Evaluation Of Therapeutic Efficacy Research Articles

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

Case Report: A 5 Yea kan r Old Girl with Diphtheria

Background: Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. It is characterized by the formation of pseudomembranes in the tonsils, pharynx, and/or nasal cavity, which can lead to severe complications such as airway obstruction, myocarditis, and paralysis of the palate muscles. Aims: This study aims to detail the clinical course and treatment of a pediatric diphtheria case, emphasizing the importance of early diagnosis and appropriate therapeutic interventions. Methods: The case of a 5-year-old girl presenting with a 3-day history of fever at K.R.M.T Wongsonegoro Hospital is described. Clinical evaluation, including history, physical examination, and supportive tests, led to a diagnosis of diphtheritic tonsillitis. Findings: The patient exhibited classic symptoms of diphtheria, including sore throat, fever, and the presence of a dirty, greyish-white pseudomembrane on the tonsils. The membrane extended to adjacent structures, causing a condition known as bullneck. The treatment protocol included the administration of diphtheria antitoxin (DAT), antibiotics, antipyretics, corticosteroids, and symptomatic management. Conclusion: Diphtheria remains a serious infectious disease requiring prompt diagnosis and treatment to prevent complications. The case highlights the importance of early intervention, continuous monitoring, and the evaluation of therapeutic efficacy to improve patient outcomes. Implications: This study underscores the necessity of vigilant clinical practices in managing diphtheria cases, particularly in pediatric patients, to reduce morbidity and mortality.

The Role of Adrenomedullin as a Predictive Marker of the Risk of Death and Adverse Clinical Events: A Review of the Literature.

Adrenomedullin (ADM) is a vasodilatory peptide that plays a crucial role in maintaining cardiovascular health through its various biological functions. ADM was discovered in the acidic extract of human pheochromocytoma tissue and has been recognized for its significant effects on the vascular system. The main functions of ADM include vasodilation, controlling blood pressure and maintaining vascular integrity, although its role on cardiovascular health is broader. Research has shown that elevated levels of adrenomedullin have been observed in a large number of severe diseases, with high risk of death. In this work, we examined the role of ADM as a predictive molecule of the risk of mortality and adverse clinical outcome through a narrative review of the scientific literature. The results were divided based on the pathologies and anatomical districts examined. This review demonstrates how ADM shows, in many diseases and different systems, a close correlation with the risk of mortality. These results prove the value of ADM as a prognostic marker in various clinical contexts and diseases, with utility in the stratification of the risk of clinical worsening and/or death and in the evaluation of therapeutic efficacy. The results open new perspectives with respect to the concrete possibility that ADM enters clinical practice as an effective diagnostic and prognostic marker of death as well as a molecular target for therapies aimed at patient survival.

Early prediction of neoadjuvant chemotherapy efficacy for mass breast cancer based on dynamic contrast‐enhanced magnetic resonance imaging radiomics

AbstractRadiomics uses automated algorithms to extract high‐order features from images, which can contribute to clinical decisions such as therapeutic efficacy evaluation. We assessed the value of a dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI)‐based radiomics model for predicting pathological complete response (pCR) after a second cycle of neoadjuvant chemotherapy (NAC) in patients with mass breast cancer. We retrospectively analyzed data from 149 patients with mass breast cancer who underwent NAC between January 2017 and December 2022. Using DCE‐MRI, before NAC and after a second cycle of NAC, the least absolute shrinkage and selection operator and logistic regression (LR) algorithms were applied for feature selection and radiomics modeling. We found significant differences in two clinical imaging features (molecular subtypes, background parenchymal enhancement changes) and two radiomics features. Clinical and radiomics features were employed to build clinical, radiomics, and combined models to predict pCR. The LR model that combined clinical and radiomics features had an area under the curve of 0.811, higher than that for the imaging or radiomics model. Our findings suggest that a combined model based on imaging and radiomics features can improve early prediction of NAC efficacy for patients with mass breast cancer.

