bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal effects of blood cells on breast cancer: Evidence from bidirectional Mendelian randomization combined with meta-analysis
Authors: Liu Qi , Jia Wei , Zhang Yi , Lu Jun , Luo Qingbin , Yang Lin , Wan Dongdong
Published: February 2025

Recent studies suggest blood cells influence breast cancer, but no Mendelian randomization (MR) studies have confirmed a causal relationship between specific blood cell phenotypes and breast cancer. MR analysis of blood cell phenotypes used breast cancer data from Finngen R11, UKB, and open genome-wide association study databases. Meta-analyzed inverse variance weighted results were adjusted for multiple comparisons. The reverse relationship was also explored. MR and meta-analysis identified significant associations between specific blood cell phenotypes and breast cancer: neutrophil perturbation response (side fluorescence standard deviation of neutrophil 4 in response to alhydrogel perturbation): odds ratio (OR) = 0.967, P = .0009; neutrophil perturbation response (forward scatter median of neutrophil 4 in response to Pam3CSK4 perturbation): OR = 0.972, P = .031; white blood cell perturbation response (side scatter coefficient of variation of WBC 2 in response to nigericin perturbation): OR = 0.972, P = .031; white blood cell perturbation response (forward scatter coefficient of variation of WBC in response to Pam3CSK4 perturbation): OR = 1.042, P = 8.15 × 10−5. And there was no reverse result. Neutrophil perturbation response (side fluorescence standard deviation of neutrophil 4 in response to alhydrogel perturbation) and white blood cell perturbation response (side scatter coefficient of variation of WBC 2 in response to nigericin perturbation) are protective factors for breast cancer. Conversely, neutrophil perturbation response (forward scatter median of neutrophil 4 in response to Pam3CSK4 perturbation) and white blood cell perturbation response (forward scatter coefficient of variation of WBC in response to Pam3CSK4 perturbation) are risk factors for breast cancer.
Beneficial effects and possible mechanism of intake coffee for COVID-19: A meta-analysis and molecular docking
Authors: Fan Yong-Zheng , Duan Yun-Li , Zhang An-Na , Wang Yu
Published: February 2025

Background:

To systematically evaluate the effectiveness of regular coffee intake in the prevention or treatment of COVID-19 infection, and to explore its possible mechanism of action using computer molecular docking technology.

Methods:

We searched for relevant ClinicalTrials.gov, Cochrane Library, PubMed, Web of Science, Embase, and China Biomedicine, Wanfang, CNKI, VIP databases to summarize studies on the effectiveness of coffee in preventing or treating COVID-19. The search period lasted until August 1, 2024. The 2 researchers screened the literature and data using Rev Man 5.4 software (the Cochrane Collaboration, 2020) for data analysis and used Schrodinger 2018-1 software to explore possible mechanisms of action.

Results:

A total 5 studies with 39,290 participants were included. The results showed that compared with the control group that drank less or no coffee, the experimental group that drank more than 1 cup of coffee per day had significantly higher benefit rates (RD = 0.17, 95% confidence intervals [CI] = 0.08–0.27, P = .0005), including lower infection rates and improved recovery rates from COVID-19 (RD = 0.24, 95% CI = 0.13–0.35), P < .0001). Molecular docking showed that CGA and caffeine present in coffee could combine with key amino acid residues of ACE2 or 3CL proteins to form hydrogen bonds.

Conclusions:

Regular consumption of coffee may have certain preventive or therapeutic effects on COVID-19, and the mechanism of action may be that CGA or/caffeine in coffee may be related to the formation of hydrogen bonds by key amino acid residues such as ARG273/HIE345 of ACE2 and CYS145 of 3CL. Owing to the limited number and quality of the included studies, the effect evaluation needs to be further confirmed using clinical randomized controlled trials. The exact mechanism of action requires further verification at the molecular level, both inside and outside cells.
Primary cardiac angiosarcoma: A clinical report of 1 case and review of the literature
Authors: Sun Jiubo , Li Jing , Wang Xiaofei , Huo Xiaoguang , Xu Wenzhe , Li Fei
Published: February 2025

Rationale:

Primary cardiac angiosarcoma is very rare with a poor prognosis, and there is no recognized guideline for its diagnosis and treatment. Currently, there is no standardized adjuvant chemotherapy regimen following radical surgery for cardiac angiosarcoma. To date, the literature lacks reports on the use of albumin-bound paclitaxel as an adjuvant chemotherapy agent in this context. This case report aims to document and evaluate the imaging characteristics of the disease and the efficacy of albumin-bound paclitaxel as adjuvant chemotherapy, thereby providing valuable insights for clinical diagnosis and treatment.

Patient concerns:

We report a 70-year-old patient with right atrial angiosarcoma, who presented with atrial fibrillation as the initial symptom.

Diagnoses:

Transesophageal echocardiography, chest computed tomography, and cardiac magnetic resonance imaging showed a right atrial mass.

Interventions:

After radical resection, the patient was given 4 cycles of albumin-bound paclitaxel adjuvant chemotherapy.

Outcomes:

Multiple metastases occurred in a short period of time, and the patient died 13 months after surgery. Surgical resection is the most important treatment for cardiac angiosarcoma, and the optimal adjuvant therapy needs to be further studied.

