bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of the ‘Dysphagia Screening Tool for Geriatric Patients’ (DSTG) compared to Flexible Endoscopic Evaluation of Swallowing (FEES) for assessing dysphagia in hospitalized geriatric patients – a diagnostic study
Authors: Thiem Ulrich , Jäger Martin , Stege Holger , Wirth Rainer
Published: December 2023

Background

Oropharyngeal dysphagia is highly prevalent among hospitalized geriatric patients. The screening instruments used to date have been evaluated primarily in stroke patients. This diagnostic study aimed to validate a new screening instrument for oropharyngeal dysphagia, the ‘Dysphagia Screening Tool for Geriatric Patients’ (DSTG), as compared to one of the gold standards, flexible endoscopic evaluation of swallowing (FEES).

Materials and methods

Geriatric inpatients admitted to five geriatric hospitals in Germany were consecutively evaluated using both DSTG and FEES in random order and by different evaluators blinded to the results of the other evaluation. In the FEES examination, a score of more than 3 on Rosenbek’s Penetration Aspiration Scale was considered evidence of clinically relevant oropharyngeal dysphagia. Sensitivity, specificity and further measures of test performance were calculated for DSTG.

Results

The 53 volunteers recruited were on average 85 years of age, 56.6% were women. Twenty patients (37.7%) were diagnosed with dysphagia using FEES. Of these, 12 were screened as positive on DSTG. Of the 33 FEES negative patients, 4 tested positive on DSTG. The following test parameters were calculated for DSTG: sensitivity: 0.60, 95% confidence interval [0.39 ; 0.78], specificity 0.88 [0.73 ; 0.95], positive predictive value 0.75 [0.51 ; 0.90], negative predictive value 0.78 [0.63 ; 0.89], positive likelihood ratio 4.95 [1.85 ; 13.27], negative likelihood ratio 0.46 [0.26 ; 0.79]. In a receiver-operator characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.77 [0.62 ; 0.91]. No adverse events occurred.

Conclusion

The DSTG appears to be a valid instrument for screening of oropharyngeal dysphagia in geriatric inpatients.
Determinants of late-stage cervical cancer presentation in Ethiopia: a systematic review and meta-analysis
Authors: Zewdie Amare , Shitu Solomon , Kebede Natnael , Gashaw Anteneh , Eshetu Habitu Birhan , Eseyneh Tenagnework , Kasahun Abebaw Wasie
Published: December 2023

Introduction

Behind breast, colorectal, and lung cancers, cervical cancer is the fourth most common cancer affecting females. Despite, it is a preventable form of cancer both the incidence and mortality figures reflect it as a major reproductive health problem. Late-stage cervical cancer diagnosis is associated with complicated clinical presentation which can result in short survival time and increased mortality. Several factors contribute to the late-stage presentation of cervical cancer patients. In Ethiopia nationally summarized evidence on the level and the factors contributing to late-stage cervical cancer diagnosis is scarce. Therefore, this systematic review and meta-analysis aimed to assess the pooled prevalence of late-stage cervical cancer diagnosis and its determinants in Ethiopia.

Method

A systematic review and meta-analysis were conducted using PRISMA guidelines. Comprehensive literature was searched in PubMed, Embase, Google Scholar, and African Online Journal to retrieve eligible articles. A weighted inverse variance random effect model was used to estimate pooled prevalence. Cochrane Q-test and I2 statistics were computed to assess heterogeneity among studies. Funnel plot and Egger’s regression test were done to assess publication bias.

Result

Overall, 726 articles were retrieved and finally 10 articles were included in this review. The pooled prevalence of late-stage cervical cancer diagnosis in Ethiopia was 60.45% (95%CI; 53.04%-67.85%). Poor awareness about cervical cancer and its treatment (AOR = 1.55, 95% CI: (1.03 – 2.33, longer delay to seek care (AOR = 1.02, 95% CI: (1.01 – 1.03)) and rural residence (AOR = 2.07, 95% CI:( 1.56 – 2.75)) were significantly associated to late-stage diagnosis.

