Polishing systems for modern aesthetic dental materials: a narrative review.

Objectives To review the current literature surrounding chairside polishing systems for resin composites, zirconia and lithium disilicate restorations.Methods A literature search was undertaken and databases were hand-searched for the most relevant articles.Discussion The current marketplace contains a wide variety of polishing systems, each with different abrasive compounds and number of steps. Current efforts are aimed at reducing the number of steps required for polishing to improve clinical effectiveness. Reduced step systems showed some comparable results to the more traditional multi-step protocols, but the most effective results were achieved with the use of polishing paste as an additional step.Conclusions Based on the current available literature, the use of material-specific polishing systems is effective for chairside polishing of direct and indirect restorative materials. However, it is important to emphasise that, for optimum outcomes, it is essential to follow manufacturers' recommendations for each step, with particular considerations of the handpiece speed, time spent per step and use of adjunct water coolant.

Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects.

Sarcomas, a diverse group of malignant tumors originating from connective tissues, present substantial diagnostic challenges due to their histological heterogeneity. Traditional diagnostic methods include histomorphology along with immunohistochemistry is necessary for primary evaluation. Fluorescence in situ hybridization (FISH) is a supplementary tool that helps with additional findings. However it is very difficult sometimes to accurately classify sarcoma subtypes despite all these tools. Recent advancements in DNA methylation profiling have emerged as a promising approach to enhance the precision of sarcoma diagnosis. This paper delves into the role of DNA methylation classifiers in diagnosing sarcomas, emphasizing their potential to improve diagnostic accuracy, inform treatment decisions, and ultimately enhance patient outcomes.

Unicentric Castleman disease masquerading as a gluteal mass: A diagnostic challenge.

Castleman disease, a rare lymphoproliferative disorder characterized by non-neoplastic lymph node enlargement, typically presents as nodal involvement, while extranodal manifestations are uncommon. We present a unique case of unicentric Castleman disease localized to the gluteal region in a 27-year-old female. Initially mistaken for a neurogenic or vascular tumour, fine needle aspiration cytology (FNAC) revealed a polymorphous population of lymphoid cells with numerous traversing capillaries suggestive of reactive hyperplasia, possibly Castleman disease, which was later confirmed by histopathology. This case highlights the diagnostic challenges posed by rare extranodal presentations of Castleman disease and underscores the importance of interdisciplinary collaboration in accurate diagnosis and management.

Application of the WHO reporting system for soft tissue cytopathology with assessment of risk of malignancy: a retrospective study.

INTRODUCTION: Soft tissue tumors are complex neoplasms requiring accurate diagnosis, often through fine needle aspiration (FNA). The World Health Organization (WHO) classification system aims to standardize cytopathological diagnoses and assess the risk of malignancy (ROM) for these tumors. MATERIALS AND METHODS: This retrospective study reviewed cytological specimens from January 2022 to June 2023. Samples were categorized using the WHO classification into 6 categories: nondiagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy (SFM), and malignant. Histopathological correlation was performed, and ROM, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. RESULTS: A total of 203 samples were analyzed: 62.5% benign, 13.8% SFM, and 9.9% malignant. ROMs were 33.3% (nondiagnostic), 1.2% (benign), 40% (atypical), 25% (soft tissue neoplasm of uncertain malignant potential), 80% (SFM), and 100% (malignant). Histopathological correlation was available for 117 cases. Sensitivity and diagnostic accuracy were highest (77.3% and 93.9%) when SFM and malignant categories were combined as positive for malignancy. Specificity was highest (100%) when only malignant cases were considered positive. The interobserver agreement was moderate (Cohen's kappa 0.45). CONCLUSION: The WHO classification system for soft tissue cytopathology improves diagnostic accuracy and standardizes reporting. It effectively categorizes soft tissue tumors and guides clinical management, though further refinement is needed for broader applicability.

Molecular prevalence, epidemiology, and phylogenetic analysis of Babesia microti in dogs with a note on its impact on host hematological profile.

