This study aims to review the development trends of clinical trials for lung cancer cellular therapy systematically, analyze the spatiotemporal distribution, research entities, cell types, target selection quantitatively, thus, trial design characteristics and reveal the evolutionary patterns, driving factors, and scientific challenges in this field. The findings are intended to provide a reference for subsequent research, policy formulation, and clinical translation. Clinical trials of cellular therapies for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) worldwide up to July 2025 were retrieved. A cross-referencing strategy was applied to include interventional clinical studies in the process of excluding non-cellular therapies and records with missing key information. Two researchers independently screened and extracted data, 452 trials were included ultimately. Descriptive statistical methods were used to make analysis of core indicators, such as annual trends, geographical distribution, funding entities, target mechanisms, research phases, and trial status. Results Global clinical trials for lung cancer cellular therapy entered a rapid development phase, which started in 2016, peaked in 2024 (51 trials). Trials were highly concentrated on early stages, with Phase I and Phase I/II studies accounting for 79.9% (361/452). Only 7 Phase III studies were conducted, this gave a highlight of significant translational bottlenecks. Geographically, a bipolar driving pattern emerged between China and the United States. China experienced explosive growth post-2016 and leaded globally in trial numbers by 2024 (31 trials). Funding entities shifted from early public sector dominance to industry-led by small and medium-sized biotech companies. In terms of targets, PD-1 (25 trials) and IL-2Rα (22 trials) were the most popular, while emerging targets, for instance, cancer-testis antigen 1B and mesothelin gradually gained prominence. Mechanistically, immuno-oncology therapies and T-cell stimulators predominated. Among therapies such as CAR-T, NK, TCR-T, TIL, and DC vaccines, CAR-T and TIL, all showed the highest recent activity, while DC vaccines were relatively mature. This study systematically analyzed the current status and trends of global clinical trials for lung cancer cellular therapy, which demonstrated the rapid development driven by technological breakthroughs, policy support, and capital investment. Nevertheless, lung cancer cellular therapy still faces scientific challenges, such as target selection, efficacy enhancement, and safety optimization. Future research should explore deeply to give a promotion of clinical translation and application.
Hamstring tightness is a common musculoskeletal concern that can impair posture, restrict mobility, and predispose individuals to lower limb injuries. Various stretching techniques are employed to enhance flexibility, yet their comparative effectiveness remains debated. The aim of this study was to evaluate the effects of Post-Isometric Relaxation (PIR) and Active Static Stretching (ASS) on the hamstring flexibility of allied health sciences students. A parallel-group, assessor-blinded, single-center randomized controlled trial was carried out at the University of Health Sciences, Lahore's Department of Physiotherapy (ClinicalTrials.gov Identifier: NCT07153510). Fifty-two students aged 18-25 years with hamstring tightness and Active Knee Extension (AKE) > 20° from full extension were randomly allocated to PIR (n = 26) group and ASS (n = 26) groups. After baseline treatment, Group A, PIR underwent sub-maximal isometric hamstring contraction for 7 s, followed by 15 s of passive stretch, repeated 10 times. Group B, ASS group performed active hamstring stretch held for 30 s, repeated 10 times. Both groups received 12 supervised sessions over four weeks (three sessions per week). Primary outcome was hamstring flexibility (AKE). Secondary outcomes included resolution of hamstring tightness. The Statistical Package of Social Sciences (SPSS) version 25.0 was used to analyze the data. At baseline, both groups were comparable in AKE values (PIR: 150.73° ± 7.94; ASS: 148.31° ± 8.32; p = 0.288). Both groups showed notable within-group increases following the intervention, but the PIR group's flexibility gains were noticeably larger. (165.69° ± 6.61 vs. 158.69° ± 8.23; p = 0.001). A universal goniometer was used to objectively measure hamstring flexibility during the Active Knee Extension (AKE) test. When AKE < 20° from full extension, resolution was taken into consideration. Hamstring tightness resolved in 67.3% of participants overall, with higher improvement rates in the PIR group. No adverse events were reported. Both PIR and ASS effectively improved hamstring flexibility in young adults; however, Post-Isometric Relaxation produced significantly superior improvements. The results suggest that PIR may be a preferred clinical and preventive strategy for enhancing flexibility and reducing the risk of hamstring tightness-related dysfunctions in student and general populations.Trial Registration ClinicalTrials.gov Identifier: NCT07153510. Registered prospectively, Registration Date: 10th July, 2025.