Conclusion

In Ethiopia, six in every ten cervical cancer cases are diagnosed at the late stage of the disease. Poor awareness about cervical cancer and its treatment, long patient delay to seek care, and rural residence were positively associated with late–stage diagnosis. Therefore intervention efforts should be made to improve public awareness about cervical cancer, minimize patient delay to seek care, and expand screening services specifically in the rural residing segment of the population to detect the disease early and improve survival.
Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression
Authors: Lee Junwoo , Kim Kiyoung , Kim Eung Suk , Yu Seung-Young , Kang Min Seok
Published: December 2023

Purpose

To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression.

Methods

This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment.

Results

BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022).

Conclusions

Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.
Hyperglycemia with hypogonadism and growth hormone deficiency in a 17-year-old male with H syndrome: the first case report from Syria
Authors: Hamsho Suaad , Alaswad Mohammed , Sleiay Mouhammed , Alhusseini Ayham
Published: December 2023

Background

The nucleoside transport capabilities of the human equilibrative nucleoside transporter-3 (hENT3) are disrupted by mutations in SLC29A3 (10q22.2), which are genes for the nucleoside transporter and are the cause of the unusual autosomal recessive disease known as H syndrome. As a result, histiocytic cells invade a number of organs.

Case presentation

A 17-year-old Syrian male was admitted to the internal medicine department with a one-month history of polyuria, polydipsia, general weakness, and pallor. He had a history of progressive bilateral sensorineural hearing loss and failure to gain weight for three years. Physical examination revealed various abnormalities, including scrotal mass, small penis and testicles, absence of pubic and axillary hair, joint abnormalities, short stature, hallux valgus, fibrous protrusion near the navel, and hyperpigmented non-itchy painful skin plaques. Clinical signs along with laboratory test results confirmed hyperglycemia, primary hypogonadism, osteopenia, and growth hormone deficiency. After a review of the relevant medical literature, this patient’s presentation of hyperglycemia with hypogonadism, hyperpigmentation, hallux valgus, hearing loss, hematological abnormalities, and short stature suggested the diagnosis of H syndrome. The patient received treatment with insulin and testosterone, leading to a significant improvement in his presenting symptoms.

Conclusions

H syndrome is a very rare condition, and the fact that the first case has only recently been reported in Syria serves to emphasize how rare it is. H Syndrome should be suspected if a patient has short stature with signs of hyperglycemia and other endocrine and cutaneous abnormalities. We are reporting this case to increase physicians’ awareness of this exceedingly rare and unique syndrome.
Exploring knowledge, attitude, and intention towards advance care planning, advance directive, and the patient self-determination act among hemodialysis patients
Authors: Tsai Shang-Feng , Chang Ching-Yi , Yang Jia-Yi , Ho Yu-Ying , Hsiao Ching-Ching , Hsu Shu-Chuan , Chen Shih-Yun , Lin Huan-Yi , Yeh Te-Feng , Chen Cheng-Hsu
Published: December 2023

Background

Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (AD), and patient self-determination acts (PSDA) remains limited. Our objective was to examine the current status of ACP, AD and PSDA and potential opportunities for enhancement.

Methods

We developed a novel questionnaire to assess individuals’ knowledge, attitudes, and intentions regarding ACP, AD, and PSDA. We also collected baseline characteristics and additional inquiries for correlation analysis to identify potential factors. Student’s t-test and Analysis of Variance were employed to assess significance.

Results

Initially, a cohort of 241 patients was initially considered for inclusion in this study. Subsequently, 135 patients agreed to participate in the questionnaire study, resulting in 129 valid questionnaires. Among these respondents, 76 were male (59.9%), and 53 were female (41.1%). Only 13.2% had signed AD. A significant portion (85.3%) indicated that they had not discussed their dialysis prognosis with healthcare providers. Additionally, a mere 14% engaged in conversations about life-threatening decisions. Ninety percent believed that healthcare providers had not furnished information about ACP, and only 30% had discussed such choices with their families. The findings revealed that the average standardized score for ACP and AD goals was 84.97, while the attitude towards PSDA received a standardized score of 69.94. The intention score stood at 69.52 in standardized terms. Potential candidates for ACP initiation included individuals aged 50 to 64, possessing at least a college education, being unmarried, and having no history of diabetes.

