Low Count Research Articles

Diagnostic Value of Metagenomic next-generation sequencing and X-pert in Bronchoalveolar lavage fluid for pneumonia in HIV-infected and HIV-uninfected patients

BackgroundThe pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. MethodsBetween January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. ResultsHIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/μL vs. 31 cells/μL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

Factors associated with fall risk increasing drug use in older black and white men and women: the Health ABC Study

BackgroundMost older adults use medications that may increase falls, often defined as fall risk increasing drugs or “FRIDs”. Two definitions for FRIDs, the Centers for Disease Control and Prevention’s (CDC) Stopping Elderly Accidents, Deaths & Injuries (STEADI-Rx) and Swedish National Board of Health and Welfare (SNBHW) definitions, are widely accepted, though include different FRIDs in their definitions. Whether factors associated with FRID use in older adults differ by definition is unknown.MethodsWe hypothesized that factors for FRID use will vary by FRID definition in 1,352 community-dwelling older Black and White adults with medication information in the Health, Aging and Body Composition Study (Health ABC; 2007–08 clinic visit; 83.4 ± 2.8 years; 54.1% women; 65.1% White). Multivariable logistic regression and multivariable negative binomial regression, progressively entering groups of covariates (demographics, lifestyle/behavior factors, and multimorbidity), modeled FRID use (yes/no) and count.ResultsOf 87.0% participants using SNBHW FRIDs, 82.9% used cardiac medications, with lower use of all other FRIDs (range:1.1-12.4%). Of 86.6% participants using STEADI-Rx FRIDs, 80.5% used cardiac medications, with lower use of all other FRIDs (range:1.1-16.1%). Participants with FRID use by either definition were more likely to have chronic health conditions, a hospitalization in the prior year, higher non-FRIDs medication counts, higher Center for Epidemiologic Studies Depression Scale (CES-D) scores, and less physical activity (all p < 0.05). Participants with STEADI-Rx FRID use had poorer vision and higher Modified Mini-Mental State (3MS) scores. In multivariable logistic regression for SNBHW use, hypertension, body mass index (BMI), 3MS scores, and non-FRID count were positively associated with FRID use and poorer vision and Digit Symbol Substitution Test (DSST) scores were negatively associated. In addition to SNBHW factors, higher CES-D scores were associated with STEADI-Rx FRID use. In multivariable negative binomial regression, hypertension, higher BMI, CES-D scores, and non-FRID count were associated with higher FRID count and sleep problems with lower FRID count for both definitions. Higher 3MS and lower DSST scores were associated with higher STEADI-Rx FRID count. Women had lower SNBHW FRID count after adjustments.ConclusionsRisk factors for FRID use in older adults differ slightly by STEADI-Rx and SNBHW FRIDs definition, but are largely similar.

Physical activity and sedentary behavior among ambulatory children with cerebral palsy using accelerometer: a cross-sectional study.

Physical activity (PA) is paramount for childhood development and growth. However, children diagnosed with Cerebral Palsy (CP) were often considered sedentary, and their physical inactivity was associated with adverse health conditions and complications. Therefore, this study aimed to objectively describe and compare the PA levels and SB levels of children with and without CP of the same age group. It also studied the factors correlating with PA, SB, and step count per day in children with CP. A cross-sectional study using a wrist-worn accelerometer was conducted. PA and SB were measured over seven consecutive days. Eighty-five children aged 6-12 years, consisting of 41 children with CP and 44 TD children, participated in this study with a mean age of 9.18 ± 1.95 and 8.45 ± 1.78 years, respectively. According to the gross functional measures, 53.6% of children with CP were classified as first classification. A significant amount of time was spent in SB and Light PA (LPA) by children with CP compared to TD children, and no significant differences were observed in moderate PA (MPA) or step count. Gender mainly affected MPA as girls spent more time in MPA than boys. The age, height, and weight of children with CP correlate significantly with SB. As children's age, height, and weight increase, SB increases. Additionally, children with higher weights have lower step counts per day. This study showed that children with CP spend more time in LPA and SB than typically developed children. Therefore, concerted efforts are needed to encourage physical activity and reduce the sedentary lifestyle, to take into account the gender and anthropometric measures of children to enhance the quality of life among children with CP, and to consider gender and anthropometric measures of the children.