Relapse after curative‑intent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) is common and may become clinically apparent only after a delay in conventional imaging and CA19‑9 monitoring. Liquid biopsy offers serial access to tumor‑derived signals, but post‑operative minimal residual disease (MRD) is often near the assay limit of detection, raising risks of false positives, over‑imaging, and premature treatment escalation outside trials. We performed a scoping review of clinical studies evaluating circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vehicles (EVs) in resected or curatively treated PDAC, focusing on recurrence prediction, lead time, and practical implementation. Across cohorts, tumor‑informed ctDNA and longitudinal CTC kinetics show consistent prognostic value and may precede radiographic recurrence by weeks to months, although sensitivity varies with tumor shedding patterns and assay design. EV markers and signatures provide complementary biology and may be informative in low‑shedding states, but reproducibility is limited by pre‑analytical and platform heterogeneity, necessitating conservative interpretation. We propose a pragmatic, confirmation‑gated trigger algorithm for "liquid‑positive, imaging‑negative" scenarios: borderline signals are considered indeterminate and prompt repeat sampling and/or orthogonal confirmation; imaging is expedited when ctDNA converts on serial draws or when concordant positivity is observed across two analytes (ctDNA/CTC/EV); and systemic therapy changes should be avoided outside prospective utility‑driven trials. Finally, we outline trial designs (ctDNA‑positive escalation, ctDNA‑negative de‑escalation, and strategy comparisons) incorporating survival, decision‑curve, and health‑economic endpoints to establish clinical utility.
Our previous findings demonstrated the promising antitumor activity and manageable safety of sintilimab-lenvatinib conversion therapy. The current study aimed to evaluate long-term survival outcomes in patients with unresectable hepatocellular carcinoma (HCC) who underwent sequential surgical resection after successful conversion therapy. In this prospective, single-arm, expansion, phase II trial, patients with unresectable HCC received lenvatinib plus sintilimab conversion therapy. Hepatectomy was performed in consenting patients after successful conversion therapy. The primary endpoint was the conversion rate; secondary endpoints included median overall survival (OS), 5-year survival rates, and recurrence-free survival (RFS). Successful conversion was achieved in 67 of 120 patients (56%, 67/120). Independent imaging review per mRECIST and RECIST v1.1 criteria demonstrated objective response rates of 58.3% (70/120) and 45.8% (55/120), respectively. With a median follow-up of 41.0 months (95% confidence interval [CI], 39.5-42.5) for the entire cohort, the median OS was 36.0 months (95% CI, 25.0 to not estimable [NE]), with a 5-year OS rate of 42.6% (95% CI, 34.0-53.0). Following multidisciplinary team evaluation and consideration of patient preferences, 60 patients underwent surgical resection, achieving a median RFS of 40.0 months (95% CI, 24.0 to NE) and a 5-year survival rate of 73.9% (95% CI, 62.7-87.1). Grade ≥3 treatment-related adverse events occurred in 37 patients (31%). Approximately half of the patients with unresectable HCC achieved successful conversion after sintilimab plus lenvatinib therapy. Among those who achieved successful conversion, subsequent curative surgery demonstrated not only a favorable safety profile but also significant survival benefits. Trial registration number: ChiCTR1900023914.
