bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Differences in Perioperative Complications, Readmissions, and Mortalities After Elective Spine Surgery in the United States: A Systematic Review Using AI-Assisted Bibliometric Analysis
Authors: Akosman Izzet , Kumar Neerav , Mortenson Richard , Lans Amanda , De La Garza Ramos Rafael , Eleswarapu Ananth , Yassari Reza , Fourman Mitchell S.
Published: June 2023

Study Design

Systematic Review and Meta-analysis.

Objectives

To evaluate the impact of race on post-operative outcomes and complications following elective spine surgery in the United States.

Methods

PUBMED, MEDLINE(R), ERIC, EMBASE, and SCOPUS were searched for studies documenting peri-operative events for White and African American (AA) patients following elective spine surgery. Pooled odds ratios were calculated for each 90-day outcome and meta-analyses were performed for 4 peri-operative events and 7 complication categories. Sub-analyses were performed for each outcome on single institution (SI) studies and works that included <100,000 patients.

Results

53 studies (5,589,069 patients, 9.8% AA) were included. Eleven included >100,000 patients. AA patients had increased rates of 90-day readmission (OR 1.33, P = .0001), non-routine discharge (OR 1.71, P = .0001), and mortality (OR 1.66, P = .0003), but not re-operation (OR 1.16, P = .1354). AA patients were more likely to have wound-related complications (OR 1.47, P = .0001) or medical complications (OR 1.35, P = .0006), specifically cardiovascular (OR 1.33, P = .0126), deep vein thrombosis/pulmonary embolism (DVT/PE) (OR 2.22, P = .0188) and genitourinary events (OR 1.17, P = .0343). SI studies could only detect racial differences in re-admissions and non-routine discharges. Studies with <100,000 patients replicated the above findings but found no differences in cardiovascular complications. Disparities in mortality were only detected when all studies were included.

Conclusions

AA patients faced a greater risk of morbidity across several distinct categories of peri-operative events. SI studies can be underpowered to detect more granular complication types (genitourinary, DVT/PE). Rare events, such as mortality, require larger sample sizes to identify significant racial disparities.
Assessing Market Integration Between MINT and Developed Economies: Evidence from Dynamic Cointegration
Authors: Siddiqui Saif , Kaur Rajbeer
Published: June 2023

This study examines the static and time-varying cointegration between Mexico, Indonesia, Nigeria, and Turkey (MINT), and developed stock markets in USA and Japan by applying conventional cointegration methodology and rolling multivariate trace statistics over the period of 10 years. Overall, the findings of bivariate cointegration test suggested that MINT stock markets do not have significant long running relationship with Japan stock market. Hence, the scope of diversification exists accordingly. However, rolling trace statistics revealed the time-varying nature of integration between the markets considered in the study. The varying degree of cointegration is more likely to be caused by major economic, financial, and political events. Hence, the presence of equilibrium relationship among the markets in the sub-periods may limit the potential portfolio diversification benefits. Thus, lack of consistency in the findings of the static and dynamic cointegration analysis highlights the limitation of the static assessment. On the short-term linkage, the examination of dynamic conditional correlation (DCC) for each MINT-developed market pair suggested that Indonesia exhibits least correlation with USA and Japan and hence, offering highest portfolio avenues.
Immediate Prepectoral Breast Reconstruction Without Acellular Dermal Matrices: Preliminary Results
Authors: Bouhadana Gabriel , Chocron Yehuda , Azzi Alain J. , Davison Peter G.
Published: June 2023

Background: In an effort to shed light on the recent resurgence of prepectoral breast reconstruction and mounting concerns regarding acellular dermal matrices (ADMs), the senior author's experience with non-ADM-assisted immediate prepectoral breast reconstruction and its associated complications are presented. Methods: A retrospective cohort study of the senior author's prepectoral breast reconstruction practice without ADM from November 2019 to May 2021 was carried out. Data regarding patient demographics, oncologic management, and surgical outcomes were recorded. Results: A total of 66 patients (88 breasts) were included, with an average follow-up of 7.8 months (SD: 5.4). Of these, 24 (36.4%) underwent immediate expander and 42 (63.6%) direct-to-implant (DTI) reconstructions. Major complications included nipple-areolar complex necrosis (2%), hematoma (3%), device exposure (2%), and periprosthetic infections (5.7%). The overall rate of implant failure was 5.7%. Minor complications included simple cellulitis (10%) and minor wound dehiscence (4.5%). Increasing implant size ( p < .005) in the DTI cohort and increasing body mass index (BMI) were associated with an increased likelihood of adverse events. Postmastectomy radiation had no effect on surgical complications. Conclusions: The authors hope that in the absence of large, prospective trials, our data demonstrate the safety of immediate prepectoral breast reconstruction without ADM. Our data demonstrate that our algorithm is particularly safe in patients with a low BMI and with an implant size <500cc in DTI reconstruction. Further large prospective studies are required to further support our data in demonstrating that foregoing ADM in immediate prepectoral reconstruction is a safe option.
The Lifeworld of Law: Methodological Multiplicity in Legal Pedagogy
Authors: Singh Anushka
Published: June 2023