KAN-ODEs: Kolmogorov–Arnold network ordinary differential equations for learning dynamical systems and hidden physics

Kolmogorov–Arnold networks (KANs) as an alternative to multi-layer perceptrons (MLPs) are a recent development demonstrating strong potential for data-driven modeling. This work applies KANs as the backbone of a neural ordinary differential equation (ODE) framework, generalizing their use to the time-dependent and temporal grid-sensitive cases often seen in dynamical systems and scientific machine learning applications. The proposed KAN-ODEs retain the flexible dynamical system modeling framework of Neural ODEs while leveraging the many benefits of KANs compared to MLPs, including higher accuracy and faster neural scaling, stronger interpretability and generalizability, and lower parameter counts. First, we quantitatively demonstrated these improvements in a comprehensive study of the classical Lotka–Volterra predator–prey model. We then showcased the KAN-ODE framework’s ability to learn symbolic source terms and complete solution profiles in higher-complexity and data-lean scenarios including wave propagation and shock formation, the complex Schrödinger equation, and the Allen–Cahn phase separation equation. The successful training of KAN-ODEs, and their improved performance compared to traditional Neural ODEs, implies significant potential in leveraging this novel network architecture in myriad scientific machine learning applications for discovering hidden physics and predicting dynamic evolution.

A comparative retrospective study of pre-fibrotic primary myelofibrosis versus overtly fibrotic stage in Qatar: clinicopathological, genetic landscape, risk stratification and survival data (2008–2021) – a single center experience

ABSTRACT Background In MENA region, there is a lack of evidence on Primary Myelofibrosis (PMF), leading to its underrepresentation in medical literature. This study marks the first comprehensive report on PMF data in Qatar, presenting findings from a single-center study spanning 13 years (2008-2021). Methods Clinicopathological data, genetic features, and disease progression parameters of pre-PMF and overt PMF subgroups were collected. Overall survival (OS), progression-free survival (PFS), DIPSS plus four categories and merged low and high-risk DIPSS scoring groups were assessed. Results Pre-PMF patients showed higher hemoglobin (P < 0.001), and platelet counts (P < 0.05) but lower blast counts, LDH levels, constitutional symptoms (P < 0.0001), and splenomegaly (P < 0.010) than overt PMF patients. JAK2 V617F mutation was more common in pre-PMF (P = 0.059), while unfavorable karyotypes were exclusive to overt PMF (P = 0.028). Median overall survival was significantly longer at 276.9 months (IQR: 315.9, 276.9 months) to what was previously reported. Overt PMF patients predominantly fell into the higher DIPSS risk category (P < 0.001) and showed greater disease progression than pre-PMF (P < 0.0001). Complications including refractory anaemia (P < 0.001) and leukemic transformation (P = 0.043), increased notably in the high-risk group. Furthermore, 86.2% of high-risk patients required treatment versus 59.4% of the lower-risk group (P = 0.020). Conclusions To the best of our knowledge our research represents the first and largest published dataset on PMF in MENA region to be published. Merged DIPSS plus scoring came to be a pragmatic tool for defining high-risk patients who significantly differ in mortality, progression, need for treatment and leukemic transformation.

