and the complications of PTBD were compared statistically according to the hepatic approach and method. Univariate logistic regression analysis was performed to determine significant factors associated with PTBD success and complications.

Results:

Sixty patients were included in our study (32 men, 28 women; mean age: 67.14±13.61 y). The most common indication was malignant bile duct obstruction (90%). The obstruction was mostly at the level of the common bile duct (46.7%). The success rate of PTBD was the highest with the left-side external biliary drainage approach (left-side external biliary drainage, 81.2%; right-side internal-external biliary drainage, 77.8%; right-side external biliary drainage, 69.2%; P=0.596). The complication rate was higher for right-side access (right side 15.9%, left side 12.5%, P=0.744). Univariate logistic regression analysis revealed that PTBD success in females was 5 times higher than in males [Exp(B): 5.000, β: 1.609, P<0.05]. Univariate logistic regression analysis revealed that methods used, entry lobes, and entry levels did not significantly affect PTBD success and complication incidence (P>0.05).

Conclusion:

All approaches and methods used during PTBD were associated with low complications and high success rates. Nevertheless, external biliary drainage with right hepatic access has the lowest clinical success rate and a higher complication rate than the left-lobe approach. We observed that left-sided external biliary drainage was the most successful method and had fewer complications.
Electroacupuncture alleviated chronic cerebral hypoperfusion damages via targeting aquaporin 4 to prevent amyloid-beta accumulation
Authors: Zhang Ying , Wu Lei , He Kelin , Cheng Yingying , Li Lu , Han Dexiong
Published: November 2024

The present study aimed to investigate the therapeutic effects of electroacupuncture (EA) on chronic cerebral hypoperfusion (CCH). We first applied the Morris water maze approach to determine the effects of EA and TGN-020 [an inhibitor of aquaporin 4 (AQP4)] on the learning and memory ability of CCH rats. The hematoxylin and eosin, and Nissl staining were further used to investigate the effects of EA and TGN-020 on the neuropathological changes of the dentate gyrus. Next, the ELISA kits were adopted to determine the effects of EA and TGN-020 on the content of amyloid-beta (Aβ) in the cerebrospinal fluid of CCH rats. Finally, we respectively employed technologies of immunohistochemical staining, quantitative real-time PCR, and Western blot to further explore the effects of EA and TGN-020 on the mRNA expression level of amyloid precursor protein (APP) and AQP4 as well as the protein expression level of Aβ1-42 and AQP4 in the dentate gyrus of CCH rats. Our results indicated that EA not only enhanced the learning and memory abilities of CCH rats but also improved the neuropathological damages of CCH rats by upregulating the mRNA and protein expression level of AQP4 to reduce the accumulation of Aβ, especially for the reduction of the mRNA expression level of APP and the protein expression level of Aβ1-42, but TGN-020 effectively reversed the therapeutic effects mentioned above of EA. In summary, we proved that EA, as the activator of AQP4, prevents the accumulation of Aβ during the treatment of CCH.
Early Life Safety Profiling of Gene Therapy for Spinal Muscular Atrophy: A Case Series Analysis
Authors: Spellman Rebecca G. , Ha Leillani L. , Duarte Lepez Salomé Da Silva , Arruda Elizabeth A. , Rodrigues Emma , Swoboda Kathryn J. , Alves Christiano R. R.
Published: November 2024

The present study examines the safety profile of intravenous onasemnogene abeparvovec gene therapy in a real world setting, both alone or in combination with intrathecal antisense oligonucleotide nusinersen therapy in two cohorts of patients with spinal muscular atrophy (SMA). The first cohort included 8 presymptomatic infants treated solely with onasemnogene abeparvovec, while the second cohort comprised 6 symptomatic infants receiving onasemnogene abeparvovec and nusinersen co-therapy. All patients received the corticosteroid prednisolone coincident with gene therapy. Circulating alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were measured to determine potential hepatoxicity, the primary focus of this study. Elevated ALT and AST levels, but no change in GGT levels were observed in 1 pre-symptomatic and 3 symptomatic patients post-treatment. However, all values normalized within three months of onasemnogene abeparvovec injection. Nusinersen treatment received previously or coincident with gene therapy did not impact the elevation of liver transaminases, which was transient. This study highlights the importance of early intervention with molecular treatments for SMA and indicates that prior or coincident treatment with nusinersen is unlikely to impact safety of onasemnogene apoparvovec and could theoretically improve clinical outcomes in symptomatic infants or in those with gene therapy delayed beyond the immediate neonatal period.
Clinico-Epidemiological Profile of Type II Diabetes Mellitus in India – A Multicentric Institutional-Based Survey
Authors: Kalra Pramila , Mohan Gurinder , Tiewsoh Iadarilang , Raveendra K R , Ravi Kiran M , Kumar Sreejith N , Ghosh Sujoy , Dharmalingam Mala , Bhattacharya Prasanta Kumar , Akanth R , Chitra S , Pandit Kaushik , Lyngdoh Monaliza , Subramani Prabhu , Mukhopadhyay Pradip , Thaman Richa Ghay , Chandey Manish , Ramakrishna B S , Holigi Sivaranjani , Jain Smitha , Sundararaman R , Vedantha Srinivas J , Sreejith Veena , Jamil M D , Rahman Shafiq , Elizabeth R Mercy , Sekhar Theertha , Sreelakshmi P R , Vempadapu Monika , Sharma Aditi , Singh Reetu , Odedra Karan
Published: November 2024

