bluuebunny/crossref_metadata_2025 huggingface dataset:
Causes of embryo implantation failure: A systematic review and metaanalysis of procedures to increase embryo implantation potential
Authors: Bulletti Francesco M. , Sciorio Romualdo , Conforti Alessandro , De Luca Roberto , Bulletti Carlo , Palagiano Antonio , Berrettini Marco , Scaravelli Giulia , Pierson Roger A.
Published: February 2025

Introduction

Infertility is characterized by the failure to conceive after 12 months of unprotected sexual intercourse. In assisted reproduction technologies (ARTs), in-vitro fertilization and embryo transfer (IVF-ET) are pivotal, with the quality of embryo quality essential for successful implantation.

Objective

This systematic review with meta-analysis aimed to explore the prevalence of embryonic factors involved in the implantation process, concentrating on the following research inquiries: 1) the implantation rates of euploid versus untested embryo transfers; 2) the efficiency of transferring good embryos in different age groups; 3) the impact of age on good embryo transfers to gestational carriers; and 4) the transfer of donated gametes/embryos. The goal is to identify critical points in implantation to improve therapies.

Methods

A comprehensive literature search identified 1474 relevant papers, 11 of which met the inclusion criteria. The information was gathered using a standardized form, and the risk of bias was evaluated. A meta-analysis of subgroups to determine euploid embryo transfer efficiency was conducted to synthesize and explore the results. Furthermore, data extracted from registries document the persistent secondary role of extraembryonic determinants in successful implantation.

Results

The meta-analysis demonstrated that preimplantation genetic testing for aneuploidy (PGT-A) significantly increased the odds of implantation. Age was found to influence extraembryonic factors, with older women experiencing reduced embryo implantation as gestational carriers. However, the overall incidence of extraembryonic factors was low. This review highlights the need to focus on PGT-A, diagnostic hysteroscopy, and endometrial receptivity for improving implantation rates.

Conclusion

Implantation success in ARTs largely depends on embryo euploidy. While achieving three euploid embryos greatly increases success rates, it is challenging in older women. Extraembryonic factors, although present, have a marginal impact. Subsequent studies ought to concentrate on modulating endometrial responses immunologically and developing algorithms to improve the precision of predicting implantation success; as well as the timing of endometrial receptivity and the occurrence of dormant embryo phenomena also warrants further investigation.
A case report of a MODY6 patient coexistence with Charcot-Marie-Toothe 1A syndrome
Authors: Wang Jianyu , Wang Chunhua , Chen Yujie , Qi Shuang , Wang Min
Published: February 2025

Monogenic diabetes, which encompasses neonatal diabetes (NDM), maturity onset diabetes of the young (MODY), and several diabetes-associated syndromes, primarily arises from impaired function or abnormal development of the islets of Langerhans, particularly pancreatic β-cells responsible for insulin secretion. This condition is typically associated with a single pathogenic genetic mutation. Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary demyelinating neuropathy that is caused by a duplication of the PMP22 gene located on chromosome 17. Herein, we report a case of a young Chinese patient with MODY6 harboring a novel mutation (c. 317C>T, p. Ala106Val) in the NEUROD1 gene. Additionally, this patient concurrently presents with CMT1A, which is characterized by a large segmental duplication within the exon of the PMP22 gene and its adjacent regions. Considering the patient’s compromised islet function, we treat him with insulin and oral hypoglycemic agents (metformin, acarbose). This represents the first reported instance of a patient with NEUROD1-MODY coexisting with CMT1A.
Case report: Long-term survival in synchronous double primary malignancies of lung adenocarcinomas and esophageal squamous cell carcinoma treated with definitive chemoradiotherapy and SBRT combined with anti-PD-1
Authors: Zeng Rui , Zhou Xiaoyun , Ou Kexin , Chen Wei , Yang Chen , Wang Ting , Li Yani , Zha Yawen , Li Minying , Zhang Jingjing
Published: February 2025

Background

The occurrence of multiple primary cancers has become common, and the treatment of such patients is very complex, so it is necessary to combine a variety of individualized treatment methods to achieve better treatment results.

Case description

This report describes a patient with double primary tumors of lung and esophageal cancer had more than 36 months survival with non-operation treatment. The patient diagnosed as lung adenocarcinomas (LADC) and esophageal squamous cell carcinoma (ESCC), was treated with albumin-bound paclitaxel, nedaplatin, and anti-programmed death 1 (anti-PD-1). The esophageal lesions achieved complete response (CR) after finishing two courses of induction chemotherapy combined with anti-PD-1 followed by definitive chemoradiotherapy (CRT). Radiation pneumonitis (RP) occurred one month after the completion of CRT. The pneumonia was relieved after dexamethasone and moxifloxacin treatment. Then, the lung lesion was treated with oral chemotherapy followed by stereotactic body radiation therapy (SBRT). As of July 2024, the patient has survived for more than 3 years after the above treatments, and the current efficacy evaluation is CR of esophageal lesions, PR of pulmonary lesions.