Experimental study on emissions and particulate characteristics of diesel engine fueled with plastic waste oil, acetone-butanol-ethanol and diesel blends

Plastic waste poses a significant environmental challenge due to its non-biodegradable nature and accumulation in landfills. Converting plastic waste into usable fuel could offer a promising solution for mitigating these issues while addressing the emission-related challenges of diesel engines. This study investigates the impact of plastic waste oil (WPO) obtained through pretreatment and catalytic pyrolysis, blended with acetone-butanol-ethanol (ABE) and diesel fuel, on diesel engine. The aim was to evaluate how these blends affect gaseous emissions, organic compounds, and particle-bound carbon, focusing on their potential to reduce harmful pollutants compared to pure diesel fuel. The results indicated that the ABE5W15D blend significantly reduced smoke and CO emissions by 35.7 % and 17.43 %, respectively, with a slight decrease in HC emissions. However, the ABE20W blend showed elevated NOx levels due to higher ignition delay and increased cylinder pressure. Compared to pure diesel (D100), ABE10W10D and ABE5W15D blends reduced total polycyclic aromatic hydrocarbons (PAHs) emissions by 26.8 % and 37.4 %, respectively. Naphthalene was the dominant PAH, remarkably increasing with W20D use, while longer-chain alkanes associated with lubricant oil had higher W20D emissions. The ABE5W15D blend notably reduced organic carbon (OC) emissions by approximately 38.26 % compared to D100. ABE20D exhibited lower elemental carbon (EC) emissions than D100, although it had higher EC than OC. The W20D blend resulted in larger particle diameters, whereas ABE10W10D showed lower particle counts in the 7–15 nm range. In conclusion, blending plastic waste oil with ABE and diesel fuel can effectively mitigate certain pollutants, depending on the blend composition.

HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir.

Nearby and non-nested genes in the human genome have more similar genotype tissue expression.

Neighboring genes within a shared promoter arrangement (i.e. opposite direction with the neighboring ends as the transcriptional start sites) are expected to have a high similarity in genotype tissue expression due to the potential overlap in the promoter region. This raises the question of whether similarity in expression profiles depends on orientation of the neighboring genes and whether there exist thresholds of locality where the similarity diminishes. Thus, in this work, we compared genotype tissue expression profiles at different genomic orientations and localities. Interestingly, there exist gene pairs in the human genome with very high or low expression similarity. Shorter chromosomes tend to have more similarly expressed genes. Also, a cluster of 3 adjacent genes within the average range of 20 to 60 kilobase pairs can have very similar expression profiles regardless of their orientations. However, when genes are nested and in opposite orientations, a lower than expected similarity was observed. Lastly, in cases where genotype tissue expression data does not exist or have low read counts (e.g. non-coding RNA), our identified influencing range can be a first estimate of the genotype tissue expression.

Existence, uniqueness, and efficiency of numerically unbiased attenuation pathlength estimators for photon counting detectors at low count rates.

The first step in computed tomography (CT) reconstruction is to estimate attenuation pathlength. Usually, this is done with a logarithm transformation, which is the direct solution to the Beer-Lambert Law. At low signals, however, the logarithm estimator is biased. Bias arises both from the curvature of the logarithm and from the possibility of detecting zero counts, so a data substitution strategy may be employed to avoid the singularity of the logarithm. Recent progress has been made by Li etal. [IEEE Trans Med Img 42:6, 2023] to modify the logarithm estimator to eliminate curvature bias, but the optimal strategy for mitigating bias from the singularity remains unknown. The purpose of this study was to use numerical techniques to construct unbiased attenuation pathlength estimators that are alternatives to the logarithm estimator, and to study the uniqueness and optimality of possible solutions, assuming a photon counting detector. Formally, an attenuation pathlength estimator is a mapping from integer detector counts to real pathlength values. We constrain our focus to only the small signal inputs that are problematic for the logarithm estimator, which we define as inputs of<100 counts, and we consider estimators that use only a single input and that are not informed by adjacent measurements (e.g., adaptive smoothing). The set of all possible pathlength estimators can then be represented as points in a 100-dimensional vector space. Within this vector space, we use optimization to select the estimator that (1) minimizes mean squared error and (2) is unbiased. We define "unbiased" as satisfying the numerical condition that the maximum bias be less than 0.001 across a continuum of 1000 object thicknesses that span the desired operating range. Because the objective function is convex and the constraints are affine, optimization is tractable and guaranteed to converge to the global minimum. We further examine the nullspace of the constraint matrix to understand the uniqueness of possible solutions, and we compare the results to the Cramér-Rao bound of the variance. We first show that an unbiased attenuation pathlength estimator does not exist if very low mean detector signals (equivalently, very thick objects) are permitted. It is necessary to select a minimum mean detector signal for which unbiased behavior is desired. If we select two counts, the optimal estimator is similar to Li's estimator. If we select one count, the optimal estimator becomes non-monotonic. The oscillations cause the unbiased estimator to be noise amplifying. The nullspace of the constraint matrix is high-dimensional, so that unbiased solutions are not unique. The Cramér-Rao bound of the variance matches well with the expected scaling law and cannot be attained. If arbitrarily thick objects are permitted, an unbiased attenuation pathlength estimator does not exist. If the maximum thickness is restricted, an unbiased estimator exists but is not unique. An optimal estimator can be selected that minimizes variance, but a bias-variance tradeoff exists where a larger domain of unbiased behavior requires increased variance.