Babesia (B.) microti is an intra-erythrocytic protozoan parasite that infects humans as well as domestic and wild animals. Prevalence of B. microti was investigated in 654 apparently healthy dogs belonging to 55 different breeds from three districts in Punjab province (Muzaffargarh, Bahawalpur and Jhang) and two districts in Khyber Pakhtunkhwa province (Dir Upper and Charsadda) in Pakistan. The hematological profile of dogs, risk factors associated with the infection and phylogenetic diversity of the detected isolates were also evaluated. In total, 29 blood samples (4 %) scored PCR positive. Sanger sequencing of partial 18S rRNA gene confirmed the presence of B. microti. The phylogenetic analysis of the sequences based on the 18S rRNA gene displayed global phylogenetic similarity with the isolates that were previously documented from Russia, France, Poland, Spain, China, Japan and USA. The infection rate was consistent across different sampling sites and dog breeds. Sex or presence of ectoparasites on dog was also not associated with B. microti prevalence. Babesia microti infected dogs had elevated red cell distribution width-coefficient of variation (%) than uninfected animals. This study presents updated data about the prevalence of B. microti among local Pakistani dogs and will be helpful in designing control strategies against this tick-borne pathogen as the tick infesting a B. microti infected dog may transmit this parasites to human as well.

A Flexible and Optical Transparent Metasurface Absorber with Broadband RCS Reduction Characteristics.

Metasurface absorbers (MSAs) are of significant importance in a wide range of applications, such as in the field of stealth technology. Nevertheless, conventional designs demonstrate limited flexible characteristics and a lack of transparency, hence constraining their suitability for certain radar stealth applications. This study introduces a novel MSA operating in the broad microwave range, which exhibits both optical transparency and flexibility. The structure consists of a flexible substrate made of polyvinyl chloride (PVC), along with a resistive film composed of indium tin oxide (ITO). The proposed structure exhibits the ability to effectively absorb over 90% of the energy carried by incident electromagnetic (EM) waves across the frequency range of 9.85-41.76 GHz within an angular range of 0° to 60°. In addition, to assess the efficacy of the absorption performance, an examination of the radar cross-section (RCS) characteristics is conducted. The results indicate a reduction of over 10 dB across the aforementioned broad frequency spectrum, regardless of the central angle.

Photo-induced changes in tissue stiffness alter epithelial budding morphogenesis in the embryonic lung.

Extracellular matrix (ECM) stiffness has been shown to influence the differentiation of progenitor cells in culture, but a lack of tools to perturb the mechanical properties within intact embryonic organs has made it difficult to determine how changes in tissue stiffness influence organ patterning and morphogenesis. Photocrosslinking of the ECM has been successfully used to stiffen soft tissues, such as the cornea and skin, which are optically accessible, but this technique has not yet been applied to developing embryos. Here, we use photocrosslinking with Rose Bengal (RB) to locally and ectopically stiffen the pulmonary mesenchyme of explanted embryonic lungs cultured ex vivo . This change in mechanical properties was sufficient to suppress FGF-10-mediated budding morphogenesis along the embryonic airway, without negatively impacting patterns of cell proliferation or apoptosis. A computational model of airway branching was used to determine that FGF-10-induced buds form via a growth-induced buckling mechanism and that increased mesenchymal stiffness is sufficient to inhibit epithelial buckling. Taken together, our data demonstrate that photocrosslinking can be used to create regional differences in mechanical properties within intact embryonic organs and that these differences influence epithelial morphogenesis and patterning. Further, this photocrosslinking assay can be readily adapted to other developing tissues and model systems.

Molecular surveillance based on anaplasmosis in domestic small ruminants: First report on zoonotic Anaplasma capra and phylogenetic insights from Faisalabad, Pakistan.