Metformin is widely used for diabetes, but its effects on bone health are uncertain. This meta-analysis study found that it reduces markers of both bone loss and bone formation. It is still unclear whether this benefits or harms bones long term, highlighting the need for larger, longer clinical studies. Metformin is a widely used antidiabetic drug that has shown potential effects on bone metabolism. However, its impact on bone turnover markers remains unclear. This systematic review and meta-analysis aimed to assess this effect. A comprehensive search was conducted across PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases, identifying clinical trials published up to February 04, 2026, that evaluated the effects of metformin on validated bone turnover markers. The quality and risk of bias were assessed using the Modified Jadad Scale, and Cochrane Collaboration's risk of bias tool, respectively. A random-effects meta-analysis was performed to estimate the standardized mean difference (SMD) with a 95% confidence interval. Fourteen studies met the inclusion criteria, involving diabetic and non-diabetic populations. Metformin significantly reduced both bone resorption, bone formation markers (SMD: -1.28 [95% CI: -2.03, -0.52], I2 = 99.33%), and (-0.18 [-0.28, -0.08], I2 = 67.78%), respectively. These findings suggest a pattern consistent with reduced bone turnover rather than selective modulation of either bone resorption or bone formation. However, substantial statistical heterogeneity was observed across studies, especially for bone resorption markers, limiting the precision and generalizability of pooled estimates. Metformin appears to lower overall bone turnover, reducing both bone resorption and bone formation markers. However, given the high heterogeneity across studies and the reliance on surrogate biochemical endpoints rather than fracture or bone mineral density outcomes, the clinical significance of these findings remains uncertain. Larger, long-term trials are needed to determine whether metformin provides real benefits or risks for osteoporosis.
Preserving pulp vitality in deep carious lesions remains a clinical challenge. Indirect pulp capping with bioactive calcium silicate materials such as Biodentine has shown favorable biological outcomes, while diode laser irradiation has been proposed as an adjunct to enhance hemostasis, disinfection, and pulpal healing. However, evidence regarding their combined use is limited. This randomized controlled clinical trial compared the clinical and radiographic outcomes of indirect pulp capping using Biodentine alone and diode laser pre-treatment followed by Biodentine. Patients with deep carious lesions were randomly allocated to either Biodentine alone (Group I) or diode laser pre-treatment plus Biodentine (Group II). Changes in dentin thickness were evaluated using cone-beam computed tomography at baseline, 3 months, and 12 months. Tooth discoloration was assessed spectrophotometrically using CIE Lab* parameters, while pulp vitality, pain, and sensitivity were clinically recorded. Data were analyzed using repeated-measures ANOVA (p < 0.05). Both groups demonstrated significant increases in dentin thickness over time (p < 0.001). Group II exhibited significantly greater dentin formation at 3 and 12 months compared with Group I (p < 0.05). No significant differences in tooth discoloration were observed between groups, and all ΔE values remained within clinically acceptable limits. Pulp vitality was preserved in all cases, with significantly lower postoperative pain scores in the diode laser group. Within the limitations of this randomized clinical trial, diode laser pretreatment was associated with a greater increase in radiographically detectable dentin thickness following vital pulp therapy with Biodentine.
Breast cancer surgery is frequently associated with moderate to severe postoperative pain. While the serratus anterior plane block (SAPB) provides effective anterolateral chest wall analgesia, it may inadequately cover the anterior intercostal nerve branches. This study aimed to determine whether adding a superficial parasternal intercostal plane block to SAPB improves postoperative opioid consumption, pain scores, and dermatomal sensory coverage. In this prospective, randomized, double-blind trial, 64 patients aged 18-65 years undergoing elective breast surgery were randomly allocated into two groups. Group S (n = 32) received a preoperative SAPB with 30 mL of 0·25% bupivacaine combined with a parasternal injection of 10 mL saline. Group S + P (n = 32) received a SAPB with 30 mL of 0·25% bupivacaine plus a parasternal block with 10 mL of 0·25% bupivacaine. All patients were managed with an identical multimodal postoperative analgesia protocol. The primary outcome was postoperative opioid consumption. Secondary outcomes included visual analogue scale (VAS) pain scores, dermatomal sensory analysis and side effects. Baseline demographic characteristics and surgical variables were comparable between groups (p > 0·05). Sensory blockade of the T3, T4, and T5 dermatomes was significantly more frequent in the S + P group than in the S group (p < 0·05). However, postoperative VAS pain scores at rest and during movement, as well as total opioid consumption, were comparable between groups (p > 0·05). Although the addition of a superficial parasternal intercostal plane block to SAPB resulted in wider anterior chest wall dermatomal coverage, it did not confer additional benefit in terms of postoperative pain scores or opioid consumption under a multimodal analgesia regimen. These findings suggest that SAPB-based strategies, when combined with systemic analgesics, may provide sufficient postoperative analgesia in patients undergoing mastectomy.