Lessons:

The limitation of this case report is its reliance on a single case, resulting in a limited sample size. To comprehensively characterize cardiac angiosarcoma and evaluate the efficacy of albumin-bound paclitaxel chemotherapy, future studies should collect additional cases and conduct long-term follow-up.
The long-term impact of the covid-19 pandemic on patients with obsessive–compulsive disorder
Authors: Uçar Bostan Büşra , Aksoy Poyraz Cana , Kara Esen Beril , Usta Sağlam Nazife Gamze
Published: February 2025

We investigated how patients with obsessive–compulsive disorder (OCD) were affected by coronavirus disease of 2019 (COVID-19)-related stress over the long term compared to healthy individuals. We explored how the pandemic affected changes in obsessive–compulsive symptoms and their contributing factors. The study included 100 patients with OCD and 100 sex-matched healthy controls whose sociodemographic and clinical information were gathered. Participants in the study were recruited between December 2021 and May 2022 from individuals attending to the outpatient clinics of the University Department of Psychiatry. The Depression Anxiety Stress Scale-21, Perceptions and Attitudes Towards COVID-19 Questionnaire, COVID-19 Compliance with Prevention Measures Scale, and COVID-19 Stress Scale were used in this study. Patients were assessed using the Yale-Brown Obsession Compulsion Scale based on their conditions before and during the pandemic. Patients with OCD perceived COVID-19 disease as more dangerous and contagious (respectively P = .01, P = .01) compared to the controls. Fifty percent of the patients with OCD experienced an increase in symptoms. Disease severity was increased in mild and moderate OCD, while no significant change was found in severe OCD. Perceiving COVID-19 disease as more dangerous (P = .031), COVID-19-related traumatic stress (P = .013), compulsive control (P = .022), xenophobia (P = .005), and COVID-19-related thoughts (P = .008) were more frequent in OCD patients with clinical worsening. In regression analysis, younger age (OR: 0.95, 95% CI (0.91–0.99)) and higher levels of COVID-19-related stress (OR: 1.03 95% CI (1.01–1.05)) are associated with worsening OCD symptoms. Patients with OCD were adversely affected by the COVID-19 pandemic. Close monitoring of patients with OCD during the pandemic is recommended.
Krill oil for knee osteoarthritis: A meta-analysis of randomized controlled trials
Authors: Meng Jiahao , Wang Xuanyu , Li Yinghui , Xiang Yuqing , Wu Yumei , Xiong Yilin , Liu Pan , Gao Shuguang
Published: February 2025

Background:

Knee osteoarthritis, a prevalent musculoskeletal disorder, significantly impacts global health and quality of life. Unfortunately, there is no disease modifying osteoarthritis drugs until now. Krill oil is being explored as a potential alternative, however its efficacy in managing knee symptoms remains unclear. Therefore, the meta-analysis of krill oil in knee osteoarthritis would be interesting and useful.

Methods:

We conducted a systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases from their inception through November 28, 2024, employing predefined search terms, including “krill oil” and “knee osteoarthritis.” We included all relevant randomized controlled trials to ensure a comprehensive analysis. Visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of pain, stiffness and function were served as primary outcomes. Moreover, blood markers and adverse events were also included.

Results:

Five randomized controlled trials involving 730 participants were included. Relative to the usual care group, the krill oil group demonstrated no significant improvement in knee osteoarthritis as measured by visual analog scale; however, it exhibited significant benefits in terms of pain (standardized mean difference [SMD] −0.60; 95% confidence interval [CI] −0.99 to −0.21), stiffness (SMD −0.59; 95%CI −1.04 to −0.14), and functional outcomes (SMD −0.68; 95% CI −1.09 to −0.27) based on WOMAC assessments. Analysis of blood markers also revealed no significant effects of krill oil group compared to the usual care group. Moreover, adverse events in the krill oil group and usual care group also showed no statistical difference. The safety profiles were similar between the 2 groups.

Conclusion:

Krill oil presents as a promising safe therapeutic option for knee osteoarthritis; however, its efficacy in pain relief requires further investigation.
DNA methyltransferase 3A: A prognostic biomarker and potential target for immunotherapy in gastric cancer
Authors: Wei Zijie , Kou Ziqian , Luo Yun , Cheng Yu
Published: February 2025

DNA methyltransferase 3A (DNMT3A) has been associated with the occurrence or progression of various tumors, including gastric cancer. However, the role of DNMT3A in the efficacy of immune-cell infiltration in the tumor microenvironment and immunotherapy in gastric cancer remains less explored. DNMT3A expression level was analyzed using TIMER 2.0, Sangerbox 3.0, and The Cancer Genome Atlas database and further verified by immunohistochemical staining and RT-qPCR. The UALCAN, chi-square test, and Kaplan–Meier plotter databases were performed to assess the correlation of DNMT3A with clinicopathological characteristics and prognosis. The GeneMANIA database, STRING database, and R package were used to construct a DNMT3A co-expression gene network. Gene set enrichment analysis was used to identify the signaling pathways related to DNMT3A expression. The correlations between DNMT3A and cancer immune infiltrates were investigated using TIMER 2.0, Sangerbox 3.0, Kaplan–Meier Plotter, R package, and TISIDB databases. The TISIDB database and R package were used to construct the correlation between DNMT3A and immunomodulators and Immune cell Proportion Score. The association of DNMT3A expression with tumor mutational burden (TMB), microsatellite instability, and tumor dryness was evaluated using the TMB function of the R package, TIMER 2.0. Finally, the biological function of DNMT3A in gastric cancer cells was further assessed by CCK-8, cloning formation, and transwell assay. DNMT3A expression was remarkably upregulated in gastric cancer. The high expression of DNMT3A was associated with poor clinical features and poor survival in patients with gastric cancer. Moreover, gene set enrichment analyses showed that DNMT3A and its related genes were involved in various pathways that promoted cancer occurrence and progression by influencing the tumor microenvironment. Finally, DNMT3A was significantly related to tumor-infiltrating immune cells, immunomodulators, TMB, microsatellite instability, and immune checkpoints in gastric cancer. Moreover, knockdown of DNMT3A reduced the proliferation and migration of gastric cancer cells. Our findings highlight the potential of DNMT3A as a prognosis biomarker and an immunotherapeutic target for gastric cancer.
Examination of the frequency and localization of sigmoid canal with CBCT: A retrospective study
Authors: Kaya Menduh Sercan , Dogan Mehmet Emin , Kotanli Sedef
Published: February 2025