Radiolabeling and Preclinical Evaluation of Therapeutic Efficacy of 225Ac-ch806 in Glioblastoma and Colorectal Cancer Xenograft Models.

The epidermal growth factor receptor (EGFR) protein is highly expressed in a range of malignancies. Although therapeutic interventions directed toward EGFR have yielded therapeutic responses in cancer patients, side effects are common because of normal-tissue expression of wild-type EGFR. We developed a novel tumor-specific anti-EGFR chimeric antibody ch806 labeled with 225Ac and evaluated its invitro properties and therapeutic efficacy in murine models of glioblastoma and colorectal cancer. Methods: 225Ac-ch806 was prepared using different chelators, yielding [225Ac]Ac-macropa-tzPEG3Sq-ch806 and [225Ac]Ac-DOTA-dhPzPEG4-ch806. Radiochemical yield, purity, apparent specific activity, and serum stability of 225Ac-ch806 were quantified. In vitro cell killing effect was examined. The biodistribution and therapeutic efficacy of 225Ac-ch806 were investigated in mice with U87MG.de2-7 and DiFi tumors. Pharmacodynamic analysis of tumors after therapy was performed, including DNA double-strand break immunofluorescence of γH2AX, as well as immunohistochemistry for proliferation, cell cycle arrest, and apoptosis. Results: [225Ac]Ac-macropa-tzPEG3Sq-ch806 surpassed [225Ac]Ac-DOTA-dhPzPEG4-ch806 in radiochemical yield, purity, apparent specific activity, and serum stability. [225Ac]Ac-macropa-tzPEG3Sq-ch806 was therefore used for both invitro and invivo studies. It displayed a significant, specific, and dose-dependent invitro cell-killing effect in U87MG.de2-7 cells. 225Ac-ch806 also displayed high tumor uptake and minimal uptake in normal tissues. 225Ac-ch806 significantly inhibited tumor growth and prolonged survival in both U87MG.de2-7 and DiFi models. Enhanced γH2AX staining was observed in 225Ac-ch806-treated tumors compared with controls. Reduced Ki-67 expression was evident in all 225Ac-ch806-treated tumors. Increased expression of p21 and cleaved caspase 3 was shown in U87MG.de2-7 and DiFi tumors treated with 225Ac-ch806. Conclusion: In glioblastoma and colorectal tumor models, 225Ac-ch806 significantly inhibited tumor growth via induction of double-strand breaks, thereby constraining cancer cell proliferation while inducing cell cycle arrest and apoptosis. These findings underscore the potential clinical applicability of 225Ac-ch806 as a potential therapy for EGFR-expressing solid tumors.

Evaluation of therapeutic efficacy of tranexamic acid compared to modified Kligman formula in the management of melasma

Background: Facial melanoses (FM) are a common presentation in Indian patients, causing cosmetic disfigurement with considerable psychological impact. Melasma is an acquired non-inflammatory hypermelanosis of multifactorial etiology with significant cosmetic deformity. Different treatment modalities have been tried in different studies with varying outcomes. Recent clinical trials with tranexamic acid (TXA) are promising. Objective: To compare the therapeutic efficacy of TXA topical application after micro-needling and intralesional TXA with the modified Kligman formula in the management of melasma. Materials and Methods: This is a prospective, randomized, open-label study with a sample size of 45 patients with melasma fulfilling inclusion and exclusion criteria. They were randomly divided into three groups of 15 each. Group A individuals were advised to apply a modified Kligman formula daily at night for 3 months, Group B individuals weekly micro-needling followed by TXA application for 3 months, and Group C individuals intralesional TXA (4 mg/mL) weekly for 3 months. Clinical and dermoscopic images were taken at each visit, including modified Melasma Area Severity Index (MASI) scoring, patient global assessment, and physician global assessment to assess the clinical response. Results: Group A showed a 42% improvement in MASI score by the end of 12 weeks, Group B showed a 30% improvement, and Group C showed a 36% improvement. When statistically compared with the Analysis of Variance test, there was no significant difference (P = 0.62) between the three groups. However, in individual groups, there was a significant difference (P < 0.05) in MASI at 0 and 12 weeks. Dermoscopic images showed perilesional hypopigmentation and telangiectasias with a modified Kligman formula, which was not seen with TXA. Patient assessment score revealed satisfaction with the modified Kligman formula because of home application and lack of pain. Conclusion: The modified Kligman formula is found to be superior in the treatment of melasma, because of the synergistic activity of its components. However, it has its demerits of long-term usage like hypopigmentation and telangiectasias. Hence, TXA that showed comparable results with the Kligman formula can be used either as a primary modality or as an adjuvant supportive therapy for maintenance.