Proteinuria and albuminuria among a global primary CVD prevention cohort of PWH: prevalence and associated factors.

To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors. Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial. REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results. Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values. Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.

Clinical, oncological, and prognostic differences of patients with subsequent skeletal-related events in bone metastases.

Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. This retrospective study included 3,814 adult patients who received local treatment - surgery and/or radiotherapy - for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher's exact test, and Kaplan-Meier curve. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians' experiences when treating the initial SRE are not similar when treating a subsequent SRE. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs.

Differential roles of eosinophils in cardiovascular disease.

Eosinophils are essential innate immune cells in allergic responses. Accumulating evidence indicates that eosinophils also participate in the pathogenesis of cardiovascular diseases (CVDs). In clinical studies, high blood eosinophil counts and eosinophil cationic protein levels have been associated with an increased risk of CVD, including myocardial infarction (MI), cardiac hypertrophy, atrial fibrillation, abdominal aortic aneurysm (AAA) and atherosclerosis. However, low blood eosinophil counts have also been reported to be a risk factor for MI, heart failure, aortic dissection, AAA, deep vein thrombosis, pulmonary embolism and ischaemic stroke. Although these conflicting clinical observations remain unexplained, CVD status, timing of eosinophil data collection, and tissue eosinophil phenotypic and functional heterogeneities might account for these discrepancies. Preclinical studies suggest that eosinophils have protective actions in MI, cardiac hypertrophy, heart failure and AAA. By contrast, cationic proteins and platelet-activating factor from eosinophils have been shown to promote vascular smooth muscle cell proliferation, vascular calcification, thrombomodulin inactivation and platelet activation and aggregation, thereby exacerbating atherosclerosis, atrial fibrillation, thrombosis and associated complications. Therefore, eosinophils seem to promote calcification and thrombosis in chronic CVD but are protective in acute cardiovascular settings. In this Review, we summarize the available clinical and preclinical data on the different roles of eosinophils in CVD.

Leucocytosis during induction therapy with all-trans-retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predicts differentiation syndrome and treatment-related complications.

All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represent the standard of care for low-intermediate risk acute promyelocytic leukaemia (APL). Leucocytosis during induction with ATRA-ATO represents a common complication with an incidence of up to 60%. To identify predictive factors for this complication, we studied a cohort of 65 low-intermediate risk APL patients treated with ATRA-ATO in three highly specialized Italian centres. Overall, 39/65 (60%) patients developed leucocytosis, with a peak in leucocyte count being most frequent in the second week from diagnosis. All cases were successfully managed with hydroxyurea. Predictive factors for leucocytosis in univariate analysis were lower platelet counts (odds ratio [OR] 0.98, 0.97-1.00, p = 0.018), lower fibrinogen levels (OR 0.36, 0.17-0.66, p = 0.003), higher bone marrow blast infiltration (OR 1.03, 1.01-1.07, p = 0.021) and CD117 expression by flow (OR 1.04, 1.01-1.08, p = 0.012). Multivariate analysis confirmed lower levels of fibrinogen at diagnosis as the strongest predictive factor for the development of leucocytosis (OR 0.36, 0.15-0.72, p = 0.009). Differentiation syndrome (DS) occurred only in patients developing leucocytosis showing a strict correlation with rising leucocytes counts (16/39 vs. 0/26, p < 0.001). In addition, other treatment-related complications including QTc prolongation, cardiac events, liver, and haematological toxicities were significantly more frequent in patients experiencing leucocytosis (22/39 vs. 3/26, p < 0.001). In conclusion, APL patients undergoing ATRA-ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment-related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications.