Multidisciplinary studies in the field of law in India in the last two decades or so have gained traction. The grudging acceptance of insights from social sciences into the technical discipline of law has expanded the horizon of its study. The presence of insights from other disciplines, however, has not predominantly altered the approach to legal education in India and they have at best remained alternate modes of legal analyses juxtaposed with a technical-doctrinal study of law. The methodological challenge is to think of ways to dovetail the insights to co-produce legal knowledge which is shared across disciplines. This paper is an attempt in that direction by bringing in a synthesis between the ‘external’ and the ‘internal’ perspectives, arguing in favour of interdisciplinarity as a pedagogical frame. The approach towards legal pedagogy is heuristic where methodical perspectives are not imparted but demonstrated. This paper undertakes this task in relation to how criminal law in India can be taught through a case study on the law of sedition—Section 124A of the Indian Penal Code, examining it from three different perspectives—the doctrinal, the instrumentalist and the constitutivist. The learnings from different vantage points and the exchange between them create lessons for legal pedagogy.
Leukocytoclastic Vasculitis in a Patient With Crohn Disease: A Case Report
Authors: Bugada Mark Daniele , Emani Vamsi K.
Published: June 2023

Leukocytoclastic vasculitis (LCV) is an idiopathic small vessel vasculitis. Leukocytoclastic vasculitis can be found in a spectrum of diseases and is noted as a rare extraintestinal manifestation of Crohn disease. This case report examines a 55-year-old man with a previous diagnosis of Crohn disease who was admitted after 5 days with a persistent rash. A biopsy confirmed LCV, and the patient followed up with dermatology for outpatient treatment. This study adds to the sparse medical literature on LCV cases relating to Crohn disease.
Effectiveness of Comprehensive Physical Activity Health Promotion Program on the Essential Physical Functions of Older Patients With Multiple Diseases and Dementia in Rural Area
Authors: Lin Lain-Li , Liu Chih-Chi
Published: June 2023

Against the backdrop of aging populations worldwide, physical activity programs aimed at promoting the health of older adults have begun to flourish. However, few studies have focused on elderly residents in rural areas who may have multiple comorbidities. Therefore, the current study aimed to investigate the effects of a 12-week physical activity program on health promotion among rural elderly with multiple diseases. The study included 18 elderly participants, with a mean age of 82.39 years, who had dementia and one or more additional diseases. Among the participants, 89% were female. The results showed that the 12-week physical activity program intervention significantly improved participants’ walking speed and range of motion of the arm joints. Based on these findings, it is hoped that this study will provide a reference for future researchers and practitioners targeting rural or elderly populations who may have multiple diseases to develop more comprehensive physical activity programs.
Measuring and Explaining a College Dignity Divide in America
Authors: Andersson Matthew A. , Hitlin Steven
Published: June 2023

Prominent, multidisciplinary perspectives on inequality in America contend that receiving a four-year college degree matters not just for life chances but also for achieving a sense of dignity or respect from others. In this study, the authors assess subjective dignity, or dignity as perceived in one’s own life, according to four-year college degree status and how it overlaps with different economic and psychosocial college-linked resources. Drawing on multiple years of national Gallup survey data (2017 and 2021), the authors find a college gap in subjective dignity as large as the difference linked to full-time work itself. Consistent with Lamont’s perspective on America’s dignity crisis, a lack of perceived socioeconomic standing in society most strongly coincides with why those without a college degree also perceive a lack of dignity within their lives, although finances, work, perceived control, and mattering to others all significantly coincide with the college dignity gap as well.
Medication error during nonoperating room anesthesia—a case report
Authors: Kostadinov Ivan , Stecher Adela , Novak-Jankovic Vesna , Poredos Peter
Published: June 2023