Recently, a variational canal starting from the sigmoid notch and extending in the ramus has been reported. The aim of this study was not only to investigate the presence and localization of the sigmoid canal (SC) between the sexes, which has not been studied before, but also to define the morphometric characteristics of the SC. The possible complications that this anatomical variation may cause are also being discussed. Between 2022 and 2024, a total of 546 cone beam computed tomography images obtained in sagittal, coronal, and horizontal planes were retrospectively analyzed. The presence, localization, and morphometric characteristics of the SCs were recorded and evaluated using statistical analysis software. The presence of SC was observed in 5.5% of the images and it was determined that 4.0% of these canals were unilateral and 1.5% were bilateral. The rate of right SC was 3.3% and the rate of left SC was 3.7%. When morphometric evaluation is made, the average value of the length of the SC is 8.0 mm, with a minimum value of 3.1 mm and a maximum value of 13.9 mm. Knowledge of the SC will prevent possible complications in surgical procedures, provide a more accurate diagnosis at the diagnostic stage and ensure that the treatment plan is created appropriately. More studies are needed on this subject.
Clinical study to evaluate the efficacy and safety of home-used LED and IRED mask for crow’s feet: A multi-center, randomized, double-blind, sham-controlled study
Authors: Park Sang Hyun , Park Seong Oh , Jung Jae-A
Published: February 2025

Background:

As the elderly population continues to grow, the demand for antiaging products is increasing concurrently. On our face, wrinkles begin to form first around the eyes, where the skin is the thinnest. Previous studies have suggested that irradiating the skin with light-emitting diode (LED)/infrared emitting diode (IRED) light at 600 to 660 nm/800 to 860 nm, stimulates the cells of the dermis and epidermal tissue and is effective in wrinkle improvement and antiaging. Therefore, we aimed to evaluate the efficacy and safety of low-level light therapy masks.

Materials and methods:

A randomized, sham device-controlled, double-blind clinical trial was conducted at 2 institutions. Sixty Asian descent individuals between the ages of 30 and 65 years who showed type II to V skin type on the Fitzpatrick scale were included. Among participants with a score of 2 to 4 on the crow’s feet grading scale (CFGS) at rest (without expression), those who sought temporary improvement in both crow’s feet were selected. The participants were categorized into 2 groups: the experimental group, which used a device with a combination of 630 nm LED (max 10 mW/cm3) and 850 nm IRED (max 10 mW/cm3), and the control group, which used the sham device. Efficacy evaluation included various evaluations, including the CFGS as rated by independent raters, CFGS scores assigned by investigators, and the Global Aesthetic Improvement Scale evaluation by both investigators and the participants.

Results:

After using the LED mask for 16 weeks, the CFGS score of the independent raters and investigators showed significant differences at 8, 12, and 16 weeks. In addition, considering the success criteria of this study, a comparison of independent raters showed an improvement rate of ≥69.2% (full analysis set [FAS]: 86.2%, per-protocol set [PPS]: 89.3%) and a difference of ≥49.2% from the control group (FAS: 69.5%, PPS: 72.6%). The change in scores from the baseline showed significant differences between the test group and the control groups at 8, 12, and 16 weeks for both independent raters and investigators.

Conclusion:

LED and IRED phototherapies at 630 nm and 850 nm, respectively, are effective, safe, well-tolerated, and painless treatment for skin rejuvenation.
High glycemic variability serves as an independent risk factor for postoperative infection-related complications in patients undergoing radical surgery for gastric, colon, and rectal cancer
Authors: Yang Zhensong , Jiang Fangjie , Jian Mi , Liu Yang , Zhang Yifei , Zhang Zhenbin , Yao Zengwu , Zhou Baocai , Chen Cheng , Li Miaomiao , Jiang Lixin
Published: February 2025

Patients with gastrointestinal surgery have a higher incidence of infection-related complications than the rest of those who undergo clean cut surgery. It can lead to a worse prognosis for patients. This study aimed to assess the association between glycemic variability (GV) and postoperative infection-related complications of gastrointestinal cancer patients. A total of 438 patients were included in this study. Using univariate and multivariate regression analyses, the risk factors for postoperative complications were determined. And nomogram prediction models were constructed through machine learning. The performance of the nomogram was assessed with respect to the calibration curves. Univariate and multivariate regression analysis showed that high GV on post operation day (POD)1 (P < .001), high leukocytes on POD4 (P = .003 < .01) and alcohol consumption (P = .005 < .01) were independent risk factors for postoperative infection-related complications in patients with gastrointestinal cancers. The area under the curve (AUC) showed that these 3 prediction models established through logistic regression (AUC = 0.81), XGBoost (AUC = 0.82) and random forest (AUC = 0.78) all performed well. Our study confirmed that higher GV on POD1 were independent risk factors for postoperative infection-related complications within 30 days of surgery in patients with gastrointestinal cancers. And the nomogram prediction model confirmed its capable for predicting infection-related complications.
Evolving strategies for osteoporosis management in postmenopausal women: From tradition to innovation
Authors: Akbar Anum , Zaheer Amna , Kharal Manahil Mansha , Komel Aqsa , Khan Muhammad Hamza , Ahsan Areeba , Singh Achit Kumar
Published: February 2025