Do conference-journal articles receive more citations? A case study in physics

Conference-journal articles, which are expanded versions of conference proceedings papers, play an essential role in disseminating scientific knowledge but remain understudied. In the context of increasingly stringent research evaluation systems, this study focuses on conference-journal articles, examining the effectiveness of journals in selecting conference-derived publications. We also explore the factors influencing the citations of conference-journal articles. Here, we focused on Physics, analyzing 59,329 conference-journal articles published between 2012 and 2020, matched with general journal articles and conference proceedings papers based on the conference and journal. Results show that conference-journal articles receive significantly more citations than conference proceedings papers but fewer than general journal articles. Conference-journal articles in special issues receive fewer citations than those in regular issues. A U-shaped pattern emerges between the duration from the conference convening to the journal publication and the citation. We also found that conferences with sponsorship and those held in OECD member countries are more likely to produce highly cited conference-journal articles. Additionally, results indicate that conferences held in the USA, Japan, France, China, and Poland produce the most conference-journal articles, with articles from conferences in the USA, Japan, and France receiving relatively high citation counts. In contrast, articles from conferences held in China and Poland receive relatively low citation counts. This research provides valuable insights for academic conference committees, journal managers, and conference participants.

Dehydrozingerone ameliorates arsenic-induced reproductive toxicity in male Wistar rats.

Arsenic (As3+), a significant environmental pollutant that has garnered global attention, is widely recognized for its adverse effects on reproductive health. This study assesses the aphrodisiac activity of Dehydrozingerone (DHZ) against As3+ induced sexual dysfunction in male Wistar rats. Male Wistar rats were divided into control, As3+, and As3++DHZ groups. The As3+ group received 5mg/kg sodium arsenite (NaAsO2) orally while As3++DHZ group received 50mg/kg synthesized DHZ along with As3+ for 42 days. Following administration, mount and intromission latency, frequency, and average time were measured to assess aphrodisiac and reproductive toxicity in male Wistar rats which had 1:1 coitus with female rats. On days 14th, 28th, and 42nd, sexual behaviour was measured. Further on 43rd day, animals were sacrificed, blood was collected to measure oxidative parameters and LH hormone, and then testes were collected to profile reproductive damage. As3+ treated rats had lower sperm counts, motility, and abnormalities. These alterations reduced sexual hormones. In addition, As3+ toxicity depleted antioxidant indicators including SOD, GSH and elevated ROS. Compared to the As3+ group, As3++DHZ showed a substantial (p < 0.05) increase in sperm count, motility, and reduced abnormalities. DHZ also reversed the rise in luteinizing hormone caused by As3+ therapy, restored oxidative indicators, and improved seminiferous tubule structural damage. 42 days As3+ exposure slightly increased rats' sexual desire but not sperm quality. However, As3++DHZ lower libido and sperm quality. Thus, DHZ therapy enhanced rat sexual desire and sperm quality compared to As3+.

Vitamin B12 Deficiency in Thrombotic Thrombocytopenic Purpura-Like Cases.

Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM-TMA). A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient's low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 μg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient's microangiopathic hemolytic anemia. This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management. Vitamin B12 deficiency can be a cause of thrombotic microangiopathy.