Despite a lot has already been done in the field of safety improvement during anesthesia, medication errors still occur during everyday practice. Syringe or ampule swaps are usually the most frequent type of medication error. Recent studies prove that nearly 80% of these errors are preventable. In our case, 30 mg (3 ml) of dopamine (Dopamin Fresenius 10 mg/ml) was injected to the patient’s intravenous line instead of 3 mg (3 ml) midazolam (Midazolam Accord 1 mg/ml) during the preparation for the carotid artery stenting procedure in nonoperating room environment. The error was realized immediately after the application. Besides temporary fulminant hypertensive reaction, tachycardia, restlessness, skin rush, troponin leak, and temporary ST-segment depression, there were no permanent consequences to the patient's health. The team was able to perform the planned procedure 30 min after the event. This medication error of ampule swap, packages of which were stored in the medication cupboard one above the other, was caused by alignment of the latent vulnerable layers of the safety system (Swiss Cheese Model of System Error and Hot Cheese Model) plus the influence of the environmental factors and active failures done by the anesthesia staff. After this event, new safety measures were established by introducing color-coded ISO 26825:2020 syringe labeling, new anesthesia trolleys with color-coded medication compartments, and color-coded medication storage cupboards. Besides this safety committee was formed for the promotion of medication safety education programs.
A conceptual review of Sustainable Development Goal 17: Picturing politics, proximity and progress
Authors: Stanberry Joanna , Bragan Balda Janis
Published: June 2023

We outline the discursive origins of United Nations Sustainable Development Goal (SDG) 17, describing its ambiguous marching orders, which are further confused by shifting and contested stakeholder approaches. The widespread effect is to obscure the primary aim of making the tropics and other vulnerable countries more resilient, and also globally overcoming barriers to their development. We argue that ecological reflexivity, as developed and advanced by deliberative democracy and the Earth System Governance Project, belongs at the apex of those capacities needed for implementing the Agenda for Transformation. Ecological reflexivity conceptually grounds inclusive, open, critical, and consequential engagement of discourses situated among capable representatives, advocates, and citizens. SDG-related partnerships – whether designed around funding, technology, knowledge generation, or business innovation – are the locus in which this gets worked out. We advance this aim by proposing adjustment of the focal point using a Picturing framework that can enable both scholarly and practitioner approaches to SDG 17 to correct distortions and also materially ‘strengthen the means of implementation’. Using this framework, which entails Picturing politics, Picturing proximity to the poor, and Picturing progress, actors can shift attention to the accompanying discursive properties that affect implementation of the 2030 Agenda. Picturing is given concrete application through five case examples aligned to the research lenses of the Earth System Governance Research Framework. By drawing on studies spanning Barbados, Grenada, Bolivia, Ghana, Zambia, Peru, India and Fiji we demonstrate potential for the Picturing framework to provoke novel development pathways for a more sustainable future in the tropics.
Mesenchymal stromal cells ameliorate chronic GVHD by boosting thymic regeneration in a CCR9-dependent manner in mice
Authors: Zhang Xin , He Jiabao , Zhao Ke , Liu Shiqi , Xuan Li , Chen Shan , Xue Rongtao , Lin Ren , Xu Jun , Zhang Yan , Xiang Andy Peng , Jin Hua , Liu Qifa
Published: June 2023

Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Mature donor T cells within the graft contribute to severe damage of thymic epithelial cells (TECs), which are known as key mediators in the continuum of acute GVHD (aGVHD) and cGVHD pathology. Mesenchymal stromal cells (MSCs) are reportedly effective in the prevention and treatment of cGVHD. In our previous pilot clinical trial in patients with refractory aGVHD, the incidence and severity of cGVHD were decreased, along with an increase in levels of blood signal joint T-cell receptor excision DNA circles after MSCs treatment, which indicated an improvement in thymus function of patients with GVHD, but the mechanisms leading to these effects remain unknown. Here, we show in a murine GVHD model that MSCs promoted the quantity and maturity of TECs as well as elevated the proportion of Aire-positive medullary TECs, improving both CD4+CD8+ double-positive thymocytes and thymic regulatory T cells, balancing the CD4:CD8 ratio in the blood. In addition, CCL25-CCR9 signaling axis was found to play an important role in guiding MSC homing to the thymus. These studies reveal mechanisms through which MSCs ameliorate cGVHD by boosting thymic regeneration and offer innovative strategies for improving thymus function in patients with GVHD.
High mobility group box 1 and a network of other biomolecules influence fatigue in patients with Crohn’s disease
Authors: Kvivik Ingeborg , Grimstad Tore , Bårdsen Kjetil , Jonsson Grete , Kvaløy Jan Terje , Omdal Roald
Published: June 2023