Evaluation of Therapeutic Efficacy of Mucus and Tissue Extracted from Biomphalaria alexandrina Snails on Mice Infected with Schistosoma mansoni

Abstract Schistosomiasis is a neglected tropical disease with considerable morbidity. Praziquantel though safe and efficacious does not prevent reinfection and the emergence of drug resistance is of great concern. This study was done to evaluate the therapeutic efficacy of mucus and nucleoproteins extracted from Biomphalaria alexandrina snails on miracidia, cercariae and Schistosomamansoni adults in vitro and assess their in vivo effect on mice experimentally infected with Schistosoma mansoni through parasitological, pathological and biochemical parameters.The in vitro study proved that the mucus had a better lethal effect on cercariae than miracidia, on contrast to NPs which was better on miracidia. The mucus effect surpassed the NPs as regard the lethal effect on adults in vitro. The effect of mucus on S. mansoni females and males was almost equivocal except for the effect after 72 hours where 80 µg/ml caused 100% lethal effect on adult females. The effect of NPs on S. mansoni adult females was better than adult males at the highest used concentration of 100 µl/ml after 72 hours with a 60% lethal effect. However, at 48 hours the same concentration had a better lethal impact on males (25%) than females (20%). The in vivostudy proved that the combined NPs or mucus to PZQ added to the effect of individual PZQ considering its effect on ova count, oogram pattern and granuloma parameters. The histopathological results denoted a relevant potential for NPs when compared to the rest of the groups and the control though, the PZQ still showed the best findings. The effect of PZQ alone or combined with mucus or NPs was equivocal resulting in 100% TWB reduction. As regard oxidative stress markers, NO decreased level was best shown by combined PZQ and NPs, while, as regard GSH level, the individual PZQ showed the best increased level. This study concluded that mucus and NPs had cercaricidal, miracidial and antischistosomal effect in vitro and that their combination could be considered as a sharing therapeutic adding to PZQ potentiality in vivo for the treatment of schistosomiasis for further investigations.

Research Progress on the Treatment of Qi Deficiency and Blood Stasis Type Hand-foot Syndrome by Buyang Huanwu Decoction

Hand-foot syndrome (HFS) is one of the common adverse reactions in the treatment of malignant tumors, and its incidence is gradually increasing with the widespread use of antitumor drugs. HFS seriously affects patients' daily social and life, and even leads to drug dosage reduction or early discontinuation of medication, which delays treatment. Modern medicine has not yet fully clarified the understanding of its etiology and pathogenesis, the lack of uniform standards for the evaluation of therapeutic efficacy, and the poor effect of targeted systemic therapy. Chinese medicine classifies HFS into the category of "blood paralysis", and considers that the disease is located in the hands and feet, with deficiency as the main cause, and the deficiency as the underlying cause, and the mixture of deficiency and reality. BHD is from the book "Reform and Error Correction of Medical Forests" written by Qing Dynasty physician Wang Qingren, which has the effects of tonifying qi, activating blood and clearing collaterals. The formula is rigorous and well formulated, and is now widely used in all kinds of diseases with qi deficiency and blood stasis, with remarkable results. In recent years, with the rapid development of modern pharmacology, the research on the microscopic mechanism of action of BHD has been developing and deepening, which provides new ideas for the treatment of the disease. In this paper, we review BHD in HFS in the treatment of malignant tumors from the aspects of its formula and modern pharmacological research, with a view to providing clinical basis and reference for the future treatment of HFS of qi deficiency and blood stasis type by BHD.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.