Conclusion

The multi-modality approach of systemic therapy combined with localized radiotherapy is an effective treatment in the patients of the double primary malignant tumors of LADC and ESCC. The safety and toxicity of radiotherapy for the thoracic double primary tumors demonstrate acceptability.
Bioactive lipid signaling and lipidomics in macrophage polarization: Impact on inflammation and immune regulation
Authors: Rodríguez Juan P. , Casas Javier , Balboa María A. , Balsinde Jesús
Published: February 2025

Macrophages, crucial innate immune cells, defend against pathogens and resolve inflammation, maintaining tissue balance. They perform phagocytosis, present antigens to T cells, and bond innate and adaptive immunity through various activation states. Classical activation is associated with Th1 responses and interferon γ production, while alternative activation, induced by interleukin 4, is characterized by increased endocytosis, reduced secretion of pro-inflammatory cytokines, and roles in immunoregulation and tissue remodeling. Although these represent opposite extremes observed in vitro, the remarkable plasticity of macrophages allows for a wide spectrum of activation phenotypes that are complex to characterize experimentally. While the application of omics techniques has resulted in significant advances in the characterization of macrophage polarization, lipidomic studies have received lesser attention. Beyond their role as structural components and energy sources, lipids function as signaling molecules that regulate macrophage activation and polarization, thereby shaping immune responses. This work reviews the interaction between lipid signaling and macrophage polarization, exploring how lipid metabolism influences macrophage phenotype and function. These insights offer potential therapeutic strategies for immune-mediated diseases and inflammation-related disorders, including inflammaging.
Gruberi bursitis in rheumatic patients with foot and ankle pain: a retrospective sonographic study
Authors: Todorov Plamen , Mekenyan Lili , Levterova Boryana , Batalov Anastas
Published: February 2025

Introduction

Foot and ankle pain is a common problem in rheumatic patients. One often underrecognized cause of this complaint is Gruberi (or subtalar) bursitis. The Gruberi bursa is a structure that originates from the sinus tarsi and extends over the dorsal talar surface. It reduces the friction of the extensor digitorum longus tendon over the convex contour of the head of the talus. On ultrasound, Gruberi bursitis is characterized by a well-defined fluid collection in the dorsolateral foot, located between the talus and the tendon of the extensor digitorum longus. Our study aimed to determine the frequency of Gruberi bursitis in patients with various rheumatic diseases who presented with foot and ankle pain at our institution and to describe its sonographic features in detail.

Materials and methods

A descriptive, observational, retrospective study was conducted on patients over 18 years old who visited a tertiary university hospital between 1 July 2022 and 31 December 2023. Details regarding the patients’ medical history, age, gender, and primary rheumatic disease were obtained from their medical records. Descriptive statistics were utilized to present the data.

Results

Of the 608 patients examined for foot and ankle pain at our institution during the study period, 78 cases of Gruberi bursitis were identified in 63 patients. The average age of the participants was 61.7 years (range: 25–85 years), and 71% (n = 45) of the participants were women. The sonographic features of Gruberi bursitis included a monocular, anechoic fluid collection typically located between the extensor digitorum longus tendon and the dorsolateral surface of the head of the talus. The mean largest dimension of fluid collections in the oblique plane (from the sinus tarsi and across the dorsal talus) was 16 mm (range: 8–29 mm).

Conclusion

Gruberi bursitis is easily identifiable through ultrasound due to its characteristic location and appearance. In total, we identified this condition in 9% of our rheumatic patients with foot and ankle pain.
Lipid profile in the aqueous humor of diabetic macular edema patients
Authors: Su Mengru , Song Qinglu , Cheng Ruiwen , Zhang Ye , Sun Xinghong , Jiang Feng , Liu Qinghuai
Published: February 2025

Diabetic macular edema (DME) has become a global public health focus due to its increasing prevalence and significant impact on central vision. The aim of this study is to analyze the lipid profile characteristics of aqueous humor in DME patients and to identify differential lipid compounds that may serve as potential biomarkers for the pathogenesis and therapeutic intervention. A non-targeted lipidomics approach based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to analyze the lipid profiles of aqueous humor from patients with diabetic macular edema (DME group, 11 cases), diabetic cataracts (DC group, 14 cases), and age-related cataract (ARC group, 15 cases). The validation of identified lipid compounds through Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) was conducted to examine possible varied lipid markers, setting the parameters of VIP > 1 and p < 0.05. Additionally, correlation network analysis, community classification, and functional enrichment analysis were performed on the differential lipids. 90 lipid compounds were identified, encompassing a range of 13 lipid categories. There were significant differences in the lipid profiles of the aqueous humor in DME. The lipid profile characteristics of aqueous humor in patients with DME are described for the first time. Compared to the control group. Various lipid metabolic disorders, such as sphingolipids particularly ceramide, phospholipids, and triglycerides, are involved in the pathogenesis of DME, and can be further studied as potential diagnostic and therapeutic lipid biomarkers.
A CRISPR-Cas-based recombinase polymerase amplification assay for ultra-sensitive detection of active Trypanosoma brucei evansi infections
Authors: Álvarez-Rodríguez Andrés , Li Zeng , Jin Bo-Kyung , Stijlemans Benoit , Geldhof Peter , Magez Stefan
Published: February 2025

Introduction

Control of Trypanosoma brucei evansi (T. b. evansi) infections remains a significant challenge in managing Surra, a widespread veterinary disease affecting both wild and domestic animals. In the absence of an effective vaccine, accurate diagnosis followed by treatment is crucial for successful disease management. However, existing diagnostic methods often fail to detect active infections, particularly in field conditions. Recent advancements in CRISPR-Cas technology, combined with state-of-the-art isothermal amplification assays, offer a promising solution. This approach has led us to the development of a TevRPA-CRISPR assay, a highly sensitive and specific T. b. evansi diagnostic tool suitable for both laboratory and field settings.