Anaplasma is an intracellular alphaproteobacteria that infects diverse blood cell types in animal hosts including small ruminants. Epidemiological and risk factors information on zoonotic anaplasmosis with respect to anaplasmosis in sheep and goats are scarce. Therefore, the objective of the current study was to estimate the prevalence, risk factors of anaplasmosis and phylogenetic investigation of A. capra in sheep and goats from Faisalabad district, Pakistan. Briefly, 384 blood samples were randomly collected from sheep and goats of Faisalabad district, Pakistan, during January to May 2022. The samples were processed for the detection of Anaplasma targeting 16S rRNA gene using PCR. The data regarding disease determinants were collected using a predesigned questionnaire. Out of 384 samples, 131 samples were found positive for Anaplasma spp. with a prevalence rate of 34.11%. The results indicated a significantly higher prevalence of anaplasmosis in goats (41.88%) compared to sheep (22.00%). In addition, the chi square indicated that housing type, tick infestation, gender, tick control practices, age, mix farming, and hygiene were significantly associated with the occurrence of disease. The analysis of multivariate logistic regression expressed gender as the significant risk factor (p = 0.0001, OR = 1.757, CI = 1.305-2.366). The acquired sequences revealed four novel isolates of A. capra (Genbank accession numbers ON834323, ON838209, ON838210, and ON838211). The phylogenetic analysis of the 16S rRNA gene of A. capra revealed three distinct clusters with 99-100% homology with other isolates from different countries. Our isolates showed higher similarity with isolates from China (KM206273, KP314237, MT799937), Pakistan (ON238129, ON238130, ON238131), Angola (MT898988), India (MZ558066), Iran (MW692362), and Turkey (MT632469) isolated from human, sheep, ticks, goats, cattle, Gaddi goat, Persian Onager (Equus hemionus onager), and Turkish goats, respectively. In conclusion, A. capra is endemic in Punjab, Pakistan, there is a need to conduct large scale surveillance studies to assess the status of this pathogen at human-animal interface as well as to develop effective preventive and control strategies to reduce the economic losses associated with anaplasmosis in small ruminants.

Genetic polymorphisms in FABP2, CYP2E1, and TP53 genes are potentially associated with colorectal cancer susceptibility.

Colorectal cancer (CRC) is among the most prevalent cancers with a high mortality rate. Both genetic and environmental factors contribute to CRC development. This study aimed to assess the association of single nucleotide polymorphisms (SNPs) in the fatty acid binding protein-2 (rs1799883), Cytochrome P450 2E1 (rs3813865), TP53 (rs1042522), and Murine double minute 2 (rs1042522) genes with CRC. A cross-sectional case-control study was conducted at the Institute of Molecular Biology and Biotechnology from May 2020 to March 2021, involving CRC patients (N = 100) and controls (N = 100) recruited from the Multan district in Pakistan. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) were employed to investigate the studied SNPs. The association of SNPs in all genes with CRC was examined either individually or in various combinations. Genotypes at three SNPs, rs1799883 in FABP2, rs3813865 in CYP2E1, and rs1042522 in TP53, were found to be associated with the development of CRC, while rs1042522 in MDM2 was not. Patients who were married, smoked, lacked exercise habits or had a family history of CRC were at a greater risk of acquiring the disease. FABP2 gene rs1799883, CYP2E1 gene rs3813865, and TP53 gene rs1042522 polymorphisms are significant in the development of CRC in Pakistani participants.

Immunodeficiency: Quantitative and qualitative phagocytic cell defects.

The immune system is divided into two major branches: innate and adaptive. The innate immune system is the body's first line of defense and rapidly responds in a nonspecific manner to various microorganisms, foreign materials, or injuries. Phagocytes, which include macrophages, monocytes, and neutrophils, are innate immune cells that can surround and kill microorganisms, ingest foreign material, and remove dead cells. They also indirectly boost both innate and adaptive immune responses through various activation signals. Phagocytic defects characteristically lead to fungal and bacterial infections of the respiratory tract, lymph nodes, skin, and other organ systems, and they are commonly associated with inflammatory bowel disease. This primer will review high-yield innate defects of phagocytic cells, including defects of respiratory (oxidative) burst, defects of neutrophil migration, cyclic and severe congenital neutropenias and associated disorders, and other phagocyte defect disorders.