Assessment of PD-L1 Expression in Non-Small Cell Lung Cancers Using [68Ga]Ga-DOTA-WL12 PET/CT.

Assessing programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [68Ga]Ga-DOTA-WL12 micro-PET/CT imaging are performed. [68Ga]Ga-DOTA-WL12 PET/CT and [18F]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi-quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target-to-background ratio (TBR). DOTA-WL12 exhibits robust PD-L1 binding with a KD value of 0.2nM. Subsequent human studies reveal significant correlations between PD-L1 expression and the [68Ga]Ga-DOTA-WL12 SUVmax in primary and metastatic lesions, surpassing the [18F]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [68Ga]Ga-DOTA-WL12 imaging discerned SUVmax and TBR differences between PD-L1 TPS ≤1% and PD-L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [68Ga]Ga-DOTA-WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [68Ga]Ga-DOTA-WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD-L1-expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management.

Paraoxonase-2 agonist vutiglabridin promotes autophagy activation and mitochondrial function to alleviate non-alcoholic steatohepatitis.

Only limited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH). Glabridin, a promising anti-obesity candidate, has only limited druggability due to its low in vivo chemical stability and bioavailability. Therefore, we developed vutiglabridin (VUTI), which is based on a glabridin backbone, and investigated its mechanism of action in treating NASH in animal models. Anti-NASH effects of VUTI were determined in in vitro fatty liver models, spheroids of primary human hepatocytes and L02 normal liver cell lines. To identify VUTI possible cellular target/s, biotin-labelled VUTI was synthesized and underwent chemical proteomic analysis. Further, the evaluation of VUTI therapeutic efficacy was carried out using an amylin-NASH and high-fat (HF) diet-induced obese (DIO) mouse models. This was carried out using transcriptomic, lipidomic and proteomic analyses of the livers from the amylin-NASH mouse model. VUTI treatment markedly reduces hepatic steatosis, fibrosis and inflammation by promoting lipid catabolism, activating autophagy and improving mitochondrial dysfunction, all of which are hallmarks of effective NASH treatment. The cellular target of VUTI was identified as paraoxonase 2 (PON2), a newly proposed protein target for the treatment of NASH, VUTI enhanced PON2 activity. The results using PON2 knockdown cells demonstrated that PON2 is important for VUTI- activation of autophagy, promoting mitochondrial function, decreasing oxidative stress and alleviating lipid accumulation under lipotoxic condition. Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome

BackgroundIn the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is “stationarity” of the underlying responses – i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary.MethodsAEPs were recorded to simple 100 Hz tones from 18 RTT and 27 age-matched controls (Ages: 6–22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures.ResultsSubstantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a “neural unreliability” account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident.ConclusionsTo accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Neurokinin-1 Receptor Antagonism Reduces Nonallergic Ocular Redness in a Rabbit Model.

Purpose: To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Methods: Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%). The NK1R antagonist L-703,606 was topically applied to the eye at the same time of induction or 20 min after induction, and phosphate buffered saline (PBS) treatment served as the control. Superior bulbar conjunctival images were taken every 30 s for the first 2 min, followed by every 4 min for 8 min, and then every 10 min until 1 h. The severity of ocular redness was evaluated on the images using ImageJ-based ocular redness index (ORI) calculations. Results: The ORI scores were significantly increased after the application of 0.5%, 1%, 2%, or 5% dapiparzole at each time point evaluated, with the most severe redness induced by the 5% dapiprazole that led to a maximal mean increase in ORI score of 14 at 20 min post-induction and thus used for subsequent evaluation of therapeutic efficacy of NK1R antagonism. Topical L-703,606, when applied at the same time as dapiprazole induction, significantly suppressed the increase of ORI scores at all time points (∼40% decrease). Furthermore, when applied at 20 min after dapiprazole induction, L-703,606 rapidly and effectively suppressed the increase of ORI scores at 30, 40, 50, and 60 min (∼30% decrease). Conclusions: Topical blockade of NK1R effectively prevents and alleviates nonallergic ocular redness in a novel animal model.