Osteoporosis is a chronic condition primarily affecting postmenopausal women, significantly impacting their well-being and quality of life. Traditional treatment approaches include medications, vitamins, and exercise, but there is a growing interest in alternative therapies that enhance bone health. This review was conducted by searching multiple databases, including PubMed, Medline, and Google Scholar, for studies related to osteoporosis treatment. Articles focusing on both traditional therapies such as bisphosphonates, calcium, and vitamin D supplementation, and newer advancements like vibration therapy and bone-building devices such as Osteoboost were included. Traditional treatments, such as vitamin supplementation, exercise, and bisphosphonates, remain foundational in osteoporosis management, helping to maintain bone density and reduce fracture risks. Recent developments, including vibration therapy and Osteoboost, show promising results in bone regeneration without the use of medication. While traditional therapies continue to play an essential role, advancements like vibration therapy present novel alternatives for managing osteoporosis. Further research is necessary to optimize these approaches, ensuring they maximize benefits while minimizing risks, ultimately improving patient outcomes and quality of life.
Estimated pulse wave velocity is associated with all-cause and cardiovascular mortality in individuals with stroke: A national-based prospective cohort study
Authors: Li Jiazheng , Jiang Cheng , Ma Jialiang , Bai Feng , Yang Xulong , Zou Qi , Chang Peng
Published: February 2025

Extensive evidence underscores the potential of estimated pulse wave velocity (ePWV) as a robust tool for predicting disease prevalence and mortality. However, its comparative effectiveness in forecasting all-cause and cardiovascular disease (CVD) mortality, particularly among stroke populations, remains inadequately characterized in relation to the traditional Framingham Risk Score (FRS) model. This prospective study included 1202 individuals with stroke from the National Health and Nutrition Examination Survey conducted between 1999 and 2014, with comprehensive follow-up data. Survey-weighted Cox regression models were employed to examine the association between ePWV and the risks of all-cause and CVD mortality. Subgroup analyses were performed to evaluate the stability of ePWV in predicting these outcomes. A generalized additive model was utilized to explore the dose–response relationship between ePWV and mortality risk. Receiver operating characteristic curves were then used to assess and compare the prognostic capabilities of ePWV and FRS models for 10-year all-cause and CVD mortality. After adjustment for relevant covariates, each 1 m/s increase in ePWV was associated with a 44% and 65% increase in all-cause and CVD mortality, respectively. ePWV demonstrated consistent prognostic performance across the majority of stroke subpopulations. Notably, ePWV exhibited a nonlinear relationship with all-cause mortality (P for nonlinearity = .045) while maintaining a linear association with CVD mortality (P for nonlinearity = .293). Furthermore, ePWV outperformed the FRS model in predicting 10-year all-cause (Integrated Discrimination Improvement = 0.061, 95% confidence interval: 0.031–0.095, P = .007) and CVD mortality (95% confidence interval: 0.005–0.083, P = .02). ePWV is an independent risk factor for both all-cause and CVD mortality in individuals with stroke, demonstrating superior predictive value compared to the traditional FRS model for forecasting these outcomes.
Dietary factors and the risk of gastric and colorectal cancers: A Mendelian randomization study
Authors: Zhang Yunda , Xia Haiqun , Yang Shengfei , Yu Weixuan , Liu Ming , Li Dongwei
Published: February 2025

Dietary factors can significantly affect the development of gastric and colorectal cancers; however, observational findings on the impact of micronutrients and macronutrients on the risk of gastric and colorectal cancers are inconsistent. It is crucial to clarify these relationships to create nutritional recommendations for cancer prevention. A two-sample Mendelian randomization investigation was performed to examine the impact of circulating levels of 15 micronutrients (such as vitamin A, folate, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, β-carotene, calcium, copper, iron, magnesium, phosphorus, selenium, and zinc), along with adjusted relative macronutrient intake (including protein, carbohydrate, sugar, and fat), on the risk of gastric and colorectal cancers. Genetically predicted relative protein intake is significantly associated with the risk of colorectal cancer (odds ratio [OR] 95% confidence interval [CI] = 0.41 [0.24, 0.69]; P = .0007). Evidence suggests that genetically predicted macronutrients, such as carbohydrate (OR 95% CI = 1.88 [1.13, 3.14]; P = .0154), and micronutrients, such as vitamin C (OR 95% CI = 0.81 [0.69–0.94]; P = .008) and vitamin B12 (OR 95% CI = 1.16 [1.04, 1.28]; P = .006), may also influence the risk of colorectal cancer. Evidence suggests that intake of sugar (OR 95% CI = 0.47 [0.24, 0.90]; P = .02), and vitamin C (OR 95% CI = 0.78 [0.62, 0.99]; P = .04) may influence the risk of gastric cancer. However, no significant associations were observed between other nutrients and gastrointestinal malignancy. Taken together, these findings suggest that the intake of protein, carbohydrate, sugar, vitamin C, and vitamin B12 may influence the risk of gastric and colorectal cancers. However, further in-depth studies are needed to confirm this.
Maternal knowledge of pediatric first aid in Riyadh: Addressing gaps for improved child safety and women’s health outcomes
Authors: Alwasedi Afnan Mohammed , Al-Wathinani Ahmed M. , Gómez-Salgado Juan , Abahussain Mohammed A. , Alnajada Asem , Goniewicz Krzysztof
Published: February 2025