Toxoplasma gondii infection affects the complete blood count and disturbs the markers of oxidative stress from the vital organs of wild rodents.

Rodents are the synanthropic mammals that are existing in close proximity to humans and their belongings and have the potential to act as the reservoir for a variety of parasites having zoonotic potential. Present study was designed to report the molecular prevalence and phylogenetic evaluation of Toxoplasma gondii in the blood samples of four wild rodent species [Rattus rattus (N = 122), Mus musculus (N = 64), Rattus norvegicus (N = 57) and Dryomys nitedula (N = 1)] that were trapped during May 2022 till July 2023 from three districts in Punjab (Jampur, Dera Ghazi Khan and Multan) and three districts (Upper Dir, Mardan and Bunar) in Pakistan. Results revealed that 44/244 (18%) rodents amplified ITS-1 gene of Toxoplasma gondii through PCR. Parasite prevalence varied between the rodent species. Highest rate of infection was found in Rattus norvegicus followed by Rattus rattus and Mus musculus. For both rat species, Toxoplasma gondii infection significantly varies between the sampling districts. DNA sequencing and BLAST analysis confirmed the presence of Toxoplasma gondii in rodent blood samples. Phylogenetic analysis showed that Pakistani isolates were genetically diverse and clustered with the isolates that were reported from worldwide countries. Complete blood count analysis revealed that parasite infected rodents had disturbed lymphocyte, mean platelet volume, mean corpuscular volume (and mean corpuscular hemoglobin concentration. Markers of oxidative stress analysis revealed that infected rodent had elevated malondialdehyde levels in liver and kidney while disturb catalase concentrations in kidney and heart as compared to uninfected animals. In conclusion, we are reporting a relatively high prevalence of Toxoplasma gondii in Pakistani rodents. Infection leads to disturbed complete blood count and markers of oxidative stress in the vital organs. We recommend large scale studies in various geo-climatic regions of Pakistan to report the incidence and prevalence of this pathogen among the rodents in order to prevent their infections in local people as well as in livestock.

Identifying the hidden parasitic intruders: Molecular insights into the health of common Myna.

Birds are known to act as the parasite reservoir and can transmit them to other organisms through food chains. This study aims to report the molecular prevalence and phylogenetic evaluation of various blood borne pathogens (Toxoplasma gondii, Isospora spp., Plasmodium spp., Haemoproteus spp., Leucocytozoan spp. and Neospora caninum) in blood samples of common Myna (Acridotheres tristis: N = 80) collected from four region (Jhang, Khanewal, Multan and Muzaffargarh) in Punjab Pakistan. Effect of pathogens on the complete blood count of the host was also determined. Results revealed by 2/80 Myna (2.5 %) amplified ITS-1 gene of Toxoplasma (T.) gondii (confirmed by DNA sequencing) while 2/80 (2.5 %) birds amplified 18S rDNA gene and Isospora spp. Phylogenetic analysis of both pathogens showed that Pakistani isolates were clustered together and were closely related to isolates that were reported from worldwide countries. Risk factor analysis revealed that prevalence of both pathogens was not restricted to a particular sampling site or a particular bird sex (P > 0.05). T. gondii infected birds had elevated red cell distribution width while Isospora sp. infected birds had elevated % monocytes and platelet distribution width while decreased mean cell hemoglobin, mean corpuscular hemoglobin concentration and platelets hematocrit than their respective uninfected birds. In conclusion, we are reporting the presence of T. gondii and Isospora sp. among Pakistani common Myna that had disturbed the complete blood count parameters that may have affected their normal physiology.

Diagnostic Accuracy of the Second Edition of the Paris System for Reporting High-Grade Urothelial Carcinoma in Urinary Cytology.

