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Search Results (609)

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Keywords = stage III (N2)

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17 pages, 1908 KB  
Article
Manual Dexterity Rehabilitation in Parkinson’s Disease and Paranoid Schizophrenia: A Controlled Study
by Tatiana Balint, Alina-Mihaela Cristuta, Adina Camelia Slicaru, Ilie Onu, Daniel Andrei Iordan and Ana Onu
Life 2026, 16(2), 196; https://doi.org/10.3390/life16020196 - 24 Jan 2026
Viewed by 196
Abstract
Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine [...] Read more.
Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine physiotherapy (PT). Objective: This study investigated the effects of a structured, progressive PT program incorporating targeted MD training on upper limb function in patients with PD and PS. Methods: A prospective, exploratory, interventional study was conducted in 30 patients, allocated to either an experimental group (EG, n = 20) or a control group (CG, n = 10). Participants had PD (Hoehn and Yahr stages II–III) or chronic, clinically stable PS. MD was assessed using the Purdue Pegboard Test, Coin Rotation Task, and Kapandji opposition score. The EG completed a four-phase, 40-week dexterity-oriented rehabilitation program, while the CG received standard disease-specific PT. Between-group differences in change scores were analyzed using one-way ANOVA. Results: The EG showed significantly greater improvements than the CG in thumb opposition, psychomotor processing speed, and unilateral and bilateral fine motor performance (p < 0.001 for all), with large to very large effect sizes (η2 = 0.45–0.76). No significant between-group differences were observed for complex sequential assembly tasks. Conclusions: Integrating targeted MD training into structured PT programs significantly improves fine motor performance in patients with PD and PS, supporting its inclusion in rehabilitation protocols for residential and outpatient care settings. Full article
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18 pages, 1272 KB  
Article
Lymphadenectomy and Postoperative Complications in Stage III Melanoma: A Single-Center Analysis
by Francesca Tauceri, Fabrizio D’Acapito, Valentina Zucchini, Daniela Di Pietrantonio, Massimo Framarini and Giorgio Ercolani
Surgeries 2026, 7(1), 16; https://doi.org/10.3390/surgeries7010016 - 23 Jan 2026
Viewed by 139
Abstract
Background/Objectives: Over the last decade, the role and timing of lymph node dissection (LND) in stage III melanoma has shifted from completion LND after a positive sentinel node to a mainly therapeutic procedure for clinically evident nodal disease, driven by randomized evidence showing [...] Read more.
Background/Objectives: Over the last decade, the role and timing of lymph node dissection (LND) in stage III melanoma has shifted from completion LND after a positive sentinel node to a mainly therapeutic procedure for clinically evident nodal disease, driven by randomized evidence showing no survival benefit for routine completion dissection. In this evolving landscape, real-world data on postoperative morbidity—by nodal basin—and on whether complications may influence melanoma-specific survival (MSS) and disease-free survival (DFS) remain limited. We evaluated 90-day postoperative complications after cervical, axillary, and inguino–iliac–obturator LND and explored their association with survival outcomes and treatment era. Methods: We retrospectively analyzed 185 consecutive stage III melanoma patients undergoing LND at a single tertiary center (January 2004–August 2025). Postoperative morbidity was recorded up to 90 days and graded by Clavien–Dindo; given the very low rate of grade > II events, the primary endpoint was a composite of loco-regional surgical field–related complications (persistent seroma, wound dehiscence, surgical-site infection, limb lymphedema). Risk factors were assessed using logistic regression; Firth’s penalized models were applied when appropriate. MSS and DFS were estimated by Kaplan–Meier and explored with Cox models. Results: Median follow-up was 105 months. Surgical field–related complications occurred in 16.8% (31/185), and postoperative mortality was 1.0% (2/185). In multivariable analyses, inguino–iliac–obturator LND was associated with higher odds of overall complications (OR 4.03) and specifically wound dehiscence (OR 4.79) and infection (OR 7.18) versus axillary LND. MSS (n = 179) was 82% at 1 year, 55% at 5 years, and 49% at 10 years; DFS (n = 171) was 63%, 42%, and 41%, respectively. In era-based comparisons, nodal yield decreased in the post–MSLT-II period without clear separation of MSS/DFS curves; exploratory models did not show a consistent independent signal linking postoperative complications to MSS/DFS. Conclusions: In stage III melanoma, LND was associated with low major morbidity, but clinically meaningful locoregional complications persisted—most notably after inguino–iliac–obturator dissection. These data support careful patient selection and basin-tailored strategies to reduce groin morbidity within modern multidisciplinary management. Full article
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12 pages, 671 KB  
Article
How Do Gait Outcomes Evolve in Adults with Spastic Cerebral Palsy Who Received Orthopedic Treatment in Childhood?
by Anne Tabard-Fougère, Alice Bonnefoy-Mazure, Geraldo de Coulon, Oscar Vazquez and Stéphane Armand
Children 2026, 13(1), 158; https://doi.org/10.3390/children13010158 - 22 Jan 2026
Viewed by 25
Abstract
Background/Objectives: Cerebral palsy (CP) is the most common cause of physical disability in childhood. While gait improvements are often observed during childhood, it remains unclear whether these gains are sustained into adulthood. This study aimed to evaluate the long-term evolution of gait [...] Read more.
Background/Objectives: Cerebral palsy (CP) is the most common cause of physical disability in childhood. While gait improvements are often observed during childhood, it remains unclear whether these gains are sustained into adulthood. This study aimed to evaluate the long-term evolution of gait outcomes from childhood to adulthood in individuals with CP who received orthopedic care early in life. Methods: This retrospective study included 83 adults with cerebral palsy (44 unilateral/uCP, 39 bilateral/bCP; GMFCS I–III) who underwent clinical gait analysis in childhood and again as adults (minimum 4 years between visits, n = 249 CGA). Gait was assessed using the modified Gait Profile Score (mGPS) and normalized walking speed (NWS). The effects of life stage (childhood, adolescence, early adulthood, and adulthood) were analyzed using Kruskal–Wallis tests with post hoc comparisons. Individual clinical transitions were quantified from early adulthood to adulthood, with a minimal clinically important difference (MCID) change in mGPS (1.6°) and NWS (0.20 s−1) for improvement or decline. Results: Longitudinal analysis revealed that while group-average mGPS improved from childhood to adulthood, NWS declined significantly for all patients (p < 0.01). However, individual trajectories from early adulthood to adulthood diverged by CP type. Those with bCP GMFCS II and III had a more frequent clinical decline in mGPS (4/14, 29%), with minimal potential for improvement (1/14, 17%). In contrast, individuals with uCP had less frequent decline (1/17, 6%) and a greater improvement (3/17, 18%). Conclusions: While significant improvements in gait quality are achieved by early adulthood, substantial clinical decline occurs during adulthood in bCP (GMFCS II–III) patients. These findings highlight the need for lifelong monitoring, with re-evaluation regarding the need for surgical interventions from early adulthood to adulthood in bCP patients with greater motor impairments. Full article
(This article belongs to the Collection Advancements in the Management of Children with Cerebral Palsy)
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39 pages, 13928 KB  
Article
Genesis of the Hadamengou Gold Deposit, Northern North China Craton: Constraints from Ore Geology, Fluid Inclusion, and Isotope Geochemistry
by Liang Wang, Liqiong Jia, Genhou Wang, Liangsheng Ge, Jiankun Kang and Bin Wang
Minerals 2026, 16(1), 99; https://doi.org/10.3390/min16010099 - 20 Jan 2026
Viewed by 302
Abstract
The Hadamengou gold deposit, hosted in the Precambrian metamorphic basement, is a super-large gold deposit occurring along the northern margin of the North China Craton. Despite extensive investigation, the genesis of the gold mineralization is poorly understood and remains highly debated. This study [...] Read more.
The Hadamengou gold deposit, hosted in the Precambrian metamorphic basement, is a super-large gold deposit occurring along the northern margin of the North China Craton. Despite extensive investigation, the genesis of the gold mineralization is poorly understood and remains highly debated. This study integrates a comprehensive dataset, including fluid inclusion microthermometry and C-H-O-S-Pb isotopes, to better constrain the genesis and ore-forming mechanism of the deposit. Hydrothermal mineralization can be divided into pyrite–potassium feldspar–quartz (Stage I), quartz–gold–pyrite–molybdenite (Stage II), quartz–gold–polymetallic sulfide (Stage III), and quartz–carbonate stages (Stage IV). Four types of primary fluid inclusions are identified, including pure CO2-type, composite CO2-H2O-type, aqueous-type, and solid-daughter mineral-bearing-type inclusions. Microthermometric and compositional data reveal that the fluids were mesothermal to hypothermal, H2O-dominated, and CO2-rich fluids containing significant N2 and low-to-moderate salinity, indicative of a magmatic–hydrothermal origin. Fluid inclusion assemblages further imply that the ore-forming fluids underwent fluid immiscibility, causing CO2 effusion and significant changes in physicochemical conditions that destabilized gold bisulfide complexes. The hydrogen–oxygen isotopic compositions, moreover, support a dominant magmatic water source, with increasing meteoric water input during later stages. The carbon–oxygen isotopes are also consistent with a magmatic carbon source. Sulfur and lead isotopes collectively imply that ore-forming materials were derived from a hybrid crust–mantle magmatic reservoir, with minor contribution from the country rocks. By synthesizing temporal–spatial relationships between magmatic activity and ore formation, and the regional tectonic evolution, we suggest that the Hadamengou is an intrusion-related magmatic–hydrothermal lode gold deposit. It is genetically associated with multi-stage magmatism induced by crust–mantle interaction, which developed within the extensional tectonic regimes. Full article
(This article belongs to the Section Mineral Deposits)
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12 pages, 448 KB  
Article
Clinicopathological Predictors of Axillary Pathological Complete Response and Its Prognostic Significance in Clinically Node-Positive (cN+), HER2-Positive Breast Cancer Following Neoadjuvant Therapy
by Şahin Bedir, Uğur Alp Yeşilova, Merve Tokoçin, Burçin Çakan Demirel, Yakup Bozkaya, Abdilkerim Oyman, Murad Guliyev, Hamza Abbasov, Nebi Serkan Demirci, Ezgi Değerli, Gamze Usul, Ebru Şen, Nilüfer Bulut and Gökmen Umut Erdem
Medicina 2026, 62(1), 200; https://doi.org/10.3390/medicina62010200 - 18 Jan 2026
Viewed by 138
Abstract
Background and Objectives: This study aimed to identify clinicopathological factors associated with axillary pathological complete response (ApCR) in patients with HER2-positive breast cancer presenting with clinically node-positive disease (cN+) confirmed by biopsy who received neoadjuvant therapy (NAT), and to assess the prognostic [...] Read more.
Background and Objectives: This study aimed to identify clinicopathological factors associated with axillary pathological complete response (ApCR) in patients with HER2-positive breast cancer presenting with clinically node-positive disease (cN+) confirmed by biopsy who received neoadjuvant therapy (NAT), and to assess the prognostic significance of ApCR on survival outcomes. Materials and Methods: A total of 221 patients with clinically node-positive (cN+) HER2-positive invasive breast cancer, with nodal involvement confirmed by fine-needle aspiration or core needle biopsy, who received neoadjuvant therapy (NAT) and subsequently underwent surgery at three centers between January 2015 and January 2025 were retrospectively reviewed. The association between clinicopathological factors and axillary pathological complete response (ApCR) was analyzed using logistic regression. Survival analyses were performed using the Kaplan–Meier method. Results: The median follow-up duration was 34.3 months. Axillary pathological complete response (ApCR) was achieved in 67.9% of patients. The ApCR rate was higher in stage II disease compared with stage III (76.9% vs. 62.9%). Patients with HER2 3+ tumors demonstrated a higher ApCR rate (70.8%) than those with HER2 2+/FISH+ tumors (46.2%). In multivariable logistic regression, HER2 3+ status (OR = 2.745; 95% CI: 1.138–6.619; p = 0.025) and lower clinical stage (OR = 2.251; 95% CI: 1.182–4.287; p = 0.014) were independently associated with a higher likelihood of achieving ApCR. In survival analyses, the 3-year event-free survival rate was 92% (95% CI: 86–98%) in the ApCR group, compared with 75% (95% CI: 63–87%) in the non-ApCR group. Kaplan–Meier analysis demonstrated that ApCR was a significant prognostic factor for EFS (p = 0.001). Median overall survival (OS) was not reached in either group due to the limited number of death events. Conclusions: ApCR was frequent in node-positive HER2-positive breast cancer after neoadjuvant therapy. HER2 3+ status and lower clinical stage independently predicted ApCR, which in turn was associated with improved event-free survival. These findings underscore the prognostic relevance of ApCR in this setting. Full article
(This article belongs to the Collection Frontiers in Breast Cancer Diagnosis and Treatment)
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12 pages, 859 KB  
Article
Salivary Cortisone as a Potential Alternative to Cortisol in Periodontitis Severity Assessment
by Dimitar Dimitrov, Antoaneta Mlachkova and Velitchka Dosseva-Panova
Int. J. Mol. Sci. 2026, 27(2), 805; https://doi.org/10.3390/ijms27020805 - 13 Jan 2026
Viewed by 117
Abstract
Salivary cortisol is widely used to investigate stress–periodontitis interactions, but its measurement is affected by methodological limitations. Cortisone, the predominant salivary glucocorticoid, may offer analytical advantages, yet its role in periodontitis remains unexplored. This study evaluated salivary cortisone in relation to periodontal disease [...] Read more.
Salivary cortisol is widely used to investigate stress–periodontitis interactions, but its measurement is affected by methodological limitations. Cortisone, the predominant salivary glucocorticoid, may offer analytical advantages, yet its role in periodontitis remains unexplored. This study evaluated salivary cortisone in relation to periodontal disease severity and compared its performance with cortisol. Sixty-seven periodontitis patients were classified as Stage I/II (n = 32) or Stage III/IV (n = 35). A comprehensive periodontal examination was performed, including FMPS, FMBS, PPD, CAL, BoP, and the BL/Age ratio. Unstimulated morning saliva samples were analyzed for cortisone and cortisol using liquid chromatography–tandem mass spectrometry, and for IL-1β and IL-6 using ELISA. Both cortisone and cortisol levels were significantly higher in Stage III/IV periodontitis (p = 0.014). Cortisone correlated strongly with cortisol (ρ = 0.523, p < 0.001) and was positively associated with IL-6 (ρ = 0.322, p = 0.008) and multiple clinical indicators of periodontal disease severity. ROC analysis showed comparable discriminatory performance for cortisone and cortisol (AUC = 0.675), with cortisone demonstrating higher specificity (94%) for Stage III/IV periodontitis. Our findings suggest that salivary cortisone performs similarly to cortisol and warrants further investigation as an alternative salivary glucocorticoid marker in periodontal research. Full article
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13 pages, 369 KB  
Article
One-Stage Versus Two-Stage ACL Reconstruction with Concomitant MCL Surgery in Combined ACL and MCL Injuries: A Minimum 2-Year Follow-Up Study
by Kwangho Chung, Hyun-Soo Moon, Sung-Hwan Kim, Seung Ho Yoon and Min Jung
J. Clin. Med. 2026, 15(2), 583; https://doi.org/10.3390/jcm15020583 - 11 Jan 2026
Viewed by 208
Abstract
Background: The optimal timing and staging of anterior cruciate ligament reconstruction (ACLR) in patients with concomitant medial collateral ligament (MCL) injury remain controversial. This study aimed to compare clinical outcomes between a one-stage ACLR group and a two-stage ACLR group in patients with [...] Read more.
Background: The optimal timing and staging of anterior cruciate ligament reconstruction (ACLR) in patients with concomitant medial collateral ligament (MCL) injury remain controversial. This study aimed to compare clinical outcomes between a one-stage ACLR group and a two-stage ACLR group in patients with combined ACL and MCL injuries in which the MCL was surgically managed. Methods: This retrospective study included 68 patients with combined ACL and grade III MCL injuries treated with ACLR and MCL surgery. Patients were divided into the one-stage ACLR group (n = 42) and the two-stage ACLR group (n = 26) according to the timing and staging of ACLR relative to MCL surgery. Clinical outcomes, including knee stability, patient-reported outcomes, and range of motion (ROM), were compared between groups. Results: After a minimum 2-year follow-up, both groups demonstrated significant improvements in clinical and stability outcomes, with enhanced anterior knee stability, improved patient-reported outcomes, and better objectively assessed knee function. No significant differences were found between groups in anterior, valgus (one-stage: 1.8 ± 1.1 mm, two-stage: 2.3 ± 1.3 mm; p = 0.160), or rotational stability. Likewise, there were no significant differences in mean flexion deficits (one-stage: 2.6 ± 4.1°, two-stage: 1.0 ± 2.0°; p = 0.137), mean extension deficits (one-stage: 1.5 ± 2.5°, two-stage: 1.3 ± 2.0°; p = 0.137), flexion deficits ≥10° (one-stage: 9.5% [4/42], two-stage: 0%; p = 0.290), extension deficits ≥ 5° (one-stage: 9.5% [4/42], two-stage: 3.8% [1/26]; p = 0.642), or additional procedures for postoperative stiffness (one-stage: 16.7% [7/42], two-stage: 11.5% [3/26]; p = 0.730). Patient-reported outcomes, including the Lysholm and IKDC subjective scores, were also comparable between groups. Conclusions: Both the one-stage ACLR group and the two-stage ACLR group for surgically managed combined ACL and MCL injuries yielded comparable clinical and stability outcomes, suggesting that one-stage ACLR can be performed without an apparent increase in the risk of postoperative stiffness or ROM limitations. However, given the limited sample size, these results should be interpreted cautiously because the study may have been insufficiently powered to detect small clinically meaningful differences. Full article
(This article belongs to the Special Issue Clinical Perspectives on Surgical Management of Knee Injuries)
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11 pages, 1713 KB  
Review
Feasibility of Laparoscopic Radical Colpectomy in Locally Advanced Vaginal Cancer: A Case Report and Literature Review
by Davut Dayan, Hannes Endres, Stefan Lukac, Wolfgang Janni, Florian Ebner, Mandana Shirin Khodawandi and Jasmina Veta Darkovski
J. Clin. Med. 2026, 15(1), 385; https://doi.org/10.3390/jcm15010385 - 5 Jan 2026
Viewed by 346
Abstract
Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation [...] Read more.
Objectives: Due to the rarity of primary vaginal carcinoma, standardized treatment approaches are limited. Radical surgery is rare, especially in advanced stages. This report evaluates the feasibility, technical aspects and outcomes of laparoscopic en bloc resection in advanced vaginal carcinoma. Case presentation: A 67-year-old woman presented with pain and vaginal bleeding. Clinical examination revealed a stenosing vaginal tumour up to 2 cm above the introitus, extending to the urethra and right vulva. Biopsies confirmed invasive squamous cell carcinoma with VAIN/VIN III. Imaging revealed enlarged pelvic lymph nodes, but no distant metastases. Methods: The surgical procedure comprised laparoscopic en bloc resection, including bilateral pelvic lymphadenectomy, radical hysterectomy with bilateral salpingo-oophorectomy, and total vaginal excision down to the pelvic floor. Additionally, inguinal bilateral ICG-guided sentinel lymph node dissection, vulvectomy with clitoral preservation, and partial urethral resection were performed, followed by transvaginal specimen removal. Vaginal closure was achieved via combined transvaginal and laparoscopic pelvic floor reconstruction. The postoperative course was uneventful, with early recovery of urinary and bowel function. Final histology confirmed complete tumor resection with clear margins (pT3, pN0, L0, V0, Pn0, R0). Functional outcomes remained excellent, with no recurrence or functional impairment at one-year follow-up. Conclusions: Laparoscopic en bloc resection appears to be a feasible option for selected patients with locally advanced vaginal carcinoma, enabling complete tumour removal with preservation of pelvic floor function and resulting in favourable postoperative and oncological outcomes. Full article
(This article belongs to the Section Oncology)
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11 pages, 483 KB  
Article
Failure to Achieve 70% of Recommended Protein Intake at One Year Predicts 13-Fold Higher Mortality After Gastrectomy
by Jou-Huai Lin, Shao-Ciao Luo, Li-Chun Liu, Ya-Ling Wang, Chiann-Yi Hsu and Pin-Kuei Fu
Nutrients 2026, 18(1), 120; https://doi.org/10.3390/nu18010120 - 30 Dec 2025
Viewed by 400
Abstract
Background and Aims: Gastric cancer remains a major health burden in East Asia. Gastrectomy is a primary treatment, yet postoperative malnutrition—particularly inadequate protein intake—adversely affects outcomes. This study assessed the association between achieving ≥70% of the recommended protein intake one year after gastrectomy [...] Read more.
Background and Aims: Gastric cancer remains a major health burden in East Asia. Gastrectomy is a primary treatment, yet postoperative malnutrition—particularly inadequate protein intake—adversely affects outcomes. This study assessed the association between achieving ≥70% of the recommended protein intake one year after gastrectomy and three-year survival. Methods: In this prospective, single-center, observational study, 69 patients with newly diagnosed gastric cancer who underwent gastrectomy between January 2021 and August 2023 were enrolled. Four patients who died within one year postoperatively were excluded, leaving 65 patients for analysis. Protein intake achievement rate (PIAR) at 12 months was calculated based on a recommended intake of 1.2 g/kg/day, and patients were stratified as PIAR ≥ 70% or <70%. Overall survival was analyzed using time-to-event methods, with a median follow-up of 2.1 years. Results: Among the 65 patients (median age 62 years, IQR 56–68; 56.9% male), 75.4% underwent subtotal gastrectomy. At 12 months, 7 patients (10.8%) failed to achieve a PIAR ≥ 70%. Compared with patients achieving adequate protein intake, those with inadequate intake more frequently underwent total gastrectomy (71.4% vs. 19.0%, p = 0.008) and had advanced-stage disease (Stage III–IV: 85.7% vs. 39.7%, p = 0.039). Kaplan–Meier analysis demonstrated significantly lower survival in the inadequate protein group, with a hazard ratio of 13.02 (95% CI 2.53–66.93); the wide confidence interval reflects the small number of patients with inadequate intake (n = 7). Conclusions: Failure to achieve ≥70% of recommended protein intake one year after gastrectomy is a strong independent predictor of mortality, associated with a 13-fold higher risk of death. Nutritional monitoring and early intervention are crucial, particularly for patients with total gastrectomy or advanced disease. Full article
(This article belongs to the Special Issue Diet and Nutrition for Cancer Survivors)
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19 pages, 1452 KB  
Article
Neoadjuvant Therapy in Resectable Advanced Melanoma: Swiss Real-World Data
by Ann-Kathrin Blumenröther, Yongxing Fang, Tamara El Saadany, Egle Ramelyte, Omar Hasan Ali, Thomas Kündig, Daniela Mihic-Probst, Sarah Steiner, Alexander Maurer, Reinhard Dummer, Joanna Mangana and Lara V. Maul
Cancers 2026, 18(1), 98; https://doi.org/10.3390/cancers18010098 - 28 Dec 2025
Viewed by 461
Abstract
Background/Objectives: Neoadjuvant and perioperative treatment regimens for melanoma have demonstrated significantly longer event-free survival (EFS) compared with adjuvant therapy in the NADINA and SWOG S1801 trials. While these studies yielded promising results, real-world effectiveness and safety remain to be clarified. Methods: [...] Read more.
Background/Objectives: Neoadjuvant and perioperative treatment regimens for melanoma have demonstrated significantly longer event-free survival (EFS) compared with adjuvant therapy in the NADINA and SWOG S1801 trials. While these studies yielded promising results, real-world effectiveness and safety remain to be clarified. Methods: We performed a retrospective, real-world study of all patients with advanced, resectable cutaneous or mucosal melanoma stage III/IV who received neoadjuvant treatment at the Department of Dermatology, University Hospital Zurich, Switzerland between April 2023 and September 2025. Primary endpoints were pathologic and radiologic response, EFS, recurrence-free survival (RFS), and safety. Results: In total, 31 patients were analyzed (52% female; median age 65 years), including 5 patients without lymph node involvement. Eighteen patients (58%) with cutaneous melanoma received neoadjuvant immunotherapy according to the NADINA protocol, three patients (10%) with mucosal melanoma received ipilimumab (1 mg/kg) and nivolumab (3 mg/kg), and ten patients (32%) were treated according to the SWOG S1801 protocol. A major pathologic response (MPR) was achieved in 12 of 31 patients (38%) overall, including 5 of 18 (28%) in the NADINA cohort, 6 of 10 (60%) in the SWOG S1801 cohort, and 1 of 3 (33%) in the mucosal cohort. We observed a pathologic partial response (pPR) in 7 of 31 patients (23%) overall, including 6 of 18 (33%) in the NADINA cohort and 1 of 3 (33%) in the mucosal cohort. A pathologic non-response (pNR) was seen in 9 of 31 patients (29%) overall, including 5 of 18 (28%) in the NADINA cohort, 3 of 10 (30%) in the SWOG S1801 cohort, and 1 of 3 (33%) in the mucosal cohort. Among all patients without lymph node involvement, 1 of 5 achieved MPR (20%), 2 had pPR (40%), and 2 showed pNR (40%). At data cutoff (median follow-up, 9.2 months), the 9-month EFS was 77% in the NADINA cohort, 74% in the SWOG S1801 cohort, and 33% in the mucosal cohort. In the whole cohort, 6-month RFS for the subgroups of MPR, pPR and pNR was 72.9%, 85.7% and 72.9%. Radiologic response evaluation with FDG-PET/CT after neoadjuvant therapy correlated significantly with pathologic response (p = 0.02). No patient with complete metabolic response (CMR) or partial metabolic response (PMR) recurred until data cutoff. In total, 6 of 31 patients (19%) showed stable metabolic disease (SMD), and 8 of 31 patients (26%) showed progressive metabolic disease (PMD). The 6-month RFS in the subgroups of SMD and PMD was 62.5% in each case. Adverse events (AEs) of grade 3 or higher were reported in 13 of 31 patients (42%) in the total real-world cohort, 8 of 18 in the NADINA cohort (44%), 2 of 10 (20%) in the SWOG S1801 cohort (20%), and 3 of 3 (100%) in the mucosal cohort. The most frequent grade 3/4 toxicities were immune-related (ir) Colitis (n = 3, 10%), irHepatitis (n = 2, 6%) and irMyocarditis (n = 2, 6%). Conclusions: Neoadjuvant immunotherapy is effective in real-world practice with a similar safety profile as shown in the clinical studies. Nevertheless, MPR rates in the NADINA real-world cohort were lower compared to the phase III trial. Larger multicenter studies are needed to validate our findings and to better understand response patterns, even in patients without lymph node involvement and in rare melanoma subtypes. Full article
(This article belongs to the Special Issue Immunotherapy for Skin Cancers)
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19 pages, 1390 KB  
Article
Heterotrophic Soil Microbes at Work: Short-Term Responses to Differentiated Fertilization Inputs
by Florin Aonofriesei, Alina Giorgiana Brotea (Andriescu) and Enuță Simion
Biology 2026, 15(1), 41; https://doi.org/10.3390/biology15010041 - 26 Dec 2025
Viewed by 346
Abstract
The interaction between organic and inorganic nutrients, bacterial communities, and soil fertility has been well documented over time. Conventional agricultural systems heavily utilize both inorganic and organic fertilizers, each exerting distinct effects on soil microbial dynamics and plant growth. The objective of our [...] Read more.
The interaction between organic and inorganic nutrients, bacterial communities, and soil fertility has been well documented over time. Conventional agricultural systems heavily utilize both inorganic and organic fertilizers, each exerting distinct effects on soil microbial dynamics and plant growth. The objective of our experiments was to identify the most effective fertilization strategy for improving the biological quality of a microbiologically impoverished and low-productivity soil. To this end, four fertilization strategies were evaluated: (i) organic fertilizers characterized by a high content of organic carbon (Fertil 4-5-7—variant 1); (ii) organic fertilizers with 12% organic nitrogen from proteins (Bio Ostara N—variant 2) (iii) combined inorganic–organic fertilizers (P35 Bio—variant 3) and (iv) mineral (inorganic) fertilizers (BioAktiv—variant V4). This study aimed to assess the short-term effects of fertilizers with varying chemical compositions on the density of cultivable heterotrophic bacteria and their associated dehydrogenase (DH) activity in a petrocalcic chernozem soil containing pedogenic carbonates. Soil sampling was conducted according to a randomized block design, comprising four replicates per treatment (control plus four fertilizer types). The enumeration of cultivable bacteria was performed using Nutrient Agar and A2R Agar media, whereas dehydrogenase activity (DHA) was quantified based on the reduction of 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) to 1,3,5-triphenyl-tetrazolium formazan (TPF) by bacterial dehydrogenase enzymes. Marked differences were observed in both parameters between the plots amended with inorganic fertilizers and those treated with organic fertilizers, as well as among the organic fertilizer treatments of varying composition. The most pronounced increases in both bacterial density and dehydrogenase activity (DHA) were recorded in the plots receiving the fertilizer with a high organic nitrogen content. In this treatment, the maximum bacterial population density reached 6.25 log10 CFU g−1 dry soil after approximately two months (May), followed by a significant decline starting in July. In contrast, DHA exhibited a more rapid response, reaching its peak in April (42.75 µg TPF g−1 soil), indicating an earlier DHA activation of microbial metabolism. This temporal lag between the two parameters suggests that enzymatic activity responded more swiftly to the nutrient inputs than did microbial biomass proliferation. For the other two organic fertilizer variants, bacterial population dynamics were broadly similar, with peak densities recorded in June, ranging from 5.98 log10 CFU g−1 soil (V3) to 6.03 log10 CFU g−1 soil (V1). A comparable trend was observed in DHA: in V3, maximum DHA was attained in June (30 µg TPF g−1 soil), after which it remained relatively stable, whereas in V1, it peaked in June (24.05 µg TPF g−1 soil) and subsequently declined slightly toward the end of the experimental period. Overall, the temporal dynamics of bacterial density and DHA demonstrated a strong dependence on the quality and biodegradability of the organic matter supplied by each fertilizer. Both parameters were consistently lower under inorganic fertilization compared with organic treatments, suggesting that the observed increases in microbial density and activity were primarily mediated by the enhanced availability of organic substrates. The relationship between the density of culturable heterotrophic bacteria and dehydrogenase (DH) activity was strongly positive (r = 0.79), indicating a close functional linkage between bacterial density and oxidative enzyme activity. This connection suggests that the culturable fraction of the heterotrophic microbial community plays a key role in the early stages of organic matter mineralization derived from the applied fertilizers, particularly in the decomposition of easily degradable substrates. Full article
(This article belongs to the Special Issue The Application of Microorganisms and Plants in Soil Improvement)
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14 pages, 1746 KB  
Article
Does Retroperitoneal vNOTES Sentinel Lymph Node Mapping Represent a Feasible Staging Option in Presumed Early-Stage Endometrial Cancer?
by Behzat Can, Kevser Arkan, Ali Deniz Erkmen and Sedat Akgol
Medicina 2026, 62(1), 43; https://doi.org/10.3390/medicina62010043 - 25 Dec 2025
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Abstract
Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates [...] Read more.
Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates the SLN detection rates, perioperative outcomes, and 12-month oncologic outcomes oncologic results of retroperitoneal vNOTES mapping in presumed early-stage EC. Materials and Methods: This single-center retrospective cohort study analyzed consecutive patients undergoing retroperitoneal vNOTES staging (hysterectomy, BSO, and SLN mapping) for presumed EC between February 2023 and January 2024. Eligible patients had radiologically uterine-confined disease and were candidates for transvaginal surgery. Following cervical methylene blue injection, SLN mapping was executed via the retroperitoneal vNOTES route. Mapped and suspicious nodes were excised, with side-specific lymphadenectomy performed for failed mapping per algorithm. While perioperative outcomes were assessed for the full cohort, oncologic analyses (FIGO 2023 staging, nodal metastasis) were restricted to patients with confirmed carcinoma. Results: Of 98 patients (median age 54; BMI 31 kg/m2), final pathology confirmed carcinoma in 78 (73 endometrioid, 5 serous) and EIN in 20. Bilateral SLN mapping succeeded in 87.8% (86/98), necessitating side-specific lymphadenectomy in the remaining 12.2%. The obturator fossa was the predominant nodal basin (43.9%). Within the carcinoma cohort (n = 78), 57.7% were Grade 1 and 74.4% FIGO Stage I. Nodal metastases (FIGO IIIC1) were identified in 12.8% (10/78), all prompting adjuvant therapy. At a median follow-up of 12 months, no disease recurrences were observed. The complication rate was 6.1% (5.1% Clavien–Dindo ≥ III), with no conversions required. At 12-month follow-up, no recurrences were detected, though the absence of systematic lymphadenectomy precluded formal sensitivity analysis. Conclusions: Retroperitoneal vNOTES represents a feasible and safe strategy for SLN mapping in early-stage EC, demonstrating high bilateral detection with minimal morbidity. However, reliance on methylene blue and limited follow-up necessitate caution. Broader implementation requires validation through prospective, comparative trials utilizing indocyanine green and long-term oncologic surveillance. Full article
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15 pages, 795 KB  
Article
An Above-Average Lymph Node Yield Removed During Curative Neck Dissection in Advanced Head and Neck Squamous Cell Carcinomas Improves Survival
by Miray-Su Yılmaz Topçuoğlu, Thiemo Seidler, Patrick J. Schuler, Christel Herold-Mende, Rolf Warta and Gerhard Dyckhoff
Cancers 2026, 18(1), 68; https://doi.org/10.3390/cancers18010068 - 25 Dec 2025
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Abstract
Objectives: The lymph node yield of a curative neck dissection for advanced head and neck squamous cell carcinoma (HNSCC) is an important factor in improving patient outcomes. Achieving adequate resection while minimising surgical risk is important. This retrospective study investigated the role of [...] Read more.
Objectives: The lymph node yield of a curative neck dissection for advanced head and neck squamous cell carcinoma (HNSCC) is an important factor in improving patient outcomes. Achieving adequate resection while minimising surgical risk is important. This retrospective study investigated the role of the lymph node yield for the survival of patients with HNSCC. Methods: A total of 234 patients with advanced HNSCC who were treated at a German university hospital between 1997 and 2018 were analysed. The analysis included patient data, tumour-specific characteristics, and the extent of neck dissection performed. Statistical analysis was performed using multivariate Cox proportional hazards models, supplemented by Kaplan–Meier analyses. Results: The median age was 60.0 years (range: 30–85 years, interquartile range: 12.3 years). The follow-up period covered up to 25 years. According to the Union for International Cancer Control, n = 64 patients had UICC-stage III, and 170 patients had UICC-stage IV. The above-average lymph node yield was superior to average, but especially to below-average lymph node yields in bilateral (2.9-fold), ipsilateral (2.6-fold), and contralateral (10.7-fold) neck dissection. In particular, contralateral neck dissection was found to correlate with a significantly better prognosis in terms of overall survival when a higher number of lymph nodes were removed. Conclusions: The study suggests that a thorough and careful neck dissection involving the removal of a greater number of lymph nodes and including the contralateral side could significantly improve the survival for patients with advanced HNSCC. Full article
(This article belongs to the Section Methods and Technologies Development)
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35 pages, 3221 KB  
Article
Hazard- and Fairness-Aware Evacuation with Grid-Interactive Energy Management: A Digital-Twin Controller for Life Safety and Sustainability
by Mansoor Alghamdi, Ahmad Abadleh, Sami Mnasri, Malek Alrashidi, Ibrahim S. Alkhazi, Abdullah Alghamdi and Saleh Albelwi
Sustainability 2026, 18(1), 133; https://doi.org/10.3390/su18010133 - 22 Dec 2025
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Abstract
The paper introduces a real-time digital-twin controller that manages evacuation routes while operating GEEM for emergency energy management during building fires. The system consists of three interconnected parts which include (i) a physics-based hazard surrogate for short-term smoke and temperature field prediction from [...] Read more.