Conclusion

Patients undergoing hemodialysis exhibited a significant knowledge gap concerning ACP, AD, and the PSDA. Notably, a substantial number of dialytic patients had not received adequate information on these subjects. Nevertheless, they displayed a positive attitude, and a considerable proportion expressed a willingness to sign AD. It is imperative for nephrologists to take an active role in initiating ACP discussions with patients from the very beginning.
Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice
Authors: Aldayel Tahany Saleh , Gad El Hak Heba N. , Nafie Mohamed S. , Saad Raneem , Abdelrazek Heba M. A. , Kilany Omnia E.
Published: December 2023

The current research intended to evaluate the antitumor properties of Moringa oleifera oil extract (MOE). Fifty-six female Swiss albino mice were employed in this study. Animals were assigned into four groups: control (C) group, moringa oil extract (MOE) group administered (500 mg/kg b. wt) MOE daily via gavage, Ehrlich ascites carcinoma (EAC) group and EAC group administered daily with (500 mg/kg b.wt) MOE for two weeks (EAC/MOE). The results showed that MOE significantly ameliorated the EAC increase in body weight and reduced the EAC cell viability. In addition, they upgraded the levels of hepatic and renal functions, inflammatory cytokines, oxidative stress markers and EAC-induced hepatic and renal histopathological changes. Treatment of EAC with MOE induced antitumor, anti-inflammatory and antioxidant effects and normalized most of the tested parameters besides the histopathological alterations in both renal and hepatic tissues. HPLC for the MOE identified Cinnamic acid, Ellagic acid, Quercetin, Gallic acid, Vanillin and Hesperidin as major compounds. The molecular docking study highlighted the virtual binding of the identified compounds inside the GSH and SOD proteins, especially for Quercetin which exhibited promising binding affinity with good interactive binding mode with the key amino acids. These results demonstrate that the antitumor constituents of MOE against EAC induced oxidative stress and inflammation by preventing oxidative damage and controlling EAC increase.
Precision cancer medicine and the doctor-patient relationship: a systematic review and narrative synthesis
Authors: Grauman Å. , Ancillotti M. , Veldwijk J. , Mascalzoni D.
Published: December 2023

Background

The implementation of precision medicine is likely to have a huge impact on clinical cancer care, while the doctor-patient relationship is a crucial aspect of cancer care that needs to be preserved. This systematic review aimed to map out perceptions and concerns regarding how the implementation of precision medicine will impact the doctor-patient relationship in cancer care so that threats against the doctor-patient relationship can be addressed.

Methods

Electronic databases (Pubmed, Scopus, Web of Science, Social Science Premium Collection) were searched for articles published from January 2010 to December 2021, including qualitative, quantitative, and theoretical methods. Two reviewers completed title and abstract screening, full-text screening, and data extraction. Findings were summarized and explained using narrative synthesis.

Results

Four themes were generated from the included articles (n = 35). Providing information addresses issues of information transmission and needs, and of complex concepts such as genetics and uncertainty. Making decisions in a trustful relationship addresses opacity issues, the role of trust, and and physicians’ attitude towards the role of precision medicine tools in decision-making. Managing negative reactions of non-eligible patients addresses patients’ unmet expectations of precision medicine. Conflicting roles in the blurry line between clinic and research addresses issues stemming from physicians’ double role as doctors and researchers.

Conclusions

Many findings have previously been addressed in doctor-patient communication and clinical genetics. However, precision medicine adds complexity to these fields and further emphasizes the importance of clear communication on specific themes like the distinction between genomic and gene expression and patients’ expectations about access, eligibility, effectiveness, and side effects of targeted therapies.
Exploring influential factors on patient safety culture in delirium nursing care within long-term care facilities: a cross-sectional survey
Authors: Kim Se Hee , Moon Kyoung Ja
Published: December 2023

Background

Elderly residents with physical and cognitive impairments in long-term care facilities are vulnerable to safety risks.

Purpose

This study investigated factors that influence patient safety cultures in delirium nursing care in long-term care facilities.

Methods

A cross-sectional survey was conducted among 214 nurses working in 12 long-term care facilities using a structured questionnaire from February 15, 2022, to March 14, 2022. Data analysis was performed using Pearson’s correlation coefficients and hierarchical analysis with SPSS/WIN 25.0 software.

Results

Significant factors associated with patient safety culture were identified. Organizational factors included the availability of delirium care manuals, nursing education and experience in delirium care, and the perceived necessity of delirium education. Individual factors included nurse-to-patient ratios, and nurses marital status.