Background

The epidemic of diabetes mellitus is one of the leading causes of mortality globally. Therefore, the goal of the registry is to create a database on individuals with diabetes mellitus that may be utilized to provide data on the clinico-epidemiological profile of Diabetes Mellitus in the real world.

Methods

Data for this registry is captured at seven sites across India recognized by the Biotechnology Industry Research Assistance Council (BIRAC). This observational multi-centric study registered around 25077 Diabetic patients over three years (December 2023).

Results

Out of 25077 patients, 12793 (51%) were male and 12284 (49%) females. There were 11443 (46%) rural patients and 13575 (54%) urban patients. Most patients registered were over 50 years old (74.05±2.42). Diabetes was seen as a burden for 46% of individuals and their families. Less than 40% of patients exercised. Over half of the patients had a family history of diabetes. This explains the exponential rise of diabetes mellitus over generations and the significance of preventing it.

Conclusion

This registry revealed the impact of the clinico-epidemiological aspects of Diabetes Mellitus on a larger number of samples. Future healthcare planners, researchers, and government officials will benefit from this diabetes registry in developing primary and secondary preventive initiatives that might minimize the rising healthcare burden of diabetes.
Exploratory analysis of cumulative fatigue derived from volume and intensity indicators in stage races of professional cycling
Authors: Machado AS. , De la Fuente C. , Javaloyes A. , Moya-Ramón M. , Mateo-March M. , Carpes FP.
Published: November 2024

Objective

Here, we discuss cumulative fatigue based on volume and power output from 12 professional male cyclists during two consecutive editions of the Giro d’Italia.

Methods

Volume and power output were recorded and described according to time at different intensity zones based on power output (Z0 lower to Z7 higher). Correlations, principal component analysis (PCA), Gaussian clustering, and two-way ANOVA were performed (type error I of 5%).

Results

The higher intensity zones elicited higher power output in those shorter stages (R2= 0.54). In contrast, the lower intensity zones were predominant in longer stages. The time spent in Z1 to Z3 (r = 0.67, 0.84, and 0.73) correlated more with stage’s volume duration than time in Z4 to Z7 (r = 0.48, 0.44, and 0.51, and 0.38). The normalized volume declined between stages 2 to 4, 8 to 10, 13 to 15, and 18 to 19. Negative slopes of time spent in Z4 and Z6 occurred one or two stages before Z1 presented negative slopes. In contrast, positive slopes of higher intensity zones were observed with a negative slope of Z1. Different clusters distributions of time volume to complete the grand tour were found (p<0.05). Finally, average power in Z1, Z2, Z3, Z4, Z5, Z6, and Z7 explained 63.62%, 18.20%, 8.12%, 5.84%, 2.98%, 1.20%, and 0.02% of the total variance in the normalized time volume, respectively. Volume and power zone data can recognize cumulative fatigue and performance recovery during a grand tour. Rest days favored the performance recovery, mostly the second rest day.
DEVELOPING NEW DUAL-ACTION ANTIVIRAL/ANTI-INFLAMMATORY SMALL MOLECULES FOR COVID-19 TREATMENT USING IN SILICO AND IN-VITRO APPROACHES
Authors: Ivanov Vladimir V. , Zakharov Anton B. , Anokhin Dmytro O. , Mykhailenko Olha O. , Kovalenko Sergiy M. , Yevsieieva Larysa V. , Georgiyants Victoriya A. , Korinek Michal , Chen Yu-Li , Fang Shu-Yen , El-Shazly Mohamed , Hwang Tsong-Long , Kalugin Oleg M.
Published: November 2024

This study aims to develop new molecular structures as potential therapeutic agents against COVID-19, utilizing bothin silicoandin vitrostudies. Potential targets of cepharanthine (CEP) against COVID-19 to reveal its underlying mechanism of action were evaluated usingin silicoscreening experiments. A library of new molecules was docked into the receptor binding domain of the SARS-CoV-2 spike glycoprotein complex with its receptor, human ACE2, to identify promising compounds. Receptor-oriented docking was performed using the most likely macromolecular targets, aimed at inhibiting key viral replication pathways and reducing inflammatory processes in damaged tissues. The hit molecules showed potential inhibition of Mpro and PLpro proteases of SARS-CoV-2, which are involved in viral replication. They also showed a potential inhibitory effect on Janus kinase (Jak3), which mediates intracellular signaling responsible for inflammatory processes.

