Three-dimensional Analysis of Presurgical Nasoalveolar Molding Outcomes in Patients with Unilateral Cleft Lip and Palate: A Preliminary Study Using LED Surface Scanning Technology.

OBJECTIVES: Presurgical infant orthopedic appliances, such as presurgical nasoalveolar molding (PNAM) devices, are used to attain optimal conditions for primary repair of the lip and nose (PRoLN) in patients with cleft lip. We aimed to analyze the three-dimensional (3D) outcomes of PNAM using an LED surface scanner. METHODS: Fifteen patients with unilateral cleft lip and palate (CLP) were included in this study and treated using a PNAM device. The patients' faces were digitized pre- and post-PNAM using an Artec Space Spider scanner, and the scanned data were analyzed using 3D software (Geomagic Control X and ANSYS SpaceClaim). The columellar angle (CA), nostril curvature (NC) on the affected (NC_A) and unaffected (NC_U) sides, gap of cleft lip (GCL), alar width (AW), and nasal tip angle (NTA) were measured. RESULTS: CA increased significantly by 10.00° and NC_A by 0.030 mm-1 (p<0.001). GCL decreased by 4.98 mm2 on average and NC_U by 0.015 mm-1 (p=0.029 and 0.046, respectively). AW also decreased by approximately 1.22 mm pre- and post-treatment (p=0.002), and NTA, which shows a lateral profile, decreased by approximately 3.32° (p=0.002). CONCLUSIONS: This study confirmed the orthopedic benefits of PNAMd treatment through 3D analysis using an LED surface scanner. Further studies involving a larger number of participants are warranted to study the effects of PNAM and analyze longitudinal changes in patients with CLP. CLINICAL SIGNIFICANCE: This study shows that PNAM effectively corrects columellar deviation and nostril shape in patients with unilateral cleft lip, with 3D scanners enhancing primary lip and nose repair outcomes.

Vascularized platforms for investigating cell communication via extracellular vesicles.

The vascular network plays an essential role in the maintenance of all organs in the body via the regulated delivery of oxygen and nutrients, as well as tissue communication via the transfer of various biological signaling molecules. It also serves as a route for drug administration and affects pharmacokinetics. Due to this importance, engineers have sought to create physiologically relevant and reproducible vascular systems in tissue, considering cell-cell and extracellular matrix interaction with structural and physical conditions in the microenvironment. Extracellular vesicles (EVs) have recently emerged as important carriers for transferring proteins and genetic material between cells and organs, as well as for drug delivery. Vascularized platforms can be an ideal system for studying interactions between blood vessels and EVs, which are crucial for understanding EV-mediated substance transfer in various biological situations. This review summarizes recent advances in vascularized platforms, standard and microfluidic-based techniques for EV isolation and characterization, and studies of EVs in vascularized platforms. It provides insights into EV-related (patho)physiological regulations and facilitates the development of EV-based therapeutics.

Assessing the utility of large language models for phenotype-driven gene prioritization in the diagnosis of rare genetic disease.

Phenotype-driven gene prioritization is fundamental to diagnosing rare genetic disorders. While traditional approaches rely on curated knowledge graphs with phenotype-gene relations, recent advancements in large language models (LLMs) promise a streamlined text-to-gene solution. In this study, we evaluated five LLMs, including two generative pre-trained transformers (GPT) series and three Llama2 series, assessing their performance across task completeness, gene prediction accuracy, and adherence to required output structures. We conducted experiments, exploring various combinations of models, prompts, phenotypic input types, and task difficulty levels. Our findings revealed that the best-performed LLM, GPT-4, achieved an average accuracy of 17.0% in identifying diagnosed genes within the top 50 predictions, which still falls behind traditional tools. However, accuracy increased with the model size. Consistent results were observed over time, as shown in the dataset curated after 2023. Advanced techniques such as retrieval-augmented generation (RAG) and few-shot learning did not improve the accuracy. Sophisticated prompts were more likely to enhance task completeness, especially in smaller models. Conversely, complicated prompts tended to decrease output structure compliance rate. LLMs also achieved better-than-random prediction accuracy with free-text input, though performance was slightly lower than with standardized concept input. Bias analysis showed that highly cited genes, such as BRCA1, TP53, and PTEN, are more likely to be predicted. Our study provides valuable insights into integrating LLMs with genomic analysis, contributing to the ongoing discussion on their utilization in clinical workflows.