Design of a high voltage gain converter using coupled inductor with reduced voltage stress for photovoltaic energy based systems

This paper presents the design and analysis of a high voltage gain converter utilizing a coupled inductor with reduced voltage stress, specifically for photovoltaic energy-based systems. The proposed converter employs a two-winding coupled inductor and voltage multiplier cells to achieve an increase in output voltage while mitigating voltage stress across semiconductor components. Additionally, the voltage multiplier cells function as voltage clamps for the power switch, further enhancing the converter's performance. The converter features a single switch design, which simplifies control, reduces cost, and improves reliability. Key advantages of the converter include a low component count, a common ground between input and output ports, and high efficiency. The converter's performance is thoroughly investigated through mode analysis and steady-state analysis. Comparative evaluations with similar converters are conducted to highlight the benefits and performance of the proposed design. To validate the theoretical analysis, a 125 W prototype with 26 V input and 200 V output voltages operating at a 50 kHz switching frequency is developed, and experimental results are presented, demonstrating the effectiveness and practicality of the proposed high voltage gain converter.

Evaluating the Effects of Prostate Radiotherapy Intensified with Pelvic Nodal Radiotherapy and Androgen Deprivation Therapy on Myelosuppression: Single-Institution Experience.

Prostate cancer (PCa) management commonly involves the utilization of prostate radiotherapy (PRT), pelvic nodal radiotherapy (PNRT), and androgen deprivation therapy (ADT). However, the potential association of these treatment modalities with bone marrow (BM) suppression remains inadequately reported in the existing literature. This study is designed to comprehensively evaluate the risk of myelosuppression associated with PRT, shedding light on an aspect that has been underrepresented in prior research. We conducted a retrospective analysis of 600 patients with prostate cancer (PCa) treated with prostate radiotherapy (PRT) at a single oncology center between 2007 and 2017. Patients were categorized into four cohorts: PRT alone (n = 149), PRT + ADT, (n = 91), PRT + PNRT (n = 39), and PRT + PNRT + ADT (n = 321). To assess the risk of myelosuppression, we scrutinized specific blood parameters, such as hemoglobin (HGB), white blood cells (WBCs), neutrophils (NEUT), lymphocytes (LYM), and platelets (PLT) at baseline, mid-treatment (mRT), immediately post-RT (pRT), 1 month post-RT (1M-pRT), and 1 year post-RT (1Y-pRT). The inter-cohort statistical significance was evaluated with further stratification based on the utilized RT technique {3D conformal radiotherapy (3D-CRT), and intensity-modulated radiation therapy (IMRT)}. Significant statistical differences at baseline were observed in HGB and LYM values among all cohorts (p < 0.05). Patients in the PRT + PNRT + ADT cohort had significantly lower HGB at baseline and 1M-pRT. In patients undergoing ADT, BMS had a significant impact at 1M-pRT {odds ratio (OR) 9.1; 95% Confidence Interval (CI) 4.8-17.1} and at 1Y-pRT (OR 2.84; CI 1.14-7.08). The use of 3D-CRT was linked to reduced HGB levels in the PRT + PNRT + ADT group at 1 month pRT (p = 0.015). Similarly, PNRT significantly impacted BMS at 1M-pRT (OR 6.7; CI 2.6-17.2). PNRT increased the odds of decreased WBC counts at 1Y-pRT (OR 6.83; CI: 1.02-45.82). Treatment with any RT techniques (3D-CRT or IMRT), particularly in the PRT + PNRT and PRT + PNRT + ADT groups, significantly increased the odds of low LYM counts at all time points except immediately pRT (p < 0.05). Furthermore, NEUT counts were considerably lower at 1M-pRT (p < 0.05) in the PRT + PNRT + ADT group. PLT counts were significantly decreased by PRT + PNRT + ADT at mRT (OR 2.57; 95% CI: 1.42-4.66) but were not significantly impacted by the RT technique. Treatment with PRT, ADT, PNRT, and 3D-CRT is associated with BMS. Despite this statistically significant risk, no patient required additional interventions to manage the outcome. While its clinical impact appears limited, its importance cannot be underestimated in the context of increased integration of novel systemic agents with myelosuppressive properties. Longer follow-up should be considered in future studies.

