Nevin Manimala

Alzheimers Res Ther. 2023 Nov 4;15(1):191. doi: 10.1186/s13195-023-01324-4.

ABSTRACT

BACKGROUND: Alzheimer’s disease is a prevalent disease with a heavy global burden. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working for better biomarkers. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels.

METHODS: We firstly enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples, and conducted an LC-MS/MS analysis. In parallel, clinical data were collected, and clinical examinations were performed. After statistical and bioinformatics analyses, significant risk factors and differential urinary proteins were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM.

RESULTS: Fifty-seven AD patients, 43 MCI patients, and 62 CN subjects were enrolled. A total of 3366 proteins were identified, and 608 urine proteins were finally included in the analysis. There were 33 significantly differential proteins between the AD and CN groups and 15 significantly differential proteins between the MCI and CN groups. AD diagnostic panel included DDC, CTSC, EHD4, GSTA3, SLC44A4, GNS, GSTA1, ANXA4, PLD3, CTSH, HP, RPS3, CPVL, age, and APOE ε4 with an AUC of 0.9989 in the training test and 0.8824 in the test set while MCI diagnostic panel included TUBB, SUCLG2, PROCR, TCP1, ACE, FLOT2, EHD4, PROZ, C9, SERPINA3, age, and APOE ε4 with an AUC of 0.9985 in the training test and 0.8143 in the test set. Besides, diagnostic proteins were weakly correlated with cognitive functions.

CONCLUSIONS: In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN.

PMID:37925455 | DOI:10.1186/s13195-023-01324-4

J Transl Med. 2023 Nov 4;21(1):783. doi: 10.1186/s12967-023-04663-w.

ABSTRACT

Prior research has shown that the deconvolution of cell-free RNA can uncover the tissue origin. The conventional deconvolution approaches rely on constructing a reference tissue-specific gene panel, which cannot capture the inherent variation present in actual data. To address this, we have developed a novel method that utilizes a neural network framework to leverage the entire training dataset. Our approach involved training a model that incorporated 15 distinct tissue types. Through one semi-independent and two complete independent validations, including deconvolution using a semi in silico dataset, deconvolution with a custom normal tissue mixture RNA-seq data, and deconvolution of longitudinal circulating tumor cell RNA-seq (ctcRNA) data from a cancer patient with metastatic tumors, we demonstrate the efficacy and advantages of the deep-learning approach which were exerted by effectively capturing the inherent variability present in the dataset, thus leading to enhanced accuracy. Sensitivity analyses reveal that neural network models are less susceptible to the presence of missing data, making them more suitable for real-world applications. Moreover, by leveraging the concept of organotropism, we applied our approach to trace the migration of circulating tumor cell-derived RNA (ctcRNA) in a cancer patient with metastatic tumors, thereby highlighting the potential clinical significance of early detection of cancer metastasis.

PMID:37925448 | DOI:10.1186/s12967-023-04663-w

Pneumonia (Nathan). 2023 Nov 5;15(1):17. doi: 10.1186/s41479-023-00119-3.

ABSTRACT

BACKGROUND: The Novel Coronavirus disease (COVID-19) pandemic has become a global threat. Determining the time to recovery from COVID-19 is intended to assist healthcare professionals in providing better care, and planning logistics. So, the study aimed to identify the factors that affect the time to recovery from COVID-19 for patients treated at Assosa COVID-19 treatment center, Benishangul Gumuz Regional State, Western Ethiopia.

METHODS: A retrospective study design was conducted on 334 randomly selected COVID-19 patients at Assosa COVID-19 treatment center from February 2021 to July 2021. The median survival time, Kaplan-Meier survival estimate, and Log-Rank test were used to describe the data and compare the survival time between groups. The study used the Cox PH model to analyze the time to the first recovery of COVID-19 patients, where hazard ratio, p-value, and 95% CI for hazard ratio were used for testing significance. Schoenfeld and Cox-Snell residuals were used for checking the model assumption.