Quantitative PCR for early detection of human cytomegalovirus end-organ disease in immunocompetent host: A retrospective single-center study.

BACKGROUND: Tissue-invasive end-organ disease (EOD) caused by cytomegalovirus (CMV) is less frequently reported in immunocompetent patients compared to immunocompromised patients. In this study, we investigated the association between CMV viremia and CMV end-organ disease in immunocompetent patients. METHODS: Adult patients (≥18 years old) with CMV viremia were screened from January 2010 to June 2022. The primary outcome was the presence of CMV EOD. Risk factors associated with CMV EOD were analyzed, and a receiver operating characteristic curve was plotted to determine the most accurate cutoff value of the CMV titer for the prediction of CMV EOD. RESULTS: Among the 106 immunocompetent patients with CMV viremia, 31 exhibited CMV EOD. Gastrointestinal tract disease was the most common. The log10 value of the CMV titer was significantly associated with the occurrence of CMV EOD in immunocompetent patients with CMV viremia. The optimal cut-off CMV titer for the prediction of CMV EOD was 749 IU/mL. CONCLUSIONS: Our study suggests the potential association between high CMV titers and the development of CMV end-organ diseases and describes the diagnostic performance and utility of quantitative PCR as a surrogate marker for predicting the occurrence of CMV EOD in immunocompetent patients.

Convergent dwarfism consequences of minipigs under independent artificial selections.

BACKGROUND: Currently, diverse minipigs have acquired a common dwarfism phenotype through independent artificial selections. Characterizing the population and genetic diversity in minipigs is important to unveil genetic mechanisms regulating their body sizes and effects of independent artificial selections on those genetic mechanisms. However, full understanding for the genetic mechanisms and phenotypic consequences in minipigs still lag behind. RESULTS: Here, using whole genome sequencing data of 41 pig breeds, including eight minipigs, we identified a large genomic diversity in a minipig population compared to other pig populations in terms of population structure, demographic signatures, and selective signatures. Selective signatures reveal diverse biological mechanisms related to body size in minipigs. We also found evidence for neural development mechanism as a minipig-specific body size regulator. Interestingly, selection signatures within those mechanisms containing neural development are also highly different among minipig breeds. Despite those large genetic variances, PLAG1, CHM, and ESR1 are candidate key genes regulating body size which experience different differentiation directions in different pig populations. CONCLUSIONS: These findings present large variances of genetic structures, demographic signatures, and selective signatures in the minipig population. They also highlight how different artificial selections with large genomic diversity have shaped the convergent dwarfism.

Nanofiber Graft Therapy to Prevent Shoulder Stiffness and Adhesions after Rotator Cuff Tendon Repair: A Comprehensive Review.

Stiffness and adhesions following rotator cuff tears (RCTs) are common complications that negatively affect surgical outcomes and impede healing, thereby increasing the risk of morbidity and failure of surgical interventions. Tissue engineering, particularly through the use of nanofiber scaffolds, has emerged as a promising regenerative medicine strategy to address these complications. This review critically assesses the efficacy and limitations of nanofiber-based methods in promoting rotator cuff (RC) regeneration and managing postrepair stiffness and adhesions. It also discusses the need for a multidisciplinary approach to advance this field and highlights important considerations for future clinical trials.

Epsti1 Regulates the Inflammatory Stage of Early Muscle Regeneration through STAT1-VCP Interaction.