The paper introduces a real-time digital-twin controller that manages evacuation routes while operating GEEM for emergency energy management during building fires. The system consists of three interconnected parts which include (i) a physics-based hazard surrogate for short-term smoke and temperature field prediction from sensor data (ii), a router system that manages path updates for individual users and controls exposure and network congestion (iii), and an energy management system that regulates the exchange between PV power and battery storage and diesel fuel and grid electricity to preserve vital life-safety operations while reducing both power usage and environmental carbon output. The system operates through independent modules that function autonomously to preserve operational stability when sensors face delays or communication failures, and it meets Industry 5.0 requirements through its implementation of auditable policy controls for hazard penalties, fairness weight, and battery reserve floor settings. We evaluate the controller in co-simulation across multiple building layouts and feeder constraints. The proposed method achieves superior performance to existing AI/RL baselines because it reduces near-worst-case egress time (T95 and worst-case exposure) and decreases both event energy Eevent and CO2-equivalent CO2event while upholding all capacity, exposure cap, and grid import limit constraints. A high-VRE, tight-feeder stress test shows how reserve management, flexible-load shedding, and PV curtailment can achieve trade-offs between unserved critical load Uenergy  and emissions. The team delivers implementation details together with reporting templates to assist researchers in reaching reproducibility goals. The research shows that emergency energy systems, which integrate evacuation systems, achieve better safety results and environmental advantages that enable smart-city integration through digital thread operations throughout design, commissioning, and operational stages. Full article
(This article belongs to the Special Issue Smart Grids and Sustainable Energy Networks)
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13 pages, 3450 KB  
Article
ROMO1 as a Diagnostic Biomarker in Cervical Neoplasia: Evidence from Normal, Pre-Invasive, and Invasive Lesions
by Eva Tsoneva, Polina Damyanova, Metodi V. Metodiev, Velizar Shivarov, Mariela Vasileva-Slaveva, Zornitsa Gorcheva, Yonka Ivanova, Yavor Kornovski, Stoyan Kostov, Stanislav Slavchev, Margarita Nikolova, Angel Yordanov and Rafał Watrowski
Diagnostics 2026, 16(1), 24; https://doi.org/10.3390/diagnostics16010024 - 21 Dec 2025
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Abstract
Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of [...] Read more.
Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of cervical cancer are caused by persistent infection with oncogenic high-risk human papillomavirus (HPV). This malignancy usually exhibits a gradual development through well-defined precursor stages, known as cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3, before evolving into invasive carcinoma. In diagnostic practice, several biomarkers have been implemented to improve the detection of high-risk cervical lesions. p16 and Ki-67 greatly aid in identifying HPV-driven dysplasia, but they cannot always reliably distinguish progressive lesions from regressive or transient HPV infections. These limitations highlight the need for novel biomarkers with better predictive accuracy to complement current screening and diagnostic algorithms. ROMO1 has become a possible marker of a high-ROS, high-risk tumor phenotype in a number of cancers. Although oxidative stress, HPV, and cervical carcinogenesis have been linked, nothing is known about ROMO1’s involvement in cervical neoplasia. There is currently a lack of thorough information regarding the expression of ROMO1 in normal vs. precancerous lesions and in cervical cancer, as well as on whether or not its expression is correlated with the severity of the disease. In order to define ROMO1 expression throughout the course of cervical squamous neoplastic development, the current study was created. Methods: We performed immunohistochemical analysis of ROMO1 expression on cervical tissue samples from three groups: healthy cervix (n = 30), cervical intraepithelial neoplasia (CIN) (n = 41), and invasive cervical carcinoma (n = 205). ROMO1 expression in invasive carcinoma was evaluated using an H-score scale. Results: ROMO1 expression was basal in all normal cervix samples (0/30 cases). In contrast, CIN lesions showed 100% ROMO1 expression in the suprabasal layers of abnormal cells in all CIN cases. In invasive cervical carcinomas, ROMO1 expression was heterogeneous. In our cancer cohort (n = 205), ROMO1 H-score showed no significant association with the following: FIGO stage I vs. II vs. III (p = 0.25); histologic grade G1 vs. G2 vs. G3 (p = 0.46); lymphovascular invasion (no vs. yes; p = 0.80); nodal status N0 vs. N1 (p = 0.67); patient age (≤50 y vs. >50 y; p = 0.38). However, ROMO1 expression did vary by histologic subtype (AC vs. ASC vs. SCC; p = 0.02), with SCC enriched for strong staining compared to AC/ASC. With regard to tumor stage (pT stage), pT2a tumors exhibited significantly lower ROMO1 (pT1b1–pT2b; p = 0.035) than pT1b1 (p = 0.04). No other clinicopathologic variable remained significant. Notably, ROMO1 expression was highest in stage I tumors and declined in more advanced stages of cervical carcinoma. Conclusions: These results show a clear pattern of ROMO1 expression across the cervical neoplasia spectrum: it is attenuated in invasive tumors (with a peak in early-stage illness), significantly raised in pre-cancerous CIN lesions, and negligible in normal epithelium. The idea that oxidative stress may be the primary cause of early malignant transformation in the cervix is supported by the noticeable overexpression of ROMO1 in early lesions. For the detection of early-stage cervical carcinoma and high-grade precancerous lesions, ROMO1 may be a useful auxiliary biomarker. Full article
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