Ultra-low anterior resection for low rectal cancer is associated with profound perioperative physiologic stress and systemic inflammation, contributing to impaired functional recovery and adverse long-term outcomes. Whether the perioperative host response can be effectively modulated to improve both recovery and survival remains unclear. In this single-center, randomized controlled trial, 194 patients with stage I-III low rectal adenocarcinoma undergoing curative ultra-low anterior resection were assigned to standard enhanced recovery after surgery care or enhanced recovery after surgery plus an integrated perioperative host-response optimization program. The intervention combined structured perioperative optimization strategies targeting stress regulation, sleep normalization, and individualized nutritional support, delivered from the preoperative period through postoperative month 6. Primary outcomes included postoperative functional recovery, assessed by validated measures of bowel, sleep, psychological, and sexual function. Secondary outcomes comprised postoperative inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-α), short-term recovery metrics, and 24-month disease-free survival and overall survival. Compared with standard enhanced recovery after surgery care, the intervention group demonstrated significantly attenuated systemic inflammation on postoperative day 7 (C-reactive protein, interleukin-6, and tumor necrosis factor-α; all P < .001), accompanied by a faster return of bowel function and a shorter hospital stay. Functional recovery across bowel, sleep, psychological, and sexual domains was significantly improved and exceeded prespecified minimal clinically important difference thresholds. At 24 months, disease-free survival was 92.8% in the intervention group vs 77.3% in controls, and overall survival was 95.9% vs 83.5%, respectively. In multivariable Cox models adjusted for age, TNM stage, baseline depressive symptoms, and postoperative inflammatory markers, the intervention was independently associated with improved disease-free survival (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87) and overall survival (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89). Integrated perioperative optimization targeting the host inflammatory and stress response significantly improves functional recovery and is associated with superior disease-free survival and overall survival after ultra-low anterior resection for rectal cancer. These findings support perioperative host-response modulation as a clinically actionable strategy to enhance both short- and long-term surgical outcomes.
To assess the benefit of night-time compression in addition to daytime compression on arm excess volume after 3 months of maintenance treatment in patients with secondary upper limb breast cancer-related lymphedema (BCRL). This multicenter, controlled, randomized study was carried out in six centers in France and Turkey. Women with upper limb BCRL who had undergone the intensive phase of decongestive lymphedema therapy (DLT) were randomized into two groups: the Control group wore a daytime compression sleeve without any night compression for 3 months and the MOBIDERM Autofit (MobA) group used a night-time compression sleeve in addition to the daytime compression. The primary outcome was the change in arm excess volume between day 0 (D0) and D90. The main secondary endpoints were: quality of life (QoL), sleep quality, skin thickness and suppleness, satisfaction, compliance, and safety. Fifty-six patients were recruited (mean (± SD) age: 61.4 ± 12.3 years). Between D0 and D90, the mean excess volume decreased by 29.2% in the MobA group and increased by 10.7% in the Control group (p = 0.001). Only 3.6% of patients in the MobA group presented with treatment failure vs. 23.1% in the Control group. At D90, patients in the MobA group had a significantly greater improvement in QoL (p < 0.05), sleep quality (p = 0.018), skin suppleness (p = 0.01) reduced skin thickness (p = 0.025) compared with the Control group. MOBIDERM Autofit used in addition to daytime compression for 3 months during the maintenance phase after DLT was superior to daytime compression alone for the reduction of arm excess volume. Registered on ClinicalTrials.gov (NCT04203069; 17/12/2019).