Childhood injuries are a major cause of morbidity and mortality worldwide, with mothers often being the first responders in such emergencies. In Saudi Arabia, despite high educational attainment, maternal preparedness for pediatric first aid remains underexplored. This study aims to evaluate maternal knowledge, attitudes, and practices (KAP) concerning pediatric first aid in Riyadh, with a focus on identifying key gaps and informing interventions in line with Saudi Arabia’s Vision 2030. This descriptive cross-sectional study surveyed 385 mothers residing in Riyadh between May and September 2023. Data were collected through a structured and validated questionnaire available in Arabic and English, distributed via social media platforms. The questionnaire assessed socio-demographic characteristics, knowledge, attitudes, and practices regarding pediatric first aid. Statistical analysis was conducted using SPSS version 23, with descriptive statistics and non-parametric tests (Mann–Whitney U and Kruskal–Wallis) employed to analyze group differences. The reliability of the instruments was measured using Cronbach’s alpha (α = 0.867). The majority of mothers (69.2%) were aged between 20 and 40 years, and 66.1% held a university degree. While 97.4% of the respondents reported being aware of first aid, significant gaps in knowledge were observed. Although 76.8% of the participants knew how to apply pressure to a bleeding wound, only 42.3% correctly identified how to preserve a lost tooth, and just 12.3% knew the appropriate response to seizures. Mothers with formal first aid training had significantly higher knowledge scores (P < .01), and education level was a significant predictor of better knowledge (P < .05). Social media was the most frequently cited source of information (37.6%), followed by first aid training courses (27.4%). Despite high awareness, this study identifies substantial gaps in maternal knowledge of first aid for pediatric emergencies, particularly in managing specific situations such as seizures and dental injuries. These findings highlight the urgent need for structured first aid training programs tailored to mothers in Riyadh. Incorporating first aid education into Saudi Arabia’s public health initiatives, particularly Vision 2030, could significantly improve maternal preparedness and enhance child safety.
Unique Presentation of Autoinflammatory Disease-like Symptoms and Development of Leukemic Cell Lysis Pneumopathy in Childhood KMT2A::LASP1-positive Acute Monocytic Leukemia
Authors: Kim Hyunho , Akahane Koshi , Tamai Minori , Kasai Shin , Kobayashi Anna , Goto Miwa , Goi Kumiko , Inukai Takeshi
Published: February 2025

In the literature, long-term autoinflammatory disease (AID)-like symptoms are extremely rare in childhood acute leukemia cases. Here, we report a 14-month-old girl with KMT2A::LASP1-positive acute monocytic leukemia diagnosed after a 7-month course of AID-like symptoms. KMT2A::LASP1 fusion was retrospectively detected in her bone marrow at the initial presentation of AID-like symptoms, suggesting the involvement of leukemia cells in her AID-like symptoms. Immediately after starting chemotherapy, the patient sequentially developed leukemic cell lysis pneumopathy (LCLP), which was successfully overcome by the continuation of chemotherapy under intensive respiratory support, thus suggesting a possible association of her AID-like symptoms with the development of LCLP.
Ovarian Stem Cells: Will the Dream of Neo-Folliculogenesis After Birth Become Real?
Authors: Canosa Stefano , Silvestris Erica , Carosso Andrea Roberto , Ruffa Alessandro , Evangelisti Bernadette , Gennarelli Gianluca , Cormio Gennaro , Loizzi Vera , Rolfo Alessandro , Benedetto Chiara , Revelli Alberto
Published: February 2025

Importance

Ovarian stem cells (OSCs) represent a promising tool in reproductive medicine, particularly for the treatment of premature ovarian failure and fertility preservation.

Objective

Herein, we summarize the main characteristics of adult stem cells, their status, needs, and new challenges in the application in reproductive medicine.

Evidence Acquisition

Clinical studies have shown that OSCs transplantation can restore ovarian function and stimulate neo-folliculogenesis in patients with premature ovarian failure, enabling them to conceive naturally or through in vitro fertilization techniques. Moreover, OSCs gained increasing interest as a chance to preserve fertility in cancer patients undergoing gonadotoxic treatments affecting their fertility, as chemotherapy or radiotherapy.

Results

The recruitment of OSCs from fresh or thawed ovarian fragments coupled with their capability to differentiate in vitro to mature oocytes could provide a novel opportunity to verify their suitability to be expanded in vitro as oocyte like cells.