RESULTS: The overall incidence rate was 13.79 per 100 (95% CI: 10.04, 18.95) person-days observations. The median time to recovery was 16 days. At the end of the follow-up, 77.2% of the patients had developed an event of recovery, and the rest 22.8% were censored. The mean age of patients was 45.22 years. Severe COVID-19 patients (AHR = 0.7876, 95% CI: 0.7090, 0.8748), presence of symptoms (AHR = 0.2814, 95% CI: 0.1340, 0.5914), comorbidity (AHR = 0.1627, 95% CI: 0.1396, 0.1897), ≥ 90 oxygen saturation (AHR = 3.2370, 95% CI: 2.161, 4.848), and being older age (AHR = 0.9840, 95% CI: 0.971, 0.9973) were found to have statistically significant association with the time to recovery from COVID-19.

CONCLUSION: The study concludes that severe COVID-19 patients, male patients, patients having comorbidity, older age, and patients having symptoms as poor prognostic factors of COVID-19 disease and also prolonged recovery time. Therefore, health providers in treatment centers should give strict follow-up and priority to older patients, severe COVID-19 patients, and patients having another co-morbid illness by focusing on respiratory difficulties and underlying pre-existing medical conditions to manage the disease severity and recover quickly.

PMID:37925445 | DOI:10.1186/s41479-023-00119-3

BMC Vet Res. 2023 Nov 4;19(1):230. doi: 10.1186/s12917-023-03791-1.

ABSTRACT

The reproductive activity of the male dromedary camel (Camelus dromedarius) as a seasonal breeder is affected by various seasonal changes that reflect on the reproductive performance. In the current study, we explored a differential cellular localization of lectins in eight dromedary camel testes utilizing lectin histochemistry (LHC). The glycoconjugates’ localizations were detected within the testicular tissue utilizing 13 biotin-labeled lectins (PNA, ConA, LCA, RCA120, GS IB4, WGA, BPL, DBA, ECA, PHA-E4, UEA-1, PTL-II, and SBA) distributed into six sets. The cellular structures revealed diverse lectins distribution that may reflect various glycoproteins’ structures and their compositional modifications during spermatogenesis. Some of the investigated lectins were restricted to acrosomes of spermatids that will help study different stages during the spermatogenic cycle of dromedary camel, particularly PNA, and ECA. The statistical analysis showed a marked positive correlation between the response intensity of various lectins and the breeding season (P < 0.05). We can conclude that lectins have a fundamental role during camel spermatogenesis and are associated with the reproductive activity of dromedary camel.

PMID:37925435 | DOI:10.1186/s12917-023-03791-1

BMC Public Health. 2023 Nov 4;23(1):2161. doi: 10.1186/s12889-023-17124-2.

ABSTRACT

BACKGROUND: Due to the restricted availability of health services in Thailand, there are still some transgender women (TGW) who do not have access to HIV counseling and testing. Telehealth, which is accessible to individuals who are reluctant to undergo face-to-face interviewing, played an especially important role during the COVID-19 epidemic. The objectives of this study are to compare the characteristics, pattern of accessing HIV testing, and the HIV-positive rates of TGW between the face-to-face and telemedicine services.

METHODS: We conducted a cross-sectional study to compare the access to HIV testing and the HIV-positive rates among TGW via face-to-face service and telemedicine services and examined the influence of potential associated factors on the risk of being HIV-positive.

RESULTS: Of the 637 TGW participants, 26 (4.1%) were HIV-positive. Accessing the telemedicine service increased in the third and fourth COVID-19 waves (28.1% in the first and second vs. 71.9% in the third and fourth). There was no difference in the risk of being HIV-positive between the types of service. Having sex work experience (adjusted odds ratio (aOR) = 5.92; 95% confidence interval (CI): 1.57-22.30) and either never having been or tested more than 1 year ago were independently significantly associated with a higher risk of being HIV-positive (aOR = 4.05; 95% CI: 1.11-14.77).

CONCLUSION: The telemedicine service became more popular among TGW during the COVID-19 pandemic and was not related to a higher risk of being HIV-positive. Moreover, it proved to be an effective alternative channel to access HIV testing, especially for intravenous drug users. Sex work experience and irregular HIV testing are key risk factors for HIV infection in TGW seeking either the telemedicine or face-to-face service.