Covert hepatic encephalopathy (CHE) is associated with cognitive impairment and adverse clinical outcomes; however, randomized evidence supporting therapeutic intervention remains limited. To evaluate the efficacy of rifaximin (RFX) as a treatment for CHE. In this multicentre, open-label randomized controlled trial, patients with CHE associated with liver cirrhosis were randomized (1:1) to receive RFX or no treatment and followed for 12 weeks. The primary endpoint was the change in Stroop test performance. Secondary endpoints included NCT-B scores, serum ammonia levels, cirrhosis-related adverse events, and gut microbiota composition. Fifty patients were randomized and completed follow-up. Stroop test performance improved significantly in the RFX group (p = 0.006) but not in controls (p = 0.400), with a trend toward greater improvement with RFX (Δ Stroop test: -4.45 ± 7.12 vs. -0.98 ± 5.74 s; p = 0.056). Among patients not receiving synthetic disaccharides at baseline, improvement was significantly greater with RFX (Δ Stroop test: -3.73 ± 5.96 vs. -0.80 ± 5.86 s; p = 0.049). No significant changes were observed in NCT-B scores or serum ammonia levels. Cirrhosis-related adverse events were significantly reduced in the RFX group (p = 0.006). Overall, gut microbial diversity did not differ between groups; however, RFX selectively altered specific taxa, including loss of the [Eubacterium] brachy group. RFX improved cognitive performance assessed by the Stroop test and reduced cirrhosis-related adverse events in patients with CHE. These randomized data support RFX as an effective therapeutic option and highlight the Stroop test as a sensitive endpoint for treatment response.
Obesity is a complex health condition marked by an excessive accumulation of adipose tissue. Bariatric surgery continues to be the most efficacious intervention for attaining significant and enduring weight loss. This study aimed to assess a 6-month probiotics supplementation effect on quality of life (QoL), bowel habits, excess weight loss (EWL) and changes in stool composition and fecal Calprotectin in severely obese patients undergoing different types of bariatric surgeries. This prospective randomized controlled trial involved 200 cases underwent standardized bariatric procedures. Cases were randomized into two equal groups: Probiotic group received either Enterogermina® 6 billion sachets or Lacteol forte® sachets, one sachet twice daily for 6 months postoperatively and control group: Patients received standard postoperative care without probiotics. At 1 month postoperatively, the probiotics group showed a significantly higher QOL and EWL% (p < 0.001) compared to controls. At 3 months, the probiotics group had a significantly higher QOL and EWL% (p < 0.001). At 6 months, the probiotics group showed a statistically significant improvements across all measured outcomes, including QOL, BHQ, and EWL% compared to the control group(p < 0.001). Probiotic group had a significantly lower fecal calprotectin compared to control group (p < 0.001). The probiotic use post-bariatric surgery offers measurable benefits in QOL, weight loss, and gastrointestinal inflammation, regardless of the surgical type. Although procedures like RYGB and OAGB yield superior weight loss, they may induce higher gut inflammation. Meanwhile, sleeve gastrectomy appears to be the most gut-friendly in terms of inflammatory markers and bowel consistency.
Stuttering is a neurodevelopmental disorder that typically emerges in childhood and may persist into adulthood. The current study hypothesized that adults with persistent stuttering who received active anodal transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus would demonstrate significantly greater improvements in speech fluency compared to those who received sham stimulation. A randomized, double-blind, sham-controlled clinical trial was conducted to evaluate the efficacy of a combined therapeutic approach. Thirty adults diagnosed with moderate to severe stuttering (6 females, 24 males; M = 30.60 years, SD = 10.15) were randomly assigned to either an anodal tDCS group or a sham stimulation group. Participants in the anodal group received fluency shaping therapy concurrently with anodal transcranial direct current stimulation (2 mA), while those in the sham group underwent the same behavioral therapy alongside sham stimulation. The tDCS was targeted over the left inferior frontal gyrus. Each participant completed ten 20-minute sessions over five consecutive days. Speech fluency outcomes were measured pre- and post-intervention. The anodal tDCS group demonstrated significantly greater reductions in %SS, NAT, and SR compared to the sham group across all post-intervention time points (p < .05). Regarding the OASES, no significant between-group differences were observed at any time point; however, both groups demonstrated significant within-group improvements from baseline to the 3-month follow-up. These findings suggest that tDCS, when combined with behavioral fluency interventions, can enhance speech fluency in adults who stutter. tDCS may therefore serve as a promising adjunctive technique to augment the effectiveness of conventional fluency therapies.