Conclusions and Relevance

Research into OSCs and their applications in reproductive medicine is still in its infancy, but the results so far are promising and offer new possibilities for patients suffering from premature ovarian failure or cancer.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner will be better able to (1) describe the main characteristics of stem cells and the sources from which they can be isolated; (2) discuss the presence of OSCs in the ovary of adult women and how they can support the process of neo-folliculogenesis; and (3) explain how OSCs may be used as a possible therapeutic strategy for cancer patients or patients at risk of premature ovarian insufficiency.
The Clinical Utility of Measures of Ovarian Reserve
Authors: Baker Katherine M. , FernandezCriado Rodolfo , Eaton Jennifer L. , Mensah Virginia A.
Published: February 2025

Importance

Measures of ovarian reserve, particularly anti-Müllerian hormone, have been increasingly and inaccurately utilized as “fertility tests.” It is important to understand the available measures of ovarian reserve and how to appropriately interpret and integrate their use into clinical practice.

Objective

The objectives of this article are to review the process of reproductive aging, define ovarian reserve, describe the available measures of ovarian reserve, and discuss the clinical utility of these measures.

Evidence Acquisition

A literature search was performed using the electronic database PubMed. Relevant guidelines, systematic reviews, and original research articles investigating ovarian reserve parameters and their clinical utility were reviewed.

Results

The fecundity of women gradually declines with increasing reproductive age as oocyte quantity and quality decline. Ovarian reserve is defined as the quantity of oocytes remaining in the ovary. Ovarian reserve can be measured indirectly with the use of serum blood tests or ultrasound imaging. Measures of ovarian reserve are clinically useful in several circumstances, particularly for use during fertility treatment and cycles of assisted reproductive technology. However, measures of ovarian reserve are poor predictors of reproductive potential and should not be used as “fertility tests.”

Conclusions and Relevance

Measures of ovarian reserve are poor predictors of reproductive potential and should not be used as “fertility tests.” Age remains a stronger predictor of reproductive success than measures of ovarian reserve.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner will be better able to define ovarian reserve, describe the available measures of ovarian reserve, and discuss the clinical utility of measures of ovarian reserve.
Fertility Outcomes Several Years After Urgent Fertility Preservation for Patients With Breast Cancer
Authors: Peigné Maëliss , Mur Pauline , Laup Laëtitia , Hamy Anne-Sophie , Sifer Christophe , Mayeru Anne , Eustache Florence , Sarandi Solmaz , Vinolas Claire , Rakrouki Sophia , Benoit Alexandra , Grynberg Michaël , Sonigo Charlotte
Published: February 2025

(Abstracted from Fertil Steril 2024;122:504–513)

The most common cancer among women in their childbearing years is breast cancer (BC), and many patients who are diagnosed in this period of their lives are not yet finished building their families. In cases such as these, fertility preservation can be undertaken, and patients can potentially be good candidates for pregnancy after completing cancer treatment.
Simulation-Based Mastery Learning Curriculum Development Workbook
Authors: McGaghie William C. , Barsuk Jeffrey H. , Salzman David H.
Published: February 2025

Summary Statement

This Workbook and its Action Plans and Notes aim to equip health professions educators with the information and guidance needed to develop and implement a simulation-based mastery learning curriculum. The Workbook begins with an introductory statement about mastery learning curriculum developers and teachers and also about expected behavior of learners in a mastery context. The Workbook continues with 10 connected sections on simulation-based mastery learning curriculum development: (1) problem identification and needs assessment, (2) targeted needs assessment, (3) goals and objectives, (4) education strategies, (5) learner assessment goals and tools, (6) standard setting, (7) curriculum implementation, (8) feedback and debriefing, (9) unexpected collateral effects, and (10) program evaluation. These sections are modeled after the Thomas and Kern (Curriculum Development for Medical Education: A Six-Step Approach. 4th ed. Baltimore: Johns Hopkins University Press; 2022) steps for curriculum development and add several steps needed to incorporate simulation-based mastery learning goals. Curriculum development is an iterative process and each decision impacts preceding and subsequent steps. In addition, steps often change and evolve as a curriculum is developed and revised. Users are encouraged to record and refine their curriculum development plans as they move, back-and-forth, through the Workbook and Action Plans and Notes. References are provided throughout the document to amplify the text and provide detailed examples of the curriculum development steps and procedures. The intended outcome is a simulation-based mastery learning curriculum plan that can be implemented and used to educate learners to a very high standard of achievement.
Transitive to cyclic dominance in eco-evolutionary dynamics of strategic species
Authors: Roy Sourav , Majhi Soumen , Perc Matjaž , Ghosh Dibakar
Published: February 2025

Eco-evolutionary game dynamics explores the intricate interplay between ecological processes and evolutionary strategies. Here we unveil various transition mechanisms from transitive dominance to cyclic dominance within ecological communities, using evolutionary game theory to model strategic interactions among species. Specifically, we choose a multigame framework that incorporates games that exhibit transitive and cyclic dominance. By integrating appropriate models for transitive dominance and cyclic dominance, and through rigorous numerical simulations and analytical approaches, we explore evolutionary game dynamics under varying conditions. We show that, under specific conditions, communities can change from a linear hierarchy, or transitive dominance, to a cyclical structure, or cyclic dominance, which significantly affects ecosystem community structures. We also show that not only game-independent factors, but also intrinsic game parameters can drive a transition from transitive dominance to cyclic dominance. More precisely, we show how changes in the probability of game selection can lead to this transition. Moreover, we demonstrate that even benefits arising from free space can facilitate the shift from transitive to cyclic dominance. Our study thus explores the mechanisms that drive transitions between these dominance patterns and, in so doing, we underscore the importance of multiple game dynamics for accurately describing the intricacies of natural ecosystems.
Protein folding stability estimation with an explicit consideration of unfolded states
Authors: Lee Heechan , Park Hahnbeom
Published: February 2025

Thermal folding stability is a critical requirement for the vast majority of proteins. Computational methods suggested to date for the absolute folding stability (ΔG) prediction – including those driven from protein structure prediction AIs – show clear limitations on reproducing quantitative experimental values. Here we present IEFFEUM, a deep neural network that jointly estimates ΔGand the equilibrium ensemble of folded and unfolded states represented by their residue-pair distance probability distributions. This joint learning considerably enhances the ΔGprediction accuracy against the scenario where ΔGprediction was learned alone. To improve the model, we further extend the dataset compared to previous related works, which includes the Mega-scale small proteins and disordered proteins for training, as well as wild-type natural proteins with sizes up to 900 residues for thorough validation. We show that IEFFEUM is robust to various protein types and sizes, and can be applied to more general types of mutational effects such as sequence insertions or deletions.
Combing the haystacks: The search for highly pathogenic avian influenza virus using a combined clinical and research-developed testing strategy
Authors: Adams Gordon C. , Devlin Jamie E. , Klontz Erik , Laing Rachel A. , Branda John A. , Chowdhury Navid , Kwon SunYoung , Sabeti Pardis C. , Stachler Elyse , Thiriveedhi Vamsi , Shenoy Erica S. , Lemieux Jacob E , Turbett Sarah E
Published: February 2025

Background

Highly pathogenic H5 avian influenza A has caused sporadic human infections, increasing the risk for potential human-to-human spread. In 2024, the U.S. experienced outbreaks among poultry and cattle, prompting enhanced surveillance.

Objective

To evaluate an H5 testing algorithm in subjects with respiratory symptoms presenting for routine care during low influenza A virus circulation.

Design

Observational study using clinical- and research-developed nucleic acid amplification tests (NAATs) and pooled screening methods.

Setting

Academic medical center in Boston, MA.

Participants

5,400 symptomatic individuals contributing 6,935 respiratory specimens from June 23 to August 28, 2024.

Measurements

Specimens underwent initial respiratory pathogen testing per clinical protocols, which did not routinely include influenza due to low summer-month prevalence. Influenza A-positive specimens were subtyped using a clinical assay for H5 assessment. SARS-CoV-2-negative specimens not tested for influenza were screened in pooled batches. Positive pools were deconvoluted to individual specimens and screened for H5 using quantitative polymerase chain reaction.

Results

Influenza A was detected in 40 of 6,935 specimens (0.6%), comprising 35 of 5,400 unique subjects (0.7%). No H5 infections were identified. Of the 35 influenza-positive individuals, 10 cases (29%) were found through research-specific screening of SARS-CoV-2–negative specimens. No deaths attributed to influenza were recorded.

Limitations

Single center design, convenience sampling, absence of ocular specimens, and minimal sampling in high-risk areas may limit generalizability.

Conclusion

Expanded influenza testing using pooled NAATs successfully identified low-prevalence influenza A and ruled out H5 in this cohort. These data support targeted influenza screening to enhance surveillance for emerging subtypes rather than a broad-based clinical testing strategy for influenza A testing.

Primary Funding Source

Supported by institutional resources and Center for Disease Control and Prevention contracts.
Integrative Epigenomic Landscape of Alzheimer’s Disease Brains Reveals Oligodendrocyte Molecular Perturbations Associated with Tau
Authors: Oatman Stephanie R. , Reddy Joseph S. , Atashgaran Amin , Wang Xue , Min Yuhao , Quicksall Zachary , Vanelderen Floor , Carrasquillo Minerva M. , Liu Chia-Chen , Yamazaki Yu , Nguyen Thuy T. , Heckman Michael , Zhao Na , DeTure Michael , Murray Melissa E. , Bu Guojun , Kanekiyo Takahisa , Dickson Dennis W. , Allen Mariet , Ertekin-Taner Nilüfer
Published: February 2025

Alzheimer’s disease (AD) brains are characterized by neuropathologic and biochemical changes that are highly variable across individuals. Capturing epigenetic factors that associate with this variability can reveal novel biological insights into AD pathophysiology. We conducted an epigenome-wide association study of DNA methylation (DNAm) in 472 AD brains with neuropathologic measures (Braak stage, Thal phase, and cerebral amyloid angiopathy score) and brain biochemical levels of five proteins (APOE, amyloid-β (Aβ)40, Aβ42, tau, and p-tau) core to AD pathogenesis. Using a novel regional methylation (rCpGm) approach, we identified 5,478 significant associations, 99.7% of which were with brain tau biochemical measures. Of the tau-associated rCpGms, 93 had concordant associations in external datasets comprising 1,337 brain samples. Integrative transcriptome-methylome analyses uncovered 535 significant gene expression associations for these 93 rCpGms. Genes with concurrent transcriptome-methylome perturbations were enriched in oligodendrocyte marker genes, including known AD risk genes such asBIN1, myelination genesMYRF, MBPandMAGpreviously implicated in AD, as well as novel genes likeLDB3. We further annotated the top oligodendrocyte genes in an additional 6 brain single cell and 2 bulk transcriptome datasets from AD and two other tauopathies, Pick’s disease and progressive supranuclear palsy (PSP). Our findings support consistent rCpGm and gene expression associations with these tauopathies and tau-related phenotypes in both bulk brain tissue and oligodendrocyte clusters. In summary, we uncover the integrative epigenomic landscape of AD and demonstrate tau-related oligodendrocyte gene perturbations as a common potential pathomechanism across different tauopathies.
Genomic tree scans identify loci underlying adaptive peaks inAntirrhinum
Authors: Richardson Daniel M. , Bradley Desmond , Copsey Lucy , Whibley Annabel , Burrus Monique , Andalo Christophe , Zhu Sihui , Field David L. , Xue Yongbiao , Coen Enrico
Published: February 2025