Methods

First, the TevCRISPR-Cas12b cleavage assay was developed and optimized, and its analytical sensitivity was evaluated. Next, this technology was integrated with the TevRPA to create the TevRPA-CRISPR test, with the reaction conditions being optimized and its analytical sensitivity and specificity assessed. Finally, the test’s accuracy in detecting both active and cured T. b. evansi infections was evaluated.

Results

The optimized TevCRISPR-Cas12b cleavage assay demonstrated the ability to detect T. b. evansi target DNA at picomolar concentrations. Integrating TevCRISPR-Cas12b with RPA in Two-Pot and One-Pot TevRPA-CRISPR tests achieved up to a 100-fold increase in analytical sensitivity over RPA alone, detecting attomolar concentrations of T. b. evansi target DNA, while maintaining analytical specificity for T. b. evansi. Both assays exhibited performance comparable to the gold standard TevPCR in experimental mouse infections, validating their effectiveness for detecting active infections and assessing treatment efficacy.

Discussion

The TevRPA-CRISPR tests prove highly effective for diagnosing active infections and assessing treatment efficacy, while being adaptable for both laboratory and field use. Thus, the TevRPA-CRISPR assays emerge as a promising addition to current diagnostic tools, offering efficient and reliable detection of active T. b. evansi infections.
Delirium following mechanical thrombectomy for ischemic stroke – individuals at risk, imaging biomarkers and prognosis
Authors: Hahn Marianne , Brockstedt Lavinia , Gröschel Sonja , Geschke Katharina , Grauhan Nils F. , Brockmann Marc A. , Othman Ahmed E. , Gröschel Klaus , Uphaus Timo
Published: February 2025

Aim

Post-stroke-delirium has been linked to worse outcome in patients with acute cerebrovascular disease; identification of individuals at risk may prevent delirium and thereby improve outcome. We investigate prognosis and factors associated with post-stroke-delirium in patients with large vessel occlusion (LVO) ischemic stroke treated by mechanical thrombectomy (MT).

Methods

747 patients (53.4% female) prospectively enrolled in the Gutenberg-Stroke-Study from May 2018–November 2022 were analyzed with regard to diagnosis of delirium. Group comparison of patient-, stroke- and treatment characteristics as well as computed tomography(CT)-imaging based parameters of cerebral atrophy (global cortical atrophy [GCA], posterior atrophy [Koedam], medial temporal lobe atrophy [MTA] scores) and white matter lesions (Fazekas score) was conducted. Independent predictors of delirium and the association of delirium with functional outcome at 90-day follow-up was investigated by multiple logistic regression analyses.

Results

We report 8.2% of patients (61/747) developing delirium following MT of LVO. Independent predictors were older age (aOR[95%CI] per year: 1.034[1.005–1.065], p = 0.023), male sex (aOR[95%CI]: 2.173[1.182–3.994], p = 0.012), general anesthesia during MT (aOR[95%CI]: 2.455[1.385–4.352], p = 0.002), infectious complications (aOR[95%CI]: 1.845[1.031–3.305], p = 0.039), “other determined” etiology of stroke (aOR[95%CI]: 2.424[1.100–5.345], p = 0.028), and a MTA score exceeding age-specific cut-offs (aOR[95%CI]: 2.126[1.065–4.244], p = 0.033). Delirium was independently associated with worse functional outcome (aOR[95%CI]: 2.902[1.005–8.383], p = 0.049) at 90-day follow-up.

Conclusion

Delirium is independently associated with worse functional outcome after MT of LVO, stressing the importance of screening and preventive measures. Besides conventional risk factors, pathological MTA scores and use of general anesthesia during MT may be easy-to-apply criteria to identify individuals at risk of delirium and implement prevention strategies.
Relationships of hematocrit concentration with dementia from a multiethnic population-based study
Authors: Roh David J. , Liu Minghua , Strobino Kevin , Assuras Stephanie , Guzman Vanessa A. , Levin Bonnie , Spitalnik Steven L. , Rundek Tatjana , Wright Clinton B. , Elkind Mitchell S. V. , Gutierrez Jose
Published: February 2025

Objective

Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship.

Methods

A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships.

Results

We studied 1,207 NOMAS participants (mean age 71 ± 9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01–3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia.

Conclusion

Low hematocrit associated with dementia risk in our diverse population cohort. However, our study limitations in laboratory and neuroimaging timing in addition to clarifying mechanistic underpinnings for our observations necessitates further work to clarify whether anemia can serve as a trackable, preventable/treatable risk factor for dementia.
Cynaroside: a potential therapeutic agent targeting arachidonate 15-lipoxygenase to mitigate cerebral ischemia/reperfusion injury
Authors: Cao Wenpeng , Hu Yufeng , Yu Xingyu , Long Tingting , Sun Baofei , Lei Shan , Xie Peng , Yu Wenfeng
Published: February 2025

Introduction

Due to the anti-inflammatory and antioxidant properties of cynaroside (Cyn), it may be useful in the treatment of cerebral ischemia/reperfusion injury (I/R). This study aims to evaluate the effect of Cyn on cerebral ischemia/reperfusion injury.