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The present study evaluated clinically and radiographically the effectiveness of Regenerative endodontic procedures (REPs) using platelet-rich fibrin (PRF) versus induced bleeding (IB) in treating mature necrotic teeth. Fifty patients with necrotic mature teeth with periapical lesions were randomly divided into two groups, Group 1, IB (n = 25), and Group 2, PRF (n = 25). Treated teeth were assessed clinically and radiographically at 6 and 12 months. Survival rate, success rate, and clinical outcome measures were analyzed. Survival rate was 98% at the 12-month follow-up period, with no significant difference between the groups (P=0.166). A statistically significant increase in periradicular healing was found in both groups at 6 and 12 months, compared to that at baseline (P< 0.001). A significant difference was found in final treatment success between the two groups (p = 0.0219). The IB group achieved a 100% success rate (23/23), while the PRF group showed a 75% success rate (18/24). The overall success rate was 85.4%. All teeth treated with either IB or PRF survived throughout the follow-up period. The preliminary results of this study showed comparable clinical outcomes between the two treatment modalities, although teeth treated with IB showed higher overall success rate than those treated with PRF this should be interpreted within the framework of early phase clinical evidence as the study was not adequately powered to confirm superiority. REPs may represent a viable treatment option for mature necrotic teeth, offering a biologically based approach that aims to restore tissue function. Longer follow-up as planned in the second phase of this study, will allow for a more definitive comparison between IB and PRF approaches.
Immune checkpoint inhibitors (ICIs) have transformed cancer care, extending survival across multiple malignancies. Yet quality-of-life (QoL) outcomes remain underreported and inconsistently integrated into research and practice. Standard frameworks and instruments do not fully capture immune-related adverse events (irAEs) and may overlook the experiences of racially, socioeconomically, linguistically, and digitally marginalized groups. This review examines how methodological limitations, and systemic inequities constrain the assessment of QoL in immune checkpoint inhibitor (ICI) therapy. It evaluates existing QoL instruments and frameworks guiding patient-reported outcomes (PROs) and identifies opportunities for advancing equity-centered, patient-informed approaches. This narrative review synthesized evidence identified through literature searches and reference screening across oncology, regulatory science, digital health, equity, and community-engaged research. QoL assessment domains analyzed included methodological rigor, trial design, digital integration, intersectionality, literacy, and social determinants of health. Quality-of-life reporting in ICI trials remains limited, with only about 14% of trials publishing PRO results and fewer than 12% including them in the primary publication. Existing tools inadequately capture irAEs, while trial designs neglect long-term survivorship and diverse populations. Frameworks such as SPIRIT-PRO and CONSORT-PRO improve methodological rigor, but provide limited guidance on equity, cultural adaptation, or caregiver perspectives. Barriers, including digital exclusion, linguistic gaps, and underrepresentation of racial and age groups, further bias QoL evidence. Quality of life should be recognized as a core clinical endpoint and an indicator of equity in ICI therapy evaluation. Future research must integrate culturally validated instruments, inclusive digital strategies, and community-engaged approaches to ensure survivorship outcomes reflect the realities of all patients. By moving beyond survival, QoL assessment can anchor cancer care in equity and patient-centered lived experience.
