Cigarette paper as evidence: Forensic profiling using ATR-FTIR spectroscopy and machine learning algorithms.

This research highlights the underestimated significance of cigarette paper as evidence at crime scenes. The primary objective is to distinguish cigarette paper from similar-looking alternatives, addressing the first research objective. The second objective involves identifying cigarette paper brands using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning (ML) algorithms. Accurate differentiation of cigarette paper from normal paper is emphasized. ATR-FTIR spectroscopy, coupled with principal component analysis (PCA) for dimensionality reduction, is employed for brand identification. Among fifteen ML algorithms compared, the CatBoost classifier excels for both objectives. This research presents a non-destructive, effective method for studying cigarette paper, contributing valuable insights to crime scene investigations.

Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study.

Background: Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD). Materials and Methods: In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks. Results: A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level. Conclusion: Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

Neoadjuvant combination treatment with checkpoint inhibitors, chemotherapy, and BRAF/MEK inhibitors for BRAFV600E glioblastoma results in sustained response: A case report.

Radiation's confounding and adverse effects on tumor microenvironment and normal brain could potentially be delayed by upfront combination treatment. We present a patient with newly diagnosed BRAF V600E-mutant, PD-L1-positive glioblastoma treated with off-label RAF/MEK inhibitors encorafenib/binimetinib after progressing on postoperative immune checkpoint blockade and temozolomide (no radiation administered: NCT03425292). Complete response occurred 6 months after adding encorafenib/binimetinib, and clinical benefit was sustained for over 20 months. Treatment was well tolerated with manageable toxicities, with quality of life and cognitive function maintained throughout treatment. Adding encorafenib/binimetinib to immunotherapy and temozolomide conferred favorable and lasting efficacy for our BRAF V600E -mutant glioblastoma patient, justifying future studies.

Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicology of Ruellia tuberosa L.: A Review.

Natural Products continue to be the purest source of physiologically active molecules employed in the identification of possible lead compounds in the drug discovery process. Acanthaceae is a big plant family with around 2500 species, found primarily in subtropical and tropical regions, as well as the Mediterranean, Australia, and the United States. Several species of the Acanthaceae family have been used traditionally to treat a variety of diseases, including gastrointestinal and cardiovascular ailments, etc. Ruellia tuberosa commonly known as "Mexican Bluebell" is a perennial herb that originated in Central America and has spread to some countries in the Southern tropics and Southeast Asia. It has been utilized as a traditional Rasayana plant from ancient times. R. tuberosa extracts and phytochemicals showed potent bioactivities, such as anticancer, anti-inflammatory, wound healing, antifungal, antimicrobial, anti-diabetic, hypoglycemic, hypolipidemic, gastro-protective, and anthelminthic activities. Chemical analyses have unveiled a range of bioactive constituents within the plant, including alkaloids, flavonoids, saponins, and phenolic compounds, suggestive of its therapeutic potential. Collectively, this review provides an overview of R. tuberosa, encompassing its traditional uses, ethnomedicinal importance, phytochemistry, pharmacological properties, and toxicity.

Novel physiologic predictors of positive airway pressure effectiveness (NICEPAP) study: rationale, design and methods.

PURPOSE: Continuous positive airway pressure (CPAP) is the primary therapy for obstructive sleep apnea (OSA); however the effectiveness of CPAP remains suboptimal. We describe the Novel PhysIologiC prEdictors of Positive Airway Pressure Effectiveness (NICEPAP) study. Its purpose is to determine whether physiological traits of OSA contribute to CPAP effectiveness. METHODS: NICEPAP (NCT05067088) is a prospective, observational cohort study conducted at an academic sleep center. Adults newly diagnosed with OSA (n = 267) are assessed for OSA traits of loop gain, arousal threshold, pharyngeal collapsibility, and muscle compensation from baseline polysomnography. We perform a comprehensive assessment of covariates relevant to CPAP adherence, efficacy, and patient-centered outcomes. Participants are followed for 12 months. Primary outcomes include (1) CPAP adherence (hours/night), (2) CPAP efficacy (apneas-hypopneas/hour), and (3) quality of life at six months measured by objective CPAP data and Functional Outcomes of Sleep Questionnaire. Secondary outcomes include sleep quality, sleepiness, insomnia, and neurocognitive function. RESULTS: Data on covariates, including demographics, sleep symptoms, medical history, medications, sleep quality, OSA and treatment self-efficacy, decisional balance, and socio-economic and social and partner support, are collected using validated instruments. The analysis for primary outcomes includes a generalized linear mixed model for an outcome (e.g., CPAP adherence) with OSA traits as exposures followed by the addition of relevant covariates. CONCLUSION: The findings of the NICEPAP study will inform research aimed to enhance CPAP effectiveness. Understanding the role of physiological OSA traits in CPAP effectiveness is a crucial step toward a precision medicine approach to OSA.

A Microfluidic, Multi-Antibody Cell Capture Method to Evaluate Tumor Cells in Cerebrospinal Fluid in Patients With Suspected Leptomeningeal Metastases.

CONTEXT.­: Leptomeningeal disease (LMD) is a clinical sequela of central nervous system metastasis involving the cerebrospinal fluid (CSF), often seen in late-stage solid tumors. It has a grave prognosis without urgent treatment. Standard of care methodologies to diagnose LMD include CSF cytology, magnetic resonance imaging, and clinical evaluation. These methods offer limited sensitivity and specificity for the evaluation of LMD. Here, we describe the analytic performance characteristics of a microfluidic-based tumor cell enrichment and detection assay optimized to detect epithelial cells in CSF using both contrived samples as well as CSF from patients having suspected or confirmed LMD from carcinomas. OBJECTIVE.­: To demonstrate the feasibility of using a microfluidic, multi-antibody cell capture assay to identify and quantify tumor cells in CSF. DESIGN.­: An artificial CSF solution was spiked with 34 different human carcinoma cell lines at different concentrations and assayed for the ability to detect tumor cells to assess analytic accuracy. Two cell lines were selected to assess linearity, intra-assay precision, interinstrument precision, and sample stability. Clinical verification was performed on 65 CSF specimens from patients. Parameters assessed included the number of tumor cells, coefficient of variation percentage, and percentage of tumor cell capture (TCC). RESULTS.­: Among contrived samples, average tumor cell capture ranged from 50% to 82% (261 of 522; 436 of 531), and coefficients of variation ranged from 7% to 67%. The cell capture assay demonstrated a sensitivity of 92% and a specificity of 95% among clinical samples. CONCLUSIONS.­: This assay demonstrated the ability to detect and enumerate epithelial cells in contrived and clinical specimens in an accurate and reproducible fashion. The use of cell capture assays in CSF may be useful as a sensitive test for the diagnosis and longitudinal monitoring of LMD from solid tumors.

Association between rheumatoid arthritis and atrial fibrillation: A systematic review and meta-analysis.

Rheumatoid arthritis (RA) is an autoimmune disorder with a varying range of organs involved leading to adverse outcomes. However, very little is known, with conflicting results about the association between RA and atrial fibrillation (AF). We aim to evaluate the association between RA and AF, and other clinical outcomes. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until September 10, 2023. Primary clinical outcomes were AF. Secondary outcomes were acute coronary syndrome (ACS), stroke, and all-cause mortality (ACM). A total of 4 679 930 patients were included in the analysis, with 81 677 patients in the RA group and 4 493 993 patients in the nonrheumatoid arthritis (NRA) group. The mean age of the patients was 57.2 years. Pooled analysis of primary outcomes shows that RA groups of patients had a significantly higher risk of AF (odds ratios [OR], 1.53; 95% confidence interval [CI]: [1.16-2.03], p < .001) compared with NRA groups. Secondary Outcomes show that the RA group of patients had significantly higher odds of ACS (OR, 1.39; 95% CI: [1.26-1.52], p < .001), and ACM (OR, 1.19; 95% CI: [1.03-1.37], p = .02) compared with the NRA groups. However, the likelihood of stroke (OR, 1.02; 95% CI: [0.94-1.11], p = .61) was comparable between both groups of patients. Our study shows that RA groups of patients are at increased risk of having AF, ACS, and ACM.

Ovarian Cystic Lymphangioma.

Lymphangioma are benign, slow-growing and rare lymphatic tumors, which may emerge at any location in the body with ovary being a very rare location. Axillary region and neck are the most common sites, while retroperitoneum and mesentery account for <1%. We present a case of a young female of 33 years who had symptomatic pelvic mass and was presented with a complaint of lower abdominal pain of six-month duration and weight loss. Investigation revealed an oval-shaped complex cystic density lesion in the right adnexal region, which was likely neoplastic. Elective laparotomy with right ovarian cystectomy was performed. Histopathological examination revealed ovarian lymphangioma.

RNA-Small-Molecule Interaction: Challenging the "Undruggable" Tag.

RNA targeting, specifically with small molecules, is a relatively new and rapidly emerging avenue with the promise to expand the target space in the drug discovery field. From being "disregarded" as an "undruggable" messenger molecule to FDA approval of an RNA-targeting small-molecule drug Risdiplam, a radical change in perspective toward RNA has been observed in the past decade. RNAs serve important regulatory functions beyond canonical protein synthesis, and their dysregulation has been reported in many diseases. A deeper understanding of RNA biology reveals that RNA molecules can adopt a variety of structures, carrying defined binding pockets that can accommodate small-molecule drugs. Due to its functional diversity and structural complexity, RNA can be perceived as a prospective target for therapeutic intervention. This perspective highlights the proof of concept of RNA-small-molecule interactions, exemplified by targeting of various transcripts with functional modulators. The advent of RNA-oriented knowledge would help expedite drug discovery.

Patient reported outcome for physical function in idiopathic inflammatory myopathy.

OBJECTIVES: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population. METHODS: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months. RESULTS: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size. CONCLUSIONS: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.

A novel approach using ATR-FTIR spectroscopy and chemometric analysis to distinguish male and female human hair samples.

This article presents an attempt to discriminate between human male and female hair samples using a single strand of scalp hair. The methodology involves the non-destructive application of ATR-FTIR spectroscopy coupled with chemometric analysis. A total of 96 hair samples, evenly distributed between 48 male and 48 female volunteers from India, were collected. Spectral analysis revealed subtle differences between the two groups, and reliance on visual interpretation might introduce biasness. To avoid subjective biases, chemometric techniques such as principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were employed for enhanced data visualization and separation. PCA results revealed that the first 10 principal components accounted for 93% of the total variance, with three significant PCs. The PLS-DA model demonstrated a remarkable sensitivity and specificity in sex discrimination from hair samples, establishing its efficacy as a robust classification tool. Furthermore, the proposed model exhibited 100% accuracy in predicting unknown samples, underscoring its potential applicability in real-world scenarios. These outcomes affirm the viability of our approach for non-invasive classification of human male and female hair based on single-strand scalp hair analysis.

A Path of Novelty from Nanoparticles to Nanobots: Theragnostic Approach for Targeting Cancer Therapy.

Pharmaceutical development of cancer therapeutics is a dynamic area of research. Even after decades of intensive work, cancer continues to be a dreadful disease with an ever-increasing global incidence. The progress of nanotechnology in cancer research has overcome inherent limitations in conventional cancer chemotherapy and fulfilled the need for target-specific drug carriers. Nanotechnology uses the altered patho-physiological microenvironment of malignant cells and offers various advantages like improved solubility, reduced toxicity, prolonged drug circulation with controlled release, circumventing multidrug resistance, and enhanced biodistribution. Early cancer detection has a crucial role in selecting the best drug regime, thus, diagnosis and therapeutics go hand in hand. Furthermore, nanobots are an amazing possibility and promising innovation with numerous significant applications, particularly in fighting cancer and cleaning out blood vessels. Nanobots are tiny robots, ranging in size from 1 to 100 nm. Moreover, the nanobots would work similarly to white blood cells, watching the bloodstream and searching for indications of distress. This review articulates the evolution of various organic and inorganic nanoparticles and nanobots used as therapeutics, along with their pros and cons. It also highlights the shift in diagnostics from conventional methods to more advanced techniques. This rapidly growing domain is providing more space for engineering desired nanoparticles that can show miraculous results in therapeutic and diagnostic trials.

