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29 pages, 8562 KB  
Review
Efficiency and Sustainability in Industrial Biogas Plants: Bibliometric Review of Key Operating Parameters and Emerging Process Metrics
by Yoisdel Castillo Alvarez, Johan Joel Cordero Noa, Gerald Vasco Quispe Soto and Reinier Jiménez Borges
Sci 2026, 8(4), 71; https://doi.org/10.3390/sci8040071 - 26 Mar 2026
Viewed by 276
Abstract
Industrial-scale Anaerobic Digestion (AD) is a key technology for the energy recovery of agro-industrial and municipal waste and for the mitigation of greenhouse gas emissions; however, the actual operational performance of industrial biodigesters continues to show significant discrepancies with respect to the theoretical [...] Read more.
Industrial-scale Anaerobic Digestion (AD) is a key technology for the energy recovery of agro-industrial and municipal waste and for the mitigation of greenhouse gas emissions; however, the actual operational performance of industrial biodigesters continues to show significant discrepancies with respect to the theoretical values reported in the scientific literature. In this context, there is still a lack of systematic analysis to identify which operating parameters are consistently monitored in industrial settings and which remain insufficiently explored, particularly those that describe the overall state of the digestion environment. To address this gap, a systematic literature review was conducted in the Scopus database for the period 2000–2026, complemented by a bibliometric analysis using VOSviewer software v1.6.18. 3. After applying inclusion criteria focused exclusively on industrial-scale and pilot systems, 1327 documents corresponding to the category of operating parameters were selected and analyzed using keyword co-occurrence networks and evaluation of occurrence frequencies and total link intensities. The analysis shows a marked concentration of the literature on a small set of classic parameters, highlighting pH (154 occurrences, 3667 link intensities), temperature (147 occurrences, 3255 link intensities), and ammonia (131 occurrences, 2824 link intensities) as the most recurrent variables in the industrial operation of anaerobic digesters. Complementarily, parameters such as chemical oxygen demand, total and volatile solids, and hydrogen sulfide have progressively increased their presence since 2015, mainly associated with effluent quality assessment, nutrient recovery, and overall process sustainability. In contrast, variables that integrate the state of the environment, such as electrical conductivity, oxidation-reduction potential, and the rheological properties of digestate, appear in less than 5% of the studies analyzed, despite their ability to integrate information on stability, buffer capacity, and overall operating conditions. Taken together, these findings highlight an imbalance between the intensive use of traditional parameters and the limited incorporation of integrative indicators in industrial monitoring, suggesting that their systematic inclusion, together with the development of soft sensors and predictive models, could contribute to improving operational control and reducing the gap between the theoretical performance and actual behavior of industrial biodigesters. Full article
(This article belongs to the Section Environmental and Earth Science)
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19 pages, 786 KB  
Article
Improvement of Bone Mineral Density in Patients with Type 1 Gaucher Disease Treated with Velaglucerase Alfa: Results from Clinical Studies
by Ari Zimran, Jaco Botha, Richard Eastell, Can Ficicioglu, Richard D. Finkelman, Dafna Frydman, Pilar Giraldo, Ozlem Goker-Alpan, Priya S. Kishnani, Heather Lau, Noa Ruhrman-Shahar and Derralynn A. Hughes
J. Clin. Med. 2026, 15(7), 2537; https://doi.org/10.3390/jcm15072537 - 26 Mar 2026
Viewed by 278
Abstract
Background: Despite the availability of effective therapies for Gaucher disease (GD), management of skeletal disease manifestations remains challenging. Methods: This phase 4 SHP-GCB-402 study evaluated the effect of velaglucerase alfa on lumbar spine (LS) bone outcomes in patients with type 1 GD. Results: [...] Read more.