Background

Fatigue is common in patients with chronic inflammatory and autoimmune diseases, often with a severe impact on the patient’s daily life. From a biological point of view, fatigue can be regarded as an element of the sickness behavior response, a coordinated set of responses induced by pathogens to enhance survival during an infection and immunological danger. The mechanisms are not fully understood but involve activation of the innate immune system, with pro-inflammatory cytokines, in particular interleukin (IL)-1β, acting on cerebral neurons. These mechanisms are also active during chronic inflammatory conditions. High mobility group box 1 (HMGB1) protein has interleukin-1 like properties and is a strong inducer of innate immune responses. Its role in generation of fatigue is not clarified. Emerging evidence indicates that also other biomolecules may influence sickness behavior. We aimed to elucidate how HMGB1 influences fatigue in patients with Crohn’s disease, and how the protein interacts with other candidate biomarkers of fatigue.

Methods

In 56 patients with newly diagnosed Crohn’s disease, fatigue was evaluated using three different fatigue instruments: the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and the vitality subscale of Medical Outcomes Study Short-Form Health Survey (SF-36vs). The biochemical markers IL-1 receptor antagonist (RA), soluble IL-1 receptor type 2 (sIL-RII), heat shock protein 90 alpha (HSP90α), HMGB1, anti-fully reduced (fr)HMGB1 antibodies (abs), hemopexin (HPX), and pigment epithelium-derived factor (PEDF) were measured in plasma. Multivariable regression and principal component analyses (PCA) were applied.

Results

Multivariable regression analyses revealed significant contributions to fatigue severity for HMGB1 in the FSS model, HSP90α in the fVAS model and IL-1RA in the SF-36vs model. Depression and pain scores contributed to all three models. In PCA, two components described 53.3% of the variation. The “inflammation and cellular stress dimension” was dominated by IL-1RA, sIL-1RII, HSP90α, HPX, and PEDF scores, where the “HMGB1 dimension” was dominated by HMGB1, anti-frHMGB1 abs, and fVAS scores.

Conclusion

This study supports the hypothesis that HMGB1 and a network of other biomolecules influence fatigue severity in chronic inflammatory conditions. The well-known association with depression and pain is also acknowledged.
A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA
Authors: Zhao Rui , Yang Zhenming , Zhao Bo , Li Wenjing , Liu Yaohui , Chen Xiaoxue , Cao Jing , Zhang Jiarui , Guo Yan , Xu Licheng , Wang Jinpeng , Sun Yanan , Liu Ming , Tian Linli
Published: June 2023

Background

Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear.

Methods

We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT–PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC.

Results

tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells.

Conclusions

Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.
Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature
Authors: Wisniewski Piotr , McCool Isaac , Walsh John C. , Ausman Chelsea , Edmondson Jenifer , Perry Alexandra , Ewers Evan C. , Maves Ryan C.
Published: June 2023

Background

Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy.

Case summary

We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic.

Conclusions

Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.
Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants
Authors: Madewell Zachary J. , Yang Yang , Longini Ira M. , Halloran M. Elizabeth , Vespignani Alessandro , Dean Natalie E.
Published: June 2023

Background

The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9–5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87–5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants.

Methods

This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: (“serial interval” or “generation time”), (“Omicron” or “Delta”), and (“SARS-CoV-2” or “COVID-19”). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported.

Results

There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3–5.8 days for Delta and 2.1–4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4–4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9–3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8–3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7–3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6–3.1) (three studies).

Conclusions

Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.
Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report
Authors: Shimamoto Yuki , Takahashi Naoki , Katoh Nagaaki , Matsui Yuki , Mochizuki Yusuke , Ito Masanori , Yazaki Masahide , Kametani Fuyuki , Kasuno Kenji , Sekijima Yoshiki , Naiki Hironobu , Iwano Masayuki
Published: June 2023

Background

Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.

Case presentation

We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.