PMID:37925430 | DOI:10.1186/s12889-023-17124-2

BMC Womens Health. 2023 Nov 4;23(1):570. doi: 10.1186/s12905-023-02725-1.

ABSTRACT

BACKGROUND: Ovarian reserve is the number of oocytes remaining in the ovary and is one of the most important aspects of a woman’s reproductive potential. Research on the association between thyroid dysfunction and ovarian reserve has yielded controversial results. In our study, we aimed to investigate the relationship between thyroid-stimulating hormone (TSH) levels and ovarian reserve markers.

METHODS: From 1443 women seeking infertility care, the data of 1396 women aged between 20-45 years old who had a body mass index between 18-30 kg/m² were recruited for this retrospective study. The anti-Müllerian hormone (AMH) and TSH relationship was analyzed with generalized linear and polynomial regression.

RESULTS: Median age, follicle-stimulating hormone (FSH), AMH, and TSH levels were 36.79 years, 9.55 IU/L, 3.57 pmol/L, and 1.80 mIU/L, respectively. Differences between TSH groups were statistically significant in terms of AMH level, antral follicle count (AFC), and age (p = 0.007 and p = 0.038, respectively). A generalized linear regression model could not explain age-matched TSH levels concerning AMH levels (p > 0.05). TSH levels were utilized in polynomial regression models of AMH, and the 2^nd degree was found to have the best fit. The inflection point of the model was 2.88 mIU/L.

CONCLUSIONS: Our study shows a correlation between TSH and AMH values in a population of infertile women. Our results are as follows: a TSH value of 2.88 mIU/L yields the highest AMH result. It was also found that AMH and AFC were positively correlated, while AMH and FSH were negatively correlated.

PMID:37925426 | DOI:10.1186/s12905-023-02725-1

Eur Urol Oncol. 2023 Nov 2:S2588-9311(23)00231-6. doi: 10.1016/j.euo.2023.10.015. Online ahead of print.

ABSTRACT

BACKGROUND: Cabazitaxel frequently causes severe neutropenia. A higher cabazitaxel systemic exposure is related to a lower nadir absolute neutrophil count (ANC).

OBJECTIVE: To describe the effect of cabazitaxel systemic exposure on ANC by a population pharmacokinetic/pharmacodynamic (POP-PK/PD) model, and to identify patients at risk of severe neutropenia early in their treatment course using a PK threshold.

DESIGN, SETTING, AND PARTICIPANTS: Data from five clinical studies were pooled to develop a POP-PK/PD model using NONMEM, linking both patient characteristics and cabazitaxel systemic exposure directly to ANC.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A PK threshold, predictive of severe neutropenia (grade ≥3), was determined using a receiver operating characteristic curve.

RESULTS AND LIMITATIONS: Ninety-six patients were included with a total of 1726 PK samples and 1081 ANCs. The POP-PK/PD model described both cabazitaxel PK and ANC accurately. A cabazitaxel plasma concentration of >4.96 ng/ml at 6 h after the start of infusion was found to be predictive of severe neutropenia, with a sensitivity of 76% and a specificity of 65%.

CONCLUSIONS: Early cabazitaxel plasma levels are predictive of severe neutropenia. Implementation of the proposed PK threshold results in early identification of almost 76% of all severe neutropenias. If prospectively validated, patients at risk could benefit from prophylactic administration of granulocyte colony stimulating factors, preventing severe neutropenia in an early phase of treatment. Implementation of this threshold permits a less restricted use of the 25 mg/m² dose, potentially increasing the therapeutic benefit.

PATIENT SUMMARY: Treatment with cabazitaxel chemotherapy often causes neutropenia, leading to susceptibility to infections, which might be life threatening. We found that a systemic cabazitaxel concentration above 4.96 ng/ml 6 h after the start of infusion is predictive of the occurrence of severe neutropenia. Measurement of systemic cabazitaxel levels provides clinicians with the opportunity to prophylactically stimulate neutrophil growth.

PMID:37925350 | DOI:10.1016/j.euo.2023.10.015

Cancer Radiother. 2023 Nov 2:S1278-3218(23)00221-4. doi: 10.1016/j.canrad.2023.05.006. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to use respiratory motion-managed radiotherapy (RT) to reduce side effects and to compare dosimetric factors with free-breathing planning in patients with lung cancer.

MATERIALS AND METHODS: Simulation images were obtained in 10 respiratory phases with free breathing using four-dimensional computed tomography (4D-CT) scanner. Planning target volume (PTV) was created with 5mm margins in each direction of the internal target volume delineated using the maximum intensity projection. A volumetric arc treatment (VMAT) plan was created so that the prescribed dose would cover 98% of the PTV. Target volumes for the free-breathing VMAT plan were created according to ICRU Reports 62 and the same prescribed dose was used.

RESULTS: Patients were evaluated during January 2020. Median 63Gy (59.4-64) RT was administered. Median PTV volumes were 173.53 and 494.50cm³ (P=0.008) and dose covering 95% of PTV volume was 62.97 and 60.51Gy (P=0.13) in 4D-CT based and free-breathing VMAT plans, respectively. The mean and V50 heart dose was 6.03Gy (vs. 10.36Gy, P=0.043) and 8.2% (vs. 33.9%, P=0.007), and significantly lower in 4D-CT based VMAT plans and there was also found a non-significant reduction for other risky organ doses.

CONCLUSION: Ten patients treated with respiratory motion-managed RT with 4D-CT based VMAT technique. It was observed that PTV did not increase, the target was covered with 95% accuracy, and with statistical significance in heart doses, all risky organ doses were found to be less.

PMID:37925346 | DOI:10.1016/j.canrad.2023.05.006

Transfus Apher Sci. 2023 Oct 22:103838. doi: 10.1016/j.transci.2023.103838. Online ahead of print.

ABSTRACT

BACKGROUND: Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure.

METHODS: In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not.

RESULTS: Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 10⁶/kg in the DM group, while it was 8.2 (1.7-37.3) × 10⁶/kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02).

CONCLUSION: DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients.

PMID:37925340 | DOI:10.1016/j.transci.2023.103838

Pancreatology. 2023 Oct 24:S1424-3903(23)01825-2. doi: 10.1016/j.pan.2023.10.013. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatitis is one of the leading causes of gastrointestinal-related hospitalization, with significant morbidity and mortality. SARS-COV-2 virus can access the pancreas via angiotensin-converting enzymes and can cause direct and indirect injury to the pancreatic parenchyma. The objective of this study to understand clinical outcomes of hospitalized patients with COVID-19 with and without pancreatitis utilizing National Inpatient Sample database.

METHODS: We utilized the United States National Inpatient Sample database to study clinical outcomes in hospitalized patients with COVID-19 infection (a total of 1,659,040 hospitalized patients with 10,075 (0.6 %) with pancreatitis) between January 1 to December 31, 2020, along with propensity matching.

RESULTS: While after propensity matching, we did not find a statistical difference in in-hospital mortality amongst COVID-19 patients with pancreatitis compared to COVID-19 patients without pancreatitis (13.2 % vs 10.3 %, adjusted odds ratio: 0.7 [95 % CI 0.5-1], p = 0.11). Patients with COVID-19 and pancreatitis had more episodes of septic shock, higher incidence of acute kidney injury and acute kidney injury requiring hemodialysis. We also found an increased prevalence of NASH cirrhosis, alcohol liver cirrhosis, and a lesser incidence of pulmonary embolisms in the COVID-19 with pancreatitis cohort.

CONCLUSION: Worse in-hospital outcomes, including increased incidence of septic shock, acute kidney injury, and acute kidney injury requiring hemodialysis in hospitalized patients with COVID-19 infection and pancreatitis, emphasize the need for more research to understand the effect of COVID-19 disease in hospitalized patients with pancreatitis and in the role of vaccination to improve long term outcome in this patient population.

PMID:37925334 | DOI:10.1016/j.pan.2023.10.013