Conclusion

To foster a strong patient safety culture, attention should be given to the availability of delirium care resources, the promotion of specialized and ongoing education and experience, and adequate staffing levels.
Contextual factors affecting integration of eye health into school health programme in Zanzibar: a qualitative health system research
Authors: Chan Ving Fai , Yard Elodie , Mashayo Eden , Mulewa Damaris , Drake Lesley , Omar Fatma
Published: December 2023

Background

Short-term school eye health programmes supported by external funders have sustainability issues. This study aimed to understand the contextual factors affecting integrating eye health into the school health programme.

Methods

We elicited responses from 83 respondents, purposefully selected from the Ministry of Health (n = 7), Ministry of Education and Vocational Training (n = 7), hospitals/eye centres (n = 5), master trainers (4) and schools (n = 60) who participated in in-depth interviews. Their responses were analysed and grouped into contextual factors according to the WHO Consolidated Framework for Implementation Research: stakeholders/political, institutional, physical, cultural, delivery system and others. Themes were then generated, and quotations were presented to illustrate the findings.

Results

The six contextual factors affecting the integration of eye health into the school eye health programme were i) Stakeholders/political (Good ministry coordination, defined departmental roles and resource mobilisation from multiple stakeholders; Good stakeholder synergies and address current gaps); ii) Institutional (Institutional coordination and adequate clinic space; Securing human and financial resources; Strategic advocacy for institutional resources); iii) Physical (Long travel distance to service points); vi) Cultural (low eye health awareness among parents, teachers and children); iv) Delivery system (Practical approach to increase screening coverage using teachers as screeners; Balance teachers’ workload, increase screening sensitivity and follow up and; v) Others (Comprehensive training material and effective training delivery; Improved curriculum, teacher selection and supervision and incentives).

Conclusion

Integrated school eye health delivery is generally well-received by stakeholders in Zanzibar, with the caveat that investment is required to address the six contextual factors identified in the study.
Prognostic implications of obstructive sleep apnea in patients with acute coronary syndrome stratified by homocysteine level: a prospective cohort study
Authors: Chen Xiuhuan , Zhen Lei , Ai Hui , Que Bin , Fan Jingyao , Wang Xiao , Yan Yan , Li Siyi , Zhang Zekun , Zhou Yun , Gong Wei , Nie Shaoping
Published: December 2023

Background

Sporadic studies have examined the impact of OSA on ACS patients by homocysteine (Hcy) level. This study attempted to comprehensively evaluate the effects of the interaction between Hcy and OSA on long-term cardiovascular outcomes in ACS patients.

Methods

In this prospective, large-scale cohort study, 2160 patients admitted for ACS were recruited to undergo overnight sleep monitoring. OSA was diagnosed when apnea–hypopnea index ≥ 15 events/h. Patients with normohomocysteinemia (NHcy) were defined as having serum Hcy ≤ 15 μmol/L, and the others had hyperhomocysteinemia (HHcy). The primary endpoint was major adverse cerebrocardiovascular event (MACCE), a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization and hospitalization for unstable angina and heart failure.

Results

A total of 1553 eligible ACS patients (average age: 56.3 ± 10.5 years) were enrolled, among which 819 (52.7%) had OSA, and 988 (63.6%) were with NHcy. OSA did not significantly affect the level of Hcy. During a median follow-up of 2.9 (1.6, 3.5) years, after adjustment for clinical confounders, OSA was associated with increased risk for MACCE occurrence versus non-OSA ones in ACS patients with NHcy (adjusted hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.02–1.83, P = 0.039), but not in those with HHcy (adjusted HR = 0.92, 95%CI 0.62–1.36, P = 0.668). There was an absence of interaction between homocysteine level and OSA in relation to MACCE (interaction P = 0.106).

Conclusions

OSA was independently associated with worse prognosis in ACS patients with NHcy. Our study emphasized the necessity to identify potential presence of OSA in such a population.

Trial registration: ClinicalTrials.gov; Number: NCT03362385; URL: www.clinicaltrials.gov.
A novel minimally invasive fixation method for flail chest management in a Canine model: an animal research
Authors: Li Zhe , Zhu Weiwei , Zhang Bing , Zhang Yaxiao , Li Huixian , Lv Baolei , Zhen Qiang , Liu Lin , Liu Lijun , Wu Yanxin , Li Shujun
Published: December 2023

Background

Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries.