Conclusions

This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.
Fan beam CT-guided online adaptive external radiotherapy of uterine cervical cancer: a dosimetric evaluation
Authors: Peng Haibo , Zhang Jie , Xu Ningyue , Zhou Yangang , Tan Huigang , Ren Tao
Published: June 2023

Purpose

To discuss the dosimetric advantages and reliability of the accurate delivery of online adaptive radiotherapy(online ART) for uterine cervical cancer(UCC).

Methods and materials

Six UCC patients were enrolled in this study. 95% of the planning target volume (PTV) reached 100% of the prescription dose (50.4 Gy/28fractions/6weeks) was required. The patients were scanned with uRT-Linac 506c KV-FBCT then the target volume (TV) and organs at risk (OARs) were delineated by doctors. The dosimeters designed and obtained a routine plan (Plan0). KV-FBCT was used for image guidance before subsequent fractional treatment. The online ART was processed after registration, which acquired a virtual nonadaptive radiotherapy plan (VPlan) and an adaptive plan (APlan). VPlan was the direct calculation of Plan0 on the fractional image, while APlan required adaptive optimization and calculation. In vivo dose monitoring and three-dimensional dose reconstruction were required during the implementation of APlan.

Results

The inter-fractional volumes of the bladder and rectum changed greatly among the treatments. These changes influenced the primary gross tumor volume (GTVp) and the position deviation of GTVp and PTV and positively affected the prescription dose coverage of TV. GTVp decreased gradually along with dose accumulation. The Dmax, D98, D95, D50, and D2 of APlan were superior to those of VPlan in target dose distribution. APlan had good conformal index, homogeneity index and target coverage. The rectum V40 and Dmax, bladder V40, the small bowel V40 and Dmax of APlan were better than that of VPlan. The APlan’s fractional mean γ passing rate was significantly higher than the international standard and the mean γ passing rate of all cases after the three-dimensional reconstruction was higher than 97.0%.

Conclusion

Online ART in external radiotherapy of UCC significantly improved the dose distribution and can become an ideal technology to achieve individualized precise radiotherapy.
Secular trend of non-communicable chronic disease prevalence throughout the life span who endured Chinese Great Famine (1959–1961)
Authors: He Xiaoxue , Shi Xiaojuan , Pan Degong , Wang Huihui , Zhang Xue , Pu Lining , Luo Mingxiu , Li Jiangping
Published: June 2023

Background

Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood.

Objective

This study aims to explore long-term trends in the impact of China’s Great Famine (1959–1961) on NCDs in China.

Methods

This study used data from the 2010–2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18–85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010–2020 and the effect of famine on the risk of NCDs in terms of cohort effects.

Results

The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs.

Conclusions

Experiencing famine at an early age or the experience of famine in a close relative’s generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.
Exploring the effects of health behaviors and mental health on students’ academic achievement: a cross-sectional study on lebanese university students
Authors: Hammoudi Halat Dalal , Hallit Souheil , Younes Samar , AlFikany Mira , Khaled Sanaa , Krayem Maha , El Khatib Sami , Rahal Mohamad
Published: June 2023

Background

High academic achievement, an important determinant of future success, is known to be influenced by many factors including dietary behavior, lifestyle and mental health, among others. The objectives of the current study were to explore university students’ nutritive habits, daily lifestyle, and mental status, and to scrutinize the associations between these factors and students’ academic achievement.

Methods

A cross-sectional study was conducted among students of a private Lebanese university, using an electronic survey. Diet, eating habits, physical activity, sleep, and smoking were evaluated, and mental health was assessed using a validated Arabic version of the combined Depression, Anxiety, Stress Score (DASS-8). Academic achievement was measured using the Subjective Academic Achievement Scale (SAAS).

Results

A total of 1677 students participated in the questionnaire. The results of a linear regression taking the SAAS score as the dependent variable, showed that students who have a non-scientific versus scientific major (Beta = 0.53), and having breakfast ≥ 4 days per week compared to less than 2 days (Beta = 0.28) were significantly associated with higher SAAS scores. More psychological distress (Beta = − 0.06) and a higher number of days of eating out (Beta = − 0.07) were significantly associated with lower SAAS scores.