Species can be considered to occupy different peaks in a fitness landscape, visualised as an undulating surface, with height corresponding to fitness and horizontal coordinates to genotype1. A key evolutionary problem is to understand how populations traverse fitness valleys to reach different peaks. Hypothetical solutions include shifting balance theory2, peak movements due to environmental changes1,3, or peak connectivity in high-dimensional fitness spaces4,5. However, testing hypotheses is not straightforward because identifying loci and epistatic interactions underlying fitness peaks remains challenging6. Here we analyse the genetic architecture of a fitness landscape by studying barrier loci that reduce gene flow between populations. We identify barrier loci in an unbiased way, by scanning the genome for regions with deep-rooted trees with a common topology. Applying this method to populations ofAntirrhinum, we identify seven barrier loci, all of which control flower colour. We propose these loci underlie two peaks in a fitness landscape, the heights and positions of which vary depending on genotype-environment interactions, allowing them to have been accessed without traversing a fitness valley. Our findings provide a model for how reproductive barriers between species can arise through populations taking diverse paths in fitness space.
Overcoming Cisplatin Resistance in TP53-null Colon Cancer Organoids
Authors: Khalili Sana , Heine Paige , Khazan Minou , Banister Carolyn E. , Morrison Sidney E. , Buckhaults Phillip J.
Published: February 2025

Cisplatin chemotherapy of colorectal cancer (CRC) is associated with dose-limiting side effects and the development of drug resistance, resulting in reduced therapeutic effectiveness. The resistant phenotype in colon cancer is primarily due to changes in p53-regulated DNA damage signaling and /or defects in the cellular mismatch-repair pathway. Therefore, enhancing the efficacy of cisplatin chemotherapy remains a significant challenge. In this study, we used a TP53-KO patient-derived colon tumor organoid model to perform a genome-wide CRISPR KO screen in the absence and presence of cisplatin and identified gene knockouts that re-sensitize cisplatin-resistant TP53-KO colon cancer organoids to cisplatin treatment. Knockout of genes in the DNA Repair pathways, including Fanconi Anemia (FA cause re-sensitization of TP53-KO colon cancer cells to cisplatin. Inhibition of genes ERCC6, FANCL, and BRIP1 enhances cisplatin-induced cell death in TP53-KO colon cancer organoids. These findings suggest that targeting these pathways could be an effective approach to overcome chemoresistance of TP53-muatnt colon cancer cells to cisplatin.
Phenotypic similarity of NAD(P)-Malic Enzymes in Tomato: Unveiling Patterns of Convergent and Parallel Evolution
Authors: Martinatto Andrea , Böhm Jonas M. , Bustamante Claudia A. , Pancaldi Francesco , Schranz Eric , Tronconi Marcos A.
Published: February 2025

TheSolanum lycopersicum(tomato) genome encodes seven malic enzymes (MEs): three cytosolic NADP-ME isoforms (SlNADP-ME1, -2, and -3), two plastidic NADP-ME proteins (SlNADP-ME4a and -4b), and two mitochondrial NAD-dependent subunits (SlNAD-ME1 and -2) of a heteromeric enzyme. Except for SlNADP-ME3, which is almost exclusively expressed in the root, all the genes are active in the major tissues of flowering plants (leaf, stem, flower, and root), with SlNADP-ME2 and -4b transcripts accumulating at relative high levels. During the cell expansion and ripening phases of fruit development,SlNADP-ME3and-4bexpression increased in the pericarp and seeds whileSlNADP-ME2remained at a high level. In green fruit,SlNADP-ME3and-4bare down-regulated by ethylene, withSlNAD-ME1and-2being up-regulated. A correlation between SlNADP-ME4b accumulation and NADP-ME activity was observed from the early immature green to the mature green fruit stages, linking this plastidic isoform to starch and lipid biosynthesis.SlNADP-ME1and-4aexpression increase with temperature, suggesting involvement in defense mechanisms and supported bycis-elements composition in their promoters. Interesting, SlNADP-ME3 biochemical properties and its accumulation in seeds is part of an inherited and long-conserved genetic lineage in Angiosperms including Arabidopsis NADP-ME1, involved in normal seed germination. By analyzing the phylogeny and synteny ofSlNAD(P)-MEgenes and determining the biochemical properties of the recombinant proteins, we seek functional similarities to Arabidopsis NAD(P)-ME members. Our findings enhance the understanding of malate metabolism in tomatoes, which could inform strategies to improve fruit quality. Additionally, they prompt a re-evaluation of pre-existing notions regarding the functional orthology of enzymes based on phylogenetic relationships.

SIGNIFICANCE STATEMENT

Enzyme functional orthology among distant plant species cannot be inferred through phylogenetic analysis because of the large independent rearrangements of genomes during evolution. A comprehensive characterization of the tomato NAD(P)-ME family and their comparison with members from an unrelated plant species, such as Arabidopsis, allowed us to evaluate the impact of selective pressures on orthologous genes. This approach reveals that the phenotypic similarity of an entire enzyme family in different species is achieved through diverse evolutionary events such as ancestry, parallelism, and genetic convergence.