Thein vitrostudy examined the effects of the selected hit molecules on the generation of superoxide anions and the release of elastase in activated neutrophils, which are factors that exacerbate tissue inflammation and worsen the clinical manifestations of COVID-19. It was demonstrated that 2-((5-((4-isopropylphenyl)sulfonyl)-6-oxo-1,6-dihydropyrimidin-2-yl)thio)-N-(3-methoxyphenyl)acetamide (Hit15) inhibited virus infection by 43.0% at 10μM using pseudovirus assay and suppressed fMLF/CB-induced superoxide anion generation and elastase release in human neutrophils with IC50values 1.43 and 1.28μM, respectively.Hit15showed promising activity against coronavirus that can be further developed into a therapeutic agent.

Graphical Abstract
Aldolase B and Angiotensinogen are associated with weekly chronic multisite spinal pain in men
Authors: Ruotsalainen Hilla , Drouard Gabin , Pedersen Andreas , Ståhl Minna , Kanninen Katja M. , Kaprio Jaakko
Published: November 2024

Spinal pain problems increase with age, but already 21% of Finnish young adults suffer from a musculoskeletal disorder. Chronic widespread pain (CWP) significantly increases one’s disability level and up to 50% of people experiencing chronic pain report symptoms of depression. Diagnosing pain is challenging, as it is a subjective feeling and current clinical pain descriptors are not accurate enough to determine pain perception. In this study, variation in the human plasma proteome was investigated with untargeted Mass Spectrometry in young adult twins with weekly chronic multisite spinal pain (n=94), twins with weekly chronic local neck pain (n=99), and healthy twin individuals (n=236). The association of depression with pain and sex-specific proteins in the studied associations was also investigated. The main data analysis approach included multiple regressions which were done with Generalized Linear Mixed Models (GLMM). Of the 411 studied proteins, Aldolase B and Angiotensinogen were negatively associated with weekly chronic concomitant neck and back pain in men. These proteins are known to relate to muscle atrophy and might thus contribute to the development of musculoskeletal pain. In addition, individuals with weekly chronic concomitant neck and back pain had more symptoms of depression than individuals with weekly chronic local neck pain. Further research is needed to identify the key proteins for clinical settings and upcoming pain proteomics research should include both women and men to examine sex differences.
Quality of life of Type II Diabetic patients
Authors: Ghimire Sulochana , Neupane Gita , Sah Chanda , Ghimire Mahesh Raj , Soti Binita
Published: November 2024

Objective

Diabetes mellitus poses significant challenges to individuals’ well-being, affecting various aspects of their lives beyond the physical symptoms of the disease. Understanding the multidimensional aspects of QoL among diabetic patients is crucial for providing holistic healthcare interventions and improving overall health outcomes. The study aims to evaluate the quality of life of Type II Diabetes Mellitus patients.

Research Design and Methods

Descriptive cross-sectional study was conducted among 334 diagnosed cases of Type 2 Diabetes Mellitus for more than or equal to 6 months attending the outpatient department of UCMS-TH. Non-probability purposive sampling technique was used to select samples for the study. The WHOQOL-BREF questionnaire was used to measure QoL. Data were analyzed with descriptive statistics (frequency, percentage, mean, standard deviation) and inferential statistics (t-tests or one way ANOVA) to explore associations between QoL domains and sociodemographic characteristics.

Results

More than half (56.6%) of the respondents were between the age group of 41-60 years with mean age of 58.42. Highest mean score ± SD was found in social domain (60.77 ± 13.83) followed by environmental domain (56.05 ± 10.38) and psychological domain (55.67 ±8.44) with least mean domain score in physical domain (49.99 ± 14.53). The results show that diabetic patients, particularly women and those with comorbid conditions, report lower quality of life in all domains. Additionally, no significant association was found between having a family history of diabetes and quality of life. There was high positive correlation between physical and environmental domain of quality of life (r = 0.70, p < 0.001).

Conclusion

Comprehensive management strategies focusing on all dimensions of health is necessary to improve the quality of life of patients with Diabetes Mellitus.