Methods

Transient middle cerebral artery occlusion model (tMCAO) and oxygen and glucose deprivation/reperfusion (OGD/R) microglia models were used to evaluate the effect of Cyn. The direct interaction between Cyn and Alox15 was investigated through bioinformatics, molecular docking and biolayer interferometry.

Results

tMCAO mice treated with Cyn show improved neurological deficits, reduced infarct volume and edema, and inhibition of microglial activation. In addition, Cyn inhibited tMCAO-induced Alox15 expression. Cyn significantly reduced the overproduction of the M1 microglia-regulated pro-inflammatory cytokines NLRP3, ASC, and cleaved caspase-1, as well as the overproduction of IL-1β and IL-18, induced by tMCAO or OGD/R. Cyn also inhibits the expression of Tfrc, COX2, and Acsl4 in tMCAO and OGD/R-treated mice and BV-2 cells.

Discussion

These results suggest that Cyn may attenuate cerebral ischemia/reperfusion injury by inhibiting Alox15 to reduce inflammation and reduce ferroptosis. This study reveals the underlying molecular mechanism of Cyn in the treatment of ischemic stroke.
Case report: A study on disease diagnosis and treatment outcome of a case of bilateral malignant solitary fibrous tumor of the kidneys
Authors: Cui Yujie , Li Bingjie , Liang Jinlong , He Liya , Zhang Hongzhen
Published: February 2025

Solitary fibrous tumor (SFT) is widely present in human connective tissues. It is mostly found in the pleura and other extrapleural sites. There is limited literature on malignant SFT in the retroperitoneum. In this study, we retrospectively reviewed the clinical data of a case of bilateral malignant SFT patient admitted to our hospital in May 2021.The patient had a huge tumor load and multiple bone metastases at the first diagnosis. Due to the need for lifelong hemodialysis after double nephrectomy and multiple bone metastases, the patient gave up surgical treatment, underwent drug treatment, and finally survived for 30 months.
Emerging drivers of female bladder cancer: a pathway to precision prevention and treatment
Authors: Zhang Jianbin , Jia Haixia , Han Hui
Published: February 2025

Purpose

Bladder cancer is a public health concern, with smoking and occupational exposure being major risk factors. However, specific risks in women, particularly hormonal, lifestyle, and environmental factors, are underexplored. This study aimed to assess these risk factors in women, focusing on smoking, occupational exposure, recurrent urinary tract infections (UTIs), body mass index (BMI), menopausal status, and family history of cancer.

Materials and methods

This retrospective cohort study included 850 women diagnosed with bladder cancer (2018–2023) and age-matched controls. Data on smoking, occupational exposure, UTIs, BMI, menopausal status, and family history were collected from medical records: multivariate logistic regression and propensity score matching identified independent risk factors. Subgroup analysis explored interactions between menopausal status and other factors.

Results

Smoking (OR = 2.15, p = 0.002), occupational exposure (OR = 1.89, p = 0.007), and recurrent UTIs (OR = 1.72, p = 0.013) were significant risk factors, particularly in post-menopausal women. Menopausal status amplified the effects of smoking and UTIs but was not an independent predictor. BMI and family history showed no significant associations.

Conclusion

Smoking, occupational exposure, and recurrent UTIs are key risk factors for bladder cancer in women, especially post-menopausal women, highlighting the need for targeted prevention strategies.
Laparoscopic radical antegrade modular pancreatosplenectomy vesus laparoscopic distal pancreatosplenectomy for left-sided pancreatic cancer: a systematic review and meta-analysis
Authors: Jiang Xutao , Zhu Yu , Li Jianwei , Li Wei , Zheng Weizong , Xu Caiming , Zhang Guixin
Published: February 2025

Objective

We aimed to compare the perioperative outcomes and postoperative complications of laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) versus laparoscopic distal pancreatosplenectomy (L-DPS) for left-sided pancreatic cancer through a meta-analysis.

Methods

A systematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were performed. Literature searches were conducted in PubMed, Web of Science, Cochrane Library, and Embase for studies published from their inception up to June 14th, 2024.

Results

A total of three retrospective studies involving 242 patients were included in this meta-analysis, with 116 patients in the L-RAMPS group and 126 in the L-DPS group. The meta-analysis results indicated that L-RAMPS was associated with the retrieval of more lymph nodes (MD: 3.06; 95% CI: 2.51 to 3.62, p < 0.00001) and longer operative time (MD: 20.05; 95% CI: 13.97 to 26.12, p < 0.00001) compared to L-DPS for left-sided pancreatic cancer patients. However, no significant differences were observed between the two groups in terms of R0 resection margins, the incidence of pancreatic fistula (Grade B and C), postpancreatectomy hemorrhage, or postoperative complications (Clavien-Dindo Grades II and III).