During muscle regeneration, interferon-gamma (IFN-γ) coordinates inflammatory responses critical for activation of quiescent muscle stem cells upon injury via the Janus kinase (JAK) - signal transducer and activator of transcription 1 (STAT1) pathway. Dysregulation of JAK-STAT1 signaling results in impaired muscle regeneration, leading to muscle dysfunction or muscle atrophy. Until now, the underlying molecular mechanism of how JAK-STAT1 signaling resolves during muscle regeneration remains largely elusive. Here, we demonstrate that epithelial-stromal interaction 1 (Epsti1), an interferon response gene, has a crucial role in regulating the IFN-γ-JAK-STAT1 signaling at early stage of muscle regeneration. Epsti1-deficient mice exhibit impaired muscle regeneration with elevated inflammation response. In addition, Epsti1-deficient myoblasts display aberrant interferon responses. Epsti1 interacts with valosin-containing protein (VCP) and mediates the proteasomal degradation of IFN-γ-activated STAT1, likely contributing to dampening STAT1-mediated inflammation. In line with the notion, mice lacking Epsti1 exhibit exacerbated muscle atrophy accompanied by increased inflammatory response in cancer cachexia model. Our study suggests a crucial function of Epsti1 in the resolution of IFN-γ-JAK-STAT1 signaling through interaction with VCP which provides insights into the unexplored mechanism of crosstalk between inflammatory response and muscle regeneration.

PEMF Potentiates Doxorubicin-induced Late G2 Arrest in MDA-MB-231 Breast Cancer Cells.

BACKGROUND/AIM: Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of cancer, including breast cancer. However, the effect of PEMF stimulation on the efficacy of doxorubicin and the underlying mechanisms remain unclear. Thus, this study aimed to investigate the effect of PEMF stimulation on the anticancer activity of doxorubicin in MDA-MB-231 human breast cancer cells. MATERIALS AND METHODS: MDA-MB-231 cells were seeded and allowed to incubate for 48 h. The cells were treated with doxorubicin, cisplatin, 5-fluorouracil, or paclitaxel for 48 h. Subsequently, the cells were stimulated with a 60-min PEMF session thrice a day (with an interval of 4 h between each session) for 24 or 48 h. Cell viability was assessed by trypan blue dye exclusion assay and cell-cycle analysis was analyzed by flow cytometry. Molecular mechanisms involved in late G2 arrest were confirmed by a western blot assay and confocal microscopy. RESULTS: MDA-MB-231 cells treated with a combination of doxorubicin and PEMF had remarkably lower viability than those treated with doxorubicin alone. PEMF stimulation increased doxorubicin-induced cell-cycle arrest in the late G2 phase by suppressing cyclin-dependent kinase 1 (CDK1) activity through the enhancement of myelin transcription factor 1 (MYT1) expression, cell division cycle 25C (CDC25C) phosphorylation, and stratifin (14-3-3σ) expression. PEMF also increased doxorubicin-induced DNA damage by inhibiting DNA topoisomerase II alpha (TOP2A). CONCLUSION: These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.

Case report: Magnetic resonance imaging features with postoperative improvement of atypical cervical glioma characterized by predominant extramedullary distribution in a dog.

Introduction: Intramedullary cord tumors present diagnostic and therapeutic challenges. Furthermore, spinal cord tumors can move across compartments, making antemortem diagnosis difficult, even with advanced imaging. This report presents a rare case of a cranial cervical spinal glioma, confirmed by surgical histopathology, with postoperative improvement in a dog. Case description: A 9-year-old female Maltese dog presented with kyphotic posture, progressive left hemiparesis, and decreased appetite. Neurological examination revealed neck pain and decreased proprioception in the left limbs along with intact deep pain perception. Two days later, the patient developed non-ambulatory tetraparesis. Magnetic resonance imaging (MRI) revealed an ovoid, well-defined mass with homogeneously marked contrast enhancement in the second cervical spinal cord that severely compressed the spinal cord. This mass was heterogeneously hyperintense on T2-weighted images and iso-to-hypointense on T1-weighted images, showing an appearance resembling the "golf-tee" and "dural tail" signs. The MRI findings suggested an intradural extramedullary tumor. Intraoperatively, a well-demarcated mass which was locally adherent to the spinal meninges was removed. Both histopathological and genomic tumor tests were indicative of a glioma. Approximately 2 weeks postoperatively, the patient's neurological signs returned to normal. Conclusion: This case report describes an atypical cervical glioma with complicated MR characteristics in a dog, where MRI helped guide surgical intervention.

Anomalous coherent and dissipative coupling in dual photon-magnon hybrid resonators.