Conclusions

This is the first investigation on a Lebanese university students’ academic success in relation to lifestyle and mental profiles. Better academic achievement was demonstrated by students having healthier dietary and lifestyle habits, as well as less distressing mental status. Such results, in light of the compounded and unprecedented crises with which Lebanon has been assailed, suggest the need to focus on promoting healthy habits among students in higher education as a possible driver of better academic success.
Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
Authors: Chen Ying , Rui Rong , Wang Li , Wang Hao , Zhu Bingbing , Cao Aili
Published: June 2023

Purpose

This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice.

Methods

Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed.

Results

HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice.

Conclusion

HQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.
Differentially expressed chaperone genes reveal a stress response required for unidirectional regeneration in the basal chordate Ciona
Authors: Jeffery William R. , Li Bo , Ng Mandy , Li Lianwei , Gorički Špela , Ma Li
Published: June 2023

Background

Unidirectional regeneration in the basal chordateCiona intestinalisinvolves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury. However, after theCionabody is bisected, regeneration occurs in the proximal but not in the distal fragments, even if the latter include a part of the branchial sac with stem cells. A transcriptome was sequenced and assembled from the isolated branchial sacs of regenerating animals, and the information was used to provide insights into the absence of regeneration in distal body fragments.

Results

We identified 1149 differentially expressed genes, which were separated into two major modules by weighted gene correlation network analysis, one consisting of mostly upregulated genes correlated with regeneration and the other consisting of only downregulated genes associated with metabolism and homeostatic processes. Thehsp70,dnaJb4, andbag3genes were among the highest upregulated genes and were predicted to interact in an HSP70 chaperone system. The upregulation of HSP70 chaperone genes was verified and their expression confirmed in BS vasculature cells previously identified as stem and progenitor cells. siRNA-mediated gene knockdown showed thathsp70anddnaJb4,but notbag3,are required for progenitor cell targeting and distal regeneration. However, neitherhsp70nordnaJb4were strongly expressed in the branchial sac vasculature of distal fragments, implying the absence of a stress response. Heat shock treatment of distal body fragments activatedhsp70anddnaJb4expression indicative of a stress response, induced cell proliferation in branchial sac vasculature cells, and promoted distal regeneration.

Conclusions

The chaperone system geneshsp70,dnaJb4, andbag3are significantly upregulated in the branchial sac vasculature following distal injury, defining a stress response that is essential for regeneration. The stress response is absent from distal fragments, but can be induced by a heat shock, which activates cell division in the branchial sac vasculature and promotes distal regeneration. This study demonstrates the importance of a stress response for stem cell activation and regeneration in a basal chordate, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates.
Dopamine modulates the retinal clock through melanopsin-dependent regulation of cholinergic waves during development
Authors: Kinane Chaimaa , Calligaro Hugo , Jandot Antonin , Coutanson Christine , Haddjeri Nasser , Bennis Mohamed , Dkhissi-Benyahya Ouria
Published: June 2023

Background

The mammalian retina contains an autonomous circadian clock that controls various aspects of retinal physiology and function, including dopamine (DA) release by amacrine cells. This neurotransmitter plays a critical role in retina development, visual signalling, and phase resetting of the retinal clock in adulthood. Interestingly, bidirectional regulation between dopaminergic cells and melanopsin-expressing retinal ganglion cells has been demonstrated in the adult and during development. Additionally, the adult melanopsin knockout mouse (Opn4−/−) exhibits a shortening of the endogenous period of the retinal clock. However, whether DA and / or melanopsin influence the retinal clock mechanism during its maturation is still unknown.

Results

Using wild-type Per2Luc and melanopsin knockout (Opn4−/−::Per2Luc) mice at different postnatal stages, we found that the retina generates self-sustained circadian rhythms from postnatal day 5 in both genotypes and that the ability to express these rhythms emerges in the absence of external time cues. Intriguingly, only in wild-type explants, DA supplementation lengthened the endogenous period of the clock during the first week of postnatal development through both D1- and D2-like dopaminergic receptors. Furthermore, the blockade of spontaneous cholinergic retinal waves, which drive DA release in the early developmental stages, shortened the period and reduced the light-induced phase shift of the retinal clock only in wild-type retinas.

Conclusions

These data suggest that DA modulates the molecular core of the clock through melanopsin-dependent regulation of acetylcholine retinal waves, thus offering an unprecedented role of DA and melanopsin in the endogenous functioning and the light response of the retinal clock during development.
Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer’s disease
Authors: Li Wenwen , Pang Yana , Wang Yan , Mei Fan , Guo Mengmeng , Wei Yiping , Li Xinyue , Qin Wei , Wang Wei , Jia Longfei , Jia Jianping
Published: June 2023

Background

The identification of pathogenic mutations in Alzheimer’s disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer’s disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aβ production; however, these genetic defects occur in only about 10–20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure.