Methods

Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes.

Results

Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery withPvalues greater than 0.05. However, the interior group canines had better RR and PO2values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48thhour. It took longer operation time to complete the minimally invasive interior fixation surgery (Pvalue less than 0.001), but the total blood loss was less than the exterior fixation group (Pvalue less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility.

Conclusions

The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.
Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects
Authors: Li Xue , Pei Pei , Shen Jinying , Yu Juan , Wang Fang , Wang Lei , Liu Changyun , Wang Shan
Published: December 2023

Background

Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined.

Results

Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis.

Conclusion

Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.
O-GlcNAcylation: the sweet side of epigenetics
Authors: Dupas Thomas , Lauzier Benjamin , McGraw Serge
Published: December 2023

Histones display a wide variety of post-translational modifications, including acetylation, methylation, and phosphorylation. These epigenetic modifications can influence chromatin structure and function without altering the DNA sequence. Histones can also undergo post-translational O-GlcNAcylation, a rather understudied modification that plays critical roles in almost all biological processes and is added and removed by O-linked N-acetylglucosamine transferase and O-GlcNAcase, respectively. This review provides a current overview of our knowledge of how O-GlcNAcylation impacts the histone code both directly and by regulating other chromatin modifying enzymes. This highlights the pivotal emerging role of O-GlcNAcylation as an essential epigenetic marker.
Microbiota promotes recruitment and pro-inflammatory response of caecal macrophages during E. tenella infection
Authors: Tomal F. , Sausset A. , Le Vern Y. , Sedano L. , Techer C. , Lacroix-Lamandé S. , Laurent F. , Silvestre A. , Bussière F. I.
Published: December 2023

Background

Eimeria genus belongs to the apicomplexan parasite phylum and is responsible for coccidiosis, an intestinal disease with a major economic impact on poultry production. Eimeria tenella is one of the most virulent species in chickens. In a previous study, we showed a negative impact of caecal microbiota on the physiopathology of this infection. However, the mechanism by which microbiota leads to the physiopathology remained undetermined. Macrophages play a key role in inflammatory processes and their interaction with the microbiota during E. tenella infection have never been investigated. We therefore examined the impact of microbiota on macrophages during E. tenella infection. Macrophages were monitored in caecal tissues by immunofluorescence staining with KUL01 antibody in non-infected and infected germ-free and conventional chickens. Caecal cells were isolated, stained, analyzed and sorted to examine their gene expression using high-throughput qPCR.

Results

We demonstrated that microbiota was essential for caecal macrophage recruitment in E. tenella infection. Furthermore, microbiota promoted a pro-inflammatory transcriptomic profile of macrophages characterized by increased gene expression of NOS2, ACOD1, PTGS2, TNFα, IL1β, IL6, IL8L1, IL8L2 and CCL20 in infected chickens. Administration of caecal microbiota from conventional chickens to germ-free infected chickens partially restored macrophage recruitment and response.

Conclusions

Taken together, these results suggest that the microbiota enhances the physiopathology of this infection through macrophage recruitment and activation. Consequently, strategies involving modulation of the gut microbiota may lead to attenuation of the macrophage-mediated inflammatory response, thereby limiting the negative clinical outcome of the disease.
Effect of systemic atorvastatin on bone regeneration in critical-sized defects in hyperlipidemia: an experimental study
Authors: Öztürk Kübra , Kuzu Turan Emre , Ayrıkçil Semih , Gürgan Cem Abdulkadir , Önder Gözde Özge , Yay Arzu
Published: December 2023

Purpose

Hypocholesterolemic medications similar to atorvastatin are efficient in lowering blood lipid levels; however, compared to other medications in the statin family, their impact on bone metabolism is claimed to be insufficient. The impact of atorvastatin on bone regeneration in dental implantology in individuals with hyperlipidemia who received atorvastatin in the clinic is doubtful.

Methods

In the study, 16 male New Zealand rabbits of 6 months were used. All rabbits were fed a high-cholesterol diet for 8 weeks, and hyperlipidemia was created. It was confirmed that the total cholesterol level in rabbits was above 105 mg/dl. A critical-sized defect was created in the mandible. The defect was closed with xenograft and membrane. Oral 10 mg/kg atorvastatin was started in the experimental group, and no drug was administered in the control group. At 16th week, animals were sacrificed. For histomorphological examination, the new bone area, osteoclast, and osteoblast activities were evaluated.