BACKGROUND: Urinary cytology, a non-invasive screening tool, is essential for detecting high-grade urothelial neoplasms. The Paris System (TPS) standardizes reporting practices to improve diagnostic accuracy. TPS 2.0, introduced in 2022, categorizes samples into six diagnostic groups, emphasizing high-grade urothelial carcinoma (HGUC). MATERIALS AND METHODS: This retrospective study analyzed urine cytology samples from June 2023 to May 2024, correlating with histopathology when available. Samples were classified under TPS 2.0 categories, and statistical metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for three groups based on malignancy criteria. RESULTS: Out of 180 samples, the distribution was ND (3.9%), NHGUC (65.6%), AUC (10%), SHGUC (11.7%), and HGUC (8.9%). Histopathological correlation was available for 30.6% of cases. risk of malignancy values were: ND (33.3%), negative for HGUC (29.4%), AUC (66.7%), suspicious for HGUC (94.1%), and HGUC (100%). Group A showed the highest sensitivity (86.49%) and diagnostic accuracy (84.62%), while group C had 100% specificity and PPV. CONCLUSION: The study confirms TPS 2.0's efficacy in improving diagnostic accuracy for HGUC, with high specificity and sensitivity. Compared to TPS 1.0, TPS 2.0 offers clearer diagnostic criteria, enhancing clinical decision-making and patient outcomes. The findings support the continued use of TPS 2.0 in clinical practice, ensuring reliable identification of HGUC.

A rare Encounter with Pediatric Malignant Peripheral Nerve Sheath Tumor in Nasal Sinuses and Orbit.

This case report explores a rare and aggressive Malignant Peripheral Nerve Sheath Tumor (MPNST) in a 7-year-old child affecting nasal sinuses, maxilla, and orbit, an exceptionally uncommon pediatric manifestation unrelated to Neurofibromatosis 1. The child presented with alarming symptoms-nasal obstruction, snoring, epistaxis, and difficulty swallowing-underscoring the case's urgency. Non-contrast computed tomography revealed an extensive mass infiltrating nasopharynx, nasal cavity, maxillary sinus, ethmoid sinuses, and orbit, causing destructive consequences. Histopathology confirmed a high-grade MPNST, marked by rapid growth and early metastasis, highlighting management challenges. The rarity of pediatric MPNST in the nasal cavity is discussed, emphasizing the need for a broad differential diagnosis. Treatment involves surgical resection and adjuvant chemoradiation with a grim prognosis due to diagnostic complexities and morphological mimicry in young patients.

Clinical and histopathological spectrum of congenital pulmonary airway malformations: A case series.

BACKGROUND: Congenital pulmonary airway malformations (CPAM) are a spectrum of cystic and non-cystic anomalies arising from abnormal airway development in utero, with an incidence of 1 in 25,000 to 35,000 births. CPAM can present prenatally or postnatally with respiratory distress, recurrent infections, or occasionally as an incidental finding. This case series aims to highlight the clinical, radiological, and histopathological characteristics of CPAM through three pediatric cases, which include types 1, 2, and 3 CPAM. CASE PRESENTATION: Case 1: A four-month-old male presented with cough, cold, and respiratory distress. Imaging revealed hypoattenuation and overinflation of the left upper lobe with mediastinal shift. Left upper lobectomy confirmed CPAM type 2. Case 2: A one-month-old female presented with recurrent respiratory distress and infections. Imaging showed a large cystic lesion in the right middle lobe. Right middle lobectomy confirmed CPAM type 3. Case 3: A two-month-old male presented with dyspnea. Imaging showed a large bullae in the right chest with mediastinal shift. Right upper lobectomy confirmed CPAM type 1. CLINICAL DISCUSSION: CPAM is a rare congenital lung malformation characterized by abnormal bronchial development and localized glandular overgrowth. Management involves surgical resection, with the timing of surgery dependent on symptomatology. Early identification and intervention are crucial for preventing complications such as pulmonary hypoplasia and recurrent infections. Histopathological examination post-resection is essential for accurate classification and management of CPAM. CONCLUSION: This case series provides valuable insights into the clinical, radiological, and histopathological features of CPAM, including the types encountered in each case. It underscores the importance of early diagnosis and timely surgical intervention, advocating for routine prenatal and postnatal screenings to effectively identify and manage CPAM.