Artificial intelligence (AI) is progressively utilized in cardiology; nonetheless, the overarching advantages across various care domains remain ambiguous. We conducted a search of PubMed, Embase, CINAHL, and trial registries for randomized controlled trials up to January 16, 2026, assessing prospectively applied interventions based on machine/deep-learning algorithms while excluding rule-based systems. Endpoints were categorized according to NICE evidence tiers: workflow efficiency (Tier A), patient engagement/health promotion (Tier B), and clinical outcomes (Tier C). The risk of bias was evaluated using RoB 2.0. In 32 randomized controlled trials (27 of which were meta-analyzed), artificial intelligence improved all levels. Tier A: workflow time reduced (SMD - 0.71; 95% CI - 1.04 to -0.39), corresponding to a diagnostic time that is 30-120 s shorter and a decrease of 1.0-4.2 hospital days in trials reporting length of stay. Tier B: Behavioral nudging enhanced medication adherence (RR 1.59; 95% CI 1.01-2.50; NNT = 12). Tier C: decision-support implementations decreased all-cause mortality (RR 0.84; 95% CI 0.75-0.94; I² = 8%; NNT = 32). Limitations encompassed restricted blinding and insufficient sham-AI controls. Data-driven clinical AI yields quantifiable efficiency improvements, enhances engagement, and reduces adverse outcomes when integrated with actionable decision support, hence informing a structured framework for governance and implementation.
Listeners have difficulty understanding speech in noisy environments, confusing similar sounding words. Cognitive control may be important for segregating the speech signal from background noise and/or selecting between phonological competitors in the mental lexicon. Although cognitive control abilities may be related to speech recognition in noise, the extent to which engaging cognitive control causally improves speech recognition in background noise is unclear. The present study presented pictures that matched (congruent trials) or were phonological neighbors (incongruent trials) of the spoken word to manipulate cognitive control during speech recognition in multitalker babble at + 6 and + 8 dB signal-to-noise ratios (SNRs). As conflict increases cognitive control levels, performance following incongruent trials indexes the effect of cognitive control on recognizing speech in noise. Following conflict, participants became faster and more accurate at repeating back speech at + 6 dB SNR and more accurate at + 8 dB SNR. When comparing across SNRs (including a + 4 dB SNR from a previous study), higher SNRs reduced the interference effect, predicting better recognition on incongruent trials; however, SNR did not significantly modulate postconflict improvements in word recognition. Results suggest engaging cognitive control improves speech recognition in noise across SNR levels where recognition is challenging but possible.
Hydroxychloroquine (HCQ) usage in COVID patients was a popular topic of study, especially during the first wave of the pandemic. However, the long-term impact of HCQ therapy on infected COVID-19 patients remains unclear. Holding a PROSPERO registration (CRD42025113906), this study aimed to investigate the impact of long-term treatment with HCQ in patients with autoimmune diseases on mortality, as well as on the development of disease-related complications. A comprehensive search was conducted across multiple databases. Full-text reports were included for clinical trials and observational studies on adult patients with autoimmune disease and confirmed COVID-19 infection subjected to HCQ therapy. The search process has identified 1,126 studies, of which 17 observational studies were included.No randomized controlled trials meeting the inclusion criteria were found. Eligible studies involved 229,142 autoimmune patients treated with HCQ, of which 197,118 patients were diagnosed with COVID-19. In 14 observational studies (196,965 patients), HCQ use was associated with a lower overall mortality rate by 21% in patients with autoimmune diseases and COVID-19 (RR 0.79; 95% CI: 0.64-0.97, p = 0.02). This association may reflect a potential survival benefit; however, given the observational nature of the studies included, causal inference cannot be established, and the findings should be interpreted cautiously. There was no significant difference between HCQ-treated patients and untreated patients regarding hospitalization (12 studies with 2,238 patients included), ICU admission (8 studies with 527 patients included), mechanical ventilation (8 studies with 546 patients included), sepsis (2 studies with 132 patients included), or thrombo-embolic events rates (2 studies with 195 patients included) (RR 0.92, 95% CI 0.75- 1.14; p = 0.46), (RR 1.45; 95% CI; 0.82- 2.56, p = 0.2) and (RR 1.28; 95% CI; 0.68- 2.4, p = 0.44), (RR 1.44; 95% CI; 0.57 - 3.65, p = 0.44), (RR 0.89; 95% CI; 0.16-4.97, p = 0.89), respectively. Nonetheless, the incidence of Acute Kidney Injury (AKI) in 2 studies (136 patients) was higher in HCQ-treated groups compared to the untreated groups (RR 2.31; 95% CI; 1.29-4.12, p = 0.0047). HCQ was associated with a significantly lower overall mortality rate in patients with autoimmune diseases and COVID-19; this association is consistent with its known immunomodulatory properties. On the other hand, it does not prevent COVID-19-related complications and could be associated with an increased risk for developing AKI. However, given the observational nature of all included studies, causal inference cannot be established. Future research is needed to confirm these observed survival benefits and to establish clear safety parameters regarding renal toxicity.