Results

While new bone area (45,924 µm2, p < 0.001) and AP intensities (105.645 ± 16.727, p = 0.006) were higher in the atorvastatin group than in the control group, TRAP intensities in the control group (82.192 ± 5.346, p = 0.021) were higher than that in the atorvastatin group.

Conclusions

It has been found that high blood lipid levels will adversely affect bone graft healing and the use of systemic atorvastatin contributes to bone healing. Clinicians should pay attention to the selection of surgical materials, considering the importance of questioning drug use in their patients and the risks in cases of non-use.
Can intravitreal injections with higher volume cause higher intraocular eye pressure? Considerations for anti-complement injections in normal and glaucomatous eyes
Authors: Meyer Carsten H. , Melo Gustavo Barreto , Khanani Arshad M.
Published: December 2023

The approval of Syfovre® (pegcetacoplan) and Iverzay® (avacincaptad pegol) for the treatment of geographic atrophy (GA) marks a significant advancement in retinal disease therapy, offering both complement 3 and complement 5 inhibitors. With this breakthrough, an increase in intravitreal injections (IVI) is expected to treat GA, raising questions about potential effects on intraocular pressure (IOP). This concern is exacerbated by the larger injection volume required for GA treatment, potentially impacting IOP. Previous studies have shown that IVI can lead to a temporary increase in IOP with a 0.05 ml injection. This transient elevation is challenging to manage with glaucoma drops, and a preventive approach, such as paracentesis immediately before IVIs, may be more effective. Despite concerns, clinical significance and long-term effects of IOP changes with a 0.05 ml injection remain uncertain. To address these concerns, routine evaluations including macular optical coherence tomography (OCT), fundus autofluorescence, IOP measurements, and retinal nerve fiber layer OCT before the first IVI with avacincaptad pegol and pegcetacoplan are recommended to detect potential changes early. Further research is needed to determine the extent to which IOP changes impact GA patients and whether cumulative effects occur with repeated IVIs, especially in those with additional eye conditions.
Identification of ceRNA-vsiRNA-mRNA network for exploring the mechanism underlying pathogenesis of sugarcane mosaic virus in resistant and susceptible maize inbred lines
Authors: Gao Xinran , Hao Kaiqiang , Du Zhichao , Zhang Sijia , Wang Zhiping , An Mengnan , Xia Zihao , Wu Yuanhua
Published: December 2023

RNA silencing plays an important role in plant antiviral responses, which trigger the production of virus-derived small interfering RNAs (vsiRNAs). The competing endogenous RNA (ceRNA) hypothesis revealed a unique mechanism in which circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can interact with small RNAs to regulate the expression of corresponding target mRNAs. Sugarcane mosaic virus (SCMV) infection causes severe economic losses in maize (Zea mays L.) production worldwide. This study compared and analyzed characteristics of vsiRNAs derived from SCMV and their target genes in resistant (Chang7-2) and susceptible (Mo17) maize inbred lines through whole-transcriptome RNA sequencing and degradome sequencing. The results showed that 706 transcripts were targeted by 204 vsiRNAs, including 784 vsiRNA-target gene pairs. Furthermore, ceRNA networks of circRNA/lncRNA-vsiRNA-mRNA in response of maize to SCMV infection were obtained, including 3 differentially expressed (DE) circRNAs, 36 DElncRNAs, 105 vsiRNAs, and 342 DEmRNAs in Mo17 plants, and 3 DEcircRNAs, 35 DElncRNAs, 23 vsiRNAs, and 87 DEmRNAs in Chang7-2 plants. Our results also showed that the transcripts of ZmDCLs, ZmAGOs, and ZmRDRs were differentially accumulated in resistant and susceptible maize inbred lines after SCMV infection. These findings provide valuable insights into the relationship between SCMV-derived vsiRNAs and potential ceRNAs fine-tuning the SCMV-maize interaction and offer novel clues to reveal the mechanism underlying the pathogenesis of SCMV.
Delivery of nucleic acids using nanomaterials
Authors: Qin Yuyang , Ou Liyuan , Zha Lili , Zeng Yue , Li Ling
Published: December 2023