Background: Despite the availability of effective therapies for Gaucher disease (GD), management of skeletal disease manifestations remains challenging. Methods: This phase 4 SHP-GCB-402 study evaluated the effect of velaglucerase alfa on lumbar spine (LS) bone outcomes in patients with type 1 GD. Results: Twenty-one patients with documented bone pathology received ≥1 dose of velaglucerase alfa 60 U/kg; 16 completed this study. The primary endpoint—change from baseline to 24 months in an LS bone mineral density (BMD) Z-score measured by dual-energy X-ray absorptiometry—showed a numerical improvement from baseline (mean [SD] −1.93 [0.88]) to 24 months (−1.76 [1.00]), although statistical significance was not reached (p = 0.1077). These changes are not consistent with previous velaglucerase alfa studies. To contextualize these findings, a pooled analysis of 24-month data from previous velaglucerase alfa trials was conducted. In this cohort (n = 40), a statistically significant mean (SD) increase in the LS BMD Z-score of 0.55 (0.58; p < 0.0001) was observed, supporting the therapeutic potential of velaglucerase alfa in improving skeletal outcomes. Additionally, SHP-GCB-402 demonstrated a significant reduction in the bone marrow burden (BMB) score (mean change from baseline: −3.0 [2.27]; p = 0.0005), indicating a positive effect on bone marrow infiltration. All patients experienced ≥1 treatment-emergent adverse event, mostly of mild/moderate severity. Conclusions: The observed numerical improvements in BMD and significant improvements in BMB in SHP-GCB-402 along with pooled BMD data suggest that velaglucerase alfa may confer skeletal benefits while maintaining a consistent safety profile. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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22 pages, 5895 KB  
Article
Susceptibility of the Oral Commensal Bacterium Streptococcus sanguinis to ZnO Nanoparticles
by Raphaelle Emram, Ronit Vogt Sionov, Adi Aharoni, Sarah Gingichashvili, Noa E. Cohen, Vitaly Gutkin, Moshe Amitay, Asaf Wilensky, Doron Steinberg and Rawi Assad
Int. J. Mol. Sci. 2026, 27(6), 2782; https://doi.org/10.3390/ijms27062782 - 19 Mar 2026
Viewed by 202
Abstract
Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; [...] Read more.
Streptococcus sanguinis (S. sanguinis) is an oral commensal and early colonizer of the tooth surface that contributes to dental biofilm homeostasis. Zinc oxide nanoparticles (ZnO NPs) are often incorporated into dental restorative materials to enhance mechanical performance and confer antibacterial properties; however, their effects on S. sanguinis have not been thoroughly studied. Here, we investigated the antimicrobial and antibiofilm efficacy of ZnO NPs against this bacterial species. ZnO NPs exhibited a minimal inhibitory concentration (MIC) of 100 µg/mL and caused rapid, dose-dependent suppression of intracellular ATP levels and overall metabolic activity within 2–4 h of exposure. ZnO NPs induced reactive oxygen species (ROS) production in a dose-dependent manner. The free radical scavenger α-tocopherol partly prevented the antibacterial effect of ZnO NPs, suggesting that lipid peroxidation contributes to ZnO NP-mediated toxicity, although it is not the sole mechanism involved. Short-term exposure (2 h) to ZnO NPs did not significantly affect membrane integrity or cellular morphology, whereas prolonged treatment (24 h) resulted in pronounced membrane permeabilization, membrane hyperpolarization, and cellular swelling. Computational morphometric analyses of high-resolution scanning electron microscopy (HR-SEM) images of planktonic growing bacteria after a 24 h treatment confirmed a significant, dose-dependent increase in cell surface area and surface roughness. Importantly, ZnO NPs also reduced the metabolic activity and compromised the structural integrity of mature, preformed biofilms. Collectively, these findings demonstrate that ZnO NPs exert antimicrobial and antibiofilm effects against S. sanguinis through early metabolic inhibition associated with oxidative stress followed by progressive membrane dysfunction. Full article
(This article belongs to the Special Issue Advanced Research on Antimicrobial Nanomaterials)
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9 pages, 641 KB  
Brief Report
Real-World Assessment of the Xpert MTB/XDR for Detecting Isoniazid and Second-Line Drug Resistance Among TB Patients
by Andrei Makhon, Sivan Fuchs, Mor Rubinstein, Maya Brodsky, Zeev Dveyrin, Noa Tejman-Yarden and Yelena Losev
Int. J. Mol. Sci. 2026, 27(6), 2597; https://doi.org/10.3390/ijms27062597 - 12 Mar 2026
Viewed by 345
Abstract
Rapid and accurate detection of drug-resistant tuberculosis (DR-TB) is critical for effective treatment and containment. The Xpert® MTB/XDR (GXXDR) assay is designed to detect Mycobacterium tuberculosis complex (MTBC) and resistance to isoniazid and second-line anti-TB drugs directly from clinical specimens. We evaluated [...] Read more.
Rapid and accurate detection of drug-resistant tuberculosis (DR-TB) is critical for effective treatment and containment. The Xpert® MTB/XDR (GXXDR) assay is designed to detect Mycobacterium tuberculosis complex (MTBC) and resistance to isoniazid and second-line anti-TB drugs directly from clinical specimens. We evaluated the clinical performance of GXXDR using 61 MTBC-positive specimens with available phenotypic drug susceptibility testing results. GXXDR results were compared to a phenotypic drug susceptibility test (pDST) and whole-genome sequencing (WGS) to assess sensitivity, specificity, and concordance. Resistance to isoniazid, fluoroquinolones, amikacin, capreomycin, and ethionamide was analyzed. Sensitivity comparisons between GXXDR, WGS, pDST, and manufacturer data were performed using Fisher’s exact and Tango tests. GXXDR demonstrated a high specificity for most drugs and a strong sensitivity for isoniazid (93.8%) and fluoroquinolone (92.3%), consistent with manufacturer reports. In contrast, the sensitivity for amikacin (58.3%), capreomycin (35.7%), and ethionamide (27.3%) was significantly lower than stated by the manufacturer (91.9%, 84.0% and 64.7%, respectively), likely due to resistance mutations outside the assay’s target regions. Sensitivity concordance of GXXDR with WGS was high for all drugs, except ethionamide. The GXXDR assay enables rapid and reliable detection of isoniazid and fluoroquinolone resistance in clinical settings, though sensitivity for certain second-line drugs may be affected by regional genetic diversity. These findings underscore the importance of integrating local epidemiological data to optimize molecular diagnostics for DR-TB. Full article
(This article belongs to the Special Issue Genetic Susceptibility in Human Diseases)
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18 pages, 2320 KB  
Article
Understanding the Oxidation Electrochemistry of Adsorbed Eugenol on a Glassy Carbon Electrode Modified with Electrochemically Partially Reduced Graphene Oxide: A Theoretical and Experimental Approach
by Gastón Darío Pierini, Edgardo Maximiliano Gavilán-Arriazu, Sergio Antonio Rodriguez, Sebastián Noel Robledo, Héctor Fernández and Adrian Marcelo Granero
Int. J. Mol. Sci. 2026, 27(5), 2461; https://doi.org/10.3390/ijms27052461 - 7 Mar 2026
Viewed by 282
Abstract
The electro-oxidation of eugenol (EUG) natural antioxidant was studied by cyclic voltammetry in phosphate buffer solutions (PBS) of different pH at electrochemically partially reduced graphene oxide (GCE/ePRGO). The voltammetric responses were mainly controlled by adsorption at this modified electrode. Current values were higher [...] Read more.
The electro-oxidation of eugenol (EUG) natural antioxidant was studied by cyclic voltammetry in phosphate buffer solutions (PBS) of different pH at electrochemically partially reduced graphene oxide (GCE/ePRGO). The voltammetric responses were mainly controlled by adsorption at this modified electrode. Current values were higher at pH 2.0 PBS, therefore, this pH was chosen to perform all experiments. DFT calculations of pKa’s and standard potentials defined the possible pathways of eugenol and its oxidation products. These pathways were evaluated through the comparison of voltammetric simulations of adsorbed species with experiments at pH 2.0, which also allowed for the estimation of the values of the kinetic parameters involved in electrochemistry. Our findings suggest a multi-step redox process in which Eugenol is first oxidized to the radical species and then to a cationic product. At this stage, the pathways branch into to methylenquinone and a 4-allyl-1,2-diquinone molecules. 4-allyl-1,2-diquinone is finally reduced in single or double reversible electrochemical step to the hydroquinone species. The present physicochemical work allows for a deeper understanding of the eugenol oxidation mechanism, which was only partially proposed in previous studies. Full article
(This article belongs to the Special Issue Advances in Electrochemical Detection Research: A Molecular Insight)
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14 pages, 1412 KB  
Article
Improving Lung Cancer Screening Selection: A Comparative Analysis of Risk Models and Traditional Criteria in a Western European General Population
by Danrong Zhong, Grigory Sidorenkov, Marcel J. W. Greuter, Colin Jacobs, Pim A. de Jong, Hester A. Gietema, Harry J. M. Groen, Firdaus A. A. Mohamed Hoesein, Noa Antonissen, Ralph Stadhouders, Harriet L. Lancaster, Marjolein A. Heuvelmans, Rozemarijn Vliegenthart and Geertruida H. de Bock
Cancers 2026, 18(5), 724; https://doi.org/10.3390/cancers18050724 - 24 Feb 2026
Viewed by 432
Abstract
Background/Objectives: The objective of this study is to evaluate the performance of the traditional age/smoking criteria and existing risk prediction models in selecting high-risk populations for lung cancer screening from a Western European general population. Methods: Baseline data from the Dutch [...] Read more.
Background/Objectives: The objective of this study is to evaluate the performance of the traditional age/smoking criteria and existing risk prediction models in selecting high-risk populations for lung cancer screening from a Western European general population. Methods: Baseline data from the Dutch population-based Lifelines cohort, collected between 2006 and 2013, were linked to the Dutch cancer registry to confirm lung cancer diagnoses. Five-year lung cancer risk was estimated based on traditional age/smoking criteria (NLST, NELSON, SPSTF-2021) and risk prediction models (LLPv2, PLCOm2012, Hoggart, Bach and Shanghai-LCM). For every strategy, the number of individuals eligible was determined, and total lung cancer cases in the eligible groups versus the ineligible groups were calculated. Results: Among 139,120 participants (aged ≥18 years), 218 (0.2%) developed lung cancer within five years. Age/smoking criteria identified 2161–6295 (1.6–4.5%) participants as eligible, comprising 62–92 (28.4–42.2%) lung cancer cases. Risk prediction models identified 2372–4315 (1.7–3.1%) participants as eligible, comprising 40–85 (18.4–38.9%) lung cancer cases. Among lung cancers in ineligible groups, 46.2–59.6% occurred in individuals who formerly smoked, and 28.7–39.3% occurred in individuals who currently smoke. Additionally, 41.2–70.0% of lung cancer cases in ineligible groups were in individuals younger than 50, and 44.3–72.3% in individuals who had quit smoking > 15 years prior to diagnosis. Conclusions: In a Western European population, current lung cancer screening selection criteria resulted in identifying only 18–42% of lung cancer cases. Cases in ineligible groups predominantly concern individuals who currently smoke and are below the threshold age and individuals who quit smoking > 15 years ago, highlighting the opportunity for more personalized risk-based screening strategies to increase lung cancer detection. Full article
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13 pages, 870 KB  
Article
Natural Language Processing-Assisted Incidental Pulmonary Nodule Evaluation Program: Impact on Lung Cancer Outcomes
by Noa Tamam Shenholz, Keren Hod, Liat Toderis, Noam Fink, Arnon Makori, Michael Peer, Evgeni Gershman, Merav A. Ben-David and Elizabeth Dudnik
Med. Sci. 2026, 14(1), 104; https://doi.org/10.3390/medsci14010104 - 21 Feb 2026
Viewed by 248
Abstract
Introduction: Early detection and timely treatment (Tx) initiation are critical to improving lung cancer (LC) outcomes. This study assessed the natural language processing (NLP)-assisted incidental pulmonary nodule (IPN) evaluation program, which employs chest computer tomography (CT) report analysis as an LC diagnostic [...] Read more.
Introduction: Early detection and timely treatment (Tx) initiation are critical to improving lung cancer (LC) outcomes. This study assessed the natural language processing (NLP)-assisted incidental pulmonary nodule (IPN) evaluation program, which employs chest computer tomography (CT) report analysis as an LC diagnostic screening (LCS) tool to identify suspicious lung findings (SLF) necessitating further investigation, and evaluated its impact on prognosis and diagnostic work-up and Tx timelines for patients with LC. Materials and Methods: Consecutive LC patients (n = 200) diagnosed at Assuta Medical Centers (AMC) between January 2019 and December 2022 were retrieved from the AMC electronic database using the MDClone big data platform, and divided into two groups: group A (NLP-assisted IPN evaluation, n = 100) and group B (traditional referral for evaluation of SLF by the community physician, n = 100). Stage at diagnosis, different diagnostic work-up and Tx timelines, and overall survival (OS) were assessed. Results: The NLP-assisted IPN evaluation program led to a significant stage shift (stage I disease: 48% vs. 27% in groups A and B, respectively, p = 0.013). Although the time from imaging to Tx initiation was similar (2.1 ± 5.3 months vs. 2.6 ± 5.9 months in groups A and B, respectively, p = 0.654), the time to systemic Tx (p = 0.035) and the time to radiotherapy (p = 0.044) were significantly shorter in group A. Conclusions: Implementing an NLP-assisted IPN evaluation program may enable earlier LC detection, driving a stage shift towards earlier diagnosis, improved diagnostic efficiency, and expedited time-critical interventions. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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12 pages, 239 KB  
Article
Rationale and Design of the SMILE Registry: A Comprehensive Approach to Predicting Treatment Outcomes in Mitral Regurgitation
by Myrthe J. M. Welman, Ralph A. L. J. Theunissen, Noa S. A. Wolfs, Sebastian A. F. Streukens, Caroline Jaarsma, Geert Tjeerdsma, Loes P. Hoebers, Peter Luyten, Jindrich Vainer, Patrique Segers, Peyman Sardari Nia, Samuel Heuts, Arnoud W. J. van ‘t Hof and Pieter A. Vriesendorp
J. Clin. Med. 2026, 15(4), 1495; https://doi.org/10.3390/jcm15041495 - 14 Feb 2026
Viewed by 282
Abstract
Background: Mitral valve regurgitation (MR) is associated with an impaired prognosis. Due to its frequently asymptomatic presentation, MR often leads to undertreatment, which can delay diagnosis. In addition, the optimal timing and choice of intervention remain unclear. The Significant Mitral Insufficiency Limburg [...] Read more.
Background: Mitral valve regurgitation (MR) is associated with an impaired prognosis. Due to its frequently asymptomatic presentation, MR often leads to undertreatment, which can delay diagnosis. In addition, the optimal timing and choice of intervention remain unclear. The Significant Mitral Insufficiency Limburg Evaluation (SMILE) registry aims to provide a comprehensive real-world characterisation of patients with moderate-to-severe mitral regurgitation. Methods and Results: The SMILE registry is a multicentre prospective registry initiated in 2020, enrolling all consecutive patients with moderate-to-severe MR from all hospitals in Limburg, the Netherlands. Treatment approaches include surgical, catheter-based, and conservative (medical) options, with decision-making from an expert multidisciplinary team. Data are collected via Castor EDC, ensuring compliance with the General Data Protection Regulation using pseudonymisation. The co-primary endpoints are all-cause mortality and heart failure hospitalisations during the five-year follow-up. Secondary objectives include describing management strategies, characterising disease progression and cardiac remodelling, evaluating associations between baseline clinical and echocardiographic characteristics and long-term outcomes, identifying predictors of treatment success, and assessing longitudinal changes in health-related quality of life. Conclusions: The SMILE registry represents an important step towards improving MR management. Its broad data collection, including conservative care and patient-reported outcomes, provides valuable real-world insights beyond procedure-focused studies. The registry may refine intervention timing and personalise treatment strategies to enhance patient outcomes and improve their quality of life. Full article
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16 pages, 728 KB  
Article
Factors Contributing to Complications and Failures of Impacted Canines Undergoing Surgical Orthodontic Treatment: A Retrospective Cohort Study
by Yifat Manor, Maayan Kaganovich, Mor Gamliel, Noa Sadan and Tom Shmuly
J. Clin. Med. 2026, 15(4), 1463; https://doi.org/10.3390/jcm15041463 - 13 Feb 2026
Viewed by 427
Abstract
Objectives: This study aims to assess the prevalence of complications and failures associated with impacted canine eruption in a specialized referral center, with the goal of identifying factors that contribute to these outcomes. Methods: This retrospective cohort study included cases of impacted canines [...] Read more.
Objectives: This study aims to assess the prevalence of complications and failures associated with impacted canine eruption in a specialized referral center, with the goal of identifying factors that contribute to these outcomes. Methods: This retrospective cohort study included cases of impacted canines treated at the School of Dental Medicine between 2010 and 2020. Clinical and radiographic data were collected and evaluated for failures and complications by two independent clinicians (MK, MG). In addition, specialists in oral and maxillofacial surgery and orthodontics (YM, TS, NS) independently assessed all complications and failures. Results: Among the 214 impacted maxillary canines included, 23 (10.7%) failed to erupt following initial surgical–orthodontic treatment and required re-intervention. Eruption difficulty was attributed to orthodontic factors in 43.5% of cases, surgical factors in 13.0%, and combined factors in the remainder. Following a second procedure, 15 canines erupted successfully, while 8 did not, resulting in an overall failure rate of 3.7%. Treatment failure was significantly associated with both anatomical and procedural factors. Canines with centrally positioned crowns exhibited a significantly higher failure rate than those with buccal or palatal positions (χ2 test, p = 0.025). Failure was also more common when the canine root apex was located in close proximity to a cortical plate. Lateral incisor root resorption was significantly associated with treatment complications (p = 0.030). In the multivariable logistic regression analysis, root resorption remained an independent predictor of treatment failure, increasing the odds of failure approximately fourfold (OR = 0.255, CI = 0.077–0.843, p = 0.025). Timing and surgical technique were also significantly associated with treatment outcome. Surgical exposure performed shortly after diagnosis was linked to an increased risk of treatment complications (p = 0.006). Closed surgical exposure demonstrated a significantly higher failure rate compared with open exposure (Pearson exact test, p = 0.009). Although open exposure was associated with a greater likelihood of successful eruption, it was also significantly associated with increased gingival morbidity (Fisher’s test, p = 0.030). Conclusions: Failure of impacted maxillary canine eruption following combined surgical–orthodontic treatment is uncommon but is significantly associated with distinct anatomical and procedural risk factors. Central crown position, cortical plate involvement, lateral incisor root resorption, early surgical exposure, and the use of closed exposure techniques all increase the likelihood of treatment failure and complications. Although open exposure enhances the probability of successful eruption, it may also negatively affect gingival outcomes, underscoring the need for individualized, multidisciplinary treatment planning. Full article
(This article belongs to the Topic Advances in Dental Health, 2nd Edition)
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19 pages, 1226 KB  
Article
Fertility Outcomes in Men with Nonobstructive Azoospermia Due to Hypogonadotropic Hypogonadism After Gonadotropin Therapy
by Athanasios Zachariou, Athanasios Zikopoulos, Eleftheria Markou, Sotirios Koukos, Grigorios Daligaros, Sotirios Skouros, Fotios Dimitriadis, Michael Chrisofos, Nikolaos Sofikitis and Aris Kaltsas
J. Clin. Med. 2026, 15(3), 1204; https://doi.org/10.3390/jcm15031204 - 3 Feb 2026
Viewed by 763
Abstract
Background/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction [...] Read more.
Background/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction (microTESE) for persistent azoospermia, and assisted reproduction when indicated. Methods: A retrospective cohort study included 35 men treated between 2010 and 2022. Human chorionic gonadotropin (hCG), with or without follicle-stimulating hormone (FSH), was administered to induce spermatogenesis. Outcomes included sperm appearance in the ejaculate, microTESE sperm retrieval rate in persistent azoospermia, and pregnancy and live birth outcomes after natural conception or in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) when required. Results: Mean gonadotropin therapy duration was 12.0 months (range 6–24). Sperm appeared in the ejaculate in 27/35 men (77%). The remaining 8/35 (23%) underwent microTESE, with sperm retrieved in 7/8 (88%). Seven couples proceeded to IVF-ICSI, undergoing 11 cycles that yielded 6 clinical pregnancies (55% per cycle) and 5 live birth deliveries, including 2 twin pregnancies. Among responders, 13 natural pregnancies occurred, resulting in 13 live birth deliveries, including 2 twin pregnancies. Overall, 18/35 men (51%) achieved biological fatherhood, corresponding to 18 live birth delivery events (4 twin and 14 singleton deliveries) and 22 newborns. Conclusions: In men with HH-related NOA, exogenous gonadotropin therapy is expected to induce spermatogenesis in most patients. MicroTESE provides high sperm retrieval rates for those without ejaculatory sperm. Through an integrated approach of hormonal induction, microsurgical sperm retrieval, and assisted reproduction, approximately half of patients may ultimately achieve biological fatherhood in longer-term follow-up, depending on baseline severity and partner factors. Full article
(This article belongs to the Special Issue Challenges in Diagnosis and Treatment of Infertility—2nd Edition)
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22 pages, 13863 KB  
Article
AI-Based Augmented Reality Microscope for Real-Time Sperm Detection and Tracking in Micro-TESE
by Mahmoud Mohamed, Ezaki Yuriko, Yuta Kawagoe, Kazuhiro Kawamura and Masashi Ikeuchi
Bioengineering 2026, 13(1), 102; https://doi.org/10.3390/bioengineering13010102 - 15 Jan 2026
Viewed by 818
Abstract
Non-obstructive azoospermia (NOA) is a severe male infertility condition characterized by extremely low or absent sperm production. In microdissection testicular sperm extraction (Micro-TESE) procedures for NOA, embryologists must manually search through testicular tissue under a microscope for rare sperm, a process that can [...] Read more.
Non-obstructive azoospermia (NOA) is a severe male infertility condition characterized by extremely low or absent sperm production. In microdissection testicular sperm extraction (Micro-TESE) procedures for NOA, embryologists must manually search through testicular tissue under a microscope for rare sperm, a process that can take 1.8–7.5 h and impose significant fatigue and burden. This paper presents an augmented reality (AR) microscope system with AI-based image analysis to accelerate sperm retrieval in Micro-TESE. The proposed system integrates a deep learning model (YOLOv5) for real-time sperm detection in microscope images, a multi-object tracker (DeepSORT) for continuous sperm tracking, and a velocity calculation module for sperm motility analysis. Detected sperm positions and motility metrics are overlaid in the microscope’s eyepiece view via a microdisplay, providing immediate visual guidance to the embryologist. In experiments on seminiferous tubule sample images, the YOLOv5 model achieved a precision of 0.81 and recall of 0.52, outperforming previous classical methods in accuracy and speed. The AR interface allowed an operator to find sperm faster, roughly doubling the sperm detection rate (66.9% vs. 30.8%). These results demonstrate that the AR microscope system can significantly aid embryologists by highlighting sperm in real time and potentially shorten Micro-TESE procedure times. This application of AR and AI in sperm retrieval shows promise for improving outcomes in assisted reproductive technology. Full article
(This article belongs to the Special Issue Artificial Intelligence-Based Medical Imaging Processing)
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20 pages, 2483 KB  
Systematic Review
Diffusion Tensor Imaging Biomarkers to Predict Neurological Outcomes in Brain Surgery: A Systematic Review
by Noa Ben Dor, Giovanni Sighinolfi, Vittoria Rosetti, Filippo Friso, Giada Garufi, Salvatore Massimiliano Cardali, Caterina Tonon, Raffaele Lodi and Alfredo Conti
Life 2026, 16(1), 115; https://doi.org/10.3390/life16010115 - 13 Jan 2026
Viewed by 680
Abstract
Diffusion tensor imaging (DTI) tractography is routinely employed in neurosurgical planning; however, the prognostic significance of quantitative DTI metrics for postoperative functional outcomes remains unclear. We conducted a PRISMA-informed systematic review of PubMed (January 2005–1 December 2025), supplemented by additional indexed sources, to [...] Read more.
Diffusion tensor imaging (DTI) tractography is routinely employed in neurosurgical planning; however, the prognostic significance of quantitative DTI metrics for postoperative functional outcomes remains unclear. We conducted a PRISMA-informed systematic review of PubMed (January 2005–1 December 2025), supplemented by additional indexed sources, to synthesize the evidence on quantitative DTI measures associated with postoperative motor, language, and cognitive outcomes following intracranial surgery. Thirty-seven studies were included, primarily single-center studies, and predominantly focused on glioma surgery. Motor outcomes exhibited the most consistent associations, with reduced corticospinal tract integrity and adverse postoperative diffusion changes correlating with muscle weakness and poorer recovery. Recovery from supplementary motor area syndrome was associated with interhemispheric callosal connectivity, with greater disconnection predicting a prolonged symptom duration. Language outcomes demonstrated reproducible structure–function relationships: higher preoperative integrity of the dorsal language pathways was associated with milder postoperative aphasia and better recovery, whereas postoperative tract disruption and diffusivity changes predicted persistent naming and fluency deficits, and ventral pathway alterations were specifically linked to lexico-semantic impairment. In epilepsy surgery, language performance correlated with contralateral and distributed network diffusion changes, consistent with reorganization. Evidence for cognition and gait outcomes was limited and mainly involved the association, limbic, and callosal pathways. Overall, quantitative DTI provides clinically relevant markers of tract and network disruption and postoperative remodeling; however, methodological heterogeneity and limited external validation currently preclude universal prognostic thresholds. Full article
(This article belongs to the Special Issue New Advances in Neuroimaging and Brain Functions: 2nd Edition)
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18 pages, 2552 KB  
Article
Transgenic Citrus sinensis Expressing the Pepper Bs2 R-Gene Shows Broad Transcriptional Activation of Defense Responses to Citrus Canker
by Lorena Noelia Sendín, Verónica Andrea Ledesma, Rocío Liliana Gómez, Qibin Yu, Frederick G. Gmitter, Patricia Albornoz, Esteban Mariano Pardo, Ramón Enrique, Atilio Pedro Castagnaro and María Paula Filippone
Agronomy 2026, 16(2), 187; https://doi.org/10.3390/agronomy16020187 - 12 Jan 2026
Viewed by 589
Abstract
The pepper Bs2 resistance gene confers resistance to susceptible Solanaceae plants against pathogenic strains of Xanthomonas campestris pv. vesicatoria carrying the avrBs2 avirulence gene. Previously, we generated Bs2-transgenic Citrus sinensis plants that exhibited enhanced resistance to citrus canker caused by Xanthomonas citri [...] Read more.
The pepper Bs2 resistance gene confers resistance to susceptible Solanaceae plants against pathogenic strains of Xanthomonas campestris pv. vesicatoria carrying the avrBs2 avirulence gene. Previously, we generated Bs2-transgenic Citrus sinensis plants that exhibited enhanced resistance to citrus canker caused by Xanthomonas citri subsp. citri (Xcc), although the underlying mechanisms remained unknown. To elucidate the molecular basis of the early defense response, we performed a comparative transcriptomic analysis of Bs2-expressing and non-transgenic plants 48 h after Xcc inoculation. A total of 2022 differentially expressed genes (DEGs) were identified, including 1356 up-regulated and 666 down-regulated genes. In Bs2-plants, 36.8% of the up-regulated DEGs were associated with defense responses and biotic stress. Functional annotation revealed major changes in genes encoding receptor-like kinases, transcription factors, hormone biosynthesis enzymes, pathogenesis-related proteins, secondary metabolism, and cell wall modification. Among hormone-related pathways, genes linked to ethylene biosynthesis and signaling were the most strongly regulated. Consistently, endogenous ethylene levels increased in Bs2-plants following Xcc infection, and treatment with an ethylene-releasing compound enhanced resistance in non-transgenic plants. Overall, our results indicate the Bs2 expression activates a complex defense network in citrus and may represent a valuable strategy for controlling canker and other Xanthomonas-induced diseases. Full article
(This article belongs to the Section Pest and Disease Management)
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20 pages, 3867 KB  
Article
Geraniin Mitigates Neuropathic Pain Through Antioxidant, Anti-Inflammatory, and Nitric Oxide Modulation in a Rat Model of Chronic Constriction Injury
by Chih-Chuan Yang, Mao-Hsien Wang, Yi-Wen Lin, Chih-Hsiang Fang, Yu-Chuan Lin, Kuo-Chi Chang and Cheng-Chia Tsai
Int. J. Mol. Sci. 2026, 27(1), 507; https://doi.org/10.3390/ijms27010507 - 3 Jan 2026
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Abstract
Neuropathic pain (NPP) remains therapeutically challenging, with oxidative/nitrosative stress and neuroinflammation—amplified by nitric oxide (NO)—as key drivers. This study investigated geraniin (GRN), a naturally occurring hydrolyzable ellagitannin widely distributed in various plant species, including Phyllanthus spp. and Nephelium lappaceum (rambutan), in a rat [...] Read more.