We explored the distinctive behavior of coherent and dissipative photon-magnon coupling (PMC) in dual hybrid resonators, each incorporating an Inverted Split-Ring Resonator (ISRR) paired with a Yttrium Iron Garnet (YIG) film, positioned in close proximity but with varying relative split-gap orientations. These orientations led to notable shifts in the dispersion spectra, characterized by level repulsion and attraction, signaling coherent and dissipative coupling, respectively, in single ISRR/YIG hybrids at certain orientations. Through analytical modeling, we determined that the observed shifts in coupling types are primarily due to the effect of photon-photon (ISRR-ISRR) interactions altering the phase difference between the coupled ISRR and magnon modes. Our findings highlight that precise manipulation of the relative split-gap orientations in the ISRR resonators enables controlled coherent and dissipative coupling within planar PMC systems. This capability opens new avenues for applications in quantum information technologies and quantum materials.

Presurgical Reduction of the Cleft Palate: Serendipitous Benefit of the Stanford Orthodontic Airway Plate Treatment (SOAP) for Infants with Robin Sequence.

OBJECTIVE: Narrowing of the palatal cleft is often observed in infants with Robin sequence (RS) treated with the Stanford Orthodontic Airway Plate treatment (SOAP) even though SOAP is utilized primarily to establish airway patency. The current study quantified dimensional changes of the cleft palate (CP) in infants with RS treated with SOAP. DESIGN: A retrospective chart review. PATIENTS: Infants with RS and CP who completed SOAP and had maxillary arch models at both pre- and post-treatment time points at a single tertiary referral hospital between September 2019 and July 2023. SETTING AND OUTCOME MEASURE: Maxillary arch models were measured and analyzed using Bivariate statistical analysis. RESULTS: Seventeen infants were included in the study. The median age (min, max) was 6.7 weeks (1.1, 21.9) at pre-treatment and 26.6 weeks (18.7, 37.0) at post-treatment. The median Obstructive Apnea Hypopnea Index was 36.2 events/hour (8.1, 103.1) at pre-treatment and 4.1 events/hour (1.9, 8.6) at post-treatment. The pre-treatment width of CP decreased by an average (± standard diviation) of 6.37 mm (± 3.55, p < 0.001) at post-treatment. The ratio of the posterior cleft width to the total maxillary arch width decreased from 40% (± 9.1) at pre-treatment to 22% (± 11) at post-treatment (p < 0.001). CONCLUSION: The dimensions of CP reduced significantly during SOAP in infants with RS and CP treated for their severe upper airway obstruction. The findings highlight a potential benefit of SOAP that may contribute favorably to the palate repair surgery.

Maxillary Bone Necrosis in Post-COVID-19 Patients: Possibility of Medication-Related Osteonecrosis of Jaws (MRONJ) Induced by Tocilizumab.

Medication-related osteonecrosis of the jaws (MRONJ) is a serious condition often linked with antiresorptive, immune modulating, and antiangiogenic drugs, initially associated with bisphosphonates but now including a broader range of medications. Tocilizumab, an interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody used for conditions like rheumatoid arthritis and recently for COVID-19 to reduce IL-6 activity and alleviate symptoms, has raised concerns over its potential to induce MRONJ, particularly in post-COVID-19 patients. A case involving a 36-year-old male who developed tooth mobility and pain in the right maxillary posterior region after COVID-19 treatment with tocilizumab and dexamethasone is highlighted. Despite treatments like antibiotics, the necrosis persisted until more extensive surgery was performed, leading to improvement without recurrence over 2 years. This case emphasizes the need for awareness and research into the risk of MRONJ in patients treated with tocilizumab after COVID-19, underlining the importance for healthcare professionals to recognize and manage this complication.

Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro.

Many cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem-cell derived cardiomyocytes (iPSC-CMs) in a dose-dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze-like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low-intensity magnetic field and on-site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.

Pulsed Electromagnetic Field Enhances Caffeic Acid Phenethyl Ester-induced Death of MCF-7 Breast Cancer Cells.

BACKGROUND/AIM: Caffeic acid phenethyl ester (CAPE) exerts anticancer effects against several cancer types, including breast cancer. Pulsed electromagnetic field (PEMF) improves the efficiency of some chemotherapeutic drugs. In this study, we examined the effects of PEMF stimulation on the anticancer activity of CAPE in MCF-7 breast cancer cells and the underlying signal transduction pathways. MATERIALS AND METHODS: MCF-7 cells were seeded and incubated for 24 h. Each of the drugs (5-fluorouracil, paclitaxel, gefitinib, or CAPE) was added to the cells on day 0. Then, cells were immediately stimulated with a 60-min PEMF session thrice a day (with 4-h interval between sessions) for 1-3 days. Cell death and viability were assessed by flow cytometry and trypan blue dye exclusion assay. Molecular mechanisms involved in cell death were confirmed by western blot assay. RESULTS: Compared with treatment with CAPE alone, co-treatment with CAPE and PEMF more strongly reduced the viability of MCF-7 cells, further increased the percentage of the sub-G1 population, poly (ADP-ribose) polymerase (PARP) cleavage, activation of apoptotic caspases, up-regulation of pro-apoptotic proteins, such as Fas cell surface death receptor (FAS) and BCL2 associated X, apoptosis regulator (BAX), and reduced the expression of anti-apoptotic proteins, such as BCL-2 apoptosis regulator (BCL-2), MCL-1 apoptosis regulator, BCL-2 family member (MCL-1), and survivin. PEMF stimulation also increased CAPE-induced phosphorylation of p53, and inhibition of p53 partially restored the PEMF-reduced viability of CAPE-treated MCF-7 cells. CONCLUSION: PEMF stimulation enhanced CAPE-induced cell death by activating p53, which regulates the expression of apoptosis-related molecules, subsequently activating the caspase-dependent apoptotic pathway in MCF-7 cells, suggesting that PEMF can be utilized as an adjuvant to enhance the effect of CAPE on breast cancer cells.

Microwave-transparent metallic metamaterials for autonomous driving safety.

Maintaining the surface transparency of protective covers using transparent heaters in extreme weather is imperative for enhancing safety in autonomous driving. However, achieving both high transmittance and low sheet resistance, two key performance indicators for transparent heaters, is inherently challenging. Here, inspired by metamaterial design, we report microwave-transparent, low-sheet-resistance heaters for automotive radars. Ultrathin (approximately one ten-thousandth of the wavelength), electrically connected metamaterials on a millimetre-thick dielectric cover provide near-unity transmission at specific frequencies within the W band (75-110 GHz), despite their metal filling ratio exceeding 70 %. These metamaterials yield the desired phase delay to adjust Fabry-Perot resonance at each target frequency. Fabricated microwave-transparent heaters exhibit exceptionally low sheet resistance (0.41 ohm/sq), thereby heating the dielectric cover above 180 °C at a nominal bias of 3 V. Defrosting tests demonstrate their thermal capability to swiftly remove thin ice layers in sub-zero temperatures.

Audiologic Outcomes After Vestibulotomy in Patients With Congenital Absence of the Oval Window.

OBJECTIVE: To examine the clinical features and surgical outcomes in patients with congenital absence of the oval window (CAOW), and to investigate the potential factors that affect audiologic results. STUDY DESIGN: A retrospective chart review. SETTING: A tertiary academic center. PATIENTS AND INTERVENTION: A total of 17 ears among 16 patients were confirmed to have CAOW. Among them, 13 ears underwent vestibulotomy for hearing reconstruction. Clinical parameters associated with the hearing outcomes were analyzed. MAIN OUTCOME MEASURES: A mean air-bone gap (ABG) after 6-month and long-term follow-up was compared with preoperative measurements. RESULTS: Intraoperative findings showed that anomalies of the malleus or incus were observed in 11 ears (64.7%), stapes anomalies were present in all ears (100%), and facial nerve anomalies were present in 10 ears (58.8%). Because of unfavorable facial nerve anomalies, hearing reconstruction was aborted in four cases (23.5%). In the hearing reconstruction group, the mean ABG at 6 months postoperation was significantly reduced after compared with the preoperative value (44.0 ± 8.4 dB versus 58.8 ± 9.1 dB, p = 0.006). After dividing ears into a success subgroup (ABG ≤ 30 dB, seven ears) and non-success subgroup (ABG > 30 dB, six ears), the use of a drill during vestibulotomy was significantly related to a poor hearing outcome (100% versus 16.7%, p = 0.015). The long-term follow-up result (mean, 60 mo) revealed no deterioration compared with the 6-month postoperative result. Five ears (29.4%) underwent revision surgery, and three of them showed ABG improvements. No serious complications were reported. CONCLUSION: Vestibulotomy is an effective and safe option for hearing restoration in patients with CAOW, particularly when the use of a drill is not required. The long-term audiologic outcome is also reliable.