Methods

We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aβ and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining.

Results

We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aβ retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21T209S/T209S mice, possibly contributing to Aβ production. Palmitoyltransferase inhibitors reversed synaptic function impairment.

Conclusions

ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.
The predictive value of atherogenic index of plasma for cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention with LDL-C below 1.8mmol/L
Authors: Wang Yue , Wang Shen , Sun Shuaifeng , Li Fadong , Zhao Wenxin , Yang Hongxia , Wu Xiaofan
Published: June 2023

Background

The potential predictive significance of atherogenic index of plasma (AIP) for cardiovascular outcomes in patients with acute coronary syndrome (ACS) and who have undergone percutaneous coronary intervention (PCI), with low-density lipoprotein-cholesterol (LDL-C) below 1.8mmol/L, has not been well explored.

Methods

The retrospective cohort analysis included 1,133 patients with ACS and LDL-C levels below 1.8mmol/L who underwent PCI. AIP is calculated as log (triglyceride/high-density lipoprotein-cholesterol). Patients were divided into two groups according to the median value of AIP. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke or unplanned repeat revascularization. The association between AIP and the prevalence of MACCE was evaluated using multivariable Cox proportional hazard models.

Results

Over a median follow-up of 26 months, the incidence of MACCE was higher in the high AIP group compared to the low AIP group (9.6% vs. 6.0%, P log-rank = 0.020), and the difference was mainly derived from an increased risk of unplanned repeat revascularization (7.6% vs. 4.6%, P log-rank = 0.028). After adjusting for multiple variables, elevated AIP was independently associated with an increased risk of MACCE, regardless of whether AIP was considered a nominal or continuous variable (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.04–2.53 or HR 2.01, 95% CI 1.09–3.73).

Conclusions

The present study demonstrates that AIP is a significant predictor of adverse outcomes in ACS patients undergoing PCI with LDL-C < 1.8mmol/L. These results suggest that AIP may offer supplementary prognostic information for ACS patients with optimally managed LDL-C levels.
Independent and joint associations between the triglyceride-glucose index and NT-proBNP with the risk of adverse cardiovascular events in patients with diabetes and acute coronary syndrome: a prospective cohort study
Authors: Wang Man , Zhou Li , Su Wen , Dang Wenxi , Li Hongwei , Chen Hui
Published: June 2023

Background

Elevated triglyceride-glucose (TyG) index and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased risk of major adverse cardio-cerebral events (MACCEs) in diabetic patients with the acute coronary syndrome (ACS), but have not been evaluated jointly. We sought to investigate the independent and joint association of the TyG index and NT-proBNP with MACCEs risk.

Methods

Data from 5046 patients with diabetes and ACS were recorded in the Cardiovascular Center Beijing Friendship Hospital Database Bank between 2013 and 2021, including measurements of fasting triglycerides, plasma glucose, and NT-proBNP. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Associations of the TyG index and NT-proBNP with MACCEs risk were assessed using flexible parametric survival models.

Results

During 13589.9 person-years of follow-up, 985 incident MACCEs of the 5046 patients (65.6 years of age and 62.0% men) were observed. Elevated TyG index (HR: 1.18; 95% CI 1.05‒1.32 per 1 unit increase) and NT-proBNP categories (HR: 1.95; 95% CI: 1.50‒2.54 for > 729 pg/ml compared to < 129 pg/ml) were independently associated with MACCEs risk in the fully adjusted model. According to the joint categories of the TyG index and NT-proBNP, patients with the TyG index > 9.336 and NT-proBNP > 729 pg/ml were at the highest risk of MACCEs (HR: 2.45; 95% CI 1.64‒3.65) than the ones with TyG index < 8.746 and NT-proBNP < 129 pg/ml. The test for interaction was not significant (Pinteraction = 0.49). Incorporating these two biomarkers into the established clinical model, the Global Registry of Acute Coronary Events (GRACE) risk score, resulted in a significant improvement in risk stratification.

Conclusions

The TyG index and NT-proBNP were independently and jointly associated with the risk of MACCEs in patients with diabetes and ACS, suggesting that patients with both markers elevated should be aware of the higher risk in the future.