Efficacy of FOLFIRI plus bevacizumab versus FOLFIRI plus cetuximab in RAS-mutant metastatic colorectal cancer: Final update on patients with RAS-mutant metastatic colorectal cancer treated in FIRE-3.

3550 Background: Doublet chemotherapy plus bevacizumab is a well-established standard of care in the first-line treatment of RAS-mutant (RASmut) metastatic colorectal cancer (mCRC). The FIRE-3 trial was the first randomized study to compare FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC. Since this trial initially included patients irrespective of RAS mutation status, the present analysis performs an updated evaluation of therapeutic efficacy of targeted therapy with bevacizumab versus cetuximab in RASmut mCRC. Methods: FIRE-3 trial included 752 patients. Initially, pyrosequencing (PSeq) was used to identify RAS mutations. In a subsequent investigation next-generation sequencing (NGS) was applied in 373 available tumors. A 5% mutant allele cutoff was used for both PSeq and NGS both of which were done centrally. Results: Of the 224 RASmut and BRAF wild-type patients, 187 were identified by polymerase chain reaction (PCR) and PSeq, 122 by NGS. 86 tumors were PCR positive and NGS positive (PCR+/NGS+), 36 tumors PCR negative and NGS positive (PCR-/NGS+). In the overall RASmut cohort of 224 patients, no overall survival (OS) benefit was observed when cetuximab was compared to bevacizumab (20.3 months vs 21.1 months; HR 1.028; 95% CI, 0.547-1.583; P=.842). This effect was observed independent of sidedness of primary tumors (PT) for left-sided (21.5 months vs 22.1 months; HR 1.054; 95% CI, 0.763-1.456) and right-sided PT (19.2 months vs 19.5 months; HR 0.931; 95% CI, 0.547-1.583). Conclusions: While cetuximab notably is not effective in RASmut mCRC, this randomized comparison does not provide an indication for superior efficacy of bevacizumab in the first-line treatment of this patient group. Trial identification number: NCT00433927 [clinicaltrials.gov]

CRISPR/Cas12b assisted loop-mediated isothermal amplification for easy, rapid and sensitive quantification of chronic HBV DNA in one-pot

BackgroundCurrently, millions of people suffer from undiagnosed chronic hepatitis B (CHB) infection each year, which leads to high mortality rates attributed to cirrhosis and hepatocellular carcinoma. Previously reported assays, such as PCR-based assays, have limitations in terms of convenient for CHB screening in high-burden regions and resource-limited settings. Recently, diagnosis based on CRISPR/Cas, which has been considered as a potential method of point-of-care test (POCT) in resource-limited settings, offers a significant advantage in terms of high sensitivity and specificity. Therefore, there is an urgent need for the hepatitis B virus (HBV) detection utilizing CRISPR/Cas system. ResultsWe have proposed a one-pot of one-step method for CRISPR/Cas12b assisted loop-mediated isothermal amplification (LAMP) to facilitate the quick, sensitive, and precise quantification of HBV DNA. This method is designed for point-of-care testing following genomic extraction or sample heat treatment. We have optimized several critical factors, such as the reaction buffer, AapCas12b-gRNA concentration, reporter and its concentration, reaction temperature, and chemical additives, to significantly enhance the performance of the one-pot assay for HBV. Importantly, it exhibited no cross-reactivity between HBV and blood-borne pathogens. Moreover, the assay is capable of quantifying HBV DNA within 1 h with a limit of detection (LOD) of 25 copies per milliliter. Additionally, when tested on 236 clinical samples, the assay demonstrated a sensitivity of 99.00 % (198/200) and a specificity of 100.00 % (36/36) at the 99 % confidence level compared to real-time quantitative PCR. SignificanceThe utilization of convenient and reliable point-of-care diagnostic methods is crucial for reducing the burden of CHB globally. The assay we developed was helpful to improve the ability of HBV diagnosis for practical clinical translation, especially in high-burden regions and resource-limited settings. It has great advantages for rapid screening of CHB as well as evaluation of therapeutic efficacy as a companion diagnostic method.