Impact of sample refrigeration and freezing on the bacteriological counts of different bedding materials for dairy cows

BackgroundDifferent organic and inorganic bedding materials can be used in dairy farms. Among organic materials, there is an increasing interest in alternative substrates based on recycled manure solids (RMS). Microbiological analyses are crucial to monitor the microbial load and evaluate the presence of pathogens impacting animal welfare and health. However, logistic factors may hamper the possibility of immediately sending fresh samples to the laboratory, requiring storage in cooled conditions before analysis.MethodsWe assessed the impact of sample refrigeration and freezing of different organic and inorganic bedding substrates including separated raw manure solids (SRMS), anaerobically digested manure solids (ADMS), and new sand (NS), on the total bacterial count (TBC) and on different microbial classes.ResultsThe TBC was higher in fresh NS and ADMS than in refrigerated and frozen samples of the same substrates; in addition, the TBC of ADMS was higher in refrigerated than frozen samples. The TBC of SRMS did not change significantly with refrigeration and freezing. Freezing reduced the total Gram-negative bacterial count more than refrigeration in all substrates. In fresh NS, Gram-negatives were higher than in both refrigerated and frozen NS. Escherichia coli counts were significantly lower in frozen than in refrigerated SRMS. However, both refrigeration and freezing of ADMS resulted in no E. coli growth. The coliform counts were also lower in frozen than refrigerated NS and SRMS. Frozen NS and ADMS showed lower counts compared to refrigeration for Gram-negative bacteria other than E. coli and coliforms. On the other hand, cold storage did not significantly impact the streptococci and streptococcus-like organisms (SSLO) count of all evaluated bedding substrates.ConclusionRefrigeration and freezing affect the bacteriological results of bedding substrates, with freezing generally leading to lower counts than refrigeration. Whenever possible, preference should be given to analyzing fresh bedding samples, however, when necessary, refrigeration would be recommended over freezing, while acknowledging that the measured bacterial load might underestimate the actual microbial content.

The Protective Effect of Adipose-Derived Stromal Vascular Fraction on Ovarian Function in Rats with Cyclophosphamide-Induced Ovarian Damage

Objective: The aim of this study was to investigate if adipose-derived stromal vascular fraction (SVF) treatment has any protective effect on ovarian function in rats with cyclophosphamide (CP) induced ovarian damage. Design: This was an experimental animal study. Participants/Materials, Setting, Methods: 25 mature cycling Wistar-Albino rats were randomized into four groups (n = 5 per group). Rats in groups 1 and 2 received single dose of intraperitoneal (i.p.) 1 mL/kg sodium chloride 0.9% (NaCl). Groups 3 and 4 received single dose of 75 mg/kg i.p. CP. On seventh day, SVF was prepared from adipose tissues of 5 additional rats and groups 1 and 3 received 0.9% NaCl i.p. injections while groups 2 and 4 received 0.2 mL i.p. injections of SVF. On day 21 all rats were euthanized, and serum anti-mullerian hormone (AMH) levels, primordial, primary, secondary, antral, and atretic follicle counts, AMH positive staining follicle counts along with AMH staining intensity of the follicles were evaluated. Results: Among two CP induced ovarian damaged groups, SVF treated group showed significantly higher secondary and antral follicle and lower atretic follicle counts, significantly higher mean serum AMH levels, AMH positive antral follicle count and higher intensity of AMH positive follicle scores for primary, secondary, and antral follicles when compared to untreated group. Moreover, group 1 showed no significant difference for all parameters except antral follicle count and AMH positive staining intensity scores for antral follicles when compared to group 4. Limitations: This study was conducted on experimental rat model. Conclusion: Our study demonstrated a significant protective effect of SVF against CP-induced ovarian damage which reveals the apparent need for further investigation of its precise mechanisms of action as it may provide a new treatment approach for women with premature ovarian failure.