Conclusions

In patients with left-sided pancreatic cancer, L-RAMPS resulted in the retrieval of more lymph nodes, a longer operative time, and a similar incidence of postoperative complications compared to L-DPS. Larger sample sizes, extended follow-up periods, and well-conducted randomized controlled trials are needed to further validate these findings

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=558977, identifier CRD42024558977.
Predictive model for postoperative pneumonia in patients with esophageal cancer after esophagectomy
Authors: Chen Jing , Xiang Qian , Zheng Xiao-Jia , Jiang Xiao-yan
Published: February 2025

Background

Pneumonia is one of the most common complications after esophagectomy and a risk factor affecting postoperative survival of esophageal cancer. The aim of this study was to identify risk factors and construct a predictive model for postoperative pneumonia (POP) in esophageal cancer.

Methods

This retrospective cohort study included esophageal cancer patients who underwent therapeutic esophagectomy from June 2019 to December 2023. Least absolute shrinkage and selection operator (LASSO) regression was used to screen predictive factors for POP, and a nomogram was constructed based on the selected predictive factors after screening. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).

Results

A total of 667 esophageal cancer patients who underwent esophagectomy were included, of whom 61 (9.1%) developed postoperative pneumonia. After LASSO regression analysis, factors independently associated with POP included mechanical ventilation for more than 2 days (P=0.000) and blood transfusion (P=0.003). A nomogram was constructed based on these independent risk factors. The AUC of the predictive model for POP was 0.839 (95%CI: 0.768-0.911). The internal verification result showed a good discriminative power and the DCA results demonstrated a good predictive value.

Conclusion

The predictive model constructed in this study can predict the risk of POP in patients with esophageal cancer, and may promote early intervention for high-risk patients by clinicians to reduce the incidence of POP.
The optimal time interval between neoadjuvant chemoradiotherapy and surgery for patients with an unfavorable pathological response in locally advanced rectal cancer: a retrospective cohort study
Authors: Wang Litao , Fan Jianyong , Guo Yaqi , Shang Shipeng , Gao Han , Xu Jianfei , Gao Peng , Liu Enrui
Published: February 2025

Background

The focus of this study was to determine the optimal time interval between neoadjuvant chemoradiotherapy (nCRT) and surgery in patients with locally advanced rectal cancer (LARC) who had an unfavorable pathological response, as well as to investigate the correlation between long-term outcomes and the duration of this interval.

Methods

The present study retrospectively analyzed patients with locally advanced rectal cancer who underwent nCRT followed by total mesorectal excision between (TME) January 2018 and September 2021. Patients included in this study had an unfavorable pathological response, confirmed as tumor regression grade (TRG) 2-3. X-tile analysis was subsequently conducted to determine the optimal cut-off value for the time interval between nCRT and surgery. Furthermore, Cox proportional hazards regression analyses were performed to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate long-term survival.

Results

The study cohort comprised of 114 patients (51.35%) in the longer interval group (>8 weeks), while the remaining 108 patients (48.65%) belonged to the shorter interval group (≤8 weeks). Univariable and multivariate Cox proportional hazards regression analyses revealed that a longer interval time was identified as an independent risk factor for overall survival (HR: 2.14, 95% CI: 1.01-4.55, P=0.048) and disease-free survival (HR: 2.03, 95% CI: 1.09-3.77, P=0.025) among these patients. Moreover, patients in the longer interval group exhibited significantly worse OS and DFS compared to those in the shorter interval group (3-year OS: 87.2% vs 68.2%, P=0.001; 3-year DFS: 80.4% vs 62.7%, P=0.003). Furthermore, similar results were observed in subgroup analyses based on different TRG scores.

Conclusions

The surveillance and monitoring should be promptly conducted following nCRT in order to promptly identify patients with an unfavorable pathological response, who would benefit from timely radical surgery within 8 weeks.
Higher Reactive Oxygen Species and cellular aging in oral mucosal cells of young smokers: a comparative analytical study
Authors: Imdad Bushra , Abbas Uzair , Kumar Pershad , Kamran Durre Sameen , Khan Mahtab , Hussain Niaz , Khalid Muhib Ullah
Published: February 2025

Background

Cigarette smoke contains chemical components that cause excessive production of Reactive Oxygen Species (ROS), altering cell physiology and affecting key pathways. This leads to hyperinflammation, DNA damage, and cellular aging, which may cause oral and pulmonary pathologies. Our study aims to investigate the impact of smoking on ROS levels and cellular aging in oral mucosal cells. We compared Reactive oxygen Species and cellular aging between smokers and non-smokers. Secondarily, we also compared the results between young and old smokers.

Methods

Oral swabs were taken from 50 smokers and 50 nonsmokers using a cytology brush. We quantified the reactive oxygen species (ROS) by using oxidized 2'7' dichlorodihydrofluorescein-diacetate (DCFH-DA) dye. To assess cellular aging, mRNA levels of the CYR61 gene-a cellular aging marker, were compared through RT-PCR.

Results

It was found that smokers had a higher percentage of ROS in comparison to non-smokers (p value < 0.001). Additionally, there was an over-expression of the CYR61 gene in smokers as compared to non-smokers (p value = 0.001). Furthermore, when comparing ROS and cellular aging between young smokers and old smokers, it was noted that there was a significantly higher percentage of ROS and up-regulation of mRNA levels of CYR61 gene in young smokers in comparison to old smokers (p value 0.001 and <0.0001 respectively).