Preparation, characterization and functional evaluation of soy protein isolate-peach gum conjugates prepared by wet heating Maillard reaction.

This study was conducted to formulate a conjugate of soy protein isolate (SPI) and peach gum (PG) with improved functional properties, interacting at mass ratios of 1:1, 1:2, 1:3, 2:1, and 2:3 by Maillard reaction via wet heating method. Conjugation efficiency was confirmed by grafting degree (DG) and browning index (BI). Results indicated that DG increased with increasing concentration of PG, and decreased with increasing pH, whereas no remarkable change was observed with increasing reaction time. The conjugates were optimized at a ratio of 1:3. SDS-PAGE confirmed conjugate formation, Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) verified conjugate secondary structural changes, and scanning electron microscopy (SEM) indicated significant overall structural changes. The functional properties, solubility, emulsifying stability, water holding, foaming, and antioxidant activity were significantly improved. This study revealed the wet heating method as an effective approach to improve the functional properties of soy protein.

Prediction-error signals in anterior cingulate cortex drive task-switching.

Task-switching is a fundamental cognitive ability that allows animals to update their knowledge of current rules or contexts. Detecting discrepancies between predicted and observed events is essential for this process. However, little is known about how the brain computes cognitive prediction-errors and whether neural prediction-error signals are causally related to task-switching behaviours. Here we trained mice to use a prediction-error to switch, in a single trial, between responding to the same stimuli using two distinct rules. Optogenetic silencing and un-silencing, together with widefield and two-photon calcium imaging revealed that the anterior cingulate cortex (ACC) was specifically required for this rapid task-switching, but only when it exhibited neural prediction-error signals. These prediction-error signals were projection-target dependent and were larger preceding successful behavioural transitions. An all-optical approach revealed a disinhibitory interneuron circuit required for successful prediction-error computation. These results reveal a circuit mechanism for computing prediction-errors and transitioning between distinct cognitive states.

Phase-Based Gait Prediction after Botulinum Toxin Treatment Using Deep Learning.

Gait disorders in neurological diseases are frequently associated with spasticity. Intramuscular injection of Botulinum Toxin Type A (BTX-A) can be used to treat spasticity. Providing optimal treatment with the highest possible benefit-risk ratio is a crucial consideration. This paper presents a novel approach for predicting knee and ankle kinematics after BTX-A treatment based on pre-treatment kinematics and treatment information. The proposed method is based on a Bidirectional Long Short-Term Memory (Bi-LSTM) deep learning architecture. Our study's objective is to investigate this approach's effectiveness in accurately predicting the kinematics of each phase of the gait cycle separately after BTX-A treatment. Two deep learning models are designed to incorporate categorical medical treatment data corresponding to the injected muscles: (1) within the hidden layers of the Bi-LSTM network, (2) through a gating mechanism. Since several muscles can be injected during the same session, the proposed architectures aim to model the interactions between the different treatment combinations. In this study, we conduct a comparative analysis of our prediction results with the current state of the art. The best results are obtained with the incorporation of the gating mechanism. The average prediction root mean squared error is 2.99° (R2 = 0.85) and 2.21° (R2 = 0.84) for the knee and the ankle kinematics, respectively. Our findings indicate that our approach outperforms the existing methods, yielding a significantly improved prediction accuracy.

Comparison of the modified Masood's scoring index versus international academy of cytology Yokohama system in the categorization of breast fine needle aspirates.

CONTEXT: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system. AIMS: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system. CONCLUSION: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases.