Higher tumor mutational burden is associated with inferior outcomes among pediatric patients with neuroblastoma.

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.

Evolving treatment paradigms for platinum-resistant ovarian cancer: An update narrative review.

Platinum-resistant ovarian cancer (PROC) refers to disease progression within 6 months after the completion of platinum-based chemotherapy. Historically, treatment options for PROC were limited with a poor prognosis and non-platinum single agent plus bevacizumab has been the mainstay of treatment. Fortunately, there have been notable advancements in recent years, leading to an advance in treatment paradigms for this challenging disease. Various combinations of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy are being explored for an improved treatment outcome. Antibody-drug conjugates targeting folate receptor alpha, which deliver a cytotoxic payload directly to cancer cells, have emerged as a promising therapeutic approach for PROC. WEE1 inhibitors, such as adavosertib, function by inhibiting the WEE1 kinase activity, leading to premature entry of a cell into mitosis phase and thus increased DNA damage. It has been observed that cancer cells with TP53 mutations may be more sensitive to WEE1 inhibitors. Biomarker testing such as analysis of the expression level of folate receptor alpha or mutation in TP53 may be applicable for identifying patients who are more likely to respond to the specific therapy, enabling a more personalized treatment approach. This overview summarizes key clinical findings on the efficacy and safety of theses novel biomarker-driven therapeutic approaches.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

The Presence of TGFß3 in Human Ovarian Intrafollicular Fluid and Its Involvement in Thromboxane Generation in Follicular Granulosa Cells through a Canonical TGFßRI, Smad2/3 Signaling Pathway and COX-2 Induction.

Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor ß (TGFß), TNF-α, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGFß3 in regulating TX generation in human ovarian follicular GCs. TGFß3 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 ± 12.38 and 112.55 ± 14.82 pg/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGFß3 induced TX generation/secretion and the converting enzyme-COX-2 protein/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGFßRI and Smad2/3 signaling was mainly required for COX-2 induction, ERK1/2 appeared to regulate TX secretion. The participation of Smad2/3 and COX-2 in TGFß3-induced TX generation/secretion could be further supported by the observations that Smad2/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGFß3. Taken together, the results presented here first demonstrated that FF TGFß3 levels differ significantly in IVF patients' large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGFß3 can provoke TX generation by induction of COX-2 mRNA/protein via a TGFßR-related canonical Smad2/3 signaling pathway, and TX secretion possibly by ERK1/2. These imply that TGFß3 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation.

Survival rate of teeth adjacent and nonadjacent to dental implants: A retrospective cohort study.

BACKGROUND: The aim of this retrospective study was to investigate the risk of tooth loss for teeth adjacent and nonadjacent to dental implants. METHODS: A total of 787 patients with an average follow-up of 57.1 months were examined to define the tooth loss, cumulative survival rate, and odds ratio (OR) for teeth adjacent versus nonadjacent to implants. A multivariate logistic regression was employed to assess the association between dental history and various recorded etiologies of tooth loss among teeth adjacent to implants. RESULTS: The incidence of tooth loss for teeth adjacent to implants was 8.1% at the tooth level and 15.1% at the patient level, while 0.7% and 9.5% at the tooth and patientlevel for teeth nonadjacent to implants. The 10-year cumulative survival rate for teeth adjacent to implants was 89.2%, and the primary etiology of tooth loss was root fracture (45.2%). The risk of tooth loss among teeth adjacent versus nonadjacent to implants was significantly higher (OR 13.15). Among teeth adjacent to implants, root canal-treated teeth had a significantly higher risk of tooth loss due to root fracture (OR 7.72), a history of existing restoration significantly increased the risk of tooth loss due to caries (OR 3.05), and a history of periodontitis significantly increased the risk of tooth loss due to periodontitis (OR 38.24). CONCLUSION: The present study demonstrated that after patients received dental implant treatment, teeth adjacent to implants showed a 13.2-fold higher risk of tooth loss compared to teeth nonadjacent to implants, with the primary etiology being root fracture.

Cardiopulmonary Resuscitation Without Aortic Valve Compression Increases the Chances of Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest: A Prospective Observational Cohort Study.

OBJECTIVES: Following current cardiopulmonary resuscitation (CPR) guidelines, which recommend chest compressions at "the center of the chest," ~50% of patients experiencing out-of-hospital cardiac arrest (OHCA) undergo aortic valve (AV) compression, obstructing blood flow. We used resuscitative transesophageal echocardiography (TEE) to elucidate the impact of uncompressed vs. compressed AV on outcomes of adult patients experiencing OHCA. DESIGN: Prospective observational cohort study. SETTING: Single center. PATIENTS: This study included adult OHCA patients undergoing resuscitative TEE in the emergency department. Patients were categorized into AV uncompressed or AV compressed groups based on TEE findings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was sustained return of spontaneous circulation (ROSC). The secondary outcomes included end-tidal co2 (Etco2) during CPR, any ROSC, survival to ICU and hospital discharge, post-resuscitation withdrawal, and favorable neurologic outcomes at discharge. Additional analyses on intra-arrest arterial blood pressure (ABP) were also conducted. The sample size was pre-estimated at 37 patients/group. From October 2020 to January 2023, 76 patients were enrolled, 39 and 37 in the AV uncompressed and AV compressed groups, respectively. Intergroup baseline characteristics were similar. Compared with the AV compressed group, the AV uncompressed group had a higher probability of sustained ROSC (53.8% vs. 24.3%; adjusted odds ratio [aOR], 4.72; p = 0.010), any ROSC (56.4% vs. 32.4%; aOR, 3.30; p = 0.033), and survival to ICU (33.3% vs. 8.1%; aOR, 6.74; p = 0.010), and recorded higher initial diastolic ABP (33.4 vs. 11.5 mm Hg; p = 0.002) and a larger proportion achieving diastolic ABP greater than 20 mm Hg during CPR (93.8% vs. 33.3%; p < 0.001). The Etco2, post-resuscitation withdrawal, and survival to discharge revealed no significant intergroup differences. No patients were discharged with favorable neurologic outcomes. Uncompressed AV seemed critical for sustained ROSC across all subgroups. CONCLUSIONS: Absence of AV compression during OHCA resuscitation is associated with an increased chance of ROSC and survival to ICU. However, its effect on long-term outcomes remains unclear.

Rational design of comb-like 1D-1D ZnO-ZnSe heterostructures toward their excellent performance in flexible photodetectors.

One-dimensional (1D) Zn-based heterostructures have attracted considerable interest in the field of photodetection because of their tunable properties, flexibility, and unique optoelectronic properties. However, designing 1D multi-component Zn-based heterostructures for advanced photodetectors is still a great challenge. Herein, comb-like 1D-1D ZnO-ZnSe heterostructures with ZnO and ZnSe nanowires (NWs) comprising the shaft and teeth of a comb are reported. The length of the ZnO NWs can be modulated in the range of 300-1200 nm. Microstructural characterizations confirm that the 1D heterostructure clearly shows the spatial distribution of individual components. The well-designed structure displays an extended broadband photoresponse and higher photosensitivity than pure ZnSe NWs. Furthermore, ZnSe NWs with an appropriate length of ZnO branches show increased photoresponses of 3835% and 798% compared to those of pure ZnSe NWs under green and red-light irradiation, respectively. In addition, the integrated flexible photodetector presents excellent folding endurance after 1000 bending tests. This well-designed structure has significant potential for other 1D-based semiconductors in optoelectronic applications.

Proteomic profiling of tumor microenvironment and prognosis risk prediction in stage I lung adenocarcinoma.

OBJECTIVES: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. MATERIALS AND METHODS: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. RESULTS: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. CONCLUSION: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.

Terminal deoxynucleotidyl transferase expression in different subtypes of childhood B-cell acute lymphoblastic leukemia.

The lack of expression of terminal deoxynucleotidyl transferase (TdT) is frequently associated with KMT2A-rearranged subtype of pediatric acute lymphoblastic leukemia (ALL). However, this association has not been investigated extensively in the Asian population. A retrospective analysis of TdT expression in pediatric B-cell ALL (B-ALL) was performed in patients treated using the Taiwan Pediatric Oncology Group (TPOG) ALL 2002 and 2013 protocols. Among the 331 patients with B-ALL, 12 patients showed TdT negativity at initial diagnosis. Among these, eight patients showed KMT2A rearrangement (66.7%). Other patients showing negative TdT expression had ETV6::RUNX1, MEF2D-rearranged, and other B-ALL subtypes. However, in the context of KMT2A-rearranged B-ALL (n = 20), only eight patients showed TdT negativity. The 5-year event-free survival and overall survival of patients with and without TdT expression were 83.8% versus 46.8% (P <0.001) and 86.3% versus 55.4% (P = 0.004), respectively. Moreover, several aberrant markers, such as CD2, CD56, CD7, and CD117, were rarely expressed in the B-ALL samples, and if expressed, they were enriched in specific genetic subtypes. The results of this study indicate that immunophenotypic features are correlated with specific genetic subtypes of childhood B-ALL.

Screening for Delirium During Pediatric Brain Injury Rehabilitation.

OBJECTIVE: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: 144 children (median 10.8 years) with ABI (N=144). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. RESULTS: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. CONCLUSIONS: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.

Copper affects virulence and diverse phenotypes of uropathogenic Proteus mirabilis.

BACKGROUND: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. METHODS: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. RESULTS: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. CONCLUSION: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.

Avalanches and Extreme Value Statistics of a Mesoscale Moving Contact Line.

We report direct atomic force microscopy measurements of pinning-depinning dynamics of a circular moving contact line (CL) over the rough surface of a micron-sized vertical hanging glass fiber, which intersects a liquid-air interface. The measured capillary force acting on the CL exhibits sawtoothlike fluctuations, with a linear accumulation of force of slope k (stick) followed by a sharp release of force δf, which is proportional to the CL slip length. From a thorough analysis of a large volume of the stick-slip events, we find that the local maximal force F_{c} needed for CL depinning follows the extreme value statistics and the measured δf follows the avalanche dynamics with a power law distribution in good agreement with the Alessandro-Beatrice-Bertotti-Montorsi (ABBM) model. The experiment provides an accurate statistical description of the CL dynamics at mesoscale, which has important implications to a common class of problems involving stick-slip motion in a random defect or roughness landscape.

Autotetraploid Induction of Three A-Genome Wild Peanut Species, Arachis cardenasii, A. correntina, and A. diogoi.

A-genome Arachis species (AA; 2n = 2x = 20) are commonly used as secondary germplasm sources in cultivated peanut breeding, Arachis hypogaea L. (AABB; 2n = 4x = 40), for the introgression of various biotic and abiotic stress resistance genes. Genome doubling is critical to overcoming the hybridization barrier of infertility that arises from ploidy-level differences between wild germplasm and cultivated peanuts. To develop improved genome doubling methods, four trials of various concentrations of the mitotic inhibitor treatments colchicine, oryzalin, and trifluralin were tested on the seedlings and seeds of three A-genome species, A. cardenasii, A. correntina, and A. diogoi. A total of 494 seeds/seedlings were treated in the present four trials, with trials 1 to 3 including different concentrations of the three chemical treatments on seedlings, and trial 4 focusing on the treatment period of 5 mM colchicine solution treatment of seeds. A small number of tetraploids were produced from the colchicine and oryzalin gel treatments of seedlings, but all these tetraploid seedlings reverted to diploid or mixoploid states within six months of treatment. In contrast, the 6-h colchicine solution treatment of seeds showed the highest tetraploid conversion rate (6-13% of total treated seeds or 25-40% of surviving seedlings), and the tetraploid plants were repeatedly tested as stable tetraploids. In addition, visibly and statistically larger leaves and flowers were produced by the tetraploid versions of these three species compared to their diploid versions. As a result, stable tetraploid plants of each A-genome species were produced, and a 5 mM colchicine seed treatment is recommended for A-genome and related wild Arachis species genome doubling.

The Effect of Anti-Depressants on Dental Implant Failure: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this systematic review and meta-analysis is to analyze the risk of dental implant failure for patients who had a history of anti-depressant use. MATERIALS AND METHODS: An electronic search was performed up to June 2023 in three databases, including PubMed/MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials with data on comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at the patient level and implant level were performed. RESULTS: Eleven clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% confidence interval= 1.75 to 3.39, p< 0.0001) and 2.44 (95% CI= 1.73 to 3.46, p< 0.0001) for the implant failure at the patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other type of anti-depressants had a higher risk of implant failure than those who were not on any anti-depressants. CONCLUSIONS: The current review demonstrates the use of anti-depressants, such as SSRIs, may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to warrant this finding.

Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC.

BACKGROUND & AIMS: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS: A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS: In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS: These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.