Conclusion

It has been observed that smokers have a higher amount of ROS production and cellular aging in their oral mucosal cells. In young smokers, ROS and cellular aging were found to be higher compared to older smokers. This is quite concerning and could be a major factor leading to oral pathologies in smokers.
Exploring fishers’ and fisherfolk’s knowledge and perspectives on water pollution in India: insights from Chilika Lake
Authors: Mengo Elena , Murali Rashmi , Govindan Mini , Hoehn Danja
Published: February 2025

Approximately 16 million fisherfolk in India depend on fisheries for their income, food, and nutritional security. However, aquatic ecosystems across India are heavily polluted, resulting in significant challenges for communities dependent on fisheries. While research on pollution and waste management in India has progressed, local coastal communities’ knowledge and perspectives are still overlooked in environmental decision-making. To address this gap, we focused on the Chilika Lake area, employing a mixed-method approach. We surveyed 161 fishers and conducted focus group discussions (FGDs) in local communities. Our findings indicate that, although fisheries serve as the primary source of livelihood, water pollution adversely affects the quantity and quality of fish, ultimately impacting the household income. Tourism and agriculture, including aquaculture are considered major contributors to aquatic pollution. While fishing-related litter does contribute to pollution in coastal areas, fishers infrequently encounter derelict gear compared to plastic bags and bottles. Solid waste disposal and management issues are widespread, largely due to inadequate waste collection and disposal facilities, resulting in the prevalence of informal waste management systems. The outcomes of the research highlight the need for targeted education and outreach initiatives in coastal areas to address waste mismanagement, promote active participation among local communities to initiatives such as beach clean ups, as well as encourage practices of recycling and reusing materials. Similarly, developing alternative livelihoods can reduce dependency on fisheries and contribute to sustainable development and biodiversity conservation.
Heart Transplantation and Donation After Circulatory Death in Children. A Review of the Technological, Logistical and Ethical Framework
Authors: Kenny Louise Amelia , Armstrong Liz , Berman Marius , Brierley Joe , Crossland David , Dark John , Gardiner Dale , Large Stephen Ralph , Manas Derek , Nassar Mohamed , Shaw David , Simpson Emma
Published: February 2025

Heart transplant for adults following Donation after Circulatory Death (DCD) is well established in many parts of the world, including the United Kingdom (UK). Small child DCD hearts have now been recovered in the UK and internationally utilising novel technologies. Despite these recent advances, extension of this practice to pediatric cardiac transplantation has been slow and difficult despite the severe shortage of donors for children leading to a high number of deaths annually of children waiting for heart transplant. This is in direct contrast with the thriving UK programme of adult DCD heart transplant and pediatric DCD donation for non-cardiac organs. There has been insufficient action in addressing this inequality thus far. Barriers to development of a pediatric cardiac DCD programme are multifaceted: ethical concerns, technological paucity, financial and logistical hurdles. We describe the background, live issues, current developments and how we are driving resources toward a sustainable DCD programme for small children in the UK to provide valuable insights to other countries of the elements and principles at play. This is a call to responsible bodies to take urgent and achievable actions to establish an equitable paediatric DCD cardiac programme for donors, recipients and their families.
Progress in Porcine Kidney Transplantation to Non-Human Primates
Authors: Le Bas-Bernardet Stéphanie , Blancho Gilles
Published: February 2025

Renal xenotransplantation has recently made considerable progress in overcoming the barrier to its use in humans. This progress has been made possible owing to the use of preclinical pig-to-primate models. Overall, renal xenotransplantation has long been associated with lower survival rates than that of porcine hearts (mainly due to its life-sustaining nature). However, the use of the latest strains of genetically modified porcine donors, combined with progress in the control of the anti-porcine immune response and coagulation, has now enabled survival of up to 2 years. Although the pig-to-primate combination has long been considered a perfect reflection of the human situation, it has several limitations, particularly in terms of different natural anti-porcine antibodies. This fact, in association with survival prolongation, which is considered a prerequisite, has led some pioneering teams to cross the line of human application. However, use in humans will remain anecdotal, and further progress in renal xenotransplantation will be difficult to achieve without the use of non-human primates, which will remain complementary, particularly with regard to major innovations that have never been tested in humans.
Effect of Foliar and Root Silicon Supply on Yielding and Gray Mold Incidence in Strawberry Pot Cultivation
Authors: Jarosz Zbigniew , Dzida Katarzyna , Zydlik Zofia , Jarosz Magdalena , Kamiński Szymon , Pitura Karolina
Published: February 2025

Climate changes increase environmental stress pressure, limiting the yields of crops, e.g., strawberries. The green transformation introduced in the European Union, eliminating the use of chemical plant protection agents, requires the development of a technology that will simultaneously mitigate stresses and increase plant yields. The basis of this type of technology may be the targeted application of stabilized orthosilicic acid. The validation of this silicon-based technology was carried out through the pot cultivation of strawberries cv. ‘Falco’ in controlled conditions, compatible with their production. The experiment consisted of the foliar and intra-root (A) application of stabilized orthosilicic acid at concentrations of 0, 240, and 360 g Si·ha−1 (B). A significant increase in the total and marketable yield, the weight of single fruits, and the number of fruits in the silicon-treated variants was noted in this study. The intra-root application of silicon had a more potent effect on the yield performance than foliar feeding. The intra-root application of the tested silicon doses significantly reduced the occurrence of gray mold (Botrytis cinerea) during the fruit harvest period. The application of the tested silicon doses in strawberry cultivation exerted a positive effect on the post-harvest shelf life of the fruits. Higher levels of Lascorbic acid, nitrates (V), and TSS were determined in strawberry fruits treated with stabilized orthosilicic acid. The leaves of plants treated with stabilized orthosilicic acid had lower contents of nitrogen, calcium, magnesium, iron, manganese, zinc, and boron and higher levels of potassium and copper.
The Effect of Arable Land Management on the Reaction of Anaerobic Ammonium Oxidation (Anammox): A Meta-Analysis
Authors: Yang Qiannan , Gong Lingxuan , Zhang Xiaolei , Zhang Guilong , Wang Lili
Published: February 2025

Soil anaerobic ammonium oxidation (anammox) can eliminate reactive nitrogen (N) without generating nitrous oxide and is a key factor in N loss in agricultural ecosystems. Nevertheless, it remains unclear what determines the anammox rate and hzs gene abundance under various cropland management. This study synthesized 100 observations to elucidate the effects of cropland management (including biochar, manure, straw amendment, and N fertilization) on the anammox rate and hzs gene abundance and the governing factors of anammox processes from cropland systems. Our meta-analysis revealed that biochar addition significantly increased the anammox rate by 415%, while manure and N fertilization enhanced the anammox rate by 107% and 60%, respectively. The hzs gene abundance was increased by 240% and 68% under biochar amendment and N fertilization, respectively. Furthermore, biochar increased the anammox rate during the long-term duration (>10 years) at low N application rates and enhanced hzs gene abundance in acidic soil due to increased soil pH. For manure amendment and N fertilization, the anammox rate was significantly promoted in warm, wet climates with lower C/N and higher NH4+-N content. The hzs gene abundance was enhanced in wetter environments (high MAP and aridity index) combined with higher NH4+-N content. This study highlights that alkaline, humid, warm environments, lower C/N, and higher NH4+-N play important roles in determining anammox rate and related bacterial activity. This study provides a new insight into understanding and potentially managing the effects of anammox in cropland cultivation.
Non-Targeted Metabolomics Reveals Tobacco Metabolites Associated with Roasted Tobacco Quality Under Organic Substitution
Authors: Tian Feng , Zhang Li , Niu Lina , Fan Xinglong , Han Yongliang , Liu Yuanshang , Qian Jiancai , Huang Shihang , Ou Xixian , Li Qiang
Published: February 2025

The present study investigated the effect of the replacement of chemical fertilizers by organic fertilizers on agronomic traits of tobacco at maturity as well as on the conventional chemical quality of post-roasted tobacco leaves. To better understand the relationship between tobacco metabolites and roasted tobacco under organic nitrogen replacement treatments, post-roasting tobacco leaves were analyzed by an untargeted metabolomics analytical approach to identify key metabolites applicable to predicting tobacco quality. Methods: Yunyun Tobacco 87 was adopted as the test material in a field plot experiment with five fertilization treatments: T1 (100% chemical nitrogen fertilizer), T2 (25% organic nitrogen fertilizer + 75% chemical nitrogen fertilizer), T3 (50% organic nitrogen fertilizer + 50% chemical nitrogen fertilizer), T4 (75% organic nitrogen fertilizer + 25% chemical nitrogen fertilizer), and T5 (100% organic nitrogen fertilizer). Additionally, the non-targeted metabolomics approach was employed for the in-depth analysis of metabolites in roasted tobacco leaves. Results: The targeted metabolomic analysis identified 991 metabolites in the positive ion pattern and 673 in the negative ion pattern across all treatments. Among these, certain pathways such as alanine, aspartate, and glutamate metabolism, D-amino acid metabolism, purine metabolism, tryptophan metabolism, and galactose metabolism were up-regulated, whereas other pathways such as starch and sucrose metabolism, betalain biosynthesis, and biosynthesis of unsaturated fatty acids were down-regulated and significantly enriched with differential metabolites. This study revealed the significant differences in the metabolite composition under different fertilization conditions, with a strong correlation between metabolites and tobacco quality indices. Organic fertilizers were observed to enhance tobacco quality by influencing tobacco metabolism, providing a scientific basis for optimizing fertilization strategies and improving tobacco quality.
Brown Algae Polysaccharides Alleviate Diquat-Induced Oxidative Stress in Piglets and IPEC-J2 Cells via Nrf2/ARE Signaling Pathway
Authors: Hou Chunjie , Yu Zirou , Shi Chenyu , Huang Ya , Liu Hu
Published: February 2025