Clinical evaluation of therapeutic efficacy of a Siddha herbo mineral formulation “Kumaara Veeriya Kaantha Chenduram’’ with “Nellikkai Legiyam” (internal) in the treatment of Iron Deficiency Anemia

Abstract: Background: Kumaara veeriya kaantha chenduram (KVKC) is a siddha herbomineral formulation indicated for paandunoi in Siddha literature (1).Paandu noi is a disease characterized by changes in the body's natural color andpallor found in the skin, nails and conjunctiva. Objectives: To determine the efficacy of the KVKC, the open labed clinical study was conducted in National Institute of Siddha OPD. Materials and Methods: The 30 patients with Iron deficiency anaemiawere selected and treated with KVKC orally with the dose of 260 milli gram twice in a day with Nellikailegiyam6 gram continuously for 45 days. Laboratory investigations for hemoglobin was done on 1st day and every 15 days once of the study. Results: Clinical assessment was done, based on the before and after treatment scores which was compared statistically and recorded.Regarding Hemoglobin level, 24(80%) patients showed increase of 1 to 3 grams from base level, 6(20%) patients showed increase of 0.1 to 0.9 grams from base level.Regarding Serum Ferritin, out of 30 patients, 9 (30%) patients showed 0.1-3.5 ng/ml increase from its base level, 21 (70%) patients showed 3.6-7.0 ng/ml increase from its base level.From the Statistical studies, the Mean ± Standard deviation for Haemoglobin before treatment was 9.7 ± 0.93 and after treatment was 11.18 ± 1.08 which was statistically highly significant (p&lt;0.0001).And Serum ferritin before treatment was 9.27 ± 3.31, after treatment was 13.5 ± 3.49 which was statistically significant (p&lt;0.0001).

Evaluation of Safety and Therapeutic Efficacy of CAR-T Therapy

Chimeric antigen receptor (CAR)-T therapy has been developed as revolutionary treatment in cancer treatment. It has been clinically proven to be effective and durable towards certain subtypes of blood cancer especially in B-cell leukemia or lymphoma. CARs are synthetic receptor which are designed to redirect T lymphocytes to eliminate cancer cells with a specific antigen on the surface. However, limited therapeutic efficacy and safety concern of CAR-T therapy present as obstacles to its application in both solid and hematological cancer. Hence more research is being conducted to study the mechanism behind therapeutic limitation and how to improve its therapeutic effectiveness. Furthermore, innovative strategies should be investigated to limit its toxicities. This review firstly explains the process of CAR-T therapy and its current milestone. Then the review discusses its current challenges and characterize some reasons for its limited therapeutic applications and strategies to improve its efficacy and safety in clinical settings.

Evaluation and Comparison of Therapeutic Efficacy of Various Hormonal Protocols in Anoestrus Buffalo Heifers of Semi-Arid Region

To assess and compare different hormonal protocols' treatment efficacy in anoestrus buffalo heifers in a semi-arid region. Forty buffalo heifers with a history of anoestrus were chosen randomly from the semi-arid region of Banaskanth and divided into four equal groups.Group-I: Heatsynch protocol (n = 10), Group-II Ovsynch protocol (n = 10), Group-III Doublesynch protocol (n = 10) and Group-IV Control (n = 10) are followed by artificial insemination at a predetermined period in treated buffalo heifers and insemination during spontaneous estrus in group-IV buffalo heifers. In Groups I, II, and III, the corresponding percentages of estrus induction were 90, 80, and 80 percent. Major symptoms such as edoema, erythema, dampness of vulva and estrus mucus secretion were present during the expression of estrus. Fifty percent of the buffalo heifers in Group IV displayed estrus at varying intervals. After three consecution services, Group II had the highest overall fertility rate (50%) followed by Group III (40%), Group I (30%), and Group IV (30%). In true anoestrus buffalo heifers, the Heatsynch, Ovsynch, and Doublesynch procedure can be applied with success to induce estrus. Buffalo heifers that follow the Ovsynch protocol may have a higher conception rate.

Evaluation of therapeutic efficacy of Emustil drops for ocular discomfort and tear film osmolarity using different treatment management modes under dry environmental conditions

BackgroundWe aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities.MethodsThe subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI).ResultsThe mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved.ConclusionCEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.

Abstract 5337: Profiling of human CD34+ donors in a myeloid-supportive HIS model provides increased predictability and facilitates study design for evaluation of immuno-oncology therapeutics

Abstract Background: Humanized immune system (HIS) mice are critical immuno-oncology tools for in vivo evaluation of therapeutic target engagement and efficacy. HIS mice require a human donor source of CD34+ hematopoietic stem cells to provide the human immune cell system. However, variance across donors complicates study design and hypothesis testing. To determine if parameters critical to drug discovery are consistent across batches of HIS mice from the same donor, we evaluated two independent cohorts of human tumor xenograft-bearing mice made using a common set of five different CD34+ cell donors. Our study included evaluation of tumor growth kinetics, human immune reconstitution and phenotype, and the pharmacokinetics and anti-tumor efficacy of a therapeutic monoclonal antibody directed against a human target expressed on tumor-associated macrophages (TAMs). Method: HIS NOG-EXL (huNOG-EXL) mice were created using CD34+ cells from five donors in two independent cohorts (~12 weeks apart). Baseline immune reconstitution in blood was assessed at 10 weeks post engraftment. MDA-MB-231 cells were inoculated bilaterally and mice were randomized into groups for immune profiling, pharmacokinetics, and efficacy studies. Body weight, clinical observations, endogenous hIgG levels, and tumor growth were measured. For efficacy, tumors grew to ~100 mm3 and mice were dosed intraperitoneally every five days (6 doses total). Separate cohorts of mice were used for immune phenotyping and the single-dose PK study. Results: Donor consistency was seen for some of the parameters assessed but not all. The overall health outcomes for a given donor appeared to have an impact on the consistency of important parameters (e.g. efficacy). Donors that had poor health outcomes (body condition scores [BCS] &amp;lt;3) showed less consistency than those that experienced good (BCS=3) outcomes. The health trajectory, peripheral human immune cell engraftment, and PK profiles were similar across experiments for a given donor. Total human immune cell infiltration in tumors was similar across experiments, but there were notable shifts in immune cell composition. Whereas mice in the first cohort showed a dominant TAM phenotype within the tumor (~&amp;gt;50% of all hCD45+ cells), mice across donors in the second cohort had reduced TAMs and corresponding increases in several T cell subsets. Efficacy was consistent in donors with good health outcomes (Donors 1 and 4) and was inconsistent in those with poor outcomes (Donors 3 and 5). Conclusion: Our study demonstrates that a return-to-donor approach can provide information that is reproducible across cohorts to help build a donor profile. An understanding of this profile should afford greater predictability and facilitate study design for drug discovery applications. Citation Format: Janell R. Richardson, Megan M. MacBride, Esther Andino, Emily Sack, Nicholas Smith, Po Y. Ho, Fang Xiao, Katelynn A. McEachin, David T. Omstead, Rachel Grgich, Michael N. Alonso, Justin A. Kenkel, Shelley E. Ackerman. Profiling of human CD34+ donors in a myeloid-supportive HIS model provides increased predictability and facilitates study design for evaluation of immuno-oncology therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5337.