The FTO rs9939609 SNP has been linked to higher BMI, insulin resistance, and breast cancer risk. Weight loss by bariatric surgery lowers breast cancer risk, particularly in women with baseline hyperinsulinemia, but it is unclear whether this effect varies by FTO genotype. In the Swedish Obese Subjects (SOS) study, 2596 women with severe obesity were followed for a median of 23.9 years to examine breast cancer incidence after bariatric surgery compared with usual care. Genotyping for rs9939609 was performed, and breast cancer events were identified via the Swedish National Cancer Registry. Among 135 breast cancer cases (77 in the control group and 58 in the surgery group), surgery was associated with a lower breast cancer incidence in carriers of the risk allele (TA/AA) (adjusted HR = 0.53 [0.34-0.83], P = 0.005), but not in non-carriers (TT) (adjusted HR = 1.19 [0.65-2.15], P = 0.573; P for treatment-genotype interaction = 0.031). These findings suggest that the FTO rs9939609 genotype may modify the association between bariatric surgery and breast cancer incidence. Trial registration: ClinicalTrials.gov, identifier: NCT01479452.
The optimal strategy for combining radiotherapy (RT) and immunotherapy remains under intensive investigation. Here we developed TRIDENT (Triple Radio-Immunotherapy-Driven ENhanced Therapy), a novel triple-modality regimen combining immunomodulatory low-dose RT (LDRT) to large tumor(s), immunogenic high-dose RT (HDRT) to small tumor(s), and PD-1 blockade. In our phase I trial of 29 patients with treatment-naïve, PD-L1-positive advanced non-small cell lung cancer (NSCLC), TRIDENT achieved a median overall survival (mOS) of 51.3 months (95% CI, 20.7-not reached), higher than outcomes typically reported with contemporary standard (chemo)immunotherapy. This durable survival signal was corroborated in an independent real-world cohort of 97 patients with advanced lung cancer (mOS: 41.5 months; 95% CI, 26.3-63.7). Mechanistically, TRIDENT elicited neutrophil-dependent, systemic antitumor immunity and induced a distinct population of antitumor TNF-α⁺ neutrophils marked by increased MHC and costimulatory molecule expression. Neutrophil recruitment was driven by the CXCL-CXCR2 axis, and polarization toward an antitumor state was programmed by treatment-induced IFN-γ and GM-CSF. TNF-α⁺ neutrophils enhanced CD8⁺ T-cell function via ICAM-1-LFA-1 interactions, and adoptive transfer confirmed their intrinsic antitumor activity in vivo. Spatial transcriptomics of patient tumor tissues further identified a TNF-α+ neutrophil-effector CD8+ T-cell niche after TRIDENT, providing a stimulatory signal to effector CD8⁺ T cells. In line with these mechanistic findings, clinical biomarker analyses linked neutrophil number with prolonged survival. TRIDENT activates an RT-driven neutrophil-CD8⁺ T-cell axis and promotes survival-associated neutrophil activation. These mechanistic insights, coupled with durable survival in our phase I trial, position TRIDENT as a promising strategy for metastatic NSCLC currently undergoing randomized phase II evaluation. Our study also highlights TNF-α+ neutrophils as a promising therapeutic strategy to enhance antitumor efficacy.