Characterization of the novel HLA-B*15:05:01:02 allele by sequence-based typing.

HLA-B*15:05:01:02 differs from HLA-B*15:05:01:01 by one nucleotide change in intron 2 at position 517 (C > A).

One nucleotide substitution in the 3'UTR generated the novel allele HLA-B*40:01:02:47 in a North Indian individual.

HLA-B*40:01:02:47 differs from HLA-B*40:01:02:01 by one nucleotide change in the 3'UTR at position 2739 (A>T).

A single nucleotide substitution in intron 3 generated the novel HLA-A*11:01:01:68 allele.

HLA-A*11:01:01:68 differs from HLA-A*11:01:01:01 by one nucleotide change in intron 3 at position 1474 (G > A).

Mastalgia - The Burden Beneath.

Objective: Mastalgia is the most common breast-related complaint. A multitude of hormonal changes and lifestyle associated factors have been implicated in its causation. A long list of treatment modalities have been tried with varying success rates. To identify the most common risk factors and the most effective management strategies for mastalgia in our clinic population. Materials and Methods: A total of 100 women between 18-65 years of age presenting to the breast clinic with mastalgia were followed throughout their course of diagnosis and management. Stepwise treatment was provided, starting with reassurance and breast support and progressing to include pharmacological measures, when necessary. The risk factors and outcomes of treatment were analysed. Results: The majority (66%) were aged 25-47 years and the left breast was found to be most frequently involved. Involvement of the upper outer quadrant was significantly more common. Lump/nodularity was the most prevalent risk factor. Most patients showed a positive response to non-steroid anti-inflammatories (NSAIDs) in addition to reassurance, breast support and dietary changes. Conclusion: A detailed history and clinical examination helps to identify the risk factors and the best approach for the management of mastalgia. Educating women regarding breast self-examination at regular intervals helps in early presentation and diagnosis of the underlying condition. Reassurance, breast support and lifestyle changes are the first line treatment and have good results in a significant number of patients. In our practice topical and oral NSAIDs, evening primrose oil and vitamin E were frequently used as additional treatments to non-pharmacological methods.

Advancing automobile identification and brand discrimination from tyre rubber through Machine learning algorithms for forensic investigations.

Criminal instances involving collision accidents, hit-and-run incidents, abduction, hostage-taking, and the unauthorised transit of forbidden items generally include evidence involving rubber traces from automobile tyres. These traces can be located on the road surface, in clothing, on the victim(s) themselves, or on items as skid marks following sudden stopping and spinning around. These traces serve as crucial evidence by reducing the range of suspects by revealing linkages between the getaway vehicle, the site of the crime, and the perpetrator through the tyre's brand, producer, or origin. This study offered a way for classifying 220 tyre rubber samples from different brands using various machine learning algorithms in PyCaret in conjunction with rapid and non-destructive ATR-FTIR spectroscopy equipped with diamond crystal. On spectral information from ATR-FTIR, pre-processing tools such as baseline correction, smoothing, derivatization, and normalisation were also implemented prior to machine learning. This approach has the potential to be advantageous for efficiently and non-destructively identifying rubber traces as forensic evidence and for facilitating brand recognition of automobile tyres.

Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

Response to OKN-007 and NAC in a Patient with Unilateral Hearing Loss and Chronic Tinnitus from Vestibular Schwannoma.

BACKGROUND: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. OBJECTIVE: To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. PATIENT CASE: We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. RESULTS: Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. CONCLUSIONS: This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation.