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A real-time web-based telemedicine framework based on AI and IoMT for emergency triage and initial diagnostics: the TeleMedQuick solution
(Elsevier, 2025) Mohsin, Sura Saad; Salman, Omar H.; Jasim, Abdulrahman Ahmed; Yahya, Marwan Zakariya; Alwindawi, Hajer
Background: Rapid medical decision-making for emergency and chronic conditions remains a global challenge, especially in under-resourced and remote settings. Traditional triage models often rely on narrowly focused algorithms or limited sensor inputs, which can hinder timely diagnosis and treatment. The goal of this study is to introduce telemedquick: This web-based telemedicine system helps with emergency triage and initial diagnosis by using organised clinical rules based on medical guidelines and approved by doctors. Methods: TeleMedQuick integrates Internet of Medical Things (IoMT) devices with a rule-based expert inference engine comprising 76,229 clinical rules. These rules were developed through a combination of medical guideline reviews and direct consultations with certified emergency physicians. The system evaluates vital signs, symptoms, demographics, and patient history for conditions such as stroke, diabetes, hypertension, respiratory disorders, and heart attacks. Results: The system was evaluated on a medically annotated dataset of 750 patients under expert review. It achieved a triage accuracy of 99.1%, confirmed through expert validation and performance metrics, including F1-scores across all urgency levels. Rule design minimises symptom overlap and allows understandable, rapid decisions. Conclusion: As an expert system, TeleMedQuick bridges the gap between IoMT sensing and clinical reasoning in telemedicine. It enables scalable, real-time triage and initial diagnostic support with validated transparency, making it suitable for prehospital care, especially in low-access or high-demand contexts.
Donor impact on allogeneic transplant outcomes with PTCy for severe aplastic anemia: a study of the SAAWP EBMT
(Scientific & Medical Division, 2025) Montoro, Juan; Eikema, Dirk-Jan; Piepenbroek, Brian; Tuffnell, Joe; Halahleh, Khalid; Kulagin, Alexander; AlAhmari, Ali; Adaklı Aksoy, Başak; Remenyi, Peter; Itala-Remes, Maija; Gülbaş, Zafer; McDonald, Andrew; Apte, Shashikant; Kwon, Mi; Rovira, Montserrat; Kharya, Gaurav; Potter, Victoria; Gambella, Massimilano; Schroeder, Thomas; Giammarco, Sabrina; Bazarbachi, Ali; Aljurf, Mahmoud; Ho, Aloysius; Dalle, Jean-Hugues; Vydra, Jan; Sanz, Jaime; Perez-Simon, Jose Antonio; Colita, Anca; Collin, Matthew; Tanase, Alina; Halkes, Constantijn; Kulasekararaj, Austin; Risitano, Antonio; de Latour, Regis Peffault
The use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in severe aplastic anemia (SAA) remains understudied, particularly beyond haploidentical transplants. We analyzed outcomes of SAA patients who underwent stem cell transplantation (SCT) with PTCy from haploidentical donors (n = 209), HLA-matched sibling donors (MSD, n = 70), and unrelated donors (UD, n = 69) using EBMT data from 2010 to 2022. Median age was 22 years, and median time to transplantation was 8.6 months. For haploidentical, MSD, and UD cohorts, the 100-day cumulative incidence of grade II-IV acute GVHD was 19%, 11%, and 14% (p = 0.15), while grade III-IV was 6%, 3%, and 2% (p = 0.1). Two-year chronic and extensive chronic GVHD were 14%, 13%, and 14% (p = 0.1) and 5%, 6%, and 2% (p = 0.5), respectively. Non-relapse mortality at two years was 24% for haploidentical, 7% for MSD, and 10% for UD (p = 0.003). Two-year overall survival (OS) and GVHD- and relapse-free survival were 66% and 54% for haploidentical, 92% and 70% for MSD, and 81% and 66% for UD (p < 0.001, p = 0.06). In multivariable analysis, MSD and UD were associated with superior OS and GRFS compared to haploidentical. PTCy is safe and effective in SAA patients, though haploidentical SCT had higher NRM, leading to lower survival.
A Cross-sectional Analysis of Immunological and Hematological Parameters in Patients With Chronic Opioid Use
(Lippincott Williams & Wilkins, 2025) Ergelen, Mine; Usta Sağlam, Nazife Gamze; Arpacıoğlu, Mahmut Selim; Yalçın, Murat; İzci, Filiz
Background and Aim: Previous research has recognized the dual role of opioids [agonists at μ-opioid receptors (MOP-r agonists)] in modulating immunity and neuroinflammation in individuals with opioid use disorder (OUD). This cross-sectional study investigates the interplay between chronic use of MOP-r agonists and inflammatory parameters in individuals with OUD, with the goal of providing insights into the relationship between immunological responses and OUD. Materials and Methods: A cohort of 129 patients with OUD seeking treatment at an addiction detoxification center underwent detailed clinical assessments. Blood samples were collected for analyses of serum alanine aminotransferase, aspartate aminotransferase, and C-reactive protein levels, and a complete blood count. Participants were categorized into inflammation and noninflammation groups based on C-reactive protein levels. Hematological and inflammation indices, along with pain severity, were compared between these groups. Results: Significant differences were observed between the inflammation and noninflammation groups on variables such as duration of MOP-r agonist intake, daily buprenorphine/naloxone dose, consumption route, severity of withdrawal symptoms, and level of self-reported pain. The inflammation group exhibited higher neutrophil counts and an increased neutrophil-to-lymphocyte ratio. The binary logistic regression models revealed that self-reported pain level, daily buprenorphine/naloxone dosage, Beck Depression Inventory scores, and age were significant predictors of inflammation. Conclusions: This study contributes to our understanding of OUD as a chronic inflammatory condition, shedding light on the intricate relationships between MOP-r agonist addiction, inflammatory responses, and withdrawal-related parameters. The findings offer valuable perspectives on effective management, emphasizing the need for further research in diverse populations to enhance understanding of this complex condition.
Structural Changes in the Temporomandibular Joint After Botulinum Toxin Injection Into the Masseter Muscle in Experimentally Induced Osteoarthritis in Rats
(Blackwell Scientific Publications, 2025) Coşkun, Ümmügülsüm; Yılmaz Altıntaş, Nuray
Background: Botulinum neurotoxin (BoNT) injections into the masticatory muscles have been used as a treatment to improve symptoms related to temporomandibular joint (TMJ) disorders. However, its safety and long-term effects on TMJ structures remain inconclusive and are still under discussion. Objective: The purpose of this study is to evaluate whether the effects of BoNT injection into the masseter affect the mandibular condyle in a rat model of TMJ osteoarthritis (TMJ-OA). Methods: Sixteen male Wistar albino rats were used. The 32 TMJ joints were divided into four groups: (1) TMJ-OA with BoNT (OA + BTX), (2) TMJ-OA without BoNT (OA), (3) BoNT without TMJ-OA (BTX) and (4) control. TMJ-OA was induced by CFA injections. One week later, BoNT was administered to the masseter in the OA + BTX and BTX groups. Micro-CT imaging was performed 8 weeks later to assess the TMJ condyle. Results: The analysis revealed significant differences in bone mineral density and microarchitectural changes between the BTX/control and the OA/OA-BTX groups, except for trabecular separation (p < 0.05). The OA and OA + BTX groups exhibited lower bone volume fraction and bone mineral density compared to the BTX and control groups. No significant differences were observed between the BTX and the groups without BoNT, suggesting that BoNT did not result in bone loss in healthy TMJs or in TMJ-OA cases. Conclusions: BoNT does not have a significant effect on healthy or existing degenerative conditions in the TMJ. Long-term experimental studies and clinical trials are needed to validate the safety of BoNT in managing TMJ-OA.
Protocol for an umbrella review of systematic reviews evaluating the efficacy of digital health solutions in supporting adult cancer survivorship care
(Public Library of Science, 2025) Keane, Danielle; Calbimonte, Jean-Paul; Pawlowska, Ewa; Kassianos, Angelos P.; Medina, Joan C.; Gregorio, Joao; Serra-Blasco, Maria; Celebic, Aleksandar; Meglio, Antonio Di; Asadi-Azarbaijani, Babak; Foster, Claire; Donohoe, Claire L.; Mafra, Allini; Backes, Claudine; Ochoa-Arnedo, Cristian; Gezer, Derya; Bozkul, Gamze; Taşvuran Horata, Emel; Özkan, Esra; Prue, Gillian; İşcan, Gökçe; Dural, Gül; Bahçecioğlu, Gülcan; Ersöğütçü, Filiz; Berzina, Guna; Bektaş, Hicran; Vaz-Luis, Ines; Mlakar, Izidor; Rocha-Gomes, Joao; O'Connor, Mairead; Clara, Maria Ines; Karekla, Maria; Hagen, Marte Hoff; İmançer, Merve Saniye; Çöme, Oğulcan; Mevsim, Vildan; Aksoy, Nilay; Martins, Rui Miguel; Yokuş, Sıdıka Ece; Bayram, Şule Bıyık; Akçakaya Can, Aysun; Brandao, Tania; Saab, Mohamad M.; Bayar Muluk, Nuray; Yıldırım, Zeynep; Podina, Ioana R.; Karadağ, Songül; Erden, Sevilay; Semerci, Remziye; Aydın, Aydanur; Frountzas, Maximos; Üzen Cura, Şengül; Ruveyde, Aydın; Billis, Antonios; Calleja-Agius, Jean; Vojvodic, Katarina; Jaswal, Poonam; Şahin, Eda; Ilgaz, Ayşegül; Pilleron, Sophie; Hegarty, Josephine
Introduction The growing number of people living with, through and beyond cancer poses a new challenge for sustainable survivorship care solutions. Digital health solutions which incorporate various information and communication technologies are reshaping healthcare; offering huge potential to facilitate health promotion, support healthcare efficiencies, improve access to healthcare and positively impact health outcomes. Digital health solutions include websites and mobile applications, health information technologies, telehealth solutions, wearable devices, AI-supported chatbots and other technologically assisted provision of health information, communication and services. The breadth and scope of digital health solutions necessitate a synthesis of evidence on their use in supportive care in cancer. This umbrella review will identify, synthesise, and compare systematic reviews which have evaluated the efficacy or effectiveness of digital solutions for adult cancer survivorship care with a particular focus on surveillance and management of physical effects, psychosocial effects, new cancer/ recurring cancers and supporting health promotion and disease prevention. Methods and analysis An umbrella review of published systematic reviews will be undertaken to explore the types of digital health solutions used, their efficacy or effectiveness as a form of supportive care, and the barriers and enablers associated with their implementation. The umbrella review will be reported according to the Preferred Reporting Items for Overviews of Reviews (PRIOR) checklist. A search will be conducted across key databases. Records will be assessed independently by two review authors for eligibility against predefined criteria and will undergo two stage title, abstract and full text screening. All systematic reviews that meet the inclusion criteria will be assessed for quality using the AMSTAR 2 checklist with quality assessment and data extraction by two reviewers. The degree of publication overlap of primary studies across the included reviews will also be calculated and a mapping of the evidence will also be presented.
Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial
(Elsevier, 2025) Paz-Ares, Luis; Borghaei, Hossein; Liu, Stephen V.; Peters, Solange; Herbst, Roy S.; Stencel, Katarzyna; Majem, Margarita; Şendur, Mehmet Ali Nahit; Czyzewicz, Grzegorz; Caro, Reyes Bernabe; Lee, Ki Hyeong; Johnson, Melissa L.; Karadurmuş, Nuri; Grohe, Christian; Baka, Sofia; Csoszi, Tibor; Ahn, Jin Seok; Califano, Raffaele; Yang, Tsung-Ying; Kemal, Yasemin; Ballinger, Marcus; Cuchelkar, Vaikunth; Graupner, Vilma; Lin, Ya-Chen; Chakrabarti, Debasis; Bhatt, Kamalnayan; Cai, George; Iannone, Robert; Reck, Martin; IMforte investigators
Background: Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide. Methods: IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment. Findings: Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43–0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57–0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3–4 adverse events. The most common grade 3–4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group. Interpretation: IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting. Funding: F Hoffmann-La Roche and Jazz Pharmaceuticals.
Association between clinical findings and 3T MRI features in temporomandibular joint disorders
(BioMed Central, 2025) Özel, Şelale; Tunç, Selmi; Şenol, Abdullah Utku
Background: Temporomandibular joint disorders (TMD) commonly cause restricted mouth opening and pain, significantly affecting patients’ quality of life. This study aims to explore the relationship between common clinical symptoms—clicking and limited mouth opening—and MRI findings in patients diagnosed with TMD. Methods: A total of 46 patients, with either clicking sounds or limited mouth opening, were examined using a 3T MRI scanner. The study evaluated disc position, disc deformity, and signs of osteoarthrosis, comparing MRI findings with clinical symptoms. Results: Results revealed that disc deformation was positively correlated with clicking. In contrast, limited mouth opening was significantly associated with anterior disc displacement without reduction and osteoarthrosis, indicating joint degeneration. Conclusions: The findings highlight that limited mouth opening is a more reliable clinical indicator of TMD than joint clicking, which may not always reflect underlying disc displacement. Although clicking was observed in discs with and without displacement, limited mouth opening showed a strong correlation with degenerative changes in the temporomandibular joint. The study underscores the reliability of clinical symptoms of TMD, which play a crucial role in treatment planing. Clinical trial number: Not applicable.
The comorbidities of hidradenitis suppurativa
(J.B. Lippincott, 2025) Aşkın, Özge; Ferhatoğlu, Özge Altan; Özkoca, Defne; Küçükoğlu Cesur, Seher; Tüzün, Yalçın
Hidradenitis suppurativa is a chronic inflammatory disease that dramatically decreases the quality of life of afflicted patients. A number of factors may coexist with hidradenitis suppurativa, including stigmatization, social isolation, tobacco use, alcohol abuse, suicidal ideation, depression, other psychiatric disorders, and medical comorbidities such as obesity, diabetes mellitus, hypertension, dyslipidemia, metabolic syndrome, coronary artery disease, and polycystic ovarian syndrome. These comorbidities should be kept in mind while planning the treatment. A rare but important long-term complication of hidradenitis suppurativa is squamous cell cancer; men with perianal, gluteal, or perineal lesions are at increased risk, and multiple biopsies should be taken in case of any suspicious lesions.
Barriers to healthcare access and continuity of care among Ukrainian war refugees in Europe: findings from the RefuHealthAccess study
(FRONTIERS MEDIA SA, 2025) Kardas, Przemyslaw; Mogilevkina, Iryna; Aksoy, Nilay; Agh, Tamas; Garuoliene, Kristina; Lomnytska, Marta; Istomina, Natalja; Urbanavice, Rita; Wettermark, Björn; Khanyk, Nataliia
Introduction: The Russian invasion of Ukraine displaced over 14 million people. By 2024, around 6 million Ukrainian refugees settled in Europe under the EU Temporary Protection Directive, providing permit of residence, work and health care. This influx strained European healthcare systems, particularly in addressing acute injuries. As the stay of refugees in EU countries prolongs, the management of chronic conditions becomes increasingly important. However, there is limited information available about Ukrainian refugees' access to various healthcare services. Aim: The aim of this study was to evaluate perceived accessibility of healthcare services in Europe for Ukrainian war refugees and to identify barriers to healthcare access, in order to inform improvements in healthcare provision. Methods: A cross-sectional online survey was conducted across Europe from July 2023 to April 2024, targeting adult Ukrainian war refugees. Survey explored areas defined as key health care needs. Descriptive, parametric and non-parametric statistical analysis methods were employed in data analysis. Results: Of 659 respondents, 550 (83.4%) were included in the final analysis due to having reported need to use healthcare services in the past year. The most prevalent needs included dental care (82.9%), prescription medication (81.6%), care for acute (78.4%), and chronic conditions (64.0%). Perceived access to care varied across services, with vaccinations rated highest, while chronic condition care rated lowest. Around ¼ of respondents reported that they had to temporarily return to Ukraine for services not available in the countries where they stayed, these being mostly dental and gynaecologic care. The most prevalent barriers reported were long waiting times (64.2%), information barriers (55.5%), and high service costs (49.1%). Discussion: The survey identified several barriers in the access to healthcare system for Ukrainians, particularly for chronic conditions care. Some barriers may be subjective, relating to limited access to information. However, others point to potential shortcomings within national healthcare systems, suggesting areas that require further review and improvement. Conclusions: Addressing language barriers, improving information dissemination, and enhancing chronic condition management were identified as crucial for improving healthcare access for Ukrainian war refugees. Coordinated strategies are needed to support refugees and ensure the sustainability of host healthcare systems. Copyright
Anatomy exam model for the circulatory and respiratory systems using GPT-4: a medical school study
(Springer International, 2025) Tekin, Ayla; Karamus, Nizameddin Fatih; Çolak, Tuncay
Purpose: The study aimed to evaluate the effectiveness of anatomy multiple-choice questions (MCQs) generated by GPT-4, focused on their methodological appropriateness and alignment with the cognitive levels defined by Bloom's revised taxonomy to enhance assessment. Methods: The assessment questions developed for medical students were created utilizing GPT-4, comprising 240 MCQs organized into subcategories consistent with Bloom's revised taxonomy. When designing prompts to create MCQs, details about the lesson's purpose, learning objectives, and students' prior experiences were included to ensure the questions were contextually appropriate. A set of 30 MCQs was randomly selected from the generated questions for testing. A total of 280 students participated in the examination, which assessed the difficulty index of the MCQs, the item discrimination index, and the overall test difficulty level. Expert anatomists examined the taxonomy accuracy of GPT-4's questions. Results: Students achieved a median score of 50 (range, 36.67-60) points on the test. The test's internal consistency, assessed by KR-20, was 0.737. The average difficulty of the test was 0.5012. Results show difficulty and discrimination indices for each AI-generated question. Expert anatomists' taxonomy-based classifications matched GPT-4's 26.6%. Meanwhile, 80.9% of students found the questions were clear, and 85.8% showed interest in retaking the assessment exam. Conclusion: This study demonstrates GPT-4's significant potential for generating medical education exam questions. While it effectively assesses basic knowledge recall, it fails to sufficiently evaluate higher-order cognitive processes outlined in Bloom's revised taxonomy. Future research should consider alternative methods that combine AI with expert evaluation and specialized multimodal models.
Naples Prognostic Score Predicts New-Onset Atrial Fibrillation in Patients with ST-Elevated Myocardial Infarction Undergoing Primary Angioplasty
(Sociedad Brasileira De Cardiologia, 2025) Okşen, Doğaç; Arslan, Şükrü; Heja Geçit, Muhammed; Ertürk Tekin, Esra; Oktay ,Veysel; Abacı, Okay
Background: New-onset atrial fibrillation (NOAF) is a typical complication in patients with ST-segment elevated myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). Previous studies have investigated inflammation as a NOAF predictor. The Naples prognostic score (NPS) is a novel marker of inflammation and nutritional status. Objective: The objective of this study was to evaluate the predictive power of the NPS for NOAF. Methods: This study enrolled 1537 consecutive STEMI who underwent pPCI. The patients who presented NOAF during hospital admission and those who remained in sinus rhythm (RSR) were compared in terms of baseline characteristics. Univariate and multivariate analyses were carried out to identify variables predicting NOAF development, and p< 0.05 was considered statistically significant. Results: NOAF was detected in 7.74% (n: 119) of the participants. The mean age (67.03±13.48 vs 57.84±11.31; p <0.001) and NPS (2.53±1.17 vs 2.25±1.10, p=0.008) were significantly higher in the NOAF group. Multivariate analysis revealed age (Odds ratio [OR]: 1.045 for a year, 95% confidence interval [CI]: 1.019–1.071, p=0.001), NPS (OR: 1.645, 95% CI: 0.984–2.748, p=0.037) and left atrial dimensions (OR: 2.542 for cm, 95% CI: 1.488–4.342, p=0.001) as independent predictors of NOAF. Conclusions: The NPS was an independent predictor of NOAF in STEMI patients, in addition to classical factors such as age and left atrial dimensions. This score, mostly related to an inflammatory burden, may help to predict NOAF incidence and select better potential therapies aimed at abating inflammation after myocardial infarction.
Advances in vaccine adjuvant development and future perspectives
(Taylor and Francis Ltd., 2025) Sinani, Genada; Şenel, Sevda
Use of highly purified antigens to improve vaccine safety has led to reduced immunogenicity and efficacy, resulting in the need for adjuvants to increase and/or modulate the immunogenicity of the vaccine. Despite the need for potent and safe vaccine adjuvants, currently, there are still very few adjuvants in licensed human vaccines. Advances in immunology and molecular biology, especially in the last decade, have allowed researchers to understand better how the adjuvants work and enhance immune responses. While aluminum salts are still the most widely used adjuvants, research has shifted toward the rational design of adjuvant systems containing immunostimulatory molecules. Application of systems biology, which is based on high-throughput technologies using mathematical and computational modeling, has provided a deeper understanding of the biological events elicited by vaccination as well as the influence of other factors such as sex, age, microbiota, genetics and metabolism on the immune response. By this means, it became possible to tailor potential vaccine adjuvants more precisely for a successful vaccine with enhanced efficacy, safety and protection. In this review, after describing the mechanism of action of the adjuvants, current adjuvants in licensed vaccines, as well as those under clinical development will be mentioned in detail. Finally, new approaches in vaccine adjuvant development using systems biology and artificial intelligence will be reviewed, and future directions in vaccine research in regard to efficacy, safety and quality aspects will be discussed.
Thin endometrium restricts peri-ovulatory physiological transition between anti-adhesive and adhesive receptivity modulators
(Reproductive Healthcare Ltd., 2025) Çelik, Önder; Erşahin, Aynur; Güngör, Nur D.; Uluğ, Ulun; Çelik, Nilüfer; Yardım, Meltem; Tektemur, Ehmet; Dalkılıç, Semih; Kuloğlu, Tuncay; Erşahin, Suat Süphan; Çelik, Sudenaz; Akkoç, Ramazan F.
Research question: Does endometrial thinning affect the physiological transition of the endometrium from a non-receptive to a receptive state? Design: Fifty-eight women who underwent total embryo freezing were divided into three groups according to their endometrial thickness (EMT): group 1, EMT ≤ 7 mm; group 2, 7 mm < EMT ≤ 10 mm; and group 3, EMT > 10 mm. Group 1 was considered as having a thin EMT and groups 2 and 3 as a normal EMT. Endometrial sampling was performed at the time of oocyte retrieval. Anti-adhesive podocalyxin (PDX), adhesive homeobox A10 and A11 (HOXA10, HOXA11) and leukaemia inhibitory factor (LIF) mRNA, proinflammatory cytokines, oxidative stress markers and collagen deposition were determined. Results: Compared with groups 2 and 3, the relative expression of HOXA10, HOXA11 and LIF mRNA was down-regulated in group 1 (all P < 0.001), while PDX levels significantly increased (P < 0.001). The nuclear factor-κB, long pentraxin 3 (PTX3), tumour necrosis factor-α and total oxidant status of the thin endometrium group were significantly higher than those of participants with normal endometrium (all P < 0.001), while total antioxidant status was significantly lower (P < 0.001). The histoscore values for PTX3, PDX and Masson's trichrome were significantly higher in the thin endometrium group (P < 0.001 for each). Each millimetre increase in EMT decreased the risk of down-regulation of adhesive receptivity genes. The adjusted odds ratio for PDX was 1.69, representing a 69% increase in PDX expression. Conclusion: Endometrial thinning causes defective expression of anti-adhesive and adhesive receptivity modulators, restricting the transition of the endometrium from a non-receptive to a receptive state.
Postmortem Inductively Coupled Plasma Mass Spectrometry Analysis Reveals Elevated Heavy Metal Concentrations in Coronary Arteries: A Comparative Autopsy Study Supporting a Toxic Inflammatory Hypothesis for Atherosclerosis
(S. Karger, 2025) Yolay, Onur; KAsapbaşı, Emine Esra; Tezcan, Erdem; Küçük, Ceyhun; Karaoğlu, Hasan; Cantürk, Emir; İnan, Bekir; Okşen, Doğaç; Çetinarslan, Özge; Umihanic, Fadil; Albayrak, Serdar Baki; Olcay, Ayhan
Introduction: A large number of studies have been carried out for the etiology of atherosclerosis and many risk factors have been identified, including environmental factors and heavy metals, which are related to the pathogenesis. This study aimed to determine the effects of heavy metals, which have activation and inhibition effects on various metabolic pathways, on atherosclerosis by examining coronary arteries obtained from autopsy series. Methods: Coronary arteries of 28 autopsy cases were analyzed by inductively coupled plasma mass spectrometry method. Sixteen of the cases had coronary atherosclerotic plaques and 12 of the coronaries were normal. Twenty trace metal concentrations were examined from the samples obtained. Results: Twenty-eight coronary artery samples (16 with atherosclerosis, 12 normal) were analyzed using ICP-MS. Levels of Mg, K, Ca, P, Fe, Zn, Al, S, As, Pt, Sb, Hg were significantly higher in atherosclerotic arteries (e.g., Ca: 51,384 vs. 1,723 ppm, p = 0.005; P: 30,791 vs. 3,443 ppm, p = 0.003; Hg: 3.2 vs. 0 ppm, p < 0.001). Elements such as lead, cobalt, and cadmium remained below detection limits in both groups. Conclusion: Heavy metals through inflammation, oxidative stress, and disrupted antioxidant pathways are independent risk factors that increase the risk of atherosclerosis. These findings provide tissue-level evidence that heavy metal accumulation may contribute to atherosclerosis through oxidative stress, inflammation, and disruption of antioxidant defenses.
Is age a determinant in cervical cancer screening in women aged 18 to 29?: An observational study
(Lippincott Williams & Wilkins, 2025) Küçükyurt, Ayça K.; Atakul, Nil; Kolcu, Selma Atiye; Özcan, Ayşet Janet; Abdullazade, Narmin
This study aims to analyze the impact of aging on cervical cancer screening among women aged 20 to 29. Specifically, it examines the occurrence of abnormal histological results and Cervical Intraepithelial Neoplasia (CIN) (+) lesions within these age groups. We retrospectively analyzed women aged 18 to 29 (<30) who underwent cervical cancer screening through cytology between 2014 and 2024. A total of 842 women who visited the gynecology outpatient clinic were included, and their Pap smear, colposcopy, and loop electrosurgical excision procedure/conization results were reviewed. Patients were divided into 2 age groups (18-25 and 26-29) for comparative analysis. Among the 842 women who underwent cytological evaluation: 744 (88.4%) had normal results, 51 (6.1%) were diagnosed with atypical squamous cells of undetermined significance (ASC-US), 31 (3.7%) with low-grade squamous intraepithelial lesion (LSIL), 8 (1.0%) with atypical squamous cells - cannot exclude high-grade lesion (ASC-H), 4 (0.5%) with High-Grade Squamous Intraepithelial Lesion (HSIL), and 4 (0.5%) with Atypical Glandular Cells (AGC). HPV (Human Papillomavirus) testing was performed on 75 women, and 40 (53.3%) tested positive for HPV. Colposcopy was conducted on 53 women, revealing CIN + lesions in 38 cases, while conization confirmed CIN + lesions in 23 cases. Colposcopy results revealed the presence of CIN 1, CIN 2, and CIN 3 lesions in both age groups. However, CIN 3 lesions were observed less frequently in the > 26 age group. Similarly, conization results showed a lower incidence of CIN 3 lesions in women older than 26. Women aged 18 to 25 had a higher likelihood of CIN 3 diagnosis. These findings emphasize the importance of considering age in the diagnosis of CIN (+) lesions during cervical cancer screening.
Investigation of APOE2 rs7412 and APOA2 rs5082, APOA5 rs662799 and MTHFR rs1801133 Polymorphisms in Diabetic Obese and Non-Obese Diabetic Groups in Turkey
(Pleiades Publishing, 2025) Özyavuz, M. K.; Durak, S.; Çelik, F.; Aksoyer Sezgin, S.B.; Gürol, A.O.; Doğan, Z.; Zeybek, U.
Abstract: Obesity caused by an abnormal increase in adiposyte, is linked to type 2 diabetes. Diabetes is a metabolic-disease that is caused by insulin-deficiency. Type 2 diabetes is a serious implication of obesity and genetic polymorphisms. Apolipoprotein E2 (APOE2)(rs7412), Apolipoprotein A2 (APOA2) (rs5082), Apolipoprotein A5 (APOA5) (rs662799), Methylenetetrahydrofolate reductase (MTHFR) (rs1801133) polymorphisms which were determined to play role in the development of obesity and diabetes, were evaluated with the RT-qPZR in the study. We included 99 diabetic obese and 99 diabetic non-obese people. We investigated the effect of obesity on variants of all gene polymorphisms in diabetic patients. As a result, APOA2, APOE2 polymorphisms were significant, APOA5, MTHFR polymorphisms were not significant in genotype/allele frequency between groups. APOA2 CC-homozygous carriers had high low-density-lipoprotein-c, glucose, body-mass-index in diabetic-obese patients. APOE2 C-allele carriers had significantly high-Triglyceride and low high-density-lipoprotein versus TT-genotype in non-obese diabetic patients. The present study was first in the Turkey population and evaluates the polymorphisms of genes indicated in diabetic patients.
Dynamic Alteration of HALP Score as a Predictor in Patients with Receiving Immunotherapy for Advanced Non-Small Cell Lung Cancer
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Koçanoğlu, Abdulkadir; Karakaya, Serdar; Zeynelgil, Esra; Düzköprü, Yakup; Doğan, Özlem
Background and Objectives: This study aimed to investigate the prognostic value of the hemoglobin–albumin–lymphocyte–platelet (HALP) score—a marker reflecting both inflammatory and nutritional status—in patients with metastatic non-small cell lung cancer (NSCLC) undergoing immunotherapy. We also sought to determine whether dynamic changes in the HALP score during treatment could predict therapeutic success and help distinguish between pseudoprogression and hyperprogression. Materials and Methods: A retrospective analysis was conducted on 160 patients diagnosed with metastatic NSCLC and treated with immunotherapy at the Ankara Atatürk Sanatorium Training and Research Hospital. Chemotherapy regimens, metastatic sites, baseline and third-month hemograms and biochemistry parameters, and survival data were recorded. Survival outcomes were analyzed using the Kaplan–Meier method with the log-rank test and the Cox proportional hazards regression model using IBM SPSS Statistics. Results: The median overall survival (OS) for the entire cohort was 15 months (95% CI: 11.88–18.12). HALP1 score (p = 0.048), HALP2 score (p = 0.026), and hyperprogression (p < 0.001) were statistically significant predictors of OS. Regarding progression-free survival (PFS), the HALP2 score (p = 0.031), line of immunotherapy (p = 0.046), and hyperprogression (p < 0.001) were found to be significant. When comparing patients with increasing versus decreasing HALP scores, those with increasing HALP scores demonstrated significantly better outcomes for both OS (p = 0.034) and PFS (p = 0.007). Conclusions: In patients with metastatic NSCLC undergoing immunotherapy, the HALP score and its dynamic alterations during treatment appear to be non-invasive, easily calculable biomarkers that may predict both OS and PFS.
Day 4 Versus Day 5 Fresh Embryo Transfer in In Vitro Fertilization: Is It All About Timing?
(MDPI, 2025) Şişmanoğlu, Alper; Oğlak, Süleyman Cemil; Özcan, Cenk; Uluğ, Ulun
Objective: Most studies concentrate on comparisons between the cleavage stage and blastocyst stage of embryos during in vitro stimulation treatment. We aimed, in this study, to compare the pregnancy rates of day 4 or day 5 blastocyst transfers, all derived from fresh, antagonist-regulated in vitro fertilization (IVF) cycles, and to evaluate the factors affecting pregnancy success. Methods: This retrospective cohort study evaluated 3681 fresh embryo transfer cycles conducted at a private IVF center between 2019 and 2021. Patients were divided into two groups based on the day of embryo transfer: day 4 (Group 1) and day 5 (Group 2). Subgroup analyses were performed according to age (≤40 vs. >40 years) and the number of oocytes retrieved (≤4 vs. >4). All patients underwent ovarian stimulation with FSH alone or in combination with hMG, and GnRH antagonist protocols were used for pituitary suppression. Final oocyte maturation was triggered with recombinant hCG, and fertilization was achieved via intracytoplasmic sperm injection (ICSI) for all cases. Embryos were cultured in sequential media and assessed daily until transfer on day 4 or day 5, based on embryo morphology and clinic logistics. Results: Pregnancy was more likely among women under 40 than among women over 40. There were a total of 1217 women who underwent day 4 transfer and 2464 women who underwent day 5 transfer. A total of 660 (54.2%) of the women transferred on day 4 developed pregnancy. Among those transferred on day 5, 1610 (65.3%) developed pregnancy. When compared to the 4th day, a single embryo transfer on the 5th day enhances pregnancy success by 1.8 times, while two embryo transfers raise it by 1.6 times. Furthermore, when the number of oocytes is greater than four and the number of embryos transferred is two, the pregnancy success rate is 2.5 times higher when embryo transfer is performed on the fifth day versus the fourth day. Regardless of age, oocyte count, or number of embryos transferred, 5th-day fresh embryo transfers enhanced pregnancy success by 1.9 times compared to 4th-day transfer. Conclusions: Transfers of fresh embryos on day 5 are superior to those on day 4 and should be favored, especially for people over the age of 40, regardless of the number of embryos transferred, even if that individual has fewer than four oocytes.
Antimicrobial Lock Therapy: Is it a Real Savior in Pediatric Hematopoetic Stem Cell Transplant (HSCT) Patients?
(Turkish Society of Haematology, 2025) Kara, Manolya; Sürçü, Murat; Adaklı Aksoy, Başak; Zengin Ersoy, Gizem; Başoğlu Öner, Özlem; Yaman, Ayhan; Özbek, Ahmet; Bozkurt, Ceyhun; Fışgın, Tunç
Objective: Central line-associated bloodstream infection (CLABSI) is a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Antimicrobial lock treatment (ALT), when utilized alongside systemic antibiotics, may be lifesaving when catheter removal (CR) is not feasible. Materials and methods: This retrospective study analyzed the clinical, laboratory, and microbiologic characteristics of CLABSI episodes of pediatric patients who underwent HSCT and applied ALT. Results: There were 137 cases of CLABSI (63.5 male) who were given ALT. The median age was 48 (3-204) months. The most common causative microorganism was Gram-negative bacteria, encountered in 85 patients (62%). Forty-six patients (33.6%) had Gram-positive bacterial growth, whereas 6 had (4.4%) fungal infection. ALT was successful in 77.4% of the patients (n=106). CR was required in 25 patients (18.2%). The CLABSI-related mortality rate was 12.4%. When the outcome of ALT was evaluated, post-transplantation cyclophosphamide (PTCy) use, fungal growth, persistent bacteremia/fungemia, re-HSCT, inappropriate empirical antibiotic use, hypotension, and pediatric intensive care unit admission were significantly more common in the "unsuccessful" ALT group. The patients in the unsuccessful group had higher C-reactive protein [110.2 (1.10-323.5) mg/L] levels when compared to the successful ALT group [58 (0.2-450.3) mg/L] (p=0.029). The presence of hypotension, HLA-mismatch transplantation, and persistent bacteremia/fungemia were independent risk factors for ALT failure. Conclusion: ALT can be an effective catheter-saving strategy in HSCT pediatric patients. Nevertheless, patients should be monitored very closely during ALT, and the presence of certain risk factors should be taken into account.
Clinical and economic consequences of medication nonadherence: a review of systematic reviews
(Frontiers Media, 2025) Achterbosch, Maria; Aksoy, Nilay; Obeng, George D.; Ameyaw, David; Agh, Tamas
Background: Medication efficacy observed in clinical trials may differ from its effectiveness during real-world usage. Medication nonadherence is one of the key factors being responsible for this efficacy-effectiveness gap. The World Health Organization estimated that only 50% of chronic medication users is adherent and nonadherence results in both negative health outcomes for the patient and higher societal costs. An overview of the consequences across disease groups may allow some comparison and could contribute to identification of priority clinical areas. Objective: We aimed to provide an overview the impact of nonadherence on clinical and economic outcomes. Method: We narratively reviewed systematic reviews published between 2014 and 2024 on the effect of medication nonadherence on clinical and economic outcomes. Results: Overall, 43 systematic reviews were identified, including over 410 original studies on clinical outcomes and 174 on economic outcomes, covering different clinical areas (e.g., organ transplantation, cardiovascular diseases, diabetes, depression and chronic lung diseases [asthma/COPD]). Beyond diminished treatment effects, medication nonadherence has been associated with elevated mortality, increased healthcare utilization (including hospital admissions), and higher direct (e.g., more healthcare provider visits) and indirect financial cost burden (e.g., work productivity losses due to absenteeism and presenteeism) for patients and society. Conclusion: Medication nonadherence is associated with poor clinical and economic outcomes across disease areas. Given the significant impact of nonadherence, raising awareness among healthcare professionals and policymakers, early stakeholder engagement in intervention design, and eventually implementation of cost-effective interventions on both health policy, system and individual patient level are urgently required.

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