Prevalence and risk factors of postoperative laryngeal edema in patients undergoing neck dissection.

PURPOSE: Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated. METHODS: A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343). RESULTS: PLE occurred in 29.4% [95%CI 24.4-34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166-7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160-20.529]) were significant risk factors for PLE. CONCLUSIONS: PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.

Diagnostic value of ultrasonography in identifying unilateral ovarian luteoma in a dog.

Background: Diagnosing ovarian tumors in dogs can be challenging since the clinical symptoms are often generic. The present case report underscores a rare case in which a suspected unilateral ovarian tumor in a dog was initially identified using ultrasonography and subsequently confirmed to be a luteoma through postoperative histopathology. Case Description: An 8-year and 6-month-old female Maltese dog presented with a 10-day history of vulvovaginal bleeding, hematuria, and decreased appetite. Physical examination revealed only vaginal bleeding, with no other abnormalities. Laboratory examinations showed no abnormalities, while abdominal radiography revealed the presence of cystic calculi as the sole abnormality. Abdominal ultrasound revealed an enlarged right ovary with regular contour and echogenicity, featuring unusual cystic components surrounding the right ovarian parenchyma. Furthermore, irregular thickening with multiple cystic lesions was observed in the endometrial wall of the bilateral uterine horns, indicative of cystic endometrial hyperplasia. Ultrasonographic findings suggested unilateral right ovarian disease. During ovariohysterectomy, the right ovary was slightly larger than the left ovary and adhered to the surrounding mesenteric fat layer and right pancreatic parenchyma. Histopathological examination confirmed the diagnosis of luteoma in the right ovary. Three days after surgery, the patient's clinical signs exhibited complete improvement, with the return of normal appetite. Conclusion: This case report highlights a rare diagnosis of unilateral ovarian luteoma based on mild ultrasonographic abnormalities, which was ultimately confirmed on histopathological examination.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

Assessing the Utility of Large Language Models for Phenotype-Driven Gene Prioritization in Rare Genetic Disorder Diagnosis.

Phenotype-driven gene prioritization is a critical process in the diagnosis of rare genetic disorders for identifying and ranking potential disease-causing genes based on observed physical traits or phenotypes. While traditional approaches rely on curated knowledge graphs with phenotype-gene relations, recent advancements in large language models have opened doors to the potential of AI predictions through extensive training on diverse corpora and complex models. This study conducted a comprehensive evaluation of five large language models, including two Generative Pre-trained Transformers series, and three Llama2 series, assessing their performance across three key metrics: task completeness, gene prediction accuracy, and adherence to required output structures. Various experiments explored combinations of models, prompts, input types, and task difficulty levels. Our findings reveal that even the best-performing LLM, GPT-4, achieved an accuracy of 16.0%, which still lags behind traditional bioinformatics tools. Prediction accuracy increased with the parameter/model size. A similar increasing trend was observed for the task completion rate, with complicated prompts more likely to increase task completeness in models smaller than GPT-4. However, complicated prompts are more likely to decrease the structure compliance rate, but no prompt effects on GPT-4. Compared to HPO term-based input, LLM was also able to achieve better than random prediction accuracy by taking free-text input, but slightly lower than with the HPO input. Bias analysis showed that certain genes, such as MECP2, CDKL5, and SCN1A, are more likely to be top-ranked, potentially explaining the variances observed across different datasets. This study provides valuable insights into the integration of LLMs within genomic analysis, contributing to the ongoing discussion on the utilization of advanced LLMs in clinical workflows.