This study investigated the effect of Brown algae polysaccharides (BAPs) on diquat-induced oxidative stress in piglets and IPEC-J2 cells through Nrf2/ARE signaling pathway. In the in vivo model, 24 male piglets of the Duroc × Landrace × Large White breed were selected and divided into 4 groups (n = 6), including the CON group (basal diet), DIQ group (10 mg/kg Diquat), BAP group (1000 mg/kg BAP), and BAP+DIQ group (1000 mg/kg BAP + 10 mg/kg Diquat). Compared with the DIQ group, BAP improved growth performance and the BAP+DIQ group reduced the levels of IL-1β, IL-6, TNF-α, and DAO in plasma, increased VH and VCR, improved jejunal tissue morphology, decreased MDA levels, and increased T-AOC (p < 0.05). Additionally, the BAP+DIQ group elevated mRNA levels of ZO-1, and enhanced the protein levels of Occludin, Claudin1, CAT, SOD1, and HO-1 (p < 0.05). In the in vitro model, the BAP+DIQ group decreased MDA levels, increased T-AOC, elevated mRNA levels of ZO-1, CAT and SOD2, as well as protein levels of Claudin1, SOD1, HO-1, and total Nrf2 compared with the DIQ group (p < 0.05). Furthermore, BAP increased nuclear Nrf2 protein levels, and promoted the translocation of Nrf2 from the cytoplasm to the nucleus compared with the DIQ group (p < 0.05). In conclusion, BAPs are crucial for enhancing piglets’ antioxidant capacity via Nrf2 pathway activation. These findings highlight BAP’s potential as a natural feed additive to mitigate oxidative stress and improve overall health in piglets. Further research is warranted to explore BAPs as a dietary supplement to support gut health and reduce oxidative stress.
Decade-Long Trends in Antibiotic Prescriptions According to WHO AWaRe Classification Among Severe Acute Respiratory Infection Patients at Tertiary Hospitals in Bangladesh (2011–2020)
Authors: Chowdhury Fahmida , Bhuiya Saju , Abdul Aleem Mohammad , Shuvo Tanzir Ahmed , Mamun Gazi Md. Salahuddin , Kumar Ghosh Probir , Shahrin Lubaba , Khan Samin Yasar , Islam Md Ariful , Rahman Mahmudur
Published: February 2025

Background: To aid in the development of antimicrobial stewardship programs (ASPs), we analyzed the patterns and trends in antibiotic prescriptions for patients with severe acute respiratory infection (SARI), utilizing the WHO’s AWaRe classification. Methods: We analyzed data from hospital-based influenza surveillance from January 2011 to December 2020 across nine Bangladeshi tertiary-level hospitals. Surveillance physicians collected WHO-defined SARI patient data, including demographics, clinical characteristics, and antibiotic prescriptions. Descriptive statistics and parametric and non-parametric tests were used for the analysis. Results: Of 21,566 SARI patients [median age 20 years (IQR: 1.33–45), 66% male], 91% were prescribed at least one antibiotic. A total of 25,133 antibiotics were prescribed, of which 47.0% were third-generation cephalosporins, 16.5% were macrolides, and 11.1% were beta-lactam/beta-lactamase inhibitors. According to the AWaRe classification, 28.7% were in the Access group, while 71.3% were in the Watch group, and none were from the Reserve group. A downward trend in Access group (30.4% to 25.1%; p = 0.010) and an upward trend in Watch group antibiotic prescription (69.6% to 74.9%; p = 0.010) were observed. We identified that patients aged < 5 years (aOR: 1.80; 95% CI: 1.44–2.25), who were treated in government hospitals (aOR: 1.45; 95% CI: 1.35–1.57), patients with the presence of lung diseases (aOR: 1.56; 95% CI: 1.35–1.80) had an increased likelihood of being prescribed Watch group antibiotics. Conclusions: This study reveals a concerning pattern of antibiotic overuse among SARI patients in Bangladesh, with a growing trend over the past decade towards increased Watch group antibiotic prescriptions. Only one-third of the prescribed antibiotics were from the Access group, falling short of the two-thirds threshold recommended by the WHO. Effective ASPs are crucial to optimize antibiotic prescriptions and mitigate the risk of antimicrobial resistance.
An Elegant Multi-Agent Gradient Descent for Effective Optimization in Neural Network Training and Beyond
Authors: Sakka Mohammad , Bahrami Mohammad Reza
Published: February 2025

Non-convex optimization problems often challenge gradient-based algorithms, such as Gradient Descent. Neural network training, a prominent application of gradient-based methods, heavily relies on their computational efficiency. However, the cost function in neural network training is typically non-convex, causing gradient-based algorithms to become trapped in local minima due to their limited exploration of the solution space. In contrast, global optimization algorithms, such as swarm-based methods, provide better exploration but introduce significant computational overhead. To address these challenges, we propose Multi-Agent Gradient Descent (MAGD), a novel algorithm that combines the efficiency of gradient-based methods with enhanced exploration capabilities. MAGD initializes multiple agents, each representing a candidate solution, and independently updates their positions using gradient-based techniques without inter-agent communication. The number of agents is dynamically adjusted by removing underperforming agents to minimize computational cost. MAGD offers a cost-effective solution for non-convex optimization problems, including but not limited to neural network training. We benchmark MAGD against traditional Gradient Descent (GD), Adam, and Swarm-Based Gradient Descent (SBGD), demonstrating that MAGD achieves superior solution quality without a significant increase in computational complexity. MAGD outperforms these methods on 20 benchmark mathematical optimization functions and 20 real-world classification and regression datasets for training shallow neural networks.