The increasing number of approved nucleic acid therapeutics demonstrates the potential for the prevention and treatment of a broad spectrum of diseases. This trend underscores the significant impact and promise of nucleic acid-based treatments in the field of medicine. Nevertheless, employing nucleic acids as therapeutics is challenging due to their susceptibility to degradation by nucleases and their unfavorable physicochemical characteristics that hinder delivery into cells. Appropriate vectors play a pivotal role in improving nucleic acid stability and delivering nucleic acids into specific cells. The maturation of delivery systems has led to breakthroughs in the development of therapeutics based on nucleic acids such as DNA, siRNA, and mRNA. Non-viral vectors have gained prominence among the myriad of nanomaterials due to low immunogenicity, ease of manufacturing, and simplicity of cost-effective, large-scale production. Here, we provide an overview of the recent advancements in nanomaterials for nucleic acid delivery. Specifically, we give a detailed introduction to the characteristics of polymers, lipids, and polymer-lipid hybrids, and provide comprehensive descriptions of their applications in nucleic acid delivery. Also, biological barriers, administration routes, and strategies for organ-selective delivery of nucleic acids are discussed. In summary, this review offers insights into the rational design of next-generation delivery vectors for nucleic acid delivery.
Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study
Authors: Pott Christiane , Jurinovic Vindi , Trotman Judith , Kehden Britta , Unterhalt Michael , Herold Michael , Jagt Richard van der , Janssens Ann , Kneba Michael , Mayer Jiri , Young Moya , Schmidt Christian , Knapp Andrea , Nielsen Tina , Brown Helen , Spielewoy Nathalie , Harbron Chris , Bottos Alessia , Mundt Kirsten , Marcus Robert , Hiddemann Wolfgang , Hoster Eva
Published: December 2023

PURPOSE

We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968 ) trial.

PATIENTS AND METHODS

Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis.

RESULTS

MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse.

CONCLUSION

MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
Four Additional Doses of PEG-L-Asparaginase During the Consolidation Phase in the AIEOP-BFM ALL 2009 Protocol Do Not Improve Outcome and Increase Toxicity in High-Risk ALL: Results of a Randomized Study
Authors: Conter Valentino , Valsecchi Maria Grazia , Cario Gunnar , Zimmermann Martin , Attarbaschi Andishe , Stary Jan , Niggli Felix , Dalla Pozza Luciano , Elitzur Sarah , Silvestri Daniela , Locatelli Franco , Möricke Anja , Engstler Gernot , Smisek Petr , Bodmer Nicole , Barbaric Draga , Izraeli Shai , Rizzari Carmelo , Boos Joachim , Buldini Barbara , Zucchetti Massimo , von Stackelberg Arend , Matteo Cristina , Lehrnbecher Thomas , Lanvers-Kaminsky Claudia , Cazzaniga Giovanni , Gruhn Bernd , Biondi Andrea , Schrappe Martin
Published: December 2023

PURPOSE

The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome.

PATIENTS AND METHODS

A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE.

RESULTS

By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10−4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively ( P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively ( P < .001).

CONCLUSION

Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.
Planetary Rifting and the Paleogeography of Care
Authors: Clark Nigel , Whittle Rebecca
Published: December 2023

With their specter of intergenerational betrayal, global environmental crises increasingly entangle politics with matters of care, attachment, and love—especially the unconditional bonds we are so often assumed to share with our offspring. As a contribution to the nascent field of paleoenvironmental humanities, this article’s approach to questions of care and responsibility turns from future horizon-scanning to the realm of human origins. It focuses on two broad sets of paleo stories that share a concern with rifts or stress points that complicate originary events and scenes. The first of these is a family of hypotheses which propose that pivotal evolutionary developments took place in the climatically variable and tectonically active terrain of the East African Rift. The second is the cooperative breeding hypothesis, which contends that communally distributed childcare arrangements are a definitive characteristic of the genus Homo, while also highlighting the conditionality and precariousness of human intergenerational care. Taken together, these approaches point to deep-seated fault lines running through both our home planet and our own psychosocial being. Confronting these rifts might help loosen the hold of notions of ontological reconciliation between humans and nature that risk exacerbating the very problems they seek to resolve, while also helping us to seek attachments that are more conducive to living with and through earthly volatility.
Casual Planetarities
Authors: Ballestero Andrea
Published: December 2023