Neuropathic pain (NPP) remains therapeutically challenging, with oxidative/nitrosative stress and neuroinflammation—amplified by nitric oxide (NO)—as key drivers. This study investigated geraniin (GRN), a naturally occurring hydrolyzable ellagitannin widely distributed in various plant species, including Phyllanthus spp. and Nephelium lappaceum (rambutan), in a rat model of sciatic nerve chronic constriction injury (CCI), focusing on NO-pathway involvement. Male Wistar rats (n = 8/group) received intraperitoneal GRN (3, 10, 30, or 100 mg/kg) or vehicle (1% DMSO in saline) daily for 21 days. Behavioral (thermal hyperalgesia, mechanical allodynia, sciatic functional index), electrophysiological (nerve conduction velocity), and biochemical markers—oxidative/nitrosative stress (nitrite, MDA), antioxidant defenses (GSH, SOD, CAT), inflammation (TNF-α, IL-1β, IL-6, MPO), and apoptosis (caspase-3)—were quantified. L-arginine or L-NAME was co-administered to probe NO signaling. GRN at 30 and 100 mg/kg produced significant antinociceptive and neuroprotective effects; 30 mg/kg was selected for detailed analysis. By day 21, GRN improved pain thresholds and nerve conduction, enhanced antioxidant capacity, suppressed inflammatory mediators, and reduced caspase-3 activity. L-arginine reversed, whereas L-NAME potentiated these effects, confirming NO-dependent modulation. Collectively, GRN mitigates CCI-induced NPP via coordinated antioxidant, anti-inflammatory, and anti-apoptotic actions, supporting its potential as a multi-target candidate for pharmacokinetic and translational development. Full article
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15 pages, 3205 KB  
Article
Extending Hexagon-Based Metal–Organic Frameworks—Mn(II) and Gd(III) MOFs with Hexakis(4-(4-Carboxyphenyl)phenyl)benzene
by Henrik Björck, William Reinholdsson, Ocean Cheung, Guojon Zhou, Zhehao Huang, Francoise M. Amombo Noa and Lars Öhrström
Inorganics 2026, 14(1), 12; https://doi.org/10.3390/inorganics14010012 - 27 Dec 2025
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Abstract
Hexakis(4-(4-carboxylphenyl)phenyl)benzene, H6cbb, was used to prepare the rod-based metal–organic frameworks (rod-MOFs) [Mn4(cbb)(dmf)2(OAc)2] CTH-50 and [Gd3(cbb)(dmf)2(H2O)(OAc)3] CTH-51 by solvothermal synthesis (dmf = N,N-dimethylformamide) with single crystal diffraction revealing [...] Read more.
Hexakis(4-(4-carboxylphenyl)phenyl)benzene, H6cbb, was used to prepare the rod-based metal–organic frameworks (rod-MOFs) [Mn4(cbb)(dmf)2(OAc)2] CTH-50 and [Gd3(cbb)(dmf)2(H2O)(OAc)3] CTH-51 by solvothermal synthesis (dmf = N,N-dimethylformamide) with single crystal diffraction revealing that CTH-50 (by X-ray) and CTH-51 (by electron diffraction) can be described as 5- and 6-connected yav-nets. Gas sorption analysis gave a BET surface area of 787 m2/g for CTH-50 and 187 m2/g for CTH-51, with CTH-50 having an Ideal Adsorbed Solution Theory (IAST) selectivity for SF6 of 35 at 10 kPa, and thermogravimetry indicated the possible stability of CTH-50 to 300 °C and CTH-51 to 400 °C. Full article
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