Planetary awareness has become synonymous with awareness of large-scale temporal, geographic, and geologic events. Given the scalar multiplicities and instabilities of life on earth, concepts such as planetarity, the Anthropocene, and even the global have provided analytic reprieve. They name that which is difficult to objectify: the geographic and historical vastness of geological presence. But those concepts grow from knowledge habits inherited from imperial and Cold War logics and can presume the existence of an all-encompassing observer who can grasp the unity of the planet as such. This article explores alternative assumptions. It asks how other practices of the earth deal with planetary scales of sense-making. It conceptualizes those practices as forms of casual planetarity that, instead of drawing on preexisting scales such as the planet or the Anthropocene, produce senses of closeness and/or distance between everyday life and the geological implications of human presence. It follows the work of geologists in Costa Rica who rely on a 3D physical model to bring about scalar oscillations that connect human experiences with the vastness of underground worlds. This association is made possible by focusing on the movement of water as a hydro-geo-social choreography of everyday life. The article shows how the resonant power of the 3D model geologists use to enact these choreographies opens pathways for people to come to terms with their geological presence without having to see the planet as a whole or presume the capacity for total observation.
The complex interactions between nutrition, immunity and infection in insects
Authors: Ponton Fleur , Tan Yin Xun , Forster Casey C. , Austin Alexander J. , English Sinead , Cotter Sheena C. , Wilson Kenneth
Published: December 2023

Insects are the most diverse animal group on the planet. Their success is reflected by the diversity of habitats in which they live. However, these habitats have undergone great changes in recent decades; understanding how these changes affect insect health and fitness is an important challenge for insect conservation. In this Review, we focus on the research that links the nutritional environment with infection and immune status in insects. We first discuss the research from the field of nutritional immunology, and we then investigate how factors such as intracellular and extracellular symbionts, sociality and transgenerational effects may interact with the connection between nutrition and immunity. We show that the interactions between nutrition and resistance can be highly specific to insect species and/or infection type – this is almost certainly due to the diversity of insect social interactions and life cycles, and the varied environments in which insects live. Hence, these connections cannot be easily generalised across insects. We finally suggest that other environmental aspects – such as the use of agrochemicals and climatic factors – might also influence the interaction between nutrition and resistance, and highlight how research on these is essential.
RESERVE - REporting of SystEmatic ReViews in Ethics: development, explanations and examples
Authors: Kahrass Hannes , Borry Pascal , Gastmans Chris , Ives Jonathan , van der Graaf Rieke , Strech Daniel , Mertz Marcel
Published: December 2023

Background Systematic reviews (SR) are well elaborated and established for synthesizing statistical information, for example of clinical studies, for determining whether a clinical intervention is effective. SRs are also becoming more and more popular in bioethics. However, the established approach of conducting and reporting cannot be transferred to SRs on ethically sensible questions directly. This is because the object of investigation is not statistical information, but conceptual or normative information, e.g. ethical norms, principles, arguments or conclusions. There is evidence that the quality of reporting of SRs on ethics literature could be improved in many regards. Although insufficient reporting is not a problem specific to bioethics, as poorly reported manuscripts are also very common in SRs in e.g. medicine, authors of such SRs have the possibility to follow existing reporting guidelines (e.g. PRISMA). Method An international group of authors with years of experience in conducting and reviewing SRs on ethics literature developed a reporting guideline for this specific area of application (RESERVE). The relevant background was provided by two reporting guidelines: PRISMA for systematic reviews and ENTREQ due to the importance of qualitative research approaches. Results RESERVE has 22 items and is intended to provide authors of SRs on ethics literature with all information necessary for an adequate reporting. It also allows readers, reviewers and journal editors critically evaluating the presented results and conclusions made. In this paper, we explain the rationale and give examples for each item. Conclusions While we acknowledge heterogeneity on how to conduct a SR on ethics literature, we still maintain that there is a need for general reporting standards for improving transparency, understandability and verifiability. We invite authors of SRs on ethics literature to test and evaluate the usefulness of RESERVE. We hope for a critical discussion of the guideline and welcome its broad implementation.